PNEUMONIA
(Diagnosis, Diagnostics, Immunodiagnosis,
Immunodiagnostics, Pathogenesis, Vaccines
& Drugs)
ABSTRACTS
1393. Aikio O. Vuopala K. Pokela
ML. Hallman M. Diminished inducible
nitric oxide synthase expression in fulminant
early-onset neonatal pneumonia.
Pediatrics. 105(5):1013-9, 2000
May.
Abstract
OBJECTIVE: Fulminant early-onset neonatal
pneumonia is associated with ascending intrauterine infection (IUI),
prematurity, persistent pulmonary hypertension (PPHN), and septicemia. Nitric
oxide (NO) as an inflammatory mediator is included in antimicrobial
defense and has a role in pathogenesis of septic shock. The aim was to
study the role of inflammatory NO in neonatal pneumonia.
METHODS: Lungs from 36 autopsies were studied: 12 had fulminant early-onset
neonatal pneumonia, 5 pneumonia of later onset, and 19 controls had similar
gestational and postnatal age. In addition, airway specimens from 21
intubated newborns were analyzed: 7 with fulminant early-onset pneumonia, 7
apparently noninfected infants born prematurely attributable
to IUI, and 7
premature infants of similar gestation. Specimens were analyzed for inducible NO synthase (NOS2) and
nitrotyrosine, an indicator of NO toxicity.
The degree of staining was analyzed. RESULTS: In fulminant pneumonia,
alveolar macrophages (AM) showed significantly less NOS2
immunoactivity than the controls. In the airway specimens, the infants with fulminant
pneumonia 0 to 2 days after birth had significantly lower intracellular
NOS2 and nitrotyrosine and significantly lower interleukin-1beta and
surfactant protein-A than apparently noninfected IUI infants. NOS2 and
the other indices increased significantly during the recovery.
CONCLUSIONS: For the first time, we report NOS2 expression by macrophages from
human neonates. In fulminant early-onset neonatal pneumonia, delayed
production rather than excess of pulmonary inflammatory NO is associated with
severe symptoms.
1394. Aurora R. Milite F.
Vander Els NJ. Respiratory emergencies. [Review] [117 refs] Seminars in
Oncology. 27(3):256-69, 2000 Jun.
Abstract
Respiratory emergencies may originate from disease in the airways, thoracic vessels, and pulmonary parenchyma. Airway obstruction may be amenable to bronchoscopic therapies, including laser ablation photodynamic therapy (PDT) and stent placement. Asthma is common, but may be mimicked by endobronchial metastasis. Superior vena cava syndrome (SVCS) is seen most commonly with bronchogenic carcinoma and lymphoma. Emergent treatment need not precede tissue diagnosis in the absence of associated tracheal obstruction. Pulmonary embolism (PE) may now be diagnosed with spiral computed tomography (CT), but ventilation perfusion scintigraphy remains the first-line test. Parenchymal lung disease may result from infections, with neoplastic and iatrogenic etiologies. The incidence of Pneumocystis carinii pneumonia (PCP) is increasing among cancer patients, but it can be prevented by prophylaxis. Attempts to treat adult respiratory distress syndrome (ARDS) through modification of inflammatory mediators have been disappointing, and the prognosis remains poor.
1395. Bandyopadhyay T. Gerardi DA.
Metersky ML. A comparison of induced and expectorated sputum for the
microbiological diagnosis of community
acquired pneumonia. Respiration. 67(2):173-6, 2000.
Abstract
BACKGROUND: Sputum induction has proved
useful in the diagnosis of Pneumocystis carinii pneumonia and
mycobacterial infections but there are scant data on its use in the diagnosis of
community-acquired pneumonia (CAP). OBJECTIVE: To better define the sage
of sputum induction by hypertonic saline in the setting of CAP.
METHODS: A retrospective review of records of patients admitted to a
community teaching hospital in the year 1995 with a diagnosis of CAP. RESULTS:
Of 492 patients admitted with CAP, 71 (14%) had attempted sputum
induction. A group of 66 patients with CAP and attempted sputum collection by
spontaneous expectoration was compared with this group. Sputum induction
failed to yield a sample in 22 patients (31%). Forty-five of 49 patients
(92%) with induced sputum had received prior antibiotics as compared to 23
of 34 patients (68%) with expectorated samples (p < 0.05), due to
sputum induction often being attempted later in the hospital course. The
diagnostic yield of sputum induction was 14 of 71 (20%) compared to 16
out of 66 (24%) for attempted spontaneously expectorated samples.
Antibiotic therapy was changed for 5 of 34 patients (15%) who spontaneously
expectorated samples and for 9 of 49 patients (18%) with successful induction.
CONCLUSIONS: Sputum induction is effective in obtaining sputum in some patients with CAP who fail to
expectorate a sample. Attempting induction
early, preferably before starting antibiotics, may increase its
diagnostic yield. Copyright 2000 S. Karger AG, Basel.
1396. Baughman RP. Protected-specimen
brush technique in the diagnosis of ventilator-associated pneumonia. [Review]
[0 refs] Chest. 117(4 Suppl
2):203S-206S, 2000 Apr.
1398. Carrigan DR. Adenovirus infections
in immunocompromised patients. [Review] [05 refs] American Journal of
Medicine. 102(3A):71-4, 1997 Mar 17.
Abstract
Adenovirus infections have been reported in
as many as one-fifth of bone marrow transplant (BMT) recipients and
patients with acquired immunodeficiency syndrome (AIDS), and in a
lesser, though still prominent, proportion of organ transplant recipients.
The relative contributions of primary infections versus reactivations from
latency in immunocompromised patients remain unclear. Compared with adult
BMT recipients, pediatric BMT recipients appear to be infected by
adenovirus more frequently and earlier in the post-transplant period. The diagnosis
of adenovirus infection is complicated by the existence of > 40
viral serotypes, although certain subgroups are more likely to be involved in
certain patient populations. Adenoviruses are responsible for a broad
range of clinical diseases that may be associated with high mortality,
including pneumonia, hepatitis, encephalitis, hemorrhagic cystitis, and
gastroenteritis. The clinical and histopathologic features of adenovirus
disease may resemble those of cytomegalovirus disease, potentially
complicating the diagnosis. Risk factors for clinical adenovirus disease
include the number of sites from which the virus is cultured and, in BMT
recipients, the presence of moderate to severe acute graft-versus-host
disease.
1399.
Carvalho Neves Forte W. Ferreira
De Carvalho Junior F. Damaceno N. Vidal
Perez F. Gonzales Lopes C. Mastroti RA. Evolution of IgA deficiency to
IgG subclass deficiency and common variable
immunodeficiency. Allergologia et Immunopathologia. 28(1):18-20, 2000 Jan-Feb.
Abstract
FIRST REPORT: male child with repeated
pulmonary infections from the age of 4 months. He was diagnosed as IgA
deficiency (undetectable IgA levels) at the age of 3 years, when he presented
repeated bouts of pneumonia and tonsillitis. Several immunologic evaluations
were made between the ages of 4 months and 8 years. At 8 years and 9
months, the diagnosis of IgA deficiency was confirmed, and associated
IgG2 and IgG4 deficiency (29.0 mg/dl y 0.01 mg/dl) with normal total IgG
serum level was found. With the administration of intravenous gammaglobulin,
the lung infections remitted and the subsequent clinical course has been
uneventful up to now. SECOND REPORT: a boy with repeated infections since
the age of 2 months. IgA deficiency was diagnosed at 1 year 7 months
(undetectable serum IgA levels). At age 51/2 years, his clinical
course worsened and more serious infections appeared. A new immunologic study
revealed IgA deficiency associated with CD4 cell deficiency (432
cells/mm3) and normal CD3, CD19, and CD8 levels. Despite intensive antibiotic
treatment and care, the child died. The findings suggest an association of
IgA deficiency and common variable immunodeficiency.
1400. Chaudhry R. Nazima N. Dhawan B. Kabra SK. Prevalence of Mycoplasma pneumoniae and Chlamydia pneumoniae in children with community acquired pneumonia [published erratum appears in Indian J Pediatr 1998 Nov-Dec;65(6):866]. Indian Journal of Pediatrics. 65(5):717-21, 1998 Sep-Oct.
Abstract
A prospective one year study was performed
on 62 children admitted at the All India Institute of Medical Sciences with
community acquired pneumonia (CAP) for the prevalence of Mycoplasma
pneumoniae and Chlamydia pneumoniae. Diagnosis of infection with M.
pneumoniae was based on serological tests viz microparticle
agglutination test for detection of IgM antibodies and indirect
immunofluorescence test for antigen detection from throat swabs (sensitivity 85.7%,
specificity 93.3%). The indirect solid-phase enzyme immunoassay for detection
of IgG antibodies was used to determine the prevalence of C. pneumoniae
(sensitivity 88.8%, specificity 75.8%). Seventeen patients (27.4%) were
found to have serological evidence of M. pneumoniae infection whereas only 4
(6.4%) patients were seropositive for C. pneumoniae. Results of this
study indicate that M. Pneumoniae plays a significant role in CAP
in infants and young children. Thus specialized laboratory testing for
these agents should be more widely used thereby affecting empiric antibiotic
regimens.
1401. Chugh
K. Pneumonia due to unusual organisms in children. [Review] [34 refs] Indian
Journal of Pediatrics. 66(6):929-36,
1999 Nov-Dec.
Abstract
Generally antimicrobials for treatment of pneumonia are chosen to target the usual bacterial etiological agents. Such regimens are unable to cure patients of pneumonia caused by 'unusual organisms' mycoplasma, chlamydia, Pneumocystis carinii and Legionella pneumophilus). Thus, there is a need to anticipate their presence in appropriate cases and to plan the initial antimicrobial therapy accordingly. Studies in Europe as well as India have shown that such infections form a fairly substantial percentage of community acquired pneumonia in children. Mycoplasma pneumoniae and Chlamydia pneumoniae are common in school age children while Chlamydia trachomatis occurs in early infancy. Pneumocystis carinii is an important pathogen in immunocompromised children. Routine laboratory tests and radiological features are not specific enough to give accurate diagnosis of these infections for which one has to depend on sophisticated culture techniques, immunological tests for the antigens or antibodies and polymerase chain reaction. Mycoplasma, chlamydia and legionella infections respond to macrolide antibiotics and for pneumocystis infections, trimethoprim-sulfamethaxozole or pentamidine is the drug of choice. Overall prognosis with appropriate treatment is good except for P. carinii infection in immunocompromised host which carries a high mortality and recurrence rate.
1402. Clark
CE. Coote JM. Silver DA. Halpin DM.
Asthma after childhood pneumonia: six year follow up study. BMJ. 320(7248):1514-6, 2000 Jun 3.
Abstract
OBJECTIVE: To establish the long term
cumulative prevalence of asthma in children admitted to hospital with pneumonia
and to examine the hypothesis that some children admitted to hospital with
pneumonia may be presenting with undiagnosed asthma. DESIGN: Prospective
study of a cohort of children previously admitted to hospital with pneumonia, followed up by postal
questionnaires to their general
practitioners and the children or their parents. SETTING: General practices in
southwest England. PARTICIPANTS: 78 children admitted to the Royal Devon and
Exeter Hospital between 1989 and 1991 with a diagnosis of pneumonia confirmed
on independent review of x ray films. MAIN OUTCOME MEASURES: Any
diagnosis of asthma, use of any treatment for asthma, and asthma symptom
scores. RESULTS: On the basis of a 100% response rate from general
practitioners and 86% from patients or parents, the cumulative prevalence of asthma
was 45%. A diagnosis of asthma was associated with a family history
of asthma (odds ratio 11.23; 95% confidence interval 2.57 to 56.36;
P=0.0002). Mean symptom scores were higher for all children with asthma (mean
score 2.4; chi(2)=14.88; P=0. 0001) and for children with asthma not being
treated (mean 1.4; chi(2)=6.2; P=0.01) than for those without
asthma (mean 0.2). CONCLUSIONS: A considerable proportion of children
presenting to a district general hospital with pneumonia either already have unrecognised asthma or subsequently develop asthma. The high
cumulative prevalence of asthma suggests that careful follow up of such
children is worth while. Asthma is undertreated in these children; a structured
symptom questionnaire may help to identify and reduce morbidity due to
undertreatment.
1403. Craven
DE. Epidemiology of ventilator-associated pneumonia. Chest. 117(4 Suppl 2):186S-187S, 2000 Apr.
Abstract
In summary, the method of diagnosis used for VAP accounts for reported differences in etiology, pathogenesis, and outcomes. Further studies are needed to assess outcomes related to various diagnostic methods rather than to assess the sensitivity and specificity of these methods.
1404. Dudas
V. Hopefl A. Jacobs R. Guglielmo BJ.
Antimicrobial selection for hospitalized patients with presumed
community-acquired pneumonia: a survey of nonteaching US community hospitals.
Annals of Pharmacotherapy.
34(4):446-52, 2000 Apr. Abstract
OBJECTIVE: To describe and evaluate empiric
antimicrobial regimens chosen for hospitalized patients with presumed
community-acquired pneumonia (CAP) in US hospitals, including compliance with the
American Thoracic Society (ATS) guidelines. Secondary outcomes
included length of stay (LOS) and mortality associated with the choice of
therapy. METHODS: A nonrandomized, prospective, observational study was performed in 72 nonteaching hospitals
affiliated with a national group purchasing organization. Patients with an
admission diagnosis of physician-presumed
CAP and an X-ray taken within 72 hours of admission were eligible for the
study. Demographic, antibiotic
selection, and outcomes data were collected
prospectively from patient charts. RESULTS: 3035 patients were
enrolled; 2963 were eligible for analysis. Compliance with the ATS guidelines
was 81% in patients with nonsevere CAP. The most common antibiotic
regimen used for empiric treatment was ceftriaxone alone or in
combination with a macrolide (42%). The overall mortality rate was 5.5%. The
addition of a macrolide to either a second- or third-generation cephalosporin
or a beta-lactam/beta-lactamase inhibitor was
associated with decreased mortality and reduced LOS. CONCLUSIONS: Most
hospitalized patients with CAP receive antimicrobial therapy consistent
with the ATS guidelines. The addition of a macrolide may be associated
with improved patient outcomes.
1405. Easterbrook
PJ. Yu LM. Goetghebeur E. Boag
F. McLean K. Gazzard B. Ten-year
trends in CD4 cell counts at HIV and AIDS diagnosis in a London HIV clinic.
AIDS. 14(5):561-71, 2000 Mar 31.
Abstract
OBJECTIVE: To examine temporal trends
(1986-1996) in the CD4 cell count at first HIV-1 positive test and initial AIDS
diagnosis, and the influence of selected patient characteristics and
treatment factors on these trends. DESIGN: A retrospective clinic-based study.
SETTING: Three hospital-based clinics in West London. PATIENTS: A group of
5921 adult HIV-1-seropositive persons and 2835 reported patients with AIDS
over a 10-year period from 1 January 1986 to 1 October 1996. METHODS: The
CD4 cell count at HIV diagnosis (CD4HIV) was defined as the nearest
CD4 cell count to within 2 months of HIV diagnosis; and the CD4 cell
count at AIDS diagnosis (CD4AIDS) as the last CD4 cell count in the
two months prior to the development of AIDS. Simple and multiple
linear regression analysis were used to examine the influence of selected covariates on CD4HIV and
CD4AIDS. RESULTS: The percentage of patients
with an available CD4HIV and CD4AIDS increased from less than 5% in 1987
to 53% and 40%, respectively, in 1990, and 79% and 48%, respectively, in 1996.
Patients with a missing CD4HIV or CD4AIDS were younger and less
likely to have received antiretroviral therapy or prophylaxis for
Pneumocystis carinii pneumonia (PCP). There was no significant change in
CD4HIV over a 10-year period (median 334 x 10(6) cells/l), but a lower
CD4HIV was associated with older age at presentation and injecting drug use. There was a delay in the onset
of clinical AIDS, with a fall in the median
CD4AIDS value from 99 x 10(6) cells/l prior to 1987, to 58 x 10(6) cells/l
in 1990, 68 x 10(6) cells/l in 1994 and 60 x 10(6) cells/l in 1996; this
decline in onset was seen for PCP as well as for cytomegalovirus and
atypical mycobacterial infections. At all time periods, a lower CD4AIDS was
associated with combined use of antiretroviral therapy and PCP prophylaxis.
After adjustment for use of antiretroviral therapy and PCP prophylaxis
prior to AIDS diagnosis, year of diagnosis was no longer associated with CD4AIDS. There was a
significant trend towards an improved
survival following AIDS diagnosis from 20.1 months prior to 1988, to 20.3
months (1989-1990), 21.0 months (1991-1992) and 22.1 (1993-1994) (P <
0.0005). CONCLUSIONS: The observed decline in CD4AIDS value was related to the
introduction of antiretroviral therapy in 1988, and PCP prophylaxis in
1989. Temporal changes in the CD4 cell count at HIV and AIDS diagnosis among
different demographic groups can provide insights into the changing natural history of the HIV epidemic
and access to medical care. We recommend monitoring of the CD4 cell count
at new HIV and AIDS diagnosis and at
initiation of antiretroviral therapy as additional measures in national HIV/AIDS
surveillance.
1406. Englund JA. Piedra PA. Whimbey E. Prevention and treatment of respiratory syncytial virus and parainfluenza viruses in immunocompromised patients. American Journal of Medicine. 102(3A):61-70; discussion 75-6, 1997 Mar 17.
Abstract
Immunocompromised patients are vulnerable to
severe infections due to respiratory syncytial virus (RSV) and
parainfluenza viruses (PIV), and therefore prevention and treatment
strategies must be considered. The prevention of RSV disease with high-titer RSV-specific immune globulin has
been documented in very young children but
has not been systematically studied in high-risk adults. Vaccines
against RSV and PIV are under development, but their use in
immunocompromised patients is problematic. Ribavirin aerosol therapy is licensed for
the treatment of RSV in pediatric patients and has also been used to
treat RSV disease in adults and PIV disease in severely immunocompromised children and adults.
Uncontrolled trials show that early therapy with ribavirin aerosol may be
beneficial, but treatment of pneumonia in
patients with respiratory failure is rarely successful. Other
potential treatments for RSV or PIV disease include high-dose, short-duration
ribavirin therapy; combined immunoglobulin and ribavirin therapy;
polyclonal and monoclonal antibodies; and, potentially,
immunomodulators.
1407. Franquet
T. Gimenez A. Roson N. Torrubia S. Sabate JM.
Perez C. Aspiration diseases:
findings, pitfalls, and differential diagnosis. Radiographics. 20(3):673-85, 2000 May-Jun.
Abstract
The aspiration of different substances into the airways and lungs may cause a variety of pulmonary complications. These disease entities most commonly involve the posterior segment of the upper lobes and the superior segment of the lower lobes. Esophagography and computed tomography (CT) are especially useful in the evaluation of aspiration disease related to tracheoesophageal or tracheopulmonary fistula. Foreign body aspiration typically occurs in children and manifests as obstructive lobar or segmental overinflation or atelectasis. An extensive, patchy bronchopneumonic pattern may be observed in patients following massive aspiration of gastric acid or water. CT is the modality of choice in establishing the diagnosis of exogenous lipoid pneumonia, which can result from aspiration of hydrocarbons or of mineral oil or a related substance. Aspiration of infectious material manifests as necrotizing consolidation and abscess formation. The relatively low diagnostic accuracy of chest radiography in aspiration diseases can be improved with CT and by being familiar with the clinical settings in which specific complications are likely to occur. Recognition of the varied clinical and radiologic manifestations of these disease entities is imperative for prompt, accurate diagnosis, resulting in decreased morbidity and mortality rates.
1408. Gupta
R. Faridi MM. Gupta P. Neonatal empyema thoracis. Indian Journal of
Pediatrics. 63(5):704-6, 1996 Sep-Oct.
Abstract
Empyema thoracis, a serious complication of pneumonia, fortunately remains a less common cause of respiratory distress in neonates. Only 14 cases of neonatal empyema thoracis have been described in the world literature. The condition is characterized by its rarity, inability to identify any consistent predisposing factors, uncertain pathogenesis, rapid course, lack of consensus on management and a high mortality. We describe here two cases of empyema aged 6 and 8 days caused by E. Coli and Klebsiella respectively. Out of them one survived. A brief review of literature follows the above account.
1409. Hammerschlag
MR. Activity of gemifloxacin and other new quinolones against Chlamydia
pneumoniae: a review. [Review] [33 refs] Journal of Antimicrobial Chemotherapy. 45 Suppl 1:35-9, 2000
Apr.
Abstract
Quinolones are currently used as empirical
therapy for treatment of community-acquired lower respiratory
infections as they are effective against a broad range of conventional
bacterial and 'atypical' pathogens, including Chlamydia pneumoniae. C. pneumoniae is estimated to be
associated with 10-20% of community-acquired
pneumonia in adults, and has recently been suggested to play a role in
several non-respiratory conditions, including atherosclerosis. The
newer, third-generation quinolones have enhanced activity against
Gram-positive bacteria, including Streptococcus pneumoniae, and
prolonged serum half-lives that permit once-daily dosing. Although
gemifloxacin (SB-265805) and other new quinolones have good activity against C.
pneumoniae in vitro, practically all published treatment studies have relied
on serological diagnosis. Consequently, the microbiological efficacy
of these agents in human infection has not been assessed. This paper
reviews what is known to date of the in vivo microbiological efficacy of
the quinolones against C. pneumoniae, and demonstrates the importance
of assessing this parameter when evaluating the clinical utility of
these agents in C. pneumoniae infection.
1410. Hendrickson RC. Douglass JF. Reynolds LD. McNeill PD. Carter D. Reed SG. Houghton RL. Mass spectrometric identification of mtb81, a novel serological marker for tuberculosis. Journal of Clinical Microbiology. 38(6):2354-61, 2000 Jun.
Abstract
We have used serological proteome analysis
in conjunction with tandem mass spectrometry to identify and sequence a
novel protein, Mtb81, which may be useful for the diagnosis of tuberculosis
(TB), especially for patients coinfected with human immunodeficiency virus
(HIV). Recombinant Mtb81 was tested by an enzyme-linked immunosorbent
assay to detect antibodies in 25 of 27 TB patients (92%) seropositive for HIV
as well as in 38 of 67 individuals (57%) who were TB positive
alone. No reactivity was observed in 11 of 11 individuals (100%) who were HIV
seropositive alone. In addition, neither sera from purified protein
derivative (PPD)-negative (0 of 29) nor sera from healthy (0 of 45) blood
donors tested positive with Mtb81. Only 2 of 57 of PPD-positive
individuals tested positive with Mtb81. Sera from individuals with
smear-positive TB and seropositive for HIV but who had tested
negative for TB in the 38-kDa antigen immunodiagnostic assay were also tested for
reactivity against Mtb81, as were sera from individuals with lung cancer
and pneumonia. Mtb81 reacted with 26 of 37 HIV(+) TB(+) sera (70%) in
this group, compared to 2 of 37 (5%) that reacted with the 38-kDa antigen.
Together, these results demonstrate that Mtb81 may be a promising complementary antigen
for the serodiagnosis of TB.
1411. Hwang
JH. Lee KS. Rhee CH. Recent advances in radiology of the interstitial lung disease. [Review] [46 refs] Current
Opinion in Pulmonary Medicine. 4(5):281-7,
1998 Sep.
Abstract
Idiopathic interstitial pneumonias are
currently classified into four categories of disease: usual, desquamative,
and acute interstitial pneumonia, and nonspecific interstitial
pneumonia and fibrosis. Usual interstitial pneumonia appears on high-resolution CT (HRCT) as patchy
subpleural areas of ground-glass opacity, irregular lines, and
honeycombing. Desquamative interstitial
pneumonia presents as patchy subpleural areas of ground-glass opacity in
middle and lower lung zones. Acute interstitial pneumonia presents as
extensive bilateral airspace consolidation and patchy or diffuse
bilateral areas of ground-glass opacity. Nonspecific interstitial pneumonia
and fibrosis appears as patchy or diffuse areas of ground-glass opacity
with associated areas of consolidation and irregular lines. In a
subset of patients with diffuse lung disease (especially in those with
chronic interstitial lung disease), accurate diagnosis can be made with HRCT
findings only, without surgical biopsy. However, HRCT provides a lower level
of confidence in the diagnosis of acute or subacute interstitial
lung disease such as infection, diffuse alveolar damage, drug reaction, or hemorrhage.
Additional expiratory HRCT scans and scans
with patients prone help to narrow the differential diagnosis among
various diseases and help diagnose or exclude subtle disease in the posterior
part of the lung, respectively. HRCT provides a reproducible method for
evaluating the global extent of disease. It also discriminates between
fibrotic and reversible inflammatory diseases. [References: 46]
1412. Jacobs JA. De Brauwer EI. Cornelissen EI. Drent M. Accuracy and precision of quantitative calibrated loops in transfer of bronchoalveolar lavage fluid. Journal of Clinical Microbiology. 38(6):2117-21, 2000 Jun.
Abstract
Quantitative cultures of bronchoalveolar lavage (BAL) fluid are important in the diagnosis of ventilator-associated pneumonia, and calibrated loops are commonly used to set up these cultures. In this study, the performances of calibrated 0.010- and 0.001-ml loops in the transfer of BAL fluid were determined. Five loops of one lot from seven manufacturers were tested. Calibrations were performed by the gravimetric method (0.010-ml loops) and the colorimetric method (0.001-ml loops). Most of the 0.010-ml loops displayed a precision that was less than 10%, but six of them showed very poor accuracies as they transferred a deficiency (nichrome loops) or an excess (disposable loops) of BAL fluid that exceeded +/-10%. The mean maximum and minimum BAL fluid volumes delivered by the 0.010-ml loops differed by a factor 3. The 0.001-ml loops displayed acceptable precision. Five of them showed inaccuracies of </=+/-10%, and mean maximum and minimum BAL fluid volumes had a range of a factor of 2. For all loops, the volumes of BAL fluid sampled were larger than the volumes of reagent-grade water sampled. Results of the colony counting experiments confirmed these findings and revealed a high intra-assay variability for the 0.001-ml loops. We conclude that, when BAL fluid samples are cultured with calibrated loops, (i) proper verification of the calibration of these loops is mandatory, (ii) calibrations should be performed with BAL fluid as the test solution, and (iii) borderline quantitative culture results should be interpreted with knowledge of the inaccuracy values of these loops.
1413. Jasmer RM. Edinburgh KJ. Thompson A. Gotway MB. Creasman JM. Webb WR. Huang L. Clinical and radiographic predictors of the etiology of pulmonary nodules in HIV-infected patients. Chest. 117(4):1023-30, 2000 Apr.
Abstract
STUDY OBJECTIVES: To determine the etiology and the clinical and radiographic predictors of the etiology of pulmonary nodules in a group of HIV-infected patients. DESIGN: Retrospective analysis. SETTING: A large urban hospital in San Francisco, CA. PATIENTS: HIV-infected patients evaluated at San Francisco General Hospital from June 1, 1993, through December 31, 1997, having one or more pulmonary nodules on chest CT. Main outcome measures: Three physicians reviewed medical records for clinical data and final diagnoses. Three chest radiologists blinded to clinical data reviewed chest CTs. Univariate and multivariate analyses were performed to determine clinical and radiographic predictors of having an opportunistic infection and the specific diagnoses of bacterial pneumonia and tuberculosis. RESULTS: Eighty seven of 242 patients (36%) had one or more pulmonary nodules on chest CT. Among these 87 patients, opportunistic infections were the underlying etiology in 57 patients; bacterial pneumonia (30 patients) and tuberculosis (14 patients) were the most common infections identified. Multivariate analysis identified fever, cough, and size of nodules < 1 cm on chest CT as independent predictors of having an opportunistic infection. Furthermore, a history of bacterial pneumonia, symptoms for 1 to 7 days, and size of nodules < 1 cm on CT independently predicted a diagnosis of bacterial pneumonia; a history of homelessness, weight loss, and lymphadenopathy on CT independently predicted a diagnosis of tuberculosis. CONCLUSIONS: In HIV-infected patients having one or more pulmonary nodules on chest CT scan, opportunistic infections are the most common cause. Specific clinical and radiographic features can suggest particular opportunistic infections.
1414. Jha R. Narayan G. Jaleel MA. Sinha S. Bhaskar V. Kashyap G. Rayudu BR. Prasad KN. Pulmonary infections after kidney transplantation. Journal of the Association of Physicians of India. 47(8):779-83, 1999 Aug.
Abstract
OBJECTIVE: To retrospectively analyse the epidemiology, aetiology, temporal profile and outcome of lung infection following kidney transplantation. METHODS: Out of 142 consecutive renal transplant (RT) recipients who underwent live donor transplantation from June, 1990 to May, 1998, 43 (33%) had serious infection requiring hospitalisation of which 27 were pulmonary. All such pneumonia were included for retrospective analysis. All had a minimum follow up of six months (if alive) and were on triple drug immunosuppression. All had detailed and appropriate investigations for definitive diagnosis. RESULTS: The aetiological agents were Gram negative bacterial infection (2), Gram positive bacterial infection (1), nocardia (2), tuberculosis (10), aspergillosis (2), mixed bacterial and fungal infection (4), Pneumocystis (2) and unconfirmed (4). Four patients had pneumonia because of probable nosocomial exposure. Radiologically lobar/segmental pneumonia was observed in five, nodular lesion six, reticulonodular lesion eight, patchy consolidation five and pleural effusion three. Nodular pneumonias were due to aspergillosis or nocardiosis. Four patients developed secondary cavitation. Pulmonary infections were significantly associated with leucopenia (8/27) (p < 0.01) but not with renal dysfunction (creat > 2 mg%), diabetes, old age or additional immunosuppression (p > 0.05). There were 11 deaths. Mortality was related to failure to reach diagnosis (3) and delayed institution of therapy (6 patients). Pneumonia within first six months had a higher mortality (9/16) compared to late pneumonia (2/11). Immunomodulating virus (CMV 4, HEP B 2) was present in six patients of whom four succumbed. CONCLUSION: Pulmonary infection is a common and serious post-transplant infection requiring hospitalisation, is associated with high mortality. Patients with leucopenia are predisposed to these infections. Prophylaxis for Pneumocystis, Nocardia and tuberculosis needs strong consideration to reduce mortality of such infection. Nosocomial exposure risk needs careful consideration in outbreaks of opportunistic infection.
1415. Kabra SK. Kabra M. Ghosh M. Verma IC. Cystic fibrosis--an Indian perspective on recent advances in diagnosis and management. [Review] [49 refs] Indian Journal of Pediatrics. 63(2):189-98, 1996 Mar-Apr.
Abstract
Cystic fibrosis (CF) is a common inherited disorder in caucasians. The estimated incidence of CF in Asians varies from 1:10,000 to 1:12,000. Indian data is restricted to few case reports. The gene for CF is located on the long arm of chromosome 7 at position 7q13. There are more than 300 identified mutations in CF. The basic defect in CF is a mutational change in the gene for chloride conductance channel. Failure of chloride conductance by epithelial cells leads to dehydration of secretions that are too viscid and difficult to clear. The disease is characterized by abnormal secretions in the respiratory, gastrointestinal and reproductive tract and sweat glands. The common clinical manifestations include meconium ileus in neonatal period, recurrent lower respiratory tract infections (pseudomonas pneumonia, bronchiectasis), steatorrhoea, azoospermia, and in late stages hepatobiliary and endocrine pancreatic dysfunctions. The diagnosis of disease is established by clinical criteria and sweat chloride concentration more than 60 mEq/L. Facilities for DNA diagnosis of common CF mutations are now available in India. The treatment of CF includes early diagnosis, daily clearance of respiratory passages, appropriate antibiotic therapy, aerosolised recombinant human DNase and antibiotics, and nutritional supplementation. The latter include changes in diet composition, pancreatic enzyme supplementation and vitamins and trace mineral supplementation. Gene therapy for the pulmonary manifestations is being tried in a number of centres abroad. Other considerations include heart lung transplantation and ameloride inhalation therapy.
1416. Khare MD. Sharland M. Pulmonary manifestations of pediatric HIV infection. [Review] [26 refs] Indian Journal of Pediatrics. 66(6):895-904, 1999 Nov-Dec.
Abstract
Vertically acquired HIV infection is
becoming increasingly common in India. The main clinical manifestations of
HIV in childhood are growth failure, lymphadenopathy, chronic cough and
fever, recurrent pulmonary infections, and persistent diarrhoea. Pulmonary disease is the major cause
of morbidity and mortality in pediatric
AIDS, manifesting itself in more than 80% of cases. The most common causes
are Pneumocystis carinii pneumonia (PCP), lymphocytic interstitial
pneumonitis (LIP), recurrent bacterial infections which include bacterial
pneumonia and tuberculosis. The commonest AIDS diagnosis in infancy is
PCP, presenting in infancy with tachypnea, hypoxia, and bilateral
opacification on chest-X-ray (CXR). Treatment is with
cotrimoxazole. LIP presents with bilateral reticulonodular shadows on CXR. It may be
asymptomatic in the earlier stages, but children develop recurrent
bacterial super infections, and can progress to bronchiectasis. LIP is a good
prognostic sign in children with HIV infection in comparison to PCP. HIV
should be considered in children with recurrent bacterial pneumonia,
particularly with a prolonged or atypical course, or a recurrence after
standard treatment. Pulmonary TB is common in children with HIV, but little data
is available to guide treatment decisions. Much can be done to
prevent PCP and bacterial infections with cotrimoxazole prophylaxis
and appropriate immunisations, which may reduce hospital admissions and
health care costs.
1417. Lakari E. Paakko P. Pietarinen-Runtti P. Kinnula VL. Manganese superoxide dismutase and catalase are coordinately expressed in the alveolar region in chronic interstitial pneumonias and granulomatous diseases of the lung. American Journal of Respiratory & Critical Care Medicine. 161(2 Pt 1):615-21, 2000 Feb.
Abstract
Free radicals have been suggested to play an important role in the pathogenesis of interstitial lung diseases, the most important of which are chronic interstitial pneumonias such as usual interstitial pneumonia (UIP) and desquamative interstitial pneumonia (DIP) and granulomatous lung diseases such as sarcoidosis. Because manganese superoxide dismutase (MnSOD) and catalase are two important intracellular antioxidant enzymes that probably play a central role in lung defense, the localization and intensity of these two enzymes were assessed by immunohistochemistry in biopsies of UIP (n = 9), DIP (n = 11), pulmonary sarcoidosis (n = 14), and extrinsic allergic alveolitis (n = 6). The mRNA of these enzymes in selected samples of bronchoalveolar lavage was assessed by Northern blotting. Catalase, but not MnSOD, was constitutively expressed, especially in type II pneumocytes of the healthy lung of nonsmoking individuals. In contrast, manganese SOD immunoreactivity was markedly upregulated in all of the interstitial lung diseases investigated, whereas no increased expression of catalase could be detected in any case. Both enzymes were expressed, especially in type II pneumocytes and alveolar macrophages of DIP and UIP, in the well-preserved areas of the lung, in the acute fibromyxoid lesions of UIP, and in the granulomas of sarcoidosis and extrinsic allergic alveolitis. The simultaneous expression of MnSOD and catalase in the alveolar region suggests their protective role against the progression of lung disease.
1418. Lange M. Community-acquired pneumonia: an approach to antimicrobial therapy. [Review] [8 refs] Allergy & Asthma Proceedings. 21(1):33-8, 2000 Jan-Feb.
Abstract
Community-acquired pneumonia (CAP), the sixth leading cause of death in the United States, has undergone significant changes in the past 30 years. In addition to the fact that it increasingly is a disease affecting the elderly and those patients with underlying comorbidities, the spectrum of microbiological agents causing pneumonia has greatly expanded and includes in addition to Streptococcus pneumoniae many other agents including Mycoplasma, Chlamydia, and respiratory viruses. A major problem encountered by the clinician facing a patient with CAP derives from the imprecise clinical presentation, which in most instances does not permit a precise diagnosis of the etiological agent. As pneumonia, if untreated, is frequently a rapidly progressive illness, the clinician usually chooses antimicrobial agents on an empirical basis. Careful attention to historical, physical, and laboratory findings, as well as age and presence of comorbidities has led to a categorization of CAP into four groupings that assist in deciding whether the patient should be hospitalized and what empirical antimicrobial regimen should be started. Careful follow-up and familiarity with the clinical pneumonic syndromes associated with different microbial agents is essential to assure a successful outcome.
1419. Leal-Noval SR. Marquez-Vacaro JA.
Garcia-Curiel A. Camacho-Larana
P. Rincon-Ferrari MD. Ordonez-Fernandez A. Flores-Cordero JM. Loscertales-Abril J. Nosocomial pneumonia in patients undergoing
heart surgery. Critical Care Medicine. 28(4):935-40, 2000 Apr.
Abstract
OBJECTIVE: To determine the risk factors
related to the presence of postsurgical nosocomial pneumonia (NP) in
patients who had undergone cardiac surgery. DESIGN: A case-control
study. SETTING: Postcardiac surgical intensive care unit at a university
center. PATIENTS: A total of 45 patients with NP and 90 control patients
collected during a 4-yr period. INTERVENTIONS: Pre-, intra-, and
postoperative factors were collected and compared between two groups of
patients (cases vs. controls) to determine their influence on the
development of NP. The diagnosis of NP was always microbiologically confirmed as
pulmonary specimen brush culture of > or =10(3) colony-forming units/mL or
positive blood culture/pleural fluid culture by the growth of identical
microorganisms isolated at the lung. For each patient diagnosed with NP, we
selected control cases at a ratio of 1:2. MEASUREMENTS AND MAIN RESULTS:
The incidence of NP was 6.5%. Multivariate analysis found a probable
association of the following variables with a greater risk for the development of NP:
reintubation (adjusted odds ratio [AOR], 62.5; 95%
confidence interval [CI], 8.1-480; p = .01); nasogastric tube (AOR, 19.7; 95% CI,
3.5-109; p = .01), transfusion of > or =4 units of blood derivatives
(AOR, 12.8; 95% CI, 2-82; p = .01) and empirical treatment with broad-spectrum antibiotics
(AOR, 6.6; 95% CI, 1.2-36.8; p = .02).
Culture results showed 13.3% of the NP to be of polymicrobial origin, whereas
77.3% of the microorganisms isolated were Gram-negative bacteria. The
mortality (51 vs. 6.7%, p < .01) and the length of stay in the intensive care
unit (25+/-14.8 days vs. 5+/-5 days, p < .01) were both greater in
patients with NP. CONCLUSIONS: We conclude that the surgical risk factors,
except the transfusion of blood derivatives, have little effect on the
development of NP. Reintubation, nasogastric tubing, previous
therapy with broad-spectrum antibiotics, and blood transfusion are
factors most likely associated with NP acquisition.
1420. McCracken GH Jr. Etiology and treatment of pneumonia. [Review] [22 refs] Pediatric Infectious Disease Journal. 19(4):373-7, 2000 Apr.
Abstract
BACKGROUND: Lower respiratory tract
infections are a common cause of morbidity among children. Among these
infections pneumonia is the most serious illness and can be difficult to
diagnose. The etiology of pneumonia is still partly unknown, primarily
because of difficulty in obtaining adequate samples and lack of
reliable diagnostic methods. ETIOLOGY OF PNEUMONIA: Streptococcus
pneumoniae is recognized as an important cause of pediatric pneumonia
regardless of age in both the inpatient and outpatient setting. In
developed countries S. pneumoniae probably accounts for 25 to 30% of cases of
pediatric community-acquired pneumonia. Viruses (mostly respiratory
syncytial virus) are responsible for approximately 20% of cases, and
Chlamydia pneumoniae and Mycoplasma pneumoniae occur commonly in older children.
FUTURE CHALLENGES: Despite the effectiveness of antimicrobial therapy,
the emergence of resistant bacterial pathogens has resulted in
increased interest in developing more effective vaccines. If conjugate pneumococcal vaccines prove effective at
eradicating carriage of pneumococci in the
nasopharynx, immunization may be an important tool against the spread of
pneumococcal disease. Future challenges include implementation of
effective intervention strategies, production of simple diagnostic tools and
development of effective vaccines.
1421. Mesquita
CT. Morandi Junior JL. Perrone FT.
Oliveira C da S. Barreira LJ. Nascimento SS. Pareto Junior
RC. Mesquita ET. Fatal pulmonary
embolism in hospitalized patients. Clinical diagnosis versus pathological
confirmation. Arquivos Brasileiros de
Cardiologia. 73(3):251-8, 1999 Sep.
Abstract
OBJECTIVE: To assess the incidence of fatal
pulmonary embolism (FPE), the accuracy of clinical diagnosis, and the
profile of patients who suffered an FPE in a tertiary University Hospital.
METHODS: Analysis of the records of 3,890 autopsies performed at the
Department of General Pathology from January 1980 to December 1990. RESULTS:
Among the 3,980 autopsies, 109 were cases of clinically suspected FPE; of
these, 28 cases of FPE were confirmed. FPE accounted for 114 deaths,
with clinical suspicion in 28 cases. The incidence of FPE was 2.86%. No
difference in sex distribution was noted. Patients in the 6th decade of
life were most affected. The following conditions-were more commonly
related to FPE: neoplasias (20%) and heart failure (18.5%). The conditions
most commonly misdiagnosed as FPE were pulmonary edema (16%), pneumonia (15%) and myocardial infarction
(10%). The clinical diagnosis of FPE showed
a sensitivity of 25.6%, a specificity of 97.9%, and an accuracy of
95.6%. CONCLUSION: The diagnosis of pulmonary embolism made on clinical
grounds still has considerable limitations.
1422. Meyer CA. White CS. Sherman KE. Diseases of the hepatopulmonary axis. Radiographics. 20(3):687-98, 2000 May-Jun.
Abstract
Hepatopulmonary syndrome is the most widely
recognized of the processes associated with end-stage liver disease.
Chronic liver dysfunction is associated with pulmonary manifestations due
to alterations in the production or clearance of circulating cytokines and other mediators.
Hepatopulmonary syndrome
results in hypoxemia due to pulmonary vasodilatation with significant
arteriovenous shunting and ventilation-perfusion mismatch. Hepatic hydrothorax may develop in
patients with cirrhosis and ascites. Rarely,
pulmonary hypertension occurs in the setting of portal hypertension. A
second group of disorders may primarily affect the lungs and liver (the
hepatopulmonary axis). Among these are the congenital conditions alpha(1)-antitrypsin deficiency and
cystic fibrosis. Autoimmune liver disease
may be associated with lymphocytic interstitial pneumonitis,
fibrosing alveolitis, intrapulmonary granulomas, and bronchiolitis obliterans
with organizing pneumonia. Sarcoidosis affects the lung and liver in up
to 70% of patients. Medications such as amiodarone can result in
a characteristic radiologic appearance of pulmonary and hepatic toxic
effects. Knowledge of these associations will assist the radiologist in forming a meaningful
differential diagnosis and may influence
treatment decisions.
1423. Miller
RF. Howling SJ. Reid AJ.
Shaw PJ. Pleural effusions in patients with AIDS. Sexually Transmitted
Infections. 76(2):122-5, 2000 Apr.
Abstract
OBJECTIVE: To describe the range of pathology causing pleural effusions in HIV infected patients with acute respiratory episodes and to attempt to identify whether any associated radiological abnormalities enabled aetiological discrimination. METHODS: Prospective study of chest radiographs of 58 consecutive HIV infected patients with pleural effusion and their microbiological, cytological, and histopathological diagnoses. RESULTS: A specific diagnosis was made in all cases. Diagnoses were Kaposi's sarcoma, 19 patients; para-pneumonic effusion, 16 patients; tuberculosis, eight patients; Pneumocystis carinii pneumonia, six patients; lymphoma, four patients; pulmonary embolus, two patients; and heart failure, aspergillus/leishmaniasis, and Cryptococcus neoformans, one case each. Most effusions (50/58) were small. Bilateral effusions were commoner in Kaposi's sarcoma (12/19) and lymphoma (3/4) than in para-pneumonic effusion (3/16). Concomitant interstitial parenchymal shadowing did not aid discrimination. A combination of bilateral effusions, focal air space consolidation, intrapulmonary nodules, and/or hilar lymphadenopathy suggests Kaposi's sarcoma. Unilateral effusion with focal air space consolidation suggests para-pneumonic effusion if intrapulmonary nodules are absent: if miliary nodules and/or mediastinal lymphadenopathy are detected, this suggests tuberculosis. CONCLUSIONS: A wide variety of infectious and malignant conditions cause pleural effusions in HIV infected patients, the most common cause in this group was Kaposi's sarcoma. The presence of additional radiological abnormalities such as focal air space consolidation, intrapulmonary nodules, and mediastinal lymphadenopathy aids aetiological discrimination.
1424. Nakajima H. Harigai M. Hara M. Hakoda M. Tokuda H. Sakai F. Kamatani N. Kashiwazaki S. KL-6 as a novel serum marker for interstitial pneumonia associated with collagen diseases. Journal of Rheumatology. 27(5):1164-70, 2000 May.
Abstract
OBJECTIVE: To investigate the diagnostic value of the serum concentrations of KL-6, a mucinous glycoprotein expressed on type II pneumocytes, for interstitial pneumonia (IP) in various collagen diseases. METHODS: Serum KL-6 levels were measured by ELISA. RESULTS: The mean values and the positive rates of serum KL-6 levels for patients with rheumatoid arthritis, systemic sclerosis, or polymyositis/dermatomyositis with IP were significantly higher than those without IP. Sensitivity, specificity, positive and negative predictive values of serum KL-6 level for IP associated with collagen diseases were 60.7, 98.9, 97.4, and 77.1%, respectively. The mean serum KL-6 level of patients with active IP was significantly (p = 0.0001) higher than that of patients with inactive IP. Serum KL-6 levels increased with the deterioration of IP, while the successful treatment of IP resulted in a significant decrease of these levels. CONCLUSION: Serum KL-6 concentration levels are a useful marker for diagnosis and evaluation of the disease activity of IP associated with collagen diseases.
1425. Okano M. Yamada M. Ohtsu M. Kawamura N. Sakiyama Y. Aoi K. Gandoh S. Fujita M. Kobayashi K. Successful treatment with methylprednisolone pulse therapy for a life-threatening pulmonary insufficiency in a patient with chronic granulomatous disease following pulmonary invasive aspergillosis and Burkholderia cepacia infection. Respiration. 66(6):551-4, 1999 Nov-Dec.
Abstract
A 14-year-old boy with X-linked chronic granulomatous disease developed severe invasive pulmonary aspergillosis. He was treated with itraconazole and amphotericin B. owever, he deteriorated with progressive pulmonary lesions. Burkholderia cepacia was isolated from his bronchoalveolar lavage. Finally, he was given granulocyte transfusions. Following this procedure, his condition rapidly worsened leading to respiratory failure. His lung biopsy demonstrated organizing pneumonia at his right middle lobe. Then, a methylprednisolone pulse therapy was initiated together with the administration of appropriate antibiotics and adequate amounts of amphotericin B. Dramatically, his condition improved. Therefore, a methylprednisolone pulse therapy with appropriate antimicrobial drugs seems to be beneficial for severe pulmonary insufficiency in this type of patients. Copyright Copyright 1999 S. Karger AG, Basel
1426. Osann
KE. Lowery JT. Schell MJ. Small cell lung cancer in women:
risk associated with smoking, prior respiratory disease, and occupation. Lung
Cancer. 28(1):1-10, 2000 Apr.
Abstract
Small cell carcinoma of the lung (SCLC)
occurs most frequently in heavy smokers, yet exhibits a lesser predominance
among men than other smoking-associated lung cancers. Incidence
rates have increased more rapidly in women than men and at a faster
rate among women than other cell types. To investigate the importance of
smoking and other risk factors, a case-control study of SCLC in women was
conducted. A total of 98 women with primary SCLC and 204 healthy controls,
identified by random-digit dialing and frequency matched for age,
completed telephone interviews. Data collected include demographics, medical
history, family cancer history, residence history, and lifetime smoking habits. Odds ratios
(ORs) and 95% confidence intervals (95% CI) were calculated using logistic
regression analysis. Risk for small cell
carcinoma in women is strongly associated with current use of cigarettes.
Ninety-seven of 98 cases had smoked cigarettes; 79% of cases were current
smokers and 20% were former smokers at the time of diagnosis compared to
13% current and 34% former smokers among controls. The ORs associated
with smoking are 108.7 (95% CI 14.8-801) for ever-use of cigarettes, 278.9
(95% CI 37.0-2102) for current smoking, and 31.5 (95% CI 4. 1-241) for
former smoking. Risk increases steeply with pack-years of smoking and
decreases with duration of smoking cessation. After adjusting for age,
education, and lifetime smoking history, medical history of
physician-diagnosed respiratory disease including chronic bronchitis, emphysema,
pneumonia, tuberculosis, asthma, and hay fever is not associated with a
significant increase in lung cancer risk. Employment in blue collar, service, or
other high risk occupations is associated with a two to three-fold non-significant increase in risk
for small cell carcinoma after adjusting for
smoking.
1427. Overweg
K. Kerr A. Sluijter M. Jackson
MH. Mitchell TJ. de Jong AP.
de Groot R. Hermans PW. The
putative proteinase maturation protein A of Streptococcus pneumoniae is a
conserved surface protein with potential to elicit protective immune responses. Infection & Immunity. 68(7):4180-8, 2000 Jul.
Abstract
Surface-exposed proteins often play an important role in the interaction between pathogenic bacteria and their host. We isolated a pool of hydrophobic, surface-associated proteins of Streptococcus pneumoniae. The opsonophagocytic activity of hyperimmune serum raised against this protein fraction was high and species specific. Moreover, the opsonophagocytic activity was independent of the capsular type and chromosomal genotype of the pneumococcus. Since the opsonophagocytic activity is presumed to correlate with in vivo protection, these data indicate that the protein fraction has the potential to elicit species-specific immune protection with cross-protection against various pneumococcal strains. Individual proteins in the extract were purified by two-dimensional gel electrophoresis. Antibodies raised against three distinct proteins contributed to the opsonophagocytic activity of the serum. The proteins were identified by mass spectrometry and N-terminal amino acid sequencing. Two proteins were the previously characterized pneumococcal surface protein A and oligopeptide-binding lipoprotein AmiA. The third protein was the recently identified putative proteinase maturation protein A (PpmA), which showed homology to members of the family of peptidyl-prolyl cis/trans isomerases. Immunoelectron microscopy demonstrated that PpmA was associated with the pneumococcal surface. In addition, PpmA was shown to elicit species-specific opsonophagocytic antibodies that were cross-reactive with various pneumococcal strains. This antibody cross-reactivity was in line with the limited sequence variation of ppmA. The importance of PpmA in pneumococcal pathogenesis was demonstrated in a mouse pneumonia model. Pneumococcal ppmA-deficient mutants showed reduced virulence. The properties of PpmA reported here indicate its potential for inclusion in multicomponent protein vaccines.
1428. Reddy TS. Smith D. Roy TM. Primary meningococcal pneumonia in elderly patients. American Journal of the Medical Sciences. 319(4):255-7, 2000 Apr.
Abstract
Neisseria meningitidis infection in humans
usually manifests as meningitis and septicemia with skin manifestations. Infections
of the respiratory tract with N meningitidis have been
documented in the past, but often this organism is not routinely considered in the
differential diagnosis of pneumonia. The pathogenic role of N
meningitidis in lower respiratory tract infections may be underestimated
because its isolation is difficult, particularly when oropharyngeal flora are
present. We profile 2 elderly patients with primary meningococcal
pneumonia to show the importance of Gram stain and culture in early diagnosis.
These modalities helped guide treatment and prophylactic measures.
1429. Shimizu A. Tanabe O. Anzai C. Uchida K. Tada H. Yoshimura K. Detection of measles virus genome in bronchoalveolar lavage cells in a patient with measles pneumonia. European Respiratory Journal. 15(3):619-22, 2000 Mar.
Abstract
Measles is frequently complicated with
pneumonia that could be fatal in numerous occasions. However, a prompt and
precise diagnosis of measles is not easily made particularly in the early
stage of the disease, or in immunocompromised individuals because of the
lack of typical clinical features or the defect in antigen-specific antibody production. In the
present paper, we describe a 27-yr-old male
who developed fever, skin rash typical of measles, and diffuse pulmonary
infiltrates associated with respiratory failure. Infection of lung cells
with measles virus was proved by detection of viral genome ribonucleic
acid within alveolar macrophages and lymphocytes recovered by bronchoalveolar
lavage using reverse transcription-polymerase chain reaction
amplification. These techniques may offer a useful tool to make the swift
and precise diagnosis of measles pneumonia, thus allowing appropriate
therapeutic approaches to the disease.
1430. Shinefield
HR. Black S.Title Efficacy of
pneumococcal conjugate vaccines in large scale field trials. [Review] [29 refs]
Pediatric Infectious Disease Journal. 19(4):394-7, 2000 Apr.
Abstract
BACKGROUND: Each year Streptococcus
pneumoniae causes approximately 1.2 million deaths worldwide from pneumonia. In
the United States S. pneumoniae is estimated to cause 500,000
cases of pneumonia and 7 million episodes of acute otitis media annually.
CONJUGATE VACCINES: The current pneumococcal polysaccharide vaccine is ineffective in children <2 years
old and may not produce an adequate antibody
response until children reach the age of 5 years. Pneumococcal conjugate
vaccines are immunogenic after primary and booster vaccination in young
children and in children and adults with immunodeficiencies. Immunization
with conjugate vaccines also induces a strong and rapid anamnestic
response and enhanced functional activity of antibodies. Two large scale
field trials of pneumococcal conjugate vaccines were initiated in 1995, 1
in California and 1 in Finland. The California trial, involving 37,868 children, evaluated the
efficacy of a 7-valent conjugate for the
prevention of invasive pneumococcal disease and secondarily
evaluated its efficacy for acute otitis media and pneumonia. RESULTS:
Preliminary results indicate 94% efficacy against invasive pneumococcal
disease caused by serotypes included in the vaccine in fully or partially vaccinated children.
Preliminary evidence from large scale field
trials indicates that pneumococcal conjugate vaccines are
effective in reducing invasive pneumococcal disease as well as acute otitis
media and pneumonia in children and represents a significant
advance in the prevention of childhood infectious diseases.
1431. Smulian
AG. Sullivan DW. Theus SA. Immunization with recombinant
Pneumocystis carinii p55 antigen provides partial protection against infection:
characterization of epitope recognition associated with immunization. Microbes
& Infection. 2(2):127-36, 2000 Feb.
Abstract
Many therapeutic options exist for the
treatment of Pneumocystis carinii pneumonia, a common fungal opportunistic
pulmonary pathogen, but treatment is often complicated by side effects and
toxicity and, more recently, markers of drug resistance have been described. The development of
immunotherapetic modalities such as active
immunization or passive immunotherapy may play an increasing
important role in the prevention and treatment of infection. Passive
immunotherapy with polyclonal anti-P. carinii reagents, such as serum or T cells,
and monospecific reagents reactive with the major surface glycoprotein
(MSG or gpA), such as monoclonal antibodies or MSG primed T cells,
reduce the severity or eradicate infection. Active immunization
with whole P. carinii, P. carinii extracts or MSG has afforded partial
protection against the subsequent development of P. carinii pneumonia in some
animal models. Identification of additional antigens with protective
benefits will aid in the development of vaccines or other reagents.
The p55 antigen of rat-derived P. carinii is well recognized by animals
following natural exposure to the organism. This 414 amino acid residue antigen
found within the cell wall of P. carinii contains 7 repeats of a glutamic acid-rich motif in the
carboxyl portion of the molecule. Both
humoral and cellular immune responses reactive with this repeated domain
are present following natural infection while, the amino terminal portion
of the molecule is immunologically silent. In this study,
immunization with recombinant p55 elicited significant humoral and cellular
immune responses which persisted during 10 weeks of immunosupression in
corticosteroid treated rats; rp55 immunization resulted in a significant
reduction in organism burden, improved histological score, lower lung weight to body weight ratio (a
marker of infection or lung inflammation)
and improved survival (P < 0.01). Greater protection was afforded by
immunization with a peptide containing amino acid residues 1-200, than
by the entire rp55 molecule. Epitope recognition by serum from animals
immunized with rp55 differed from that of naturally exposed animals with
oligoclonal responses to residues 22-92 and residues 196-218. This
study demonstrates that protection against P. carinii can be
afforded by immunization with antigen preparations other than whole extracts of P.
carinii or the major surface antigen, MSG. This antigen moiety will
likely be most useful as a vaccine candidate in combination with other
immunogens which provide similar partial protection.
1432. Swingler
GH. Chest radiography in ambulatory children with acute lower respiratory infections: effective tuberculosis case-finding?. Annals of Tropical
Paediatrics. 20(1):11-5, 2000 Mar.
Abstract
A study was performed to determine the proportion of ambulatory children with acute lower respiratory infections in whom clinical management was changed by findings on routine chest radiography that suggested tuberculosis. The children studied were aged between 2 and 59 months and met the World Health Organization's case definition for pneumonia. They lived in an area with a very high prevalence of tuberculosis. Exclusion criteria included a cough of more than 14 days' duration and a history of a current household contact with active tuberculosis. Twelve (4.4%) of 273 children had radiological findings suggesting tuberculosis, nine of which were suspected mediastinal lymphadenopathy. Eight children were further investigated for tuberculosis: seven of them did not require treatment for tuberculosis and one was lost to follow-up. It is concluded that chest radiography in ambulatory children with acute lower respiratory infections of less than 14 days' duration and not in contact with active tuberculosis does not result in a meaningful increase in the diagnosis of tuberculosis.
1433.
Torres A. El-Ebiary M. Bronchoscopic BAL in the
diagnosis of ventilator-associated pneumonia. [Review] [0 refs] Chest. 117(4 Suppl 2):198S-202S, 2000 Apr.
1434. Tripp
RA. Jones L. Anderson LJ. Brown MP.
CD40 ligand (CD154) enhances the Th1 and antibody responses to respiratory
syncytial virus in the BALB/c mouse. Journal of Immunology. 164(11):5913-21, 2000 Jun 1.
Abstract
CD40 ligand (CD40L) is a cell surface costimulatory molecule expressed mainly by activated T cells. CD40L is critically important for T-B cell and T cell-dendritic cell interactions. CD40L expression promotes Th1 cytokine responses to protein Ags and is responsible for Ig isotype switching in B cells. Respiratory syncytial virus (RSV) is an important pathogen of young children and the elderly, which causes bronchiolitis and pneumonia. Studies of mice infected with RSV suggest that a Th2 cytokine response may be responsible for enhanced pulmonary disease. To investigate the effect CD40L has on RSV immunity, mice were infected simultaneously with RSV and either an empty control adenovirus vector or one expressing CD40L or were coimmunized with plasmid DNA vectors expressing CD40L and RSV F and/or G proteins and subsequently challenged with RSV. The kinetics of the intracellular and secreted cytokine responses, the cytotoxic T lymphocyte precursor frequency, NO levels in lung lavage, rates of virus clearance, and anti-RSV Ab titers were determined. These studies show that coincident expression of CD40L enhances the Th1 (IL-2 and IFN-gamma) cytokine responses, increases the expression of TNF-alpha and NO, accelerates virus clearance, and increases the anti-F and anti-G Ab responses. These data suggest that CD40L may have the adjuvant properties needed to optimize the safety and efficacy of RSV vaccines.
1435. Voloudaki AE. Kofteridis DP. Tritou IN. Gourtsoyiannis NC. Tselentis YJ. Gikas AI. Q fever pneumonia: CT findings. Radiology. 215(3):880-3, 2000 Jun.
Abstract
PURPOSE: To evaluate the computed tomographic (CT) features of Q fever pneumonia. MATERIALS AND METHODS: The authors retrospectively reviewed the chest radiographs and CT scans obtained in 12 patients, who were selected on the basis of chest CT availability from a group of patients with a definite diagnosis of acute Q fever infection during an 8.5-year period. RESULTS: In all cases, CT depicted lesions indicative of airspace involvement, which was expressed as lobar (n = 3), segmental (n = 3), patchy (n = 3), or a combination of these patterns (n = 3). Involvement of more than one lobe was observed in seven (58%) patients. In one patient with multiple patchy areas of consolidation, nodular lesions with a vascular connection and a halo of ground-glass opacity, which were suggestive of an angioinvasive process, were demonstrated. In addition, CT performed in a patient with acute Coxiella burnetii infection who abused alcohol revealed necrotizing pneumonia. Pleural effusions were seen at both CT and radiography in three patients, and mild lymph node enlargement in isolated regions was seen at CT in four patients. Chest radiography was less accurate than CT in the detection of segmental and patchy areas of consolidation. CONCLUSION: The typical CT findings of Q fever pneumonia consisted mainly of multilobar airspace consolidation. A nodular pattern accompanied by a halo of ground-glass opacification and vessel connection, and necrotizing pneumonia in the setting of impaired immunity were less frequent.
1436. Weinstein M. Index of suspicion. Case: 3. Diagnosis: lipoid pneumonia. Pediatrics in Review. 21(5):173, 176-7, 2000 May.
1439.
Wunderink RG. Radiologic diagnosis of
ventilator-associated pneumonia.
Chest. 117(4 Suppl 2):188S-190S,
2000 Apr.
1438. Wunderink RG. Pharmacoeconomics of pneumonia. [Review] [38 refs] American Journal of Surgery. 179(2A Suppl):51S-57S, 2000 Feb.
Abstract
Because diagnosis and treatment are so intimately linked, the pharmacoeconomics of treatment of ventilator-associated pneumonia (VAP) is impossible to discuss without discussing the cost-effectiveness of VAP diagnosis. The cost of VAP treatment is more complex than simply drug acquisition and administration costs. The critical factor in cost-effective therapy is the avoidance of inappropriate or ineffective therapy. The second most important benefit of a more accurate diagnostic strategy, such as the use of quantitative cultures, is the ability either to stop or to withhold antibiotics if the quantitative culture is negative. Therefore, the benefit of any diagnostic strategy must be evaluated principally from the aspect of these resultant changes in management. Reassurance or concern about an alternative site of infection or cause of fever will also add to the benefit or cost of more accurate diagnosis of VAP. The baseline antibiotic treatment strategy of the specific intensive care unit (ICU) will determine, to a large degree, the cost of antibiotics and the efficacy of empiric regimens. In the final analysis, pharmacy costs and cost of diagnostic testing for VAP must be based on outcome analysis, including comparison of the more expensive aspects of care, such as mortality, length of mechanical ventilation, and length of ICU stay.
1437.
Wunderink RG.
Clinical criteria in the diagnosis of ventilator-associated pneumonia.
Chest. 117(4 Suppl 2):191S-194S, 2000
Apr.
1440. Zedtwitz-Liebenstein
K. Podesser B. Peck-Radosavljevic M. Graninger W. Intestinal tuberculosis presenting as fever of unknown origin in
a heart transplant patient.
Infection. 27(4-5):289-90, 1999.
Abstract
Patients undergoing transplantation have an
increased risk of developing infections such as tuberculosis,
Pneumocystis carinii pneumonia, Candida infections or cytomegalovirus infections
because of their immunosuppressive therapy with cyclosporin A, azathioprine and steroids.
Mycobacterial infection is well recognized
as a complication in the immunocompromised host but diagnosis and
therapy are very difficult.
1826.
Authors
Adegbola RA. Obaro SK.
Title
Diagnosis of childhood pneumonia in the tropics. Annals of Tropical Medicine & Parasitology. 94(3):197-207, 2000 Apr.
Abstract
Recent global estimates indicate that there
are 10 million deaths annually of children aged < 5 years and that 99%
of these deaths occur in developing countries, with 70% caused by
infections. Pneumonia is the leading cause of the infection-attributable
mortality in this age-group, accounting for > 2 million of the deaths.
These deaths are potentially preventable if appropriate clinical and laboratory tools are in place to
facilitate early detection of the pneumonia,
identification of the pathogen involved, and institution of
appropriate therapy or, even better, implementation of appropriate vaccination
schedules. The currently available tools for the diagnosis of acute,
lower-respiratory-tract infections in children have low sensitivity
and are, in any case, grossly underutilized. Consequently, there is a
great shortage of the data necessary for implementing potentially
effective, intervention measures. This review is of the common aetiological
agents of childhood pneumonia in the tropics and of the clinical and
laboratory techniques currently available for routine diagnosis. Although
there are newer and more sensitive diagnostic tools, they are
expensive and are not likely to be
within reach of most developing countries in
the tropics. There is, however, considerable scope to improve the
use of the cheaper techniques, and so facilitate the development and
implementation of effective control measures. [References: 40]
1827.
Amundsen T.
Torheim G. Waage A. Bjermer L.
Steen PA. Haraldseth O. Perfusion magnetic resonance imaging of the
lung: characterization of pneumonia and chronic obstructive pulmonary
disease. A feasibility study. Journal of Magnetic Resonance Imaging. 12(2):224-31, 2000 Aug.
Abstract
Perfusion magnetic resonance (MR) imaging is
a promising new method for detection of perfusion defects in the
diagnosis of pulmonary embolism. In the present study we evaluated the
first-pass characteristics of perfusion MR imaging in patients with pneumonia or
chronic obstructive pulmonary disease (COPD), frequent differential
diagnoses to pulmonary embolism. Dynamic contrast-enhanced MR images of 12
patients with acute pneumonia and 13 patients with exacerbation of COPD
were acquired in both the coronal and transaxial planes (an inversion
recovery prepared gradient-echo sequence using 0.05 mmol/kg
gadodiamide/injection). The MR images and the signal intensity (SI) versus
time curves were characterized for each disease entity and compared with
normal lung and the findings in pulmonary embolism from our previous study.
The perfusion MR images of pneumonia showed distinct regions of
increased contrast enhancement; in COPD with signs of emphysema (11 of the 13
COPD patients), the images showed a coarse pattern of reduced contrast
enhancement. The SI versus time curves of pneumonia, COPD with signs of
emphysema, and normal lung were statistically different, the respective
pooled SI values (+/-95% CI) being as follows: mean baseline SI, 20.7
(1.1), 7.4 (0.4), and 8.5 (0.3); mean peak SI, no peak, 12.9 (1.5), and 27
(4.6); and mean max change of SI in percent, 110 (27), 79 (22), and 205 (52).
Perfusion MR imaging of pneumonia and COPD with signs of emphysema
showed first-pass that were characteristics promising for diagnostic
use. Both the MR images and the SI versus time curves were different from
the perfusion characteristics in normal lung and pulmonary embolism shown
previously.
1828. Aouifi A.
Piriou V. Bastien O. Blanc P.
Bouvier H. Evans R. Celard M.
Vandenesch F. Rousson R. Lehot JJ. Usefulness of procalcitonin for diagnosis of
infection in cardiac surgical patients. Critical Care Medicine. 28(9):3171-6, 2000 Sep.
Abstract
OBJECTIVE: To determine the value of procalcitonin
(PCT) as a marker of postoperative infection after cardiac
surgery. DESIGN: A prospective single institution three phase study.
SETTING: University cardiac surgical intensive care unit (31 beds). PATIENTS: Phase 1: To determine the normal
perioperative kinetics of PCT, 20
consecutive patients undergoing elective cardiac surgery with cardiopulmonary bypass
were included. Phase 2: To determine whether PCT may be useful for
diagnosis of postoperative infection, 97 consecutive patients with
suspected infection were included. Phase 3: To determine the ability of PCT to
differentiate patients with septic shock from those with cardiogenic
shock, 26 patients with postoperative circulatory failure were
compared. MEASUREMENTS AND MAIN RESULTS: Phase 1: Serum samples were drawn
for PCT determination after induction of anesthesia (baseline), at the
end of surgery, and daily until postoperative day (POD) 8. Baseline serum
PCT concentration was 0.17 +/- 0.08 ng/mL (mean +/- SD). Serum PCT
increased after cardiac surgery with a peak on POD 1 (1.08 +/- 1.36). Serum PCT
returned to normal range on POD 3 and remained stable thereafter. Phase 2: In
patients with suspected infection, serum PCT was measured at the
same time of C-reactive protein (CRP) and bacteriologic samples. Among the
97 included patients, 54 were infected with pneumonia (n = 17), bacteremia
(n = 16), mediastinitis (n = 9), or septic shock (n = 12). In the 43 remaining patients, infection was
excluded by microbiological examinations. In
noninfected patients, serum PCT concentration was 0.41 +/- 0.36 ng/mL
(range, 0.08-1.67 ng/mL). Serum PCT concentration was markedly higher in
patients with septic shock (96.98 +/- 119.61 ng/mL). Moderate increase in
serum PCT concentration occurred during pneumonia (4.85 +/-3.31 ng/mL) and
bacteremia (3.57 +/- 2.98 ng/mL). Serum PCT concentration remained low
during mediastinitis (0.80 +/- 0.58 ng/mL). Five patients with
mediastinitis, two patients with bacteremia, and one patient with pneumonia
had serum PCT concentrations of <1 ng/mL. These eight patients were administered antibiotics previously
and serum PCT was measured during a
therapeutic antibiotic window. For prediction of infection by PCT, the best cutoff
value was 1 ng/mL, with sensitivity 85%, specificity 95%, positive
predictive value 96%, and negative predictive value 84%. Serum CRP was
high in all patients without intergroup difference. For prediction of
infection by CRP, a value of 50 mg/L was sensitive (84%) but poorly specific
(40%). Comparing the area under the receiver operating characteristic
curves, PCT was better than CRP for diagnosis of postoperative sepsis (0.82 for PCT vs. 0.68 for CRP).
Phase 3: Serum PCT concentration was
significantly higher in patients with septic shock than in those with cardiogenic
shock (96.98 +/- 119.61 ng/mL vs. 11.30 +/- 12.3 ng/mL). For
discrimination between septic and cardiogenic shock, the best cutoff value was
10 ng/mL, with sensitivity of 100% and specificity of 62%. CONCLUSION:
Cardiac surgery with cardiopulmonary bypass influences serum PCT
concentration with a peak on
1829. Arancibia F. Ewig S. Martinez JA. Ruiz M.
Bauer T. Marcos MA. Mensa J. Torres A.
Antimicrobial treatment failures in patients
with community-acquired pneumonia: causes and prognostic
implications. American Journal of Respiratory & Critical Care Medicine. 162(1):154-60,
2000 Jul.
Abstract
The aim of the study was to determine the
causes and prognostic implications of antimicrobial treatment
failures in patients with nonresponding and progressive life-threatening,
community-acquired pneumonia. Forty-nine patients hospitalized
with a presumptive diagnosis of community-acquired pneumonia during a
16-mo period, failure to respond to antimicrobial treatment, and documented
repeated microbial investigation >/= 72 h after initiation
of in-hospital antimicrobial treatment were recorded. A definite etiology
of treatment failure could be established in 32 of 49 (65%) patients, and
nine additional patients (18%) had a probable etiology. Treatment failures were
mainly infectious in origin and included primary, persistent, and
nosocomial infections (n = 10 [19%], 13 [24%], and 11 [20%] of causes,
respectively). Definite but not probable persistent infections were mostly
due to microbial resistance to the administered initial empiric
antimicrobial treatment. Nosocomial infections were particularly frequent in
patients with progressive pneumonia. Definite persistent infections
and nosocomial infections had the highest associated mortality rates (75
and 88%, respectively). Nosocomial pneumonia was the only cause of treatment failure independently
associated with death in multivariate
analysis (RR, 16.7; 95% CI, 1.4 to 194.9; p = 0.03). We conclude that the
detection of microbial resistance and the diagnosis of nosocomial pneumonia
are the two major challenges in hospitalized patients with
community-acquired pneumonia who do not respond to initial antimicrobial treatment. In order
to establish these potentially life-threatening etiologies, a
regular microbial reinvestigation seems mandatory for all
patients presenting with antimicrobial treatment failures.
1830. Caksen H. Ozturk MK. Uzum K. Yuksel S. Ustunbas HB. Pulmonary complications in patients with staphylococcal sepsis. Pediatrics International. 42(3):268-71, 2000 Jun.
Abstract
BACKGROUND: The aim of the present study was to determine the pulmonary findings in patients with sepsis caused by Staphylococcus aureus. METHODS: The clinical and laboratory findings of 32 cases (82%) of pulmonary involvement (secondary pneumonia) of 39 patients with sepsis caused by S. aureus were studied retrospectively. The criteria for the diagnosis of sepsis were clinical evidence of infection plus hyperthermia/hypothermia, tachycardia, tachypnea and white blood cell abnormalities. Secondary pneumonia was diagnosed in patients who presented with staphylococcal disease at one or more non-pulmonary sites and who developed radiologic evidence of pulmonary involvement during the course of illness. RESULTS: Of the 32 patients, 23 were male and nine were female; the male to female ratio was 2.5/1. The ages of the patients ranged from 2 months to 14 years (7.87 +/- 4.71 years). Bronchopneumonic infiltration was bilateral in 18 patients and unilateral in 14 patients (20 patients (62.5%) had lobar consolidation). Pleurisy was noted in 12 (37.5%) patients; it was on the right side in five patients, on the left in five patients and bilateral in two patients. In contrast, pneumatocele and pneumothorax were observed in seven (21.9%)and four (12.5%) patients, respectively. Closed chest tubes were placed through a closed thoracotomy in five children who developed dyspnea, orthopnea with imminent respiratory failure and mediastinal shift. As well as the pulmonary involvement, arthritis was noted in 1 3 patients, osteomyelitis in 11 patients, rash in six patients, pericarditis in five patients and renal failure in one patient. Staphylococcus aureus was isolated from blood culture in all except for seven cases. While S. aureus was isolated from blood culture in all of the 12 patients with leurisy, it was isolated from pleural fluid in only two (16.6%) patients. Six of 32 patients died; the mortality rate was 18.75%. CONCLUSIONS: It was found that the rate of pulmonary involvement was as high as 82% in sepsis caused by S. aureus, and the pulmonary findings, including bronchopneumonic infiltration and lobar consolidation, were frequently seen in S. aureus pneumonia, causing a mortality rate of 18.75%.
1831.
Chapman SW.
Bradsher RW JR. Campbell GD
Jr. Pappas PG. Kauffman CA. Practice guidelines for the management of
patients with blastomycosis. Infectious diseases society of America. Clinical Infectious Diseases. 30(4):679-83, 2000 Apr. Abstract
Guidelines for the treatment of
blastomycosis are presented; these guidelines are the consensus opinion of an
expert panel representing the National Institute of Allergy and Infectious
Diseases Mycoses Study Group and the Infectious Diseases Society of
America. The clinical spectrum of blastomycosis is varied, including asymptomatic infection, acute or
chronic pneumonia, and extrapulmonary
disease. Most patients with blastomycosis will require therapy.
Spontaneous cures may occur in some immunocompetent individuals with acute
pulmonary blastomycosis. Thus, in a case of disease limited to the lungs, cure
may have occurred before the diagnosis is made and without treatment;
such a patient should be followed up closely for evidence of disease
progression or dissemination. In contrast, all patients who are
immunocompromised, have progressive pulmonary disease, or have extrapulmonary
disease must be treated. Treatment options include amphotericin B,
ketoconazole, itraconazole, and fluconazole. Amphotericin B is the treatment
of choice for patients who are immunocompromised, have life-threatening
or central nervous system (CNS) disease, or for whom azole treatment
has failed. In addition, amphotericin B is the only drug approved for
treating blastomycosis in pregnant women. The azoles are an equally effective and less toxic
alternative to amphotericin B for treating
immunocompetent patients with mild to moderate pulmonary or extrapulmonary
disease, excluding CNS disease. Although there are no comparative
trials, itraconazole appears more efficacious than either ketoconazole or
fluconazole. Thus, itraconazole is the initial treatment of
choice for nonlife-threatening non-CNS blastomycosis.
1832. Domachowske JB. Bonville CA. Gao JL. Murphy PM.
Easton AJ. Rosenberg HF. The chemokine macrophage-inflammatory
protein-1 alpha and its receptor CCR1 control pulmonary inflammation and
antiviral host defense in paramyxovirus infection. Journal of Immunology. 165(5):2677-82, 2000 Sep 1.
Abstract
In this work, we explore the responses of
specific gene-deleted mice to infection with the paramyxovirus pneumonia
virus of mice (PVM). We have shown previously that infection of wild type
mice with PVM results in pulmonary neutrophilia and eosinophilia
accompanied by local production of macrophage-inflammatory protein-1 alpha
(MIP-1 alpha). Here we examine the role of MIP-1 alpha in the pathogenesis of this disease using mice
deficient in MIP-1 alpha or its receptor,
CCR1. The inflammatory response to PVM in MIP-1 alpha-deficient mice was
minimal, with approximately 10-60 neutrophils/ml and no eosinophils detected
in bronchoalveolar lavage fluid. Higher levels of infectious virus
were recovered from lung tissue excised from MIP-1 alpha-deficient than from
fully competent mice, suggesting that the inflammatory response
limits the rate of virus replication in vivo. PVM infection of CCR1-deficient mice was also
associated with attenuated inflammation,
with enhanced recovery of infectious virus, and with accelerated
mortality. These results suggest that the MIP-1 alpha/CCR1-mediated acute
inflammatory response protects mice by delaying the lethal sequelae of
infection.
1833. Duchini A.
Hendry RM. Redfield DC. Pockros PJ. Influenza infection in patients before and
after liver transplantation. Liver Transplantation. 6(5):531-42, 2000 Sep.
Abstract
Infection with influenza virus poses specific problems in pediatric and adult liver transplant recipients, both before and after liver transplantation. These include a higher rate of pulmonary and extrapulmonary complications, development of rejection with graft dysfunction, prolonged shedding of influenza virus, and increased drug-resistance. Hepatic decompensation may occur during influenza infection in patients with cirrhosis. Current prophylaxis includes yearly vaccination with trivalent inactivated vaccine. Appropriate diagnosis and prompt treatment of any upper respiratory infections are indicated in these patients. In this review, we describe a case of influenza viral pneumonia in an adult liver transplant recipient, review basic and clinical aspects of influenza infection in this patient population, and discuss current modes of prevention and treatment in detail.
1834.
Falsey AR.
Walsh EE. Respiratory syncytial virus infection in
adults. Clinical Microbiology Reviews. 13(3):371-84, 2000 Jul.
Abstract
Respiratory syncytial virus (RSV) is now
recognized as a significant problem in certain adult populations. These
include the elderly, persons with cardiopulmonary diseases, and
immunocompromised hosts. Epidemiological evidence indicates that the impact of RSV in older adults
may be similar to that of nonpandemic
influenza. In addition, RSV has been found to cause 2 to 5% of adult
community-acquired pneumonias. Attack rates in nursing homes are approximately 5
to 10% per year, with significant rates of pneumonia (10 to 20%)
and death (2 to 5%). Clinical features may be difficult to distinguish
from those of influenza but include nasal congestion, cough, wheezing, and low-grade fever. Bone
marrow transplant patients prior to marrow
engraftment are at highest risk for pneumonia and death. Diagnosis of RSV
infection in adults is difficult because viral culture and antigen detection
are insensitive, presumably due to low viral titers in nasal secretions,
but early bronchoscopy is valuable in immunosuppressed patients.
Treatment of RSV in the elderly is largely supportive, whereas early therapy
with ribavirin and intravenous gamma globulin is associated with improved
survival in immunocompromised persons. An effective RSV vaccine has not
yet been developed, and thus prevention of RSV infection is limited to
standard infection control practices such as hand washing and the use
of gowns and gloves.
1835. Fielding RM. Moon-McDermott L. Lewis
RO. Bioavailability of a small unilamellar
low-clearance liposomal amikacin formulation after extravascular administration.
Journal of Drug Targeting. 6(6):415-26, 1999.
Abstract
Amikacin in small, low-clearance liposomes
(MiKasome) has prol onged plasma and tissue residence and in vivo activity
against extracellular infections, including Klebsiella pneumonia
and Pseudomonas endocarditis. Small liposomes may cross endothelial
barriers, and enter the systemic circulation after extravascular administration. We compared the systemic
bioavailability (F) of low-clearance liposomal
amikacin in rats following intravenous (i.v.), intraperitoneal (i.p.), intramuscular (i.m.) and
subcutaneous (s.c.) injection (20 mg/kg) and
intratracheal (i.t.) instillation (10 mg/kg). Drug-containing
liposomes were extensively absorbed after i.p. (F = 87-146%) and i.t.
(F = 64%) administration, with maximum amikacin plasma concentrations of
171 micrograms/ml at 9 h and 80 micrograms/ml at 18 h, respectively.
Absorption was slower and less extensive following s.c. (plasma Tmax: 20.3
micrograms/ml at 48 h) and i.m. (plasma Tmax: 49.6 micrograms/ml at 19
h) injection, but a significant fraction (12-27%) of the
liposomes was absorbed. The plasma AUCs of liposomal amikacin exceeded the AUC
of conventional i.v. amikacin by at least 25-fold for all routes. Amikacin
AUCs in regional lymph nodes exceeded plasma AUCs by 4-fold after s.c.
and i.m. injection of liposomal amikacin. AUCs in tissues surrounding the
injection sites were 20- and 191-fold higher than plasma AUCs after i.m.
and s.c. injection, respectively. Thus, small low-clearance
liposomes produced sustained levels of liposome-encapsulated amikacin in
plasma, local tissues and lymph nodes after extravascular
administration, suggesting applications in perioperative prophylaxis, pneumonias and
intralesional therapy as well as sustained systemic delivery of encapsulated
drugs.
1836.
Foo RL.
Graham SM. Suthisarnsuntorn
U. Parry CM. Detection of pneumococcal capsular antigen
in saliva of children with pneumonia. Annals of Tropical Paediatrics. 20(2):161-3, 2000 Jun.
Abstract
The concentration of pneumococcal capsular
antigen (PCA) in saliva was examined in 44 Thai children aged between 2
months and 2 years admitted with community-acquired pneumonia and in 52
healthy controls. None of the children with pneumonia had a positive blood
culture. PCA was detected by latex agglutination in the saliva of 12/44
(27%) children with pneumonia compared with 9/52 (17%) of the controls.
More cases than controls had a PCA titre > or = 10 (9/44 (20%) vs 1/52
(2%), p < 0.01). Three of the five cases with a saliva PCA titre > or = 1000
were urine PCA antigen-positive. The salivary PCA titres were higher, but not
significantly, in children with
heavier pneumococcal carriage. Quantitative measurement of PCA in the saliva may be valuable in helping to make an
aetiological diagnosis in children with pneumonia.
1837. Georges H.
Leroy O. Guery B. Alfandari S. Beaucaire G. Predisposing factors for nosocomial
pneumonia in patients receiving mechanical ventilation and requiring tracheotomy.
Chest.
118(3):767-74, 2000 Sep.
Abstract
STUDY OBJECTIVES: To assess the incidence of
nosocomial pneumonia (NP) after tracheotomy in an ICU population and
to determine NP risk factors during the ICU stay, particularly on the day
of tracheotomy. DESIGN: A retrospective study using prospectively
collected data. SETTING: A 16-bed multidisciplinary ICU. PATIENTS: One hundred
thirty-five patients requiring tracheotomy for mechanical
ventilation (MV) weaning. RESULTS: The mean (+/- SD) duration of MV before
tracheotomy was 17.8 +/-13.4 days. Thirty-seven cases of NP occurred in 35
patients (25.9%), 8.7+/-7.3 days after the tracheotomy procedure. NP cases
were classified as early NP (n = 19) if they occurred within 5 days after the
procedure (mean, 2.7+/-1.1 days), and as late NP (n = 18) if they
occurred beyond the fifth day (mean, 14.4+/-6.1 days). Multivariate analysis identified the following
three independent factors associated with
early NP: the presence of positive endotracheal aspirates (EAs) with
pathogen levels of > or =10(5) cfu/mL (p = 0.0001); hyperthermia
(temperature, > or =38.3 degrees C; p = 0.002) on the day of tracheotomy; and the
continuation of sedation beyond 24 h after the tracheotomy (p = 0. 0001).
Accountable pathogens of early NP were present in EA on the day of
tracheotomy (p = 0.001). Cases of late NP were significantly associated with the
duration of sedation before the procedure (p = 0. 002) and with hyperthermia
(temperature, > or =38.3 degrees C) on the day of tracheotomy (p =
0.0005). The ICU admitting diagnosis, previous NP, duration of
administration of antimicrobial agents and MV before tracheotomy, indication for
tracheotomy, PO(2)/fraction of inspired oxygen ratio, and use of steroids
on the day of the procedure were not associated with the occurrence of
NP. The mortality rate of our population was 33.3%, and NP increased this
percentage to 54.3%. CONCLUSIONS: Our results could suggest that
tracheotomy should be delayed in mechanically ventilated patients with
bronchial colonization and hyperthermia, when sedation cannot be
discontinued after the procedure, to prevent occurrence of early NP.
1838. Goswami GK.
Jana S. Santiago JF. Buyukdereli G. Salem SS. Heiba S.
Abdel-Dayem HM. Discrepancy between Ga-67 citrate and F-18
fluorodeoxyglucose positron emission tomographic scans in pulmonary
infection. Clinical Nuclear Medicine. 25(6):490-1, 2000 Jun.
Abstract
The authors describe a patient with the
acquired immunodeficiency syndrome who had active pulmonary tuberculosis and
was receiving anti-tuberculosis treatment. High-grade fever and a
right-sided pleural effusion had recently developed. Results of a Ga-67 scan
were negative for any focal infection in the chest. Fluorine-18 fluorodeoxyglucose positron emission
tomography showed increased uptake in the
right lower lung field, which correlated with the diagnosis of concomitant
bacterial pneumonia. Anti-tuberculosis treatment can decrease the
sensitivity of the Ga-67 scan and could have contributed to this
discrepancy. The authors predict that the fluorine-18 fluorodeoxyglucose positron
emission tomographic scan will play an important diagnostic role in the
management of such a selected group of patients.
1839.
Gruson D.
Hilbert G. Valentino R. Vargas F.
Chene G. Bebear C. Allery A. Pigneux A. Gbikpi-Benissan
G. Cardinaud JP. Utility of fiberoptic bronchoscopy in neutropenic patients admitted to the
intensive care unit with pulmonary
infiltrates. Critical Care Medicine. 28(7):2224-30, 2000 Jul.
Abstract
OBJECTIVE: To analyze the impact of
fiberoptic bronchoscopy and bronchoalveolar lavage (BAL) on guiding the
treatment and intensive care unit (ICU) clinical outcome in neutropenic
patients with pulmonary infiltrates admitted to the ICU. DESIGN: Prospective collection of data.
SETTING: Medical ICU in a teaching hospital.
PATIENTS: During a 6-yr period, we analyzed the results of 93
fiberoptic bronchoscopies plus BALs performed in 93 consecutive neutropenic ICU
patients. We separated the patients into two groups according to the
cause of neutropenia (high-dose chemotherapy [n = 41] or stem cell
transplantation [SCT; n = 52]). RESULTS: Of the 93 BALs, 53 were performed
to evaluate diffuse infiltrates and 42 were performed on mechanically ventilated patients. Forty-nine
percent of BALs (46 patients) were
diagnostic, with a significantly better yield in ICU patients with high-dose
chemotherapy-induced neutropenia (26 of 41 BALs). The number of cases of proven
infectious pneumonia was significantly higher in this group of ICU
neutropenic patients. In patients who underwent SCT, diffuse
infiltrates were statistically correlated with a negative result of BAL.
Twenty-six patients who underwent diagnostic BALs changed therapy.
Sixteen complications (17%) occurred with only two intubations. The
overall mortality rate in the ICU and the mortality rate in mechanically
ventilated neutropenic patients were 71% and 93%, respectively. In
neutropenic patients who underwent SCT, the mortality rate was statistically higher
in patients in whom no diagnosis was established. Patients who had
a diagnostic BAL that changed therapy did not have an increased probability of survival compared with
patients who had a BAL that did not change therapy. CONCLUSIONS: The use
of routine diagnostic BAL in ICU neutropenic
patients with pulmonary infiltrates is difficult to establish, even
if BAL is helpful in the management of these critically ill patients.
BAL in our ICU neutropenic patient population had an acceptable overall
diagnostic yield (49%), which was higher in ICU patients with
chemotherapy-induced neutropenia. Nevertheless, in the ICU, if BAL had a low
complication rate, it had infrequently led to changed treatment and was
not associated with improved patient survival.
1840. Hardegger D. Nadal D. Bossart W. Altwegg M.
Dutly F. Rapid detection of Mycoplasma pneumoniae in
clinical samples by real-time PCR. Journal of Microbiological Methods. 41(1):45-51, 2000 Jun.
Abstract
M. pneumoniae is a common causative agent of
community-acquired pneumonia in children. The diagnosis of such
infections is usually based on serology using complement fixation or, more recently,
enzyme-immuno assays. PCR has been shown to be a promising alternative. We
have evaluated a real-time PCR assay targeting the P1 adhesion protein
gene and compared it to a conventional semi-nested PCR assay with the 16S rDNA as target. Comparison
of 147 specimens from 48 patients showed an
overall agreement of 97.4%. Real-time PCR proved to be of equal value on
clinical specimens as conventional PCR regarding sensitivity and
specificity, but is clearly advantageous regarding speed, handling and
number of samples that can be analyzed per run.
1841. Hartmann KE. Barrett KE. Reid VC. McMahon MJ.
Miller WC. Clinical usefulness of white blood cell
count after cesarean delivery. Obstetrics & Gynecology. 96(2):295-300, 2000 Aug.
Abstract
OBJECTIVE: To examine changes in white blood
cell (WBC) count after cesarean and estimate risk of postoperative
infection. METHODS: We measured complete blood cell counts at
admission and on postoperative day 1 for 458 women who had cesareans. Information
from charts was abstracted, and definitions of infectious outcomes and fever were applied by three
physicians masked to laboratory results. We
examined changes in absolute and relative WBC counts by labor status.
Likelihood ratios for postoperative infection were calculated for
statistically distinct categories of percentage changes. RESULTS:
We excluded 60 women with chorioamnionitis. Of the remainder, 34
(8.5%) developed endometritis and three (0.8%) pneumonia. Women who labored before
cesarean (n = 198) had higher antepartum (P <.001) and
postoperative day 1 (P <.001) WBC counts than those who did not (n = 200). However,
change in WBC count after cesarean relative to antepartum was similar
for both groups (P =.41), averaging a 22% increase. We grouped
percentage changes into the following three levels: up to 24%, 25-99%, and at
least 100%. The lowest level (n = 246) corresponded to a category-specific
likelihood ratio for diagnosis of serious postpartum infection of 0. 5 (95%
confidence interval [CI] 0.3, 0.8), the midlevel (n = 141) to a category-specific likelihood ratio of
1.7 (95% CI 1.2, 2.3), and the highest level
(n = 11) to a category-specific likelihood ratio of 5.8
(95% CI 1.8, 18.7). CONCLUSION: Labor influenced postcesarean WBC counts but
did not obscure changes associated with infection. Information
gained from changes in WBC counts can be used to assess risk of infection.
1842. Hashino S.
Mori A. Kobayashi S. Tanaka J.
Musashi M. Asaka M. Imamura M. Proliferation of CD4+ lymphocytes in a
patient with chronic graft-versus-host disease after allogeneic
bone marrow transplantation. International Journal of Hematology. 71(4):389-93, 2000 Jun.
Abstract
Expansion of donor-derived lymphocytes after
allogeneic stem cell transplantation is a serious and sometimes
fatal complication. Lymphoproliferative disorders are reportedly
caused mainly by reactivation of Epstein-Barr virus (EBV) and non-EBV-associated secondary lymphoma or
leukemia. In this paper, we report massive proliferation of CD4+
lymphocytes in peripheral blood of a patient
with chronic graft-versus-host disease (GVHD) following
allogeneic bone marrow transplantation (alloBMT) from an HLA-identical
sibling donor. The abnormal lymphocytes showed CD3low, CD4+,
CD8-, CD2+, CD5+, CD7+, CD25-, CD19-, CD20-, CD21-, CD16-, CD56low, T-cell receptor
(TCR)-alpha/beta- and TCR-gamma/delta- phenotypes, and no
rearrangement of either TCR-C beta 1 or IG(H)JH was detected from the lymphocytes
by Southern blot analysis. EBV was not found in the nuclei of
lymphocytes by an immunofluorescence antibody. The lymphoproliferation was
resistant against immunosuppressive drugs, administered for the treatment of
chronic GVHD, and it effectively inhibited aggravation of the chronic GVHD.
Although antithymocyte globulin and cytosine arabinoside were administered
later, the patient died of respiratory failure with bilateral pleural
effusion and interstitial pneumonia. Because we found no evidence of monoclonality of the abnormal
lymphocytes, we could not conclude that this
patient had suffered from malignant lymphoproliferation. To our
knowledge, this is the first case report of proliferation of CD4+ lymphocytes
in a patient with chronic GVHD following alloBMT. In this paper, we discuss
the possible pathophysiology of the patient.
1843. Holten KB. Onusko EM. Appropriate prescribing of oral beta-lactam antibiotics.
American Family Physician. 62(3):611-20, 2000 Aug 1.
Abstract
Beta-lactam antibiotics include penicillins,
cephalosporins and related compounds. As a group, these drugs are
active against many gram-positive, gram-negative and anaerobic organisms.
Information based on "expert opinion" and antimicrobial susceptibility testing supports certain
antibiotic choices for the treatment of
common infections, but less evidence-based literature is available to
guide treatment decisions. Evidence in the literature supports the
selection of amoxicillin as first-line antibiotic therapy for acute
otitis media. Alternative drugs, such as amoxicillin-clavulanate,
trimethoprim-sulfamethoxazole and cefuroxime axetil, can be used to treat
resistant infections. Penicillin V remains the drug of choice for the treatment
of pharyngitis caused by group A streptococci. Inexpensive
narrow-spectrum drugs such as amoxicillin or trimethoprim-sulfamethoxazole
are first-line therapy for sinusitis. Animal and human bites can be
treated most effectively with amoxicillin-clavulanate. For most outpatient
procedures, amoxicillin is the preferred agent for bacterial
endocarditis prophylaxis. Beta-lactam antibiotics are usually not the first choice
for empiric outpatient treatment of community-acquired pneumonia. Based on the literature, the
role of beta-lactam antibiotics in the
treatment of bronchitis, skin infections and urinary tract infections
remains unclear.
1844. Hopper JE.
Golbus J. Meyer C. Ferrer GA. Urine free light chains in SLE: clonal
markers of B-cell activity and potential link to in vivo secreted Ig. Journal of Clinical Immunology. 20(2):123-37, 2000 Mar.
Abstract
As a marker of in vivo B-cell activity,
urine levels of free light chain (FLC) were measured twice weekly by
radioimmunoassay (RIA) and correlated with disease activity over periods of 5-10
months in seven patients with systemic lupus erythematosus (SLE). In
addition, RIA-measured urine albumin was used to track glomerular injury,
and alpha1-microglobulin (alpha1-M) levels, 28- to 32-kDa protein,
provided control measurements on excretion of low-molecular-weight proteins.
As controls, urine FLC levels were obtained from healthy normals and in
subjects with acute pharyngitis, sickle-cell anemia, and acute sepsis or
pneumonia. The control results showed that with acute sepsis/pneumonia had
marked increases in urine FLC, while pharyngitis and sickle-cell controls
had normal FLC levels. In SLE, active patients receiving intravenous
cyclophosphamide and high-dose steroids exhibited highly increased urine FLC that fluctuated widely
during therapy and fell to normal range
levels with disease remission. During active SLE, urine albumin often was
increased, while alpha1-M levels remained in normal range. In contrast
to the increased FLC of active disease, inactive patients on
low-dose maintenance therapy had predominantly normal FLC levels throughout
the collection period. These results support our hypothesis that longitudinal levels of urine FLC can
be used to track disease-related B-cell
activity in SLE. Furthermore, we suggest that the urine FLC of active SLE
would share LC idiotype with the clonal associated in vivo secreted Ig, and
thus permit the identification of these antibodies that are targeted to the
culprit immunogen(s) responsible for the pathogenesis of SLE.
1845. Hung CC.
Chen MY. Hsieh SM. Sheng WH.
Chang SC. Clinical spectrum, morbidity, and mortality
of acquired immunodeficiency syndrome in Taiwan: a 5-year prospective
study. Journal of Acquired Immune Deficiency
Syndromes. 24(4):378-85, 2000 Aug 1.
Abstract
The clinical spectrum of AIDS and changes of
morbidity and mortality associated with HIV infection following
initiation of highly active antiretroviral therapy (HAART) are rarely
described in the less developed countries in the Asia-Pacific region. We prospectively observed on a
follow-up basis 309 HIV-infected patients
(82.8% with AIDS) at National Taiwan University Hospital in Taiwan, where
highly active antiretroviral therapy (HAART) has been provided to all
patients at no charge at any stage of HIV infection since April 1, 1997,
to describe the spectrum of HIV-associated opportunistic diseases and
evaluate changes of morbidity and mortality from June 24, 1994 through
June 23, 1999. Of the patients, 59.3% at study entry had a CD4+ lymphocyte
count of <50 cells/microliter. The five leading HIV-associated opportunistic infections included
oroesophageal candidiasis (195 patients), Pneumocystis carinii pneumonia
(93), tuberculosis (77), mucocutaneous
herpes simplex infection (74), and cytomegalovirus diseases (73). The incidence
rates of seven major AIDS-defining opportunistic diseases were
declining though the changes of the relative proportions varied. The median
duration of hospitalization decreased from 36 days in 1995 to 12 days in
1999 (p =.0001). Overestimated mortality rate declined from 148.4 per 100 patient-years in
1995 to 7.4 per 100 patient-years in 1999 (p
=.0001) whereas the underestimated mortality rate declined from
110.5 to 5.39 per 100 patient-years (p =.0001). Risk ratio (RR)
for mortality in patients who received HAART compared with those who did
not was 0.410 (95% confidence interval [CI], 0.249-0.674; p =.0004) and
the RR was 0.250 (95% CI, 0.127-0.492; p =.0001) when the analysis was
limited to patients with an initial CD4+ lymphocyte count <100
cells/microliter and follow-up duration >30 days after adjusting for their age,
gender, type of risk behavior, and CD4+ lymphocyte count. Morbidity and
mortality were declining with each study year even in a population consisting
mainly of patients at the advanced stage of HIV infection in Taiwan.
Earlier diagnosis, accumulation of clinical experience, and use of HAART
were associated with lower mortality rates.
1846.
Iino K.
Oki Y. Sasano H. A case of adrenocortical carcinoma
associated with recurrence after laparoscopic surgery. Clinical Endocrinology. 53(2):243-8, 2000 Aug.
Abstract
Laparoscopic adrenalectomy has become
increasingly popular because of its minimally invasive nature, but guidelines
for selection of cases suitable for this surgical procedure have not been
established. We report a 52-year-old woman with adrenocortical carcinoma, manifesting as Cushing's
syndrome, treated with laparoscopic
adrenalectomy. The tumour was removed in toto and had been histologically
diagnosed as adrenocortical adenoma. However, the patient developed
intra-abdominal peritoneal dissemination of carcinoma 15 months after surgery. Review of
the histopathological findings of the resected adrenocortical
tumour revealed that the neoplasm met five out of ninehistological criteria
for adrenocortical malignancy, and was diagnosed as adrenocortical
carcinoma. Histopathological examination of the tumour was also consistent
with adrenocortical carcinoma. The patient responded extremely
well to chemotherapy, including carboplatin, etoposide and o,p'-DDD (1,1-dichlorodiphenyldichloroethane),
and a subsequent CT (computed tomography)
scan 12 months after the start of chemotherapy demonstrated no evidence of
disease. However, the patient developed neurological impairment, including
dysarthria, as a side-effect of o, p'-DDD. The patient died of aspiration
pneumonia due to a decreased pharyngeal reflex. Postmortem examination
revealed no foci of residual carcinoma. This case report emphasizes the
importance of excluing possible adrenocortical malignancy in patients
considered for laparoscopic adrenalectomy, histopathological diagnosis
of adrenocortical malignancy and careful monitoring for neurotoxicity
during o,p'-DDD treatment.
1847. Ito M.
Nozu R. Kuramochi T. Eguchi N.
Suzuki S. Hioki K. Itoh T. Ikeda F. Prophylactic effect of FK463, a novel
antifungal lipopeptide, against Pneumocystis carinii infection in mice.
Antimicrobial Agents &
Chemotherapy. 44(9):2259-62, 2000 Sep.
Abstract
The prophylactic effect of FK463, a new
water-soluble echinocandin-like lipopeptide with inhibitory activity against
1, 3-beta-D-glucan synthase, against Pneumocystis carinii infection was
investigated with the severe combined immunodeficient (SCID) mouse model.
Treatment with FK463, pentamidine, and saline only was performed
for 6 weeks from the day after the SCID mice were inoculated intranasally
with infected lung homogenates. FK463 at 0.2 or 1.0 mg/kg of body weight,
pentamidine at 4 mg/kg, or saline was subcutaneously administered daily
into the backs of the SCID mice. The effects of the drugs were
evaluated by detection of P. carinii cysts in mouse lung homogenates by toluidine
blue O staining, lung histology, and PCR amplification of a P.
carinii-specific DNA fragment from the lungs. P. carinii cysts were
detected in the lungs of all mice administered saline. In contrast, no cysts
were detected in mice administered both doses of FK463 and
pentamidine. A specific DNA fragment was amplified from all mice administered
saline and at least half or more of the mice administered FK463 and
pentamidine. These results indicate that FK463 acts on cyst wall formation but
not on trophozoite proliferation and is extremely effective in preventing P.
carinii-associated pneumonia. These results
suggest that FK463 is potentially useful as a prophylactic agent
against P. carinii infection.
1848.
Jedlovsky V. Fleischman JK. Pneumocystis carinii pneumonia as the first
presentation of HIV infection in patients older than fifty. AIDS Patient Care & STDS. 14(5):247-9, 2000 May.
Abstract
A significant increase in the number of
elderly patients first diagnosed with HIV infection at the time of
presentation with an AIDS-related opportunistic infection has recently been
reported. This suggests a significant delay in the diagnosis of HIV infection.
Few data are available describing such cases and their
outcome. We restrospectively reviewed records of all elderly patients
(> 50 years of age) admitted to a New York City hospital over a 3-year period
with confirmed Pneumocystis carinii pneumonia (PCP). The mean age was
57.9 +/- 6.6 years. In 80% (8 of 10 cases), the diagnosis of HIV infection
was made at presentation with PCP. The mean CD4 count was 34.2 +/-
39.2/mm3 (1-117/mm3), indicating advanced AIDS. The clinical presentation of PCP was similar to that in
younger patients. With prompt and
appropriate therapy, a 70% survival rate for this hospitalization was achieved,
similar to that reported in younger age groups. The diagnosis of HIV infection
was not considered until presentation with PCP at an advanced stage
of AIDS in 80% of these elderly patients, thus delaying institution of HIV
treatment and counseling. Early consideration of HIV infection in the
elderly is of importance because of the rising number of AIDS cases in this age
group.
1849. Jerng JS.
Yu CJ. Liaw YS. Wu HD.
Wang HC. Kuo PH. Yang PC. Clinical spectrum of acute respiratory
distress syndrome in a tertiary referral hospital: etiology, severity,
clinical course, and hospital outcome. Journal of the Formosan Medical
Association. 99(7):538-43, 2000 Jul.
Abstract
BACKGROUND AND PURPOSE: The clinical picture
of patients with acute respiratory distress syndrome (ARDS) in
Taiwan has seldom been reported, although new definitions of ARDS have been
introduced over the past years. The purpose of this study was to investigate
the clinical characteristics, modalities of management, and outcomes in patients with ARDS treated in a
tertiary referral hospital. METHODS: Case
records were selected through a computerized search of diagnosis codified at
discharge during the period from January 1995 to June 1997. Patients who
met the criteria of the American-European Consensus Conference
definition of ARDS were included and their medical records were
retrospectively reviewed. RESULTS: A total of 145 patients (91 men, 54 women; mean age,
58 years) who fulfilled the criteria for ARDS were identified.
Malignancy (n = 53) and diabetes mellitus (n = 23) were the most common
co-morbid conditions. Pneumonia (n = 90), including community-acquired pneumonia in 45 (31%) patients, was
the most common risk factor. The lung injury
score at the time of ARDS diagnosis was 2.89 +/- 0.40 (mean +/-
standard error, SE). The worst value of PaO2/FIO2 was 86.8 +/- 3.8 mm Hg (mean
+/- SE). Among the 145 patients, 130 (90%) received mechanical ventilation
and 118 (81%) were treated in the intensive care unit. In-hospital
mortality was 87%. Seventy (48%) patients received intensive treatment for
ARDS, among whom 52 (74%) died; the most common causes of death were
multiple organ failure (54%) and respiratory failure (23%). CONCLUSIONS: The
mortality in patients with ARDS was high in this tertiary referral
institution. Our findings suggest that aggressive ventilatory, pharmacologic,
and supportive therapy may be important to achieve a higher survival rate.
1850. Johkoh T.
Muller NL. Akira M. Ichikado K.
Suga M. Ando M. Yoshinaga T. Kiyama T. Mihara N. Honda O.
Tomiyama N. Nakamura H. Eosinophilic lung diseases: diagnostic
accuracy of thin-section CT in 111 patients. Radiology.
216(3):773-80, 2000 Sep.
Abstract
PURPOSE: To determine whether various
eosinophilic lung diseases can be differentiated by means of thin-section
computed tomography (CT). MATERIALS AND METHODS: Thin-section CT scans
in 111 patients with eosinophilic lung diseases-40 with chronic
eosinophilic pneumonia, 16 with Churg-Strauss syndrome, 16 with allergic
bronchopulmonary aspergillosis (ABPA), 13 with acute eosinophilic
pneumonia, 12 with simple pulmonary eosinophilia, 11 with drug-induced
eosinophilic pneumonia, and three with hypereosinophilic syndrome-were assessed
independently by two observers. The observers recorded the abnormalities,
diagnosis, and degree of confidence in the diagnosis. RESULTS: The
two observers made a correct first-choice diagnosis on average in 61% of readings. The correct
diagnosis was made in 78% of cases of
chronic eosinophilic pneumonia; 81%, acute eosinophilic pneumonia; 44%,
Churg-Strauss syndrome; 84%, ABPA; 17%, simple pulmonary eosinophilia; 27%,
drug-induced eosinophilic pneumonia; and 33%, hypereosinophilic syndrome. The two
observers made a correct diagnosis with a high degree of confidence
in 36% of readings. There was moderate agreement between the observers for
the correct diagnosis (kappa, 0.47) and for the correct diagnosis with a high degree of confidence
(kappa, 0.59). CONCLUSION: Although
eosinophilic lung diseases often can be differentiated by means of thin-section
CT, correlation between CT findings and careful clinical evaluation are
required for a definitive diagnosis.
1851. Jones RN.
Croco MA. Kugler KC. Pfaller MA.
Beach ML. Respiratory tract pathogens isolated from
patients hospitalized with suspected pneumonia: frequency of occurrence
and antimicrobial susceptibility patterns from the SENTRY
Antimicrobial Surveillance Program (United States and Canada, 1997). Diagnostic Microbiology & Infectious
Disease. 37(2):115-25, 2000 Jun.
Abstract
Thirty-seven sentinel hospitals (29 in the
United States [US]; eight in Canada) collected bacterial isolates from
hospitalized patients with a diagnosis of pneumonia. The antimicrobial
susceptibility patterns of these pathogens were determined to more than 60
agents (40 reported) using the reference broth microdilution method
described by the National Committee for Clinical Laboratory Standards. The five
most frequently recorded species among the 2757 isolates collected
during the study were (no. tested/%): Staphylococcus aureus
(632/22.9%), Pseudomonas aeruginosa (498/18. 1%), Haemophilus influenzae
(284/10.3%), Klebsiella spp. (240/8.7%), and Streptococcus pneumoniae (213/7.7%). There was a significant difference in the susceptibility
to antimicrobials between the US and Canada for S. aureus to oxacillin
(50.1% versus 93.8% susceptible, respectively), gentamicin (78.7% versus
97.8%), and fluoroquinolones (49.5 to 53.0% versus 89.8 to 94.9%). Amikacin
(92. 8% susceptible) was the most active antimicrobial agent against P.
aeruginosa, and meropenem was the most potent beta-lactam. Against H.
influenzae, most drugs retained a high level of activity, whilst against the S.
pneumoniae, only the newer fluoroquinolones (gatifloxacin, levofloxacin,
sparfloxacin) remained highly effective in vitro. Only two
antimicrobial agents (imipenem and meropenem) were >99% active against the Klebsiella spp. and Enterobacter
spp. isolated in this survey (possess
extended spectrum beta-lactamases or hyperproduction of Amp C cephalosporins);
cefepime (95.6-100.0% susceptible) was significantly more active
than other cephalosporins tested. Clonal, epidemic outbreaks of
multiply resistant strains were very rare in monitored hospitals. In conclusion,
important differences exist between the US and Canada in the
susceptibility patterns of some respiratory tract pathogens to commonly
used
antimicrobial agents with Canadian strains generally being more
susceptible to currently available antimicrobial agents.
1852. Kammoun S.
Frikha I. Fourati K. Fendri S.
Benyoussef S. Sahnoun Y. Daoud M.
Dumesnil JG. Hydatid cyst of the heart located in the
interventricular septum. Canadian Journal of Cardiology. 16(7):921-4, 2000 Jul.
Abstract
Cardiac hydatosis is a rare condition, and
the localization of a hydatid cyst within the interventricular septum is
exceptional. A 61-year-old man found to have a hydatid cyst of the
interventricular septum is reported. Presenting manifestations were congestive
heart failure and signs suggestive of an aortic valvulopathy.
Diagnosis was made by Doppler echocardiography and confirmed by magnetic
resonance imaging. The cyst was approached surgically by right
ventriculotomy. Despite a technically successful intervention without rupture of
the cyst or appearance of a conduction delay, the patient died on the
20th postoperative day because of acute respiratory distress syndrome
complicating infectious pneumonia.
1853. Kearns PJ.
Chin D. Mueller L. Wallace K.
Jensen WA. Kirsch CM. The incidence of ventilator-associated
pneumonia and success in nutrient delivery with gastric versus small
intestinal feeding: a randomized clinical trial. Critical Care Medicine. 28(6):1742-6, 2000 Jun.
Abstract
BACKGROUND: Enteral feeding provides
nutrients for patients who require endotracheal tubes and mechanical
ventilation. There is a presumed increase in the risk of ventilator-associated pneumonia (VAP) with tube
feeding. This has stimulated the development
of procedures for duodenal intubation and small intestinal (SI) feeding
as primary prophylaxes to prevent VAP. OBJECTIVE: To investigate the
rate of VAP and adequacy of nutrient delivery with gastric (G) vs. SI
feeding. DESIGN: A prospective, randomized, controlled trial. SETTING: A
medical intensive care unit of a county hospital. PATIENTS: A total of 44
endotracheally intubated, mechanically ventilated patients requiring
enteral nutrition. INTERVENTION: Subjects were randomized to receive enteral nutrition via G
or SI feeding. Protocols directed the
placement of the feeding tube and the infusion of enteral nutrition and
defined the radiographic and clinical criteria for a diagnosis of VAP.
MEASUREMENTS AND OUTCOMES: The incidence of VAP and the adequacy of
nutritional supplementation were prospectively followed. The relative risk of
VAP with SI was 1.1 (95% confidence interval 0.96-2.44) compared with
G. The SI group received a greater percentage of their caloric
requirements (SI 69 +/- 7% vs. G 47 +/- 7%, mean +/- SEM, p < .05). Mortality
did not differ between G (26 +/- 9%) and SI (24 +/- 10, p = .86).
CONCLUSIONS: There is no clear difference in the incidence of VAP in SI compared with
G enteral nutrition. Patients given feeding into the SI do receive higher
calorie and protein intakes.
1854. Kuwano K.
Kawasaki M. Maeyama T. Hagimoto N.
Nakamura N. Shirakawa K. Hara N. Soluble form of fas and fas ligand in BAL
fluid from patients with pulmonary fibrosis and bronchiolitis
obliterans organizing pneumonia. Chest.
118(2):451-8, 2000 Aug.
Abstract
STUDY OBJECTIVES: The Fas-Fas ligand (FasL)
pathway is a representative system of apoptosis-signaling receptor
molecules. We previously described that this pathway may play an important role
in the pathogenesis of fibrosing lung diseases. In this study, we
hypothesized that soluble form of Fas (sFas) and FasL (sFasL) may also be associated with this disorder.
MEASUREMENTS AND RESULTS: We measured sFas
and sFasL levels in BAL fluid (BALF) from patients with idiopathic
pulmonary fibrosis (IPF), interstitial pneumonia associated with
collagen vascular diseases (CVD-IP), and bronchiolitis obliterans
organizing pneumonia (BOOP), using enzyme-linked immunosorbent assay. BALF from
all patients was obtained before prednisolone therapy. sFasL levels
were relatively increased in IPF patients (p = 0.084), and significantly increased in CVD-IP patients (p <
0.05) and BOOP patients (p < 0.05),
compared with control subjects. BALF sFasL levels were elevated in the IPF or
CVD-IP subgroups with an indication for prednisolone therapy,
compared with those without an indication for therapy. The BALF sFasL level
in IPF patients was correlated with the number of total cells
and lymphocytes. The BALF sFasL level
in BOOP patients was relatively or significantly correlated with the number of total cells or lymphocytes,
respectively. The BALF sFas level was significantly increased in BOOP
patients, but not in IPF or CVD-IP patients. CONCLUSIONS: We conclude that BALF
sFasL levels may be associated with the accumulation of
inflammatory cells and reflect the degree of lymphocyte alveolitis in IPF. The
elevation of sFasL may be associated with the deterioration of IPF and
CVD-IP. The elevation of the BALF
sFas level may abrogate the cytotoxicity of FasL in BOOP patients, which may be associated with better
prognosis of BOOP, compared with IPF or CVD-IP.
1855. Lalonde M.
Segura M. Lacouture S. Gottschalk M. Interactions between Streptococcus suis
serotype 2 and different epithelial cell lines. Microbiology. 146 ( Pt 8):1913-21, 2000 Aug.
Abstract
Streptococcus suis is an important swine
pathogen responsible for cases of sudden death, septicaemia, meningitis, endocarditis
and pneumonia. It is also recognized as a zoonotic agent in
people occupationally exposed to pigs or pig products. Knowledge on virulence
factors of S. suis serotype 2 is limited and the pathogenesis of the infection is poorly understood. It
has been suggested that the disease due to
S. suis serotype 2 begins with colonization of the nasopharyngeal
epithelium, followed by either spread within the respiratory tract or invasion of
the bloodstream. The mechanisms involved in the access of
bacteria from the bloodstream to the central nervous system are unknown. It is
possible that epithelial cells of the choroid plexus also play an important
role in the pathogenesis of the meningitis. Different interactions
(adhesion, invasion and toxic effects) of S. suis serotype 2 with epithelial cell lines [LLC-PK1,
PK(15), A549, HeLa and MDCK] were studied
and compared to those of a human pathogen which also causes meningitis, group
B Streptococcus (GBS). The results showed that S. suis serotype 2, in
contrast to GBS, is able to adhere to but not to invade epithelial
cells. The adhesin(s) involved seem(s) to be partially masked by the
capsule and are a part of the cell wall. The haemolysin produced by S. suis
serotype 2 is responsible for a toxic effect observed on epithelial cells.
The results described give additional evidence that pathogenesis of the
infection differs between S. suis and GBS. In particular, it is possible
that suilysin-positive S. suis strains use adherence and cell injury, as
opposed to direct cellular invasion, as part of a complicated multistep
process which leads to bacteraemia and meningitis in pigs.
1856. Light RW. Management of pleural effusions. [Review]
[57 refs] Journal of the Formosan Medical
Association. 99(7):523-31, 2000 Jul.
Abstract
This review summarizes current strategies in
the treatment of patients with pleural effusion. To determine whether
a patient has a transudative or exudative pleural effusion, Light's
criteria should be applied to measure the concentrations of protein and
lactate dehydrogenase (LDH) in the pleural fluid and serum. If the effusion
is transudative, therapy should be directed toward the underlying
congestive heart failure, cirrhosis, or nephrosis. Consideration should be given to
pleurodesis with a sclerosant if patients with recurrent
transudative effusion have severe dyspnea due to their effusion. If the
effusion is exudative, attempts should be made to define the etiology. The
diagnosis of pleural malignancy is most easily established via pleural fluid
cytology. If this is negative and the patient is suspected of having
pleural malignancy, thoracoscopy is indicated. The concentrations of adenosine
deaminase and gamma-interferon in pleural fluid are useful in the diagnosis
of pleural tuberculosis. Patients with pneumonia and pleural effusion
should undergo therapeutic thoracentesis; the pleural fluid should be
Gram-stained and cultured, and the differential cell count, glucose and LDH
concentration, and pH should be determined. Indicators of a poor
prognosis include the presence of frank pus, a positive Gram-stain, a pleural glucose concentration of less
than 2.2 mmol/L, a pH less than 7.00, the
presence of pleural loculations, and an LDH concentration greater than three
times the upper limit of normal in serum. If the pleural fluid cannot
be completely evacuated because of loculations, intrapleural
thrombolytic therapy should be considered. If thrombolytics are
ineffective, thoracoscopy or thoracotomy with decortication should be performed. Dyspneic patients with malignant
pleural effusions whose dyspnea is relieved
with therapeutic thoracentesis should be considered for pleurodesis using a
tetracycline derivative. Talc is not recommended because it induces acute
respiratory distress syndrome in about 5% of patients, with an overall
mortality of 1%.
1857. Manfredi R.
Nanetti A. Ferri M. Chiodo F. Pseudomonas spp. complications in patients
with HIV disease: an eight-year clinical and microbiological survey. European
Journal of Epidemiology. 16(2):111-8, 2000 Feb.
Abstract
Two hundred and twenty-four episodes of
Pseudomonas spp. complications that occurred in 179 consecutive patients
with HIV infection were retrospectively reviewed. Pseudomonas
spp.
organisms were responsible for 11.6% of 1933 episodes of non-mycobacterial
bacterial diseases (5.4% of 1072 episodes of sepsis), observed over an
8-year period; 20.7% of patients experienced disease relapses (45
episodes). These complications mostly involved lower airways (66 cases),
urinary tract (53 episodes), and blood (34 cases), with Pseudomonas
aeruginosa isolated in 161 episodes, and other Pseudomonas spp. in the remaining
63 cases. An advanced HIV disease was frequently present (as expressed
by a prior diagnosis of AIDS, a low CD4+ lymphocyte count, and
leukopenia-neutropenia). Indwelling intravascular and urinary catheters were
often associated with bacteremia and urinary tract involvement, respectively.
More than 60% of patients were given antibiotics and/or cotrimoxazole
in the month preceding the onset of Pseudomonas spp. disease. Bacterial
strains isolated from our
HIV-infected patients showed a favorable
sensitivity to piperacillin, ceftazidime, imipenem, amikacin, tobramycin,
and ciprofloxacin. An adequate antimicrobial treatment led to
clinical and microbiological cure in 73.2% of patients at the first episode, and in 22.3% more subjects
after one or more relapses. A lethal outcome
occurred in only eight patients of 179 (4.5%), suffering from a far
advanced HIV disease; P. aeruginosa infection directly contributed to
death in four cases (sepsis, and/or pneumonia). Nosocomial disease
occurred in 46.4% of the 224 episodes, and was significantly related to a
previous diagnosis of AIDS, concurrent neutropenia, the occurrence of
sepsis or urinary tract infection, disease relapses, the involvement
of non-aeruginosa Pseudomonas spp., and a lethal outcome, compared with community-acquired infection.
Our experience (the largest reported to
date) confirms that Pseudomonas spp. (including non-aeruginosa Pseudomonas
spp. organisms) is responsible for remarkable morbidity and mortality among
patients with HIV infection, and may pose relevant problems to clinicians
and microbiologists involved in the care of HIV-infected patients.
1858. Mann G.
Hankey GJ. Cameron D. Swallowing disorders following acute stroke:
prevalence and diagnostic accuracy. Cerebrovascular Diseases. 10(5):380-6, 2000 Sep-Oct.
Abstract
We prospectively examined 128 patients with acute first-ever stroke to determine the prevalence of swallowing disorders, the diagnostic accuracy of our clinical assessment of swallowing function compared with videofluoroscopy, and interobserver agreement for the clinical and videofluoroscopic diagnosis of swallowing disorders and aspiration. We found clinical and videofluoroscopic evidence of a swallowing disorder in 51% [95% confidence interval (CI) 42-60%] and 64% (95% CI 55-72%) of patients, respectively, and aspiration in 49% (95% CI 40-58%) and 22% (95% CI 15-29%) of patients, respectively. The optimal clinical criteria for detecting videofluoroscopic evidence of a swallowing disorder and aspiration were any clinical evidence of a swallowing disorder (sensitivity 73%, 95% CI 62-82%; specificity 89%, 95% CI 76-96%), and any clinical evidence of aspiration (sensitivity 93%, 95% CI 76-99%; specificity 63%, 95% CI 53-72%). The interobserver agreement between two speech pathologists for the clinical diagnosis of a swallowing disorder (kappa: 0.82 +/- 0.09) and aspiration (kappa: 0.75 +/- 0.09) was good, and between a speech pathologist and radiologist for the videofluoroscopic diagnosis of a swallowing disorder (kappa: 0.75 +/- 0.09) and aspiration (kappa: 0.41 +/- 0.09), it was good and fair, respectively. Although clinical bedside examination underestimates the frequency of swallowing abnormalities and overestimates the frequency of aspiration compared with videofluoroscopy, it may still offer valuable information for the diagnosis of swallowing impairment. Long-term follow-up studies are required to determine the independent functional significance of the findings of the bedside and videofluoroscopic examinations in predicting the occurrence of important outcome events such as aspiration pneumonia.
1859. Mansharamani NG. Balachandran D. Vernovsky
I. Garland R. Koziel H. Peripheral blood CD4 + T-lymphocyte counts
during Pneumocystis carinii pneumonia in immunocompromised patients
without HIV infection. Chest.
118(3):712-20, 2000 Sep.Abstract
STUDY OBJECTIVES: To assess the potential
use of peripheral blood CD4 + T-lymphocyte counts (CD4 + counts) as a
clinically useful biological marker to identify specific immunocompromised patients (without HIV
infection) at high risk for Pneumocystis carinii pneumonia (PCP). DESIGN:
Prospective observational study. SETTING:
Three hundred seventy-five-bed tertiary-care urban referral teaching
hospital, and 250-bed community-based referral hospital. PATIENTS:
One hundred seventy-one consecutive confirmed HIV-seronegative
hospitalized and ambulatory adults, including 22 patients with active PCP, 8
patients with bacterial pneumonia, 24 persons in two groups considered at high clinical risk, 38
persons in two groups considered at low or undefined risk, and 79 persons
in four groups considered not at risk for
PCP (including healthy individuals). MEASUREMENTS AND RESULTS:
Compared to counts in healthy individuals, median CD4 + counts were
significantly decreased in patients with active PCP (61 cells/microL vs 832
cells/microL; p = 0.001) where 91% of patients had a CD4 + count < 300
cells/microL at the time of PCP diagnosis. Median CD4 + counts were also
reduced in the high clinical risk groups of recent organ transplant recipients
(117 cells/microL; p = 0.007), 64% with < 300 cells/microL, and
patients receiving chemotherapy (221 cells/microL; p<0.01), 80% with <
300 cells/microL. For the low or undefined clinical risk groups, the median
CD4 + counts were not significantly reduced, although 39 to 46% of
individuals receiving long-term corticosteroid therapy (alone or
in combination with other agents) had CD4 + counts < 300 cells/microL. Median CD4 + counts in
individuals considered not at risk for PCP were similar to those in
healthy subjects. Compared to counts in
patients with active PCP, median CD4 + counts were significantly higher in
bacterial pneumonia patients (486 cells/microL; p<0.05), but similar to
those in healthy subjects. CONCLUSIONS: These data suggest that for
immunosuppressed persons without HIV infection (especially in low or
undefined PCP risk groups), CD4 + counts may be a useful clinical marker to identify specific individuals at
particularly high clinical risk for PCP and may help to guide chemoprophylaxis.
1860. Mansharamani NG. Garland R. Delaney
D. Koziel H. Management and outcome patterns for adult
Pneumocystis carinii pneumonia, 1985 to 1995: comparison
of HIV-associated cases to other immunocompromised states [see comments]. Chest. 118(3):704-11, 2000 Sep.
Abstract
STUDY OBJECTIVES: Encompassing periods
preceding and following major advances in the diagnosis and management of
HIV-related Pneumocystis carinii pneumonia (PCP), the purpose of this
study was to determine whether management and outcome patterns of non-HIV PCP parallel the
management and outcomes of AIDS-related PCP.
DESIGN: Retrospective review of medical records. SETTING: A 375-bed
tertiary-care urban teaching hospital and referral center. PATIENTS: All
adult patients with morphologically confirmed PCP from 1985 to
1995. MEASUREMENTS AND RESULTS: From 1985 to 1995, 638 confirmed cases of
PCP were identified, including 605 cases in 442 HIV-positive persons (HIV +
PCP), and 33 cases in 33 non-HIV patients (non-HIV PCP). For HIV +
PCP cases, a peak of 104 cases occurred in 1987, with a gradual decline to 23 in 1995. The proportion of
cases requiring hospitalization declined
from a peak of 91.6% in 1987 to a low of 51.6% in 1992. ICU admission was
required for 6.3 to 8.2%, and mechanical ventilation for 4.7 to 5.7%.
Overall mortality improved from 11.7 to 6.6%, although mortality for
intubated patients remained at 50 to 60%. For the non-HIV PCP cases, 97% occurred
from 1989 to 1995 with similar annual frequency, 97% required hospitalization, 69% required ICU
admission, and 66% required intubation.
Overall mortality was 39%, and mortality for intubated patients was 59%.
CONCLUSIONS: Despite major advances in diagnosis and management, PCP
remains a significant problem in non-HIV-infected patients, and respiratory
failure remains associated with a high mortality rate for patients with both
HIV + PCP and non-HIV PCP.
1861. Matsuoka S.
Uchiyama K. Kuniyasu Y. Niio Y.
Shima H. Doai K. Oishi S. Nojiri Y. Ogata H.
Abnormal pulmonary accumulation of
indium-111 chloride in pneumocystis carinii pneumonia as detected by bone marrow
scintigraphy. Clinical Nuclear Medicine. 25(5):361-3, 2000 May.
Abstract
PURPOSE: Unusual pulmonary uptake of In-111
chloride in a patient with Pneumocystis carinii pneumonia and
autoimmune hepatitis is described. METHOD: In-111 chloride bone marrow
scintigraphy was performed to evaluate the bone marrow activity associated with pancytopenia in a 56-year-old
woman with autoimmune hepatitis. RESULTS: An
In-111 chloride bone marrow scan showed increased pulmonary uptake
predominantly in both upper lung fields. P. carinii pneumonia was seen to be
developing as an immunocompromised complication after
treatment for autoimmune hepatitis. CONCLUSION: When In-111 chloride bone marrow
scintigraphy shows increased uptake in the lungs of immunocompromised
patients, a combined opportunistic inflammatory disease such as
P. carinii pneumonia should be considered in the diagnosis.
1862. McCarthy EP. Iezzoni LI. Davis
RB. Palmer RH. Cahalane M.
Hamel MB. Mukamal K.
Phillips RS. Davies DT Jr. Does clinical evidence support ICD-9-CM diagnosis coding of
complications?. Medical Care. 38(8):868-76, 2000 Aug.
Abstract
BACKGROUND: Hospital discharge diagnoses,
coded by use of the International Classification of Diseases,
9th Revision, Clinical Modification (ICD-9-CM), increasingly
determine reimbursement and support quality monitoring. Prior studies of coding
validity have investigated whether coding guidelines were met, not
whether the clinical condition was actually present. OBJECTIVE: To determine
whether clinical evidence in medical records confirms selected ICD-9-CM
discharge diagnoses coded by hospitals. RESEARCH DESIGN AND SUBJECTS:
Retrospective record review of 485 randomly sampled 1994
hospitalizations of elderly Medicare beneficiaries in Califomia and Connecticut.
MAIN OUTCOME MEASURE: Proportion of patients with specified
ICD-9-CM codes representing potential complications who had clinical
evidence confirming the coded condition. RESULTS: Clinical evidence
supported most postoperative acute myocardial infarction diagnoses, but fewer
than 60% of other diagnoses had confirmatory clinical evidence by explicit
clinical criteria; 30% of medical and 19% of surgical patients lacked
objective confirmatory evidence in the medical record. Across 11 surgical and 2 medical
complications, objective clinical criteria
or physicians' notes supported the coded diagnosis in >90% of patients
for 2 complications, 80% to 90% of patients for 4 complications, 70% to <80%
of patients for 5 complications, and <70% for 2 complications. For some
complications (postoperative pneumonia, aspiration pneumonia, and
hemorrhage or hematoma), a large fraction of patients had only a physician's
note reporting the complication. CONCLUSIONS: Our findings
raise questions about whether the clinical conditions represented by ICD-9-CM
codes used by the Complications Screening Program were in fact
always present. These findings highlight concerns about the
clinical validity of using ICD-9-CM codes for quality monitoring.
1863.
McWhinney PH. Ragunathan PL. Rowbottham
TJ. Failure to produce detectable antibodies to
Legionella pneumophila by an immunocompetent adult. Journal of Infection. 41(1):91-2, 2000 Jul.
Abstract
A case of legionella pneumonia diagnosed by
co-culture with amoebae and urinary antigen detection is described.
Diagnostic antibody tests remained negative despite prolonged follow-up.
Investigation showed no evidence of an under-lying immunodeficiency. The value
of culture-based diagnosis and consequences of missed diagnoses are
discussed.
1864.
Morrison DF. Foss DL. Murtaugh MP. Interleukin-10 gene therapy-mediated amelioration of bacterial pneumonia.
Infection & Immunity. 68(8):4752-8, 2000 Aug.
Abstract
Respiratory infection by Actinobacillus
pleuropneumoniae causes a highly pathogenic necrotizing pleuropneumonia with
severe edema, hemorrhage and fever. Acute infection is characterized by
expression of inflammatory cytokines, including interleukin-1 (IL-1),
IL-6 and IL-8. To determine if high level production of inflammatory
cytokines contributed to disease pathogenesis, we investigated if inhibiting
macrophage activation with adenovirus type 5-expressed IL-10
(Ad-5/IL-10) reduced the severity of acute disease. Porcine tracheal epithelial
cells infected with Ad-5/IL-10 produced bioactive human IL-10. When pigs
were intratracheally infected with A. pleuropneumoniae, pigs pretreated
with Ad-5/IL-10 showed a significant reduction in the amount of lung
damage when compared to adenovirus type 5-expressing beta-galactosidase (Ad-5/beta-Gal)-treated
and untreated pigs. In addition, serum zinc levels were unchanged, the
lung weight/body weight ratio (an indicator
of vascular leakage) was significantly reduced, and lung pathology
scores were reduced. Myeloperoxidase activity in lung lavage
fluid samples, an indicator of neutrophil invasion, was decreased to levels
similar to that seen in pigs not infected with A. pleuropneumoniae.
Reduction in inflammatory cytokine levels in lung lavage fluid samples
correlated with the clinical observations in that pigs pretreated with Ad-5/IL-10
showed a corresponding reduction of IL-1 and tumor
necrosis factor (TNF) compared with untreated and Ad-5/beta-Gal-treated
pigs. IL-6 levels were unaffected by pretreatment with Ad-5/IL-10, consistent
with observations that IL-6 was not derived from alveolar macrophages.
Since inflammatory cytokines are expressed at high levels in acute
bacterial pleuropneumonia, these results indicate that macrophage activation,
involving overproduction of IL-1 and TNF, is a prime factor in infection-related
cases of massive lung injury.
1865. Mulholland K. Evaluation of vaccines to prevent childhood
pneumonia: lessons relevant to planning tuberculosis vaccine trials. Clinical Infectious Diseases. 30 Suppl 3:S206-9, 2000 Jun.
Abstract
Bacterial pneumonia in children is usually
caused by one of the two leading pathogens, Streptococcus pneumoniae
(pneumococcus) and Haemophilus influenzae, either type b (Hib) or
nonencapsulated types. Hib conjugate vaccines suitable for use in infants have
been available for about a decade, and experience with a trial of one
of these vaccines in Africa showed that the vaccines can prevent Hib
pneumonia, as well as other manifestations of Hib disease. It also
showed that vaccine trials can provide useful estimates of the role of Hib
in childhood pneumonia. Trials of pneumococcal conjugate vaccines that are
currently under way have been designed to estimate disease burden and
efficacy. A major risk of vaccine trials that use bacteriologic end points is
that the vaccine may affect the diagnostic test itself, creating a
misleading impression of efficacy. Trials of future tuberculosis vaccines are
discussed in light of these experiences. It is important that the trials
are designed to measure the effect on all clinical disease, as well as
strict microbiological end points. The existence of bacille
Calmette-Guerin (BCG) complicates future trials, and such trials should take into
account possible nonspecific effects of BCG in addition to its effect on
tuberculosis.
1866.
Muto P.
Ravo V. Panelli G. Liguori G.
Fraioli G. High-dose rate brachytherapy of bronchial
cancer: treatment optimization using three schemes of therapy. Oncologist.
5(3):209-14, 2000.
Abstract
PURPOSE: Our aim is to demonstrate that a
fractionated high-dose rate endobronchial brachytherapy (HDRBT)
treatment is tolerable for patients with advanced (IIIA-IIIB) non-small cell
lung cancer and gives an improvement of symptoms. Patients and
Methods. From January 1992 to July 1997, we treated 320 patients with external
beam radiotherapy (EBRT) and concomitant HDRBT with Ir192. Eighty-four
patients received 10 Gy in one fraction from January 1992 to March 1993
(Group A); 47 patients received two fractions of 7 Gy each from April 1993
to December 1993 (Group B), and 189 patients received three fractions of 5
Gy each from January 1994 to July 1997 (Group C). RESULTS: Mean survival
from diagnosis is 11.1 months and mean survival from last HDRBT is 9.7
months. The symptomatic response rate is 90% for dyspnea, 82% for cough, 94%
for hemoptysis and 90% for obstructive pneumonia. Performance status
was improved in 70% of patients. Follow-up is in the range of 5-36 months
with 280/320 evaluable patients (87.5%) (40 patients were lost to
follow-up). For the patients treated with three fractions of HDRBT plus EBRT, a
smaller number of side effects occurred while relief from symptoms linked
to bronchial obstruction and survival was similar for the three groups.
CONCLUSIONS: A three-fraction brachytherapy results in fewer side effects,
such as bronchial fibrosis with or without stenosis, while survival and
symptomatic relief are similar in the three groups treated.
1867. Norzila MZ.
Azizi BH. Deng CT. Zulfikar A.
Devadass P. Tai A. Gastro-oesophageal reflux in children with
severe respiratory symptoms--clinical spectrum and management.
Medical Journal of Malaysia. 51(1):93-8, 1996 Mar.
Abstract
Respiratory symptoms in children may be
associated with underlying gastro-oesophageal reflux (GOR). We reviewed
the case notes of 20 children who presented to us from June 1993 to June
1994 with respiratory symptoms and GOR. The patients consisted of 16 Malays, two Chinese and two Indians with equal number of males and females.
Their age at diagnosis was less than one year in 17 patients. The earliest
age at presentation was at the third day of life. All patients had major
respiratory manifestations i.e. recurrent wheezing, recurrent cough and
pneumonia. In addition, three patients had stridor and six patients had
apparent life threatening episodes (ALTE). Fourteen patients required
ventilation because of respiratory failure. Diagnosis of GOR was based on clinical grounds
supported by barium oesophagogram in seven
patients and ultrasound examination in 11 patients. Eight patients
were fundoplicated because of ALTE and recurrent severe bronchospasm. On
follow up, 14 patients had hyperactive airways requiring inhaled
bronchodilator and steroid therapy.
1868. Nys M.
Ledoux D. Canivet JL. De Mol P.
Lamy M. Damas P. Correlation between endotoxin level and
bacterial count in bronchoalveolar lavage fluid of ventilated patients. Critical Care Medicine. 28(8):2825-30, 2000 Aug.
Abstract
OBJECTIVE: To assess the predictive value of
the endotoxin level in the bronchoalveolar lavage (BAL) and to propose
to the clinician a guide in the diagnosis of gram-negative bacterial
(GNB) pneumonia. DESIGN: Retrospective and prospective studies to
investigate the relation between endotoxin level and quantitative bacterial culture of BAL and to test the
predictive value of a defined threshold.
SETTING: University hospital general intensive care unit. PATIENTS: In
the first part of the study, 77 consecutive ventilated patients with
clinical suspicion of nosocomial pneumonia between January 1995 and January
1996. In the second part of the study, 93 consecutive ventilated patients
studied prospectively between February 1996 and April 1997. MEASUREMENTS
AND MAIN RESULTS: Quantitative cultures for aerobic bacteria were performed
directly from the fluid. Bacterial species were determined with
standard techniques. The detection of endotoxin in BAL was made using a
quantitative chromogenic Limulus assay. In the retrospective analysis, a
significant correlation between quantitative GNB cultures and BAL endotoxin
levels was observed (r2 = 0.60, p < .0001). An endotoxin level >
or = 4 endotoxin units/mL (EU/mL) distinguishes patients with a significant
GNB count from colonized patients with a sensitivity of 92.6%, a
specificity of 81.4% and a correct classification rate of 84.9%. In the prospective analysis, the 4
EU/mL threshold permits identification of infected
patients with a sensitivity of 82.2%, a specificity of 95.6%, and a
correct classification rate of 90.3%. The receiver operating characteristic
curve analysis showed that the Limulus assay still had a good
discrimination power in the prediction of significant bacterial count in BAL fluid.
CONCLUSIONS: Endotoxin detection immediately after bronchoscopy is
a distinct advantage to the clinician because antimicrobial
gram-negative therapy may be immediately justified according to the results.
1869.
Overturf GD. American Academy of Pediatrics. Committee on
Infectious Diseases. Technical report: prevention of pneumococcal
infections, including the use of pneumococcal conjugate and polysaccharide
vaccines and antibiotic prophylaxis. Pediatrics.
106(2 Pt 1):367-76, 2000 Aug.
Abstract
Pneumococcal infections are the most common
invasive bacterial infections in children in the United States. The
incidence of invasive pneumococcal infections peaks in children younger than 2
years, reaching rates of 228/100,000 in children 6 to 12 months old.
Children with functional or anatomic asplenia (including sickle cell disease [SCD]) and children with
human immunodeficiency virus infection have pneumococcal infection rates
20- to 100-fold higher than those of healthy
children during the first 5 years of life. Others at high risk of
pneumococcal infections include children with congenital immunodeficiency;
chronic cardiopulmonary disease; children receiving
immunosuppressive chemotherapy; children with immunosuppressive neoplastic diseases;
children with chronic renal insufficiency, including nephrotic syndrome;
children with diabetes; and children with cerebrospinal fluid leaks. Children of Native American
(American Indian and Alaska Native) or
African American descent also have higher rates of invasive pneumococcal disease.
Outbreaks of pneumococcal infection have occurred with increased
frequency in children attending out-of-home care. Among these children,
nasopharyngeal colonization rates of 60% have been observed, along with
pneumococci resistant to multiple antibiotics. The administration of
antibiotics to children involved in outbreaks of pneumococcal disease has had an
inconsistent effect on nasopharyngeal carriage. In contrast, continuous penicillin prophylaxis in
children younger than 5 years with SCD has
been successful in reducing rates of pneumococcal disease by 84%.
Pneumococcal polysaccharide vaccines have been recommended since 1985 for
children older than 2 years who are at high risk of invasive disease, but these
vaccines were not recommended for younger children and infants because of
poor antibody response before 2 years of age. In contrast, pneumococcal
conjugate vaccines (Prevnar) induce proposed protective antibody
responses (>.15 microg/mL) in >90% of infants after 3 doses given at 2, 4, and 6
months of age. After priming doses, significant booster responses (ie,
immunologic memory) are apparent when additional doses are given at 12 to 15
months of age. In efficacy trials, infant immunization with Prevnar
decreased invasive infections by >93% and consolidative pneumonia by 73%,
and it was associated with a 7% decrease in otitis media and a 20% decrease
in tympanostomy tube placement. Adverse events after the
administration of Prevnar have been limited to areas of local swelling or
erythema of 1 to 2 cm and some increase in the incidence of postimmunization fever when it is given with
other childhood vaccines. Based on data in
phase 3 efficacy and safety trials, the US Food and Drug Administration
has provided an indication for the use of Prevnar in children younger than
24 months.
1870. Paul VK.
Ramani AV. Newborn care at peripheral health care
facilities. Indian Journal of Pediatrics. 67(5):378-82, 2000 May.
Abstract
Primary health centres, sub-district hospitals (first referral units) and district hospitals constitute the backbone of the health services in the country. These facilities are expected to cater to the care of the newborn infants who are delivered there, as well as those brought from the community with sickness. This paper, based on a survey in Orissa, and studies in a district hospital in Himachal Pradesh and a sub-district hospital in Haryana, is an attempt to piece together the present status of neonatal care at these facilities. In Orissa, the district and sub-district hospitals cater to a median of 100 and 30 deliveries per month, respectively. Most of the deliveries at these facilities are conducted by the nurses and not the physicians. Neonates are generally kept in the facility only for a day. Hardly any deliveries take place at primary health centres. Cesarean deliveries are mostly confined to the district hospitals. The commonest diagnosis of neonates admitted in the district and sub-district facilities is sepsis (septicemia pneumonia, skin infections, diarrhea and meningitis). Primary health centres seldom admit a sick neonate. It is reassuring to note that the outcome of sick neonates admitted at a functional district or sub-district hospital manned by a pediatrician is highly rewarding with low mortality rates.
1871.
Price GE.
Ou R. Jiang H. Huang L.
Moskophidis D. Viral escape by selection of cytotoxic T
cell-resistant variants in influenza A virus pneumonia. Journal of Experimental Medicine. 191(11):1853-67, 2000 Jun 5.
Abstract
Antigenic variation is a strategy exploited by influenza viruses to promote survival in the face of the host adaptive immune response and constitutes a major obstacle to efficient vaccine development. Thus, variation in the surface glycoproteins hemagglutinin and neuraminidase is reflected by changes in susceptibility to antibody neutralization. This has led to the current view that antibody-mediated selection of influenza A viruses constitutes the basis for annual influenza epidemics and periodic pandemics. However, infection with this virus elicits a vigorous protective CD8(+) cytotoxic T lymphocyte (CTL) response, suggesting that CD8(+) CTLs might exert selection pressure on the virus. Studies with influenza A virus-infected transgenic mice bearing a T cell receptor (TCR) specific for viral nucleoprotein reveal that virus reemergence and persistence occurs weeks after the acute infection has apparently been controlled. The persisting virus is no longer recognized by CTLs, indicating that amino acid changes in the major viral nucleoprotein CTL epitope can be rapidly accumulated in vivo. These mutations lead to a total or partial loss of recognition by polyclonal CTLs by affecting presentation of viral peptide by class I major histocompatibility complex (MHC) molecules, or by interfering with TCR recognition of the mutant peptide-MHC complex. These data illustrate the distinct features of pulmonary immunity in selection of CTL escape variants. The likelihood of emergence and the biological impact of CTL escape variants on the clinical outcome of influenza pneumonia in an immunocompetent host, which is relevant for the design of preventive vaccines against this and other respiratory viral infections, are discussed.
1872. Rankine JJ. Thomas AN. Fluechter D. Diagnosis of pneumothorax in critically ill adults. Postgraduate Medical Journal. 76(897):399-404, 2000 Jul.
Abstract
The diagnosis of pneumothorax is established
from the patients' history, physical examination and, where possible, by
radiological investigations. Adult respiratory distress syndrome,
pneumonia, and trauma are important predictors of pneumothorax, as are various
practical procedures including mechanical ventilation, central line insertion, and surgical procedures in
the thorax, head, and neck and abdomen. Examination should include an
inspection of the ventilator observations
and chest drainage systems as well as the patient's cardiovascular and
respiratory systems.Radiological diagnosis is normally confined to plain
frontal radiographs in the critically ill patient, although lateral
images and computed tomography are also important. Situations are described
where an abnormal lucency or an apparent lung edge may be confused with a
pneumothorax. These may arise from outside the thoracic cavity or from
lung abnormalities or abdominal viscera inside the chest.
1873. Rossi SE.
Erasmus JJ. McAdams HP. Sporn TA.
Goodman PC. Pulmonary drug toxicity: radiologic and
pathologic manifestations. Radiographics. 20(5):1245-59, 2000 Sep-Oct.
Abstract
Pulmonary drug toxicity is increasingly
being diagnosed as a cause of acute and chronic lung disease. Numerous
agents including cytotoxic and noncytotoxic drugs have the potential to
cause pulmonary toxicity. The clinical and radiologic manifestations of
these drugs generally reflect the underlying histopathologic processes and
include diffuse alveolar damage (DAD), nonspecific interstitial
pneumonia (NSIP), bronchiolitis obliterans organizing pneumonia (BOOP), eosinophilic
pneumonia, obliterative bronchiolitis, pulmonary
hemorrhage, edema, hypertension, or veno-occlusive disease. DAD is a common
manifestation of pulmonary drug toxicity and is frequently caused by
cytotoxic drugs, especially cyclophosphamide, bleomycin, and carmustine.
It manifests radiographically as bilateral hetero- or homogeneous
opacities usually in the mid and lower lungs and on high-resolution computed
tomographic (CT) scans as scattered or diffuse areas of ground-glass opacity.
NSIP occurs most commonly as a manifestation of carmustine toxicity or of
toxicity from noncytotoxic drugs such as amidarone. At radiography, it
appears as diffuse areas of heterogeneous opacity, whereas early CT
scans show diffuse ground-glass opacity and late CT scans show fibrosis in a
basal distribution. BOOP, which is commonly caused by bleomycin and cyclophosphamide (as well as gold salts and methotrexate), appears on
radiographs as hetero- and homogeneous peripheral opacities in both upper
and lower lobes and on CT scans as poorly defined nodular
consolidation, centrilobular nodules, and bronchial dilatation. Knowledge of these
manifestations and of the drugs most frequently involved can facilitate
diagnosis and institution of appropriate treatment.
1874.
Sarangi J.
Cartwright K. Stuart J. Brookes S.
Morris R. Slack M. Invasive Haemophilus influenzae disease in
adults. Epidemiology & Infection. 124(3):441-7, 2000 Jun.
Abstract
We reviewed retrospectively all invasive Haemophilus influenzae (Hi) infections in adults ascertained from reference laboratory records and notifications from five NHS regions over the 5 years from 1 October 1990, a period encompassing the introduction of routine Hib childhood immunization (October 1992). A total of 446 cases were identified, a rate of 0.73 infections per 10(5) adults per annum. Though numbers of Hib infections in adults fell after the introduction of Hib vaccines for children (P = 0.035), and there was no increase in infections caused by other capsulated Hi serotypes, total numbers of invasive Hi infections increased due to a large rise in infections caused by non-capsulated Hi (ncHi) strains (P = 0.0067). There was an unexpectedly low rate of infections in those aged 75 years or more (P < 0.0001). The commonest clinical presentations were pneumonia with bacteraemia (227/350, 65%) and bacteraemia alone (62/350, 18%) and the highest rates of disease were in the 65-74 years age group (P < 0.0001). Clinical presentation was not influenced by the capsulation status of the invading Hi strain. 103/350 cases (29%) died within 1 month, and 207/350 (59%) within 6 months of their Hi infection. Case fatality rates were high in all age groups. Pre-existing diseases were noted in 220/350 cases and were associated with a higher case fatality rate (82% vs. 21%, P < 0.0001). After the introduction of Hib immunization in children, invasive Hib infections in unimmunized adults also declined, but the overall rate of invasive Hi disease in adults increased, with most infections now caused by non-capsulated strains. Physicians and microbiologists should be aware of the changing epidemiology, the high associatedmortality and high risk of underlying disease. Invasive haemophilus infections in adults should be investigated and treated aggressively.
1875. Singh N.
Rogers P. Atwood CW. Wagener MM.
Yu VL. Short-course empiric antibiotic therapy for
patients with pulmonary infiltrates in the intensive care unit. A
proposed solution for indiscriminate antibiotic prescription. American Journal of Respiratory &
Critical Care Medicine. 162(2 Pt 1):505-11, 2000 Aug.
Abstract
Inappropriate antibiotic use for pulmonary
infiltrates is common in the intensive care unit (ICU). We sought to
devise an approach that would minimize unnecessary antibiotic use,
recognizing that a gold standard for the diagnosis of nosocomial pneumonia does not
exist. In a randomized trial, clinical pulmonary infection score (CPIS)
(Pugin, J., R. Auckenthaler, N. Mili, J. P. Janssens, R. D.
Lew, and P. M. Suter. Diagnosis of ventilator-associated pneumonia
by bacteriologic analysis of bronchoscopic and nonbronchoscopic
"blind" bronchoalveolar lavage fluid. Am. Rev. Respir. Dis. 1991;143: 1121-1129)
was used as operational criteria for decision-making regarding
antibiotic therapy. Patients with CPIS </= 6 (implying low likelihood of pneumonia) were randomized to
receive either standard therapy (choice and
duration of antibiotics at the discretion of physicians) or ciprofloxacin
monotherapy with reevaluation at 3 d; ciprofloxacin was discontinued if
CPIS remained </= 6 at 3 d. Antibiotics were continued beyond 3 d in 90%
(38 of 42) of the patients in the standard as therapy compared with 28%
(11 of 39) in the experimental therapy group (p = 0.0001). In patients in
whom CPIS remained </= 6 at the 3 d evaluation point, antibiotics were still
continued in 96% (24 of 25) in the standard therapy group but in 0% (0
of 25) of the patients in the experimental therapy group (p = 0.0001). Mortality and length of ICU stay
did not differ despite a shorter duration (p
= 0.0001) and lower cost (p = 0.003) of antimicrobial therapy in the
experimental as compared with the standard therapy arm. Antimicrobial
resistance, or superinfections, or both, developed in 15% (5 of 37) of the
patients in the experimental versus 35% (14 of 37) of the patients in the
standard therapy group (p = 0.017). Thus, overtreatment with antibiotics
is widely prevalent, but unnecessary in most patients with pulmonary
infiltrates in the ICU. The operational criteria used, regardless of the
precise definition of pneumonia, accurately identified patients
with pulmonary infiltrates for whom monotherapy with a short course of
antibiotics was appropriate. Such an approach led to significantly lower
antimicrobial therapy costs, antimicrobial resistance, and superinfections
without adversely affecting the length of stay or mortality.
1876. Spicer PE.
Clapham G. Multiple liver abscesses: an unusual case
which demonstrates the importance of ultrasonography in the
detection of liver pathology. Papua New Guinea Medical Journal. 41(2):77-82, 1998 Jun.
Abstract
A 48-year-old caucasian male was admitted to
hospital with right-sided chest pain, pyrexia and cough. He had no
history of dysentery. He was treated with erythromycin and cotrimoxazole
for right lower lobe pneumonia but failed to respond. Tender hepatomegaly
developed and ultrasound scan demonstrated multiple abscesses in the liver. Entamoeba histolytica was
identified in his faeces. He was treated
with intravenous metronidazole, chloramphenicol and gentamicin and then oral
tinidazole, after which improvement was rapid. He was later
transferred to Australia. Subsequent abdominal CAT scan and aspiration of
abscesses confirmed the diagnosis of multiple amoebic liver abscesses with
secondary bacterial infection. Final treatment was with oral ciprofloxacin and
metronidazole for four weeks. Ultrasonography is a noninvasive technique
which is invaluable in the diagnosis of abdominal and especially liver pathology. This technique
should be available in larger centres in
tropical countries. Anyone living in or visiting the tropics should be aware
of possible exotic diseases presenting in unusual ways.
1877. Stalam M.
Kaye D. Antibiotic agents in the elderly. Infectious Disease Clinics of North
America. 14(2):357-69, 2000 Jun.
Abstract
Changes that occur in the pharmacology of
drugs in the elderly must be considered in the use of antimicrobial
agents. Although absorption of orally administered drugs is not affected in
a significant way, renal function decreases, drug-drug interactions increase, compliance with
regimens may be decreased, and drug toxicity
is increased. The most frequent infections occurring in the elderly
are pneumonia, urinary tract infection, and soft-tissue infection. CDAD
is usually a complication of antibiotic therapy. Pneumonia can be
categorized as community-acquired, LTCF, and hospital-acquired. Therapeutic
approaches vary according to which of these sites is involved. Urinary
tract infection is divided into upper tract infection, lower tract infection, and asymptomatic
bacteriuria. Upper tract infection is
treated for a longer period than lower tract infection; with few exceptions,
asymptomatic bacteriuria is usually not treated. Soft-tissue infection
is usually caused by an infected pressure ulcer or cellulitis (which
may be a complication of a diabetic foot ulcer or an ulcer due to
peripheral vascular disease). These infections have different microbial causes and require different
therapeutic approaches.
1878. Teel GS.
Engeler CE. Tashijian JH. duCret RP. Imaging of small airways disease. Radiographics. 16(1):27-41, 1996 Jan.
Abstract
High-resolution computed tomography (HRCT)
is the most useful modality for imaging of small airways disease. Direct
signs of small airways disease that appear on HRCT scans are the result of
changes in the airway wall or lumen. Abnormal small airways can be seen as
tubular, nodular, or branching linear structures on HRCT scans. Indirect signs of small airways
disease result from changes in the lung
parenchyma distal to the diseased small airway and include air trapping,
subsegmental atelectasis, centrilobular emphysema, and air-space
nodules. Diverse inflammatory and infectious processes, such as bronchiolitis
obliterans (BO), bronchiolitis obliterans with organizing pneumonia (BOOP),
smoking-related diseases, and
asthma affect the small airways of the
lungs. HRCT findings of BO include
air trapping and bronchiectasis. The
predominant findings of BOOP are
consolidation and ground-glass attenuation.
HRCT can show abnormalities
such as small nodules and areas of
ground-glass attenuation even in
asymptomatic smokers, but emphysema
predominates in smokers with moderate
or severe obstructive disease. Patients with
asthma can have thickened
airway walls, plugged large and small
airways, subsegmental atelectasis,
and air trapping, but emphysema is rarely
seen even in severe asthma
patients. HRCT scans can often accurately
depict disease processes in the
small airways and can occasionally lead to a
specific diagnosis from among
several clinically relevant possibilities.
[References: 39]
1879. Authors
Vimercati A. Greco P. Bettocchi
S. Resta L. Selvaggi L.
Title
Legionnaire's disease complicating
pregnancy: a case report with
intrauterine fetal demise.
Source
Journal of Perinatal Medicine. 28(2):147-50, 2000.
Abstract
OBJECTIVE: Legionnaire's disease
complicating pregnancy is an unusual
event that can seriously compromise both the
mother and the fetus. CASE
REPORT: We describe one case of such
association, with an unfavourable
intrauterine fetal outcome, secondary to
acute placental insufficiency,
related to infection. DISCUSSION: It is
important in these high risk
pregnancies complicated by acute pneumonia
to take into consideration the
diagnosis, as early as possible, and the
appropriate treatment or the
careful monitoring of fetal wellbeing.
1880. Authors
Wever PC.
Yzerman EP. Kuijper EJ. Speelman P.
Dankert J.
Title
Rapid diagnosis of Legionnaires' disease
using an immunochromatographic
assay for Legionella pneumophila serogroup 1
antigen in urine during an
outbreak in the Netherlands.
Source
Journal of Clinical Microbiology. 38(7):2738-9, 2000 Jul.
Abstract
A new immunochromatographic assay for rapid
qualitative detection of
Legionella pneumophila serogroup 1 antigen
in urine specimens was used
during an outbreak of legionellosis in The
Netherlands. The assay seems of
the utmost value in providing a rapid
diagnosis of Legionnaires' disease
in patients with severe community-acquired
pneumonia in an outbreak
setting.
1881. Authors
Yigla M.
Ben-Itzhak O. Solomonov A. Guralnik L.
Oren I.
Title
Recurrent, self-limited,
menstrual-associated bronchiolitis obliterans
organizing pneumonia.
Source
Chest.
118(1):253-6, 2000 Jul.
Abstract
A 39-year-old woman presented with recurrent
acute illness, characterized
by high-grade fever, pleuritic chest pain,
and unilateral nodular
infiltrate on chest radiograph. During the
follow-up period, there were
six similar episodes, each starting 2 to 3
days prior to her menstrual
period and resolving within 5 to 10 days.
Persistent symptoms in the
seventh episode led us to perform an open
lung biopsy; the specimen showed
histologic changes compatible with the
diagnosis of bronchiolitis
obliterans organizing pneumonia (BOOP). To
the best of our knowledge, this
is the first report describing BOOP in
association with a menstrual
period. This exceptional case emphasizes the
wide and unexpected spectrum
of this disease.
1882. Authors
Yu P.
Martin CM.
Title
Increased gut permeability and bacterial
translocation in Pseudomonas
pneumonia-induced sepsis.
Source
Critical Care Medicine. 28(7):2573-7, 2000 Jul.
Abstract
OBJECTIVE: Gut injury and barrier
dysfunction may contribute to the
pathogenesis of sepsis and multiple organ
dysfunction syndrome. The
objective of this study was to determine
whether gut injury could be
demonstrated in hyperdynamic, normotensive
sepsis induced by Pseudomonas
pneumonia. DESIGN: Randomized animal study.
SETTING: University
laboratory. SUBJECTS: Adult male
Sprague-Dawley rats. INTERVENTIONS:
Sepsis was induced by intratracheal
instillation of Pseudomonas
aeruginosa. MEASUREMENTS AND MAIN RESULTS:
We measured gut mucosal and
microvascular injury. In the first
experiment, gut mucosal permeability
was measured by 51Cr-EDTA uptake in control
(n = 6), pneumonia 20-hr (n =
4), and pneumonia 40-hr (n = 4) groups. In
the second experiment,
microvascular permeability was measured by
albumin extravasation, and
morphologic abnormalities were scored in
control (n = 6), pneumonia 20-hr
(n = 9), and pneumonia 40-hr (n = 11)
groups. Bacterial translocation to
mesenteric lymph nodes was determined in
both experiments. Cardiac index
increased significantly in the pneumonia
compared with control rats
(64+/-2.1, 68+/-1.3, vs. 46+/-2 mL/min/100
g, p < .05; all results are
listed in the order of pneumonia 20-hr,
pneumonia 40-hr, and control
groups as mean +/- SEM). Mean blood pressure
was normal and was not
different between groups (112+/-3, 111+/-2,
vs. 118+/-2 mm Hg). 51Cr-EDTA
recovery in urine 6 hrs after gavage
increased significantly in both
pneumonia groups vs. controls (17.5+/-2.2%,
17.9+/-7%, vs. 4+/-0.7%; p <
.05). Albumin leak (tissue/plasma ratio)
increased significantly in the
middle and distal small intestine in the
pneumonia 40-hr group vs.
controls (0.68+/-0.05, 0.76+/-0.07, vs.
0.45+/-0.04, p < .05 in the middle
small gut; 0.75+/-0.09, 0.85+/-0.07, vs.
0.51+/-0.05, p < .05 in the
distal small gut). Bacterial translocation
to mesenteric lymph nodes
increased significantly in pneumonia 40-hr
rats vs. controls (positive
culture 67% vs. 8%; p < .05).
CONCLUSIONS: This study demonstrates gut
mucosal and microvascular injury and gut
barrier dysfunction in
normotensive sepsis secondary to bacterial
pneumonia. The mechanism and
significance of the injury need to be
determined.
1883. Authors
Zaytoun GM.
Rouadi PW. Baki DH.
Title
Endoscopic management of foreign bodies in
the tracheobronchial tree:
predictive factors for complications.
Source
Otolaryngology - Head & Neck
Surgery. 123(3):311-6, 2000 Sep.
Abstract
We reviewed the records of 504 patients
admitted to the American
University of Beirut Medical Center during a
10-year period for treatment
of aspiration of a foreign body into the
tracheobronchial tree. All
underwent rigid fiberoptic bronchoscopy for
removal of the foreign body.
Complications occurred in 42 patients (8%)
and were classified as
intraoperative (7 patients), postoperative
(25 patients), and failure to
retrieve the foreign body by bronchoscopy (9
patients). These
complications included respiratory distress
necessitating tracheotomy
and/or assisted ventilation, bronchial
pneumonia, pneumothorax,
bradycardia, and cardiac arrest. Variables
that were examined were the age
and sex of the patient, history of multiple
previous bronchoscopies, delay
in diagnosis and/or treatment, duration of
the procedure, type and
location of the foreign body, and use of
corticosteroids during surgery.
The most important variables that were of
value in predicting the
occurrence of complications were the history
of previous bronchoscopy, the
duration of the procedure, and the type of
foreign body. Age, sex, delay
in diagnosis and treatment, and
intraoperative use of corticosteroids,
while important, had no predictive value.
Detailed results with guidelines
for prevention and management are presented.
PNEUMONIA
(Diagnosis, Diagnostics, Immunodiagnosis,
Immunodiagnostics, Vaccines & Drugs)
JULY 2001
2406. Benfield TL. Helweg-Larsen J. Bang D. Junge J. Lundgren JD. Prognostic markers of short-term mortality in AIDS-associated Pneumocystis carinii pneumonia. Chest. 119(3):844-51, 2001 Mar.
Abstract
BACKGROUND: Since 1990, corticosteroids have been recommended as adjunctive therapy for patients with AIDS-associated Pneumocystis carinii pneumonia (PCP) and respiratory failure. We hypothesized that the natural course of AIDS-associated PCP has changed in the era of adjunctive corticosteroid therapy. OBJECTIVE: To study variables obtained on hospital admission for possible prognostic value of short-term (3-month) outcome of PCP. DESIGN AND PATIENTS: Prospective observational study of 176 consecutive HIV-1-infected individuals with PCP between 1990 and 1999. METHOD: Cox proportional-hazards regression models. RESULTS: Univariate analysis showed that age, one or more prior episodes of PCP, use of antimicrobial therapy other than trimethoprim-sulfamethoxazole (TMP-SMZ), use of PCP prophylaxis at diagnosis, and culture of cytomegalovirus (CMV) in BAL predicted progression to death within 3 months. After adjustment, age (relative risk [RR], 4.1; 95% confidence interval [CI], 1.8 to 9.3), initial antimicrobial therapy other than TMP-SMZ (RR, 3.1; 95% CI, 1.2 to 8.5), use of PCP prophylaxis (RR, 5.6; 95% CI, 2.2 to 14.4), and culture of CMV in BAL fluid (RR, 2.7; 95% CI, 1.3 to 5.6) remained independent predictors of a poor outcome. In contrast, neither PO(2) nor serum lactate dehydrogenase, which in earlier studies were identified as prognostic markers, were predictors of mortality. CONCLUSION: Age, initial anti-PCP therapy, use of PCP prophylaxis, and BAL CMV status may be useful predictors of outcome of PCP in patients treated in the era of adjunctive corticosteroid therapy.
2408. Christenson B. Lundbergh P. Hedlund J. Ortqvist A. Effects of a large-scale intervention with influenza and 23-valent pneumococcal vaccines in adults aged 65 years or older: a prospective study. Lancet. 357(9261):1008-11, 2001 Mar 31.
Abstract
BACKGROUND: The effectiveness of influenza and pneumococcal vaccination in the prevention of hospital admissions and death has not been assessed prospectively. We have therefore examined the effects of influenza and pneumococcal vaccination in individuals aged 65 years and older in a 3-year prospective study, between Dec 1, 1998 and May 31, 1999. METHODS: All individuals in Stockholm County aged 65 years or older (259,627) were invited to take part in a vaccination campaign against influenza and pneumococcal infection. We recorded for all vaccine recipients (100,242) name, and date of birth, and whether they had been given both or one of the vaccines. All individuals (> or = 65 years) admitted to hospital in Stockholm County with influenza and pneumonia related diagnoses were identified between Dec 1, 1998, and May 31, 1999. FINDINGS: The incidence (per 100,000 inhabitants per year) of hospital treatment was lower in the vaccinated than in the unvaccinated cohort for all diagnoses: 263 versus 484 (-46% [95% CI 34-56]) for influenza; 2199 versus 3097 (-29% [24-34)) for pneumonia; 64 versus 100 (-36% [3-58]) for pneumococcal pneumonia; and 20 versus 40 (-52% and 2 over black square]; and 2 over black square]; [1 and 2 over black square] and 2 over black square]-77]) for invasive pneumococcal disease. The total mortality was 57% (55-60) lower in vaccinated than in unvaccinated individuals (15.1 vs 34.7 deaths per 1000 inhabitants). INTERPRETATION: These findings show that general vaccination leads to substantial health benefits and to a reduction of mortality from all causes in this age group.
2409. Crippa F. Corey L. Chuang EL. Sale G. Boeckh M. Virological, clinical, and ophthalmologic features of cytomegalovirus retinitis after hematopoietic stem cell transplantation. Clinical Infectious Diseases. 32(2):214-9, 2001 Jan 15.
Abstract
We identified 10 patients who developed cytomegalovirus (CMV) retinitis after HSCT during a 14-year period. The median day of diagnosis of CMV retinitis after transplantation was day 251 (range, days 106--365). CMV retinitis was associated with CMV serostatus of donor or recipient (P=0.01), CMV reactivation before day 100 (P=0.007), delayed lymphocyte engraftment (P<0.05), and chronic graft versus host disease (GVHD; P<0.001). In allogeneic recipients of HSCT who were alive at day 100 after transplantation and had chronic clinical extensive GVHD, the incidence of GVHD was 1.4% (8 of 577). Five of 10 patients had other manifestation of CMV disease before retinitis occurred (4 with gastrointestinal disease and 1 with interstitial pneumonia; median time, 70 days before onset of CMV retinitis; range, 58--279 days), and 4 others had CMV excretion. CMV retinitis was bilateral in 4 patients; 9 of 10 patients had ocular symptoms (i.e., decreased vision and floaters). Six of 7 patients responded well to ganciclovir or foscarnet systemic treatment, 1 improved only after switching to cidofovir, and 1 patient who received a transplant in 1983 did not respond to acyclovir treatment. In conclusion, CMV retinitis is an uncommon late complication after HSCT that occurs mainly in seropositive allograft recipients with previous CMV reactivation and chronic GVHD, and with delayed engraftment of lymphocytes.
2410. Cunha BA. Nosocomial pneumonia. Diagnostic and therapeutic considerations. [Review] [167 refs] Medical Clinics of North America. 85(1):79-114, 2001 Jan.
Abstract
Many patients with presumed nosocomial pneumonia probably have infiltrates on the chest radiograph, fever, and leukocytosis resulting from noninfectious causes. Because of the high mortality and morbidity associated with nosocomial pneumonias, however, most clinicians treat such patients with a 2-week empiric trial of antibiotics. Before therapy is initiated, the clinician should rule out other causes of pulmonary infiltrates, fever, and leukocytosis that mimic a nosocomial pneumonia (e.g., pre-existing interstitial lung disease, primary or metastatic lung carcinomas, pulmonary emboli, pulmonary drug reactions, pulmonary hemorrhage, collagen vascular disease affecting the lungs, or congestive heart failure). If these disorders can be eliminated from diagnostic consideration, a 2-week trial of empiric monotherapy is indicated. The clinician should treat cases of presumed nosocomial pneumonia as if P. aeruginosa were the pathogen. Although P. aeruginosa is not the most common cause of nosocomial pneumonia, it is the most virulent pulmonary pathogen associated with nosocomial pneumonia. Coverage directed against P. aeruginosa is effective against all other aerobic gram-negative bacillary pathogens causing hospital-acquired pneumonia. The clinician should select an antibiotic for empiric monotherapy that is highly effective against P. aeruginosa, has a good side-effect profile, has a low resistance potential, and is relatively inexpensive in terms of its cost to the institution. The preferred agents for empiric monotherapy for nosocomial pneumonia are cefepime, meropenem, and piperacillin. Single organisms are responsible for nosocomial pneumonia, not multiple pathogens. S. aureus rarely, if ever, causes nosocomial pneumonia but is mentioned frequently in studies based on cultures of respiratory tract secretions. S. aureus, unless accompanied by a necrotizing pneumonia with rapid cavitation within 72 hours, in the sputum indicates colonization rather than infection and should not be addressed therapeutically. Antibiotics associated with a high resistance potential should not be used as monotherapy or included in combination therapy regimens (i.e., ceftazidime, ciprofloxacin, imipenem, or gentamicin). Combination therapy is more expensive than monotherapy and is indicated only when P. aeruginosa is extremely likely, based on its characteristic clinical presentation, or is proved by tissue biopsy. Therapy should not be based on respiratory secretion cultures regardless of technique. Optimal combination regimens include cefepime or meropenem plus levofloxacin or piperacillin or aztreonam or amikacin. Nosocomial pneumonias usually are treated for 14 days. Lack of radiographic or clinical response to appropriate empiric nosocomial pneumonia monotherapy after 14 days suggests an alternate diagnosis. In these patients, a tissue biopsy specimen should be obtained to determine the cause of the persistence of pulmonary infiltrates unresponsive to appropriate antimicrobial therapy. [References: 167]
2413. Eron LJ. Passos S. Early discharge of infected patients through appropriate antibiotic use. Archives of Internal Medicine. 161(1):61-5, 2001 Jan 8.
Abstract
BACKGROUND: Patients with infections are usually discharged from the hospital with antibiotics when afebrile and clinically improved. OBJECTIVES: To compare outcomes of early vs conventionally discharged patients and to examine the role of antibiotic use in the discharge process. METHODS: One hundred eleven patients hospitalized with cellulitis, community-acquired pneumonia, or pyelonephritis (urinary tract infection) discharged from the hospital early in their clinical course before defervescence by an infectious diseases hospitalist (L.J.E.) were compared in a case-controlled study with 112 patients discharged from the hospital according to conventional standards of care by internal medicine (IM) hospitalists. Patients were matched for age, sex, diagnosis, and comorbidities. Outcomes were determined for average lengths of stay, readmission to the hospital within 30 days with the same diagnosis, satisfaction with their discharge program, and time to return to their normal activities of daily living. RESULTS: Patients cared for by the infectious diseases hospitalist had a shorter average length of stay (mean difference, 1.7 days), no readmissions, higher satisfaction scores, and a shorter time to return to their activities of daily living, compared with those cared for by the IM hospitalists. Analysis of the antibiotics that patients were discharged with revealed that the infectious diseases hospitalist used outpatient parenteral antibiotic therapy more frequently than IM hospitalists in the treatment of cellulitis, and switched from intravenous to oral antibiotics sooner than IM hospitalists for patients with community-acquired pneumonia and urinary tract infection. CONCLUSIONS: The infectious diseases hospitalist discharged patients from the hospital earlier than the IM hospitalists by more efficient use of antibiotics. The earlier discharge did not adversely affect outcomes.
2114. Fiel S. Guidelines and critical pathways for severe hospital-acquired pneumonia. [Review] [24 refs] Chest. 119(2 Suppl):412S-418S, 2001 Feb.
Abstract
Hospital-acquired pneumonia (HAP) is associated with high morbidity and mortality. Early, appropriate, and adequate empiric therapy can increase the chance of survival. In 1995, the American Thoracic Society provided guidelines for the initial treatment of immunocompetent HAP patients, which is one of the principal HAP management approaches available to physicians today. However, these guidelines have several important limitations, including a lack of recommendations for duration of therapy and no recognition of newer drugs such as cefepime, trovafloxacin, and meropenem. Furthermore, they fail to distinguish among similar compounds (ie, beta-lactam/beta-lactamase inhibitor combinations) or to recommend specific antibiotics. The clinician using these guidelines needs to address local patterns of antimicrobial resistance, especially in ICUs. Effective computerized antibiotic management programs that incorporate information on local patterns of antimicrobial resistance can assist physicians in empiric therapy decision making, improve patient quality of care, and reduce medical costs. [References: 24]
2415. Flanagan PG. Jackson SK. Findlay G. Diagnosis of gram negative, ventilator associated pneumonia by assaying endotoxin in bronchial lavage fluid. Journal of Clinical Pathology. 54(2):107-10, 2001 Feb.
Abstract
AIM: To investigate the usefulness of assaying endotoxin in non-directed bronchial lavage fluid (NBL), bronchoscopic bronchoalveolar lavage fluid (BAL), and sera as a means of diagnosing Gram negative, ventilator associated pneumonia. METHODS: Samples from 64 patients were investigated. Fifty nine BALs and 92 NBLs were assayed in total including specimens taken during 28 episodes of clinical ventilator associated pneumonia (VAP). RESULTS: The concentration of endotoxin in BAL from patients with VAP developing within four days of commencing ventilation was significantly higher than in those without VAP (p = 0.015). There was no significant difference in endotoxin concentration in NBL or serum when comparing patients with and without VAP. A BAL endotoxin concentration of 6 EU/ml yielded the optimal operating characteristics (sensitivity, 81%; specificity, 87%; positive predictive value, 67%; negative predictive value, 95%). However, Gram stain of BAL provided the same information as quickly as the endotoxin assay and is considerably cheaper. CONCLUSIONS: Despite its accuracy and rapidity, the BAL endotoxin assay must be shown to alter clinical management and patient outcome to be cost effective.
2417. Grenier A. Combaux D. Chastre J. Gougerot-Pocidalo MA. Gibert C. Dehoux M. Chollet-Martin S. Oncostatin M production by blood and alveolar neutrophils during acute lung injury. Laboratory Investigation. 81(2):133-41, 2001 Feb.
Abstract
Polymorphonuclear neutrophils (PMN) are involved in the pathogenesis of acute lung injury (ALI), secreting numerous mediators such as proteases, reactive oxygen species, and cytokines. Because we had recently observed the ability of normal human PMN to degranulate and synthesize oncostatin M (OSM), an IL-6-family cytokine, we quantified OSM production ex vivo by highly purified blood and alveolar PMN from 24 ventilated patients with ALI, including some patients with severe pneumonia. Most of the patients had no detectable OSM in plasma, and OSM production by cultured blood PMN was similar to that of healthy controls. However, OSM was present in bronchoalveolar lavage (BAL) fluid supernatant, with significantly higher levels during pneumonia. In addition, alveolar OSM levels correlated with the number of PMN obtained by BAL, suggesting that PMN are an important source of OSM within the alveoli. Indeed, purified alveolar PMN from all of the patients, especially those with pneumonia, strongly produced OSM. Interestingly, in the latter patients, alveolar PMN always produced more OSM than autologous blood PMN. These results document the functional duality of PMN in ALI by showing the participation of PMN in the modulation of lung inflammation.
2418. Martinez Garcia MA. de Rojas MD. Nauffal Manzur MD. Munoz Pamplona MP. Compte Torrero L. Macian V. Perpina Tordera M. Respiratory disorders in common variable immunodeficiency. Respiratory Medicine. 95(3):191-5, 2001 Mar.
Abstract
Common variable immunodeficiency (CVID) is a heterogeneous immunodeficiency syndrome characterized by hypogammaglobulinemia, recurrent bacterial infections, and various immunologic abnormalities. The clinical presentation is generally that of recurrent pyogenic sinopulmonary infections. Our objectives were to study the prevalence of lung involvement and the response to intravenous immunoglobulin replacement therapy in 19 patients with CVID. Nineteen patients (12 men) with a mean age (SD) of 33.1 (17.1) years had a previous diagnosis of CVID and were treated with intravenous immunoglobulin replacement. All patients underwent complete pulmonary function tests and high-resolution computed tomography (HRCT) examination. Bronchiectasis was diagnosed in 11 (58%) patients and eight (42%) were multi-lobar bronchiectasis. Chronic airflow limitation (CAL) was present in 10 (53%) patients and a restrictive pattern was seen in one case. Eleven patients (58%) presented a decrease in single-breath carbon monoxide diffusing capacity of the lung (DL(CO)). Before intravenous immunoglobulin replacement therapy (INIRT), 84% of patients had suffered from at least one episode of pneumonia. Episodes of lower respiratory tract infection decreased significantly from 0.28 per patient and year before replacement therapy to 0.16 per patient and year after treatment. The mean duration of replacement therapy was 7.5 years. In conclusion lung involvement was frequent in patients with CVID. Long-term administration of intravenous gammaglobulin resulted in a substantial reduction of pneumonic episodes.
2419. Mascellino MT. Delogu G. Pelaia MR. Ponzo R. Parrinello R. Giardina A.Reduced bactericidal activity against Staphylococcus aureus and Pseudomonas aeruginosa of blood neutrophils from patients with early adult respiratory distress syndrome. Journal of Medical Microbiology. 50(1):49-54, 2001 Jan.
Abstract
This study investigated the bactericidal capability of circulating neutrophils from blunt trauma patients admitted to an Intensive Care Unit against Staphylococcus aureus and Pseudomonas aeruginosa. Among those patients, two groups were considered and compared: patients who developed adult respiratory distress syndrome (ARDS) and patients who developed only pneumonia. Peripheral blood samples were drawn as soon as a diagnosis of pneumonia or ARDS was made, followed by the isolation of neutrophil cells and assessment of bacteria phagocytosis and killing. The results demonstrated that in patients with ARDS, phagocytosis and killing efficiency were significantly impaired in comparison with patients with pneumonia and healthy controls. A possible dysregulation of reactive oxygen species production involving the release of humoral mediators in early ARDS may be involved.
2421. Muller MP. Richardson DC. Walmsley SL. Trimethoprim-sulfamethoxazole induced aseptic meningitis in a renal transplant patient. [Review] [20 refs] Clinical Nephrology. 55(1):80-4, 2001 Jan.
Abstract
A 45-year-old man underwent renal transplant for end-stage renal disease complicating systemic lupus erythematosis. Within 24 hours of initiating Pneumocystis carinii pneumonia (PCP) prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX) he developed fever and confusion. Cerebrospinal fluid examination revealed a pleocytosis but cultures were negative. The patient improved within three days after cessation of the TMP-SMX but symptoms recurred rapidly upon drug rechallenge. Drug-induced aseptic meningitis is an uncommon but well described clinical entity. This is the first case described in a patient following renal transplantation. The literature is reviewed and the clinical features, diagnostic challenges and possible mechanisms of TMP-SMX-induced aseptic meningitis are discussed. This problem may be more common in the transplant population than is recognized given the difficulty of diagnosis combined with the widespread use of TMP-SMX as PCP prophylaxis. [References: 20]
2423. Nadala D. Bossart W. Zucol F. Steiner F. Berger C. Lips U. Altwegg M. Community-acquired pneumonia in children due to Mycoplasma pneumoniae: diagnostic performance of a seminested 16S rDNA-PCR. Diagnostic Microbiology & Infectious Disease. 39(1):15-9, 2001 Jan.
Abstract
A 16S rDNA-PCR assay for Mycoplasma pneumoniae applied to nasopharyngeal secretion (NPS) or pharyngeal swab (PS) from children with community-acquired pneumonia (CAP) was prospectively compared to serological tests including complement fixation (CF) test, a mu-capture enzyme immuno assay (EIA) for the detection of specific IgM, and an EIA for the detection of specific IgG. During a 24-months-period diagnosis of active M. pneumoniae infection was established in 32 (12.6%) of 253 patients for whom paired sera were available. In the acute phase, the sensitivities of PCR from NPS and PS, CF test, IgM EIA, and IgG EIA were 90.0%, 79.3%, 46.9%, 78.1%, and 59.4%, respectively. The corresponding specificities were 98.1%, 98.6%, 97.6%, 87.1%, and 72.4%, respectively. Thus, the 16S rDNA-PCR assay provides a highly sensitive and accurate tool for the rapid diagnosis of M. pneumoniae infection in children with CAP.
2424. Pesola GR. The urinary antigen test for the diagnosis of pneumococcal pneumonia. [letter; comment]. Chest. 119(1):9-11, 2001 Jan.
2427. Remiszewski P. Slodkowska J. Wiatr E. Zych J. Radomski P. Rowinska-Zakrzewska E. Fatal infection in patients treated for small cell lung cancer in the Institute of Tuberculosis and Chest Diseases in the years 1980-1994. Lung Cancer. 31(2-3):101-10, 2001 Feb-Mar.
Abstract
The study was performed to explore the frequency of infections present at death and infection as the main cause of death (fatal infection - FI) in 845 consecutive patients (pts) treated for small cell lung cancer (SCLC) at the Institute of Tuberculosis and Chest Diseases in Warsaw, in the period 1980-1994. Diagnosis of infection was based on clinical signs and symptoms, the presence of new lesions on the chest X-ray, microbiological tests and/or autopsy examination. All cases of fungal infection, Pneumocystis carinii pneumonia (PCP) and tuberculosis were proved by autopsy and microscopic examination (including special staining). FI was diagnosed if no progression of cancer was noted and no other complications occurred. Infection was present at the time of death in 116 patients (13.7%) and FI was the cause of death in 39 of them (4.6%). Nine patients died from fungal infection, eight from bacterial infection, seven from PCP and two from tuberculosis. In 13 cases the aetiology of infection found at autopsy was not determined. All FI patients received chemotherapy and corticosteroids, 16 of them also had radiotherapy on the tumour and mediastinum. Thirty-two out of 35 patients had leucopenia. The risk of death from infection was greater in patients above 60 years of age. Patients in bad performance status died of infection significantly earlier than others (P<0.05).
2428. Simsir A. Oldach D. Forest G. Henry M. Rhodococcus equi and cytomegalovirus pneumonia in a renal transplant patient: diagnosis by fine-needle aspiration biopsy. Diagnostic Cytopathology. 24(2):129-31, 2001 Feb.
Abstract
Rhodococcus equi is a common cause of pneumonia in animals. Human infection is rare. Increasing number of cases are being reported in immunosuppressed individuals mostly associated with HIV infection, but also in solid organ transplant recipients and leukemia/lymphoma patients. We report on an adult male who developed pneumonia and gastroenteritis 4 mo after receiving a renal transplant. CT scan of the lungs showed a dominant 2.5-cm upper lobe lung mass and smaller bilateral nodules. He underwent a diagnostic bronchoscopy with fine-needle aspiration biopsy of the largest lung nodule. Smears showed histiocytic granulomatous inflammation, foamy macrophages, and acute inflammatory exudate. Scattered foamy macrophages displayed intracellular coccobacilli identifiable on Diff-Quik stain. A few cells with changes suggestive of viral inclusions were identified. Cytomegalovirus (CMV) immunostain was positive in the cell block sections. Lung cultures grew R. equi. To the best of our knowledge, this is the first report of coinfection with R. equi and CMV. Copyright 2001 Wiley-Liss, Inc.
2434. Tuuminen T. Suni J. Kleemola M. Jacobs E. Improved sensitivity and specificity of enzyme immunoassays with P1-adhesin enriched antigen to detect acute Mycoplasma pneumoniae infection. Journal of Microbiological Methods. 44(1):27-37, 2001 Feb 1.
Abstract
An in-house P1-enriched (168-kDA protein) Mycoplasma pneumoniae antigen preparation was compared in IgG, IgA and IgM enzyme immunoassays (EIAs) to the respective EIAs employing crude antigen lysate, antigen prepared by Triton X-114 partition and two commercial antigens, one of which was an ether-extracted antigen and the other a P1-enriched antigen. In addition, three commercial kits from Sanofi Pasteur, Novum Diagnostica and Savyon Diagnostics were also assessed for comparison. Diagnostic sensitivity was studied with paired samples from adults (n=37) with acute respiratory illness interpreted as acute, recent or past infection to M. pneumoniae on the basis of the results of complement fixation test (CFT). If the consensus of at least two methods is taken as the true positive for acute infection, the diagnostic sensitivities of combined IgG and IgM EIAs were 100% for the Platelia(R), Sero MP and in-house EIAs whereas for the Novum EIAs and CFT- 97% and 74%, respectively. Moreover, the sensitivity of the P1-enriched antigen was proven superior on the basis of systematically highest OD(405 nm) ratios between convalescent and acute serum samples.Analytical specificity was studied by screening serum samples from 92 Finnish blood donors and 111 serum samples from cord blood. Diagnostic specificity was studied in a blind testing of 30 paired serum samples from infants with pneumonia of variable etiology. No single misinterpretation of acute infection from the group of samples with other respiratory diseases did occur.The present study confirmed and extended the earlier observations of the usefulness of P1-enriched antigen for reliable serologic diagnosis of acute M. pneumoniae infection.
2435. No Abstract
2436. No Abstract
2882. Akpek G. McAneny D.
Weintraub L. Risks and benefits of splenectomy in myelofibrosis with
myeloid metaplasia: a retrospective analysis of 26 cases. Journal of Surgical Oncology. 77(1):42-8, 2001 May.
Abstract
BACKGROUND AND OBJECTIVES: To evaluate the
outcomes of splenectomy in myelofibrosis and myeloid metaplasia (MMM). METHODS:
We retrospectively reviewed our records of 26 patients with MMM who underwent
an open splenectomy at Boston University Medical Center between 1979 and 1995.
Fourteen patients had agnogenic myeloid metaplasia (AMM) and 12 had
myelofibrosis with antecedent myeloproliferative disorders (MF). The main
indications for splenectomy were progressive transfusion-dependent anemia,
painful splenomegaly, and hypercatabolic symptoms associated with cytopenia.
RESULTS: Median time to splenectomy after the diagnosis of MMM was 29 months
ranging from 1 to 96 months. Three patients (11%) died within 1 month after the
surgery because of sepsis. The most common peri- and postoperative
complications were pneumonia and other bacterial infections (42%), cardiac
events (19%), acute bleeding (15%), ileus (15%), and venous thrombosis (12%).
Of the eight surviving patients who underwent splenectomy for transfusion
dependent anemia, six (75%) had improvement in their hematocrit levels with
abolishment of blood transfusions. A durable symptomatic palliation was
achieved in all patients. Liver enlargement was noted in seven patients at
1-year evaluation. None of these patients developed hepatic failure. Leukemic
transformation occurred in 8 of 18 patients (44%) postsplenectomy. The median
overall survival for the entire group was 58.5 and 28 months from the diagnosis
of MMM and the time of splenectomy, respectively. There was no difference in
survival rates between patients with AMM and MF. CONCLUSIONS: Splenectomy is an
effective palliative procedure with an acceptable morbidity in selected
patients with MMM. Progressive transfusion-dependent anemia should also be
considered an indication for splenectomy in the absence of leukemic evolution.
Copyright 2001 Wiley-Liss, Inc.
2883. Alano MA. Ngougmna E.
Ostrea EM Jr. Konduri GG.
Analysis of nonsteroidal antiinflammatory drugs in meconium and its relation to
persistent pulmonary hypertension of the newborn. Pediatrics. 107(3):519-23, 2001 Mar.
Abstract
OBJECTIVE: The objective of this study was
to detect fetal exposure to nonsteroidal antiinflammatory drugs (NSAIDs) by
meconium analysis and to determine the relationship between fetal exposure to
NSAIDs and the development of persistent pulmonary hypertension of the newborn
(PPHN). METHODS: In a case-control study of the inborn and outborn nurseries of
a large urban medical center, meconium was collected from 101 newborn infants
(40 with the diagnosis of PPHN based on clinical or echocardiographic criteria
and 61 randomly selected, healthy, term infants [control]) and analyzed for
NSAIDs (ibuprofen, naproxen, indomethacin, and aspirin) by gas
chromatography/mass spectrometry. The risk of developing PPHN was determined in
infants who were exposed antenatally to NSAID. RESULTS: Infants with PPHN (n =
40) had a mean gestation of 38.9 weeks and birth weight of 3524 g, which were
similar to the those of the control group (n = 61). However, the incidence of
low Apgar scores (</=6) at 1 minute and 5 minutes was significantly higher
in the PPHN group than in the control group. The diagnoses associated with PPHN
were primary PPHN (25%), meconium aspiration syndrome (35%), respiratory
distress syndrome (20%), low Apgar score/asphyxia (12.5%), and pneumonia/sepsis
(8%). Mean duration of ventilator support for the PPHN group was 11 days.
Nitric oxide (NO) was given to 19 infants (47.5%) for a mean duration of 25.4
hours. Fourteen of the 19 infants who were treated with NO (74%) required
extracorporeal membrane oxygenation, and 2 died. The overall incidence of
positive NSAID in meconium in the study population (n = 101) was 49.5%: 22.8%
were positive for ibuprofen, 18.8% for naproxen, 7.9% for indomethacin, and
43.6% for aspirin. There was poor agreement (Cohen's kappa = 0.09) between
maternal history of NSAID use and NSAID detection in meconium. PPHN was
significantly associated with 1) the presence of at least 1 NSAID in meconium
(odds ratio [OR] = 21.47; 95% confidence interval [CI] = 7.12-64.71) or 2) the
presence in meconium of aspirin (OR = 8.09; 95% CI = 3.27-20.10), ibuprofen (OR
= 12.89; 95% CI 3.93-42.32), or naproxen (OR = 3.31; 95% CI = 1.17-9.33). By
logistic regression analysis, low Apgar scores at 1 and 5 minutes and the
antenatal exposure to aspirin, naproxen, and ibuprofen were significantly
associated with PPHN and treatment with inhaled NO or extracorporeal membrane
oxygenation. CONCLUSION: We confirm by meconium analysis the results of
previous studies that demonstrated that the use of NSAIDs during pregnancy,
particularly aspirin, ibuprofen, and naproxen, is high; is grossly
underestimated by maternal history; and is significantly associated with PPHN.
Thus, the easy access to over-the-counter NSAIDs of pregnant women should be
reevaluated, and the potential dangers of these drugs to the newborn infant
should be more effectively promoted.
2884. Arakawa H. Kurihara Y.
Niimi H. Nakajima Y. Johkoh T.
Nakamura H. Bronchiolitis obliterans with organizing pneumonia versus
chronic eosinophilic pneumonia: high-resolution CT findings in 81 patients. AJR. American Journal of Roentgenology. 176(4):1053-8, 2001 Apr.
Abstract
OBJECTIVE: The objective of this research
was to compare high-resolution CT findings of bronchiolitis obliterans with
organizing pneumonia (BOOP) with those of chronic eosinophilic pneumonia (CEP)
and to determine whether high-resolution CT can differentiate the two. MATERIALS
AND METHODS: We retrospectively reviewed high-resolution CT scans of 38
patients with BOOP and 43 patients with CEP. Without knowledge of the
diagnosis, two radiologists evaluated the frequency and distribution of
high-resolution CT findings in both groups of patients and made a diagnosis
using a three-point scale of confidence. RESULTS: Nodules, nonseptal linear or
reticular opacities, and bronchial dilatation were significantly more common in
BOOP than in CEP (31.6% vs. 4.7%, p < 0.005; 44.7% vs. 9.3%, p < 0.001;
and 57.9% vs. 25.6%, p < 0.005, respectively). Septal line thickening was
more frequent in CEP than in BOOP (72.1% vs. 39.5%, p < 0.005).
Peribronchial distribution of consolidation was more frequent in BOOP than in
CEP (28.9% vs. 9.3%, p < 0.05). A correct diagnosis was made in 69.7% of
cases, and the diagnostician was confident in 21.7%. Interobserver agreement
was good (kappa = 0.6). CONCLUSION: Although several of the high-resolution CT
findings of BOOP and CEP are different, these diseases are differentiated with
confidence in only a small percentage of cases.
2885.
Bhagat
N. Read RW. Rao NA. Smith RE. Chong LP. Rifabutin-associated hypopyon
uveitis in human immunodeficiency virus-negative immunocompetent
individuals. Ophthalmology. 108(4):750-2, 2001 Apr.
Abstract
OBJECTIVE: To report the occurrence of
rifabutin-associated hypopyon uveitis in human immunodeficiency virus
(HIV)-negative immunocompetent individuals. DESIGN: Retrospective case series.
PARTICIPANTS: Three HIV-negative subjects on rifabutin and clarithromycin for
Mycobacterium avium complex infections with hypopyon uveitis are described. One
subject was iatrogenically immunosuppressed because of a prior lung transplant.
Two subjects had no known immunosuppressive conditions. INTERVENTION: Topical
and regional steroid therapy. Discontinuation of rifabutin was required in two
subjects. MAIN OUTCOME MEASURES: Visual acuity, resolution of hypopyon,
anterior uveitis, and vitreitis. RESULTS: All subjects had resolution of
hypopyon after therapy, two within 24 hours of beginning topical steroids.
Vitreitis resolved with the discontinuation of rifabutin in two subjects.
Chronic low-grade anterior uveitis and vitreitis were observed in the remaining
subject, whose rifabutin dose was lowered but not discontinued because of
active Mycobacterium avium complex osteomyelitis. CONCLUSIONS:
Rifabutin-associated uveitis is well described in HIV-positive individuals, but
it has been reported only once in an HIV-negative individual. We report two cases
of hypopyon uveitis in immunocompetent individuals and one case in an
immunosuppressed HIV-negative individual. All three subjects were receiving
concurrent rifabutin and clarithromycin. Awareness that this entity can occur
in HIV negative and nonimmunosuppressed individuals and that it can mimic
infectious endophthalmitis may spare the subject from an invasive workup of
systemic infection.
2886. Blewett CJ. Bennett WF.
Miller JD. Urschel JD. Open lung biopsy as an outpatient procedure. Annals of Thoracic Surgery. 71(4):1113-5, 2001 Apr.
Abstract
BACKGROUND: Lung biopsies are frequently
needed to diagnose diffuse interstitial lung diseases. Both limited thoracotomy
(open lung biopsy) and thoracoscopy can be used for lung biopsies, but both
procedures have traditionally required hospital admission. We report a series
of patients that underwent outpatient open lung biopsy to show the safety and
effectiveness of this practice. METHODS: We reviewed records of ambulatory,
nonoxygen dependent patients with a clinical diagnosis of diffuse interstitial
lung disease that underwent outpatient open lung biopsy between January 1997
and December 1999. All procedures were done by a senior surgeon using single
lumen endotracheal anesthesia, a small anterolateral thoracotomy without rib
spreading, stapled wedge resection, and no chest tube. Patients were discharged
the same day. RESULTS: Thirty-two patients with a clinical diagnosis of diffuse
interstitial lung disease underwent outpatient open lung biopsy. Mean age was
58 years (range, 21 to 74 years). Preoperative forced expiratory volume in 1
second was 74.3%+/-7.0% of predicted. A pathologic diagnosis was established in
all patients: usual interstitial pneumonia, 26 patients; sarcoidosis, 2;
metastatic carcinoma, 2; desquamative interstitial pneumonia, 1; and mixed dust
pneumoconiosis, 1 patient. No patient required a chest tube, overnight
observation, or hospital admission. No complications occurred. CONCLUSIONS:
Selected patients with a clinical diagnosis of diffuse interstitial lung
disease can safely and effectively undergo diagnostic outpatient open lung
biopsy. However, careful patient selection and attention to operative detail
are essential.
2887. Bregeon
F. Ciais V. Carret V. Gregoire
R. Saux P. Gainnier M. Thirion
X. Drancourt M. Auffray JP.
Papazian L. Is ventilator-associated
pneumonia an independent risk factor for death? [see comments]. Anesthesiology. 94(4):554-60, 2001 Apr.
Abstract
BACKGROUND:
Ventilator-associated pneumonia (VAP) has been implicitly accused of increasing
mortality. However, it is not certain that pneumonia is responsible for death
or whether fatal outcome is caused by other risk factors for death that exist
before the onset of pneumonia. The aim of this study was to evaluate the
attributable mortality caused by VAP by performing a matched-paired,
case-control study between patients who died and patients who were discharged
from the intensive care unit after more than 48 h of mechanical ventilation.
METHODS: During the study period, 135 consecutive deaths were included in the
case group. Case-control matching criteria were as follows: (1) diagnosis on
admission that corresponded to 1 of 11 predefined diagnostic groups; (2) age
difference within 10 yr; (3) sex; (4) admission within 1 yr; (5) APACHE II
score within 7 points; (6) ventilation of control patients for at least as long
as the cases. Precise clinical, radiologic, and microbiologic definitions were
used to identify VAP. RESULTS: Analysis was performed on 108 pairs that were
matched with 91% of success. There were 39 patients (36.1%) who developed VAP
in each group. Multivariate analysis showed that renal failure, bone marrow
failure, and treatment with corticosteroids but not VAP were independent risk
factors for death. There was no difference observed between cases and controls
concerning the clinical and microbiologic diagnostic criteria for pneumonia.
CONCLUSION: Ventilator-associated pneumonia does not appear to be an
independent risk factor for death.
2888.
Calhoun WJ. Hinton KL. Kratzenberg JJ. The effect of salmeterol on
markers of airway inflammation following segmental allergen challenge. American
Journal of Respiratory & Critical Care Medicine. 163(4):881-6, 2001 Mar.
Abstract
Inflammation is
a critical component of asthma. Drugs that control asthma generally reduce the
degree of airway inflammation. There is theoretical controversy surrounding the
effects of beta(2)-agonists on airway inflammation, with some studies
suggesting an anti-inflammatory effect, and others predicting a proinflammatory
influence. We conducted a double-blind, placebo-controlled, crossover study of
the effect of the long-acting beta(2)-agonist salmeterol on airway inflammation
induced by segmental allergen challenge (SAC). We studied 13 allergic
asthmatics controlled with as needed inhaled short-acting beta(2)-agonists
alone, and used bronchoalveolar lavage 5 min and 48 h after SAC to assess
airway inflammation, and the effects of salmeterol on this process. Salmeterol
therapy improved FEV(1), but had no significant effect on the immediate or late
cellular response to SAC. One measure of superoxide production was reduced, and
interleukin-4 (IL-4) was reduced in baseline samples, but other indices of
airway inflammation were unchanged by salmeterol therapy. We conclude that
salmeterol therapy alone does not meaningfully reduce airway inflammation
induced by SAC, but equally importantly, does not result in amplified
inflammation.
2889. Calza
L. Manfredi R. Briganti E.
Attard L. Chiodo F. Iliac osteomyelitis
and gluteal muscle abscess caused by Streptococcus intermedius. Journal of
Medical Microbiology. 50(5):480-2, 2001
May.
Abstract
Streptococcus
intermedius, included in the 'milleri group', is a commensal of the mouth and
upper respiratory tract but it has often been associated with various pyogenic
infections, such as endocarditis, pneumonia, abdominal or cerebral abscess,
rarely with osteomyelitis, and exceptionally with muscular abscess. The first
observed case of iliac osteomyelitis with gluteal muscle abscess caused by S.
intermedius is reported. It is essential to recognise members of the 'milleri
group' as possible agents of bone and muscle pyogenic infection because its
management requires a timely diagnosis and prolonged antimicrobial treatment to
achieve complete clinical and radiological recovery.
2890. Choo
S. Finn A. New pneumococcal vaccines for children. [Review] [69 refs]
Archives of Disease in Childhood.
84(4):289-94, 2001 Apr.
2891. Cooper
P. Potter S. Mueck B. Yousefi S. Jarai G. Identification of genes induced by
inflammatory cytokines in airway epithelium. [see comments]. American Journal
of Physiology - Lung Cellular & Molecular Physiology. 280(5):L841-52, 2001 May.
Abstract
Epithelial
cells lining the airways are thought to play a prominent role in respiratory
diseases. We utilized cDNA representational difference analysis to identify the
genes in which expression is induced by the proinflammatory cytokines tumor
necrosis factor-alpha and interleukin-1beta in primary human bronchial
epithelial cells and hence are relevant to airway inflammation. Hybridization
of the subtraction product to arrayed cDNAs indicated that known tumor necrosis
factor-alpha- and interleukin-1beta-inducible genes such as B94, Zfp36, and
regulated on activation normal T cell expressed and secreted were represented,
confirming the success of the subtraction experiment. A 1,152-clone library
potentially representing genes with higher transcript levels in
cytokine-treated human bronchial epithelial cells was generated and sequenced.
Sequence similarity searches indicated that these clones represented 57 genes
of known function, 1 gene of unknown function, 6 expressed sequence tags, and 2
novel sequences. The expression of 19 of these clones was studied by a combination
of Northern blotting and RT-PCR analyses and confirmation of differential
expression for 10 known genes, 2 expressed sequence tags, and a novel sequence
not represented in any of the public databases was obtained. Thus cDNA
representational difference analysis was utilized to isolate known and novel
differentially expressed genes, which putatively play a role in airway
inflammation.
2892. de
Werra I. Zanetti G. Jaccard C.
Chiolero R. Schaller MD. Yersin B.
Glauser MP. Calandra T. Heumann D. CD14 expression on monocytes and
TNF alpha production in patients with septic shock, cardiogenic shock or
bacterial pneumonia. Schweizerische
Medizinische Wochenschrift. Journal Suisse de Medecine. 131(3-4):35-40, 2001 Jan 27.
Abstract
OBJECTIVES: In
patients with septic shock, circulating monocytes become refractory to
stimulation with microbial products. Whether this hyporesponsive state is
induced by infection or is related to shock is unknown. To address this
question, we measured TNF alpha production by monocytes or by whole blood
obtained from healthy volunteers (controls), from patients with septic shock,
from patients with severe infection (bacterial pneumonia) without shock, and
from patients with cardiogenic shock without infection. MEASUREMENTS: The
numbers of circulating monocytes, of CD14+ monocytes, and the expression of
monocyte CD14 and the LPS receptor, were assessed by flow cytometry. Monocytes
or whole blood were stimulated with lipopolysaccharide endotoxin (LPS),
heat-killed Escherichia coli or Staphylococcus aureus, and TNF alpha production
was measured by bioassay. RESULTS: The number of circulating monocytes, of
CD14+ monocytes, and the monocyte CD14 expression were significantly lower in
patients with septic shock than in controls, in patients with bacterial
pneumonia or in those with cardiogenic shock (p < 0.001). Monocytes or whole
blood of patients with septic shock exhibited a profound deficiency of TNF
alpha production in response to all stimuli (p < 0.05 compared to controls).
Whole blood of patients with cardiogenic shock also exhibited this defect (p
< 0.05 compared to controls), although to a lesser extent, despite normal
monocyte counts and normal CD14 expression. CONCLUSIONS: Unlike patients with
bacterial pneumonia, patients with septic or cardiogenic shock display
profoundly defective TNF alpha production in response to a broad range of
infectious stimuli. Thus, down-regulation of cytokine production appears to
occur in patients with systemic, but not localised, albeit severe, infections
and also in patients with non-infectious circulatory failure. Whilst depletion
of monocytes and reduced monocyte CD14 expression are likely to be critical
components of the hyporesponsiveness observed in patients with septic shock,
other as yet unidentified factors are at work in this group and in patients
with cardiogenic shock.
2893. Desai SA. Minai OA.
Gordon SM. O'Neil B. Wiedemann HP. Arroliga AC. Coccidioidomycosis in non-endemic areas: a case
series. Respiratory Medicine. 95(4):305-9, 2001 Apr.
Abstract
Coccidioidomycosis is a systemic infection
caused by the soil fungus Coccidioides immitis, which is endemic to the
south-western United States. Manifestations range from flu-like illness to
pneumonia and septic shock. Diagnosis may be delayed or missed in non-endemic
areas because of the low index of suspicion. We describe a series of 23
patients with coccidioidomycosis at one institution in a non-endemic area.
Diagnosis was often delayed. In two patients, the route of exposure could not
be determined, but 20 patients had a history of residence or travel to endemic
areas, and the remaining patient had an occupational history of exposure to
fomites from an endemic region. Five patients were immunosuppressed. Most
patients responded well to medical therapy, surgery, or both. Although
coccidioidomycosis is rare in non-endemic areas, physicians must keep it in
mind when evaluating patients who have traveled to endemic areas or who are
immunosuppressed.
2894.
Dworkin
MS. Hanson DL. Navin TR. Survival of patients with AIDS,
after diagnosis of Pneumocystis carinii pneumonia, in the United States. Journal of Infectious Diseases. 183(9):1409-12, 2001 May 1.
Abstract
To examine survival after diagnosis of
Pneumocystis carinii pneumonia (PCP) and factors associated with early death
(during the month of or the month after diagnosis of PCP), data were analyzed
from the Adult and Adolescent Spectrum HIV Disease project. Among 4412 patients
with 5222 episodes of PCP during follow-up (1992-1998), survival at >1 month
after diagnosis was 82%, and survival at > or =12 months after diagnosis was
47%; 12-month survival increased from 40% in 1992-1993 to 63% in 1996-1998. By
multiple logistic regression analysis, early death was associated with history
of PCP (odds ratio [OR], 1.4), age 45-59 years (OR, 1.9) or > or =60 years
(OR, 3.7), and CD4 cell count of 0-24 cells/microL (< or =5 months before
PCP; OR, 1.8) or 25-49 cells/microL (OR, 1.4) (P<.05). Concurrent
prescription of combination antiretroviral therapy (OR, 0.2) and other
antiretroviral therapy (OR, 0.4) was associated with surviving the early
period. This study shows improved survival after diagnosis of PCP in recent
years, despite emergence of antibiotic-resistant mutant P. carinii strains.
2895. Fassas
AB. Bolanos-Meade J. Buddharaju LN. Rapoport A. Cottler-Fox
M. Chen T. Lovchik JC. Cross A. Tricot G. Cytomegalovirus infection and
non-neutropenic fever after autologous stem cell transplantation: high rates of
reactivation in patients with multiple myeloma and lymphoma. British Journal of Haematology. 112(1):237-41, 2001 Jan.
Abstract
In a
retrospective study, we examined the association between cytomegalovirus (CMV)
infection and non-neutropenic fever immediately following autologous peripheral
blood stem cell transplantation for a variety of haematological malignancies
and solid tumours. Sixty non-neutropenic febrile episodes (41 in
CMV-seropositive and 19 in CMV-seronegative patients) were evaluated. CMV
reactivation, documented by CMV antigenaemia, was detected in 16 out of 41
(39%) seropositive patients compared with 0 out of 19 seronegative patients. In
12 of these 16 patients, CMV infection was considered the sole cause of fever.
Thirteen patients had maximum antigenaemia levels > 5 cells/slide. Specific
antiviral treatment led to the resolution of the fever in all, but two,
patients, who developed fatal CMV pneumonia. Patients with multiple myeloma and
lymphoma, possibly owing to a combination of disease-related characteristics
and prior immunosuppressive treatment, had high rates of CMV reactivation and
may require more frequent diagnostic evaluation and prompt therapeutic
intervention.
2896. Fukuda
N. Jayr C. Lazrak A. Wang Y. Lucas R.
Matalon S. Matthay MA. Mechanisms of TNF-alpha stimulation of
amiloride-sensitive sodium transport across alveolar epithelium. American
Journal of Physiology - Lung Cellular & Molecular Physiology. 280(6):L1258-65, 2001 Jun.
Abstract
Because tumor
necrosis factor (TNF)-alpha can upregulate alveolar fluid clearance (AFC) in
pneumonia or septic peritonitis, the mechanisms responsible for the
TNF-alpha-mediated increase in epithelial fluid transport were studied. In
rats, 5 microg of TNF-alpha in the alveolar instillate increased AFC by 67%.
This increase was inhibited by amiloride but not by propranolol. We also tested
a triple-mutant TNF-alpha that is deficient in the lectinlike tip portion of
the molecule responsible for its membrane conductance effect; the mutant also
has decreased binding affinity to both TNF-alpha receptors. The triple-mutant
TNF-alpha did not increase AFC. Perfusion of human A549 cells, patched in the
whole cell mode, with TNF-alpha (120 ng/ml) resulted in a sustained increase in
Na(+) currents from 82 +/- 9 to 549 +/- 146 pA (P < 0.005; n = 6). The
TNF-alpha-elicited Na(+) current was inhibited by amiloride, and there was no
change when A549 cells were perfused with the triple-mutant TNF-alpha or after
preincubation with blocking antibodies to the two TNF-alpha receptors before perfusion
with TNF-alpha. In conclusion, although TNF- alpha can initiate acute
inflammation and edema formation in the lung, TNF-alpha can also increase AFC
by an amiloride-sensitive, cAMP-independent mechanism that enhances the
resolution of alveolar edema in pathological conditions by either binding to
its receptors or activating Na(+) channels by means of its lectinlike domain.
2897. Geerlings
SE. Canninga-v Dijk MR. A patient
resuscitated after an insect sting. A clinical pathological conference.
Netherlands Journal of Medicine.
58(2):45-51, 2001 Feb.
2898. Hadi A. Diagnosis of
pneumonia by community health volunteers: experience of BRAC, Bangladesh. [see
comments]. Tropical Doctor. 31(2):75-7,
2001 Apr.
Abstract
The
study assessed the validity of community health volunteers'diagnosis of
pneumonia in children through simple clinical signs. Data were collected by a
group of research physicians who observed the case management performance of
120 health volunteers in Bangladesh where the Bangladesh Rural Advancement
Committee has been providing community-based acute respiratory infection
control since mid-1992.1,166 children age 3-60 months were assessed at
household level by both a community health volunteer and a research physician.
Using physician diagnosis as gold standard, health volunteers'diagnosis of
pneumonia was 67.6% sensitive and 95.2% specific. Cohen's kappa for agreement
between volunteers and physicians was 0.67. Of the clinical signs elicited,
chest in drawing and noisy breathing predicted physician's diagnosis of
pneumonia most strongly ([positive predictive value (PPV)] 84% and 79%,
respectively). The study concludes that less educated health volunteers can be
effectively used in diagnosing pneumonia at grassroots level in developing
countries.
2899. Helbig
JH. Uldum SA. Luck PC. Harrison
TG. Detection of Legionella pneumophila
antigen in urine samples by the BinaxNOW immunochromatographic assay and
comparison with both Binax Legionella Urinary Enzyme Immunoassay (EIA) and
Biotest Legionella Urin Antigen EIA.
Journal of Medical Microbiology.
50(6):509-16, 2001 Jun.
Abstract
The new
BinaxNOW Immunochromatographic (ICT) Assay for the detection of Legionella
pneumophila antigens was used to test 535 urine specimens from patients with
and without Legionnaires' disease. The specificity, calculated by testing 112
samples from patients with pneumonia of aetiologies other than Legionella
infection, and 167 urine specimens from urinary tract infections, was found to
be 97.1% if the manufacturer's guidelines were followed. However, it was
determined that the 'false positive' results characterised by very weak bands
could be discounted by re-examination of the results at 60 min, yielding a
specificity of 100%. With this minor modification of the procedure applied to
examination of urine samples from 117 patients with legionellosis confirmed by
isolation of L. pneumophila and 70 patients who had seroconverted to L.
pneumophila serogroup 1, sensitivity was calculated to be 79.7%. In comparison,
the sensitivities of the Binax Urinary Antigen Enzyme Immunoassay (EIA) and
Biotest Urin Antigen EIA were estimated to be 79.1 and 83.4%, respectively.
Eleven cases (5.9%) were positive by BinaxNOW assay but negative by Binax or
Biotest EIA, or both. The sensitivities of all assays increased to c. 94% if
only diagnosis of cases confirmed by isolation of serogroup 1 L. pneumophila
was considered, although the sensitivity for infections caused by L.
pneumophila serogroup 1 monoclonal antibody (MAb) subgroup Bellingham was significantly
lower than for other MAb subgroups. The Biotest EIA recognised 10 (45%) of the
22 cases not caused by L. pneumophila serogroup 1, whereas the two Binax kits
detected only three each. The ICT assay BinaxNOW can be recommended as a rapid
specific test for the diagnosis of Legionnaires' diseases caused by L.
pneumophila serogroup 1, although very weak bands should be interpreted
cautiously.
2900. Hoegerle
S. Benzing A. Nitzsche EU. Moenting
JS. Reinhardt MJ. Geiger K.
Moser E. Radioisotope albumin flux measurement of microvascular lung
permeability: an independent parameter in acute respiratory failure?.
Nuklearmedizin. 40(2):44-50, 2001 Apr.
Abstract
AIM: To
evaluate the extent to which single measurements of microvascular lung
permeability may be relevant as an additional parameter in a heterogenous
clinical patient collective with Acute Lung Injury (ALI) and Acute Respiratory
Distress Syndrome (ARDS). METHODS: In 36 patients with pneumonia (13), non
pneumogenic sepsis (9) or trauma (14) meeting the consensus conference criteria
of ALI or ARDS double-isotope protein flux measurements (51Cr erythrocytes as
intravascular tracer, Tc-99m human albumin as diffusible tracer) of
microvascular lung permeability were performed using the Normalized Slope Index
(NSI). The examination was to determine whether there is a relationship between
the clinical diagnosis of ALI/ARDS, impaired permeability and clinical
parameters, that is the underlying disease, oxygenation, duration of mechanical
ventilation and mean pulmonary-artery pressure (PAP). RESULTS: At the time of
study, 25 patients presented with increased permeability (NSI > 1 x 10(-3)
min-1) indicating on exudative stage of disease, and 11 patients with normal
permeability. The permeability impairment correlated with the underlying
disease (p > 0.05). With respect to survival, there was a negative
correlation to PAP (p < 0.01). Apart from that no correlations between the
individual parameters were found. Especially no correlation was found between
permeability impairment and oxygenation, duration of disease or PAP.
CONCLUSION: In ALI and ARDS, pulmonary capillary permeability is a diagnostic
parameter which is independent from clinical variables. Permeability
measurement makes a stage classification (exudative versus non exudative phase)
of ALI/ARDS possible based on a measurable pathophysiological correlate.
2901. Hsieh
WS. Yang PH. Fu RH. Persistent
pulmonary hypertension of the newborn: experience in a single institution. Acta Paediatrica Taiwanica. 42(2):94-100, 2001 Mar-Apr.
Abstract
Persistent pulmonary hypertension of the
newborn (PPHN) remains one of the most challenging situations in the neonatal
intensive care unit, and it is associated with high mortality and morbidity.
The optimal treatment for PPHN is controversial. We report our 9-year
experience in the management of PPHN through a retrospective review of 29
neonates with persistent pulmonary hypertension. The diagnosis of PPHN is made
by echocardiography and/or preductal and postductal oxygen tension difference.
The treatment modalities include supportive medical care, vasodilator therapy,
mechanical ventilation and correction of underlying conditions. The wide
diversity of etiologies of PPHN, the complications of vasodilator therapy, the
management of assisted ventilation, the mortality and the morbidity are
evaluated. There are 29 patients enrolled in this study, including 18 male and
11 female babies. Twenty-two patients (72%) are referred from other hospitals.
The mean birth body weight is 2707 +/- 693 grams (range: 1450-4100 grams) and
the mean gestational age is 37.1 +/- 3.1 weeks (range: 31-41 weeks). The
underlying clinical conditions include meconium aspiration syndrome (n = 8),
perinatal asphyxia (n = 7), respiratory distress syndrome (n = 5), sepsis
and/or pneumonia (n = 4), congenital diaphragmatic hernia (n = 3) and
idiopathic persistent fetal circulation (n = 2). In addition to supportive
medical care and correction of underlying clinical conditions, most of the
patients receive vasodilator therapy (Tolazoline) and nonhyperventilation
respirator management. The overall mortality rate is 27.6% (8/29). The duration
on ventilator therapy in the survival group (9.3 +/- 8.6 days) is not
significantly different from in the mortality group (6.0 +/- 7.1 days) (p =
0.13). There is also no statistically significant difference between these two
groups both in the maximal alveolar-arterial oxygen tension difference (594 +/-
53 mmHg and 613 +/- 37 mmHg, p = 0.145) and in the maximal oxygenation index (49.7
+/- 29.6 and 61.1 +/- 36.9, p = 0.172) before vasodilator therapy. However,
twenty-four hours after treatment, these two parameters change significantly
with the former changes to 426 +/- 198 mmHg and 643 +/- 7 mmHg, respectively (p
< 0.001), and the latter changes to 21.6 +/- 15.8 and 82.3 +/- 54.8,
respectively (p < 0.001). Skin rash, gastrointestinal hemorrhage,
hypotension and hyponatremia are the most common complications of Tolazoline
therapy. Eight patients have pulmonary complications including pneumothorax (n
= 5) and pulmonary interstitial emphysema (n = 3). Two patients develop chronic
lung disease. Three patients have neurodevelopmental handicap. In conclusion,
we achieve a survival rate of nearly 75% in PPHN mainly with the administration
of Tolazoline therapy and the nonhyperventilation respirator approach. Further
well-controlled and multicenter studies with newer treatment modalities are
crucial for the improvement of survival of PPHN in Taiwan.
2902. Hughson MD. He Z.
Henegar J. McMurray R. Alveolar
hemorrhage and renal microangiopathy in systemic lupus erythematosus. Archives
of Pathology & Laboratory Medicine.
125(4):475-83, 2001 Apr.
Abstract
CONTEXT: Acute
alveolar hemorrhage in systemic lupus erythematosus usually occurs as a pulmonary-renal
syndrome. In most cases, the lungs show "bland" alveolar hemorrhage
with little or no inflammation. Whether this alveolar injury is similar to the
better-defined noninflammatory renal lupus vasculopathy is unresolved.
OBJECTIVES: To investigate the relationships and the mechanisms of small
vascular injury in the lung and kidney of 2 lupus patients who died of diffuse
AH. METHODS: We investigated the relationship of AH to immune complex
deposition in the lungs of 6 patients with systemic lupus erythematosus and
correlated the findings with glomerular and vascular disease in the kidney.
Lung and kidney were studied by light, immunofluorescence, and/or electron
microscopy; apoptosis was investigated using in situ nick-end labeling.
RESULTS: The clinical course of 2 patients was complicated by alveolar
hemorrhage, and the lungs of these patients revealed alveolar wall immune
complex deposits and bland alveolar hemorrhage. These 2 patients had World
Health Organization class IV lupus nephritis and renal arterioles involved by a
noninflammatory lupus vasculopathy. Apoptosis was identified in the lupus
microangiopathy and in alveolar walls within areas of alveolar hemorrhage.
Alveolar wall immune complex deposits were not found in 4 patients who had a
lupus glomerulonephritis but did not have renal lupus vasculopathy. Apoptosis
was not seen in renal arterioles or lungs of these 4 cases, except in areas of
diffuse alveolar damage or herpesvirus pneumonia. CONCLUSIONS: Our findings
indicate that alveolar hemorrhage in systemic lupus erythematosus,
characterized by bland alveolar wall changes, is pathogenetically similar to
the lupus microangiopathy of the kidney. In both lung and kidney, the
pathogenesis of the microvascular injury appears to be related to immune
complex deposition and the induction of apoptosis.
2903.
John
SD. Ramanathan J. Swischuk LE. Spectrum of clinical and radiographic findings in pediatric
mycoplasma pneumonia. Radiographics.
21(1):121-31, 2001 Jan-Feb.
Abstract
Clinical symptoms in mycoplasma infection
are nonspecific. Pulmonary involvement may be widespread or focal and segmental
and is accompanied by signs including rales, rhonchi, and decreased breath
sounds. Although manifestations of mycoplasma infection are usually confined to
the respiratory tract, a wide variety of extrarespiratory manifestations can
also occur, including more severe associated diseases such as myocarditis,
acute disseminated encephalomyelitis, and cerebral arteriovenous occlusion. The
radiographic findings in mycoplasma pneumonia are also nonspecific and in some
cases closely resemble those seen in children with viral infections of the
lower respiratory tract. Focal reticulonodular opacification confined to a
single lobe is a radiographic pattern that seems to be more closely associated
with mycoplasma infection than with other types of pediatric respiratory
illnesses, and the diagnosis of mycoplasma pneumonia should be considered
whenever focal or bilateral reticulonodular opacification is seen. Hazy or
ground-glass consolidations frequently occur, but dense homogeneous
consolidations like those seen with bacterial pneumonias are uncommon.
Atelectasis or transient pseudoconsolidations due to confluent interstitial
shadows are often seen. Radiographic findings alone are not sufficient for the
definitive diagnosis of mycoplasma pneumonia, but in combination with clinical
findings they can significantly improve the accuracy of diagnosis in this
disease.
2904. Keidar
S. Ben-Sira L. Weinberg M.
Jaffa AJ. Silbiger A. Vinograd I.
The postnatal management of congenital cystic adenomatoid malformation.
Israel Medical Association Journal: IMAJ.
3(4):258-61, 2001 Apr.
Abstract
BACKGROUND:
Routine prenatal ultrasound has increased the frequency of prenatal diagnosis
of congenital cystic lung malformation, such as cystic adenomatoid
malformation, pulmonary sequestration, congenital lobar emphysema, and
bronchogenic cyst. OBJECTIVES: To evaluate the methods of postnatal diagnosis,
the optimal age for operation since surgery is always required, and the optimal
extent of lung resection. METHODS: The clinical courses of 11 patients with
congenital lung cysts who underwent surgical lung resection (8 lobectomies and
3 segmentectomies) were reviewed. RESULTS: The diagnosis was confirmed by
computed tomography scan in all. In nine patients the diagnosis was made
prenatally. Chest X-ray was normal postnatally in all patients except for two
who had recurrent pneumonia. Postoperative follow-up showed excellent recovery
in all operated children. One patient who underwent surgery for CCAM following
episodes of severe pneumonia died from another cause 5 months later.
Postoperative chest CT scan showed no residual disease in eight patients. In
two who had undergone limited resection, tomography showed a small segment of
residual disease in one and a suspected residual lesion in the other.
CONCLUSION: With prenatal ultrasound the true frequency of congenital cystic
lung anomaly appears to be higher than previously reported. Postnatal CT is
mandatory to confirm or to rule out the diagnosis. The mere presence of cystic
lung malformation is an indication for surgery. Complete removal of the
affected lung lobe is recommended. Segmental resection may be inadequate. Early
operation is tolerated well by infants and small children and we recommend that
surgery be performed in children between 6 and 12 months of age.
2905. Khoor
A. Leslie KO. Tazelaar HD. Helmers
RA. Colby TV. Diffuse pulmonary disease
caused by nontuberculous mycobacteria in immunocompetent people (hot tub
lung). American Journal of Clinical
Pathology. 115(5):755-62, 2001 May.
Abstract
The
clinicopathologic spectrum of infections due to nontuberculous mycobacteria
(NTM) includes cavitary disease, opportunistic infection, and nodular disease
associated with bronchiectasis. We report a less well-described manifestation
of NTM infection: 10 immunocompetent patients without preexisting
bronchiectasis had radiographic evidence of diffuse infiltrative lung disease.
The most common symptoms were dyspnea, cough, hypoxia, and fever. All 10
patients had used a hot tub. Histologic examination revealed exuberant
nonnecrotizing, frequently bronchiolocentric, granulomatous inflammation in all
cases. In 1 case, necrotizing granulomas were also noted. The inflammation
often was associated with patchy chronic interstitial pneumonia and
organization. Cultures revealed NTM in all cases (Mycobacterium avium complex
in all but 1 case), but staining for acid-fast bacilli was positive in only 1
case. Four patients received corticosteroids alone for presumed
hypersensitivity pneumonia, 4 were treated with antimycobacterial therapy, and
2 received both. All patients demonstrated significant improvement at the time
of follow-up. These findings suggest that disease due to NTM may manifest as
diffuse infiltrates in immunocompetent adults and that hot tub use may be an
important risk factor for this disease pattern.
2906. MacLean LL. Vinogradov E. Crump EM. Perry MB. Kay WW.
The structure of the lipopolysaccharide O-antigen produced by
Flavobacterium psychrophilum (259-93).
European Journal of Biochemistry.
268(9):2710-6, 2001 May.
Abstract
Flavobacterium
psychrophilum, a Gram-negative bacterium, is the etiological agent of rainbow
trout fry syndrome and bacterial cold water disease, septicemic infections in
reared salmonids. In humans Flavobacterium spp. have been associated with
neonatal meningitis and septicemia, catheter-associated bacteremia, and
pneumonia. Recently, several F. psychrophilum surface molecules, including
lipopolysaccharide (LPS), have been implicated in its pathogenesis and
identified as potential vaccine and diagnostic candidate macromolecules.
Studies on the LPS produced by the bacterium are reported herein. The structure
of the antigenic O-polysaccharide contained in the LPS of F. psychrophilum was
deduced by the application of analytical NMR spectroscopy, mass spectrometry,
glycose and methylation analysis, and partial hydrolysis degradations, and was
found to be an unbranched polymer of trisaccharide repeating units composed of
L-rhamnose (L-Rhap), 2-acetamido-2-deoxy-L-fucose (L-FucpNAc) and
2-acetamido-4-((3S,5S)-3,5-dihydroxyhexanamido)-2,4-dideoxy-D-quinovose
(D-Quip2NAc4NR, 2-N-acetyl-4-N-((3S,5S)-3,5-dihydroxyhexanoyl)-D-bacillosamine)
(1 : 1 : 1) and having the structure:
-->4)-alpha-L-FucpNAc-(1-->3)-alpha-D-Quip2NAc4NR-(1-->2)-
alpha-L-Rhap-(1--> where R is (3S,5S)-CH3CH(OH)CH2CH(OH)CH2CO-.
2907. McAdams
HP. Erasmus JJ. Palmer SM.
Complications (excluding hyperinflation) involving the native lung after
single-lung transplantation: incidence, radiologic features, and clinical
importance. Radiology. 218(1):233-41,
2001 Jan.
Abstract
PURPOSE: To
determine the incidence, importance, and radiologic features of native lung
complications after single-lung transplantation. MATERIALS AND METHODS:
Seventeen (15%) of 111 single-lung transplant recipients developed native lung
complications (excluding hyperinflation) 0-58 months (mean, 17 months) after
transplantation. Complaints at presentation, culture or histopathologic
results, diagnostic or therapeutic procedures, and outcome were recorded. Chest
radiographs (n = 17) and computed tomographic (CT) scans (n = 8) obtained at
time of diagnosis were reviewed. Serial radiographs were assessed for disease
progression or improvement. RESULTS: The most common complications were
infection (n = 10), caused by bacteria (n = 4), fungi (n = 4), or mycobacteria
(n = 2), typically manifested as lobar or segmental opacities on chest
radiographs or CT scans. Lung cancer manifested as a solitary
well-circumscribed nodule (n = 1), multiple nodules (n = 1), or a hilar mass (n
= 1). Five (29%) of 17 patients died of native lung complications. Seven
patients underwent mediastinoscopy (n = 3), lobectomy (n = 2), thoracoscopic
wedge resection (n = 2), tube thoracostomy (n = 2), or pneumonectomy (n = 1)
for diagnosis or treatment. CONCLUSION: Native lung complications occurred in
17 (15%) single-lung transplant recipients, were most commonly due to infection
or lung cancer, and caused serious morbidity or mortality in 12 (71%) of 17
patients affected.
2908. Moulin F. Raymond J.
Lorrot M. Marc E. Coste J.
Iniguez JL. Kalifa G. Bohuon C.
Gendrel D. Procalcitonin in
children admitted to hospital with community acquired pneumonia. Archives of
Disease in Childhood. 84(4):332-6, 2001
Apr.
Abstract
AIMS: To assess the sensitivity,
specificity, and predictive value of procalcitonin (PCT) in differentiating
bacterial and viral causes of pneumonia. METHODS: A total of 72 children with
community acquired pneumonia were studied. Ten had positive blood culture for
Streptococcus pneumoniae and 15 had bacterial pneumonia according to sputum
analysis (S pneumoniae in 15, Haemophilus influenzae b in one). Ten patients
had Mycoplasma pneumoniae infection and 37 were infected with viruses, eight of
whom had viral infection plus bacterial coinfection. PCT concentration was
compared to C reactive protein (CRP) concentration and leucocyte count, and, if
samples were available, interleukin 6 (IL-6) concentration. RESULTS: PCT
concentration was greater than 2 microg/l in all 10 patients with blood culture
positive for S pneumoniae; in eight of these, CRP concentration was above 60
mg/l. PCT concentration was greater than 1 microg/l in 86% of patients with
bacterial infection (including Mycoplasma and bacterial superinfection of viral
pneumonia). A CRP concentration of 20 mg/l had a similar sensitivity but a much
lower specificity than PCT (40% v 86%) for discriminating between bacterial and
viral causes of pneumonia. PCT concentration was significantly higher in cases
of bacterial pneumonia with positive blood culture whereas CRP concentration
was not. Specificity and sensitivity were lower for leucocyte count and IL-6
concentration. CONCLUSIONS: PCT concentration, with a threshold of 1 microg/l
is more sensitive and specific and has greater positive and negative predictive
values than CRP, IL-6, or white blood cell count for differentiating bacterial
and viral causes of community pneumonia in untreated children admitted to
hospital as emergency cases.
2909. Ogunbanwo
JA. Agbonlahor DE. Adamu A.
Dalyop P. Elesha SO. Fagbenro-Beyioku AF. Effects of
anti-protozoal drugs and histopathological studies on trypanosome species. FEMS Immunology & Medical Microbiology. 30(1):73-83, 2001 Feb.
Abstract
The
trypanosomostatic and trypanosomicidal effects of four anti-protozoal drugs,
namely halofantrine hydrochloride, chloroquine phosphate, benzoylmetronidazole
and pyrimethamine, on species of trypanosomes, viz. Trypanosoma brucei brucei
(MBOS/NG/94/NITR) Bassa strain, T. congolense (MBOS/NG/93/NVRI) Zaria strain
and T. brucei gambiense (MHOM/NG/92/NITR) Abraka strain, were investigated. In
vitro and in vivo studies on these drugs vis-a-vis the parasites were carried
out. The histopathological changes in organs and tissues of experimentally
infected rats were also studied. Results from the in vitro studies indicated
that halofantrine hydrochloride, chloroquine phosphate, benzoylmetronidazole
and pyrimethamine appeared to be effective trypanosomicidal agents against T.
brucei brucei (Bassa strain), T. congolense (Zaria strain) and T. brucei
gambiense (Abraka strain). The in vivo studies showed that these drugs were
sub-curative by prolonging the survival period of the trypanosome-infected
rats, but not necessarily curing the infection. Histopathological findings
indicated inflammatory reactions characterised by infiltration to variable
degrees in the majority of tissues, mostly in the lungs and liver. The most consistent
lesions were interstitial pneumonia, multifocal necrosis and oedema.
Pathological findings showed the T. brucei brucei and T. brucei gambiense
strains studied to be both intravascular and extravascular parasites. These
results suggest that halofantrine hydrochloride, chloroquine phosphate,
benzoylmetronidazole and pyrimethamine could be used as supportive, suppressive
and/or synergistic/additive drugs in the treatment of African trypanosomiasis.
Their effects on species of trypanosomes have been studied and are reported for
the first time.
2910. Orlovic
D. Kularatne R. Ferraz V.
Smego RA Jr. Dual pulmonary infection with Mycobacterium tuberculosis
and Pneumocystis carinii in patients infected with human immunodeficiency
virus. Clinical Infectious Diseases. 32(2):289-94, 2001 Jan 15.
Abstract
During a
22-month period, we identified 39 patients with human immunodeficiency virus
(HIV) infection (mean CD4(+) count, 90 cells/mm(3)) who were hospitalized with
pneumonia and who had sputum and/or other specimens that tested concurrently
positive for both Mycobacterium tuberculosis and Pneumocystis carinii. The most
common chest x-ray abnormality was a reticulonodular pattern or bilateral
infiltrates (n=26). Serum lactate dehydrogenase levels were elevated in 17
(85%) of 20 of patients tested (mean value, 2208 U/L). Mean O(2) saturation and
PO(2) were 89% and 64 mm Hg, respectively. A majority (24 patients [62%])
received both antituberculous and anti-PCP therapy (17 with steroids), and 22
improved. All ten patients who received no treatment for PCP improved and were
discharged from the hospital, whereas 4 (80%) of the 5 persons who received no
antituberculous treatment had a poor outcome (P<.001; OR=43). Patients with
HIV or acquired immune deficiency syndrome may present with both TB and PCP; of
the 2, TB seems to account for the most severe features of disease.
2911. Oshima K. Kanda Y.
Nannya Y. Kaneko M. Hamaki T.
Suguro M. Yamamoto R. Chizuka A.
Matsuyama T. Takezako N. Miwa A.
Togawa A. Niino H. Nasu M.
Saito K. Morita T. Clinical and pathologic findings in 52
consecutively autopsied cases with multiple myeloma. American Journal of Hematology.
67(1):1-5, 2001 May.
Abstract
We studied
clinical features and pathologic findings in 52 consecutively autopsied
patients with multiple myeloma in our center between 1979 and 1998. Distant
extraosseous involvement was found in 33 patients (63.5%). Thirty-one patients
(59.6%) were proven to have infection at autopsy, among which pneumonia was
most common site of infection. Amyloidosis was shown in 8 patients. Second
malignancies were observed in 4 cases. The three major causes of death were
hemorrhage, infection, and renal failure, which accounted for death in
approximately 70% of the patients. Advances in the anticancer and antimicrobial
chemotherapies might have decreased deaths due to myeloma itself or infection.
Copyright 2001 Wiley-Liss, Inc.
2912. Ozdemir
V. Shear NH. Kalow W. What will be the role of pharmacogenetics in evaluating
drug safety and minimising adverse effects?. [Review] [83 refs] Drug Safety. 24(2):75-85, 2001.
Abstract
In the US,
adverse drug reactions (ADRs) rank between the fourth to sixth leading cause of
death, ahead of pneumonia and diabetes mellitus. An important reason for the high
incidence of serious and fatal ADRs is that the existing drug development
paradigms do not generate adequate information on the mechanistic sources of
marked variability in pharmacokinetics and pharmacodynamics of new therapeutic
candidates, precluding treatments from being tailored for individual patients.
Pharmacogenetics is the study of the hereditary basis of person-to-person
variations in drug response. The focus of pharmacogenetic investigations has
traditionally been unusual and extreme drug responses resulting from a single
gene effect. The Human Genome Project and recent advancements in molecular
genetics now present an unprecedented opportunity to study all genes in the
human genome, including genes for drug metabolism, drug targets and postreceptor
second messenger machinery, in relation to variability in drug safety and
efficacy. In addition to sequence variations in the genome, high throughput and
genome-wide transcript profiling for differentially regulated mRNA species
before and during drug treatment will serve as important tools to uncover novel
mechanisms of drug action. Pharmacogenetic-guided drug discovery and
development represent a departure from the conventional approach which markets
drugs for broad patient populations, rather than smaller groups of patients in
whom drugs may work more optimally. Pharmacogenetics provides a rational
framework to minimise the uncertainty in outcome of drug therapy and clinical
trials and thereby should significantly reduce the risk of drug toxicity. [References:
83]
2913. Padman
R. The child with persistent cough.
[Review] [11 refs] Delaware Medical
Journal. 73(4):149-56, 2001 Apr.
Abstract
Coughing is a
healthy reflex. Causes of a cough can vary from minor upper respiratory
illnesses to malignancy. When a child's cough continues for weeks, parents
worry. Primary care providers must decide when reassessment is needed and if a
vigorous workup and referral to a pulmonologist are required. The above
discussion should assist these physicians. [References: 11]
2914. Pryor
JP. Piotrowski E. Seltzer CW.
Gracias VH. Early diagnosis of
retroperitoneal necrotizing fasciitis. Critical Care Medicine. 29(5):1071-3, 2001 May.
Abstract
OBJECTIVE: To
report survival of retroperitoneal necrotizing fasciitis in an inmunocompromised
patient and to demonstrate early clinical signs that may help in the prompt
diagnosis and treatment of this severe infection. DESIGN: Case report and
literature review. SETTING: An adult, 18-bed intensive care unit within a
university hospital. PATIENT: A 38-yr-old man who had undergone an
uncomplicated closed hemorrhoidectomy was readmitted to the hospital on
postoperative day 5 for erythema around the hemorrhoidectomy and a dirty brown
discharge from the wound. INTERVENTIONS: Early diagnosis of retroperitoneal
necrotizing fasciitis, wide and repeated debridement, broad-spectrum
antibiotics, and eventual abdominal wall reconstruction. MEASUREMENTS AND MAIN
RESULTS: This patient manifested periumbilical and bilateral flank erythema,
reminiscent of the pattern of ecchymosis seen in cases of retroperitoneal
hemorrhage. The findings demonstrate a variation of Cullen's and Grey Turner's
sign, most often found in patients with hemorrhagic pancreatitis. An abdominal
radiograph revealed a ground glass appearance with radiolucency outlining the
bladder, consistent with retroperitoneal air. The chest radiograph showed
mediastinal air extending into the neck. Sharp debridement of the
retroperitoneal fat, the right anterior rectus sheath, and the right anterior
thigh fascia was required to gain control of the infection. Operative cultures
grew a mixed flora with Eschericha coli, beta-hemolytic streptococcus, and
Bacteroides fragilis predominating. The hospital course was complicated by
hemodynamic instability, renal failure, pneumonia, and a pelvic abscess. The
patient ultimately survived and underwent abdominal wall reconstruction with
mesh. CONCLUSION: Retroperitoneal necrotizing fasciitis is an uncommon soft
tissue infection that is often fatal. Early diagnosis in this case was
facilitated by the unique clinical findings of a modified Cullen's and Grey
Turner's sign. A review of the limited available literature suggests that
survival of retroperitoneal fasciitis is possible with prompt debridement and
antibiotic therapy.
2915. Rubegni P. Marano MR.
De Aloe G. Pianigiani E. Bilenchi R.
Fimiani M. Sweet's syndrome and
Chlamydia pneumoniae infection. Journal
of the American Academy of Dermatology.
44(5):862-4, 2001 May.
Abstract
We report the case of a patient in whom
Sweet's syndrome developed during pneumonia caused by Chlamydia pneumoniae.
Increased expression of helper T-cell type 1 cytokine secretion pattern in
peripheral blood has recently been observed in patients with this syndrome, and
chlamydia infection is known to primarily activate a helper T-cell type 1
immunologic response.
2916. Sajjan
U. Corey M. Humar A. Tullis E. Cutz E.
Ackerley C. Forstner J.
Immunolocalisation of Burkholderia cepacia in the lungs of cystic fibrosis
patients. Journal of Medical Microbiology.
50(6):535-46, 2001 Jun.
Abstract
Infection by
Burkholderia cepacia is sometimes fatal in patients with cystic fibrosis (CF),
as the organism can cause necrotising pneumonia and septicaemia (the cepacia
syndrome), and is resistant to antibiotics. To increase knowledge of the
pathogenesis of lung infection, the present study investigated the distribution
of B. cepacia in lung explants from nine CF recipients of double lung
transplants, of which six were colonised with both B. cepacia and Pseudomonas
aeruginosa and the other three with P. aeruginosa only. In one case, explants
of the donor lung (allograft) became available after the patient succumbed
post-operatively to the cepacia syndrome. Further autopsy sections were
examined from two patients who had chronic and then acute infection with B.
cepacia. A specific antibody reactive with all five genomovars of the B.
cepacia complex and another antibody specific for the 22-kDa adhesin of cable
pili, were used to localise bacteria in situ. In chronic infection, the
organisms were diffusely distributed, but most concentrated in hyperplastic
bronchiolar epithelium, inflamed peribronchial and perivascular areas, between
adjacent airway epithelial cells and in pathologically thickened alveolar
septae and luminal macrophages. In acute infections the distribution was more
focal, with B. cepacia on injured airway surfaces and in sites of pneumonia and
abscess formation. In autopsy sections from one of the patients with chronic,
then acute infection, B. cepacia was also observed in the lumen of blood
capillaries. These results suggest that B. cepacia has the capacity to be
highly invasive, migrating from the airways across the epithelial barrier to
invade the lung parenchyma and capillaries, thereby initiating septicaemia.
2917. Scheinbart EA. Integrating allopathic and alternative
therapies in the treatment of a patient with multiple myeloma and
vancomycin-resistant Staphylococcus aureus
pneumonia. Alternative Therapies in Health & Medicine. 7(3):160, 158-9, 2001 May-Jun.
2918. Schwartz DA. Christ WJ.
Kleeberger SR. Wohlford-Lenane
CL. Inhibition of LPS-induced airway hyperresponsiveness
and airway inflammation by LPS antagonists. American Journal of Physiology -
Lung Cellular & Molecular Physiology. 280(4):L771-8, 2001 Apr.
Abstract
To determine
whether the inflammatory effects of inhaled endotoxin could be prevented, we
pretreated mice with synthetic competitive antagonists (975, 1044, and 1287)
for lipopolysaccharide (LPS) before a LPS inhalation challenge. In preliminary
studies, we found that these LPS antagonists did not act as agonists in vitro
(THP-1 cells) or in vivo (after intratracheal instillation of 10 microg) and
that these compounds (at least 1 microg/ml) effectively antagonized the release
of tumor necrosis factor-alpha by LPS-stimulated THP-1 cells. Pretreatment of
mice with 10 microg of either 1044 or 1287 resulted in a decrease in the
LPS-induced airway hyperreactivity. Moreover, pretreatment of mice with 10
microg of 975, 1044, or 1287 resulted in significant reductions in LPS-induced
lung lavage fluid concentrations of total cells, neutrophils, and specific
proinflammatory cytokines compared with mice pretreated with sterile saline.
Using residual oil fly ash to induce airway inflammation, we found that the
action of the LPS antagonists was specific to LPS-induced airway disease. These
results suggest that LPS antagonists may be an effective and potentially safe
treatment for endotoxin-induced airway disease.
2919. Steingrimsdottir
H. Gruber A. Kalin M. Bjorkholm M.
Late infections after blood progenitor cell transplantation in patients with
multiple myeloma. American Journal of
Medicine. 110(4):329-30, 2001 Mar.
2920. Upcroft
P. Upcroft JA. Drug targets and
mechanisms of resistance in the anaerobic protozoa. [Review] [244 refs]
Clinical Microbiology Reviews.
14(1):150-64, 2001 Jan.
Abstract
The anaerobic protozoa Giardia duodenalis,
Trichomonas vaginalis, and Entamoeba histolytica infect up to a billion people
each year. G. duodenalis and E. histolytica are primarily pathogens of the
intestinal tract, although E. histolytica can form abscesses and invade other
organs, where it can be fatal if left untreated. T. vaginalis infection is a
sexually transmitted infection causing vaginitis and acute inflammatory disease
of the genital mucosa. T. vaginalis has also been reported in the urinary
tract, fallopian tubes, and pelvis and can cause pneumonia, bronchitis, and
oral lesions. Respiratory infections can be acquired perinatally. T. vaginalis
infections have been associated with preterm delivery, low birth weight, and
increased mortality as well as predisposing to human immunodeficiency virus
infection, AIDS, and cervical cancer. All three organisms lack mitochondria and
are susceptible to the nitroimidazole metronidazole because of similar
low-redox-potential anaerobic metabolic pathways. Resistance to metronidazole
and other drugs has been observed clinically and in the laboratory. Laboratory
studies have identified the enzyme that activates metronidazole,
pyruvate:ferredoxin oxidoreductase, to its nitroso form and distinct mechanisms
of decreasing drug susceptibility that are induced in each organism. Although
the nitroimidazoles have been the drug family of choice for treating the anaerobic
protozoa, G. duodenalis is less susceptible to other antiparasitic drugs, such
as furazolidone, albendazole, and quinacrine. Resistance has been demonstrated
for each agent, and the mechanism of resistance has been investigated.
Metronidazole resistance in T. vaginalis is well documented, and the principal
mechanisms have been defined. Bypass metabolism, such as alternative
oxidoreductases, have been discovered in both organisms. Aerobic versus
anaerobic resistance in T. vaginalis is discussed. Mechanisms of metronidazole
resistance in E. histolytica have recently been investigated using
laboratory-induced resistant isolates. Instead of downregulation of the
pyruvate:ferredoxin oxidoreductase and ferredoxin pathway as seen in G.
duodenalis and T. vaginalis, E. histolytica induces oxidative stress
mechanisms, including superoxide dismutase and peroxiredoxin. The review
examines the value of investigating both clinical and laboratory-induced
syngeneic drug-resistant isolates and dissection of the complementary data
obtained. Comparison of resistance mechanisms in anaerobic bacteria and the
parasitic protozoa is discussed as well as the value of studies of the
epidemiology of resistance. [References: 244]
2921.
Yoo
CG. Lee S. Lee CT. Kim YW. Han SK.
Shim YS. Effect of acetylsalicylic acid on endogenous I kappa B kinase
activity in lung epithelial cells. [letter; comment]. [see comments]. American
Journal of Physiology - Lung Cellular & Molecular Physiology. 280(1):L3-9, 2001 Jan.
Abstract
The anti-inflammatory effect of
acetylsalicylic acid (ASA) has been thought to be secondary to the inhibition
of prostaglandin synthesis. Because doses of ASA necessary to treat chronic
inflammatory diseases are much higher than those needed to inhibit
prostaglandin synthesis, a prostaglandin-independent pathway has been emerging
as the new anti-inflammatory mechanism of ASA. Here, we examined the effect of
ASA on the interleukin (IL)-1 beta- and tumor necrosis factor
(TNF)-alpha-induced proinflammatory cytokine expression and evaluated whether
this effect is closely linked to the nuclear factor (NF)-kappa B/I kappa
B-alpha pathway. A high dose of ASA blocked IL-1 beta- and TNF-alpha-induced
TNF-alpha and IL-8 expression, respectively. ASA inhibited TNF-alpha-induced
activation of NF-kappa B by preventing phosphorylation and subsequent
degradation of I kappa B-alpha in a prostanoid-independent manner.
TNF-alpha-induced activation of I kappa B kinase was also suppressed by ASA
pretreatment. These observations suggest that the anti-inflammatory effect of
ASA in lung epithelial cells may be due to suppression of I kappa B kinase
activity, which thereby inhibits subsequent phosphorylation and degradation of
I kappa B-alpha, activation of NF-kappa B, and proinflammatory cytokine expression
in lung epithelial cells.
2922. Yu VL. Legionnaires'
disease: seek and ye shall find.
Cleveland Clinic Journal of Medicine.
68(4):318-22, 2001 Apr.
Abstract
Legionella pneumophila is among the top
three or four microbial causes of community-acquired pneumonia, yet is often
misdiagnosed and inadequately treated. New laboratory tests should simplify the
diagnosis. Also, contrary to common perception, the disease is usually spread
via aspiration of water from contaminated hot water distribution systems, not
from air conditioning systems. The treatment of choice has shifted from
erythromycin to the newer macrolides and quinolones. Routine culturing of the
hospital water supply is a requisite first step in preventing hospital-acquired
Legionnaires' disease.
2923. Zelle-Rieser C. Ramoner R.
Bartsch G. Thurnher M. A
clinically approved oral vaccine against pneumotropic bacteria induces the
terminal maturation of CD83+ immunostimulatory dendritic cells. Immunology
Letters. 76(1):63-7, 2001 Feb 1.
Abstract
Dendritic cells (DCs) are important
antigen-presenting cells of the immune system that have attracted interest as
cellular adjuvants to induce immunity in clinical settings. We have
investigated the effects of Broncho-Vaxom, an oral vaccine composed of lysates from
eight pneumotropic bacteria, on human monocyte-derived dendritic cells (moDCs).
Broncho-Vaxom induced the terminal maturation of CD83+ moDCs. MoDCs stimulated
with Broncho-Vaxom displayed a phenotype of activated DCs with high levels of
major histocompatibility complex (MHC) molecules and increased levels of
adhesion and co-stimulatory molecules. In addition, moDCs activated with
Broncho-Vaxom exhibited enhanced T cell-stimulatory capacity in the allogeneic
mixed leukocyte reaction. Broncho-Vaxom at 100 microg/ml was as potent as
TNF-alpha at 1000 U/ml in activating human moDCs. Neither LPS-like activity nor
bacterial DNA was found to be responsible for the maturation-inducing activity
of Broncho-Vaxom, suggesting that Broncho-Vaxom contains other bacterial
factors that are capable of inducing the terminal maturation of moDCs. In
DC-based immunotherapy, Broncho-Vaxom could be used as a stimulus of DC
maturation, which meets the standards of good manufacturing practice (GMP). In
addition, vaccination with Broncho-Vaxom-loaded moDCs may be an attractive
treatment option in preventing recurrent airway infection in predisposed
individuals.