Sarcoidosis-associated pulmonary hypertension in patients with near-normal lung function.

SETTING: Tertiary care medical centre in Israel. BACKGROUND: Pulmonary hypertension (PH) is a predictor of poor outcome in patients with sarcoidosis. Early diagnosis may improve outcome. OBJECTIVE: To determine factors that might contribute to the early diagnosis of PH in sarcoidosis patients with near normal lung function tests. DESIGN: Retrospective patient review. METHODS: Data from 127 patients with sarcoidosis and near normal lung function tests (forced vital capacity > 70%, forced expiratory volume in 1 second > 70% and diffusion capacity of carbon monoxide [D(LCO)] > 60%), who underwent high resolution computed tomography (HRCT) scan, the 6-minute walk distance (6MWD) test and echocardiogram were analysed. Demographic, clinical and HRCT findings were compared between patients with and those without PH. RESULTS: Thirty-six patients (28.3%) had PH. Patients with PH tended to have lower D(LCO) (68% ± 8 vs. 75% ± 17, P = 0.038), 6MWD (308 m ± 106 vs. 486 m ± 99, P = 0.009) and exercise saturation (91 ± 4 vs. 95 ± 3, P = 0.0001) compared to those without PH. HRCT patterns in PH showed higher frequencies of interstitial thickening (P = 0.004), ground glass appearance (P = 0.01) and fibrosis (P = 0.032). In logistic regression, only 6MWD was predictive of PH (P = 0.005, 95%CI 0.970-0.995). CONCLUSION: Physiological and radiographic characteristics appeared to differentiate patients with PH from those without. Physicians should be aware of PH in patients with sarcoidosis, even in those with near normal lung function.

A 47-year-old female with shortness of breath and "reversed halo sign".

A 47-yr-old female was referred to a tertiary centre for further evaluation of chronic cough, fever, progressive exertional dyspnoea and fatigue. From a respiratory point of view she had been well until 7 months previously when she had started to experience systemic fatigue, low-grade fever and chronic dry cough. A computed tomography scan of the chest demonstrated diffuse bilateral ground-glass, ill-defined pulmonary opacities affecting all lobes. Some had central ground-glass hazy density with peripheral areas of increased opacity, which is consistent with "reversed halo sign". Cryptogenic organising pneumonia (COP) is a clinical, radiological and pathological diagnosis which is made when no definite cause, such as infection or connective tissue disease, is found. It is characterised histopathologically by the presence of patchy distribution of granulation tissue, which consists of fibroblasts and myofibroblasts embedded in a loose connective matrix, present in the lumen of the distal airspaces including alveoli, alveolar ducts and bronchioles. This case report illustrates the association of the reversed halo sign with COP. Although only seen in one fifth of patients with the disease, it appears to suggest the diagnosis of COP and, with proper clinical correlation, it may be another diagnostic adjunct.

Low uric acid levels in serum of patients with ALS: further evidence for oxidative stress?

BACKGROUND: The exact cause of amyotrophic lateral sclerosis (ALS) is unknown. Oxidative stress is one of the factors implicated in the etiology of ALS as well as in that of other neurodegenerative diseases. Uric acid is an important natural antioxidant that may reduce oxidative stress. The objective of this study was to prospectively determine the serum uric acid levels in ALS patients and allegedly healthy individuals and to correlate those values with measures of ALS disease progression among the patients. METHODS: The ALS patients and well-matched controls underwent blood tests for serum uric acid levels which were then correlated with the patients' disability status, as expressed by the ALS Functional Rating Scale (ALSFRS-R). RESULTS: Eighty-six ALS patients and 86 well-matched controls participated. The ALS patients' mean+/-SD uric acid level was significantly lower (4.78+/-1.3 mg/dl) than that of the controls (5.76+/-1.26 mg/dl) (p<0.0001). The findings were similar for a second examination performed after an interval of at least 6 months. There was a correlation between the relative decrease of serum uric acid levels among patients (the difference between the patients' level and the controls' level) and the rate of disease progression (ALSFRS-R decline) (p<0.0001, r=0.624). CONCLUSIONS: ALS patients had lower serum uric acid levels than healthy individuals. The decreased uric acid levels were correlated to the rate of disease progression (ALSFRS-R decline), further demonstrating the possible role of oxidative stress in the induction and propagation of the disease.

Macrolides in the treatment of bronchiolitis obliterans in allograft recipients.

Bronchiolitis obliterans (BO) is a serious complication of hematopoietic SCT (HSCT). The condition is believed to be the result of an inflammatory part of the GVHD. Although many BO patients receive immunosuppressive therapy, there is no clear evidence that therapeutic interventions have a positive impact. In the last 20 years, it has been recognized that macrolides have immunomodulatory effects beyond their antibiotic effect. Recent data suggest also that the use of macrolides in BO post HSCT may halt disease progression. Our objectives are to give the readers information on the background of BO post HSCT, to review the immunomodulatory properties of macrolides in general and specifically in pulmonary diseases, and to summarize the current knowledge of macrolide benefits in BO therapy. Research into macrolide immunomodulation for chronic pulmonary disorders, such as diffuse panbronchiolitis and cystic fibrosis, shows consistent positive effects. The use of macrolides for other types of pulmonary inflammatory complications is yet to be proved. The benefit for BO post HSCT was shown only in a small non-randomized trial. Additional in vivo research is needed before developing any firm conclusions.

Low-grade systemic inflammation in patients with amyotrophic lateral sclerosis.

OBJECTIVE: To prospectively determine the intensity of systemic low-grade inflammation in patients with amyotrophic lateral sclerosis (ALS). PATIENTS AND METHODS: Patients with ALS and matched healthy controls underwent blood tests for inflammation-sensitive biomarkers: erythrocyte sedimentation rate (ESR), quantitative fibrinogen, wide-range C-reactive protein (wrCRP) concentrations, leukocyte count and neutrophil-to-lymphocyte ratio (NLR). The correlation between these inflammatory biomarkers and disability status of the patients, expressed by the ALS Functional Rating Scale (ALSFRS-R), was evaluated. RESULTS: Eighty patients with ALS and 80 matched controls were included. wrCRP, fibrinogen, ESR and NLR values were significantly elevated in patients compared with controls. There was a significant correlation between the ALSFRS-R score and wrCRP, ESR and fibrinogen levels. This correlation persisted on sequential examinations. CONCLUSIONS: A systemic low-grade inflammation was detected in patients with ALS and correlated with their degree of disability. A heightened systemic inflammatory state is apparently associated with a negative prognosis in ALS.

Antibacterial class is not obviously important in outpatient pneumonia: a meta-analysis.

The aim of the present study was to systematically compare outcomes between antibiotic classes in treating outpatient community-acquired pneumonia, with regard to antibacterials active against atypical organisms, as well as between various antibacterial classes with similar atypical coverage. A meta-analysis was performed on randomised controlled trials of antibacterials for community-acquired pneumonia in outpatients aged > or = 18 yrs. The studies were independently reviewed by two reviewers. Clinical success and mortality were compared between different oral antibiotic classes, and antibacterials with atypical coverage (macrolides and fluoroquinolones) were specifically compared with other antibacterials. In total, 13 eligible studies involving a total of 4,314 patients were included. The quality of the studies was variable. Five studied macrolides and fluoroquinolones, three macrolides and beta-lactams, three fluoroquinolones and beta-lactams and two cephalosporins versus beta-lactams/beta-lactamase inhibitors. No significant difference was detected regarding clinical success or mortality, regardless of atypical coverage or between antibacterial classes with similar atypical coverage. It was not possible to demonstrate any advantage of specific antibacterials for mild community-acquired pneumonia in relatively healthy outpatients. The need for coverage of atypical pathogens in this setting was not apparent. In mild-to-moderate cases of outpatient-treated community-acquired pneumonia, it might be most appropriate to select antibacterials according to side-effects, patient preferences, availability and cost.

Reversed halo sign in lymphomatoid granulomatosis.

Lymphomatoid granulomatosis is a rare lymphoproliferative disorder which affects extranodal sites, most commonly lung. Radiologically, it typically presents with multiple nodular opacities that may wax and wane. The reversed halo sign has previously been reported in cryptogenic organizing pneumonia and more recently in South American blastomycosis. We describe a case of histologically proven lymphomatoid granulomatosis in a patient who presented initially with the more typical nodular opacities, which subsequently progressed into the reversed halo sign. To the best of our knowledge, this association has not been previously described.

[Gram-negative enteric bacteremia in children in the Negev (1989-1994)].

During 1989-1994, there were 322 episodes of Gram-negative enteric bacteremia in 308 children. The incidence increased from 31/100,000 in children younger than 15 years of age during 1989-1991, to 50/100,000 during 1992-1994. The most common pathogens were Klebsiella, E. Coli, Salmonella and Enterobacter. 39% of episodes were nosocomial and a significant increase was recorded for each species during the last 3 years of the study. Klebsiella represented the most common pathogen causing nosocomial bacteremia, while E. coli and Salmonella were the main pathogens causing community-acquired bacteremia. In this study in southern Israel, the incidence of Gram-negative enteric bacteremia was significantly higher in Bedouin children, with the exception of bacteremia due to Salmonella, which occurred mainly in Jewish children.