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J Exp Med. 2002 Nov 18;196(10):1321-33.
Recipient iNOS but not eNOS deficiency reduces luminal narrowing in tracheal allografts.

Minamoto K, Pinsky DJ.

Department of Surgery, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.

Chronic airway rejection is characterized by prolonged inflammation, epithelial damage, and eventual luminal obliterative bronchiolitis (OB). In cardiac allografts, the inducible nitric oxide synthase (iNOS) promotes acute rejection but paradoxically reduces neointimal formation, the hallmark of chronic rejection. The specific roles of NOS isoforms in modulating lymphocyte traffic and airway rejection are not known. Using a double lumen mouse tracheal transplant model, tracheal grafts from B10.A (allo) or C57BL/6J (iso) mice were transplanted into cyclosporine-treated wild-type (WT) iNOS(-/-) or endothelial NOS (eNOS)(-/-) recipients. OB was observed in WT tracheal allografts at 3 weeks (53 +/- 2% luminal occlusion vs. 17 +/- 1% for isografts, P < 0.05) with sites of obstructive lesion formation coinciding with areas of CD3(+) CD8(+) T cell-rich lymphocytic bronchitis. In contrast, allografts in iNOS(-/-) recipients exhibited reductions in local expression of proinflammatory chemokines and cytokines, graft T cell recruitment and apoptosis, and luminal obliteration (29 +/- 2%, P < 0.05 vs. WT allografts). Recipient eNOS deficiency, however, suppressed neither chemokine expression, lymphocyte infiltration, nor airway occlusion (54 +/- 2%). These data demonstrate that iNOS exacerbates luminal obliteration of airway allografts in contrast with the known suppression by iNOS of cardiac allograft vasculopathy. Because iNOS(-/-) airways transplanted into WT allograft hosts are not protected from rejection, these data suggest that iNOS expressed by graft-infiltrating leukocytes exerts the dominant influence on airway rejection.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12438423&dopt=Abstract

Fam Pract. 2000 Oct;17(5):380-5.
Antibiotics for coughing in general practice: a qualitative decision analysis.

Coenen S, Van Royen P, Vermeire E, Hermann I, Denekens J.

Centre for General Practice, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium.

BACKGROUND: In family practice, medical decisions are prompted most often by complaints about coughing. There is no single yardstick for the differential diagnosis of respiratory tract infections (RTIs). In 80% of cases, the excessive use of antibiotics in the treatment of RTIs is caused by the prescription behaviour of GPs. OBJECTIVE: Our aim was to explicate GPs' diagnostic (and therapeutic) decisions regarding adult patients who consult them with complaints about coughing, and to investigate what determines decision making. METHODS: Exploratory, descriptive focus groups were held with GPs. Hypotheses were generated on the basis of 'qualitative content analysis'. Results. Twenty-four GPs participated in four semi-structured group discussions. In order to differentiate RTIs from other possible diagnoses, less likely diagnoses were not ruled out explicitly. In the case of suspected RTI, there was a low degree of certainty in the differentiation between RTIs (e.g. between bronchitis and pneumonia). Clinical signs and symptoms, which determine the probability of disease, often left GPs with reasonable diagnostic doubt. In the end, the decision whether or not to prescribe antibiotics was taken. GPs' prescription behaviour was also determined by doctor- and patient-related factors (e.g. having missed pneumonia once, patient expectations). The 'chagrin factor' explains why these factors lead to a shift in the action threshold, in favour of antibiotics. CONCLUSION: This inductive research method enabled the generation of meaningful hypotheses regarding the complex decision processes pursued by GPs. The authors are developing an educational intervention that builds on these findings, focusing on the prescribing decision.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11021895&dopt=Abstract

Respirology. 2000 Sep;5(3):227-30.
Heat shock proteins' mRNA expression in asthma.

Tong W, Luo W.

Department of Respirology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing.

OBJECTIVE: The aim of the present study was to investigate the expression levels of heat shock proteins (HSP) mRNA in the peripheral blood mononuclear cells (PBMC) of patients with asthma and chronic bronchitis to elucidate the role of HSP in the pathogenesis of asthma and chronic bronchitis. METHOD: Using reverse transcription-DNA polymerase chain reaction, the expression levels of HSP70, HSP90alpha and HSP90beta genes in PBMC in normal state and after heat shock were investigated. RESULTS: No HSP70 gene but HSP90alpha and HSP90beta expressions were found in non-heat-shocked PBMC of normal controls; HSP90alpha and HSP90beta genes may be expressed in PBMC of all patients, independently of acute episodes. Expression of HSP70 was found in PBMC of asthmatic patients in acute episodes and three symptom-free patients with Aas 3, step 2. Among patients with chronic bronchitis, no HSP70 gene expression was found in PBMC of patients in convalescent period but in PBMC of patients in acute episode. HSP90alpha and HSP90beta genes were expressed in PBMC of both patient groups. After heat shock, expressions of the three genes increased significantly in PBMC of both normal controls and patients. CONCLUSION: Expression of HSP70 gene in PBMC of asthmatic and chronic bronchitis patients was different, indicating that HSP, especially HSP70, might be involved in the pathogenesis of asthma.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11022984&dopt=Abstract

Respirology. 2000 Sep;5(3):257-63.
Asthma is more prevalent in rural New South Wales than metropolitan Victoria, Australia.

Woods RK, Burton DL, Wharton C, McKenzie GH, Walters EH, Comino EJ, Abramson MJ.

Department of Epidemiology and Preventive Medicine, Monash Medical School and Alfred Hospital, Prahran, Victoria, Australia. Rosalie.Wooded.monash.edu.au

OBJECTIVE: The aim of this study was to compare the prevalence of adult respiratory symptoms and conditions in a rural setting with a metropolitan setting. METHODOLOGY: We used cross-sectional population surveys of respiratory health using the European Respiratory Health Survey screening questionnaire. A random sample of 4455 eligible young adults aged 20-44 years, from electoral rolls in south-eastern metropolitan Melbourne, Victoria, and 4521 from rural south-western New South Wales were surveyed. RESULTS: Response rates of 72% (n=3194) and 69% (n=3121) were achieved in Melbourne and the Riverina, respectively. Respondents from the Riverina reported significantly higher prevalences of nocturnal dyspnoea (P<0.01), chronic bronchitis (P=0.03), an asthma attack in the previous 12 months (P<0.001), ever having had asthma (P<0.001) and doctor-diagnosed asthma (P<0.001) compared to those from Melbourne. However, among those with 'asthma attacks in the last 12 months', Melbourne respondents experienced a higher frequency of attacks (P<0.05). Riverina respondents reported a higher prevalence of smoking (P<0.05) and smoked more cigarettes on average (P<0.001) than Melbourne respondents. However, annoyance from air pollution was higher in Melbourne than in the Riverina. CONCLUSIONS: These results suggest that asthma is more prevalent in rural southern New South Wales than in Melbourne but follows a different pattern of exacerbations.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11022988&dopt=Abstract

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