Renal diseases in adults with cystic fibrosis: a 40 year single centre experience.

BACKGROUND: There is a sizable literature describing renal disease in patients with cystic fibrosis. Previous studies have focused on single disease processes alone, most commonly renal stone disease or acute kidney injury. In this study we report for the first time on the prevalence of all forms of renal disease in a cystic fibrosis population. METHODS: A retrospective review of adult patients with cystic fibrosis attending the Adult Cystic Fibrosis Department at the Royal Brompton Hospital was carried out by searching the department's database to identify patients with renal problems and subsequently retrieving clinical information from medical notes. RESULTS: The prevalence of all renal diseases in our population was 5.1 %. The most commonly identified problem was renal stones. At 2.0 % the prevalence of renal stones in adult patients with cystic fibrosis was comparable to the general population. A range of other renal diseases were identified, the next most common being drug-induced acute kidney injury. CONCLUSIONS: A range of cystic fibrosis independent and attributable diseases has been identified but no cystic fibrosis specific disease. In contrast to other cystic fibrosis centres no increased prevalence of renal stones was found.

Anaemia in lung transplant patient caused by parvovirus B19.

The case history is presented of a lung transplant patient who developed prolonged parvovirus B19 infection with severe transfusion dependent anaemia. The patient was treated with intravenous immunoglobulin after which the haemoglobin rose, together with a reticulocytosis. The patient then remained transfusion free and the virus cleared more than three months after the initial immunoglobulin treatment. The clinical and social implications for this group of patients are discussed.

Methicillin-resistant Staphylococcus aureus: impact at a national cystic fibrosis centre.

In many patient populations there has been a progressive increase in the prevalence of methicillin-resistant Staphylococcus aureus (MRSA). We examined the prevalence and consequences of acquiring MRSA in the adult cystic fibrosis (CF) population at Royal Brompton. Patients who became colonized by MRSA between 1965 and 1997 were identified from an existing database and case-notes were reviewed. Clinical and microbiological data were recorded. Twenty-six patients became colonized with MRSA during this period. Median age at acquisition was 23.4 years (range 11.8-43.3 years) and median FEV1 (percent predicted) was 28.9% (range 12-81%). Twenty patients (77%) had an FEV1 of < or = 40% predicted MRSA was probably acquired by four patients at Royal Brompton. In 17 patients isolates wer first identified whilst under the care of a total of 11 other institutions. Since the first case of MRSA infection in 1982, there has been an increase in prevalence to a current rate of nine cases in the first seven months of 1997. The commonest site of colonization was the lower airway (96%); the nose (23%) and skin sites (15%) were more rarely affected. Duration of colonization was frequently brief with nine cases (35%) lasting less than one month. The identification of MRSA appeared to be of little clinical significance, and did not generally affect outcomes. Only three patients were MRSA positive at the time of death, and in only one of these was MRSA considered a possible contributing factor.

Lack of inducible nitric oxide synthase in bronchial epithelium: a possible mechanism of susceptibility to infection in cystic fibrosis.

Cystic fibrosis (CF) is an inherited disorder associated with severe inflammation and repeated bacterial infection and colonization in the lung. Airway epithelium is involved in defence against bacteria, but this system may be defective in CF. Pro-inflammatory cytokines can stimulate the expression of inducible nitric oxide synthase (iNOS), an enzyme generating nitric oxide, which functions as an important mediator in host defence mechanisms. To understand better the poor resistance to infections in the CF lung, the expression of the iNOS gene was investigated in explanted lungs from patients with cystic fibrosis (n = 13), bronchiectasis (n = 3), emphysema (n = 14), and in normal lungs (n = 8). In addition, bronchial epithelial cell lines were examined to study iNOS gene expression in vitro. Strong immunoreactivity for iNOS was seen in inflammatory cells and bronchial epithelium in all the diseased lungs, except for bronchial epithelium in CF. Quantitative analysis showed a significant reduction in the area of epithelium immunostained in CF [CF 6.8 +/- 1.6 (% +/- SEM); emphysema 18.2 +/- 2.8; normal 9.6 +/- 0.8, P < 0.01], regardless of steroid treatment. These results were supported by in situ hybridization of iNOS mRNA, which showed a pattern of gene expression in CF, emphysema, and normal lung which paralleled that of protein immunoreactivity. Stimulation with cytokines (IL-1 beta, TNF-alpha, and IFN-gamma) increased the expression of iNOS mRNA detected by reverse transcriptase-polymerase chain reaction (RT-PCR) in cultures of normal (16HBE14o-), but not CF (CFBE41o-, with delta F508 CFTR mutation) epithelial cells. Expression of iNOS in inflammatory cells suggests that the gene is normal in CF. Absence of iNOS from bronchial epithelium may be due to low expression of the gene resulting from abnormalities in the signalling system that normally causes induction, such as cytokine receptors, second messengers or transcription factors. The resulting deficiency of the nitric oxide defence system may be relevant to the susceptibility of CF patients to pulmonary bacterial colonization.

Prevalence of occupational lung disease among Botswana men formerly employed in the South African mining industry.

OBJECTIVE: To determine whether previous health experiences affect the prevalence of occupational lung disease in a semirural Botswanan community where there is a long history of labour recruitment to South African mines. METHOD: A cross sectional prevalence study of 304 former miners examined according to a protocol including a questionnaire, chest radiograph, spirometry, and medical examination. RESULTS: Overall mean age was 56.7 (range 28-93) years, mean duration of service 15.5 (range 2-42) years. 26.6% had a history of tuberculosis. 23.3% had experienced a disabling occupational injury. Overall prevalence of pnemoconiosis (> 1/0 profusion, by the International Labour Organisation classification) was 26.6%-31.0%, and 6.8% had progressive massive fibrosis (PMF). Many were entitled to compensation under South African law. Both radiograph readers detected time response relations between pneumoconiosis and PMF among the 234 underground gold miners. PMF could result from < 5 years of exposure, but was not found < 15 years after first exposure. Both pulmonary tuberculosis (PTB) and pneumoconiosis were found to be associated with airflow limitation. CONCLUSIONS: Former miners in Botswana have a high prevalence of previously unrecognised pneumoconiosis, indicative of high previous exposures to fibrogenic respirable dust. Their pneumoconiosis went unrecognised because they had no access to surveillance after employment. Inadequate radiographic surveillance or failure to act on results when employed or when leaving employment at the mines could have contributed to under recognition. Community based studies of former miners are essential to fully evaluate the effects of mining exposures. Our findings indicate a failure of established measures to prevent or identify pneumoconiosis while these miners were in employment and show that few of the social costs of occupational lung diseases are borne by mining companies through the compensation system.

AIDS prevention programmes for workers : workplace interventions

The rapidity with which HIV infection and transmission is taking place in Botswana indicated the urgency with which there was a need to develop a programme aimed at HIV/AIDS prevention through education at the workplace. The objectives of the project are to control and prevent HIV infections among workers in Botswana; to reduce the sickness absence and mortality rates due to HIV/AIDS at the workplace and to reduce the social and economic impact of HIV infection and AIDS at workplace

Effect of sulphonylurea administration on insulin secretion and amino acid metabolism in non-insulin-dependent diabetic patients.

Sulphonylureas lower blood glucose but other metabolic effects have been little studied. In an assessment of carbohydrate and amino acid metabolism in 9 patients with non-insulin-dependent diabetes mellitus (NIDDM) before and after 3 months' therapy with gliclazide, glycaemic control was improved (mean +/- S.D. glycosylated haemoglobin 13.8 +/- 1.9% before therapy, 10.2 +/- 2.1% after therapy (p less than 0.01], but fasting amino acid levels were not altered. In contrast, postprandial levels of branched chain amino acids (BCAA) were significantly reduced: total BCAA (valine, leucine, and isoleucine) 120 mins following a standard test meal fell from 717 +/- 71 mumol/l before therapy to 600 +/- 90 mumol/l after 3 months' therapy (p less than 0.01). This finding implies an increased action of endogenous insulin on skeletal muscle to promote uptake of BCAA postprandially and, in accord with this, peripheral insulin levels were significantly increased following drug treatment (peak insulin level 55.6 +/- 20.2 mU/l before therapy, 91.3 +/- 17.9 mU/l after therapy (p less than 0.01]. Sulphonylurea drugs therefore do not simply have a hypoglycaemic action but also affect amino acid metabolism in NIDDM patients.