Human and canine pulmonary Mycobacterium bovis infection in the same household: re-emergence of an old zoonotic threat?

Bovine tuberculosis (bTB), caused by Mycobacterium bovis, remains a serious animal health problem in the UK, despite longstanding statutory surveillance and control measures. Endemic infection in the Eurasian badger population is thought to complicate bTB eradication efforts. Sporadic cases of M bovis infection have also been reported in domestic animals other than cattle. Human M bovis infection is extremely rare in the native UK population in the absence of unpasteurised milk consumption or residence abroad. Here, pulmonary TB infection in a UK born female and her pet dog is described, caused by an identical strain of M bovis. Latent TB infection was also identified in a household contact. The potential routes of infection and implications of this case are discussed.

A prospective study of asthma during pregnancy and the puerperium.

Thirty-one asthmatic women recruited in an ante-natal clinic were followed during pregnancy and for six weeks of the puerperium. Subjectively 22 (69%) women considered their asthma to have improved, two were worse and in seven (22%) there was no change. Analysis of peak flow rate, symptoms score and bronchodilator use showed that in ten pregnancies there was improvement in the third trimester and that in 11 there was deterioration in the puerperium. The results suggest that in patients with mild or moderate asthma an improvement is likely to occur during pregnancy, particularly in the last trimester, but that in over one-third there may be a post-natal deterioration. Review of the literature suggests that severe asthmatics are at greater risk of deterioration, particularly late in pregnancy.

Clinical and radiographic features of psittacosis infection.

Forty three cases of psittacosis infection were identified retrospectively over a five year period. The commonest clinical presentation was of a bronchitic illness with a productive cough and features of systemic upset. In 12 (28%) cases no radiographic abnormality was detected on the chest film. Segmental shadowing was the commonest abnormality but lobar and more extensive consolidation occurred. There were no radiographic features that allowed confident differentiation from other causes of pneumonia. The total and differential white cell counts were usually normal and this feature may help to differentiate psittacosis from bacterial pneumonia.

Tuberculosis in renal transplant recipients.

Of more than 400 patients who received renal transplants in Cambridge, five subsequently developed tuberculosis. All had pulmonary involvement. Radiological abnormalities included miliary opacities, bilateral lower zone shadowing or typical upper zone shadowing with cavitation. Lung biopsy was required for diagnosis in two cases. Three patients recovered after treatment with antituberculosis drugs and none has relapsed. One died during chemotherapy despite drug-susceptible organisms. The problems encountered during chemotherapy are discussed.

A role for transglutaminase in glucose-stimulated insulin release from the pancreatic beta-cell.

Preincubation of rat islets of Langerhans with the potent inhibitors of islet transglutaminase activity, monodansylcadaverine (30-100 microM) and N-(5-aminopentyl)-2-naphthalenesulphonamide (100-200 microM), led to significant inhibition of glucose-stimulated insulin release from islets. In contrast, the respective N'-dimethylated derivatives of these two compounds, which did not inhibit islet transglutaminase activity, were much less effective as inhibitors of glucose-stimulated insulin release. None of the compounds inhibited rat spleen protein kinase C activity at concentrations which gave rise to inhibition of glucose-stimulated insulin release. When tested for their effects on calmodulin-stimulated bovine heart phosphodiesterase activity, of the compounds that inhibited insulin release, only monodansylcadaverine did not act as an effective antagonist of calmodulin at concentrations (up to 50 microM) that gave rise to significant inhibition of glucose-stimulated insulin release. Furthermore, at 50 microM, monodansylcadaverine did not inhibit methylation of islet lipids. The inhibition of glucose-stimulated insulin release by monodansylcadaverine is therefore likely to be attributable to its interference with islet transglutaminase activity. The sensitivity of islet transglutaminase to activation by Ca2+ was investigated by using a modified assay incorporating dephosphorylated NN'-dimethylcasein as a substrate protein. The Km for Ca2+ obtained (approx. 3 microM) was an order of magnitude lower than previously reported for the islet enzyme [Bungay, Potter & Griffin (1984) Biochem. J. 219, 819-827]. Mg2+ (2 mM) was found to have little effect on the sensitivity of the enzyme to Ca2+. Investigation of the endogenous substrate proteins of islet transglutaminase by using the Ca2+-dependent incorporation of [14C]methylamine into proteins of islet homogenates demonstrated that most of the incorporated radiolabel was present in cross-linked polymeric aggregates which did not traverse 3% (w/v) acrylamide gels. The radiolabelled polymeric aggregates were present in 71 000 g-sedimented material of homogenates, and their formation was transglutaminase-mediated. These findings provide new evidence for the involvement of islet transglutaminase in the membrane-mediated events necessary for glucose-stimulated insulin release.

Premenstrual exacerbation of asthma.

Questionnaires and twice daily peak expiratory flow measurements were used to evaluate the effects of the menstrual cycle in asthmatic women. Forty per cent of women reported premenstrual deterioration in their symptoms and this was confirmed by peak flow recordings. No correlations were found between premenstrual exacerbation of asthma and symptoms of premenstrual tension, consumption of aspirin, use of the contraceptive pill, cycle length, or behaviour of asthma during pregnancy.

New calmodulin antagonists inhibit in vitro growth of human breast cancer cell lines independent of their estrogen receptor status.

Calmodulin plays a key role in the regulation of cell proliferation and calmodulin antagonists may offer a new therapeutic approach in the treatment of breast cancer. Three new specific calmodulin antagonists with improved potency were synthesized and screened on human breast cancer cell lines known to be estrogen receptor (ER)-positive or -negative. These calmodulin antagonists significantly inhibited cell growth as measured by the MTT proliferation assay (p<0.001). Their IC50 values were in the low micromolar range against both ER-positive and -negative variants of the MCF-7 cell line. Two other breast cancer cell lines (ER-positive T-47D and ER-negative MDA-MB-231) were also inhibited by these calmodulin antagonists with IC50 values in a similar range. The level of inhibition was independent of any stimulation of cell growth by estradiol. Calmodulin antagonists effectively reduced cell growth of both ER-positive and -negative human breast cancer cell lines in vitro. Calmodulin antagonists represent a novel therapeutic approach requiring further investigation.

National benchmarking as a support system for clinical governance.

Audit of the management of acute asthma in hospital has developed in tandem with guidelines produced and updated by the British Thoracic Society (BTS), on the principle that agreed guidelines combined with systematic review of practice by periodic audit are more likely to result in improvements in practice than guidelines alone. A short audit data set was distilled from previous experience with more elaborate tools and made available nationally to audit departments and through letters to consultant members of the BTS. Hospitals have been able to contribute since 1990. The data set reflects key items of the process of care: peak flow measured on admission and twice daily during the hospital stay; blood gases on admission; systemic corticosteroids as an inpatient; discharged with inhaled and oral corticosteroids; written self-management plans; follow-up arrangements. Data from 4,741 admissions over a seven year period are presented. The proportion of patients nationally receiving these items of asthma care is given. The median values for hospital performance improved significantly over the seven years, although there is potential for further improvement. If these data represent the national picture, they could form the basis upon which to set national standards for the care of patients with acute asthma in hospital. A further result of the developing audit has been the recognition of the value of external benchmarking in providing a context for the interpretation of local audit results. This audit system provides hospitals with a quick and easy method of obtaining an overview of local performance, with comparative national data for the same year. This has potential as a tool for clinical governance with much wider applicability, providing the data are handled carefully, particularly as the variability between hospitals diminishes over time.

Mortality in cases of asbestosis diagnosed by a pneumoconiosis medical panel.

One hundred and fifty five male cases of asbestosis certified by the London Pneumoconiosis Medical Panel during 1968-74 were followed up during 1978-9, 4-11 (mean 7.5) years after certification. Fifty nine patients had died, 23 (39%) from lung cancer, 6 (10%) from mesothelioma, and 11 (19%) from other respiratory causes. The number of observed deaths was 2.25 times greater than expected and 7.4 times greater than expected for lung cancer. Adenocarcinoma was the commonest histological type but other cell types were also increased. Finger clubbing (p less than 0.01) and percentage of predicted FEV1 (p less than 0.01) were of value in predicting death, but increasing profusion of small opacities greater than 1/0 (ILO/U-C international classification of radiographs of pneumoconiosis, 1971), duration of exposure to asbestos, time from first exposure to asbestos, and percentage of predicted vital capacity and transfer factor did not predict death.

Significance of finger clubbing in asbestosis.

The prognostic significance of finger clubbing in asbestosis has been assessed in 167 cases certified by the London Pneumoconiosis Medical Panel from 1968 to 1974. Finger clubbing developed early in the clinical course of the disease and was associated with a lower gas transfer, a higher mortality and a greater likelihood of progression in intrapulmonary fibrosis than was found among cases without finger clubbing. Finger clubbing was not associated with heavier asbestos exposure. Its presence appears to be associated with a more severe form of disease.

Interstitial lung disease and asthma in hard-metal workers: bronchoalveolar lavage, ultrastructural, and analytical findings and results of bronchial provocation tests.

Five patients with respiratory disorders associated with hard metal exposure are described. In four patients electron microprobe analysis of bronchoalveolar lavage cells or lung tissue was used to show tungsten and other hard-metal components. Three patients had interstitial pneumonia and fibrosis with unusual multinucleate giant cells. Electron microscopy showed that the giant cells comprised both type II alveolar epithelial cells and alveolar macrophages. The multinucleate macrophages formed a distinctive feature of the bronchoalveolar lavage material but the multinucleate alveolar epithelial lining cells were evident only in lung tissue. The other two patients both suffered from work-related asthma, one of whom also had pulmonary opacities. Bronchial provocation tests in these patients supported the diagnosis of hard-metal-induced asthma and implicated cobalt as the agent responsible.

Histocompatibility antigens in coal miners with pneumoconiosis.

Twenty-five histocompatibility antigens have been measured in 100 coal miners with pneumoconiosis attending a pneumoconiosis medical panel and the results compared with a panel of 200 normal volunteers not exposed to dust. Chest radiographs were read independently by three readers according to the ILO U/C classification. On a combined score, 40 men were thought to have simple pneumoconiosis and 60 men complicated pneumoconiosis. The number of antigens tested and associations between antigens caused difficulties in assessing the statistical significance of differences in prevalence of antigens between groups of men. Using stringent criteria for statistical significance, no significant differences were found in antigen prevalences between miners and controls, or miners with simple or complicated pneumoconiosis. When a less stringent statistical approach was applied, three antigens appeared to have abnormal prevalences in these 100 miners by comparison with the normal volunteers. More detailed examination of these antigen prevalences in relation to radiographic category of pneumoconiosis did not provide any supportive evidence that these slight associations were of statistical or clinical significance. Reports on histocompatibility antigens in miners with pneumoconiosis are reviewed briefly and the results compared. There is no good evidence that any of the histocompatibility antigens so far tested are associated with a clinically important altered risk of simple or complicated pneumoconiosis when dust is inhaled.