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Biomedical subjects

J Osman

Publications and source records attributed to J Osman.

At least 19 recordsLinked to original sources
PubMed2003

Investigating and analysing workplace clusters of diseases: a Health & Safety Executive perspective.

BACKGROUND: Clusters of disease arising in workplaces cause concern among the management of the company, the workers affected and their families and friends. Chance is the most likely explanation for their occurrence, although a number of real workplace hazards have been identified through their observation and investigation. Employers have a duty to investigate such occurrences in order to assess whether some unknown or unidentified hazard is at work and to take the appropriate action. Several papers have been published over the last 15 years or so that set out a method for investigating workplace clusters of disease. Aims This paper presents the steps in the approach taken by the Health & Safety Executive in Great Britain. METHOD: An initial step identifies the relevant stakeholders at the outset, in order to maintain a realistic expectation of what the investigation can hope to achieve and to open a dialogue. The main steps in the assessment are: (1) identifying cases; (2) determining the other parameters of the investigation; (3) statistically assessing the cluster; (4) examining potential exposures and assessing their biological plausibility; and (5) determining the overall significance of the cluster. The approach is illustrated throughout by examples.

Cluster Analysis↗
PubMed2002

Participatory analysis of seasonal incidences of diseases of cattle, disease vectors and rainfall in southern Sudan.

During an investigation into a chronic wasting disease in southern Sudanese cattle, a participatory appraisal method called a 'seasonal calendar' was used to understand local perceptions of seasonal variations in cattle diseases, disease vectors, intermediate hosts and rainfall. Repetition of a standardized seasonal calendar with Dinka informants demonstrated good reproducibility of the method. Comparison of rainfall data produced by seasonal calendars and objective measures of rainfall demonstrated good validity of the seasonal calendar method. Subjective assessment of seasonal calendar scoring patterns by veterinarians indicated that herders' perceptions of seasonal populations of biting flies, ticks and snails were similar to modern veterinary knowledge. The uses of seasonal calendars in veterinary epidemiology are discussed.

Animal Husbandry↗
PubMed2001

Participatory diagnosis of a chronic wasting disease in cattle in southern Sudan.

In southern Sudan, livestock keepers identified a chronic wasting disease in adult cattle as one of their most-serious animal-health problems. Participatory-appraisal (PA) methods and conventional veterinary-investigation methods were used to characterise the chronic wasting disease and identify linkages between indigenous knowledge and modern veterinary knowledge. The local characterisation of chronic wasting encompassed trypanosomosis, fasciolosis, parasitic gastroenteritis and schistosomosis (as both single and mixed infections).A standardised PA method called matrix scoring had good reproducibility when investigating local perceptions of disease-signs and disease causes. Comparison of matrix-scoring results showed much overlap with modern veterinary descriptions of cattle diseases and the results of conventional veterinary investigation. Applications of PA methods in remote areas with very limited veterinary infrastructure are discussed. The validation of data derived from PA is discussed by reference to the low sensitivity of 'field-friendly' diagnostic tests for important cattle diseases.

Animals↗
PubMed2000

Increased microvascular reactivity and improved mortality in septic mice lacking inducible nitric oxide synthase.

Persistent vasodilation characteristic of septic shock may result from overproduction of nitric oxide and can lead to pressor-refractory hypotension and death. To evaluate the significance of cytokine-inducible nitric oxide synthase (iNOS) in the pathogenesis of sepsis, we used a clinically relevant mouse model of sepsis and compared mortality and microvascular reactivity in wild-type (WT) mice and transgenic mice deficient in iNOS. WT C57BL/6 and iNOS-deficient mice were made septic by cecal ligation and puncture. Treated mice were given fluids and antibiotics every 6 hours. Microvascular vasoconstriction in response to topical norepinephrine was measured in cremasteric arterioles (15 to 30 microm) by videomicroscopy. Mortality at 48 hours was significantly lower in treated septic iNOS-deficient mice (45%) than in treated septic WT mice (76%), untreated septic iNOS-deficient mice (87%), or untreated WT mice (100%) (P<0.01). Norepinephrine-induced vasoconstriction was decreased in WT septic mice (EC(50) 200+/-56 nmol/L) compared with WT and iNOS-deficient shams (16+/-4 and 13+/-6 nmol/L), and vasoconstriction was significantly improved in septic iNOS-deficient mice (35+/-13 nmol/L, P<0.01). Microvascular catecholamine responsiveness and survival were improved in iNOS-deficient mice in a clinically relevant model of sepsis, suggesting that iNOS plays an important, but not exclusive, role in refractory vasodilation in patients with septic shock.

Animals↗
PubMed1999

Spontaneous abortion in the British semiconductor industry: An HSE investigation. Health and Safety Executive.

BACKGROUND: The UK Health and Safety Executive (HSE) conducted a study to examine the risk of spontaneous abortion (SAB) in British female semiconductor industry workers, following reports from the USA which suggested an association between risk of SAB and work in fabrication rooms and/or exposure to ethylene glycol ethers. METHODS: A nested case-control study based on 2,207 women who had worked at eight manufacturing sites during a 5-year retrospective time frame was established; 36 cases were matched with 80 controls. RESULTS: The overall SAB rate in the industry was 10.0%. (65 SABs/651 pregnancies) The crude odds ratio (OR) for fabrication work was 0.65 (95% CI 0.30-1.40). This was essentially unchanged after adjustment for a range of potential confounding factors in the first 3 months of pregnancy and was reduced to 0.58 (95% CI 0.26-1.30) after adjustment for smoking in the previous 12 months. There were no statistically significantly elevated ORs for any work group or any specific chemical or physical exposure in the industry. CONCLUSIONS: There is no evidence of an increased risk of SAB in the British semiconductor industry. Am. J. Ind. Med. 36:557-572, 1999. Published 1999 Wiley-Liss, Inc.

Abortion, Spontaneous↗
PubMed1999

Effects of nitric oxide synthase inhibition on microvascular reactivity in septic mice.

Persistent vasodilation refractory to vasopressor agents is characteristic of septic shock. Induction of nitric oxide synthase (NOS) by sepsis-induced cytokines within the vasculature is one of the primary mediators of this refractory vasodilation. To evaluate the mechanism of vasodilation in sepsis, we used in vivo videomicroscopy to measure microvascular vasoconstrictive responses to topical suffusion of norepinephrine in mice made septic by cecal ligation and puncture, and contrasted the effects of topical superfusion of the nonselective NOS inhibitor N(G)-methyl-L-arginine (L-NMMA) and the selective inducible NOS (iNOS) inhibitor S-methyl-isothiourea (SMT). Mice with sepsis were less sensitive to the vasoconstrictive effects of norepinephrine than controls (EC50, the concentration that produces half-maximal response 2.0+/-0.6 x 10(-6) M vs. 7.9+/-2.2 x 10(-8) M, P=0.01). Selective inhibition of inducible iNOS with topical SMT (100 microM) markedly increased catecholamine reactivity in mice with sepsis but did not affect reactivity in controls (P=0.0007 for sepsis, P=0.24 for controls). Nonselective NOS inhibition with topical L-NMMA produced a similar increase in catecholamine reactivity in mice with sepsis but not controls (P=0.001 for sepsis, P=0.56 for controls). When excess (1 mM) L-arginine, the substrate for NOS, was added to the superfusion buffer along with both SMT and L-NMMA, arteriolar responsiveness to norepinephrine was decreased to the original values. These experiments demonstrate that iNOS inhibition is as effective as nonselective NOS inhibition in reversing decreased catecholamine reactivity in sepsis. This suggests a crucial role for microvascular activation of iNOS in the pathophysiology of hypotension and decreased vasopressor responsiveness in sepsis.

Animals↗
PubMed1995

Expression of ectopeptidases in scleroderma.

OBJECTIVES: To examine the expression and concentrations of three ectopeptidases likely to be involved in regulating the functional levels of adhesion molecules and the turnover of connective tissue components, in patients with scleroderma (systemic sclerosis) (SSc) and in normal individuals. METHODS: Monoclonal antibodies against these antigens were used for immunoperoxidase staining of cryostat skin sections and for flow cytometric (fluorescence activated cell sorter) analysis of cultured dermal fibroblasts grown from SSc patients and normal controls. RESULTS: Although neutral endopeptidase-24.11 (NEP) (CD10) was not detected in either SSc or normal skin, aminopeptidase N (APN) (CD13) and dipeptidyl peptidase IV (DPPIV) (CD26) were both readily visualised. However, DPPIV appeared to be present in smaller concentrations in the SSc biopsy specimens. Moreover, while fibroblasts grown in vitro from both SSc and normal skin also had similar concentrations of APN, the expression of DPPIV in the cultured SSc cells was found to be very much less than that present in the normal fibroblasts. It is noteworthy that NEP, which was not detected in the tissue sections, was nevertheless readily detected in fibroblasts in culture. CONCLUSIONS: These results show that a number of cell surface proteases are expressed by dermal fibroblasts both in vivo and in vitro, and it is suggested that the marked downregulation of DPPIV in SSc could be at least partly responsible for the increased concentrations of adhesion molecules and matrix proteins associated with the molecular pathology of this disease.

Adolescent↗
PubMed1994

Excess matrix accumulation in scleroderma is caused partly by differential regulation of stromelysin and TIMP-1 synthesis.

Scleroderma (systemic sclerosis: SSc) is an autoimmune disorder in which excessive extracellular matrix is deposited in skin and internal organs. Because of the importance of metalloproteinases in the turnover of connective tissue, in this study we have developed a novel procedure which utilises flow cytometry (FACS) to measure the production of stromelysin (MMP-3), gelatinase A (MMP-2), and the proteinase inhibitor TIMP-1, by SSc skin fibroblasts. In the presence of monensin, which prevents the secretion of these matrix proteins, there was a similar intracellular accumulation of gelatinase A in normal and SSc cells. However, whereas stromelysin levels also increased in the normal cells, no net synthesis could be detected in the SSc fibroblasts. In marked contrast, the synthesis of TIMP-1 was 50% greater in the SSc cells than in the normal fibroblasts. Our results thus show unequivocally, for the first time, that cells from SSc patients simultaneously produce less stromelysin but substantially higher amounts of TIMP-1 than do normal dermal fibroblasts, suggesting that abnormalities in the regulation of the matrix enzymes and their inhibitors play an important part in the molecular pathology of SSc.

Adolescent↗
PubMed1993

Haematological disorders and occupational hazards: a British Society for Haematology/Health and Safety Executive study.

During a 3-year period 229 patients in the U.K. with haematological disorders thought to be associated with occupational hazards were notified to the British Society for Haematology/Health and Safety Executive office. Most were suffering from malignant or premalignant states or aplastic anaemia. Benzene and ionizing radiation were the most common agents recorded. While no estimate can be made of the incidence of chemical or radiation induced disease at the present time, the data suggests that routine documentation of exposure at work is an important step in allowing more specifically focused studies.

Adult↗
PubMed1989

Skin-prick test preparations of Dermatophagoides pteronyssinus for prediction of a positive response to provocation testing.

Skin-prick testing (SPT) with allergen is widely used in the investigation of respiratory disease, yet its relationship to the results of provocation testing of the nose or bronchus remains obscure. We have studied this relationship by determining the concentration of Dermatophagoides pteronyssinus extract and the associated weal size which resulted in the lowest 'false positive' (FP) and highest 'true positive' (TP) rates when compared to the results of bronchial and nasal provocation testing. Subjects studied included those with both positive and negative bronchial or nasal provocation tests. For each of a series of concentrations of D. pteronyssinus extract, standardized in relation to content of Der pI antigen, receiver operating characteristic (ROC) curves of TP against FP rates were constructed. Optimal diagnostic concentrations for SPT were 0.112-1.122 x 10(6) IU of Der pI ml-1. However, at the lower end of this range the optimum weal areas for a positive test with the D. pteronyssinus extract were very small (less than 5 mm2). More appropriate concentrations for use in clinical practice were 0.56-1.122 x 10(6) IU Der pI ml-1 since at these concentrations more easily measurable weal areas of 5-10 mm2 (2.6-3.6 mm diameter) were almost equally predictive of a positive provocation test.

Airway Resistance↗
PubMed1988

The assessment of a computer administered questionnaire in the differential diagnosis of asthma and chronic airflow limitation.

We have tested a computer administered respiratory symptom questionnaire in patients with asthma, chronic airflow limitation, and subjects with no evidence of respiratory disease. The questionnaire was highly effective at distinguishing patients with respiratory disease from those without. However, the responses of asthmatic patients and patients with CAL to the majority of questions were similar though the responses to four out of 11 questions were significantly different. We conclude that such a computer administered questionnaire is of limited value in distinguishing patients with asthma and CAL, underlining the importance of objective tests in this differential diagnosis.

Adult↗
PubMed1987

Management of acute asthma: a survey of hospital practice and comparison between thoracic and general physicians in Birmingham and Manchester.

The assessment and treatment of 140 randomly selected patients with acute asthma admitted to hospitals in Birmingham and Manchester in 1978 were studied. A detailed history of attack severity was recorded in just over half the case notes on admission (55%) and objective evidence of severity was recorded in a smaller number (measurement of airflow obstruction in 31% and arterial blood gases in 42%). Twenty-one (31%) thoracic patients and 33 (45%) general medical patients received aerosolized bronchodilators from metered-dose inhalers alone and 31% of all patients were given no inhaled bronchodilator drugs. Although the asthma was considered severe enough to require admission to hospital 37% were not given a course of corticosteroid therapy. Response to treatment was monitored by serial peak flow measurements in only 51% overall. Discharge therapy included a bronchodilator inhaler and oral corticosteroids in less than half (43%) of patients. There was no major difference in severity of asthma in patients admitted under the care of 'thoracic' or 'general' physicians but significant differences were found in their assessment and treatment. 'Thoracic' physicians more often measured severity and the response to treatment objectively. They prescribed inhaled (rather than intravenous) bronchodilator drugs more frequently and were more likely to discharge patients with a bronchodilator inhaler, oral corticosteroids, prophylactic therapy and an outpatient follow-up appointment.

Acute Disease↗
PubMed1987

A comparison of the PD35-sGaw and PD20-FEV1 in assessment of the effect of oral anti-allergic compounds on the immediate asthmatic response to inhaled allergen.

Assessment of two methods of measuring airway response to allergen challenge showed that results obtained using FEV1 correlated well with those obtained using sGaw irrespective of pre-treatment. Significantly smaller amounts of allergen were required to reduce the sGaw by 35% than to reduce the FEV1 by 20%, although both indices discriminated equally well between the effects of drugs on airway responses to challenge.

Adult↗
PubMed1986

Asthma and rhinitis after exposure to glutaraldehyde in endoscopy units.

Four nurses working in endoscopy units complained of respiratory symptoms on exposure to alkaline glutaraldehyde used as a disinfectant for fibre-optic endoscopes. A provocation test was positive in two of these patients. This is the first report to use provocation testing to confirm a relation between exposure to alkaline glutaraldehyde and respiratory disease.

Adult↗
PubMed1985

Assessment of bronchiectasis by computed tomography.

Computed tomography and bronchography were used to assess the distribution of bronchiectasis in 15 lungs from eight patients with clinical features of the disease. Of the 36 lobes adequately displayed by bronchography, 22 were found to have bronchiectasis and 14 were found to be normal by both techniques. Cystic disease was readily identified by computed tomography but the cylindrical and varicose types of bronchiectasis could not be distinguished. Segmental localisation was less accurate, with agreement between computed tomography and bronchography in 116 out of 130 segments. It is concluded that with a modern high resolution scanner computed tomography provides a useful method of assessing lobar distribution in bronchiectasis.

Bronchiectasis↗
PubMed1984

Use of inhaled calcium channel blocking agents in the treatment of asthma.

The inhalation of drugs that are active in the respiratory tract offers the ideal route of administration, since it results in the rapid delivery of appropriate concentrations with a much reduced risk of systemic adverse effects: Problems with regard to poor absorption from the gastrointestinal tract (sodium cromoglycate) or substantial effect on liver metabolism (verapamil) can be avoided. Certain drugs such as antihistamines and ketotifen may be more effective administered by inhalation since high concentrations with reduced unwanted effects can be achieved on the bronchial surface where, in allergic asthma, the critical initial interaction between sensitized mast cells (mucosal?) and allergen with subsequent mediator release occurs. Indeed inhaled verapamil has been shown to be effective in animal models of asthma but not in man. Systemically administered nifedipine gives partial and variable protection against induced asthma in man and its efficacy (with reduced cardiovascular effects) may well be improved by inhalation.

Aerosols↗