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Biomedical subjects

D M Mitchell

Publications and source records attributed to D M Mitchell.

At least 55 records · Page 3Linked to original sources
PubMed1995

Mycobacterial infection in HIV seropositive and seronegative populations, 1987-93.

BACKGROUND: Although the causes of the worldwide resurgence of tuberculosis are multifactorial, the HIV epidemic is believed to have had a central role. Control is further threatened by the emergence of multidrug-resistant tuberculosis. METHODS: A retrospective evaluation was undertaken of trends in pulmonary and extrapulmonary culture positive mycobacterial pathology, and the prevalence of drug-resistant tuberculosis in both HIV seropositive and, presumptively, HIV seronegative patients receiving their clinical care at St Mary's Hospital, London. Five hundred and thirty eight patients (188 of whom were known to be HIV seropositive) with positive mycobacterial isolates between January 1987 and March 1993 were identified from laboratory records. These were cross referenced with drug surveillance records. RESULTS: Overall, between 1987 and 1992 there was a progressive 3.5 fold increase in positive mycobacterial isolates and a 2.5 fold increase in patients with proven mycobacterial infection. This increase was greater within the HIV seropositive population. A total of 663 positive mycobacterial isolates was evaluated; the major pathogen identified was Mycobacterium tuberculosis (379 isolates, 57%). Three hundred and fourteen patients were diagnosed as having M tuberculosis, 49 of whom were HIV seropositive. M tuberculosis was predominantly isolated from the lung. Of 358 positive cultures for M tuberculosis (68 HIV seropositive, 290 presumptively HIV seronegative), only 27 isolates (7.6%), almost exclusively derived from presumed HIV seronegative patients, were resistant to either isoniazid, rifampicin, or both drugs together. No increases in drug-resistant isolates were observed over this period. CONCLUSIONS: There has been a considerable increase in the incidence of tuberculosis in both HIV seronegative and seropositive populations during the study period. The emergence of drug-resistant tuberculosis was not observed.

Adolescent↗
PubMed1995

Pulmonary complications of HIV disease: 10 year retrospective evaluation of yields from bronchoalveolar lavage, 1983-93.

BACKGROUND: Pulmonary disease is a major contributor to morbidity and mortality in patients with HIV infection and AIDS. The aim of this study was to describe bronchoscopic findings and the spectrum of pulmonary pathogens in HIV seropositive patients undergoing investigation of respiratory disease over a 10 year period in a major UK referral centre. METHODS: Recruitment was procedure based with data being captured when bronchoscopy was clinically indicated. Data were evaluated from 580 HIV seropositive patients (559 men, age 13-65 years) over a 10 year period from June 1983 to March 1993. RESULTS: A total of 947 bronchoscopies was performed. The most frequent pulmonary pathogen isolated from bronchoalveolar lavage (BAL) fluid in 44% of all bronchoscopies was Pneumocystis carinii. Of all patients studied, 324 (55%) had at least one cytologically confirmed episode of P carinii pneumonia; this was AIDS defining in 219 (38%) of patients who underwent bronchoscopy. Between 1987 and 1993 the overall diagnostic yield from BAL fluid was 76%; 25% of all bronchoscopies yielded positive microbiological results, the most frequent isolates being Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas spp, and Haemophilus influenzae. Mycobacteria were identified in 8% of patients; M tuberculosis was the most common being identified in 3% of lavage samples and in 4% of patients. No drug-resistant M tuberculosis was found. Viral isolates (mainly cytomegalovirus) were identified in up to 31% of BAL fluid samples. Endobronchial Kaposi's sarcoma was seen in 15% of patients at bronchoscopy. CONCLUSIONS: Of the 1956 newly diagnosed HIV seropositive patients receiving clinical care at St Mary's Hospital over this period, approximately 30% underwent bronchoscopy. Diagnostic rates for P carinii pneumonia, endobronchial Kaposi's sarcoma, and bacterial and mycobacterial infection have remained largely constant since 1989. Bronchoalveolar lavage produces high diagnostic yields generally, and P carinii pneumonia remains a common cause of pulmonary disease in these patients.

Adolescent↗
PubMed1995

Growth performance, carcass composition, and pigmentation of broilers fed supplemental nickel.

Two experiments were conducted to evaluate effects of supplemental Ni on growth performance, carcass composition, and pigmentation of broilers. In Experiment 1, female broilers (n = 120) were housed in individual cages from 21 to 49 d of age and fed a commercial finisher diet that contained 2.4 +/- .1 ppm Ni. Supplementation of this diet with 6 or 12 ppm NiCl2 did not affect growth performance or carcass composition. In Experiment 2, female broilers (n = 60) housed in individual cages were fed finisher diets with 44 or 77 ppm xanthophyll and 0 or 12 ppm supplemental NiCl2. Growth performance from 21 to 49 d of age was not altered by diet. At 49 d of age, serum xanthophyll concentration as well as amount of lutein and total xanthophylls in skin were higher (P < or = .01) in broilers fed 77 ppm xanthophyll. Supplemental NiCl2 decreased (P < or = .1) yellow color of carcasses from broilers fed 44 ppm xanthophyll and increased yellow color of carcasses from broilers fed 77 ppm xanthophyll. Abdominal fat yields and concentration of total xanthophylls in skin followed a similar pattern, suggesting that supplemental NiCl2 may have indirectly influenced pigmentation by altering fat deposition. These data indicated that an adequate level of Ni was present in the basal diet to promote optimal growth performance and carcass quality.

Animal Feed↗
PubMed1994

The mortality of rheumatoid arthritis.

OBJECTIVE: To determine the risk and causes of death and to quantify mortality predictors in patients with rheumatoid arthritis (RA). METHODS: RA patients (n = 3,501) from 4 centers (Saskatoon n = 905, Wichita n = 1,405, Stanford n = 886, and Santa Clara n = 305) were followed for up to 35 years; 922 patients died. RESULTS: The overall standardized mortality ratio (SMR) was 2.26 (Saskatoon 2.24, Wichita 1.98, Stanford 3.08, Santa Clara 2.18) and increased with time. Mortality was strikingly increased for specific causes: infection, lymphoproliferative malignancy, gastroenterologic, and RA. In addition, as an effect of the SMR of 2.26, the expected number of deaths was increased nonspecifically across all causes (except cancer), with a large excess of deaths attributable to cardiovascular and cerebrovascular diseases. Independent predictors of mortality included age, education, male sex, function, rheumatoid factor, nodules, erythrocyte sedimentation rate, joint count, and prednisone use. CONCLUSION: Mortality rates are increased at least 2-fold in RA, and are linked to clinical severity.

Arthritis, Rheumatoid↗
PubMed1994

HIV-1 proviral DNA copy number in peripheral blood leucocytes and bronchoalveolar lavage cells of AIDS patients.

In this study we have determined by polymerase chain reaction (PCR) the quantity of HIV-1 proviral DNA in cells obtained by bronchoalveolar lavage (BAL) from the lung of HIV-1+ individuals. This has been compared quantitatively with the proviral DNA in peripheral blood leucocytes (PBL) obtained simultaneously from the same patients. The mean HIV DNA copy number per 10(6) cells was 391 for PBL, with a range of 1-9000, and 2971 for BAL cells, with a range of < 1-70,000. The quantity of HIV DNA detected in BAL cells was higher than that detected in the corresponding PBL samples in 44 out of 78 (56%) individuals, whilst more HIV DNA was detected in the PBL compared with BAL cells in 14 out of 78 (18%) patients. In both BAL and PBL higher levels of HIV DNA were detected in the adherent (monocyte/macrophage) enriched cell populations compared with other non-adherent cells (leucocytes). A direct relationship between HIV DNA copy number and ability to recover infectious HIV progeny in vitro by co-cultivation with cord blood leucocytes was found for both PBL and BAL cells. Individuals known to be receiving azidothymidine treatment had a lower mean HIV DNA load in all cell fractions compared with those patients on no antiretroviral therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Evidence for a Th1-like bronchoalveolar T-cell subset and predominance of interferon-gamma gene activation in pulmonary tuberculosis.

Mycobacterium-specific human helper T-cell clones produce a Th1 pattern of cytokines in vitro: interferon-gamma (IFN-gamma) and interleukin-2 (IL-2), but little or no IL-4 or IL-5. To test the hypothesis that a similar Th1-like pattern of cytokine gene expression occurs in vivo in pulmonary tuberculosis we used in situ hybridization to detect cytokine mRNA expression by bronchoalveolar lavage cells from nine patients with microbiologically confirmed tuberculosis and nine control subjects. Because IFN-gamma may also originate from alveolar macrophages, simultaneous immunocytochemistry and in situ hybridization was applied to determine whether cytokine mRNA was localized to bronchoalveolar macrophages in addition to T-lymphocytes. When samples from patients with tuberculosis and control subjects were compared, there was a significant increase in numbers of IFN-gamma mRNA-positive BAL cells per 1,000 among patients with tuberculosis (p < 0.01). Differences between the two groups in the proportions of cells expressing IL-2, IL-4, or IL-5 mRNA were not significant. Expression of IFN-gamma mRNA by macrophages was detected (median, 14.3% of IFN-gamma mRNA-positive BAL cells). However, the majority of IFN-gamma mRNA expressing BAL cells were T-lymphocytes (median, 80.7%). Activation of Th1-like bronchoalveolar T-lymphocytes, together with production of IFN-gamma by alveolar macrophages, may contribute to the local cellular immune response in pulmonary tuberculosis.

Adolescent↗
PubMed1994

Platelet-derived growth factor-beta mRNA in human alveolar macrophages in vivo in asthma.

Collagen deposition and myofibroblast proliferation beneath the epithelial basement membrane in patients with asthma is now increasingly recognized, although the molecular pathogenesis remains obscure. We have evaluated messenger ribonucleic acid (mRNA) expression of the profibrotic cytokine, platelet-derived growth factor-beta (PDGF-beta), in alveolar macrophages obtained following fibreoptic bronchoscopy and bronchoalveolar lavage in patients with asthma. Three subject groups were studied: 1) asthmatics using regular inhaled glucocorticoid medication (ASTST, n = 9), 2) asthmatics using intermittent inhaled beta 2-agonist therapy only (ASTBR, n = 10); 3) nonasthmatic control volunteers (n = 10). Alveolar macrophage mRNA was extracted and PDGF-beta mRNA quantified by reverse-transcriptase polymerase chain reaction (PCR) (RT-PCR) and expressed as the ratio to that of a control gene glyceraldehyde-3-phosphate dehydrogenase (GAPDH). There were no significant differences in PDGF-beta mRNA expression between the groups, or between all asthmatic (n = 19) and control subjects. Furthermore, there was no correlation between alveolar macrophage PDGF-beta mRNA expression and airway spirometry, or duration of glucocorticoid usage or dose. Thus, in contrast to other fibrotic lung diseases, we found little evidence of enhanced expression of PDGF-beta mRNA in alveolar macrophages in clinically stable bronchial asthma.

Adult↗
PubMed1994

Angiotensin II as a risk factor for cyclosporin nephrotoxicity in patients with psoriasis.

Abnormalities of the renin-angiotensin system after low-dose cyclosporin (5 mg/kg/day or less) have not been adequately defined in patients with normal kidneys. 27 patients with psoriasis were assessed before starting cyclosporin, after three months of cyclosporin (5 mg/kg/day or less) and then finally three months after finishing cyclosporin. On each occasion plasma renin activity (PRA), aldosterone, angiotensin II and atrial natriuretic peptide (ANP) were measured together with total renal blood flow (RBF), GFR and filtration fraction (FF) following an i.v. bolus injection of Tc-99m DTPA. Significant renal hemodynamic toxicity was defined as > 25% fall in RBF or > 20% fall in GFR. Using these criteria we identified 12 patients with hemodynamic toxicity (Group A) and 15 patients whose GFR and RBF did not fall significantly (Group B). In Group A a significant fall in GFR (p < 0.001) and reduction in renal blood flow (p < 0.04) were associated with significant rises in both ambulant and recumbent angiotensin II (p < 0.0005). PRA, aldosterone and ANP did not significantly alter. GFR partially recovered after withdrawal of cyclosporin although RBF remained significantly lower compared to initial values. In Group B there was no significant change in GFR or RBF although there was a reversible fall in FF (p < 0.02). There were no significant differences in angiotensin II, PRA, aldosterone or ANP. Circulating angiotensin II rises in patients who develop cyclosporin nephrotoxicity and may be responsible for mediating the hemodynamic effects.

Adult↗
PubMed1993

Comparative study of the isolation of human immunodeficiency virus from the lung and peripheral blood of AIDS patients.

HIV-1 proviral DNA was detected by the polymerase chain reaction (PCR) in leucocytes from the peripheral blood (PBL) and bronchoalveolar lavage (BAL) of 100% and 72%, respectively, of HIV-1 seropositive patients. Infective virus isolated by cocultivation was recovered from the PBL and BAL of 50% and 59% of individuals, respectively. Isolation of HIV-1 was more readily made from the lung of individuals undergoing Pneumocystis carinii pneumonia (PCP) than from patients with non-PCP lung infections. The concomitant infection of lung cells with cytomegalovirus did not affect the isolation rate of HIV-1 from the lung. HIV-1 was isolated from BAL of 23 out of 36 (64%) individuals receiving no antiviral chemotherapy and from 13 out of 24 (54%) patients who were receiving AZT.

AIDS-Related Opportunistic Infections↗
PubMed1993

The epidemiology of HIV-1 infection of the lung in AIDS patients.

OBJECTIVE: To examine the relationship between HIV-1 infection of cells obtained by bronchoalveolar lavage (BAL) from the lung and the pathogenesis of AIDS. DESIGN: Prospective study of 121 consecutive HIV-1-seropositive patients undergoing investigation for respiratory symptoms or abnormal chest radiograph. METHODS: Polymerase chain reaction (PCR) for the detection of HIV-1-specific proviral DNA. Cocultivation of leukocytes obtained from BAL with donor cord blood leukocytes (CBL) to isolate HIV-1. RESULTS: HIV-1 was detected by PCR in the lung cells of 78 out of 121 (65%) patients. It was detected in 55% of patients who had been seropositive for less than 1 year, but in over 80% of patients who had been seropositive for more than 3 years. HIV-1 was isolated from 61 out of 106 (58%) individuals. The ability to detect or isolate HIV-1 from the lung correlated directly to CD4 cell count in peripheral blood. HIV-1 was detected significantly more frequently in the BAL cells of smokers compared with non-smokers (P = 0.01). CONCLUSIONS: HIV-1 was frequently detected and isolated from the lung of AIDS patients undergoing a respiratory episode. HIV-1 infection of the lung became more frequent with time from serodiagnosis. Patients who smoked were more likely to succumb to HIV-1 infiltration into the lung and HIV-1 infection of the lung was associated with progression to death.

Adult↗