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Biomedical subjects

R Coker

Publications and source records attributed to R Coker.

At least 55 records · Page 3Linked to original sources

HIV positive patients first presenting with an AIDS defining illness: characteristics and survival.

OBJECTIVES: To study the presentation and survival of patients who present with their first diagnosis of being HIV positive at the same time as their AIDS defining illness. DESIGN: Retrospective study of patients presenting with AIDS between 1991 and 1993. SETTING: Department of genitourinary medicine, St Mary's Hospital, London. MAIN OUTCOME MEASURES: AIDS defining illness at presentation and survival after diagnosis of AIDS. RESULTS: Between January 1991 and December 1993, 97 out of 436 patients (22%) presented with their first AIDS defining illness coincident with their first positive result of an HIV test (group B). The remaining 339 patients (78%) had tested positive for HIV-1 infection within the previous eight years and had consequently been followed up in clinics before developing their first AIDS defining illness (group A). The two groups of patients did not differ in age and sex distribution, risk factors for HIV-1 infection, nationality, country of origin, or haematological variables determined at the time of the AIDS defining illness. However, the defining illnesses differed between the two groups. Illnesses associated with severe immunodeficiency (the wasting syndrome, cryptosporidiosis, and cytomegalovirus infection) were seen almost exclusively in group A whereas extrapulmonary tuberculosis and Pneumocystis carinii pneumonia were more common in group B. The survival of patients in group B after the onset of AIDS was significantly longer than that of patients in group A as determined by Kaplan-Meier log rank analysis (P = 0.0026). CONCLUSIONS: Subjects who are HIV positive and present late are a challenge to the control of the spread of HIV infection because they progress from asymptomatic HIV infection to AIDS without receiving health care. The finding that presentation with an AIDS defining illness coincident with a positive result in an HIV test did not have a detrimental effect on survival gives insights into the effects of medical intervention on disease progression after a diagnosis of AIDS.

AIDS Serodiagnosis↗

Marked variation in pyrimethamine disposition in AIDS patients treated for cerebral toxoplasmosis.

We have characterized the disposition of pyrimethamine in 20 adults with advanced AIDS. After the first dose, the area under concentration versus time curves (corrected for dose-size) varied 13-fold. This marked variation in drug levels was also noted during accumulation towards steady-state: pyrimethamine levels were consistently below the suggested lower end of the therapeutic range (750 mg/L) in three severely ill patients with perturbed consciousness (two of whom received the drug by nasogastric tube). Possible mechanisms for these observations are discussed. Pyrimethamine levels may be an important determinant of the rate of response to treatment by AIDS patients with toxoplasmosis: therapeutic drug monitoring may have a role.

Acquired Immunodeficiency Syndrome↗

Characterization of murine pregnancy decidua transforming growth factor beta. I. Transforming growth factor beta 2-like molecules of unusual molecular size released in bioactive form.

A novel type of bioactive transforming growth factor beta 2 (TGF beta 2)-related immunosuppressive activity, lower in molecular mass (20-23 kDa) than a conventional TGF beta 2 standard (25 kDa), has been shown to be released by non-T non-B suppressor cells of murine decidua into fetal bovine serum (FBS)-containing tissue culture medium during a 48-h incubation at 37 degrees C. Substitution of a serum-free medium has allowed direct PAGE-Western blotting and the demonstration in supernatant (prior to incubation at 37 degrees C) of a TGF beta 2-immunoreactive doublet at a higher molecular mass (26 and 27 kDa) than the standard but with apparent immunosuppressive activity. When decidua were incubated in serum-free medium at 37 degrees C, immunosuppressive activity in the supernatant increased to peak at 18 h in association with the appearance of the previously described lower molecular mass species of molecule. The doublet did not appear to be the result of glycosylation of a conventional 25-kDa TGF beta 2 and could be converted into the lower molecular mass form by incubation for 18 h at 37 degrees C, with pH 4.5 but not with pH 7.5 buffer; this incubation in the absence of decidual cells was not accompanied by increased immunosuppressive activity. This transformation could be blocked by a brief heating of the supernatant to 80 degrees C for 10 min to destroy enzymes present in supernatant prior to mixing with the acidic buffer, but biologic activity neutralizable by anti-TGF beta 2 was retained.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Case report: disseminated Pneumocystis carinii infection in a patient with the acquired immune deficiency syndrome causing thyroid gland calcification and hypothyroidism.

We present the case of a homosexual male patient with the acquired immune deficiency syndrome (AIDS) who developed disseminated infection with Pneumocystis carinii. He presented with symptoms and signs of thyroid disease, and developed thyroid gland calcification. This was later histologically proven to be due to P. carinii infection. Disseminated P. carinii infection is rare, and this case represents the first report to our knowledge of thyroid gland involvement causing both hypothyroidism and calcification.

Acquired Immunodeficiency Syndrome↗

Prevalence of hepatitis C in tropical communities: the importance of confirmatory assays.

The prevalence of antibody to hepatitis C virus (HCV) was estimated in 3 tropical populations using 2 screening ELISAs to detect antibody to the c100-3 antigen and 2 supplementary assays designed to test the specificity of these tests. Two hundred and eighty-six of 385 (74.2%) sera from Kiribati, 17 of 138 (12.3%) sera from Vanuatu, and 39 of 173 (22.5%) sera from Zaire were reactive in the initial screening assay. The proportion of reactive sera which were also reactive in the second screening ELISA varied between populations (55.1% in Kiribati, 85.1% in Vanuatu, and 39.2% from Zaire). Reactive sera were selected at random for confirmatory testing. Only 3 of 49 (6.12%) of sera from Kiribati and 1 of 14 (4.76%) of sera from Vanuatu positive in the initial ELISA were reactive in the confirmatory assays. The proportion of confirmed positive sera from Zaire was higher 8 of 28 (28.5%). Based on the results of these supplementary assays the estimated prevalence of anti-HCV in these populations is 4.8% in Kiribati, less than 1% in Vanuatu, and 6.4% in Zaire. Reliance on a single screening ELISA to estimate the prevalence of anti-HCV in stored sera from tropical communities may lead to a gross over-estimate of the true prevalence in these populations.

Antibody Specificity↗

Cytomegalovirus infection in AIDS. Patterns of disease, response to therapy and trends in survival.

Among 347 AIDS patients seen at St Mary's Hospital, London between 1983 and 1989, cytomegalovirus (CMV) disease was observed in 75 (22%). Of these, 58 (77%) had CMV retinitis, 26 (35%) CMV colitis, and 12 (16%) had CMV infection diagnosed at other sites. Relapse occurred in 71%. A favourable response to the use of ganciclovir as induction therapy for CMV retinitis was observed in 92%. Relapse of CMV retinitis occurred in 54% at a median time of 97 days. Neutropenia was the most frequent and serious side-effect of ganciclovir, 76% patients having neutrophil counts less than 1.0 x 10(9)/l and 48% less than 0.5 x 10(9)/l at some stage of therapy. Thrombocytopenia was also common, and platelet counts of less than 50 x 10(9)/l occurred in 43% patients on ganciclovir. The concurrent use of zidovudine made the development of severe neutropenia and thrombocytopenia more likely. Median survival following the diagnosis of CMV disease increased from 5-8 months between 1984 and 1987, to over 12 months in 1988. Patients with CMV colitis had a worse prognosis than patients with CMV retinitis, with median survival of 4.5 and 7 months respectively. In conclusion, CMV is an important opportunist infection in AIDS and both the disease and its treatment cause considerable morbidity. Hence, it is important to develop more effective and less toxic forms of therapy for CMV infection.

Acquired Immunodeficiency Syndrome↗

Changing patterns of Kaposi's sarcoma in N.E. Zaire.

A minor change in the pattern of Kaposi's sarcoma has been noticed in north-east Zaire. This is characterized by a small increase of the number of confirmed diagnoses, together with the appearance of the disease amongst women, who tend to be of a younger age group. These data suggests the appearance of a new aetiological factor in the area. From recent reports from other parts of Africa we speculate that this might be the appearance of HTLV-III virus.

Acquired Immunodeficiency Syndrome↗

Does the sympathetic nervous system influence sinus arrhythmia in man? Evidence from combined autonomic blockade.

The influences of vagal and sympathetic efferent activity on sinus arrhythmia in man have been studied in healthy subjects by administration of hyoscine butylbromide and atenolol alone and combined using a microcomputer-linked electrocardiogram (e.c.g.) system. Sinus arrhythmia was quantitated as the S.D. of the R-R interval. Sinus arrhythmia was reduced by hyoscine butylbromide, in some subjects to near abolition, but this end-point was unchanged by pre-treatment with atenolol. Atenolol alone prolonged the mean R-R interval and increased sinus arrhythmia. It is suggested that sinus arrhythmia in man is mediated through vagal efferents alone but that atenolol increases the arrhythmia through a central vagotonic effect.

Adult↗

Untangling Gordian knots: improving tuberculosis control through the development of 'programme theories'.

We argue that if the lessons from tuberculosis control programmes are to be drawn effectively then a more nuanced understanding is needed that takes account of the complex health system environment within which they sit. We suggest that a conceptual framework that draws upon the World Health Organization's DOTS strategy can be harnessed to assist the systematic analysis of programmes in a way that links this vertical, disease specific strategy to horizontal health system factors so that comparisons can be made. This multi-disciplinary, multi-method approach to the evaluation builds upon the work of others including Pawson and Tilley and their 'programmes theories'. This work has informed the application of an evaluation toolkit which has been successfully applied in a number of settings and assisted in the sustainable implementation of a DOTS strategy in Russia.

Directly Observed Therapy↗

Screening for cervical abnormalities in women with anogenital warts in an STD clinic: an inappropriate use of colposcopy.

An audit of the use of colposcopy in women with anogenital warts was performed. Fifty women attending a clinic for sexually transmitted diseases in a District General Hospital with anogenital warts were examined by cervical cytology and colposcopy for cervical infection by human papillomavirus (HPV) or epithelial abnormality indicating cervical intraepithelial neoplasia (CIN) or both. Collated results showed a high prevalence of both conditions in these 50 women; 20 (40%) had evidence of cervical infection by HPV and 11 (22%) epithelial abnormalities consistent with CIN 1 or 2. However, neither CIN 3 nor invasive disease was detected. Colposcopy in this setting was shown to be a specific but insensitive tool and its role in the routine management of women with anogenital warts at our institution is not warranted.

Adolescent↗