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Biomedical subjects

F A Post

Publications and source records attributed to F A Post.

13 recordsLinked to original sources
PubMed2006

Outcome of AIDS-associated cryptococcal meningitis initially treated with 200 mg/day or 400 mg/day of fluconazole.

BACKGROUND: AIDS-associated cryptococcal meningitis has a high mortality. Fluconazole was the only systemic antifungal therapy available in our centre. From 1999-2001 we used low-dose fluconazole (200 mg daily initially), and did not offer therapy to patients perceived to have poor prognoses. In 2001 donated fluconazole became available, allowing us to use standard doses (400 mg daily initially). Antiretroviral therapy was not available during the study period. METHODS: Retrospective chart review of adult patients before and after the fluconazole donation. RESULTS: 205 patients fulfilled the inclusion criteria, 77 before and 128 after the donation. Following the donation fewer patients received no antifungal treatment (5% vs 19%, p = 0.002), and more patients received standard-dose fluconazole (90% vs 6%, p < 0.001). In-hospital mortality was 25%. Impaired consciousness, no antifungal treatment received and cerebrospinal fluid antigen titre > 1,000 were independent predictors of in-hospital mortality. Concomitant rifampicin did not affect in-hospital survival. Thirteen patients were referred to the tertiary referral hospital and received initial treatment with amphotericin B for a mean of 6 days - their in-hospital survival was not different from patients who received only fluconazole (p = 0.9). Kaplan-Meier analysis showed no differences in length of survival by initial treatment with standard or low doses of fluconazole (p = 0.27 log rank test); median survival was 76 and 82 days respectively. CONCLUSION: Outcome of AIDS-associated cryptococcal meningitis is similar with low or standard doses of fluconazole. The early mortality is high. Initial therapy with amphotericin B and other measures may be needed to improve outcome.

AIDS-Related Opportunistic Infections↗
PubMed2001

Mycobacterium tuberculosis 19-kilodalton lipoprotein inhibits Mycobacterium smegmatis-induced cytokine production by human macrophages in vitro.

Vaccination of mice with Mycobacterium vaccae or M. smegmatis induces some protection against M. tuberculosis challenge. The 19-kDa lipoprotein of M. tuberculosis, expressed in M. vaccae or M. smegmatis (M. smeg19kDa), abrogates this protective immunity. To investigate the mechanism of this suppression of immunity, human monocyte-derived macrophages (MDM) were infected with M. smeg19kDa. Infection resulted in reduced production of tumor necrosis factor alpha (TNF-alpha) (P < 0.01), interleukin-12 (IL-12) (P < 0.05), IL-6 (P < 0.05), and IL-10 (P < 0.05), compared to infection with M. smegmatis vector (M. smegV). Infection with M. smeg19kDa and with M. smegV had no differential effect on expression of costimulatory molecules on MDM, nor did it affect the proliferation of presensitized T cells cocultured with infected MDM. When MDM were infected with M. smegmatis expressing mutated forms of the 19-kDa lipoprotein, including non-O-glycosylated (M. smeg19NOG), nonsecreted (M. smeg19NS), and nonacylated (M. smeg19NA) variants, the reduced production of TNF-alpha or IL-12 was not observed. When the purified 19-kDa lipoprotein was added directly to cultures of infected monocytes, there was little effect on either induction of cytokine production or its inhibition. Thus, the immunosuppressive effect is dependent on glycosylated and acylated 19-kDa lipoprotein present in the phagosome containing the mycobacterium. These results suggest that the diminished protection against challenge with M. tuberculosis seen in mice vaccinated with M. smegmatis expressing the 19-kDa lipoprotein is the result of reduced TNF-alpha and IL-12 production, possibly leading to reduced induction of T-cell activation.

Antigens, Bacterial↗
PubMed2001

AIDS in Africa--survival according to AIDS-defining illness.

OBJECTIVE: Evaluation of prognostic significance of the type of AIDS-defining illness (ADI) and performance status in a cohort of AIDS patients. DESIGN, SETTING, SUBJECTS, OUTCOME MEASURES: A retrospective analysis of 280 patients with AIDS, as defined by the proposed World Health Organisation (WHO) clinical staging system, who attended two Cape Town-based HIV clinics between 1984 and 1997. Patients were stratified according to the type of initial ADI. Survival associated with each opportunistic event was determined by Kaplan-Meier analysis. Cox proportional hazard analysis was used to determine relative risk for death associated with three strata of ADI. RESULTS: Median survival associated with various initial ADIs varied from less than 3 months (encephalopathy and wasting), to over 2 years (extrapulmonary tuberculosis and herpes simplex virus infection). This effect of ADI on outcome was most striking in patients with relatively preserved CD4 counts (CD4 > 50/microliter). A performance status score 4 predicted 50% mortality at 1 month, irrespective of co-morbidity. CONCLUSION: The type of ADI is an important determinant of survival, particularly in patients with preserved CD4 counts. The stratification of patients by type of ADI and performance status may be useful in the management of patients with advanced HIV infection in resource-limited environments.

AIDS Dementia Complex↗
PubMed1996

CD4 and total lymphocyte counts as predictors of HIV disease progression.

CD4+ T-lymphocyte (CD4) counts are a standard laboratory marker of disease progression in HIV infection, but expense precludes their use in large parts of the world. Total lymphocyte counts (TLC), in contrast, are widely available. We compared CD4 and TLC counts as predictors of developing AIDS or death in 831 HIV-positive out-patients (582 males and 249 females with both homosexual (males, n = 316) and heterosexual (n = 515) transmission patterns. The first CD4 count < 200/microliter and first TLC < 1250/microliter predicted similar (p = 0.52) survival, irrespective of clinical stage. For each clinical stage, a significant difference in progression to AIDS and mortality was predicted by TLC above or below 1250/microliter (p < 0.03). Survival and progression to AIDS occurred at similar rates in patients with a TLC < 1250/microliter or a CD4 count < 200/microliter (p > 0.1), and patients with a TLC > 1250/microliter or a CD4 count > 200/microliter (p > 0.5). A TLC < 1250/microliter preceded the development of Pneumocystis carinii pneumonia or cerebral toxoplasmosis in 76% of patients. In this longitudinal study, TLC and CD4 counts were equal predictors of disease progression. A TLC < 1250/microliter could be considered an indication for commencing cotrimoxazole prophylaxis.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Pulmonary tuberculosis in HIV infection: radiographic appearance is related to CD4+ T-lymphocyte count.

SETTING: An adult HIV outpatient clinic in Cape Town, South Africa. OBJECTIVE: To investigate the relationship between the radiographic appearance of pulmonary tuberculosis (PTB) in HIV infected patients and CD4+ T-lymphocyte count. DESIGN: Pretreatment radiographs of 150 patients with newly diagnosed PTB were reviewed. CD4+ T-lymphocyte count was used as a marker of HIV disease progression. RESULTS: Upper zone infiltrate typical of PTB reactivation was present in 18 patients. This pattern was associated with early HIV infection (mean CD4+ T-cell count 389) and had 78% positive predictive value for identifying patients with > 200 CD4+ T-lymphocytes/microL. Pleural effusion was present in 32 patients and occurred over a wide intermediate range of CD4+ T-cell counts (mean 185). Lower or midzone infiltrates, adenopathy, interstitial pattern or normal radiograph occurred in 136 patients and were associated with advanced HIV disease (mean CD4+ T-cell count 105). These patterns had 84%, 89%, 89% and 100% positive predictive value, respectively, for identifying patients with < 200 CD4+ T-cell/microL. CONCLUSION: Pulmonary tuberculosis in African HIV-positive patients presents with a spectrum of radiographic abnormalities predictive of stage of HIV disease progression. In patients dually infected with HIV and PTB, chest radiographs are a useful adjunct to clinical staging.

Adolescent↗
PubMed1995

Pituitary function after selective adenomectomy for Cushing's disease.

This retrospective analysis was undertaken to determine whether selective adenomectomy for Cushing's disease can achieve acceptable cure rates while causing minimal pituitary dysfunction. Tumour size, histology and pituitary function were evaluated in 34 consecutive patients (26 F: 8 M, mean age 33.6 years) undergoing transphenoidal adenomectomy for Cushing's disease from 1975 to 1992. Follow-up averaged 5.8 years. Cure was defined as resolution of symptoms and signs and normalization of urinary cortisol excretion. Sixty-three per cent of patients achieved cure after selective adenomectomy, repeat adenomectomy cured an additional four patients. Twenty-eight per cent required bilateral adrenalectomy and/or pituitary irradiation. Postoperative pituitary function remained completely intact in 81%. Secondary hypogonadism occurred in 8%, hypothyroidism in 155 and permanent diabetes insipidus in 4%. There was recurrence in 26% after a mean of 4.6 years (range 1-7). It is concluded that selective adenomectomy can achieve acceptable cure rates with a low prevalence of postoperative hypopituitarism, although an increase of recurrence may be the result of conservative surgery.

Adenoma↗
PubMed1994

The spectrum of endocrine dysfunction in active pulmonary tuberculosis.

OBJECTIVE: Substantial variation in the prevalence (0-55%) of hypoadrenalism in tuberculosis (TB) has been reported. The aim of this study was to prospectively evaluate adrenal, thyroid and gonadal function in patients presenting with active pulmonary TB. DESIGN: A prospective study of 50 patients admitted to a single hospital. PATIENTS: Fifty hospitalized adults with newly diagnosed sputum positive pulmonary TB (mean age 38 years, mean body mass index 18 kg/m2, mean albumin 28 g/l) were studied. MEASUREMENTS: Adrenal reserve was assessed by intravenous tetracosactrin administration with measurement of basal and stimulated cortisol concentrations. Basal ACTH, thyroid and gonadal hormones were also measured. RESULTS: The mean basal serum cortisol was 625 nmol/l (range 394-1185). Basal plasma ACTH was undetectable (< 4.4 pmol/l) in 32, normal in 17 (mean 11.45, range 4.4-24.9 pmol/l) and elevated in one (54.2 pmol/l) subjects and did not correlate with cortisol. The mean increment in cortisol following tetracosactrin was 256 nmol/l (range 0-650) and was unrelated to basal cortisol or ACTH. All 50 patients had a stimulated plasma cortisol exceeding 550 nmol/l, indicating intact adrenal reserve. Ninety-two per cent of patients had the sick euthyroid syndrome, 72% of males had hypogonadotrophic hypogonadism and 4% of patients tested positive for the human immunodeficiency virus. CONCLUSIONS: Hypoadrenalism is uncommon in active pulmonary TB despite frequent dysfunction of the thyroid and gonadal axes.

Adolescent↗
PubMed1989

Blood lymphocytes from ankylosing spondylitis patients fail to induce disease-specific cytotoxic T lymphocytes.

The intriguing observation made by Geczy et al. (1) showing the possibility of generating specific ankylosing spondylitis--cytotoxic T lymphocytes by presenting HLA-B27+AS+ cells as antigen-specific stimulator cells prompted us (by using Geczy's approach) to identify cytotoxic T lymphocytes specific for this apparent B27+AS+ target structure. Peripheral blood mononuclear cells (PBMC) of 21 healthy B27+ individuals were stimulated in primary and in short-term cultures with PBMC of an HLA-identical sibling suffering from definite AS (n = 12). In addition, PBMC in vitro modified by "Geczy bacterial products" from two healthy B27+ individuals were used to stimulate B27+ AS- lymphocytes (either autologous or from a healthy HLA-identical sibling). Effector cells raised in primary AS- versus AS+ and AS- versus "modified B27" mixed lymphocyte culture combinations showed no proliferative nor cytotoxic activity at all. The scarcely observed cytotoxic reactivity of restimulated mixed lymphocyte culture was not restricted to AS+B27+ cells. These results demonstrate that PBMC from ankylosing spondylitis patients fail to induce disease-specific cytotoxic T lymphocytes and suggest that an ankylosing spondylitis--related "modified B27" structure does not exist, at least in the patient material tested.

Cells, Cultured↗