Biomedical subjects
R Fox
Publications and source records attributed to R Fox.
Predictors of the risk of development of acquired immunodeficiency syndrome within 24 months among gay men seropositive for human immunodeficiency virus type 1: a report from the Multicenter AIDS Cohort Study.
The natural history of infection with human immunodeficiency virus type 1 (HIV-1) is characterized by a relentless decline in CD4-positive lymphocytes and the ultimate development of acquired immunodeficiency syndrome (AIDS). However, variables other than the CD4-positive lymphocyte level contribute to the measurement of risk for AIDS and can be used as predictors of AIDS onset. This study was undertaken to identify factors that, independently of the CD4-positive lymphocyte level, would predict the risk of AIDS over 24 months in a cohort of HIV-1 seropositive homosexual men receiving no antiretroviral therapy. Demographic, clinical, and laboratory data from 1,325 white, HIV-1 seropositive participants in the Multicenter AIDS Cohort Study who have been studied for 4 years were analyzed with univariate and multivariate methods. To control for stage of infection, the baseline percentage of CD4-positive lymphocytes (a known marker of disease progression), and the decline of CD4-positive cells during the first 6 months of observation were used as continuous variables. The variables that were independently associated with an increased risk of developing AIDS were: low baseline CD4 percentage, decline in the CD4 percentage during the first 6 months of follow-up, the presence of serum immunoglobulin A at baseline, decrease in hemoglobin during the first 6 months of follow-up, incident fatigue, and the interaction of decline in the CD4 percentage and incident thrush. While low CD4 percentage and other variables have been previously described as prognostic markers, decline in the CD4 percentage and the interaction of that decline and incident thrush have not previously been described as being of prognostic importance. These variables and the analytic method for estimating prognosis may prove useful for selecting and evaluating antiretroviral therapy, instituting prophylactic measures against certain opportunistic infections, and recruitment into clinical trials. Because study participants received no antiretroviral prophylaxis during the period under analysis, the method could be used to estimate the prognosis for those receiving investigational treatment were they to remain untreated, effectively making any participant in a clinical trial his own untreated control.
Effect of HIV posttest counseling on STD incidence.
OBJECTIVE: To evaluate the effectiveness of human immunodeficiency virus (HIV) testing and posttest counseling in reducing subsequent high-risk behavior. METHODS: The incidence of sexually transmitted diseases (STDs) in the Baltimore, Md, public STD clinic population after HIV testing and counseling was determined by chart review and was compared in two groups, 868 HIV-seropositive patients and 1104 HIV-seronegative patients, matched by age, sex, and month in which HIV test was conducted. Patients were observed for incident STDs at intervals of 6 through 23 months. Patients with incident STDs were classified hierarchically after being notified of the HIV test result and receiving posttest counseling. RESULTS: Of HIV-seropositive patients, 615 (71%) returned for their test results and received posttest counseling; 694 HIV-seronegative patients (63%) returned. Of all those who returned for results and posttest counseling, 60 (9.7%) of 615 HIV-seropositive patients and 61 (8.8%) of 694 HIV-seronegative patients were diagnosed at least once with definite STD (syphilis, gonorrhea, or trichomoniasis) (P, not significant). Twenty-four HIV-seropositive patients (3.9%) and 71 HIV-seronegative patients (10.2%) returned with probable STD (nongonococcal urethritis or pelvic inflammatory disease) (P less than .001). Nine HIV-seropositive patients (1.5%) and 23 HIV-seronegative patients (3.3%) returned having had an STD-infected sexual partner (P less than .03). Age, sexual orientation, and drug use behavior did not predict return with STD. CONCLUSIONS: Both HIV-seropositive and HIV-seronegative patients showed high rates of repeat STDs after posttest counseling, an important public health challenge in creating effective high-risk behavior prevention strategies.
Basic fibroblast growth factor in cells derived from Dupuytren's contracture: synthesis, presence, and implications for treatment of the disease.
Dupuytren's contracture (DC) is associated with fibroblast and endothelial cell proliferation. We have identified a fibroblast and endothelial cell mitogen, basic fibroblast growth factor (FGF), in cells derived from this tissue and characterized the effects of this growth factor on DC cells. Northern blot analysis of DC cells reveals the presence of basic FGF mRNA species, and the DC cells coexpress multiple forms of basic FGF. Radioreceptor assays establish that the DC cells have high-affinity binding sites for basic FGF and proliferate in response to exogenous recombinant basic FGF. Furthermore, a conjugate between saporin (a ribosome-inactivating protein) and basic FGF, which is cytotoxic to cells possessing the basic FGF receptor, is also cytotoxic to DC cells. The possibility that basic FGF-saporin could be a potential therapeutic agent for prevention of recurrence of the disease after surgery is discussed.
Absorption of human calcitonin across the rat colon in vivo.
1. We studied the absorption of human calcitonin across the colon of juvenile female rats in vivo. Both pharmacokinetic and pharmacodynamic parameters were monitored to measure absorption. 2. Intracolonically administered human calcitonin at doses of 0.1-5.0 mg/kg resulted in a dose-dependent reduction in plasma calcium levels. 3. The bioavailability of intracolonically administered human calcitonin at doses of 5.0, 1.0 and 0.1 mg/kg was 0.5%, 0.9% and 0.2%, respectively. 4. Immunohistochemistry showed that human calcitonin transport across the rat colon was rapid and that a significant amount was via a transcellular pathway. 5. We conclude that human calcitonin crosses the gastrointestinal tract of rats in significant amounts and that this demonstrates the feasibility of an oral form for clinical use.
Colonic absorption of human calcitonin in man.
1. Human calcitonin was administered into the distal colon and by intravenous infusion in eight healthy subjects in an open, fixed sequence, cross-over bioavailability study. 2. Intravenously infused human calcitonin elicited a standard pharmacokinetic profile in eight healthy subjects with a biphasic elimination with half-lives of 10.2 +/- 0.7 min and 37.8 +/- 2.5 min. 3. Colonoscopically administered human calcitonin was absorbed across the distal colonic mucosa in low amounts with a bioavailability of 0.00-0.22%. 4. Absorption from the distal colon was impeded by the presence of faecal material in three of the eight subjects. 5. We conclude that human calcitonin crosses the gastrointestinal epithelium of man. This may demonstrate the feasibility of an oral form for clinical use.
Antibiotic susceptibility of Enterobacteriaceae isolated from patients in northern Tanzania.
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Subclavian vein thrombosis: a late complication of ovarian hyperstimulation syndrome.
Two cases of subclavian vein thrombosis following ovarian stimulation for in-vitro fertilization and subsequent ovarian hyperstimulation syndrome (OHSS) are described. Both occurred several weeks after complete resolution of the OHSS. The site of the lesions and their timing suggest that there is a generalized disturbance of coagulation associated with OHSS, which persists beyond the duration of the clinical syndrome.
New approaches to the management of poor prognosis non-seminomatous germ cell tumours.
While most patients with disseminated non-seminomatous germ cell tumours (NSGCT) are cured by treatment with cisplatinum-based chemotherapy, a subset die from refractory or relapsing disease. Poor prognostic factors at diagnosis include bulky disease, visceral involvement, high serum marker levels and an inadequate rate of fall in these markers in response to treatment. There are a number of approaches to poorer risk patients. One is to use conventional induction chemotherapy followed by second-line salvage regimens in those who fail induction. Results with this approach have been disappointing. A second approach is to use more intensive induction regimens, in some cases with growth factor support; whether these are superior to standard treatment has yet to be established by randomised studies. A third approach, based on the chemotherapy-dose responsiveness of NSGCT, consists of the administration of very high dose chemotherapy followed by haematological rescue with autologous marrow to patients failing initial therapy. Review of autograft studies suggest that durable remissions can be obtained in most patients with responsive disease, but not if the disease is chemotherapy-refractory. A new approach may be elective early autografting in patients identified at diagnosis to have very poor prognosis disease.
Which hormone tests for the diagnosis of polycystic ovary syndrome.
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Homosexual and bisexual men's perceptions of discrimination in health services.
Questionnaires were distributed to homosexual and bisexual male participants in the Multicenter AIDS Cohort Study and to homosexual and bisexual male patients with acquired immunodeficiency syndrome (AIDS) to determine whether the men believed they had been refused medical or dental treatment because of their sexual orientation or a condition related to the human immunodeficiency virus (HIV). Men with AIDS were significantly more likely (18%) to report being refused treatment by a doctor or dentist on the basis of a known or suspected HIV-related condition than were men who were seropositive (5%) or seronegative (1%). Significantly more respondents reported refusal of dental care than of medical care.
Spurious elevation of follicle-stimulating hormone.
Serum concentrations of follicle-stimulating hormone (FSH) were measured in a 33-year-old eumenorrhoeic woman with primary infertility. Postmenopausal levels were obtained. Using an alternative assay, the patient was found to have normal levels of FSH. The probable cause of the misleading result is discussed.
Basic fibroblast growth factor in Dupuytren's contracture.
Lesions excised from nine patients undergoing surgery for Dupuytren's contracture (DC) and three normal fascia were examined for the presence of the angiogenic protein basic fibroblast growth factor (basic FGF). Endothelial cell proliferation assays established basic FGF-like activity in extracts of DC. Western blotting confirmed the presence of an 18,000-dalton protein which was localized in the lesions by immunohistochemical staining. All of the cells implicated in the progression of the disease (endothelial cells, fibroblasts, and myofibroblasts) contain the growth factor. Endothelial cells within the narrowed or occluded vessels, as well as fibroblasts surrounding these vessels, stained intensely positive. In situ hybridization using an antisense probe for human basic FGF and its receptor's (FGFR-1) mRNA established the major difference between normal and DC tissues: their levels are significantly higher than in the normal tissues. Thus the cells in DC also express both basic FGF and FGFR-1, suggesting a potential autocrine/paracrine role for basic FGF in the pathogenesis of DC. This finding is thus the first description of a nontumoral proliferative disease that can be directly associated with increased basic FGF mRNA. The possibility that therapies can be developed on the basis that basic FGF and its receptor are expressed in DC is discussed.
Longitudinal study of homosexual couples discordant for HIV-1 antibodies in the Baltimore MACS Study.
Thirty-six sexually active couples serologically discordant for human immunodeficiency virus, type 1 (HIV-1), within the Baltimore Multicenter AIDS Cohort Study (MACS) were assessed to determine whether evidence of HIV-1 infection could be detected in the HIV-1-antibody-negative partners and whether factors associated with lack of transmission of HIV from the seropositive to the seronegative partner could be ascertained. Six HIV-1 seropositive couples and 18 seronegative couples were followed concurrently for comparison. None of the seropositive subjects had an AIDS-defining illness at entry into the study, and all subjects were followed for 1 year. A separate evaluation of unprotected anal receptive and insertive intercourse between discordant couples indicated high-risk activities for a median of 40 months, as reported by the HIV seropositive partner. Despite this finding, none of the HIV-1 seronegative men in discordant couples had evidence of HIV-1 infection by viral culture, p24 antigen testing, or polymerase chain reaction for HIV-1 DNA. Discordant seronegatives and seropositives did not differ from concordant seronegatives and seropositives in numbers of circulating CD4, CD8, and natural killer lymphocytes or in prevalence of antibodies to herpes simplex virus, type 1, Epstein-Barr virus, or cytomegalovirus, except that discordant seronegative men were less likely than their seropositive partners to have antibodies to herpes simplex virus, type 2. The reason for the apparent lack of HIV-1 infection in seronegative discordant individuals remains unexplained and did not appear to be associated with type of sexual activity, T-lymphocyte subsets or natural killer cells, or early stage of HIV-1 disease.
Interpartner reliability of reporting of recent sexual behaviors.
Epidemiologic studies exploring risks for sexually transmitted diseases, including human immunodeficiency virus infection, typically rely on self-report of sexual behaviors. Estimates of the incidence and prevalence of sexual practices are important measures for assessment of behavioral interventions as well as for examining disease transmission. This study examined the degree of agreement within heterosexual couples reporting frequency and type of sexual behaviors, including condom use. Self-reports were obtained from 71 couples attending Baltimore sexually transmitted disease clinics in 1989-1990 regarding the number of days and number of episodes of three specific sexual practices (any type of sexual activity, vaginal sex, and vaginal sex with condom use) over a 30-day period. Paired t test analysis revealed both sexes to be very consistent in their reporting of recent sexual experiences. Multivariate analysis showed that agreement did not vary by socioeconomic status, by whether the partners were married to each other, or by age. These findings suggest that reliable information regarding sexual behaviors may be obtained from men or women.
Haematometra caused by hormone replacement therapy after endometrial resection.
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New TaqI polymorphism in the RRM1 gene.
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Daughters of stilboestrol.
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