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Biomedical subjects

S Allen

Publications and source records attributed to S Allen.

At least 19 recordsLinked to original sources

Confidential HIV testing and condom promotion in Africa. Impact on HIV and gonorrhea rates.

OBJECTIVE: We evaluated the impact of human immunodeficiency virus (HIV) testing and counseling on self-reported condom and spermicide use and on corresponding HIV seroconversion and gonorrhea rates in urban Rwandan women. DESIGN: Prospective cohort study with 2 years of follow-up, comparison of outcome variables before and after an intervention, and condom use measured in a control group that did not receive the intervention. SETTING: Outpatient research clinic in Kigali, the capital of Rwanda. PARTICIPANTS: One thousand four hundred fifty-eight childbearing women, 32% of whom were infected with HIV, were enrolled in a prospective study in 1988, and followed at 3- to 6-month intervals for 2 years. Follow-up was available for 95% of subjects at year 1 and 92% at year 2. INTERVENTIONS: An acquired immunodeficiency syndrome (AIDS) educational videotape, HIV testing and counseling, and free condoms and spermicide were provided to all participants and interested sexual partners. MAIN OUTCOME MEASURES: Self-report of compliance with condom-spermicide use and observed incidence of HIV and gonorrhea. RESULTS: Only 7% of women reported ever trying condoms before the intervention, but 22% reported condom use with good compliance 1 year later. Women who were HIV-positive were more likely to adopt condom use than HIV-negative women (36% vs 16%; P < .05). Independent predictors of condom use, both in HIV-positive and in HIV-negative women, included HIV testing and counseling of the male partner, having a nonmonogamous relationship, and believing condoms were not dangerous. Human immunodeficiency virus seroconversion rates decreased significantly (from 4.1 to 1.8 per 100 person-years; P < .04) in women whose partners were tested and counseled. The prevalence of gonorrhea decreased substantially (13% to 6%; P < .05) among HIV-positive women, with the greatest reduction among condom users (16% to 4%; P < .05). CONCLUSION: A confidential HIV testing and counseling program was associated with increased use of condoms and reduced rates of gonorrhea and HIV in urban Rwandan women. The lack of risk reduction in HIV-negative women whose partner's serostatus was unknown was of concern. Interventions that promote HIV testing and counseling for both members of a couple should be considered in other high-prevalence areas.

AIDS Serodiagnosis

Neuronal and glial plasma membrane carrier-mediated uptake of L-homocysteate is not selectively blocked by beta-p-chlorophenylglutamate.

The proposed action of beta-p-chlorophenylglutamate (chlorpheg) as a selective blocker of L-homocysteate uptake was studied in primary cultures of mouse brain neurons and astrocytes and in rat brain synaptosomes. The preparations were incubated with 1 microM to 10 mM L-homocysteate and D-aspartate in the absence and presence of 7.5 mM chlorpheg. In each preparation uptake of the two amino acids comprised a saturable uptake and a non-saturable (passive diffusion) component. L-Homocysteate was of at least 100-fold lower affinity than D-aspartate as a substrate for the amino acid transporter. Chlorpheg was shown to be essentially equieffective as a weak competitive inhibitor of only the saturable uptake of L-homocysteate and D-aspartate. It is concluded that chlorpheg is not a selective blocker of L-homocysteate uptake.

Amino Acid Transport Systems

Follicular cystic ovaries and cystic endometrial hyperplasia in a bitch.

Treatment of cystic ovaries in a bitch was unsuccessful with human chorionic gonadotropin, but aspiration of the follicles at laparotomy was successful. Follicular aspiration is described, with special emphasis on preventing bursal adhesions. Aspiration of persistent follicles is a simple treatment for cystic ovarian disease that is nonresponsive to parenterally administered hormones. The persistent estrus associated with cystic follicles is a primary cause of cystic endometrial hyperplasia (CEH) and severe cases of CEH are associated with infertility. Rapid intervention (surgical or hormonal) will limit the severity of CEH and, therefore, decrease infertility in breeding bitches.

Animals

Effect of serotesting with counselling on condom use and seroconversion among HIV discordant couples in Africa.

OBJECTIVE: To determine whether HIV testing and counselling increased condom use and decreased heterosexual transmission of HIV in discordant couples. DESIGN: Prospective study. SETTING: Kigali, the capital of Rwanda. SUBJECTS: Cohabiting couples with discordant HIV serology results. MAIN OUTCOME MEASURES: Condom use in the couple and HIV seroconversion in the negative partners. RESULTS: 60 HIV discordant couples were identified, of whom 53 were followed for an average of 2.2 years. The proportion of discordant couples using condoms increased from 4% to 57% after one year of follow up. During follow up two of the 23 HIV negative men and six of the 30 HIV negative women seroconverted (seroconversion rates of 4 and 9 per 100 person years). The rate among women was less than half that estimated for similar women in discordant couples whose partners had not been serotested. Condom use was less common among those who seroconverted (100% v 5%, p = 0.01 in men; 67% v 25%, p = 0.14 in women). CONCLUSIONS: Roughly one in seven cohabiting couples in Kigali have discordant HIV serological results. Confidential HIV serotesting with counselling caused a large increase in condom use and was associated with a lower rate of new HIV infections. HIV testing is a promising intervention for preventing the spread of HIV in African cities.

AIDS Serodiagnosis

Predictors of mortality among HIV-infected women in Kigali, Rwanda.

OBJECTIVE: To better characterize the natural history of disease due to human immunodeficiency virus (HIV) infection in African women. DESIGN: Prospective cohort study over a 2-year follow-up period. PARTICIPANTS: A total of 460 HIV-seropositive women and a comparison cohort of HIV-seronegative women recruited from prenatal and pediatric clinics in Kigali, Rwanda in 1988. MEASUREMENTS: Clinical signs and symptoms of HIV disease, AIDS, and mortality. MAIN RESULTS: Follow-up data at 2 years were available for 93% of women who were still alive. At enrollment, many seropositive women reported symptoms listed in the World Health Organization (WHO) clinical case definition of AIDS, but these were nonspecific and often improved over time. The 2-year mortality among HIV-infected women by Kaplan-Meier survival analysis was 7% (95% CI, 5% to 10%) overall, and 21% (CI, 8% to 34%) for the 40 women who fulfilled the WHO case definition of AIDS at entry. In comparison, the 2-year mortality in women not infected with HIV was only 0.3% (CI, 0% to 7%). Independent baseline predictors of mortality in seropositive women by Cox proportional hazards modeling were, in order of descending risk factor prevalence: a body mass index of 21 kg/m2 or less (relative hazard, 2.3; CI, 1.1 to 4.8), low income (relative hazard, 2.3; CI, 1.1 to 4.5), an erythrocyte sedimentation rate exceeding 60 mm/h (relative hazard, 4.9; CI, 2.2 to 10.9), chronic diarrhea (relative hazard, 2.6; CI, 1.1 to 5.7), a history of herpes zoster (relative hazard 5.3; CI, 2.5 to 11.4), and oral candida (relative hazard, 7.3; CI, 1.6 to 33.3). Human immunodeficiency virus disease was the cause of death in 38 of the 39 HIV-positive women who died, but only 25 met the WHO definition of AIDS before death. CONCLUSIONS: Human immunodeficiency virus disease now accounts for 90% of all deaths among child-bearing urban Rwandan women. Many symptomatic seropositive patients may show some clinical improvement and should not be denied routine medical care. Easily diagnosed signs and symptoms and inexpensive laboratory tests can be used in Africa to identify those patients with a particularly good or bad prognosis.

Acquired Immunodeficiency Syndrome

Unfolding and refolding of hen egg-white riboflavin binding protein.

The unfolding and refolding of riboflavin-binding protein (RfBP) from hen egg-white induced by addition of guanidinium chloride (GdnHCl), and its subsequent removal by dialysis have been studied by c.d. and fluorescence for both the native and reduced protein. The reduction of its nine disulphide bonds causes a reduction in the secondary structure (alpha-helix plus beta-sheet) from 63% to 33% of the amino acid residues. Unfolding of the native protein occurred in two phases; the first involving a substantial loss of tertiary structure, followed by a second phase involving loss of secondary structure at higher GdnHCl concentrations. By contrast this biphasic behaviour was not discernible in the reduced protein. The loss of ability to bind riboflavin occurred after the first phase of unfolding. Comparison of unfolding of the holoprotein and apoprotein suggested that riboflavin has only a small stabilizing effect on the unfolding process. After removal of GdnHCl, the holoprotein, apoprotein and reduced protein assumed their original conformation. The significance of the results in relation to various models for protein folding is discussed.

Animals

Effectiveness of recombinant human erythropoietin therapy in myelodysplastic syndromes.

In an attempt to determine predictors of response to recombinant human erythropoietin (r-HuEPO) therapy in 20 patients with various subtypes of myelodysplastic syndrome (MDS), plasma concentrations of transferrin receptor protein were measured before and after 4 doses of r-HuEPO. An r-HuEPO dosage of 150 U/kg was administered subcutaneously 3 times weekly and increased to 300 U/kg in patients who failed to raise plasma concentrations of transferrin receptor protein by at least one third. Ten (50%) patients had an effective clinical response to therapy by reducing (greater than 50%) or eliminating transfusion requirements, or by showing an improvement in haematocrit of greater than or equal to 6 percentage points. Changes in plasma transferrin receptor protein concentrations failed to predict which patients would eventually respond to r-HuEPO therapy. A subset of MDS patients demonstrated a delayed response to therapy in order to achieve a satisfactory clinical outcome. Precise predictors of response, either laboratory or clinical, remain to be determined. Continued research is warranted in this group of patients in order to specifically target r-HuEPO therapy. It is, however, likely that r-HuEPO therapy will have an effective and important role in this subset of MDS patients.

Anemia

Pulmonary tuberculosis in Kigali, Rwanda. Impact of human immunodeficiency virus infection on clinical and radiographic presentation.

The aim of the present study was to compare the clinical and radiographic presentation as well as the therapeutic outcome of pulmonary tuberculosis (PT) in adult patients with and without human immunodeficiency virus type 1 (HIV-1) infection in Kigali, Rwanda. Over a 17-month period 59 consecutive patients with bacteriologically and/or histopathologically documented PT were enrolled. Of these, 48 (81%) patients were HIV seropositive. Among these, 35 fit the WHO clinical criteria for AIDS (WHOCCA) at the time of admission. Significant differences were found between the HIV-seropositive and HIV-seronegative groups of patients: fever (85 versus 36%; p less than 0.001), tuberculin skin test anergy (69 versus 0%; p less than 0.01), mediastinal and/or hilar adenopathies (31 versus 0%; p = 0.05), and pleural effusion (43 versus 9%; p less than 0.05) were more frequently encountered in the HIV-seropositive group, and upper lobe infiltrates (55 versus 16%; p less than 0.02) and cavitation (91 versus 39%; p less than 0.003) were more often seen in the HIV-seronegative group. However, HIV-seropositive patients not meeting WHOCCA were less frequently anergic (0 versus 100%; p less than 0.001) and feverish (53 versus 97%; p less than 0.01) and more often had cavitation (69 versus 28%; p less than 0.02) and less often mediastinal and/or hilar adenopathies (7 versus 40%; p less than 0.04) compared with HIV-seropositive patients meeting WHOCCA. Under antituberculosis treatment, clearance of fever was slower in HIV-seropositive compared with HIV-seronegative patients, and among the HIV-seropositive group it was slower in those fitting WHOCCA.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome

Two-year incidence of tuberculosis in cohorts of HIV-infected and uninfected urban Rwandan women.

To determine the prevalence of Mycobacterium tuberculosis infection and the incidence of tuberculosis in HIV-infected and uninfected urban Rwandan women, 460 HIV-positive and 998 HIV-negative childbearing women were recruited from pediatric and prenatal care clinics and were enrolled in a prospective study in 1988 and followed for 2 yr. Tuberculin testing was administered 12 to 18 months after enrollment. Fifty-three percent of HIV-negative women had positive tuberculin tests (induration > or = 10 mm), with higher rates among older women and among women who had received BCG vaccine. Only 21% of HIV-positive women had positive tuberculin tests, with no relationship to BCG vaccine. Follow-up was available for 93% of subjects. Tuberculosis was diagnosed in 20 HIV-positive women and in two HIV-negative women. Features associated with an increased risk of tuberculosis among HIV-positive women included: age > or = 30, body mass index in the lowest quartile, low income, erythrocyte sedimentation rate > 75, positive tuberculin test, and chronic cough, chronic fever, and weight loss. Among Rwandan women who are infected with HIV, approximately half of those who are infected with M. tuberculosis do not have positive tuberculin tests. The rate ratio for development of tuberculosis among HIV-positive women was 22 (95% CI, 5 to 92). New algorithms are needed to improve the early detection of tuberculosis among HIV-positive patients in Africa.

AIDS Serodiagnosis

Smoking cessation in women concerned about weight.

BACKGROUND: Weight gain after smoking cessation is often cited by women smokers as a primary reason for not attempting to quit smoking or for relapsing after a cessation attempt. METHODS: A randomized trial of 417 women smokers was conducted to test the addition of two weight control strategies to a smoking cessation program. Participants received the standard smoking cessation program, the program plus nicotine gum, the program plus behavioral weight control, or the program plus both nicotine gum and behavioral weight control. Weight and smoking status were measured at the end of treatment and at 6 and 12 months posttreatment. RESULTS: Smoking cessation rates were highest in the group receiving the smoking cessation program plus nicotine gum. Weight gain did not vary by treatment condition, so its effect on relapse could not be examined by group. There was no significant relationship between weight gained and relapse in individuals. CONCLUSIONS: The added behavioral weight control program was attractive to the participants and did not reduce smoking cessation rates. However, it did not produce the expected effect on weight, thereby restricting our ability to examine the effect of weight control on smoking cessation and relapse.

Adult

Senior medical students as simulated patients in an objective structured clinical examination: motivation and benefits.

Third and fourth year medical students were recruited to participate as simulated patients and examiners in an Objective Structured Clinical Examination (OSCE) administered for second year medical students. Students reported they were motivated to participate, not only by the honorarium, but because they believed the OSCE would be fun and interesting and because they were interested in medical education and in improving clinical evaluation. The third and fourth year medical students benefitted academically and financially from participation. Faculty benefitted by having a readily available source of enthusiastic and knowledgeable simulated patients.

Education, Medical, Undergraduate

Systemic hypothermia in treatment of brain injury.

An extensive literature suggests that there are minimal complications of systemic hypothermia in humans at and above 30 degrees C for periods of several days. Intracranial hemorrhage has been found to complicate profound hypothermia (10-15 degrees C), and ventricular arrhythmias occur at temperatures below 30 degrees C. Our initial clinical studies were with 21 patients undergoing elective craniotomy cooled to 30-32 degrees C for 1-8 h (mean 4 h). Hypothermia was induced by surface cooling with water blankets. No complications were found. Among 11 patients with severe brain injury, cooling to levels below 32 degrees C was associated with ventricular arrhythmias in 1 patient and atrioventricular block in 1 patient. Asymptomatic hypokalemia was found routinely and treated with potassium replacement. No intracranial hemorrhage or other complications were found. With surface cooling, intravascular temperature dropped at 1.6 degrees C/h. Based on the safety of surface cooling to a core temperature of 32 degrees C for 48 h, we are conducting a randomized study of this level of hypothermia in patients with severe brain injury, cooled within 6 h of injury.

Body Temperature

Human immunodeficiency virus infection in urban Rwanda. Demographic and behavioral correlates in a representative sample of childbearing women.

OBJECTIVE: --To determine behavioral and demographic risk factors for human immunodeficiency virus (HIV) infection in central Africa. DESIGN: --Cross-sectional survey. SETTING: --Kigali, Rwanda. PARTICIPANTS: --A representative sample of 1458 childbearing women aged 19 to 37 years who were recruited from outpatient prenatal and pediatric clinics at the only community hospital in the city. MAIN OUTCOME MEASURE: --Antibodies to HIV assessed by enzyme immunoassay and confirmed by Western blot or indirect immunofluorescence. RESULTS: --The HIV seroprevalence was 32% overall. Infection rates were higher in women who were single, in those in steady relationships that began after 1981, and in the 33% of women reporting more than one lifetime sexual partner. Women in legal marriages or monogamous partnerships had lower rates of infection, but even low-risk women had prevalences on the order of 20%. History of venereal disease in the past 5 years, although the strongest risk factor in a multiple logistic analysis (odds ratio, 2.7; 95% confidence interval, 2.0 to 3.7), was reported by only 30% of those infected. Having a male sexual partner who drank alcohol or who had higher income were significant risk factors for HIV infection in the multivariate analysis, but use of oral contraceptives and having an uncircumcised partner were not. CONCLUSIONS: --The epidemic of the acquired immunodeficiency syndrome in Rwanda has spread beyond high-risk groups to the general population of women without known risk factors. For most of these women, a steady male partner is the source of their HIV risk and therefore a vital target for intervention efforts.

Adult

The behavior of a fast-responding barbituric acid potential-sensitive molecular probe in bovine heart submitochondrial particles.

The barbituric acid probe diBa-C2-(5) responds to the formation of a membrane potential (delta psi) in bovine heart submitochondrial particles (SMP) by a CCCP-reversible, 5-7 nm red shift of the probe absorption spectrum. This shift can be enhanced by the addition of nigericin, an observation that indicates that the probe is specifically sensitive to delta psi. Probe-SMP binding analyses indicate that, relative to the resting state, the ratio of the dye dissociation constant to the maximum number of binding sites decreases by a factor of 30 when delta psi is generated. This observation suggests that the origin of the potential-dependent shift of the probe absorption spectrum is increased occupancy of the SMP membrane by diBa-C2-(5). The time course of the ATP-induced diBa-C2-(5) spectral shift in SMP was complete in nominally 0.2 s and could be described by a single-exponential rate equation. There was no evidence for a slower-phase signal when the data collection time period was increased to 250 s. The apparent first-order rate constants obtained from the single exponential analyses of the barbituric acid ATP-generated signal, however, were a linear function of probe concentration at fixed SMP membrane concentration. The resulting second-order rate constant obtained by linear regression was nominally 1 x 10(7) M (dye)-1 s-1; this value is two to three orders of magnitude higher than that of a number of other well-established probes of delta psi in mitochondrial preparations. Based on the invariance of the kinetics of the oxidation of cytochromes c and c1 by ATP-driven reversed electron transport in the presence and absence of the probe, diBa-C2-(5) does not appear to permeate the SMP membrane on a time scale of milliseconds to several minutes.

Adenosine Triphosphate