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Biomedical subjects

E Singer

Publications and source records attributed to E Singer.

At least 37 records · Page 2Linked to original sources

A phase I/II trial of nimodipine for HIV-related neurologic complications.

BACKGROUND: Few effective treatments are available for AIDS dementia complex (ADC) and HIV-associated neuropathy. However, recent in vitro studies indicate that nimodipine, a voltage-dependent calcium channel antagonist, can prevent HIV-related neuronal injury and may provide a novel form of treatment for these disorders. METHODS: To determine the safety and possible efficacy of this agent, 41 patients with mild to severe ADC, including 19 patients with neuropathy, were entered into the AIDS Clinical Trial Group multicenter, phase-I and phase-II study. Nimodipine at 60 mg p.o., five times daily; 30 mg p.o., three times daily; or placebo was administered for 16 weeks as adjuvant treatment to antiretroviral therapy. RESULTS: Neuropsychological performance at baseline, measured by the composite neuropsychological Z score (NPZ-8), correlated significantly with the ADC stage and with CSF levels of neopterin, a marker of immune activation. No significant differences in toxicity were observed among the three arms. Intent-to-treat analysis showed no significant change in the NPZ-8, although improvement was suggested in the high-dose arm. In addition, a trend toward stabilization in peripheral neuropathy was observed in both nimodipine arms compared with placebo. CONCLUSIONS: Nimodipine and other similar nonantiretroviral agents may provide a safe and promising avenue of treatment for neurologic disorders associated with HIV infection. The results of this study indicate that further clinical trials are warranted.

AIDS Dementia Complex↗

A randomized trial of amitriptyline and mexiletine for painful neuropathy in HIV infection. AIDS Clinical Trial Group 242 Protocol Team.

BACKGROUND: Painful sensory neuropathy is a common complication of HIV infection. Based on prior uncontrolled observations, we hypothesized that amitriptyline or mexiletine would improve the pain symptoms. METHOD: A randomized, double-blind, 10-week trial of 145 patients assigned equally to amitriptyline, mexiletine, or matching placebo. The primary outcome measure was the change in pain intensity between baseline and the final visit. RESULTS: The improvement in amitriptyline group (0.31+/-0.31 units [mean+/-SD]) and mexiletine group (0.23+/-0.41) was not significantly different from placebo (0.20+/-0.30). Both interventions were generally well tolerated. CONCLUSIONS: Neither amitriptyline nor mexiletine provide significant pain relief in patients with HIV-associated painful sensory neuropathy.

Adrenergic Uptake Inhibitors↗

[In vitro activity of 10 antibiotics including pristinamycin and its two components (RP 12536 and 27404) against strict anaerobes].

The activities of the pristinamycin and its two components (RP 12536 and RP 27404) were investigated using the reference agar dilution method M11A3, on 175 anaerobic strains in comparison with that of erythromycin, clindamycin, metronidazole, amoxycillin either alone or combined with clavulanic acid, piperacillin, cefoxitin, cefotetan and cefotaxime. beta-lactamase production was detected for all the 55 B. fragilis group strains and 8/12 Prevotella and 2/18 Fusobacterium strains, respectively. On the whole anaerobes, resistance rates (%) were respectively: RP 27404 (69), RP 12536 (64), pristinamycin (5) erythromycin (31), clindamycin (17), metronidazole (7) amoxycillin (24), amoxycillin-clavulanic acid (2), piperacillin (7), cefoxitin (14), cefotetan (21) and cefotaxime (27). RP 27404 and 12536 had low activities on anaerobes but acted synergistically as pristinamycin. The greatest anti-anaerobic potencies were obtained with amoxycillin-clavulanic acid combination, pristinamycin, metronidazole and piperacillin. As resistance was not found for pristinamycin among Prevotella, Fusobacterium, Gram+ rods and Peptostreptococcus, this streptogramin may be an appropriate agent for the treatment of periodontitis, pulmonary, ENT, gynecologic and soft tissue infections where these anaerobes are frequently involved.

Anti-Bacterial Agents↗

Metabolite abnormalities in progressive multifocal leukoencephalopathy by proton magnetic resonance spectroscopy.

OBJECTIVE: To evaluate progressive multifocal leukoencephalopathy (PML) lesions using proton magnetic resonance spectroscopy (1H MRS). DESIGN: CSF polymerase chain reaction (PCR) detection for JC viral (JCV) DNA; MRI and localized 1H MRS in the PML lesions, normal-appearing contralateral brain regions (CONTRA), and in matched brain regions of normal subjects. SETTING: University-affiliated medical center. PATIENTS OR PARTICIPANTS: 20 AIDS patients with clinical diagnosis of PML, 16 had tissue and/or CSF evidence of JCV infection; 20 age-matched normal subjects. MAIN OUTCOME MEASURES: Metabolites from 1H MRS: N-acetyl aspartate (NA), creatine (CR), choline-containing compounds (CHO), myoinositol (MI), glutamine/glutamate (GLX), lactate, and lipids. RESULTS: CSF PCR for JCV DNA showed 86% sensitivity. MRI showed characteristic demyelinating lesions; commonest locations were frontal lobe and cerebellum. 1H MRS in the lesions showed decreased NA (-35%; p < 0.0001) and CR (-18%; p = 0.003), increased CHO (+28%; p = 0.0005), occasional increased MI, and excess lactate (15/20 lesions) and lipids (18/20). In the CONTRA, MRS showed trends for increased CR (+15%), CHO (+15%), MI (+13%), and lower GLX (-9%; p = 0.02). Six patients, studied longitudinally (4-18 months), showed progressive spectroscopic changes; two patients with longest survival showed the highest MI. CONCLUSIONS: These MRS findings are consistent with neuropathologic observations of neuronal loss, cell membrane and myelin breakdown, and increased glial activity in PML lesions. The CONTRA abnormalities may be due to remote effects of PML or direct HIV-1 infection. 1H MRS may be useful for characterization and follow-up evaluation of PML lesions.

Adult↗

A controlled evaluation of ibuprofen and diazepam for chronic orofacial muscle pain.

The clinical efficacy, side effect liability, and hormonal effects of two prototypic pharmacologic agents were evaluated for the management of chronic myogenous facial pain in a double-blind, randomized, controlled clinical trial. Thirty-nine subjects (35 women,. 4 men) with daily or near-daily orofacial pain of at least 3 months' duration and tenderness to palpation of masticatory muscles participated. Patients were randomly allocated to one of four treatments: placebo, diazepam, ibuprofen, or the combination of diazepam and ibuprofen. Pain, mood, muscle tenderness, maximal interincisal opening, and plasma levels of beta-endorphin were measured following 2-week baseline and 4-week treatment periods. Pain, as measured by a visual analog scale, was significantly decreased in the diazepam and diazepam plus ibuprofen groups but not for the ibuprofen or placebo groups. Analysis of variance showed a significant drug effect for diazepam but not for ibuprofen, indicating that pain relief was attributable to diazepam. No significant changes were noted in muscle tenderness, interincisal opening, or plasma beta-endorphin level. This study supports the efficacy of diazepam in the short-term management of chronic orofacial muscle pain. The lack of effect following administration of an anti-inflammatory analgesic suggests that inflammation is not the basis for chronic muscle pain in the orofacial region, and that the analgesic effect of such medications is not sufficient for pain relief in this condition.

Adult↗

Modulation of hepatic encephalopathy in rats with thioacetamide-induced acute liver failure by serotonin antagonists.

OBJECTIVE: Accumulated neurochemical data in different animal models of fulminant hepatic failure and in humans with hepatic encephalopathy suggest that serotoninergic tone is increased in the brain in hepatic encephalopathy. Since neurochemical alterations may not have behavioural or electrophysiological consequences the contribution of the serotoninergic system to the pathogenesis of hepatic encephalopathy was explored. METHODS: The effects of drugs modulating serotoninergic neurotransmission, the nonselective serotonin receptor antagonist methysergide and the serotonin2 receptor antagonist seganserin were tested neuropharmacologically in thioacetamide-induced acute liver failure in rats. RESULTS: Methysergide had no effect in control rats, but dose dependently increased motor activity in stage II-III hepatic encephalopathy by 232% (5 mg/kg methysergide), 531% (10 mg/kg) and 507% (20 mg/kg). In contrast, seganserin had no effect in encephalopathic rats. CONCLUSION: It is suggested that the beneficial effects of methysergide are serotonin, receptor mediated. Overall the results suggest that serotoninergic mechanisms contribute to some of the behavioural manifestations of hepatic encephalopathy in this animal model.

Animals↗

Comparison of arterial potassium and ventilatory dynamics during sinusoidal work rate variation in man.

1. The mechanisms underlying the exercise hyperpnoea have been difficult to define. Recently it has been suggested that exercise ventilation (VE) changes in proportion to changes in arterial potassium concentration ([K+]a). Similar VE and [K+]a time courses following work rate changes have been cited as supporting evidence. This study compared [K+]a and VE dynamics during moderate exercise in man. 2. We observed VE and gas exchange responses in five healthy men to sinusoidal work rate variation between 25 and approximately 105 W. Tests of approximately 30 min duration were performed at sinusoidal periods of 9, 6 and 3 min and in the steady state. In each test, during two or three sine periods, arterial blood was sampled (24 per test) and analysed for [K+] and blood gases. Response amplitude and phase (relative to work rate) were determined for each variable. 3. [K+]a fluctuated in response to sinusoidal work rate forcing with mean-to-peak amplitude averaging 0.15 mmol 1(-1). However, among tests, VE amplitude and phase were not highly correlated with [K+]a (r = 0.36 and 0.67, respectively). Further, average [K+]a amplitude in the 9 and 6 min sinusoidal studies tended to exceed the steady-state amplitude, while average VE amplitude fell progressively with increasing forcing frequency. The dissimilar dynamics of [K+]a and VE seem inconsistent with a major role for [K+]a as a proportional controller of ventilation during non-steady state moderate exercise in man. 4. Among tests, VE and CO2 output (VCO2) amplitude and phase were closely correlated (r = 0.87 and 0.94, respectively). Further, arterial CO2 pressure (Pa,CO2) and arterial pH(pHa) did not fluctuate significantly in ten of twenty and thirteen of twenty studies, respectively. In tests where sinusoidal fluctuation was detected, amplitude averaged 1.1 mmHg and 0.008 units, respectively. Thus VE demonstrated a close dynamic coupling to CO2 output, with consequent tight regulation of Pa,CO2 and pHa.

Adult↗

A randomized trial of an education and support program for HIV-infected individuals.

OBJECTIVES: To assess the effectiveness of an intervention for providing information and support to HIV-positive donors on changes in their sexual behavior, and to assess which donor characteristics are predictive of behavior change. DESIGN: Subjects were randomly assigned to a structured intervention or community referral group. Follow-up assessments were conducted every 6 months. SETTING: New York City, New York, USA. PARTICIPANTS: A cohort of 271 HIV-infected persons who donated blood to the New York Blood Center. INTERVENTION: Donors randomized to the structured intervention program met individually with a nurse for counseling and were offered a six-session support group. The program was designed to provide information, encourage safer sexual behavior and provide support. MAIN OUTCOME MEASURES: Sexual behavior, psychological distress and psychological help seeking, and immune function. RESULTS: In both groups there was a large decrease over time in reports of unsafe sexual activity. However, more than 30% of participants in both groups reported unsafe sexual activity at the 1-year follow-up visit. Donors randomized to the structured intervention program did not report significantly more behavior change at the 1-year follow-up. CONCLUSIONS: Better programs to promote behavior change in seropositive individuals are needed.

Adult↗

Crystallization and preliminary structural studies of neurotrophin-3.

Neurotrophin-3 (NT-3) has been crystallized in 2 forms. Orthorhombic crystals, space group P2(1)2(1)2, diffracted to 2.8 A and have cell dimensions a = 39.1 A, b = 54.0 A, and c = 65.5 A. The second form is space group P4(3)2(1)2, with cell dimensions a = b = 67.1 A, and c = 107.9 A. The tetragonal crystals diffract to 2.8 A at room temperature and 2.5 A at -100 degrees C. The unit cell dimensions change significantly upon freezing, a = b = 66.1 A, and c = 102.8 A. Phases for the orthorhombic form were obtained by molecular replacement using nerve growth factor as the search model. A partially refined model of the NT-3 dimer (75% complete) was then oriented and positioned in the tetragonal cell.

Chemical Phenomena↗

Depressive symptoms in blood donors notified of HIV infection.

OBJECTIVES: Understanding more about the psychological state of persons notified of human immunodeficiency virus (HIV) infection is critical for designing notification and counseling programs that will have the most positive effect. METHODS: The subjects were blood donors who had been notified of HIV infection by the New York Blood Center. A nurse elicited a medical history, performed a limited medical examination, and asked the subjects to complete a questionnaire that included questions about drug use, sexual behavior, and psychological characteristics. The subjects completed another questionnaire approximately 2 weeks later. RESULTS: The average depressive symptom scores for both men and women were substantially higher than scores typically found in representative population samples. More than a quarter of the men and more than a third of the women reported seeking psychological or psychiatric services in the first few weeks following notification. CONCLUSIONS: Anticipating and meeting individuals' psychological needs may be necessary if HIV screening programs are to address effectively the needs of persons infected with HIV.

Adaptation, Psychological↗

Public opinion about AIDS before and after the 1988 U.S. government public information campaign.

In October, 1987, the Centers for Disease Control mounted a massive public information campaign to alert the public to the dangers of AIDS and to provide information about its transmission and prevention. Using data from two Gallup surveys, one just before the campaign began and the other several months after its conclusion, we examine changes in public information and misinformation about transmission, in concern about AIDS as an epidemic, and in reported behavior to avoid exposure to AIDS. We conclude that although some changes in knowledge did take place, these were essentially a continuation of trends beginning before the public information campaign and continuing well after its conclusion. For these and other reasons, we argue that the effects of the campaign on public information were minimal. However, between 1987 and 1988 there was a small but statistically significant increase in reported condom use, an increase paralleled by increased condom sales between 1986 and 1988. In addition, there was a substantial increase in the number of people expressing concern about AIDS as an epidemic for the population at large. The campaign may well have contributed to both of these changes.

Acquired Immunodeficiency Syndrome↗

Behavior changes after notification of HIV infection.

BACKGROUND: To learn more about how people who did not volunteer for testing react to information about HIV infection, we assessed short-term behavior changes in HIV-positive blood donors. METHODS: Blood donors who were notified at the New York Blood Center that they were HIV positive were asked to participate in a study. A nurse elicited a medical history, performed a limited medical examination, and asked participants to complete a questionnaire that included questions about drug use, sexual behavior, and psychological characteristics. Participants were asked to return in 2 weeks to complete another questionnaire. RESULTS: Many fewer men and women reported engaging in unsafe sexual behaviors in the 2 weeks preceding the follow-up visit than had reported such behaviors prior to notification. These changes were greater than those other investigators have reported, but about 40% of the participants still reported unsafe sexual activity at the follow-up interview. CONCLUSIONS: To make nonvolunteer screening programs for HIV infection more effective in reducing the spread of HIV infection, we need to learn more about how to help people change their high-risk behaviors.

Adolescent↗

Trends in sociodemographic and behavioral characteristics of HIV antibody-positive blood donors.

This paper describes the sociodemographic characteristics of people who donated blood to the New York Blood Center between April 1985 and February 1988 and tested positive for antibodies to HIV. Information on HIV-related risk factors and knowledge of blood screening is presented for seropositive donors who participated in an evaluation study. The most commonly reported risk factor among men was sexual contact with another man, and many of the male seropositive donors reported sex with an intravenous (IV) drug user or use of IV drugs. The proportion of men reporting sexual contact with another man decreased over the period of the study, and the proportion reporting use of IV drugs or sex with an IV drug user increased. Awareness of blood screening for HIV antibodies increased over the study period. The greatest increase was among those donating for transfusion, but only about a quarter of seropositive donors used the confidential unit exclusion (CUE) process.

Adolescent↗

Comparison of human papillomavirus type 1 serotyping by monoclonal antibodies with genotyping by in situ hybridization of plantar warts.

Thirty plantar warts were analyzed for the presence of HPV-1 type-specific and PV genus-specific capsid antigens by immunofluorescence (IF) using monoclonal and polyclonal antibodies and type-specific HPV-1 DNA employing in situ hybridization methods. Fifteen of 30 plantar warts were positive by IF for PV genus-specific structural viral antigens. Thirteen of the 15 productively infected plantar warts expressed intranuclear HPV-1 type-specific capsid antigens and viral DNA, which were detected in the same distribution in each individual wart. The 2 productively infected plantar warts that did not react with HPV-1 type-specific MoAbs did not react with HPV-1 type-specific DNA by in situ hybridization. Thus, serotyping of HPV-1 capsid antigens by monoclonal antibodies is concordant with genotyping of HPV-1 viral DNA by in situ hybridization in productively infected plantar warts.

Antibodies, Monoclonal↗

Sociodemographic and behavioral characteristics of HIV antibody-positive blood donors.

This paper describes the sociodemographic and behavioral characteristics of 173 blood donors who were confirmed by Western blot tests to have antibodies to human immunodeficiency virus (HIV), the etiologic agent for acquired immunodeficiency syndrome (AIDS). Seropositive donors were predominantly young, unmarried, and male, and major risk factors could be identified for almost all donors. However, more than 20 per cent of the study participants were women, and many participants were not aware that they were at risk of infection. The heterogeneity of the study population, the lack of awareness among many subjects of risk factors and self-exclusion procedures, and the high level of distress among many subjects after notification, emphasize the need for intensive, well-designed education and support programs.

Adult↗