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Biomedical subjects

W Wolf

Publications and source records attributed to W Wolf.

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

F waves and motor unit size.

M responses and twitch contractions were evoked in single motor units (MUs) of the first dorsal interosseus muscle by intramuscular microstimulation of motor axons. Two-hundred nine MUs were studied in 21 subjects. Thirty-five MUs (17%) showed F waves in addition to M responses. Twitch force was used to provide an indirect measure of MU size; additionally, twitch contraction time was measured. There was no select group of MUs generating F waves with regard to the above contraction parameters. However, four of five MUs with very high twitch forces, above 70 mN, generated F waves. We conclude that MUs of all sizes produce F waves with similar probability. Only few MUs with very strong twitch forces, i.e., very large MUs, may be more subject to F-wave production and may be involved in the generation of the so-called repeater F waves.

Action Potentials

Occurrence of human express saccades depends on stimulus uncertainty and stimulus sequence.

Saccadic latencies measured in response to a step-wise displacement of the target may be substantially reduced if a gap separates the offset of the initial fixation point and the onset of the peripheral target. According to Fischer and Ramsperger (1984) this paradigm provokes a bimodal latency distribution which consists of a peak of very fast saccadic responses (express saccades) at about 110 ms and another peak arising from somewhat slower saccades (regular saccades). Using again the gap paradigm, we investigated the effect of an additional go/no-go (i.e. target trial/catch trial) decision on saccadic latencies. The experiments yielded the following results: (i) the distribution between the peaks of express and regular saccades strongly depends on the proportion of catch trials introduced into the trial sequence, which suggests the existence of different modes of operation of the decision processes for express and regular saccades. (ii) The catch trial effect on saccadic latency proved to be a local phenomenon in time: saccades which follow catch trials tend to be slower than those following target trials.

Adult

Effects on ADH activity and distribution, following selection for tolerance to ethanol in Drosophila melanogaster.

Strains of Drosophila melanogaster homozygous for either the AdhF or the AdhS allele were kept on food supplemented with ethanol for 20 generations. These strains (FE and SE) were tested for tolerance to ethanol and compared with control strains (FN and SN). The E strains showed increased tolerance to ethanol both in the adult and in the juvenile life stages. In adults the increase in tolerance was not accompanied by an increase in overall ADH activity. However, there were changes in the distribution of ADH over the body parts. Flies of the FE strain possessed significantly more ADH in the abdomen, compared with FN. Another set of FN and SN populations were started both on standard food and on ethanol food with reduced yeast concentrations. After 9 months ADH activities were determined in flies from these populations which had been placed on three different media: the food the populations had been kept on, regular food and regular food supplemented with ethanol. The phenotypic effects of yeast reduction on ADH activity were considerably, but longterm genetic effects were limited.

Abdomen

A new, semi-automated system for the micro-scale synthesis of [195mPt]cisplatin suitable for clinical studies.

A new, semi-automated system for the microscale synthesis of [195mPt]cisplatin has been developed. Radiochemical yields of up to 70% of pure [195mPt]cisplatin can be obtained routinely e.g. 555-629 MBq (15-17 mCi) from 925 MBq (25 mCi) of [195mPt]Pt metal. Chemical losses during synthesis, and radiation exposure of personnel, have been minimized. These increased yields are the consequence of the elimination of most transfers, and enhanced yields at most steps: ammination losses decreased from 27 to 7%, and at the diiodo- to di-acquo- conversion, from 34 to 11%. The versatility of such a system is discussed.

Cisplatin

Parameters of human motor unit twitches obtained by intramuscular microstimulation.

Intramuscular microstimulation of motor axons was used to study twitch responses of 209 motor units (MUs) in the first dorsal interosseus muscle (FDI) of 20 normal subjects. Twitch peak force (TF), maximum rate of rise of force (MRRF), contraction time (CT) and one-half relaxation time (HRT) were determined. The distributions of TF (mean 16.0 mN, median 10.3 mN) and MRRF (mean 0.88 N s-1, median 0.66 N s-1) were skewed to the right with the majority of the values lying in the lower ranges, whereas CT (mean 63 ms, median 62 ms) and HRT (mean 61 ms, median 58 ms) were approximately normally distributed. TF was significantly correlated with MRRF, but not with CT in contrast with studies of cat gastrocnemius muscle. TF values were similar to those obtained by spike-triggered averaging in the same muscle. The method proved to be reliable and appropriate for use in patients. Examples of MU twitch parameters from three patients with chronic partial denervation of the FDI are described.

Adult

Restricted transcription of varicella-zoster virus in latently infected human trigeminal and thoracic ganglia.

Normal human trigeminal and thoracic ganglia latently infected with varicella-zoster virus (VZV) were identified by polymerase chain reaction (PCR). Total RNA was extracted from these ganglia and treated with DNase until ganglionic RNA was free of VZV DNA as determined by PCR. Radiolabeled cDNA synthesized by priming with random oligonucleotides was hybridized to Southern blots containing recombinant clones that spanned greater than 95% of the VZV genome. The single region of the VZV genome detected was the 12.5-kb SalI C fragment located in the unique long segment of the viral genome. Two additional regions of the VZV genome, EcoRI G and SalI B, were detected in RNA from adult dorsal root ganglia and infant nervous system tissue.

Adult

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

[Is the origin of the F-wave dependent on the magnitude of the motor unit?].

It is still unknown why only few motor units (MUs) generate F-waves in response to supramaximal stimulation of a motor nerve. Therefore we investigated whether the F wave production might depend on MU-size. According to the size principle of Henneman we used the twitch force as indirect measure of MU-size. MU twitch force was determined applying the technique of intramuscular microstimulation of single motor axons. 127 MUs were analysed in 16 normal subjects. F-waves were observed in 35 MUs (27%). It was found that MUs of different sizes produced F-waves with approximately the same probability. Obviously size is not a relevant factor for the capability of a MU to produce F-waves. Only the few very large MUs of a pool may have an increased tendency to produce F-waves because four of five MUs with extremely large twitch forces (> 70 mN) generated F-waves.

Adult

[The dependence of rapid voluntary contractions on the tremor phase in parkinsonism].

Parkinsonian patients sometimes have problems to produce really fast motor responses. Often, these are significantly delayed in comparison to those of normal controls. In patients with tremor-at-rest, this delay might be induced by some attraction of the movement execution to the tremor oscillator, according to a hypothesis of Hallet et al. (1977). This study now examined the phase relationship between the on-going tremor and the onset of fast voluntary contractions in Parkinson's disease (PD), quantitatively. Five patients with prominent tremor-at-rest performed rapid isometric index finger abductions under self paced (SP) and reaction time (RT) conditions, and force and surface EMG signals from the FDI muscle were analyzed. In both conditions the SP and the RT, data showed that the onset of the contraction mostly occurs during the descending phase of the tremor oscillation and, accordingly, the phasic EMG burst synchronously with the tremor bursts confirming the above mentioned hypothesis.

Aged

[Perforation of a temporary transvenous pacemaker electrode in the left hemithorax. Diagnostic value of echocardiography].

We report a rare malposition of a temporary transvenous pacemaker electrode. A pacemaker electrode was inserted in a patient with acute postero-lateral infarction. The correct position of the electrode tip was controlled by fluoroscopy. Capture and sensing functions worked regularly. Four days later, angina-pectoris-like complaints occurred again. Chest x-ray film revealed the tip of the electrode in the left hemithorax. Echocardiographic assessment showed a penetration through the interventricular septum into the left ventricle. The electrode passed the left ventricle, penetrated the anterior-lateral free wall and reached the left pleural space. A thoracotomy was performed immediately. The electrode was retracted under visual control. A spurting arterial bleeding from the left ventricle was secured with a purse-string ligature. This case report emphasizes the value of echocardiography in the evaluation of a malposition of a transvenous pacemaker electrode.

Echocardiography

In vivo measurements of intratumoral metabolism, modulation, and pharmacokinetics of 5-fluorouracil, using 19F nuclear magnetic resonance spectroscopy.

In vivo 19F nuclear magnetic resonance spectroscopy was used to monitor and measure 5-fluorouracil and some of its cytotoxic anabolites directly in rats bearing the Walker 256 adenocarcinoma by using a 4.7-T horizontal bore magnet. A two-compartment subsystem model was used to estimate intratumoral transfer parameters. The apparent rate of formation of the nucleosides/tides in the tumor, K21, changed following methotrexate pretreatment, from a value of 6.4 +/- 2.4 to 15.5 +/- 5.0. These values were statistically significant to P less than 0.01. This 2-compartment model was validated by excising the tumors and measuring the 19F content of the acid soluble and the RNA fractions. The increase of the mean K21 value (2.4) estimated in vivo correlated favorably with the increase of the levels of the fluorinated nucleosides/nucleotides (2.2) observed by in vitro analysis. The in vitro measurements also revealed that the increase in the fluorinated nucleosides was accompanied with a similar increase in 5-fluorouracil incorporation into the RNA fraction, which suggests that increases or decreases in the relative intensity of the fluorinated nucleoside/nucleotide signals observed in vivo could be indicative of similar changes of the nuclear magnetic resonance invisible fluorinated RNA. The present study documents that it is now possible to estimate the pharmacokinetic behavior of 5-fluorouracil and of its active metabolites at its target site, tumor tissue, by using noninvasive measurements. Such measurements may provide useful means of assessing, during treatment, the possible effect of 5-fluorouracil on the tumor, and its response to treatment, both when used by itself as well as a function of biochemical modulation.

Animals

Formation of neutralizing antibodies against natural interferon-beta, but not against recombinant interferon-gamma during adjuvant therapy for high-risk malignant melanoma patients.

In an adjuvant clinical trial, 34 high-risk malignant melanoma patients were treated with natural interferon (IFN)-beta and recombinant IFN-gamma. Patients with tumor location on head, neck, and trunk received 3 million IU IFN-beta intravenously (IV) three times weekly for 24 weeks. Patients with tumor location on the extremities received subcutaneous (SC) injection of 2 million IU of IFN-beta distal the locoregional lymph nodes instead. All patients were given 50 micrograms IFN-gamma SC on 3 consecutive days every 4 weeks. Antibody formation was detected by coincubation of IFN and patients' serum and assessment of the inhibition of the cytopathic effect by a virus suspension. Soluble interleukin-2 receptors (sIL-2R) were determined by enzyme-linked immunosorbent assay (ELISA) technique. No antibodies against IFN-gamma were observed. The overall incidence of antibody formation to IFN-beta was 55.8% (19/34). Ninety-two percent of the SC-treated patients (13/14) and 30% (six of 20) of the IV-treated patients developed antibodies. Soluble interleukin-2 receptors were found to be significantly lower in antibody-positive patients than in antibody-negative patients. The authors conclude that IFN-beta antibody formation is frequent and might influence IFN induced sIL-2R elevation in vivo.

Antibodies

Simian varicella virus DNA in dorsal root ganglia.

Clinical, pathological, immunological, and virological evidence suggests that simian varicella virus (SVV) infection of primates is the counterpart of varicella-zoster virus infection of humans. To determine whether these two viruses share similarities in their properties during latency, we analyzed ganglia and brain of an African green monkey experimentally infected with SVV for the presence of viral nucleic acid using the polymerase chain reaction technique. We detected SVV DNA in dorsal root ganglia but not in brain of this monkey, which demonstrated no apparent clinical signs of SVV infection. Our results suggest that SVV becomes latent in monkey ganglia and that latency can develop in the absence of clinical varicella (chickenpox). These studies provide an animal model system to study varicella virus latency.

Animals

Three-dimensional structure of the E. coli DNA-binding protein FIS.

The factor for inversion stimulation, FIS, is involved in several cellular processes, including site-specific recombination and transcriptional activation. In the reactions catalysed by the DNA invertases Gin, Hin and Cin, FIS stimulates recombination by binding to an enhancer sequence. Within the enhancer, two FIS dimers (each 2 x 98 amino acids) bind to two 15-base-pair consensus sequences and induce bending of the DNA. Current models propose that the enhancer-FIS complex organizes a specific synapse, either through direct interactions with Gin, or by modelling the substrate into a configuration suitable for recombination. Using X-ray analysis at 2.0 A resolution, we now show that FIS is composed of four alpha helices tightly intertwined to form a globular dimer with two protruding helix-turn-helix motifs. The 24 N-terminal amino acids are so poorly defined in the electron density map as to make interpretation doubtful, indicating that they might act as 'feelers' suitable for DNA or protein (invertase) recognition. We infer from model building that DNA has to bend for tight binding to FIS.

Amino Acid Sequence

Mechanical implications of paired motor unit discharges in pathological and voluntary tremor.

Paired motor unit discharges (PDs), i.e., two discharges of the same motor unit (MU) with short interval, and their relation to tremor amplitude were studied in the first dorsal interosseous muscle (FDI) of patients with parkinsonian or essential tremor and in normal subjects mimicking tremor. In both pathological and voluntary tremor, interdischarge intervals of PDs were inversely correlated with the amplitude of the subsequent tremor beat, i.e., PDs with shorter intervals were followed by higher tremor beats. To further assess their mechanical impact, PDs were simulated by applying paired stimuli to MUs of the FDI in normal subjects using intramuscular microstimulation. Following paired stimuli, summation of twitch responses was more than linear. This was also the case with the paired stimuli applied at a tremor-like repetition rate (5 Hz). These findings stress the importance of PDs for tremor expression.

Adult

The hexachlorotechnetate reagent in the synthesis, characterization and biodistribution of two novel lipophilic complexes.

The hexachlorotechnetate reagent has been used to synthesize lipophilic complexes of technetium-99m with polydentate ligands, using ligand exchange reactions and acetonitrile as an aprotic solvent. The complexes isolated were partially characterized by chromatographic (paper and HPLC) and electrophoretic methods. Preliminary data on biodistribution studies, carried out in rabbits, are also presented. This work documents that the hexachlorotechnetate reagent is a suitable intermediate for the rapid synthesis of new lipophilic complexes of technetium-99m.

Animals

Abdominal aortic aneurysm repair after renal transplantation with extracorporeal bypass.

The successful resection of an abdominal aortic aneurysm is presented in a patient who had undergone kidney transplantation 4 years previously. Because the transplanted kidney is more sensitive to ischemia than a normal one, a femoro-femoral bypass with a pump oxygenator was used for perfusion of the transplanted kidney during crossclamping. During the clamping time of 40 minutes kidney perfusion was maintained with a perfusion pressure of 60 to 80 mmHg and the flow was 600 to 1000 ml/min. A collagen-seeded Dacron graft (diameter: 18 mm, length: 12 mm) was interposed. The postoperative course was uncomplicated. We believe that performing the femoro-femoral bypass with a pump oxygenator is an effective and simple method for kidney protection in such operations.

Aorta, Abdominal