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Biomedical subjects

W Wolf

Publications and source records attributed to W Wolf.

At least 55 records · Page 3Linked to original sources

The "gap paradigm" leads to express-like saccadic reaction times in Parkinson's disease.

Application of the "gap paradigm" reduces mean saccadic reaction time (SRT). It enhances oculomotor response, sometimes showing express-like reactions within about 100-140 ms from target onset, which are called "express saccades." Despite some controversy, there is evidence that express and regular saccades may be controlled by different pathways, but it is still not clear which pathways are involved in the generation of express saccades. It was suggested that the substantia nigra (SN) could take part in the control of these saccades. We compared saccadic reaction times of 14 patients with mild to moderate Parkinson's disease (PD), which commonly affects the SN, with those of nine elderly normal subjects. The results show a clear gap effect and no significant difference between mean saccadic reaction times and reaction time distributions of the PD and the control group. In the gap condition, express saccades are present in several subjects of both groups. Therefore, it is concluded that the deficits in the SN pars compacta due to PD, which affect directly and indirectly the activity of the SN pars reticulata that projects to SC, do not dominantly influence the process of preparing and executing express and regular saccades in patients with mild to moderate PD.

Aged↗

Long-term management of acute respiratory failure in metabolic myopathy.

OBJECTIVE: To describe how patients cope with the proposal of treatment with intermittent artificial ventilation after acute respiratory failure due to progressive respiratory muscle weakness. DESIGN: Case series, follow-up study. SETTING: Neurological intensive care unit (ICU). PATIENTS: 7 consecutive patients with metabolic myopathy treated for acute respiratory failure between 1983 and 1992. INTERVENTIONS: Intermittent positive pressure ventilation (IPPV) via tracheostomy. MEASUREMENTS AND RESULTS: Symptoms of chronic hypoventilation preceded acute respiratory failure for months. With one exception, patients were mainly disabled from respiratory muscle weakness and sleep-related breathing disorders. IPPV was recommended to prevent recurrent respiratory failure. Two of three patients who accepted home IPPV returned to full-time jobs. One patient, who decided against IPPV, died from CO2 narcosis several months after discharge. All patients adhered to the respiratory regimen once instituted. CONCLUSIONS: Acute respiratory failure in chronic myopathy is heralded by daytime drowsiness. IPPV, or at least regular monitoring of waking and sleeping partial pressure of carbon dioxide, is highly recommended even if weaning is successful. IPPV improved quality of life. The treatment strategy at discharge from the ICU should be optimal, as patients are reluctant to modify regimens.

Activities of Daily Living↗

Classification of HIV infection and disease in women from Rwanda. Evaluation of the World Health Organization HIV staging system and recommended modifications.

OBJECTIVE: To develop a human immunodeficiency virus (HIV) staging system for sub-Saharan Africa on the basis of an evaluation of the World Health Organization (WHO) system and predictors of mortality. DESIGN: Prospective cohort study with 4 years of follow-up. SETTING: Kigali, Rwanda. PATIENTS: 412 HIV-infected women recruited from prenatal and pediatric clinics. MEASUREMENTS: Clinical signs and symptoms of HIV disease, laboratory assays (including complete blood count and erythrocyte sedimentation rate), and cumulative mortality. RESULTS: The WHO staging system includes a clinical and a laboratory axis. The clinical axis was revised by inclusion of oral candidiasis, chronic oral or genital ulcers, and pulmonary tuberculosis as "severe" disease (clinical stage IV); in addition, body mass index was substituted for weight loss in the definition for the wasting syndrome. The 36-month cumulative mortality was 7% for women in modified clinical stage I ("asymptomatic"), 15% for those in stage II, 19% for those in stage III, and 36% for those in stage IV (P < 0.001). The laboratory axis was revised by replacing lymphocyte count with hematocrit and erythrocyte sedimentation rate. The 36-month mortality was 10% for women in modified stage A ("normal" laboratory results) and 33% for those in stage B (erythrocyte sedimentation rate > 65 mm/h or hematocrit < 0.38) (P < 0.001). A single staging system combining clinical and laboratory criteria is proposed, with a 36-month mortality of 7% for women in combined stage I, 10% for those in stage II, 29% for those in stage III, and 62% for those in stage IV (P < 0.001). CONCLUSIONS: On the basis of this analysis, a staging system relevant for sub-Saharan Africa is proposed that reflects the range of HIV-related outcomes, has strong prognostic significance, includes inexpensive and available laboratory tests, and can be used by both clinicians and researchers.

AIDS-Related Opportunistic Infections↗

Tremor as a factor in prolonged reaction times of parkinsonian patients.

Prolonged reaction times and tremor are symptoms of Parkinson's disease (PD). Recently, we showed the existence of a systematic phase relationship between tremor-at-rest and the onset of voluntary motor responses in PD patients. In the present study we investigated whether this phase relationship contributes to the prolongation of reaction time in PD. Eight PD patients with prominent tremor-at-rest and five age-matched controls performed rapid stimulus-evoked index finger abductions under isometric conditions. Force and surface electromyogram (EMG) signals from first dorsal interosseus muscle were recorded and analyzed off-line by means of automatic routines. Reaction times of PD patients exhibited a significant dependence of mean values and variability on the current tremor phase at the onset of the voluntary motor response. Responses with an onset of contraction during the beginning of an EMG tremor burst were substantially delayed (on average 50 ms) and showed more variability in comparison to responses initiated at later times in the tremor cycle. This effect can be modeled by a simple gating process splitting the tremor cycle into two different system states that supports and inhibits the initiation of voluntary motor responses, respectively. We conclude that attraction of voluntary motor initiation to the tremor oscillator clearly contributes to prolongation of reaction time in PD.

Aged↗

A family planning intervention to reduce vertical transmission of HIV in Rwanda.

OBJECTIVES: Since contraception is an effective way of preventing the vertical transmission of HIV, we evaluated the impact of a family planning intervention on hormonal contraceptive use and incident pregnancy in a group of HIV-positive and HIV-negative urban Rwandan women. SUBJECTS AND METHODS: In a longitudinal cohort study, 502 women who were not pregnant or infertile and who had been previously HIV tested and counseled viewed an informational video about hormonal contraception followed by a facilitated discussion. They were given access to oral or injectable hormonal contraception and Norplant at the research clinic; those who used these methods were seen every 3 months. RESULTS: Of the 330 HIV-positive and 172 HIV-negative women who underwent the intervention, 120 either became new hormonal method users (n = 40), continued their previous use of a hormonal method (n = 64), or switched to another hormonal method (n = 16) following the intervention. There was a shift to use of longer lasting hormonal methods, and the annualized attrition rate was < 15%, compared to > 50% prior to the intervention. Rates of oral and injectable contraceptive use were similar among HIV-positive and HIV-negative women. Nine per cent of HIV-positive women became pregnant in the year after the intervention compared to 22% in a prior 12 month period when contraceptives were not provided at the study site. The corresponding proportions for HIV-negative women were 20% after the intervention versus 30% before the intervention. CONCLUSIONS: Access to and information about hormonal contraceptives resulted in increased use and reduced attrition among both HIV-positive and HIV-negative women in this study. The reduction in incident pregnancy was greatest among HIV-positive women, suggesting that factors other than access to hormonal contraceptives may have influenced fertility outcomes. Knowledge of HIV serostatus may have an important influence on family planning decisions.

Adolescent↗

Association of intratumoral pharmacokinetics of fluorouracil with clinical response.

In-vivo fluorine-19 nuclear magnetic resonance spectroscopy (NMRS) allows non-invasive, real-time, chemical identification of specific fluorinated compounds inside human tumours after administration of fluorouracil (5-fluorouracil). Kinetic measures of the administered drug and metabolites allow estimation of the tumoral half-life of fluorouracil. We studied 57 patients by 19F NMRS immediately after they had received 600 mg/m2 fluorouracil intravenously. Serial spectra were acquired with the surface coil positioned on the skin above the tumour. We defined an intratumoral half-life of fluorouracil of 20 min or more as indicating trapping of the drug, based on the blood half-life of 8-12 min. 19 patients had intratumoral half-lives indicating trapping of fluorouracil, 27 had half-lives less than 20 min, and 11 had no detectable fluorouracil in their tumours. 8 of 9 evaluable patients whose tumours showed trapping had partial responses to chemotherapy that included fluorouracil compared with only 2 of 25 patients whose tumours did not trap the drug (p = 0.000021). 19F NMRS can identify patients likely to respond to chemotherapy with fluorouracil and could be used clinically to tailor optimum treatment.

Fluorouracil↗

Stimulus sequence effects on human express saccades described by a Markov model.

Express saccades predominantly occur in experiments employing the gap paradigm where the target onset is separated from the fixation point offset by a blank period. Their relative frequency is distinctly influenced by catch trials (i.e. trials without a saccadic target) mixed into the stream of regular target trials. Generalizing this concept for other stimulus uncertainties (direction, amplitude), we found that the preparation time of a saccade depends on both the type of uncertainty used and the sequence of trial type (e.g., target vs catch, left vs right) in the experiment. This stimulus sequence effect is most prominent for catch trials. A similar but less pronounced effect can still be observed in the case of direction uncertainty but not in that of amplitude uncertainty. A two-state Markov process model is proposed which is based on the dichotomy of express and regular saccades in the gap paradigm. According to this model the actual state of the saccadic system, which determines the type of saccade just in preparation, depends on the "trial history". The implications for models of saccade programming are discussed.

Adolescent↗

Assessment of human motor unit twitches--a comparison of spike-triggered averaging and intramuscular microstimulation.

We recorded twitches of single motor units (MUs) in the human first dorsal interosseus muscle using either spike-triggered averaging (STA; 236 MUs in 12 normal subjects) or low-rate intramuscular microstimulation of motor axons (IMS; 200 MUs in 20 normal subjects). We analysed twitch force (TF), maximal rate of rise of force (MRRF), contraction time (CT) and half-relaxation time (HRT). MRRF, CT and HRT were significantly smaller with STA than with IMS whereas TFs were fairly similar. Higher stimulus rates (up to 14 Hz) in IMS resembling the voluntary MU firing rates in STA were associated with a decrease of all twitch parameters because of partial fusion of the twitches (20 MUs). Concerning MRRF, CT and HRT, the reduced values matched those obtained by STA, suggesting that the underestimation of these parameters in STA can be mainly attributed to partial fusion. The reduction of TF with high rate IMS but not with STA reveals that other factors such as MU synchronization and non-linear force summation of MU contractions must counteract the effects of partial fusion in STA. We conclude that both STA and IMS are appropriate for assessing TFs in man while the time-dependent parameters MRRF, CT and HRT will be underestimated with STA.

Adult↗

Beta 2-microglobulin as a predictor of death in HIV-infected women from Kigali, Rwanda.

OBJECTIVE: To determine if beta 2-microglobulin (beta 2M) predicts death among HIV-infected African women. DESIGN: Nested case-control study. SETTING: Kigali, Rwanda. PARTICIPANTS: Two hundred and five seroprevalent women known to be HIV-infected since 1986-1987; 67 of whom died of HIV disease (cases) and 138 were alive (controls) as of November 1991. In addition, 128 women who seroconverted between 1986 and 1991. MAIN OUTCOME MEASURES: HIV serology, clinical signs and symptoms of HIV disease, hematology variables, and beta 2M concentration. RESULTS: beta 2M concentration increased over time (P < 0.001) in the seroprevalent women and seroconvertors. The average rate of beta 2M increase in women who died was 0.5 compared with 0.3 mg/l/year in the vital, seroprevalent women (P = 0.07). The strongest independent predictors of death were the rate of change of beta 2M (mg/l/year) [odds ratio (OR), 3.4; 95% confidence interval (CI), 1.7-6.8] and baseline beta 2M concentration (mg/l) [OR, 1.6; 95% CI, 1.2-2.1]. The rate of death for women with beta 2M concentration > or = 7.0 mg/l and a rate of change of beta 2M > or = 0.4 mg/l/year was 7.3 times higher than for women with beta 2M concentration < 7.0 mg/l and a rate of change of beta 2M of < 0.4 mg/l/year (95% CI, 3.1-17.2). The estimated median time from seroconversion to death assuming a constant rate of change of beta 2M was 10.6 years (95% CI, 9.9-11.2) for this cohort of HIV-infected women. CONCLUSIONS: Elevated beta 2M and a high rate of beta 2M increase were strongly associated with mortality among HIV-infected African women. Based on survival estimates using the rate of change of beta 2M, HIV-infected African women have similar survival compared with HIV-infected adults in the United States.

Adolescent↗

Contamination of genetically engineered CHO-cells by epizootic haemorrhagic disease virus (EHDV).

The characterization of a contaminating virus which was detected in genetically-engineered Chinese hamster ovary (CHO) cells during the production of biologicals is described in the present paper. Under electron microscopy, the contaminating virus had a morphology resembling that of an orbivirus. The relationship was confirmed by nucleic acid analysis which showed a RNA segment pattern characteristic of orbiviruses. With an immunoperoxidase staining of monolayer cells and through sero-neutralization tests the virus was identified as being identical to Epizootic Haemorrhagic Disease Virus (EHDV), isolate 318 (untyped) from Bahrain. Potential sources of the contaminating virus and feasible procedures to avoid adventitous virus infections in cell cultures are discussed.

Animals↗

Relationship between tremor and the onset of rapid voluntary contraction in Parkinson's disease.

It has been suggested that initiation of voluntary movement in Parkinson's disease (PD) is synchronous with tremor beats. This hypothesis was tested by examining quantitatively the onset of voluntary contraction in relation to the tremor cycle. Five PD patients with tremor at rest produced fast isometric abduction of the index finger in reaction time and self-paced trials. For each trial, the time interval from last tremor peak to contraction onset was evaluated and its frequency distribution was compared with proposed statistical models. It was found that patients most often initiated contractions during the descending phase of the tremor oscillation and that the phasic EMG burst most commonly occurred after the mid-point of the EMG tremor cycle in both self-paced and reaction time conditions. These results indicate that voluntary contraction is not initiated arbitrarily with respect to the tremor oscillation. Rather, there is a systematic phase relationship between the onset of the voluntary response and tremor. Thus attraction of voluntary movement to the tremor oscillator in PD results from abnormally synchronised motor units and failure to activate the motor neuron pool voluntarily soon after the tremor discharge.

Aged↗

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↗