Biomedical subjects

Penelope M Keyl

Publications and source records attributed to Penelope M Keyl.

6 recordsLinked to original sources

PubMed2005

Target-specific catecholamine elevation induced by anticonvulsant thalamic deep brain stimulation.

PURPOSE: Anterior thalamic nucleus (AN) deep brain stimulation (DBS) is effective in raising EEG and clonic seizure threshold in experimental models. Little is known about the specific properties of DBS that afford its anticonvulsant effect. We sought to test the hypothesis that experimental seizures and the anticonvulsant action of AN DBS alter the underlying regional neurochemistry of AN, specifically with facilitation of the serotonergic system to local electrical stimulation. METHODS: Halothane-anesthetized adult Sprague-Dawley male rats underwent stereotactically guided bilateral placement of bipolar stimulating steel electrodes and dialysis probes-guide cannulae in AN and posterior thalamus (PT), and placement of four epidural EEG screw electrodes 48 h before experiments. Both stimulated (AN DBS) and nonstimulated (NO DBS) animals (n=7 per group) were infused with i.v. pentylenetetrazol (PTZ, 5.5 mg/kg/min). Simultaneous thalamic and cortical EEG were recorded, and microdialysis samples were collected from AN and PT in 20-min epochs. AN stimulation was delivered (150 microA; 0.1-ms pulse duration) 40 min before and continued during PTZ infusion. RESULTS: Bilateral AN stimulation delayed the onset of EEG seizures compared with controls: 82+/-8 vs. 58+/-5 min (p=0.02). PTZ infusion alone, or together with stimulation, resulted in a steady increase in norepinephrine (NE), but not dopamine, at AN and PT sites (p<0.001). Although extracellular serotonin was measured at very low levels, the metabolite, 5-hydroxyindoleacetic acid (5-HIAA) increased selectively in AN after stimulation and during preconvulsant infusion of PTZ (p<0.001), returning to baseline after the first generalized seizure. CONCLUSIONS: These data suggest that PTZ and DBS together enhance the nonselective release of NE in thalamic nuclei while specifically stimulating AN-localized serotonin. Low serotonin levels at baseline and during STIM alone or PTZ infusion may indicate efficient reuptake systems for serotonin, with 5-HIAA serving as a surrogate marker for serotonergic activity. Modulation of the AN-specific serotonergic activity may be critical in altering PTZ seizure threshold and be an important neurotransmitter system underlying the efficacy of AN DBS.

Animals↗

PubMed2005

Frameless stereotactic aspiration and thrombolysis of spontaneous intracerebral hemorrhage.

INTRODUCTION: To test the feasibility and safety of a minimally invasive technique, we report our experience in treating spontaneous intracerebral hemorrhage (ICH) patients by using frameless stereotactic clot aspiration-thrombolysis and its effects on their 30-day survival. We compared the observed cohort mortality with its predicted 30-day ICH mortality, by using previously validated methods. METHODS: Selection criteria were diagnosis of hypertensive ICH > or =35 cc, reduced level of consciousness, and no brainstem compression. Frameless stereotactic puncture/clot aspiration followed by intraclot external catheter placement was performed. Two milligrams of recombinant tissue plasminogen activator (rtPA) was administered q12 hours until ICH volume < or =10 cc, or the catheter fenestrations were no longer in continuity with the clot. RESULTS: Fifteen patients were treated, mean age was 60.7 years. Hemorrhage locations included basal ganglia (13), thalamic (1), and lobar (1); mean systolic blood pressure; and admission ICH volumes were 229.3 mmHg and 59.1 cc, respectively. Median time from ictus to clot aspiration/thrombolysis was 1 (range 0-3) day. Mean hematoma volume was reduced to 17% of pretreatment size. Complications were ventriculitis (6.6%) and clot enlargement (13.3%). Two patients were dead at 30 days. Median Glasgow Coma Scale (GCS) scores were 10.5 (4-15) at admission and 11.0 (3-15) at discharge. By using the most conservative estimate for analysis, probability of observing two or fewer deaths among 15 patients with an overall probability of dying calculated at 0.33 was p = 0.079. CONCLUSIONS: In this selected cohort of patients with ICH, stereotactic aspiration and thrombolytic washout seemed to be feasible and to have a trend towards improved 30-day survival, when using their predicted mortality data as "historical control." Complications did not exceed expected incidence rates. Based on the experience presented here as well as previous similar reports, a larger, randomized study addressing dose escalation, patient selection, and best therapeutic window is needed.

Biopsy, Fine-Needle↗

PubMed2004

Intraventricular thrombolysis speeds blood clot resolution: results of a pilot, prospective, randomized, double-blind, controlled trial.

OBJECTIVE: Animal models and clinical studies suggest that intraventricular thrombolysis improves clot resolution and clinical outcomes among patients with intraventricular hemorrhage. However, this intervention may increase the rates of rebleeding and infection. To assess the safety and efficacy of intraventricular thrombolysis, we conducted a pilot, randomized, double-blind, controlled, multicenter study. METHODS: Patients with intraventricular hemorrhage requiring ventriculostomy were randomized to receive intraventricular injections of normal saline solution or urokinase (25000 international units) at 12-hour intervals. Injections continued until ventricular drainage was discontinued according to prespecified clinical criteria. Head computed tomographic scans were obtained daily, for quantitative determinations of intraventricular hemorrhage volumes. The rate of clot resolution was estimated for each group. RESULTS: Twelve subjects were enrolled (urokinase, seven patients; placebo, five patients). Commercial withdrawal of urokinase precluded additional enrollment. The urokinase and placebo groups were similar with respect to age (49.6 versus 55.2 yr, P = 0.43) and presenting Glasgow Coma Scale scores (7.14 versus 8.00, P = 0.72). Randomization to the urokinase treatment arm (P = 0.02) and female sex (P = 0.008) favorably affected the clot resolution rate. The sex-adjusted clot half-life for the urokinase-treated group was reduced 44.6%, compared with the value for the placebo group (4.69 versus 8.48 d). CONCLUSION: Intraventricular thrombolysis with urokinase speeds the resolution of intraventricular blood clots, compared with treatment with ventricular drainage alone.

Adult↗

PubMed2003

A longitudinal study of risk factors for motorcycle crashes among junior college students in Taiwan.

A cohort of 4729 junior college students in an urban and a rural area in Taiwan was followed up for a period of 20 months. Students' characteristics, including riding exposures, as well as human, vehicular, and environmental factors were collected using one initial and three follow-up questionnaires. The Anderson-Gill (AG) multiplicative intensity model was used to determine the risk of a motorcycle crash over time while also allowing for the modeling of multiple events. The average response rate for the four assessments was 92%. The adjusted relative hazard (RH) for students living in the rural as opposed to the urban area for crashes was 1.67 at the beginning of the study but decreased to 0.66 by the end. Past motorcycle crash history, number of riding days, average riding distance, risk-taking level, alcohol consumption, and traffic violations were all significantly associated with an increased risk of being involved in a crash. Conversely, increasing age, riding experience, and automobile licensure were related to a decreased risk of crashing. Furthermore, helmet use was not independently related to the risk of crashing. In conclusion, a high-risk group predisposed to involvement in a motorcycle crash, including both non-injury and injury-related crashes, can be identified using selected risk factors for crash prevention among young riders.

Accidents, Traffic↗

PubMedDate not supplied

The role of physicians in assessing older drivers: barriers, opportunities, and strategies.

BACKGROUND: Evaluation of the older driver is a difficult task for primary care physicians. We investigated the physician-perceived barriers to assessing older drivers in primary care practice. METHODS: Twenty family physicians whose patients had completed a clinical questionnaire and neuropsychological tests participated in one of 2 focus groups. Physicians were asked about barriers to assessing older drivers in primary care and the usefulness of neuropsychological tests for assessing driving ability. RESULTS: A number of themes emerged related to barriers in the assessment of the older driver. Major themes included concerns about being liable for the results of driving related screening and about patients reacting unfavorably to a driving assessment including cognitive tests. Physicians uniformly agreed that a protocol to guide driving assessment would be useful. CONCLUSIONS: Physicians encounter a number of barriers to assessing older drivers but recognize the importance of driving within the context of geriatric functional assessment.

Aged↗

PubMedDate not supplied

Prospective study of brief neuropsychological measures to assess crash risk in older primary care patients.

BACKGROUND: Practicing primary care physicians often encounter the difficult clinical situation of evaluating the older driver. We wanted to investigate the relation between self-reported driving behavior, neuropsychological measures, and crash risk to inform the development of a test battery that could predict unsafe driving behavior and was feasible for use by primary care physicians. METHODS: This study was a prospective follow-up of 107 drivers aged 65 years and older recruited from a primary care setting in 1995. Tests of attention, visual information processing, spatial orientation, and general mental status were administered at baseline. At baseline and after 2 years of follow-up, patients were asked about their driving history using the driving questionnaire. Risk for reported crashes in the follow-up period was assessed in relation to baseline driving history and measures of cognition. RESULTS: Baseline self-reports of driving habits and attitudes were associated with an increased risk of reporting a crash after 2 years of follow-up (relative risk ratio = 5.31; 95% confidence interval [CI], 0.63, 44.63). In addition, baseline tests of attention, visual information processing, and spatial orientation were associated with an increased risk of reporting motor vehicle crash at follow-up. For example, respondents with poor performance on the Trail Making Test-part A, were almost four times more likely to report a crash at follow-up (risk ratio = 3.15; 95% CI, 0.76, 13.07). CONCLUSION: Although our conclusions are tempered by small sample size, this preliminary study suggests that brief cognitive tests and simple questions about driving habits warrant further investigation as indicators of crash risk with potential utility for assessing older drivers in primary care.

Accidents, Traffic↗