Molecular Pharmacology of Topiramate: Managing Seizures and Preventing Migraine

Topiramate is a neuromodulatory compound with stabilizing properties that was initially introduced for the management of partial seizures. Topiramate has been demonstrated to modify several receptor-gated and voltage-sensitive ion channels, including voltage-activated Na⁺ and Ca²⁺ channels and non-NMDA receptors. These receptors have been implicated in the pathophysiology of both epilepsy and migraine. The pharmacological mechanisms of action for topiramate that may explain its antiepileptic and migraine preventive activities will be discussed in this review. In addition, the potential relationship between the molecular activities of topiramate and its efficacy in epilepsy and migraine prevention will be emphasized.     

Strengthening the public health workforce: three CDC programs that prepare managers and leaders for the challenges of the 21st century.

To address the need for management development in public health, the Centers for Disease Control and Prevention (CDC) established three independent workforce development initiatives aimed primarily at strengthening management and leadership capacity: the Sustainable Management Development Program, the Management Academy for Public Health, and the CDC Leadership and Management Institute. Though independently designed and implemented, the programs share similar guiding principles in their approach to management development: interactive (adult) learning, management tools that reinforce evidence-based decision making, individual feedback, continuous improvement of the learning process, posttraining support for networking and life-long learning, and teamwork. This article will discuss important lessons learned regarding best practices in management and leadership development.     

Ultrastructural morphology of early cellular changes in the synovium of primary synovial chondromatosis.

Synovial tissues taken from 13 cases of synovial chondromatosis (SC) were examined by light and electron microscopy. In three of the 13 cases, early cellular changes were observed by electron microscopy. Most of the foci were independently situated within an accumulation of fine, homogenous chondroid matrix in the sublining area of the synovium. Basal laminalike material was observed in these cells. Because this material was not apparent in the mature cartilage cells, the authors postulate that the basilaminar material affects cellular cytodifferentiation in SC during the initial phase of the disease. Ultrastructurally, these cells are morphologically similar to myofibroblasts. However, proliferation of paravascular cells with distinct basal laminae and activated secretory abilities was observed around some of the vessels. These paravascular cells may be the precursor cells of the prechondroblastic cells with basal laminalike material seen in SC.     

Prognostic factors in clinical trials

Summary Prognostic factors define the study population, help formulate the study objectives, and influence the treatment strategies. They must be accounted for in the study analysis to obtain valid estimates of the treatment differences and to evaluate results across studies. The causal relationship between a prognostic factor and the study endpoint can only be established through prospective randomized study designs. Potential factors discovered through retrospective analysis must be verified to establish their validity. Using such factors prematurely to select patient population and treatment strategy for a new study will not establish the validity of the potentially important factor.Supported by NCI 5 PO1 CA53996-15 and NCI 5 U10 CA38926-08.     

Preliminary assessment of the Dex Frame for assisting children with specific learning difficulties

A device called the Dex Frame has recently been marketed as an aid for children with specific learning difficulties. Using a test of reading speed and a test of reading accuracy we have attempted to evaluate the device. Two groups of children with learning difficulties were used, one having sole use of the device and being allowed to carry it with them and a second group who only used the device when attending for remedial tuition and assessment. The results show that no significant improvement occurred in reading performance of the groups with learning difficulties using the Dex Frame as compared with a control group. The teachers of the groups did, however, feel that on an individual basis some children (< 10%) expressed that they felt more comfortable using the device.     

Prospective assessment of biofeedback for the treatment of paradoxical puborectalis contraction

Eighteen patients with chronic constipation were diagnosed as having paradoxical puborectalis contraction (PPC) as the cause for their constipation. The diagnosis of PPC was made after office evaluation, colonic transit study, manometry, cinedefecography, and electromyography (EMG). These 18 patients had a mean duration of symptoms of 26.9 years; none of these patients had unassisted bowel movements. Fourteen patients had a mean of 4.6 laxative-induced bowel evacuations per week, and 11 patients had a mean of 4.4 enema-induced bowel evacuations per week. Patients underwent a mean of 8.9 one-hour EMG-based biofeedback sessions. At a mean follow-up of 9.1 (range, 0.5–12) months, these 18 patients had a mean of 7.3 unassisted bowel actions per week ( P <0.0001). In addition, persistent laxative use was reported by only two patients, and, in both cases, this was once a week or less ( P <0.001). Similarly, enema use was reported by only three patients, one once weekly and the other two thrice weekly ( P <0.002). No biofeedback-related complications were identified. EMG-based biofeedback is a valuable technique associated with an 89 percent success rate in the treatment of PPC.Read at the meeting of The American Society of Colon and Rectal Surgeons, Boston, Massachusetts, May 12 to 17, 1991.     

Changes in the human vocal tract due to aging and the acoustic correlates of speech production: a pilot study.

This investigation used a derivation of acoustic reflection (AR) technology to make cross-sectional measurements of changes due to aging in the oral and pharyngeal lumina of male and female speakers. The purpose of the study was to establish preliminary normative data for such changes and to obtain acoustic measurements of changes due to aging in the formant frequencies of selected spoken vowels and their long-term average spectra (LTAS) analysis. Thirty-eight young men and women and 38 elderly men and women were involved in the study. The oral and pharyngeal lumina of the participants were measured with AR technology, and their formant frequencies were analyzed using the Kay Elemetrics Computerized Speech Lab. The findings have delineated specific and similar patterns of aging changes in human vocal tract configurations in speakers of both genders. Namely, the oral cavity length and volume of elderly speakers increased significantly compared to their young cohorts. The total vocal tract volume of elderly speakers also showed a significant increment, whereas the total vocal tract length of elderly speakers did not differ significantly from their young cohorts. Elderly speakers of both genders also showed similar patterns of acoustic changes of speech production, that is, consistent lowering of formant frequencies (especially F1) across selected vowel productions. Although new research models are still needed to succinctly account for the speech acoustic changes of the elderly, especially for their specific patterns of human vocal tract dimensional changes, this study has innovatively applied the noninvasive and cost-effective AR technology to monitor age-related human oral and pharyngeal lumina changes that have direct consequences for speech production.