A Neuropharmacological Evaluation of Felbamate as a Novel Anticonvulsant

Felbamate (2-phenyl-1,3-propanediol dicarbamate, FBM) was subjected to a series of carefully selected in vivo and in vitro tests to provide additional insight into mechanism of action, margin of safety, and clinical potential. FBM was effective against intracerebroventricular (i.c.v.) N-methyl-D-aspartate (NMDA)-induced clonus and i.c.v. NMDA- and quisqualic acid (quis)-induced forelimb tonic extension in mice and ineffective against i.c.v. quis-induced clonus in mice. FBM was also effective in preventing the expression of Stage 5 kindled seizures in corneal-kindled rats. The calculated protective indices (rotorod median toxic dose divided by anticonvulsant median effective dose) ranged from 28 to 146 for those tests in which FBM displayed activity. With the in vitro tests, FBM did not significantly displace [3H]MK-801 from its binding site. In contrast, FBM was effective in blocking sustained repetitive firing in mouse spinal cord neurons grown in tissue culture (median inhibitory concentration 67 micrograms/ml). This effect on repetitive firing suggests indirectly that FBM modulates sodium channel conductance. The results, when compared to similar data for phenytoin, carbamazepine, valproate, and ethosuximide, support the concept that FBM is a relatively nontoxic agent with a unique profile of anticonvulsant action, a broad margin of safety, and a clinical potential that includes at least generalized tonic-clonic and complex partial seizures.     

Pediatric HIV-1 Infection: A Clinical Overview

Several questions remain unanswered including the timing of perinatal transmission, maternal factors predisposing to perinatal transmission of HIV-1, the best methods for early diagnosis in the neonate, and means of preventing perinatal HIV-1 infection. Significant advances have been made in the early diagnosis of HIV-1 infection, and now it is possible to make a diagnosis in most infants by 6 months of age. Unfortunately, not all these techniques are commercially available, so this capability is limited to certain institutions and laboratories. The natural history of HIV-1 infection in children continues to evolve, particularly with increased prophylaxis of P. carinii pneumonia and the availability of antiretroviral therapy. Our challenges for the future are to prevent perinatal transmission, to develop new and better therapies for opportunistic infections and HIV-associated complications, and to improve outcome and prognosis.     

Do physicians know when their diagnoses are correct?

OBJECTIVE: This study explores the alignment between physicians' confidence in their diagnoses and the "correctness" of these diagnoses, as a function of clinical experience, and whether subjects were prone to over-or underconfidence. DESIGN: Prospective, counterbalanced experimental design. SETTING: Laboratory study conducted under controlled conditions at three academic medical centers. PARTICIPANTS: Seventy-two senior medical students, 72 senior medical residents, and 72 faculty internists. INTERVENTION: We created highly detailed, 2-to 4-page synopses of 36 diagnostically challenging medical cases, each with a definitive correct diagnosis. Subjects generated a differential diagnosis for each of 9 assigned cases, and indicated their level of confidence in each diagnosis. MEASUREMENTS AND MAIN RESULTS: A differential was considered "correct" if the clinically true diagnosis was listed in that subject's hypothesis list. To assess confidence, subjects rated the likelihood that they would, at the time they generated the differential, seek assistance in reaching a diagnosis. Subjects' confidence and correctness were "mildly" aligned (kappa=.314 for all subjects, .285 for faculty, .227 for residents, and .349 for students). Residents were overconfident in 41% of cases where their confidence and correctness were not aligned, whereas faculty were overconfident in 36% of such cases and students in 25%. CONCLUSIONS: Even experienced clinicians may be unaware of the correctness of their diagnoses at the time they make them. Medical decision support systems, and other interventions designed to reduce medical errors, cannot rely exclusively on clinicians' perceptions of their needs for such support.     

Asymptomatic vasculitic neuropathy

Introduction: We performed a retrospective analysis of the clinical, pathological, and electrophysiological features of 21 cases of Asymptomatic vasculitic neuropathy (AsVN). Methods: Among 270 patients with biopsy‐proven vasculitic neuropathy, we identified 21 (7.8%) who had asymptomatic neuropathy. Results: Of the 21 patients with AsVN, 11 were women and 10 were men. Their mean age was 62.5 years. Referring physicians suspected systemic vasculitis on the basis of clinical and laboratory features, but none of the patients had neuropathy by examination. Screening nerve conduction studies identified neuropathy in all patients, leading us to perform a sural nerve biopsy, which confirmed the diagnosis of vasculitis. Twelve patients had active (type I), 6 had inactive (type II), and 3 had probable (type III) vasculitis. Vasculitis was primary in 10 patients and secondary in 11. Conclusions: Nerve conduction study is an important tool for identifying AsVN, a subtype of vasculitic neuropathy. Muscle Nerve 52 : 34–38, 2015