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Biomedical subjects

J A Cramer

Publications and source records attributed to J A Cramer.

103 records · Page 6Linked to original sources

Valproic acid in epilepsy: clinical and pharmacological effects.

The antiepileptic drug valproic acid was studied in an open clinical trial as adjunct medication for 23 patients with uncontrolled seizures of a generalized or partial type. Two-thirds of the patients experienced reduction in seizure frequency ranging from 25 to 100%. Extensive testing revealed no evidence of serious systemic toxicity due to the drug. Minor side effects (e.g., nausea, vomiting, or sedation) were usually transient. Sodium valproate syrup and valproic acid in capsules gave equivalent mean low (23.3 microgram/ml) and maximum (42.5 microgram/ml) serum concentrations. The drug had a relatively short half-life of 8.7 hours, necessitating administration in divided daily doses. During initiation of valproate therapy there was evidence of a decline in total serum phenytoin concentration (16.5 to 10.2 microgram/ml; p less than 0.001) while the percentage of free phenytoin increased (10.9 to 20%). The quantity of unbound phenytoin was relatively stable throughout. This observation was interpreted as a drug interaction: valproic acid competed with phenytoin for access to plasma protein binding sites.

Adult↗

Evaluation of liposome-entrapped radioactive tracers as scanning agents. Part 1: Organ distribution of liposome (99mTc-DTPA) in mice.

We describe the use of liposomes as a delivery system for radiopharmaceutical localization. Liposomes [99mTc-DTPA] were injected intravenously in mice and showed preferential uptake in the liver and spleen. There was a steady decline of activity in all organs, suggestive of destruction of liposomes with subsequent release of 99mTc-DTPA into the circulation. Alteration of uptake from liver to spleen, lung, and bone marrow was achieved by prior loading of the circulation with nonradioactive liposomes. The same effect was produced in dogs and demonstrated with scintigraphy. We also showed scintigraphically in dogs how 99mTc-DTPA, when administered entrapped in liposomes, follows the pattern of distribution of liposomes. Liposomes seem to be suitable carriers for radiopharmaceuticals. Further studies should show the possibility of directing liposomes to specific targets.

Animals↗

Brief report: Adolescents' attitudes toward epilepsy: further validation of the Child Attitude Toward Illness Scale (CATIS).

OBJECTIVE: To examine adolescents' attitudes toward having epilepsy using the Child Attitude Toward Illness Scale (CATIS) and to provide further psychometric validation of the scale in this population. METHODS: Participants were 197 adolescents aged 11 to 17 years who completed the CATIS at two points and two external validation scales. Test-retest and internal consistency reliability and construct validity were computed. Analysis of variance was used to examine differences in attitudes according to gender, age, and epilepsy severity. RESULTS: Girls, older adolescents, and those with more severe epilepsy had more negative attitudes toward having epilepsy than boys, younger adolescents, and those with moderate or mild epilepsy, respectively. Psychometric analyses yielded excellent internal consistency reliability and good test-retest reliability. The CATIS was moderately correlated with self-esteem and mastery, supporting its construct validity. CONCLUSIONS: The CATIS is a useful and psychometrically sound tool to assess adolescents' attitudes toward having chronic illness.

Adolescent↗

Behavioral toxicity associated with antiepileptic drugs: concepts and methods of assessment.

The BTB designed for the VA Epilepsy Cooperative Study is a conceptually organized and practical set of test procedures that can be utilized to assess change in the areas of motor integration, visual perception, speech and language, and mood that might be attributable to AED therapy. If the data warrant, these categories can be compressed into motor, attention-concentration, and mood. The unique methodological advantages of the VA Epilepsy Cooperative Study provide an opportunity to determine empirically the occurrence of behavioral toxicity for specific AED. The advantage of the BTB is the capacity to measure change from an objective baseline over an extended period during chronic AED treatment. The disadvantages are the requirements for apparatus, trained technicians, and additional time for the patient, which now limit its use to research. If BTB data confirm its sensitivity to behavioral toxicity often unappreciated during a neurological exam, the BTB will become a useful clinical tool. Additionally, a common vocabulary for communicating behavioral toxicity may emerge. This optimistic picture is presented with the simultaneous acknowledgment that a clear solution to the problem lies in accumulation of data in future studies which will have had the opportunity to examine the forthcoming results of this multicenter study.

Anticonvulsants↗

Behavioral characteristics of epilepsy patients compared with normal controls.

Using neuropsychological testing procedures, we measured the behavioral characteristics of patients with epilepsy unaffected by anticonvulsant drugs and compared these results with control subjects matched for age, sex, and education. In a nationwide VA Cooperative study, 622 patients with well-defined seizure types were given a selected battery of neuropsychological tests prior to and at 1 month after initiation of drug therapy. Seventy-four control subjects were administered the same test battery under standardized conditions at the same VA testing centers. All tests of controls were also repeated 1 month later. The patients with epilepsy scored significantly and consistently below the level of the control subjects on all but three behavioral measures. Differences reaching statistical significance were found on tests of motor function (Finger Tapping, Pegboard, Color Naming), cognitive-attention (Digit Symbol, Discriminative Reaction Time, Word Fluency), and subtests of the Profile of Mood Status (tension, depression, vigor, and confusion). These data provide a profile of behavioral characteristics of unmedicated patients with epilepsy.

Adolescent↗

Comparison of a noninstrumented immunoassay for carbamazepine to high performance liquid chromatography and fluorescence polarization immunoassay.

The accuracy, precision, and potential clinical utility of a new whole blood, noninstrumented immunochromatographic assay (AccuLevel) for carbamazepine (CBZ) was evaluated in a multicenter trial including 100 pediatric and 205 adult patients. The AccuLevel assay, a fluorescence polarization immunoassay (FPIA), and high-performance liquid chromatography (HPLC) were used to determine CBZ concentration in samples from 111 female and 194 male patients aged 2-72 years (median 25 years). Mean +/- SD plasma CBZ concentrations in all patients were 7.4 +/- 3.0 micrograms/ml with the AccuLevel assay and 7.5 +/- 2.9 micrograms/ml with FPIA. In 204 patients, the mean concentration determined by the HPLC assay was 7.7 +/- 3.0 micrograms/ml, whereas concentrations determined by the AccuLevel and FPIA assays were 8.0 +/- 3.1 and 8.1 +/- 3.1 micrograms/ml, respectively. Concentrations determined by the AccuLevel and FPIA assays were significantly higher than those quantified by HPLC (p less than 0.05), but not different from each other. In addition, the AccuLevel assay was highly correlated with FPIA (r = 0.97) and HPLC (r = 0.98). Coefficients of variation for the AccuLevel assay at 8 micrograms/ml ranged from 6.8 to 7.5% for the three institutions. We conclude that the AccuLevel assay is a simple, reliable method for determining CBZ concentration in a small volume of whole blood and is an acceptable alternative for assessment of CBZ therapy and individualization of CBZ dosage in the physician's office or emergency room.

Adolescent↗