Effect of Zonisamide (CI-912) on a Synaptic System Model

The effect of the experimental antiepileptic drug zonisamide (1,2-benzisoxazole-3-methanesulfonamide, ZNS) on the trigeminal complex of cats was compared with the effect of established antiepileptic drugs. Intravenous administration of 10-40 mg/kg ZNS significantly depresses descending excitatory mechanisms, as well as segmental and descending inhibitory mechanisms, but has only a minor effect on segmental excitatory mechanisms. This spectrum of activity is similar to that of valproate, and suggests that ZNS should also be a broad-spectrum antiepileptic drug. In agreement with our experimental observations, it has been found that ZNS is effective against complex partial, generalized tonic clonic, and myoclonic seizures. The antiepileptic profile of ZNS in conventional screening tests resembles that of carbamazepine (CBZ) and phenytoin. However, CBZ exacerbates rather than prevents myoclonic seizures. Our experimental model thus provides a more accurate prediction of ZNS's clinical spectrum of activity. The relationship of these findings to the mechanism of action of antiepileptic drugs is discussed.     

Quantitative and qualitative changes of serum proteolytic activity in rats with liver damage induced by galactosamine

Serum proteolytic activity was determined in galactosamine-treated rats and in controls. Injection of the hepatotoxin at a dose of 400 mg/kg resulted in a 3.4-fold elevation in the serum proteolytic activity, while AST (aspartate aminotransferase), ALT (alanine aminotransferase) and bilirubin were increased by factors of 3.9, 8.8 and 4.5, respectively. Studies with proteinase inhibitors revealed that the serum proteolytic activity was partially metal-dependent as well as puromycin and antipain sensitive. Differences in susceptibility to a combination of N-ethylmaleimide and antipain indicated presence of different proteolytic systems in the sera of liver damaged and control rats. Separation of serum proteinases by gel filtration showed that the galactosamine-intoxicated rat serum contained activity which did not appear in the control serum. This activity was partially metal dependent, antipain and N-ethylmaleimide sensitive, and was more susceptible to dithiothreitol than the control activity. These findings demonstrate that hepatocellular damage induced by galactosamine caused not only an increase in serum proteinases, but was also associated with the appearance of enzymes not normally released by the liver of untreated animals.Abbreviations AP alkaline phosphatase - TBil total bilirubin - AST aspartate aminotransferase - ALT alanine aminotransferase - GGT gamma-glutamyltranspeptidase - BiAc bile acids - PrAm primary amines - ProAc proteolytic activity     

Weight percentile at birth. I. Clinical data of pregnancy and relevance for early childhood development

The influence of the weight percentile at birth on childhood development was examined in a prospective study of 847 singleton pregnancies. In the first two years of life significant relationships between the birth weight percentiles and the infant's development could be proven, while at the age of four social factors were predominant. Though various clinical data in pregnancy and delivery were related to fetal growth, such as weight of the mother, previous abortions and diseases, additional biochemical and biophysical information is desirable for early recognition of intrauterine growth disorders.     

Health lifestyles and self-direction in employment among American men: A test of the spillover effect

This paper examines whether American males with a high degree of control over their work situation pursue healthy lifestyles and rate their physical health more positively than those who score low on occupational self-direction. That is, are persons who control their work more likely to also try to control their health through living in a particularly healthy manner? We found that there was no support for a spillover effect from high occupational self-direction to enhanced participation in health lifestyles or more positive self-rated health. The findings suggest health lifestyles have spread throughout occupational work groups in the U.S. and support research that maintains such lifestyles have spread across social strata in America.     

Auer rod positive dysmyelopoietic syndrome

Twenty-five patients with refractory anemia with excess blasts (RAEB) were studied. Five of these patients showed Auer rods in their myeloblasts, but met other criteria for RAEB. Median survival of the Auer rod-positive group was 14 months (range 2–27) from diagnosis with survival of 7 months after Auer rods were first observed. Median survival for the Auer rod-negative group was 12 months. Two patients developed overt acute leukemia, both from the Auer rod-negative group. The clinical course of Auer rod-positive RAEB, like that of Auer rod-negative RAEB, was one of progressive bone marrow failure complicated by infection, serious bleeding and the development of absolute transfusion requirement. These findings suggest that Auer rod-positive RAEB is a morphologic variant dysmyelopoietic syndrome that may pursue a similar clinical course to Auer rod-negative disease. Formulation of a separate treatment approach for those RAEB patients who possess Auer rods would appear ill advised.     

HLA-DR7 predicts the response to alkylating agents in steroid-sensitive nephrotic syndrome

There is a lack of reliable predictors of the response to alkylating agents in children with idiopathic nephrotic syndrome (NS). HLA-DR7 is strongly associated with the frequency of relapses in steroid-sensitive NS before cytostatic therapy. We therefore examined retrospectively the time to the first relapse and the incidence of subsequent relapses in 54 HLA-typed children with frequently relapsing NS, after treatment with cyclophosphamide (n = 49) or chlorambucil (n = 5) for 8 or 12 weeks; 38 patients were HLA-DR7 positive and 16 negative with 80% in both groups being steroid dependent. HLA typing was performed using serological or DNA typing methods. Renal biopsy showed minimal glomerular changes. A lower proportion of HLA-DR7 positive than negative patients remained in remission after 3 years (36% vs. 81%, P<0.02) and 5 years (36% vs. 72%, P<0.03). In the first 3 years after cytostatic therapy the mean number of prednisone-treated relapses was 1.3/patient per year in HLA-DR7-positive patients compared with 0.4 in negative patients (P<0.025). There was no statistically significant difference in the proportion of relapse-free patients with and without steroid dependency. The HLA status predicts the response of NS patients to alkylating agents better than the rate of previous relapses. Received September 19, 1995; received in revised form and accepted April 16, 1996     

Gd-DTPA-cascade-polymer: Potential blood pool contrast agent for MR imaging

Gadolinium-DTPA (diethylenetriaminepentaacetic acid)-cascade-polymer, a potential new blood pool contrast agent for magnetic resonance (MR) imaging, was compared with a known blood pool agent, Gd-DTPA-polylysine, in an animal model. The relative signal intensities of liver, renal cortex, pancreas, and trunk muscle were assessed in 12 pigs between 4 seconds and 120 minutes after injection of a 20 μmol/kg dose of each contrast agent, by using a FLASH (fast low-angle shot) sequence. Except for muscle, all tissues showed visible enhancement after injection of either contrast agent. After injection of Gd-DTPA-polymer, enhancement patterns in the liver, renal cortex, and pancreas were similar to those seen after injection of Gd-DTPA-polylysine. No statistically significant differences in enhancement between the two contrast agents were found at any time point. The authors conclude that the contrast kinetics of Gd-DTPA-cascade-polymer are similar to those of Gd-DTPA-polylysine and that this agent may also be used as a blood pool contrast agent for MR imaging.     

Recall of medication during pregnancy: Validity and accuracy of an adjusted questionnaire

Objective — To study the validity and accuracy of an adjusted questionnaire on medical drug use during pregnancy eight years after the pregnancy. Methods — The ability of a questionnaire on medication during pregnancy to detect actual use (= sensitivity) was tested against information collected 8 years previously (in 1983–1984) from 473 women with high-risk pregnancies who delivered at the University Hospital Nijmegen, the Netherlands. Results — For separate drug groups, the sensitivity varied between 5% and 91%. The timing of use was recalled moderately well. Although specific questions on drug groups did improve the sensitivity as compared to an earlier questionnaire, the improvement was not enough to make the questionnaire valid. High maternal education, low birth weight, low gestational age and a low 5-min Apgar score were related to better recall. The sensitivity of the questionnaire depended on the behavioural score of the child, implying recall bias. Conclusion — Questionnaire data on drug use during pregnancy obtained eight years after delivery are not a valid source of information.     

The orthopan tomoscintigram — a new application of emission computed tomography for facial bone scanning

The exact regional correlation of findings of facial bone scans, planar or SPECT, to dental orthopan X-ray films (OPT) is difficult because of the very different projection techniques. To improve correlative imaging in this regard a projection algorithm was developed that uses SPECT data of the skull for reconstructing an orthopan tomoscintigraphic projection. Fourteen conventional SPECT slices of the upper and lower jaws were obtained during bone scanning. All mandibular slices were superimposed resulting in a horseshoe shaped structure, which was marked by an ROI which was divided into segments. All 14 SPECT slices were then masked by this segmental ROI, thereby marking the teeth-carrying bone in all slices. The information from this horseshoe like ROI is then transformed into lines. Line by line arrangement results in an orthopan projection, the orthopan tomoscintigram. This new display allows 1:1 true scale superimposition with the X-ray OPT and markedly facilitates correlative imaging.