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Biomedical subjects

J L Zaidman

Publications and source records attributed to J L Zaidman.

At least 19 recordsLinked to original sources

Serum electrolyte and blood gas changes after intrathecal and intravenous bolus injections of magnesium sulphate. An experimental study in a rat model.

The effect of intrathecally administered magnesium sulphate on serum levels of magnesium, sodium, potassium, calcium and blood gas variables was studied in a rat model. Magnesium sulphate given intrathecally has previously been shown to produce segmental spinal blockade with no permanent neurological damage. The previous studies, however, had not investigated the possible systemic effects of the magnesium sulphate. The serum magnesium level increased significantly at 1 and 2 h after the intrathecal injection of both 6.3% and 12.6% magnesium sulphate (6.3%: 28% at 1 h, 24% at 2 h; 12.6%: 22% at 1 h, 16% at 2 h). These changes were not as great as occurred when the same dose of magnesium sulphate was administered intravenously. In all cases, the serum magnesium had returned to normal by 24 h. There were no significant changes in calcium, sodium or potassium levels, nor in arterial blood gas variables. These results show that intrathecally administered magnesium sulphate has little effect on electrolyte homeostasis.

Anesthesia, Spinal↗

Routine childhood screening for hyperlipidemia in Israel.

Screening of children and adolescents for hyperlipidemia is controversial. We performed a cholesterol surveillance study of 806 children aged between 6 and 14 years. The initial cholesterol screening test was done by finger stick in the non-fasting state. Children with cholesterol values exceeding 4.55 mmol/l ("borderline" risk) and their parents had their lipid profiles measured following a 12 h fast by venipuncture. The incidence of coronary risk factors in the families of children with hypercholesterolemia was estimated. Of the initial group, 71 children had total capillary cholesterol levels > or = 4.55 mmol/l, and in 65 of these children serum lipid profile was reexamined after an overnight fast. Fifty-five children were found to have total venous cholesterol (TVC) levels < 4.55 mmol/l, and 27 of the 55 had a low density lipoprotein (LDL) cholesterol level > 3.4 mmol/l ("borderline" risk). A positive correlation was found between TVC and LDL-cholesterol levels. Of the hypercholesterolemic children 49% had a parent with hyperlipidemia and 13% had a family history of premature myocardial infarction (before 55 years of age). We conclude that screening of children based on the presence of hypercholesterolemia or its possible complications in other family members may fail to identify many of the children with hypercholesterolemia. Thus, if thorough identification of young children with hypercholesterolemia is desired, inclusive population screening would be the most effective approach.

Adolescent↗

Inhibition of human red blood cell glutathione reductase by valproic acid.

Glutathione reductase (GR) one of the enzymes of the glutathione redox cycle, plays a salient role in maintaining appropriate cellular levels of reduced glutathione. The enzyme in human red blood cells is inhibited in vitro by the anticonvulsant drug valproic acid (VPA). The inhibition is dose-dependent, reversible, uncompetitive and does not depend on the redox state of the enzyme. VPA also inhibits red blood cell GR activity in children being treated with the drug. The level of serum VPA correlates significantly with the suppression of GR activity.

Adolescent↗

Amniotic fluid components and changes due to storage conditions.

The composition of amniotic fluid was found to vary in dependence on storage conditions. Catalytic concentrations of creatine kinase and lactate dehydrogenase were considerably decreased after storage at -20 degrees C, and the decreases were less marked after storage at -70 degrees C. Other analytes were more stable. Consequently, the optimal storage conditions for amniotic fluid samples may differ for various analytes. The low inter-individual variability of some analytes (Na, K, Ca, Cl) suggests that their concentrations are homeostatically controlled during the gestational period studied. In contrast, the high variability of enzyme activities may be due to more rapid quantitative changes during normal gestation; in addition, enzyme activities may be affected by certain pathological and non-pathological conditions of the fetus.

Amniotic Fluid↗

Leukocyte alkaline phosphatase and carcinoembryonic antigen in metastatic colorectal cancer patients.

Peripheral blood leukocyte alkaline phosphatase scores and plasma carcinoembryonic antigen levels in 26 patients with metastatic colorectal cancer were compared to those in 30 healthy controls. Patients had metastases to the liver and abdomen. The mean leukocyte alkaline phosphatase score in the metastatic colorectal cancer patients was significantly higher than in the control group (246 +/- 65 vs, 52 +/- 26, p less than 0.001); and the mean carcinoembryonic antigen level in the patients was also significantly higher than in the controls (110 +/- 100 vs, 4.9 +/- 3 ng/ml, p less than 0.001). One hundred percent of the metastatic cancer patients had elevated LAP scores and 73% of these patients had elevated CEA levels. There was a difference between the mean CEA levels in the patients with liver metastases and those with abdominal metastases (162 +/- 135 vs, 39 +/- 53 ng/ml, p less than 0.04). The results suggest that although both markers were elevated in metastatic colorectal cancer, the LAP score seems to be more useful in detecting metastatic disease, since we found 11% false negatives with the CEA level and 0% false negatives with the LAP score.

Abdominal Neoplasms↗

Developmental toxicity of valproic acid.

Valproic acid is a very effective anticonvulsant agent widely used in the management of various forms of epilepsy. Administration of the drug during pregnancy results in increased incidence of congenital abnormalities in both humans and experimental animals. In recent years, a significant number of research efforts have attempted to define the contributory role of valproic acid to the impairment of normal prenatal growth and development. The present report summarizes current knowledge that has emerged from clinical and research studies. The specific topics include: the placental transfer of valproic acid; the teratogenic potential; structure-teratogenicity and dose-response relationships; species and strain differences; biochemical changes evoked by the drug in the fetus.

Animals↗

Leukocyte alkaline phosphatase and carcinoembryonic antigen in colorectal cancer patients (usefulness in the assessment of the stage).

Leukocyte alkaline phosphatase (LAP) scores in peripheral blood, and plasma carcinoembryonic antigen (CEA) levels were determined in 122 colorectal cancer patients, and compared to 30 healthy persons, who served as controls. Both markers are gradually elevated according to the severity of tumor penetration. LAP scores in Dukes'C and D (157 +/- 79) were significantly higher than in Dukes'A, B1 and B2 (81 +/- 43), p less than 0.001. CEA levels were also higher in Dukes'C and D (50 +/- 95) than in patients with Dukes'A, B1 and B2 (25 +/- 54), p less than 0.07, but less significantly. The LAP score has at least the same reliability as the CEA values as a marker of stage in colorectal cancer patients.

Alkaline Phosphatase↗

Early changes in hepatic redox homeostasis following treatment with a single dose of valproic acid.

Changes in reduced glutathione (GSH) and pyridine nucleotide phosphate levels as well as in the activities of the glutathione peroxidase-reductase system and glucose-6-phosphate dehydrogenase have been studied in rats after a single i.p. administration of various doses of valproic acid (VPA). GSH level decreased in a dose-dependent relation. At the end of 180 min GSH levels either returned to control limits (lower doses) or showed a tendency to normalize (higher doses). GSH loss was paralleled by the reduction in glutathione reductase activity. A significant NADPH reduction was also seen after animal exposure to high VPA doses. At the end of 180 min a maximal NADPH decrease was reached. The activities of both glutathione peroxidase and glucose-6-phosphate dehydrogenase were suppressed irrespective of whether animals were given low or high VPA doses.

Animals↗

Neurophysiological and biochemical changes evoked by valproic acid in the central nervous system.

(1) Valproic acid is an anticonvulsant agent widely used in the management of various forms of epilepsy, including absence, myoclonic and tonic-clonic seizures. (2) It also has anticonvulsant potency in a wide variety of animal models of epilepsy. (3) This action is generally thought to be exerted through modulation of the activity of the endogenous inhibitory neurotransmitter, gamma-aminobutyric acid. (4) Evidence that valproic acid interacts with the gamma-aminobutyric acid system is presented. (5) Interactions of valproic acid with other neurotransmitters, i.e. aspartate, glutamate, taurine, serotonin, as well as with cyclic nucleotides and hormones are also considered. (6) Direct effects of valproic acid on excitable membranes and its relationships with analgesia are outlined.

Animals↗

Leukocyte alkaline phosphatase and carcinoembryonic antigen in breast cancer patients. Influence of the treatment on the markers.

Leukocyte alkaline phosphatase (LAP) scores and carcinoembryonic antigen (CEA) levels were analyzed in 53 patients suffering from breast cancer. All patients underwent mastectomy and received adjuvant treatment, and all lived more than 5 years after diagnosis without metastatic disease. Thirty-three patients received adjuvant radiotherapy, and 20 patients received adjuvant chemotherapy. The median LAP score before radiotherapy was 117 +/- 48; two months after the beginning of radiotherapy this value was 175 +/- 71, being significantly higher than the original value (p less than 0.001), and one year after the beginning of radiotherapy it was 105 +/- 63, which approximated the normal scores. The median LAP score before chemotherapy was 138 +/- 69; two months after the beginning of chemotherapy it was 194 +/- 63, i.e. significantly higher than before chemotherapy (p less than 0.002), and one year after the beginning of chemotherapy it was 150 +/- 56. Median CEA levels before radiotherapy were 6.4 +/- 5.1 ng/ml; two months after the beginning of radiotherapy this value was 6.0 +/- 5.0 ng/ml; and one year later 7.4 +/- 6.2 ng/ml. Median CEA levels before chemotherapy were 8.1 +/- 12.0 ng/ml; two months after the beginning of chemotherapy 12.6 +/- 13.0 ng/ml (p less than 0.05) in comparison with the values before chemotherapy; and one year after the beginning of chemotherapy it was 8.6 +/- 5.4 ng/ml. We concluded that the LAP scores were influenced by adjuvant radio- or chemotherapy, and the CEA levels were influenced by chemotherapy.

Alkaline Phosphatase↗

Leukocyte alkaline phosphatase and carcinoembryonic antigen in breast cancer patients: clinical correlation with the markers.

Leukocyte alkaline phosphatase (LAP) scores in peripheral blood and plasma carcinoembryonic antigen (CEA) levels were determined in 208 breast cancer patients with nonmetastatic disease. Patients were followed until clinical manifestations of metastases appeared. Then the LAP score and CEA level were analyzed in relation to the clinical appearance of metastases. Of the 208 patients studied, 58 developed metastases during the follow-up period. The LAP scores and CEA levels of this group of patients were compared to a control group of 60 breast cancer patients who did not develop metastases. Of the two markers, LAP score seems to be considerably more useful in detecting metastatic disease.

Adult↗

Induction of gamma-glutamyl transferase by dexamethasone in cultured fetal rat hepatocytes.

Hepatocytes isolated as a relatively pure population from normal fetal rats were maintained in primary monolayer culture for 4-10 days. Hepatocytes exhibited a small increase in basal gamma-glutamyl transferase (GGT) activity over time. Exposure to dexamethasone (10(-6) mol/l) elicited a rise in GGT activity after a lag of 24 h. The presence of the steroid was necessary to maintain induction, and its removal resulted in reversal of induction. The maximal response was 2- to 3-fold, 72 h after exposure to the steroid. After this maximal response, a gradual decay in enzyme activity occurred, despite the continuous presence of the hormone. Actinomycin D or cycloheximide given prior to/or simultaneously with the steroid prevented the induction, thus suggesting that both RNA and protein biosynthesis are necessary for induction to occur.

Animals↗

Heavy- and free light-chain myeloma associated with peripheral polyneuropathy.

Peripheral polyneuropathy, a rare complication of multiple myeloma, is generally associated with heavy-chain M-proteins and, in very rare instances, with free light-chain myeloma proteins. Here we describe a case of multiple myeloma and polyneuropathy with both monoclonal IgG and free lambda light chains in the blood. The patient also had free lambda light chains in the cerebrospinal fluid and urine.

Female↗

Valproic acid and the liver.

Valproic acid (VPA) is widely used as an anticonvulsant, but therapy with the drug has been associated with hepatotoxicity, either reversible hepatic dysfunction or irreversible hepatic failure. Both clinical and experimental studies have revealed several VPA-related biochemical abnormalities in the liver: inhibition of the beta-oxidation and synthesis of fatty acids and inhibition of gluconeogenesis, urea synthesis, oxidative phosphorylation, and the glycine cleavage system. Other abnormalities noted include alteration in the protein conformation of the internal mitochondrial membrane, hyperammonemia, and increased bile flow. The mechanisms of such hepatotoxicity, whether mediated by VPA or by its metabolites, are still little understood. Susceptibility to VPA hepatotoxicity may be enhanced by such conditions as starvation, inborn errors of metabolism, additional neurological disease, and concomitant administration of enzyme-inducing drugs.

Amino Acids↗

Trends in urolithiasis in various ethnic groups and by age, in Israel.

A survey of upper urinary tract stone composition was carried out over 8 years (1974-1982) in 1147 patients, following a previous survey (1966-1974). Trends in the development of stone formation were found. The most obvious differences were fewer pure calcium oxalate (0.75 versus 5.50%) and uric acid stones (6.11 versus 13.30%) and more mixed stones than in our previous study. In most ethnic groups urinary stones were composed of calcium oxalate/calcium phosphate. A higher prevalence of stones in Israeli-born Jews was noted, in comparison with our previous survey. Age group analysis showed this increase to be limited to the 21-50-year-old group, in contradistinction to a clear decrease in stone formation in Israeli-born Arabs and Jews under the age of 20 years.

Adult↗

RIA examinations of CSF hormones as a method of demonstrating leakage through the blood-brain and brain-CSF barriers.

Radioimmunoassay determinations of the levels of total T3, total T4, TSH, and prolactin in the CSF were performed on samples taken from 36 healthy individuals. The obtained reference values are the first of their kind. It is considered that RIA determinations of CSF hormone levels may provide a sensitive method for demonstrating pathological leakage through the blood-brain and brain-CSF barriers.

Blood-Brain Barrier↗