Developmental factors influencing interactions of drugs.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to S J Yaffe.
Explore the source record for details and available documents.
This report deals with quantitative and qualitative investigations of alkaline phosphatase in two unrelated infants with the severe infantile form of hypophosphatasia. Both affected infants had no detectable leukocyte alkaline phosphatase activities and both sets of parents and one sibling tended to have low but variable leukocyte enzyme activities. Normal duodenal juice alkaline phosphatase activity was present in the one patient in whom it was measured and a wide range of variation in enzymic activity was observed in the stools. There was no significant difference in the stool enzyme activity between both patients with hypophosphatasia (42.01 +/- 9.77 U) and control infants (40.55 +/- 6.29 U). However, the heterozygous parents had values significantly lower than the control adults (2.10 +/- 0.47 as compared with 19.10 +/- 4.44 U). Intestinal bacteria did not contribute significantly to the stool alkaline phosphatase activity. Enzyme activity was present in the bile of one of the patients and nearly absent in that of the other. Three "inducers" of alkaline phosphatase were given to both patients (phenobarbital, vitamin A, and corticosteroid). No clinical improvement or rise in serum alkaline phosphatase activity was observed during the trial of therapy with these agents. However, a significant increase in the activity of serum acid phosphatase was demonstrated during the course of vitamin A administration, suggesting an in vivo action of vitamin A on the lysosomes through decreasing the stability of the membrane and releasing acid phosphatase to the serum. Quantitative determination of tissue alkaline phosphatases from autopsy tissues was highly variable: no activity was found in bone, lungs, or spleen of either infant; there was a discrepancy in liver and kidney alkaline phosphatase values (zero in one patient and present in the other) and activity was present in the intestinal mucosa of both. Qualitative analysis of kidney, liver, and intestinal alkaline phosphatase revealed some differences between the patients and control subjects in heat inactivation and phenylalanine inhibition (Table 3). Starch gel electrophoresis of the liver preparation of one patient disclosed a single band which had greater mobility than that of six control subjects matched for age. Liver extracts from a premature and from full term newborns showed two bands. The single band of the patient's liver enzyme corresponded to the newborn's fast moving component. In addition, the intestinal enzyme prepared from the same patient had an extra band when compared with age-matched control subjects.
Benzo(a)pyrene hydroxylase activity was found in the bone marrow of control and 3MC-induced New Zealand white rabbits. This activity was localized in the microsomal fraction, was NADPH dependent and CO sensitive. The reaction was inhibited by 7,8-benzoflavone indicating that it was mediated by the 3MC-inducible form of cytochrome P-450. BP hydroxylase activity in rabbit bone marrow was located primarily in white cells, and was considerably higher than that previously reported for cultured human lymphocytes and monocytes. A possible role for the bone marrow mixed-function oxygenase in the production of hemopoietic toxicity is considered.
Alcohol dehydrogenase derived from the term human placenta was investigated in the 104,000xg supernatant fraction. Kinetic experiments yielded an average Vmax of 6.1 units, a Km of 5X10(-3)M and optimum activity at pH 10.0. Electrophoresis at pH 9.6 in glycine buffer showed four bands, however only two bands were observed at pH 8.6. Properties of this placental enzyme may be unique and its participation in the overall metabolic function of this tissue is unclear.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The first annual W. E. Upjohn Lecture concerned itself with the interrelationship between administration of drugs to the pregnant woman and fetal outcome. The epidemiology of drug intake (both prescribed and self-administered drugs) during pregnancy is reviewed, using data derived from several surveys conducted both in the United States and in Scotland. The complexities of establishing a causal relationship between drug intake during pregnancy and effects upon the fetus are considered. Special emphasis is given to the adverse effects of aspirin and cigarette smoking. The shortage of data is critical and the need for further research is stressed.
Explore the source record for details and available documents.
The compliance with treatment of acute otitis media in 300 pediatric outpatients was evaluated. Complete compliance in taking prescribed antibiotics was noted in 7.3% of the patients. Pharmacists dispensed less than prescribed amounts of antibiotics to 15% of patients. Bottles were incorrectly labeled 3% of the time. Volumes of 130 "teaspoons" examined varied from 2 to 9 ml. Parental understanding of the illness and of the effects of medication was inadequate and erroneous in many instances. Parents gave fewer than the prescribed number of doses in 36% of cases, and therapy was discontinued early in 37%. Recommendations for improving the quality of therapy for ambulatory pediatric patients are outlined.
Protein deficiency in post-suckling rats produced changes in the activity of hepatic drug-metabolizing enzymes. Significant decreases occurred in the N-demethylation of aminopyrine, in the azo-reduction of neoprontosil and in sulfokinase activity (using p-nitrophenylsulfate as SO4 donor). An increase was recorded for the glucuronidation of p-nitrophenol and no changes were noted in the hydroxylations of hexobarbital and aniline. Refeeding the animals for 3 weeks returned all activities to control values. An exception was the azo-reductase activity indicating either a slower recovery or a permanent change.
Evaluation of treatment given at home was studied in children with otitis media who were seen in an outpatient clinic. Full compliance was present in only 5% of the initial 100 patients (Study A). Practical factors limiting their compliance included inadequate dispensing of medication at drug stores, 15%; incorrect therapy schedule, 36%; early termination, 37%; spilled medicine, 7%; therapy shared, 5%. Because of these findings, a plan was implemented (Study B) in which hospital pharmacy personnel gave patient families verbal and written instructions for administering medications that were dispensed, together with a calibrated measuring device and a calendar to record doses taken. Full compliance was raised to 51% in this pilot group (of 33 patients) as compared with 8.5% in 20 concurrent controls who went to neighborhood drug stores. The importance of detailed therapy instructions is stressed. The potential role of the pharmacist in improving compliance is demonstrated.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Single oral doses of 6.25 mg/kg of dicloxacillin suspension were given to ten cystic fibrosis (CF) patients and eight normal subjects. Peak serum concentrations and areas under the concentration versus time curves for dicloxacillin were variable and, on average, were 2 1/2 times lower in the CF patients. The time of occurrence of the peak serum concentration was similar in both groups and the total urinary recovery of dicloxacillin was normal or increased in the CF patients, suggesting that the intestinal absorption of the drug was unaffected by the disease. The low serum concentrations in the CF patients were caused by unusually high renal clearances of dicloxacillin which average 282 +/- 135 compared to 95 +/- 28 ml/min/1.73 sq m in the normal subjects. Creatinine clearances were also elevated in the CF patients by 55% on average, while urea clearances were normal. The serum protein binding of dicloxacillin was similar in both groups of subjects. Because the rapid excretion results in low and variable serum concentrations of the antibiotic, treatment of CF patients with dicloxacillin may warrant use of increased or more frequent doses and monitoring of serum antibiotic levels.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.