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Biomedical subjects

L A Kaplan

Publications and source records attributed to L A Kaplan.

At least 37 records · Page 2Linked to original sources
PubMed1992

The clinical development of ondansetron for use in the prevention and treatment of postoperative nausea and vomiting.

An international clinical trial programme has been established to assess the efficacy and safety of ondansetron in the prevention and treatment of postoperative nausea and vomiting. The programme included nine pilot studies and six key placebo-controlled studies. These studies have evaluated both oral and intravenous formulations of ondansetron in the prevention of postoperative nausea and vomiting, and intravenously administered ondansetron in the treatment of established symptoms. Most patients included in the trials were adult women, less than 50 years of age, receiving anaesthesia for gynaecological surgery. The primary efficacy analysis for emesis was based on the assessment of complete response (i.e. absence of emetic episodes or nausea in the first 24 h postoperatively). These trials clearly demonstrated the anti-emetic efficacy of ondansetron in the prevention and treatment of postoperative nausea and vomiting.

Clinical Trials as Topic↗
PubMed1992

Sequential serum aluminum and urine aluminum: creatinine ratio and tissue aluminum loading in infants with fractures/rickets.

Aluminum toxicity is associated with the development of bone disorders, including fractures, osteopenia, and osteomalacia. Fifty-one infants with a mean (+/- SEM) birth weight of 1007 +/- 34 g, gestational age of 28.5 +/- 0.3 weeks, and serial radiographic documentation at 3, 6, 9, and 12 months for the presence (n = 16) or absence (n = 35) of fractures and/or rickets were studied at the same intervals to determine the serial changes in serum aluminum concentrations and urine aluminum-creatinine ratios. Autopsy bone samples were used to determine the presence of tissue aluminum. Serum aluminum concentrations from 46 infants were stable and similar between groups, with mean values between 15 and 22 micrograms/L. Urine aluminum-creatinine (micrograms per milligram) ratios from 14 infants were higher in infants with fractures and/or rickets (0.26 +/- 0.06 vs 0.12 +/- 0.04) at onset, and rate of decrease in aluminum-creatinine ratio was faster in infants without fractures and/or rickets. All but three infants were tolerating complete enteral feeding at all sampling points. One infant who received aluminum-containing antacid had marked increase in serum aluminum to 83 micrograms/L while urine aluminum-creatinine ratio increased from 0.09 to a peak of 8.53. Vertebrae from three infants at autopsy (full enteral feeding was tolerated for 37 and 41 days in two infants, respectively) showed aluminum deposition in the zone of provisional calcification and along the newly formed trabecula.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum↗
PubMed1991

Nitrosodiethylamine metabolism in the viviparous fish Poeciliopsis: evidence for the existence of liver P450pj activity and expression.

Several species of fish from the genus Poeciliopsis differ dramatically in their response to the carcinogen N-nitrosodiethylamine (NDEA). The differential induction of tumors among genotypes exposed to NDEA may, in part, result from differences in liver cytochrome P450pj activity (the piscine equivalent of mammalian P450j). Evidence for the existence of cytochrome P450pj activity and mRNA expression has been found in several Poeciliopsis genotypes (species and strains). Biochemical evidence suggests that a microsomal cytochrome P450 enzyme catalyzes the metabolism of NDEA to acetaldehyde and other intermediates in Poeciliopsis. This reaction was inhibited by carbon monoxide, and required molecular oxygen and reducing equivalents (NADPH). Differences were found in maximal activity as well as temperature optima among genotypes. Poeciliopsis, a livebearing fish from desert streams of northwestern Mexico, appears to have thermal optima for cytochrome P450pj activity between 25 and 30 degrees C depending on the genotype. Western blot analysis (using anti-rat P450IIE1 antibodies) detected a 55-60 kd band in microsomes isolated from rat and Poeciliopsis. Using a 49mer probe specific for rat cytochrome P450j, Northern blots revealed a 3.3 kb mRNA from livers of a Poeciliopsis genotype and rat, but none in muscle mRNA from either organism. S1 nuclease protection assays, using the same probe, revealed that a mRNA fragment protected by the probe against digestion was induced on exposure of the whole organism to ethanol (via uptake from the aquatic environment). The assays also demonstrated that ethanol treatments both induced and suppressed this mRNA, depending on concentration and exposure time.

Animals↗
PubMed1991

Chylomicron-retinyl palmitate clearance in type I hyperlipidemic families.

Our primary aim was to determine the extent to which intraplasmic retinyl palmitate (RP) transfers to other lipoprotein particles when chylomicron remnants are not produced and/or the plasma RP residence time is increased. The study was conducted on three familial type I hyperlipoproteinemic patients, four lipoprotein lipase (LpL)-deficient heterozygotes, and three controls on a metabolic research unit. To each subject, a fat load was administered containing 16% of total daily calories in type I patients, 40% in heterozygotes and controls, plus 60,000 U/m2 vitamin A. Triglyceride (TG) and RP levels were evaluated in chylomicron and nonchylomicron fractions. Delay in the clearance of chylomicron fraction RP and the marked deficiency in nonchylomicron-RP (presumed lack of remnant production) in all three type I patients suggests that RP does not demonstrate significant intraplasmic transfer from chylomicrons to existent apolipoprotein B100 particles. In contrast to noncoincident TG and RP peaking in the normal subject, heterozygotes were found to demonstrate coincident plasma TG and RP curves, which is consistent with a common catabolic pathway for both TG and RP and inconsistent with intraplasmic RP transfer. This corroborates reports on compromised chylomicron clearance in heterozygotes. We conclude that RP is an appropriate representative marker for intestinally derived particles in LpL-deficient or partially deficient individuals.

Adolescent↗
PubMed1991

Plasma catecholamine levels in cyclic antidepressant overdose.

Cyclic antidepressant overdose is a major cause of morbidity and mortality in self-poisoned patients. The major cause of mortality with cyclic antidepressant overdose is cardiotoxicity. We determined plasma catecholamine levels in 41 symptomatic acute overdose patients to identify interactions between QRS duration (a marker for cardiotoxicity) and a presumed hyper-adrenergic state. Using a linear multivariable regression analysis, QRS duration correlated with the presence of cyclic antidepressant, plasma norepinephrine levels, the ratio of norepinephrine to epinephrine level, and pulse rate (p less than 0.001, r2 = 0.42). Commensurate physiologic changes were not found in the presence of elevated catecholamine levels in the cyclic antidepressant overdose group. One possible explanation for the blunted systemic response to the elevated catecholamine levels is adrenergic desensitization. Investigation of serial catecholamine levels during cyclic antidepressant overdose may lead to modification of our current theories of cardiotoxicity and therapy.

Adolescent↗
PubMed1990

Carotenoid composition, concentrations, and relationships in various human organs.

The carotenoid content of 10 different organs obtained at autopsy from 16 humans was determined using a high-performance liquid chromatography assay. The same qualitative pattern of carotenoids found in serum was found for all the tissues, although there were important quantitative differences in the different carotenoids between organs. The median levels of zeaxanthins, lycopene and beta-carotene varied disproportionately between organs; similar levels of one carotenoid for two organs would not predict similar levels of another carotenoid for the same organs. Similarly, there was not a consistent relationship between all the carotenoids for a given organ. The uneven but wide tissue distribution of most dietary carotenoids may indicate an active biological role for these compounds.

Adult↗
PubMed1989

Initiation of cell proliferation in livers of the viviparous fish Poeciliopsis lucida with 7,12-dimethylbenz[a]anthracene.

Stimulation of liver cell proliferation by sublethal exposures to 7,12-dimethylbenz[a]anthracene (DMBA) is examined in the small, viviparous fish Poeciliopsis lucida. Poeciliopsis is susceptible to induction of liver tumors by repeated short-term exposures, under 24 hr, to waterborne DMBA at 5 ppm. Exposures to 5 ppm for 24 hr was lethal to fish under 1 month old and resulted in 60% mortality of adult females 20-25 mm in length. Response to 16-, 20-, and 22-hr exposures of 5 ppm DMBA, as measured by mitotic index, was similar in females of two size classes, 20-25 mm and 26-30 mm. Differences were observed in the onset of mitosis in livers of fish exposed for 16 hr vs 20 or 22 hr. Hepatocyte proliferation did not begin until 10-11 days after the 16-hr exposure and lasted for only 3 days. When exposure was increased to 20 or 22 hr, mitotic activity was observed earlier, 2 days following treatment, and continued for 6-8 days. The peak period of cell proliferation also varied, occurring 12 days after a 16-hr exposure, 4 days after a 20-hr exposure, and at least 10 days after a 22-hr exposure. The mitotic index was the highest on the final day specimens of the 22-hr treatment were collected. These results suggest that the toxic properties of DMBA in stimulating cell proliferation may function as an important cofactor in hepatocarcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1989

Effect of transport conditions on the stability of biochemical markers in blood.

We examined the stability of lipids, carotenoids, alpha-tocopherol, and endogenous hormones in plasma prepared from whole blood that had been mailed to a central location for processing. Initially, to simulate transport conditions, whole-blood samples were stored in the laboratory, either at room temperature or cooled, for up to 72 h before processing. In the latter samples, lipid concentrations changed up to 1.4% per day, carotenoids up to -5.5%, and hormones up to 9.5%. In a second study, analyte concentrations in plasma from cooled whole blood mailed via overnight courier were compared with those from plasma that had been immediately separated, frozen, and mailed via overnight courier. Concentrations of cholesterol, high-density lipoprotein subfraction 3, apolipoprotein B, and retinol were stable. Overall, for each marker except estradiol, the between-person variation was at least twice the within-person variation. In a third study, at least 340 micrograms of DNA was recovered from 30 mL of cool-shipped whole blood. Our results indicate that shipping whole-blood samples by overnight courier is feasible for assay of several biochemical markers of interest in epidemiological research.

Adult↗
PubMed1989

Multicenter evaluation of TDx test for assessing fetal lung maturity.

"TDx Fetal Lung Maturity," an automated assay that measures the relative concentrations of surfactant and albumin in amniotic fluid, was compared with the lecithin/sphingomyelin (L/S) ratio and phosphatidylglycerol determination at five clinical sites. A total of 695 amniotic fluid samples were analyzed, of which 312 were followed by delivery of the infant within three days of sample collection. Of these 312, 24 developed respiratory distress syndrome and seven developed transient tachypnea. With the cutoff for maturity set at a surfactant/albumin value of 50 mg/g, the assay showed a sensitivity of 0.96 and a specificity of 0.88 for all samples, compared with a sensitivity of 0.96 and a specificity of 0.83 for the L/S ratio. The combination of rapid assay (30 min), accurate results, and uniformity among testing centers makes the TDx assay a very promising method.

Albumins↗
PubMed1988

Hyperthermia, hypertension, hypertonia, and coma in a massive thioridazine overdose.

This report characterizes an atypical presentation of a thioridazine overdose. Clinical manifestations included wide Q.R.S. complex, hyperthermia, hypertension, hypertonia, and coma. Plasma catecholamine levels were markedly elevated. The patient was treated with dantrolene sodium and supportive care. The patient's condition improved over time, with questionable response to dantrolene sodium. Supportive care was the mainstay of treatment.

Acute Disease↗
PubMed1988

Aluminum and bone disorders: with specific reference to aluminum contamination of infant nutrients.

Aluminum (Al) impairment of bone matrix formation and mineralization may be mediated by its direct effect on bone cells or indirectly by its effect on parathyroid hormone and calcium metabolism. Its toxic effects are proportional to tissue Al load. Al contamination of nutrients depends on the amount of Al present naturally in chemicals or from the manufacturing process. Intravenous calcium, phosphorus, and albumin solutions have high Al (greater than 500 micrograms/L), whereas crystalline amino acid, sterile water, and dextrose water have low Al (less than 50 micrograms/L) content. Enteral nutrients including human and whole cow milk have low Al, whereas highly processed infant formulas with multiple additives, such as soy formula, preterm infant formula, and formulas for specific disorders are heavily contaminated with Al. Healthy adults are in zero balance for Al. The gastrointestinal tract excludes greater than 95% of dietary Al, and kidney is the dominant organ for Al excretion. However, even with normal renal function, only 30-60% of an Al load from parenteral nutrition is excreted in the urine, resulting in tissue accumulation of Al. The risk for Al toxicity is greatest in infants with chronic renal insufficiency, recipients of long term parenteral nutrition, i.e., no gut barrier to Al loading, and preterm infants with low Al binding capacity. The rapid growth of the infant would theoretically potentiate Al toxicity in all infants, although the critical level of Al loading causing bone disorders is not known. To minimize tissue burden, Al content of infant nutrients should be similar to "background" levels, i.e., similar to whole milk (less than 50 micrograms/L).

Aluminum↗
PubMed1988

The relation of diet, cigarette smoking, and alcohol consumption to plasma beta-carotene and alpha-tocopherol levels.

The relation of diet and nutritional supplements, cigarette use, alcohol consumption, and blood lipids to plasma levels of beta-carotene and alpha-tocopherol was studied among 330 men and women aged 18-79 years. Dietary carotene, preformed vitamin A, and vitamin E intake were estimated by a self-administered semiquantitative food frequency questionnaire. The correlation of dietary carotene with plasma beta-carotene was reduced in smokers compared with nonsmokers (r = 0.02 vs. 0.44 among men; r = 0.19 vs. 0.45 among women). Smokers had much lower plasma levels of beta-carotene than did nonsmokers (geometric mean 8.5 vs. 15.3 micrograms/dl for men; 17.3 vs. 26.3 micrograms/dl for women) despite only slightly lower intakes of carotenoids. In multiple regression analyses, men who smoked one pack per day had 72% (95% confidence interval (CI) 58-89) of the plasma beta-carotene levels of nonsmokers after accounting for dietary carotene and other variables; for women, the corresponding percentage was 79% (CI 64-99). In similar models, men drinking 20 g of alcohol per day had 76% (CI 65-88) of the beta-carotene levels of nondrinkers; women had 89% (CI 73-108) of the levels of nondrinkers. An interaction term for carotene intake and smoking was statistically significant in a model combining both sexes. These results suggest that plasma levels of beta-carotene among smokers and, perhaps, heavy consumers of alcohol may be reduced substantially below levels due to differences in diet. The correlation of calorie-adjusted intake of vitamin E with lipid-adjusted plasma levels of vitamin alpha-tocopherol was 0.53 for men (n = 137) and 0.51 for women (n = 193) and did not differ by alcohol consumption and cigarette use; these correlations were largely accounted for by use of vitamin supplements. In linear regression models, vitamin E intake and plasma lipids were significant predictors of plasma alpha-tocopherol levels.

Adolescent↗
PubMed1987

Reference ranges of retinol, tocopherols, lycopene and alpha- and beta-carotene in plasma by simultaneous high-performance liquid chromatographic analysis.

Using a high-performance liquid chromatographic procedure, age- and gender-based reference ranges for plasma retinol, alpha- and gamma-tocopherol, lycopene, and alpha- and beta-carotene have been established. In addition to confirming higher retinol levels in men than in women (p less than 0.001), this study demonstrates significantly higher plasma levels of both carotenes in women than in men (p less than 0.001). The plasma levels of retinol and beta-carotene showed a positive relationship with age after adjusting for plasma lipids (p less than 0.001 and p less than 0.02, respectively). In contrast to beta-carotene, there was no gender difference for plasma lycopene and a strong (p less than 0.001) inverse relationship of lycopene with age. These results suggest that differences may exist between beta-carotene and lycopene in their intestinal absorption, plasma transport, or tissue metabolism.

Adolescent↗
PubMed1986

Response to aluminum in parenteral nutrition during infancy.

The response to aluminum loading from parenteral nutrition (PN) solutions was determined in 20 infants with gestational ages 29 to 41 weeks and birth weights 880 to 3630 gm. Mean duration of PN was 43 days (range 5 to 175 days). Ten infants received a high Al load (from an experimental high calcium- and phosphorus-containing PN solution, with a measured Al content of 306 +/- 26 micrograms/L (mean +/- SE), n = 11), for up to 6 weeks. Ten infants received a lower Al load (from standard Ca-P solutions, measured Al content 144 +/- 16 micrograms/L, n = 11). Five infants received PN with a low Al load for longer than 6 weeks. The mean urine Al/creatinine (Cr) ratio (micrograms/mg) increased threefold, from 0.3 +/- 0.09 to 0.97 +/- 0.17 during PN in the entire group (P less than 0.001), and was significantly higher in infants who received greater Al loading (P less than 0.001). There was no significant difference between preterm and term infants in the rate of change in urine Al/Cr during the study. Urine Al was calculated to account for less than 50% of Al load. During the study, serum Al concentrations ranged from 6 to 318 micrograms/L (median 37 micrograms/L, compared with the median 18 micrograms/L for normal infants and children). Serum Al concentrations were not significantly changed during the study, or between infants in high or lower Al loading groups. Vertebrae from autopsy of two infants who received the lower Al containing PN for 71 and 152 days, respectively, stained positive for Al at the bone mineralization front. Thus, currently used PN solutions are contaminated with Al, urine Al concentration is higher with higher Al loading, and is not different in term and preterm infants. We suggest that renal elimination of Al in infants is incomplete, as assessed by lower urine Al excretion versus load, elevated serum Al concentration, and bone deposition of Al.

Aluminum↗
PubMed1985

Clinical utility of serum prostatic acid phosphatase measurements for detection (screening), diagnosis, and therapeutic monitoring of prostatic carcinoma; assessment of monoclonal and polyclonal enzymes and radioimmunoassays.

Serum prostatic acid phosphatase (PAP), measured by three different technics, was used to screen 560 men over 50 years of age for prostatic cancer. All three PAP procedures failed to detect the one subject found to have prostatic cancer on physical examination and confirmed by biopsy, and all assays had a significant number of "falsely" elevated PAP levels. Four PAP assays were assessed in 80 men undergoing prostatic biopsy/removal in whom histologic examination of prostatic tissue was made. Clinical sensitivity and specificity for detecting those patients with and without prostatic cancer ranged from 20-57% and 54-95%, respectively, with the monoclonal enzyme immunoassay being the most sensitive but the least specific, and the traditional enzyme assay being the most specific but insensitive. In men with diagnosed prostatic cancer undergoing radiation or chemotherapy, the assays were useful in distinguishing between those with active and inactive disease. The authors conclude that serum PAP assays, irrespective of the type of procedure used, has no place in screening for prostatic cancer, a minimal role in establishing a definitive diagnosis, but a useful role in monitoring therapy.

Acid Phosphatase↗
PubMed1985

Bacterial biomass, metabolic state, and activity in stream sediments: relation to environmental variables and multiple assay comparisons.

Bacterial biomass, metabolic condition, and activity were measured over a 16-month period in the surface sediments of the following four field sites with differing dissolved organic matter regimes: a woodlot spring seep, a meadow spring seep, a second-order stream, and a third-order stream. Total bacterial biomass was measured by lipid phosphate and epifluorescence microscopic counts (EMC), and viable biomass was measured by C most probable number, EMC with 2-(p-iodophenyl)-3-(p-nitrophenyl)-5-phenyl tetrazolium chloride reduction, and ATP. Bacterial metabolic condition was determined from the percentage of respiring cells, poly-beta-hydroxybutyrate concentrations, and adenylate energy charge. Activity measures included C-lipid synthesis, P-phospholipid synthesis, the rate of uptake of algal lysate dissolved organic carbon, and respiration, from which biosynthesis was calculated (dissolved organic carbon uptake corrected for respiration). Total bacterial biomass (from EMC) ranged from 0.012 to 0.354 mug of C/mg of dry sediment and was usually lowest in the third-order stream. The percentage of cells respiring was less than 25% at all sites, indicating that most bacteria were dormant or dead. Adenylate energy charge was measured only in the third-order stream and was uniformly low. Poly-beta-hydroxybutyrate concentrations were greater in the woodlot spring seep than in the second- and third-order streams. Uptake of algal lysate dissolved organic carbon ranged from undetectable levels to 166 mg of C . m . h. Little community respiration could be attributed to algal lysate metabolism. Phospholipid synthesis ranged from 0.006 to 0.354 pmol . mg of dry sediment . h. Phospholipid synthesis rates were used to estimate bacterial turnover at the study sites. An estimated 375 bacterial generations per year were produced in the woodlot spring seep, and 67 per year were produced in the third-order stream.

Journal Article↗
PubMed1984

High-performance liquid chromatographic determination of sulfinpyrazone and its metabolites in plasma.

A specific sensitive reversed-phase high-performance liquid chromatographic method for simultaneous determination of sulfinpyrazone (Anturane) and five of its metabolites (p-hydroxy-sulfinpyrazone, p-hydroxy-sulfone, sulfone, p-hydroxy-sulfide, and sulfide) in plasma is described. The compounds were extracted from plasma, back-extracted, re-extracted and separated on a 10-micron muBondapak C18 column using 10 mmol/l orthophosphoric acid-acetonitrile-ethanol as the mobile phase. Phenylbutazone was used as internal standard, which was totally separated from all other compounds. The lower limit of sensitivity for sulfinpyrazone, sulfone, p-hydroxy-sulfide and sulfide is 30 ng/ml, and 100 ng/ml for p-hydroxy-sulfinpyrazone and p-hydroxy-sulfone. Concentrations of sulfinpyrazone between 0.5 and 25 micrograms/ml were measured with an average coefficient of variation of 5.1%. Examples of application of this assay are given.

Animals↗