Urinary excretion of meso-2,3-dimercaptosuccinic acid in human subjects.

The urinary excretion of meso-2,3-dimercaptosuccinic acid (DMSA), which is an effective chelating agent for lead, was determined after the oral administration of 10 mg DMSA/kg to six normal young men. The DMSA that was absorbed was extensively biotransformed. After 14 hours only 2.53% of the administered DMSA was excreted in the urine as unaltered DMSA and 18.1% as altered forms. The unaltered DMSA was 12% of the total DMSA found in the urine. The altered form(s) of DMSA was 88% of the total urinary DMSA. The altered DMSA can be converted to unaltered DMSA by electrolytic reduction, which indicates that the altered forms of DMSA are disulfides. The excretion of altered DMSA reached a peak between 2 and 4 hours after DMSA administration. There were small but statistically significant increases in the excretion of zinc, copper, and lead after DMSA administration. DMSA did not influence the urinary excretion of 27 other metals and elements.

Kinetics of theophylline; variability and effect of arterial pH in chronic obstructive lung disease.

The pharmacokinetic behavior of theophylline was determined in 12 patients during an acute exacerbation of their chronic obstructive pulmonary disease. A 5.6 mg/kg loading dose of aminophylilne was administered, followed three hours later by a 0.9 mg/kg/hr continuous infusion. The loading dose increased the serum theophylline level an average of only 5.77 microgram/ml. After the loading dose, only five patients had levels greater than 10 microgram/ml. Mean initial drug clearance was 0.77 L/kg/hr, half-life 9.1 hr, and apparent volume of drug distribution .887 L/kg. Wide inter- and intrapatient pharmacokinetic variability was observed. The variability of drug distribution was inversely correlated with the arterial pH. These patients with chronic obstructive pulmonary disease appeared to require more theophylline when acidemic than when alkalemic to achieve similar serum theophylline concentrations.

Effect of pH on theophylline transfer across the everted rat jejunum.

The effect of pH on the cumulative transfer of theophylline across the everted rat jejunum in vitro was investigated. Intestinal integrity was assessed by light and scanning electron microscopy, while the biochemical viability of the intestine was evaluated using glucose transfer measurements. The initial (0-30 min) clearance of theophylline was directly proportional to the fraction un-ionized at pH 5.5, 7.4, 8.0, and 10.0. Plots of cumulative theophylline transfer versus time over 60 min were nonlinear, but could be subdivided into two linear segments of 30-min duration. Due to this nonlinearity, differences in theophylline transfer with pH were significant only over the first 30 min of the experiment. Intestinal tissue integrity and viability correlated with the time at which the clearance (slope) increased, while the magnitude of the increase in clearance was proportional to the degree of ionization of theophylline.

Flame atomic absorption spectrometric determination of serum zinc: collaborative study.

A method for determining serum zinc concentrations was collaboratively studied by 9 laboratories. Serum samples in polypropylene tubes are directly diluted with 0.03% Brij 35, and zinc is determined by flame atomic absorption spectrophotometry (AAS). A certified standard reference material serves as an external control. Repeatability relative standard deviations (RSDr) were 1.2 and 11.4% and reproducibility relative standard deviations (RSDR) were 6.1 and 12.9% for serum zinc concentrations of 6.36 and 0.63 micrograms/mL, respectively. The method has been approved interim official first action by AOAC.

Maternal perceptions of pediatric providers for children with chronic illnesses.

OBJECTIVE: To identify maternal perceptions of general and subspecialty pediatric providers of children with selected chronic illnesses. METHOD: Cross-sectional analyses of survey data. Sample was recruited from eight specialty and four general pediatric practices in an urban setting. Interviews were conducted with mothers of 159 children with one of four chronic illnesses: sickle cell anemia, cystic fibrosis, diabetes, and moderate/severe asthma. About 56% of the participants were white; 40% were African-American; 11% were receiving public assistance. The main outcome measures were maternal reports of which pediatric providers: are visited in the past year, are seen most frequently, have been seen over the longest period of time, relied on most, and know their family best. Rates of dissatisfaction with these providers are also reported. RESULTS: Overall, more mothers reported that they relied on their general pediatric providers, saw them more frequently, and had longer relationships with them than their subspecialty pediatric providers. However, mothers were more satisfied with the care they received from their subspecialty providers than from their primary care providers. CONCLUSIONS: Our findings illustrate the complexity of maternal perceptions of the different roles that general and subspecialty pediatric providers play in the care of children with chronic illness.

Are women carrying "basketballs" really having boys? Testing pregnancy folklore.

BACKGROUND: Antenatal ascertainment of fetal sex is a common feature of modern pregnancies. Women who opt not to learn fetal sex typically employ a variety of methods to forecast it. This study investigated the validity of prevalent folklore used to identify fetal sex before birth. METHOD: One hundred four pregnant women, who did not know the sex of the fetus, were administered a questionnaire to explore their perceptions of fetal sex and the basis for these predictions. RESULTS: Fetal sex was not systematically related to the shape of the woman's abdomen, prevalence of morning sickness, or comparisons with previous pregnancies. However, women who had more than twelve years of education correctly predicted fetal sex greater than chance (71% correct), in contrast to less educated women (43% correct). Contrary to expectations, women whose forecasts were based on psychological criteria (i.e., dreams or feelings) were more likely to be correct than those employing prevalent folklore criteria (i.e., the way a woman was carrying the pregnancy). CONCLUSIONS: In general, women were not good predictors of fetal sex. The mechanisms that promote maternal accuracy in predicting fetal sex for highly educated women are unknown. It is reasonable to expect that maternal perceptions of fetal sex contribute to the process of fetal attachment.

Pharmacokinetics of o-nitroanisole in Fischer 344 rats.

The pharmacokinetics and metabolism of o-nitroanisole (ONA) were studied in male Fischer 344 rats. Three dose levels of [14C]ONA (5.0, 50, or 500 mg/kg) were administered orally to rats and daily excreta were analyzed for 14C. Since the highest dose altered the urinary excretion rate of ONA, a dose of 25 mg/kg was used for subsequent pharmacokinetic studies. Following a single 25 mg/kg iv dose of [14C]ONA, blood, tissues, and excreta were collected at times ranging from 15 min to 7 days. Urinary excretion accounted for 82% of the dose by 24 hr and 86% by 7 days. Fecal excretion was 7.5% in 24 hr and 9.0% by 7 days. Fifteen min after ONA administration, most of the 14C content was found in muscle (20%), skin (10%), adipose tissue (6.8%), and blood (6.5%). All other tissues contained less than 5% of the dose. Within 8 hr, less than 1% of the dose was present in any tissue. The initial elimination t1/2 for 14C in all tissues was 1-2 hr and the terminal t1/2 was approximately 4 days. The elimination of parent ONA from blood followed first order biphasic elimination kinetics (initial t1/2 = 30 min; terminal t1/2 = 2.2 hr). Parent ONA was rapidly eliminated from all other tissues in a monophasic manner (t1/2 = 15 min to 2 hr). Skin and fat demonstrated an uptake phase prior to the elimination of parent. Only 0.5% of the dose was excreted as ONA in the urine. Urinary metabolites of ONA were predominantly conjugated compounds (63% as sulfates; 11% as glucuronides).

Detection of picogram levels of sufentanil by capillary gas chromatography.

Sufentanil and its two primary metabolites, N-(4-[methoxymethyl]-4-piperidinyl)-N-phenyl propanamide (MPPP), and N-(4[hydroxymethyl]-1-[2-thienylethyl]-4-piperidinyl)-N-phenyl propanamide (desmethyl sufentanil), were detected by capillary gas chromatography with a nitrogen-phosphorous detector. The detection limit for sufentanil and its metabolites is 30-50 pg/ml with minimal interfering substances in the chromatograms. This method allowed for the detection of serum sufentanil in the terminal elimination phase of sufentanil in a patient receiving 1.5 micrograms/kg and will allow for studies to determine the pharmacokinetics and metabolism of sufentanil in a wide variety of patient groups now receiving this agent.

Choroid plexus protects cerebrospinal fluid against toxic metals.

Although heavy metal ions are known to be toxic to the central nervous system (CNS), the mechanisms by which the CNS may protect itself from initial challenges of such toxic ions is unknown. The choroid plexus is the principal site of formation of the cerebrospinal fluid (CSF) which bathes the brain. We have determined in rats and rabbits that after intraperitoneal administration of lead, cadmium, mercury, and arsenic compounds, these toxic metal ions accumulated in the lateral choroid plexus at concentrations of Pb, Hg, and As that were 70-, 95-, and 40-fold higher, respectively, than those found in the CSF. Cd was not detected in the CSF. In addition, concentrations of these heavy metal ions were found to be many fold greater in the choroid plexus than in the brain or blood. The accumulation of Pb in the choroid plexus was dose-dependent and time-related. When the choroid plexus was preincubated, in vitro, with ouabain (1.5 mM), the uptake of Cd from the CSF side of the choroid plexus was inhibited 57%. Cadmium metallothionein was not found in the choroid plexus. Whereas the concentration of reduced glutathione in the choroid plexus was less than that in the brain cortex, the concentration of cystine was fourfold greater. The lateral choroid plexus sequesters Pb, Cd, As, and Hg. It appears to be one of the important mechanisms that protects the CSF and the brain from the fluxes of toxic heavy metals in the blood.