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Biomedical subjects

M Mirochnick

Publications and source records attributed to M Mirochnick.

28 records · Page 2Linked to original sources
PubMed1996

Dapsone penetrates cerebrospinal fluid during Pneumocystis carinii pneumonia prophylaxis.

Dapsone has been proposed as a prophylactic agent for both Pneumocystis carinii pneumonia (PCP) and reactivation cerebral toxoplasmosis. To determine whether dapsone penetrates the central nervous system, cerebrospinal fluid (CSF) and serum samples were drawn from patients taking dapsone for PCP prophylaxis. These samples were quantitatively assayed using high-performance liquid chromatography. Five AIDS patients and one cardiac transplant patient had CSF assayed for dapsone. Only one had evidence of CSF inflammation, resulting from a paraspinal abscess. Doses ranged from 50 mg 3 days/week to 100 mg/day, and levels were 0.30-1.61 mu g/ml, which are in the range of inhibition of Toxoplasma gondii tachyzoites. This is the first report to demonstrate that dapsone enters the CSF, and supports preliminary clinical evidence that dapsone may have protective activity against cerebral toxoplasmosis when used for PCP prophylaxis.

Adult↗
PubMed1996

Late dose-response effects of prenatal cocaine exposure on newborn neurobehavioral performance.

OBJECTIVE: To determine in a representative sample of full-term urban newborns of English-speaking mothers whether an immediate or late dose-response effect could be demonstrated between prenatal cocaine exposure and newborn neurobehavioral performance, controlling for confounding factors. METHODS: The Neonatal Behavioral Assessment Scale (NBAS) was administered by masked examiners to a total sample of 251 clinically healthy, full-term infants at 2 days and/or 17 days. Three in utero cocaine exposure groups were defined: heavily exposed (n = 44, > 75th percentile self-reported days of use during pregnancy and/or > 75th percentile of meconium benzoylecognine concentration); lightly exposed (n = 79, less than both 75th percentiles); and unexposed (n = 101, no positive biological or self-report marker). At the 3-week examination there were 38 heavily exposed, 73 lightly exposed, and 94 unexposed infants. Controlling for infant birth weight, gestational age, infant age at the time of examination, mothers' age, perinatal risk, obstetric medication, and alcohol, marijuana, and cigarette use, a regression analysis evaluated the effects of levels of cocaine exposure on NBAS performance. RESULTS: No neurobehavioral effects of exposure on the newborn NBAS cluster scores or on the qualifier scores were found when confounders were controlled for at 2 to 3 days of age. At 3 weeks, after controlling for covariates, a significant dose effect was observed, with heavily exposed infants showing poorer state regulation and greater excitability. CONCLUSIONS: These findings demonstrate specific dose-related effects of cocaine on 3-week neurobehavioral performance, particularly for the regulation of arousal, which was not observed in the first few days of life.

Cannabis↗
PubMed1995

Relation between meconium concentration of the cocaine metabolite benzoylecgonine and fetal growth.

Among 95 term infants with benzoylecgonine, the cocaine metabolite, detectable in their meconium, there was an inverse relation between the concentration of benzoylecgonine and birth weight, length, and head circumference. Multiple regression analysis confirmed these relations after controlling for gestational age and maternal use of marijuana, cigarettes, and alcohol. These data suggest a dose-response relation between the magnitude of prenatal cocaine exposure and impaired fetal growth.

Birth Weight↗
PubMed1993

Phase I evaluation of zidovudine administered to infants exposed at birth to the human immunodeficiency virus.

This study evaluated the safety, tolerability, and pharmacokinetics of zidovudine administered intravenously and orally to infants born to women infected with the human immunodeficiency virus. Thirty-two symptom-free infants were enrolled before 3 months of age. The pharmacokinetics of zidovudine were evaluated in each infant after single intravenously and orally administered doses of zidovudine on consecutive days, and during long-term oral administration of the drug for 4 to 6 weeks. As new patients were enrolled, doses of zidovudine were progressively increased from 2 to 4 mg/kg. Therapy was continued for up to 12 months in 7 of the infants proved to be infected with human immunodeficiency virus. Zidovudine was generally well tolerated; 20 children (62.5%) had anemia (hemoglobin level < 10.0 gm/dl) during therapy and 9 (28.1%) had neutropenia (neutrophil count < or = 750 cells/mm3); these hematologic abnormalities usually resolved spontaneously. The total body clearance of zidovudine increased significantly with age, from an average of 10.9 ml/min per kilogram in infants < or = 14 days of age to 19.0 ml/min per kilogram in older infants (p < 0.0001). Concurrently, there was a significant decrease in serum half-life from 3.12 hours in infants < or = 14 days to 1.87 hours in older infants (p = 0.0002). Oral absorption was satisfactory and bioavailability decreased significantly with age, from 89% in infants < or = 14 days to 61% in those > 14 days of age (p = 0.0002). Plasma concentrations of zidovudine were calculated to be in excess of 1 mumol/L (0.267 micrograms/ml) for 4.12 +/- 1.86 hours and 2.25 +/- 0.78 hours after oral doses of 2 mg/kg in infants younger than 2 weeks and 3 mg/kg in older infants, respectively. We conclude that zidovudine administered at oral doses of 2 mg/kg every 6 hours to infants aged less than 2 weeks and 3 mg/kg every 6 hours to infants older than 2 weeks resulted in plasma concentrations that are considered virustatic against human immunodeficiency virus. Zidovudine was well tolerated by infants at these doses.

Administration, Oral↗
PubMed1993

Pharmacokinetics of dapsone in children.

We studied dapsone pharmacokinetics in eight children with compromised immune function who were receiving three different preparations. Peak serum concentration was less than 0.25 microgram/ml after doses of an extemporaneous liquid preparation but ranged from 0.72 to 1.33 micrograms/ml after initial tablet or proprietary liquid doses and 1.48 to 2.48 microgram/ml during long-term proprietary liquid administration. Elimination followed first-order kinetics; the mean elimination half-life was 15.1 hours.

Biological Availability↗
PubMed1993

Cerebrospinal fluid monoamine precursors and metabolites in human neonates following in utero cocaine exposure: a preliminary study.

BACKGROUND: Cocaine acts in the central nervous system by increasing dopamine release and inhibiting the reuptake of dopamine and other monoaminergic neurotransmitters. Prenatal cocaine exposure may cause neurochemical changes in developing monoaminergic neurons and might alter brain structure and function. No data have been published on central nervous system monoamine precursors and metabolites in human neonates exposed prenatally to cocaine. METHODS: Cerebrospinal fluid (CSF) was obtained from neonates undergoing lumbar puncture to rule out infection. The CSF was analyzed for the neurotransmitter precursors and metabolites tryptophan, tyrosine, 3-methoxy-4-hydroxyphenylglycol, homovanillic acid, and 5-hydroxyindoleacetic acid. Drug exposure was ascertained by medical record review and urine and meconium assays. RESULTS: Eleven neonates were cocaine-exposed, based on positive meconium or urine assays for benzoylecgonine; 20 were unexposed, based on both negative history and assay. The exposed and unexposed groups did not differ significantly in gender, perinatal stress, clinical illness, or exposure to other illicit drugs, but did differ in mean gestational age, growth parameters, and exposure to cigarettes. Cocaine-exposed neonates had significantly lower levels of CSF homovanillic acid (mean 148.1 vs 218.5 ng/mL, P = .01). The magnitude of this difference was similar after correcting for each of four potential confounding factors, although no longer statistically significant in all cases (P values ranged from .044 to .17). No significant differences were observed for tyrosine, tryptophan, 5-hydroxyindoleacetic acid, or 3-methoxy-4-hydroxyphenylglycol. CONCLUSIONS: These preliminary results suggest an association between prenatal cocaine exposure and decreased CSF homovanillic acid, the principal metabolite of dopamine. Prenatal cocaine exposure may result in changes in central dopaminergic systems in the human neonate.

Biogenic Monoamines↗
PubMed1991

Circulating catecholamine concentrations in cocaine-exposed neonates: a pilot study.

Twenty newborns, 12 with prenatal exposure to cocaine and an unexposed control group of 8, were studied to determine concentrations of circulating catecholamines and their relationship to newborn behavior. Birth weight of the cocaine-exposed neonates was significantly lower than that of the control group. Gestational age, length, and head circumference of the cocaine-exposed neonates were also lower, although the differences did not reach statistical significance. Between 24 and 48 hours of age, circulating concentrations of norepinephrine, dopamine, and the catecholamine precursor dihydroxyphenylalanine were measured and behavior was assessed using the Neonatal Behavioral Assessment Scale. Mean dihydroxyphenylalanine concentrations were increased in the cocaine-exposed newborns (10.3 ng/mL vs 5.9 ng/mL, P = .055), while there was no difference between the groups in mean norepinephrine or dopamine concentrations. There was a significant negative correlation between norepinephrine concentration and orientation cluster score for the cocaine-exposed newborns (r2 = .6979, P = .005). norepinephrine concentration did not correlate with the score for any other behavioral cluster, nor did dopamine or dihydroxyphenylalanine concentration correlate with the score for any cluster. These preliminary data from a pilot study suggest that catecholamine activity is increased in cocaine-exposed newborns and may play a role in neurobehavioral disturbances associated with prenatal exposure to this drug.

Birth Weight↗