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Biomedical subjects

M G Henderson

Publications and source records attributed to M G Henderson.

17 recordsLinked to original sources
PubMed1993

Changes in dopamine, serotonin and their metabolites in discrete brain areas of rat offspring after in utero exposure to cocaine or related drugs.

The concentrations of dopamine (DA), serotonin (5HT) and their metabolites were quantified in 5 brain areas of rats exposed to saline, cocaine (15 mg/kg b.i.d.), amitriptyline (10 mg/kg), or amfonelic acid (AFA, 1.5 mg/kg) throughout gestation. Male pups from 3 similarly treated dams were fostered to 2 surrogate dams. The process of breeding and rearing was repeated 4 times with new dams to build the groups to 4-12, since only one pup per litter was used for any one measurement. AFA was used to mimic the dopamine (DA) uptake blockade and stimulant properties of cocaine and amitriptyline was used to mimic the other pharmacological effects of cocaine. At postnatal days (PND) 30, 60, and 180, one pup per litter was removed for HPLC analysis of monoamines. A second pup received 0.3 mg/kg haloperidol, catalepsy assessed after 1 hr, and the brain used for analysis. The cataleptic response to haloperidol was unaffected by any prenatal treatment. The striatum from PND 30 cocaine rats had decreased levels of DA without a decrease in DA metabolites. At PND 60 in cocaine exposed rats, DA and DOPAC concentrations were increased, and 5HT levels were decreased in the striatum. The amitriptyline-exposed group exhibited decreased 5HT and 5-HIAA levels in the striatum. The hypothalamus of the cocaine group had lower levels of 5-HIAA, and other brain areas had a trend for lower levels of 5HT and 5-HIAA. At PND 180, DOPAC was increased in the striatum and prefrontal cortex of the cocaine group. Haloperidol-induced altered monoamine metabolism was unaffected by any prenatal treatment at any age. These data suggest that age-related changes in the DA and 5HT neurotransmission systems occur in rats exposed prenatally to cocaine. However, the ability of the dopaminergic system to respond to a challenge by a DA receptor blocker is unaltered by these in utero treatments.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Possible involvement of dopamine in the long-term serotonin depletion by p-chloroamphetamine and beta,beta-difluoro-p-chloroamphetamine in rats.

The role of dopamine in the long-term depletion of serotonin in rat brain by p-chloroamphetamine (PCA) and related compounds was investigated by comparing effects of beta,beta-difluoro-p-chloroamphetamine (beta,beta-difluoro-PCA) and 4-methyl-alpha-ethyl-meta-tyramine (H75/12), reported to cause only short-term serotonin depletion, with those of PCA. A single dose of beta,beta-difluoro-PCA had no long-term effects on serotonin in whole rat brain, even after pretreatment with proadifen which decreased the rate at which beta,beta-difluoro-PCA disappeared from brain. The possibility that proadifen might antagonize serotonin depletion was ruled out; proadifen did not prevent long-term serotonin depletion by PCA. Long-term depletion of brain serotonin was found after repeated injections of beta,beta-difluoro-PCA (five injections 4 hr apart) and was prevented by fluoxetine pretreatment. beta,beta-Difluoro-PCA given after the monoamine oxidase inhibitor pargyline or after carbidopa/L-dopa also caused long-term serotonin depletion, although H75/12 did not. At early times after single doses producing the same initial depletion of serotonin, PCA caused a large increase in dopamine and a large decrease in the metabolite 3,4-dihydroxyphenylacetic acid in whole brain, thereby increasing the ratio dopamine/3,4-dihydroxyphenylacetic, and the other two drugs caused smaller effects. Extracellular dopamine was increased markedly by PCA, less by beta,beta-difluoro-PCA, and not at all by H75/12. These results suggest an association between dopamine release and long-term depletion of serotonin and add to evidence that dopamine release by PCA may be essential to its neurotoxic actions on brain serotonin neurons.

Amphetamines↗
PubMed1992

Dextromethorphan antagonizes the acute depletion of brain serotonin by p-chloroamphetamine and H75/12 in rats.

A role for calcium in p-chloroamphetamine-induced neurotoxicity has been inferred previously from protective effects of dextromethorphan. We found that dextromethorphan reduces rat brain concentrations of 5-hydroxyindoleacetic acid and blocks the acute, non-neurotoxic depletion of brain serotonin by p-chloroamphetamine and by H75/12. Inhibition of the membrane transporter on brain serotonin neurons by dextromethorphan in vivo might explain its protective effect against p-chloroamphetamine neurotoxicity.

Amphetamines↗
PubMed1992

MK801 antagonism of the prolonged depletion of striatal dopamine by amphetamine in iprindole-treated rats.

The administration of amphetamine to rats pretreated with iprindole to inhibit the metabolism of amphetamine results in a long-lasting depletion of striatal dopamine and its metabolites, DOPAC and HVA. Pretreatment with MK801, a noncompetitive antagonist of the NMDA (N-methyl-D-aspartate) subclass of excitatory amino acid receptors, antagonized the depletion of striatal dopamine, DOPAC and HVA 3 days after a single dose of amphetamine in iprindole-treated rats. MK801 pretreatment was effective up to 4 hours but not at 8 or 24 hours in preventing amphetamine effects on striatal dopamine, DOPAC and HVA.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

Comparative brain levels of phenylpropanolamine and amphetamine in rats.

The CNS penetration by phenylpropanolamine (PPA) [(+/-)-norephedrine] was examined and compared to that of (+/-)-amphetamine in the rat. Brain and blood levels of the drugs were measured 1 hr after injection of 0.025, 0.05 or 0.1 mmol/kg doses. Brain levels of both drugs were proportional to dose and were several-fold higher than blood levels. Phenylpropanolamine levels in brain and brain:blood concentration ratios were only slightly lower than those of amphetamine at equimolar doses. The results suggest that phenylpropanolamine penetrates the blood:brain barrier almost as well as amphetamine and that different central actions of the two drugs are probably related to pharmacodynamic differences since they could not be accounted for by the small differences in drug concentrations in brain.

Amphetamine↗
PubMed1991

Long-term consequences of prenatal exposure to cocaine or related drugs: effects on rat brain monoaminergic receptors.

Reports from both this laboratory and others indicate that prenatal exposure of rats to cocaine can produce alterations in development, activity and responses to environmental stimuli. In order to determine a biochemical basis for these effects, radioligand receptor-binding assays for different monoaminergic receptors were performed on rat brain tissues obtained from offspring of dams treated SC with saline, cocaine (15 mg/kg b.i.d.), amitriptyline (10 mg/kg) or amfonelic acid (AFA, 1.5 mg/kg). Male rat pups were fostered by surrogate dams and one rat per litter taken at 30, 60 or 180 days postnatal for determination of striatal and prefrontal cortical D2 receptors, prefrontal cortical 5HT2 receptors, cortical alpha 1-, alpha 2-, beta 1- and beta 2-adrenoceptors. Across all drug treatments and times, the only significant change was at 30 days of age when beta 1-adrenoceptors were increased 68% in the cocaine exposed pups--a time when these rats show hyperactivity--and at 180 days postnatal when a 20% decrease in DA2 receptor Bmax was observed. Also, cortical membrane Mg(2+)-dependent Na+, K(+)-ATPase activities and basal ATPase activities were unaltered by any of the treatments at any of the times. These results suggest that few changes have occurred in monoaminergic receptor sensitivity as a result of the exposure to these drugs during gestation. The behavioral changes that are known to occur following prenatal exposure to cocaine may be due to presynaptic alterations in neurotransmitter function rather than changes in postsynaptic receptors.

Aging↗
PubMed1991

Purpose of admission and resource use during cancer hospitalizations.

This study examined the role of purpose of admission (POA) in hospitalizations for lung, colon, and breast cancers, using the 1985 20-percent Medicare provider analysis and review file. Six POA categories were created from discharge abstract data. Average hospitalization charges, per diem charges, length of stay, and rates of death varied significantly by POA (p < .001). Rural and small hospitals were more likely to admit patients for palliation, while urban and large hospitals admitted relatively more patients for active interventions (p < .0001). POA and indicators of case complexity added only modestly to the ability of diagnosis-related groups to predict hospitalization charges.

Aged↗
PubMed1990

Effects of prenatal exposure to cocaine or related drugs on rat developmental and neurological indices.

Although increasing numbers of infants born to cocaine abusing mothers are of grave concern, little is known of the long term development of these children. To determine the long term effects of cocaine on a developing fetus, gravid rats were dosed SC throughout pregnancy with either saline, amfonelic acid (AFA, 1.5 mg/kg), amitriptyline (10 mg/kg) or cocaine (15 mg/kg b.i.d.) and the male pups fostered by surrogate rats. Compared to saline offspring, cocaine- and amitriptyline-exposed litters were underweight at birth, but there were no differences between groups at 15 or 30 days of age. There were more birth defects and stillbirths in cocaine-exposed offspring, however, there were no differences in male/female sex ratios or litter size in any group. Number of days to righting reflex was delayed in the cocaine-exposed group, but there were no changes in time to eye opening. Cocaine- and amitriptyline-exposed pups were hyperactive at 30 days of age, though no differences were found in an initial 15-min exploration period. Only the AFA-exposed offspring were hyperactive at 60 days postnatal. Since cocaine and amitriptyline decreased birth weights, this effect may be related to the nondopaminergic effects of cocaine. These data demonstrate that cocaine exposure in utero at relevant doses can affect neonatal outcome and long term development in rat offspring.

Amitriptyline↗
PubMed1988

Measuring quality in medical case management programs.

Private insurers and health care providers alike currently offer medical case management programs as a means of containing costs and enhancing the quality of care for patients with high-cost illnesses or injuries. Since 1986, Brandeis University's Bigel Institute for Health Policy has been involved in a project to evaluate medical case management programs. The study found that such programs have become popular because of the perception that high-cost patients are typically handled inefficiently. The study also found that greater attention needs to be given to developing systematic ways to measure and monitor the quality of the case management process and its effect on outcomes.

Catastrophic Illness↗
PubMed1988

Private sector initiatives in case management.

Case management for high-cost patients is offered by virtually all private insurers and many health management firms. Despite the proliferation of the service, little is known about the process of case management, how it varies among vendors, what its impact is on short- and long-run patient costs, and what its effects are on quality. In this article, the authors present the results of a survey of insurance-based programs that reveal some process variations that could lead to differences in program effectiveness and cost.

Catastrophic Illness↗
PubMed1985

A comparison of hospital outpatient departments and private practice.

This article addresses cost differences between primary care physicians in private practice and hospital outpatient departments (OPD's). The analysis utilizes ambulatory visit groups (AVG's), the outpatient equivalent of diagnosis-related groups (DRG's), to adjust for case mix. Major findings are that OPD's have higher per visit costs than physicians' private offices; internists are more expensive than general practitioners regardless of site; and ancillary service costs are actually slightly higher in private practice. Any prospective payment system for ambulatory care must consider these costs differences.

Costs and Cost Analysis↗