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Biomedical subjects

B S Brown

Publications and source records attributed to B S Brown.

At least 73 records · Page 4Linked to original sources
PubMed1989

Pharmacology of ACC-9653 (phenytoin prodrug).

ACC-9653, the disodium phosphate ester of 3-hydroxymethyl-5,5-diphenylhydantoin, is a prodrug of phenytoin with advantageous physicochemical properties. ACC-9653 is rapidly converted enzymatically to phenytoin in vivo. ACC-9653 and phenytoin sodium have equivalent anticonvulsant activity against seizures induced by maximal electroshock (MES) in mice following i.p., oral, or i.v. administration. The ED50 doses were 16 mg/kg for i.v. ACC-9653 and 8 mg/kg for i.v. phenytoin sodium. ACC-9653 and phenytoin sodium have similar antiarrhythmic activity against ouabain-induced ventricular tachycardia in anesthetized dogs. The total doses of ACC-9653 or phenytoin sodium necessary to convert the arrhythmia to a normal sinus rhythm were 24 +/- 6 and 14 +/- 3 mg/kg, respectively. Only phenytoin sodium displayed in vitro antiarrhythmic activity against strophanthidin-induced arrhythmias in guinea pig right atria. In anesthetized dogs, a high dose of ACC-9653 (31 mg/kg) was infused over 15, 20, and 30 min and the responses were compared to an equimolar dose of phenytoin sodium (21 mg/kg). The ACC-9653 and phenytoin sodium treatments produced similar marked reductions in diastolic blood pressure and contractile force (LVdP/dt). The maximum effects of each treatment occurred at the time of maximum phenytoin sodium levels. Acute toxicity studies of ACC-9653 and phenytoin sodium were carried out in mice, rats, rabbits, and dogs by i.v., i.m., and i.p. routes of administration. The systemic toxic signs of both agents were similar and occurred at approximately equivalent doses. Importantly, the local irritation of ACC-9653 was markedly less than phenytoin sodium following i.m. administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Comparison of the characteristics and functioning of cocaine treatment and cocaine research subjects.

Comparisons were made of the functioning and characteristics of cocaine-abusing volunteers to a research ward (N = 25) and to an outpatient treatment program (N = 33) at the same research facility. It was hypothesized that individuals volunteering for clinical studies and for treatment-related studies would represent different segments of the cocaine-abusing population, and that those differences could be significant to an understanding of study findings. Demographic/background variables were assessed through use of the Addiction Severity Index, risk-taking behaviors relative to HIV infection and AIDS through use of a structured interview schedule, intellectual functioning through use of the Shipley Institute for Living Scale, and psychiatric symptoms through use of the Hopkins Symptom Check List (SCL-90R). Significant differences were obtained for criminal activity, needle sharing, and selected psychiatric symptoms. Marital status was particularly important to an understanding of differences between research and treatment groups in that unmarried treatment subjects showed significantly greater psychopathology than research subjects on 3 of 11 symptom scores. Unmarried treatment subjects showed significantly greater deviance than married treatment subjects on 7 of 11 symptom scores. The findings suggest a relationship between marital status and the psychological functioning of treatment clients and indicates that different segments of the cocaine-abusing population volunteer for different types of research.

Adult↗
PubMed1989

The functioning of individuals on a drug abuse treatment waiting list.

Using structured interviews and the SCL-90R, study was made of the behaviors of 29 applicants to a residential treatment program for cocaine abuse who had been placed on the program's waiting list for periods ranging from 1 to 6 months. It was hypothesized that applicants waiting treatment for 3 months or less (N = 16) would be more likely to view themselves as treatment candidates and would show behaviors different from those waiting 4-6 months (N = 13). Being on the waiting list a longer period was associated with greater evidence of criminal justice involvement, but with few other differences. Nearly half the total sample (48.3%) reported having significantly reduced drug use in association with their applying for treatment, but most applicants (58.6%) were pessimistic about their long-term capacity to remain free of drug-related difficulty. The pattern of SCL-90R scores for all subjects suggested significant psychiatric symptoms, including depression. Nonetheless, a majority of all applicants (51.7%) reported themselves as having become less interested in entering treatment. Nearly all applicants reported high levels of encouragement for their decision to enter treatment from persons with whom they were living and about half reported encouragement from friends. Of the 23 applicants who were IV drug users, 10 (41.7%) reported knowing someone who had contracted AIDS, 87.0% reported having changed behaviors--chiefly needle sharing--to reduce the risk of infection, and 69.6% reported having obtained HIV testing. The difficulty encountered in locating a random sample of applicants suggests the problem of maintaining a useful waiting list for treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1989

Injured Infants Act: study compares definition, newborn records.

In a study of a teaching hospital's newborn records 1986-1987, the definition of severe neurological injury in Virginia's Injured Infants Act was found to be associated with neonatal death, prematurity, and a preexisting maternal condition likely to contribute to poor outcome. The incidence of severe neurologic injury did not approach the prevalence of severe mental retardation and cerebral palsy. Thus the ability of the Act to preempt litigation substantially is questionable, the authors state, and they recommend a broader definition.

Birth Injuries↗
PubMed1989

Birth-injured infants: legal definitions, claims frequency in Virginia.

This review of claims supports the findings of an earlier study on the incidence of injuries defined by the Injured Infant Act. Assignment of children to Virginia's definition of injury was associated with death in the neonatal period and preexisting maternal conditions likely to contribute to a poor outcome. Expanding the definition was more likely to capture living children needing substantial assistance in all phases of daily living. Further refinement of the definition appears advisable to assure that those receiving support meet the Act's intent.

Birth Injuries↗
PubMed1989

Electrophysiological effects of ACC-9358, a novel class I antiarrhythmic agent, on isolated canine Purkinje fibers and ventricular muscle.

Class I antiarrhythmic agents are heterogeneous with respect to their cardiac electrophysiological effects and have been subdivided into three categories: la, lb and lc. The purpose of the present study was to determine the classification and investigate the mechanism of action of ACC-9358 [4-hydroxy-N-phenyl-3,5-bis (1-pyrrolidinyl-methyl)benzamide], a novel class I antiarrhythmic agent currently under clinical investigation. The effects of ACC-9358 on action potentials from isolated canine Purkinje fibers and ventricular muscle were examined using standard microelectrode techniques. In Purkinje fibers, ACC-9358 (1-50 microM) exerted a dose-dependent reduction in maximum upstroke velocity (Vmax) and action potential duration at 50 and 90% repolarization (APD50 and APD90). The reduction of Vmax was voltage-dependent (greater at an extracellular potassium concentration of 6 mM than at 2.7 mM), frequency-dependent (greater at a basic cycle length of 500 than at 2000 msec) and very slow in onset (rate constant of 0.017 action potentials-1) and offset (recovery half-time of 66.9 sec). In Purkinje fibers, ACC-9358 attenuated the action potential shortening effects of lidocaine but not that of nicardipine or nicorandil and shortened APD50 to a greater extent at a basic cycle length of 2000 than at 500 msec. In ventricular muscle, ACC-9358 (1-50 microM) exerted a dose-dependent reduction in Vmax and prolongation of APD50 and APD90.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1988

Acceptance of HIV-antibody testing by persons seeking outpatient treatment for cocaine abuse.

One hundred of 101 applicants for outpatient treatment for cocaine abuse consented to voluntary HIV-antibody testing when the testing was offered as an option within the medical assessment at intake. Twelve applicants tested HIV-antibody positive; eight of these had injected drugs parenterally with syringes and needles used by other addicts and four had never taken drugs intravenously. There were no significant differences between HIV-antibody positive and negative applicants regarding the percentages who completed the evaluation, began treatment, and completed four weeks of treatment. A subgroup of 48 patients were interviewed regarding their knowledge of HIV infection, AIDS, and risk factors associated with transmission of HIV. All 48 patients had heard of HIV, AIDS, and recommendations that they use condoms as well as clean syringes and needles. None of the 48 patients reported that they used condoms; 10 reported reduced sexual activity and number of sexual partners; and none of those who shared needles reported that they had discontinued sharing other addicts' drug paraphernalia. The authors conclude that on-site, voluntary HIV-antibody testing for drug abusing patients entering treatment appears feasible and is not a deterrent to persons entering and continuing in treatment for drug abuse. The finding that persons at risk for HIV infection have knowledge of risk factors and have not changed risk-taking behaviors associated with HIV contagion points out the urgent need for further education and counseling.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Fetus in fetu: a fetiform teratoma.

Examination of a retroperitoneal fetus in fetu, diagnosed preoperatively, revealed previously unreported histologic findings in the vascular pedicle and membranous capsule that indicated that these structures are not "umbilical cord" or "amnion." These findings include nervous innervation of both structures and a well-defined lamina elastica interna and vaso vasorum in the artery of the vascular pedicle. Thus, strong support is provided for the theory that many examples of fetus in fetu are remarkably complex, well differentiated, highly organized teratomas. Additional arguments that favor the identity of fetus in fetu and teratoma are presented.

Abdominal Neoplasms↗
PubMed1988

Geriatric care needs and HMO technology. A theoretical analysis and initial findings from the National Medicare Competition Evaluation.

More than 770,000 Medicare beneficiaries were enrolled in 1986 in HMOs that have very little experience in providing health care to elderly patients. A general framework for assessing the effects of HMO as compared with fee-for-service delivery systems for the elderly is needed to guide the many studies of quality of care that are underway and will ensue. The following paper addresses the development of such a framework through analysis of the "fit" between the health care needs of the elderly and HMO technology and examination of initial findings from the National Medicare Competition Evaluation--a major project currently underway.

Aged↗
PubMed1987

Deceased co-twin as a cause of false positive amniotic fluid AFP and AChE.

A pregnancy was terminated because of persistently elevated amniotic fluid AFP (+10 S.D.) and an AChE band of low intensity on gel electrophoresis. No fetal anomalies were detected by ultrasonographic examination. Autopsy revealed an apparently normal fetus of about 20 weeks gestation. Attached to the placenta was a small sac containing a fetus papyraceus co-twin of about 8-9 weeks gestation. The small deceased co-twin and its gestational sac were not detected prenatally despite multiple ultrasonographic examinations. The difficulty in the interpretation of apparently conflicting results is emphasized.

Abortion, Therapeutic↗
PubMed1987

Networking between research and service delivery.

This paper reviews the impediments to the adoption of new models of service delivery, as those impediments are seen in the field of drug abuse. The paper further explores strategies for overcoming those obstacles with a particular view toward the translation of research materials to a language and format appropriate to the field of service delivery. Issues in the study of competing strategies of knowledge transfer are also explored.

Attitude of Health Personnel↗
PubMed1987

Antiarrhythmic, electrophysiologic and hemodynamic effects of ACC-9358.

The antiarrhythmic, electrophysiologic and hemodynamic effects of a new antiarrhythmic agent, ACC-9358, were evaluated. In anesthetized dogs, ACC-9358 converted ouabain-induced ventricular tachycardia to normal sinus rhythm at a cumulative dose equal to encainide or flecainide and less than disopyramide. In 24-hr coronary artery ligated dogs, ACC-9358 suppressed spontaneous ventricular arrhythmias for up to 6 hr after oral or i.v. administration. The antiarrhythmic effect and plasma concentrations of ACC-9358 correlated well for both oral (r = 0.88) and i.v. (r = 0.87) administration. ACC-9358, flecainide and disopyramide were equieffective in converting crush-stimulation-induced atrial flutter in anesthetized dogs to normal sinus rhythm. In alpha-chloralose-anesthetized, closed-chest dogs, ACC-9358 slowed impulse conduction through the atria, atrioventricular node, His-Purkinje system and ventricles and prolonged atrial functional refractory period. In conscious dogs, ACC-9358 increased heart rate, reduced stroke volume and had no effect on mean arterial pressure, systemic vascular resistance or cardiac output. In alpha-chloralose-anesthetized dogs, ACC-9358-induced sinus tachycardia was unaffected by propranolol but was blocked by hexamethonium or vagotomy. In isolated cat ventricular muscle, the IC50 for the negative inotropic effect of ACC-9358 was significantly greater than flecainide or disopyramide. These results indicate that ACC-9358 is a potent, broad-spectrum, long-acting, orally and intravenously active class Ic antiarrhythmic agent that 1) may be devoid of active metabolites, 2) exerts little or no vascular effects and 3) has less direct cardiodepressant activity than flecainide or disopyramide.

Animals↗
PubMed1986

Prevalence and prenatal diagnosis of neural tube defects in Nova Scotia in 1980-84.

A survey of the records of all hospitals with obstetric services in Nova Scotia revealed that during 1980-84 there were 122 pregnancies involving a neural tube defect. The mean rate was 2/1000 births. Of the affected fetuses or infants 54% had spina bifida, 35% had anencephaly and 11% had encephalocele. The records showed that in the early part of the period studied at least one prenatal ultrasonographic examination had been performed in 60% of the pregnancies; in 1984 the rate was 74%. When examinations done before 16 weeks' gestation were excluded, the overall detection rates at the first ultrasonographic examination were 100% for anencephaly and 73% for spina bifida and encephalocele; the rates improved toward the end of the study period.

Abortion, Therapeutic↗
PubMed1986

Antiarrhythmic activity of flestolol, a novel ultra-short-acting beta-adrenoceptor antagonist, in the dog.

The antiarrhythmic activity of flestolol, an ultra-short acting beta-adrenergic blocker lacking appreciable local anesthetic activity, was examined in several different canine ventricular arrhythmia models. Flestolol, at steady state infusions of 1-1,000 micrograms/kg per min, was generally ineffective in reversing either ouabain-induced or delayed ischemia-induced (24 h Harris dog) ventricular tachycardia. However, flestolol (1, 10 and 100 micrograms/kg per min) produced a dose-dependent decrease in l-norepinephrine (5 micrograms/kg i.v.)-induced ventricular tachycardia in the 5-6 day old Harris dog; the effect of 100 micrograms/kg per min flestolol, 94% suppression of norepinephrine-induced ventricular tachycardia, was completely reversed 60 min after termination of flestolol infusion. In pentobarbital-anesthetized open-chest dogs with pretreatment heart rates greater than or equal to 145 beats/min, flestolol (10 micrograms/kg per min) reduced the incidence of ventricular fibrillation resulting from abrupt coronary artery occlusion compared to placebo-treated controls (15% or 2/13 vs. 70% or 7/10, respectively). These results demonstrate that flestolol has an antiarrhythmic profile consistent with its lack of local anesthetic activity and its ultra-short duration of beta-blockade.

Adrenergic beta-Antagonists↗
PubMed1986

Long-term survival in limited-stage small cell lung carcinoma. Experience in Rochester, New York from 1975 to 1981.

All patients with limited-stage small cell lung carcinoma (SCLC) diagnosed between January 1975 and 1981 in Rochester, New York, were collected. One hundred one patients were evaluable. By reviewing an entire community's experience with long follow-up, we were able to describe the response rates and survival in a large unselected population and compare them to results from concurrent cooperative group studies. Median survival for the entire group was 51 weeks, with only 18% alive at 130 weeks. There was no evidence for improvement in response or survival during the 6 years of study. Treatment results in the community as a whole were no different from that seen with cooperative group studies. A group who had initial surgery followed by adjuvant therapy had a significantly better survival and more long-term survivors than those not receiving surgery, but rare long-term survivors were seen with all treatment categories. Except for this small surgical subgroup, no other characteristics could be identified which were predictably associated with long-term disease-free survival. The overall poor survival of patient with localized SCLC suggests a need for the development of novel initial approaches to therapy.

Adult↗