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Biomedical subjects

J R Hayes

Publications and source records attributed to J R Hayes.

At least 73 records · Page 4Linked to original sources
PubMed1987

A comparative pharmacokinetic study of conventional propranolol and long acting preparation of propranolol in patients with cirrhosis and normal controls.

1 Six male patients with alcoholic cirrhosis and seven normal control subjects were each given 80 mg twice daily of conventional propranolol for 1 week and 160 mg once daily of a long acting preparation (LA) of propranolol for 1 week. 2 Plasma propranolol levels were measured at regular intervals on the first and seventh days of both weeks and also following an acute intravenous infusion of 10 mg propranolol on a separate occasion. 3 After the single intravenous dose the elimination half-life tended to be prolonged in the cirrhotic group (median 7.15 h) compared with controls (median 2.92 h) (P = 0.055). 4 After multiple oral dosing with 80 mg twice daily of conventional propranolol the steady-state plasma concentration (Css), area under the curve (AUC tau), peak concentration (Cmax) and trough concentration (Cmin) were significantly higher in cirrhotic patients and the peak: trough ratio (Cmax/Cmin) was significantly lower than controls. 5 After multiple oral dosing with 160 mg LA once daily Cmin was significantly higher than Cmax/min significantly lower in cirrhotic patients; Css, AUC and Cmax were higher than controls but not statistically different. 6 Within both subject groups the bioavailability of 80 mg twice daily of conventional propranolol tended to be greater than 160 mg LA once daily. Cmax was significantly higher in both groups and Css higher in the cirrhotic group with conventional propranolol. 7 In the cirrhotic group the mean reduction in supine heart rate in the steady state was 31.8% with conventional 80 mg twice daily propranolol and 23.75% with 160 mg LA once daily.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Revising the Seriousness of Illness Rating Scale: modernization and re-standardization.

The burgeoning research in psychosomatic medicine requires quantitative measures reflecting important biological, psychological, and social variables. The Seriousness of Illness Rating Scale (SIRS), although twenty years old, is currently utilized in psychosomatic research as an index of illness seriousness. In light of medical advances during the past two decades, an expansion and re-standardization of the SIRS appeared warranted. Forty-six medical students, residents, and faculty rated the seriousness of 137 disease items. High inter-rater reliability was demonstrated by a concordance coefficient of 0.716 and overwhelming agreement on relative disease item rankings between the three medical groups. Thus, the Seriousness of Illness Rating Scale-Revised (SIRS-R) is an ordinal level scale which reliably measures current views on illness seriousness and can be easily employed in multivariate psychosomatic research.

Adult↗
PubMed1986

Consultation-liaison psychiatry and clinical ethics: a model for consultation and teaching.

The consultation-liaison psychiatrist is often expected to perform the role of clinical ethicist or moral arbiter in the course of responding to psychiatric consultations. This article develops the idea that certain aspects of good consultation-liaison skills make this appropriate and consultation-liaison psychiatrists ought not to shy away from helping with difficult ethical problems. However, a systematic approach to clinical ethics is usually not part of consultation-liaison training. Two simple conceptual models can provide such a systematic approach and can be used in any clinical setting. The two models can also be easily taught and lend themselves to use in structuring teaching or case conferences about clinical ethics. The first model comes from formal philosophy (summarized by Veatch) and is a four-step hierarchy of levels of moral discourse. The other model comes from clinical medicine, based on work by Siegler, and provides another four-point checklist, this time of areas that must be considered in each decision. This article presents each of these four-point frameworks, alludes to the large amount of work that underpins these ostensibly simple models, and offers a case for demonstration/discussion of how the consultation-liaison psychiatrist use the models for structuring clinical ethical decision making and teaching.

Aged↗
PubMed1986

Acute, 14-day repeated dosing, and 90-day subchronic toxicity studies of carbon tetrachloride in CD-1 mice.

CD-1 mice received carbon tetrachloride daily by gavage for 14 or 90 consecutive days. Corn oil was the vehicle used. The 14-day study involved doses of 625, 1250, and 2500 mg/kg; the 90-day subchronic study involved doses of 12, 120, 540, and 1200 mg/kg. The 14-day study revealed a dose-dependent mortality and decreased body weight in males, whereas females demonstrated mortality only at the high dose. Other dose-dependent findings included decreased fibrinogen and lymphocytes; increased LDH, SGPT (ALT), and SGOT (AST); increased liver weights and ratios in both sexes; and decreased lung, thymus, and kidney weights in males only. There were no compound-related deaths in the 90-day study. There were no consistent compound-related effects on any of the hematological or urinary parameters evaluated. LDH, SGPT (ALT), SGOT (AST), ALP, cholesterol, and bilirubin were increased in an apparent dose-dependent manner while blood glucose levels decreased at all dosage levels. Liver, spleen, and thymus weights and ratios were increased at all dosage levels in both sexes. Histopathology revealed no kidney damage, but liver damage was observed at all doses in both sexes. A no-observable-adverse-effect level was not obtained in these studies.

Animals↗
PubMed1986

Acute, 14-day repeated dosing, and 90-day subchronic toxicity studies of potassium picloram.

Potassium picloram was administered either by gavage (acute studies) or in drinking water to male and female Sprague-Dawley-derived rats (14-day and 90-day studies). The acute oral LD50 was 950 mg/kg (812-1120) for males and 686 mg/kg (599-786) for females. Depression, prostration, ataxia, tremors, and convulsions preceded death. There were no consistent biologically significant compound-related effects in rats that received 60, 190, 600 mg potassium picloram/kg/day for 14 days. In the subchronic study, rats received 60, 190, 600, or 1070 mg potassium picloram/kg/day in drinking water for 90 consecutive days. There were only 4 male and 2 female survivors out of 20 rats of each sex at the 1070 mg/kg dose and 16 male and 18 female survivors at the 600 mg/kg dose. Mortality was dose dependent. Administration of picloram appeared to exacerbate renal and hepatic lesions commonly noted in rats of this age. For example, at levels up to 1070 mg/kg mild lesions in the kidney of treated rats, especially in males at 600 mg/kg, were noted. Also noted were an increased incidence of mononuclear liver foci in male rats that received 190 and 600 mg/kg and an increased severity of mononuclear liver foci in females that received 600 mg/kg. There were no other consistent biologically significant compound-related effects. No specific organ site toxicity could be identified in these studies. Toxicity from exposure to picloram in drinking water is apparently low.

Animals↗
PubMed1986

The subchronic toxicity of tetrachloroethylene (perchloroethylene) administered in the drinking water of rats.

This study provides data on the effects of tetrachloroethylene in drinking solutions. The acute oral LD50 in male and female Charles River rats was found to be 3835 mg/kg for males and 3005 mg/kg for females. Male and female rats received theoretical daily doses of 14,400, and 1400 mg tetrachloroethylene/kg body wt/day for 90 consecutive days. There were no compound-related deaths. Body weights were significantly lower in male and female rats at the higher doses. There were no consistent dose-related effects on any of the hematological, clinical chemistry, or urinalysis parameters. 5'-Nucleotidase activity was increased in a dose-dependent manner, suggesting possible hepatotoxicity; however, other serum indicators of hepatic function were unaffected by the treatment. There were no gross pathological effects observed. Liver and kidney body weight ratios, but not brain weight ratios, were elevated at the higher doses. There was no other evidence of compound-related toxicity. These data suggest that exposure of humans to reported levels of tetrachloroethylene in drinking water (approximately 1 microgram/liter) does not constitute a serious health hazard.

Animals↗
PubMed1986

Glomerular filtration rate in children: validation and longitudinal use of determination from the 99mTc DTPA renogram.

The glomerular filtration rate (GFR) was estimated from the technetium diethylenetriaminepentacetic (99mTc DTPA) renogram by empirically correlating the renogram and clearance of the tracer as measured by plasma disappearance kinetics. To expand the potential application of this technique from its original description, minor changes in methodology were made; a new regression was generated with 30 subjects, and that formula was then validated prospectively. For the 50 children and adolescents in the prospective series whose GFR normalized for surface area (NGFR = GFR X 1.73 m2/SA; SA, surface area) was less than 120 mL/min/1.73 m2; renal function was estimated with a mean residual error of 8.0 mL/min/1.73 m2, and a mean relative error of 11%. These results are at least as good as those in the initial report, thus validating this method in a prospective series. To examine the use of this method longitudinally, 129 examinations were reviewed in 55 subjects who had NGFR estimated from the renogram (estimated) on at least two occasions. For 28 sets of serial examinations, NGFR was also measured by the plasma disappearance of 99mTc DTPA (measured). The true change in function for each set of serial examinations was defined as the increment for whichever method (estimation or measurement) was more stable. The mean longitudinal errors were 2.1 and 4.8 mL/min/1.73 m2 for measured and estimated NGFR, respectively. The increments in NGFR for these methods were correlated with a regression line near identity and r = .852. This indicates that a change in estimated NGFR reflects a change in measured NGFR of similar magnitude. This method can accurately estimate GFR from the 99mTc DTPA renogram, and it can be used longitudinally to follow children with renal disorders.

Adolescent↗
PubMed1986

Intestinal blood flow and O2 uptake during hypoxemia in the newborn piglet.

Previous work has indicated that the neonatal intestinal circulation responds to hypoxemia with vasoconstriction and subsequent intestinal ischemia. This work was carried out in newborn lambs, a ruminant species, and may not be representative of all newborns. Therefore, we measured intestinal blood flow, vascular resistance, tissue O2 uptake, and cardiac output during normoxemia and varying degrees of hypoxemia in newborn piglets, a nonruminant species. Hypoxemia was induced by adding N2 gas to the inspired gas mixture, and measurements were obtained over a wide range of arterial O2 contents (2.2-15.6 ml O2 X dl-1). Intestinal blood flow increased in response to moderate hypoxemia and decreased in response to severe hypoxemia. The changes in intestinal blood flow were primarily due to change in intestinal vascular resistance, not cardiac output. Intestinal O2 was independent of arterial O2 content until the latter decreased below approximately 6.5 ml O2 X dl-1. These data indicate that the response of the neonatal intestinal circulation to hypoxemia is species specific and that the nonruminant neonatal intestine is capable of vasodilation in response to moderate hypoxemia.

Animals↗
PubMed1986

Toxicology of haloacetonitriles.

Haloacetonitriles are by-products of water chlorination and may form in vivo from the reaction of residual chlorine with endogenous compounds such as amino acids. Dibromoacetonitrile (DBAN) was negative in selected mutagenic assays; dichloroacetonitrile (DCAN) was mutagenic in S. typhimurium, but not in S. cerevisiae. Both DBAN and DCAN may be carcinogenic. There is a paucity of basic toxicological data for these compounds. The studies described were conducted to determine the acute, subacute, and subchronic toxicity of DBAN and DCAN. The acute oral LD50 values (mg/kg) in mice and rats are: DBAN, mice: 289 (M), 303 (F); DBAN, rats: 245 (M), 361 (F); DCAN, mice: 270 (M), 279 (F); DCAN, rats: 339 (M), 330 (F). Death was preceded by slowed respiration, depressed activity, prostration, and coma. There were no apparent compound-related gross pathological effects. DBAN (in corn oil) was administered by gavage to male and female CD rats for 14 or 90 days at levels of 23, 45, 90, and 180 mg/kg/day or 6, 23, and 45 mg/kg/day, respectively. Mortality was 100% at 180 mg/kg and 40% (M) and 20% (F) at 90 mg/kg/day. Compound-related mortality was 10% (M) and 5% (F) at 45 mg/kg and 0% (M) and 10% (F) at 23 mg/kg during the 90-day study. No consistent, significant, adverse compound-related effects on any of the parameters evaluated were evident. Possible target organs might be spleen, thymus, and liver. The no-observed adverse-effect level (NOAEL) for 14 days was 45 mg/kg/day and for 90 days was 23 mg/kg/day. DCAN (in corn oil) was administered by gavage to male and female CD rats for 14 or 90 days at levels of 12, 23, 45, and 90 mg/kg/day or 8, 33, and 65 mg/kg/day, respectively. There were no deaths during the 14-day study. Compound-related mortality was 50% (M) and 25% (F) at 65 mg/kg, 10% (M) and 5% (F) at 33 mg/kg, and 5% (M) and 0% (F) at 8 mg/kg during the 90-day study. Body weights were significantly lower at 90 and 65 mg/kg/day; weight and ratios of spleen and gonads and cholesterol levels were significantly lower at 90 mg/kg/day. No consistent, significant adverse compound-related effects on any of the parameters evaluated were evident. The NOAEL for 14 days was 45 mg/kg/day and for 90 days was 8 mg/kg/day.

Acetonitriles↗
PubMed1985

Neonatal phenobarbital imprinting of hepatic microsomal enzymes in adult rats: modulation by neonatal testosterone presence.

The influence of neonatal androgen status on the ability of neonatally administered phenobarbital (PB) to program increases in adult rat hepatic microsomal enzyme activities was investigated. Male and female rat pups were injected with 30 mg/kg PB or 0.9% saline on Days 1 to 5 postpartum. Males were further divided into either neonatally castrated or sham-operated groups. Females were subdivided into groups receiving either 0.5 mg testosterone propionate or 50 microliters corn oil on Days 1, 3, and 5 postpartum. Various hepatic microsomal cytochrome P-450 system and glucuronyltransferase activities were determined at 140 days of age. Our results indicate that PB imprints both males and females. P-450 reductase, ethoxycoumarin O-deethylase, and testosterone glucuronyltransferase activities were increased to a greater degree in females than in males. These same activities were increased by neonatal PB to a greater degree in castrated males compared to sham-operated males and were increased to a lesser degree in neonatally testosterone-treated females compared to female corn oil controls. It therefore appears that neonatal testosterone presence not only alters the patterns of enzyme activity but also diminishes the response of certain activities to PB programming.

Animals↗
PubMed1985

Xenobiotic imprinting of the hepatic monooxygenase system. Effects of neonatal phenobarbital administration.

The ability of phenobarbital (PB) to neonatally "imprint" or "program" the hepatic microsomal cytochrome P-450-dependent monooxygenase system (MOS) was investigated. Phenobarbital (30 mg/kg) was administered subcutaneously to neonatal rats of both sexes on days 1-5 postpartum. Various hepatic MOS activities were measured at 6, 22, 50 and 140 days of age. Six-day-old animals of both sexes displayed the increased hepatic microsomal protein levels and enzyme activities expected from the action of phenobarbital as a transitory MOS inducer. Most of these increases dissipated by 22 and 50 days of age. However, at 140 days of age rats of both sexes that had received neonatal phenobarbital showed increased levels of cytochrome P-450, as well as both P-450 and cytochrome c reductase, ethoxycoumarin O-deethylation, glucuronyl transferase activity, in vitro covalent binding of benzo[a]pyrene to DNA and in vivo covalent binding of aflatoxin B1 to hepatic macromolecular fractions. Neonatal phenobarbital administration can alter the metabolic profile of rats in adulthood, apparently by a mechanism different from that responsible for either transitory PB induction or testosterone imprinting.

Animals↗
PubMed1985

Acute and subchronic toxicity of 2,4-dichlorophenol in CD-1 mice.

The acute oral LD50 of 2,4-dichlorophenol (2,4-DCP) employing corn oil as vehicle was determined to be 1352 mg/kg for female and 1276 mg/kg for male CD-1 mice. CD-1 mice of both sexes were exposed to 2,4-DCP in drinking water containing 10% Emulphor for 90 days at concentrations of 0.2, 0.6, and 2.0 mg/ml providing theoretical daily doses of 50, 150, and 500 mg/kg. These concentrations resulted in mean daily doses of 50, 143, and 491 mg/kg for females and 40, 114, and 383 mg/kg for males. In both sexes, fluid consumption was lower in the vehicle control group (10% Emulphor) and in the 2,4-DCP treated groups than in the naive controls (deionized water). There were no biologically significant differences in body weight gain between females or males in the vehicle control and experimental groups. No differences were found in terminal organ weights or organ weight ratios in either sex. Hematological differences were observed in males only and included an increase in leukocytes (high dose) and an increase in polymorphonuclears (low dose). Clinical chemistry parameters were altered in females only and included a decrease in creatinine (low dose), an increase in BUN/creatinine ratio (mid dose), and an increase in ALP (high dose). In an assessment of the hepatic microsomal mixed function oxidase system, no significant differences were found in the components of the system, component activity, the kinetics of ethylmorphine N-demethylase, or the metabolism of testosterone.(ABSTRACT TRUNCATED AT 250 WORDS)

2,4-Dichlorophenoxyacetic Acid↗
PubMed1985

Acute toxicity of monochlorophenols, dichlorophenols and pentachlorophenol in the mouse.

Acute oral LD50 values were determined for 2-, 3-, and 4-chlorophenol, 2,3-, 2,4-, 2,5-, 2,6-, 3,4-, and 3,5 dichlorophenol and pentachlorophenol in male and female mice. LD50 values (mg/kg) ranged from 117 (females) and 177 (males) for pentachlorophenol to 2389 (females) and 2643 (males) for 3,5-dichlorophenol. It was found that 2-chlorophenol and 3-chlorophenol were considerably more toxic than the dichlorophenol series. Values for males and females were generally similar, the major differences being with pentachlorophenol and 2,5-dichlorophenol, where in both cases the female LD50 was lower.

Animals↗
PubMed1985

A microcomputer-based tutorial program for computer-based training and patient care.

This program provides the nonprogrammer a tool to develop easily modified computer assisted tutorials, tests, and simulations with a word processor. In addition, by using the branching and query features of this program, one can easily develop text files that provide rapid access to information related to patient care such as neonatal formularies and patient care algorithms.

Computer-Assisted Instruction↗
PubMed1985

Gastrointestinal blood flow and O2 uptake in piglets: recovery from hypoxemia.

Gastrointestinal (GI) blood flow, O2 transport, and O2 uptake were measured during recovery from severe hypoxemia in newborn piglets. Hypoxemia was induced by lowering the inspired O2 concentration to 0.05 for 15 min. This resulted in an 82% decrease in GI O2 uptake. Recovery measurements were obtained 5 and 65 min after restoration of normoxia. During early recovery (5 min), GI O2 uptake increased above prehypoxemia baseline, presumably to "repay" the O2 deficit incurred during hypoxemia. This was mediated by an increase in the arteriovenous O2 content difference, as GI blood flow did not increase above prehypoxemia baseline. During late recovery (65 min), GI blood flow, O2 delivery, and arteriovenous O2 content difference decreased below prehypoxemia baseline. This resulted in a 52% decrease in GI O2 uptake below prehypoxemia baseline. Therefore, early recovery was characterized by an appropriate increase in GI O2 uptake; however, late recovery was characterized by a significant reduction in GI O2 transport and uptake. Circulatory homeostasis was not reestablished during the late recovery period.

Animals↗