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J Ham

Publications and source records attributed to J Ham.

86 records · Page 5Linked to original sources
PubMed1979

A technique for the chronic study of the hepatic uptake and excretion of substances in the conscious pig.

The pig is an ideal animal for studies of hepatic metabolism and the handling of drugs by the liver because of the many similarities in liver function to that in man. In this report we describe for the first time, in this animal, methods for the chronic implantation of sampling catheters in the major hepatic vessels and for the construction of an external biliary shunt. This model has many advantages in that it permits in the conscious animal intermittent, simultaneous and precise sampling of the hepatic uptake and clearance of substances and intermittent sampling of bile, without permanent interruption of the enterophepatic circulation. The effectiveness of this preparation has been assessed in 55 pigs. It was demonstrated that the majority of catheters remained patent for at least three days and in many cases for much longer. No significant alteration in liver function could be shown for at least seven days after surgery.

Animals↗
PubMed1978

Pharmacokinetics and pharmacodynamics of d-tubocurarine during hypothermia in the cat.

To determine the effects of hypothermia on the pharmacokinetics and pharmacodynamics of d-tubocurarine (dTc), serum, biliary, and urinary concentrations were determined and twitch tension monitored following intravenous administration of dTc, 0.7 mg/kg, at 39 (n = 5), 34 (n = 5), and 28 C (n = 6) in cats anesthetized with chloralose and urethane. Time from injection of dTc to maximum neuromuscular blockade was prolonged by hypothermia (28 C). Similarly, moderate (28 C) but not mild (34 C) hypothermia delayed recovery from paralysis. The serum half-life was prolonged 76% and the serum clearance rate decreased 60% by hypothermia (28 C). The combined biliary and urinary elimination of dTc was decreased 47% at 28 C compared with 34 and 39 C. The serum concentration of dTc necessary for neuromuscular blockade was less at 39 C (ED50 0.87 microgram/ml) than at 34 or 28 C (ED50 1.13 microgram/ml). It is concluded that, in vivo, hypothermia antagonizes a dTc-induced neuromuscular blockade but decreases the elimination of dTc. At 28 C the net effect is a prolongation of neuromuscular blockade.

Animals↗
PubMed1978

The experimental assessment of techniques of measuring biliary pressure.

A variety of different methods have been used for the measurement of pressures during operations on the biliary tract. However, there are few data on the experimental evaluation of the methods, and there has been no controlled comparative evaluation of the most commonly used techniques. In these experiments, we have compared the manometric technique of Caroli, the syringe barrel method of Daniel and White et alii, and the constant infusion apparatus of Cushieri. The experiments were performed in pigs because of the similarity of their biliary tract to that of man. Resting and opening pressures were recorded, and flow into the duodenum via the ampulla was measured simultaneously. The manometric and syringe barrel techniques gave highly reproducible measurements of resting and opening pressure, and valid measurements of opening pressure. The constant infusion apparatus gave reproducible measurements of resting pressure, but did not measure opening pressure. The manometric technique was shown to measure changes in the resistance of the choledochoduodenal junction in response to morphine and atropine.

Animals↗
PubMed1978

Hypothermia and the pharmacokinetics and pharmacodynamics of pancuronium in the cat.

We tested the effect of hypothermia on the pharmacokinetics and pharmacodynamics of pancuronium in the cat. In 14 cats given pancuronium, 120 microgram/kg i.v., we found that neuromuscular block lasted between 2.5 and 3.0 times longer at 29 degrees C (N = 5) than at 34 degrees C (N = 5) or 39 degrees C (N = 4). The apparent plasma elimination half-life was 46 +/- 7 min (S.E.) at 29 degrees C as compared to 21 +/- 2 and 25 +/- 6 min at 34 and 39 degrees C, respectively. The volume of distribution of the central compartment and total volume of distribution at steady state were less at 29 and 34 dgrees C than at 39 degrees C. Total plasma clearance was 4.3 +/- 0.4 ml/kg/min at 29 degrees C and 10.7 +/- 0.9 and 10.9 +/- 1.5 ml/kg/min at 34 and 39 degrees C, respectively. The reduced plasma clearance resulted at least in part from a markedly reduced biliary and urinary excretion of pancuronium at 29 degrees C as compared to 34 and 39 degrees C. In four other cats, the plasma concentration of pancuronium was correlated with depression of twitch tension under steady-state conditions. The ED50 of pancuronium (plasma concentration required for a 50% depression of twitch tension) was 0.035 and 0.073 microgram/ml at 29 and 38 degrees C, respectively. We conclude that a pancuronium neuromuscular block is prolonged at 29 degrees C because of an increased sensitivity of the neuromuscular junction to pancuronium and delayed biliary and urinary excretion.

Animals↗
PubMed1978

The comparative potency and pharmacokinetics of pancuronium and its metabolites in anesthetized man.

To determine the potency of pancuronium and its metabolites, 3-OH-, 17-OH- and 3,17-OH-pancuronium, cumulative dose-response curves were determined in five anesthetized patients with each drug. Pancuronium (ED50 = 0.041 mg/kg) was 2 times more potent than 3-OH-pancuronium (ED50 = 0.082 mg/kg), 50 times more potent than 17-OH-pancuronium (ED50 = 2.0 mg/kg) and 54 times more potent than 3,17-OH--pancuronium (ED50 = 2.15 mg/kg). In 21 other patients, one equipotent dose of either pancuronium or one of its metabolites was given as an i.v. bolus. Onset time and duration of neuromuscular blockade from 3-OH- and 3,17-OH-pancuronium did not differ significantly from that of pancuronium; 17-OH-pancuronium had a shorter duration of action than did pancuronium. Although pancuronium tended to have a slightly longer elimination half-life, the pharmacokinetics of the four drugs did not differ significantly. The elimination half-lifes were 110, 68, 73 and 71 min for pancuronium and its 3-OH, 17-OH and 3,17-OH derivatives, respectively. We conclude that although pancuronium is more potent than its 3-OH, 17-OH and 3,17-OH metabolites, the pharmacokinetics of these three metabolites do not differ from each other and from that of pancuronium.

Dose-Response Relationship, Drug↗
PubMedDate not supplied

Differential responses of rat cerebral somatostatinergic and cholinergic cells to glutamate agonists.

Reductions in cortical somatostatin (SRIH) and choline acetyl-transferase (ChAT) are major biochemical deficits in Alzheimer disease (AD). SRIH and ChAT were measured in fetal rat cerebral neurons after exposure to the glutamate agonists N-methyl-D-aspartate (NMDA), kainate (KA), and quisqualate (Q). NMDA (96 h incubation) stimulated SRIH release and content in a dose-dependent manner with a Bmax of 10(-5)M and EC50 of 2-3 x 10(-6)M. KA showed a small stimulation in SRIH levels at 10(-5)M, but produced marked inhibition at 10(-4)M. Q decreased both intracellular and secreted SRIH. KA (51-76% of basal) and Q (27-56% of basal) but not NMDA (91-114% of basal) also inhibited the incorporation of [35S]methionine into proteins. In similar experiments 10(-4)M Q (23 +/- 9% of basal) and KA (20 +/- 3% of basal) but not NMDA (80 +/- 16% of basal) reduced ChAT levels in hypothalamic/septal cultures. These inhibitory actions on ChAT activity by KA and Q were reversed by gamma-glutamyltaurine (GT) but not by 2-amino-5-phosphonopentanoic acid (AP5). Chronic NMDA exposure partially inhibited muscarinic acetylcholine receptor (mAChR) mediated inositol phospholipid (PI) turnover, whereas it was abolished after KA and Q pretreatment. These findings suggest that in cerebral cell cultures, NMDA has a stimulatory action on somatostatinergic neurons and non-NMDA receptor agonism could play an important role in EAA-mediated neural damage.

Animals↗
PubMedDate not supplied

A simple method to increase the FDO2 of resuscitator bags.

Four resuscitator bags were studied to see if the delivered fractional oxygen percentage (FDO2) could be affected by manually controlling the inherent reexpansion rate of the bag so as to allow a greater entrainment of oxygen rather than air into the bag. Flow rates of oxygen into the bag were varied: 5, 10, 15, and 20 liter/min. For each flow rate, bag refill (reexpansion) times were varied: 1, 2, 4 sec. The results show that such a maneuver will effectively increase the FDO2 of the bags at all flow rates tested--in certain instances to values greater than 0.8. This maneuver would be important to resuscitation situations where it is desirable to achieve better patient oxygenation.

Humans↗
PubMedDate not supplied

TRH synthesis in "mute" thyrotropinomas: cause-effect or coincidence?

In the pathogenesis of thyrotropin (TSH) immunopositive pituitary adenomas, trigger mutagenetic events are well recognized. However, the way towards a clinical significant tumor is followed under the pressure of growth factors, among which the intrapituitary synthesis of releasing factors could bring a significant contribution. In this study, the production of thyrotropin releasing hormone (TRH) and beta TSH chain was evaluated at the mRNA level by in situ hybridization and end product level by immunohistochemistry, in 18 patients submitted to neurosurgery for pituitary macroadenomas. The hormonal sampling showed abnormal secretion for FSH in 5 and TSH in 4 patients. Seven cases were immunopositive for TSH, and expressed TSH beta mRNA. All but one out of these expressed also TRH mRNA. FSH immunoreactivity was documented in 12/ 18, only one of these being negative for TRH mRNA. Paracrine TRH could contribute to the pathogenesis of these "mute" adenomas.

Adolescent↗
PubMedDate not supplied

Expression of thyrotropin-releasing hormone messenger RNA in human pituitary adenomas with follicle-stimulating hormone immunoreactivity.

OBJECTIVE: To assess the correlation between thyrotropin-releasing hormone (TRH) messenger RNA (mRNA) and the immunoreactive type of human pituitary adenomas. METHODS: Twenty-eight patients (14 to 73 years old) who had pituitary adenomas (18 nonfunctioning adenomas, 8 growth hormone-secreting adenomas, and 2 prolactinomas) underwent surgical treatment. Pituitaries removed at autopsy from four patients without evidence of pituitary disease were used as controls. Fragments of pituitary adenomas were processed for TRH mRNA by in situ hybridization (radioactive and nonradioactive) and for TRH peptide and anterior pituitary hormones (b-thyrotropin, b-follicle-stimulating hormone [FSH], bluteinizing hormone [LH], prolactin, and growth hormone) by immunohistochemistry with use of the avidinbiotin technique. Quantitative immunohistochemical studies were performed by using image analysis software. The signal was considered positive when more than 5% of the cells were stained. RESULTS: Cells expressing TRH mRNA were detected in 22 of 28 pituitary adenomas--15 of 18 nonfunctioning pituitary adenomas, 5 of 8 growth hormone-secreting adenomas, and both prolactinomas. TRH peptide was revealed in only 10 adenomas, all expressing TRH mRNA as well. All but one nonfunctioning adenoma expressing TRH mRNA in more than 5% of the cells were b-FSH immunoreactive (15 of 16 cases; P<0.005, c 2 test), whereas only 6 of 16 nonfunctioning adenomas exhibited both b-thyrotropin and TRH mRNA and only 5 of 16 were positive for both b-LH and TRH mRNA. CONCLUSION: These results confirm previous data demonstrating the presence of TRH mRNA and TRH peptide in human pituitary tumor cells. We further showed that the presence of TRH mRNA is significantly correlated with FSH immunoreactive gonadotropinomas. The release of FSH after an intravenous TRH test only in gonadotropinomas, together with local production of TRH, suggests a role for TRH in pathogenesis.

Journal Article↗