A presumed intramural injection.
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Biomedical subjects
Publications and source records attributed to M W Goodman.
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Urea excretion per gram of liver was increased 219% 2-5 h post-partial hepatectomy (Hx) and 45% 24-27 h post-Hx. Mitochondrial carbamoyl-phosphate synthetase was also increased 5 h post-Hx but was not increased at 27 h. An NH4+ load did not increase urea excretion per gram liver or the enzyme activity noticeably in the 2- to 5-h period but did increase them 24-27 h post-Hx. These results suggest that the enzyme activity and urea formation per unit weight of liver were nearly maximal early during regeneration. Orotic acid excretion per gram of liver in rats that received NH4+ was increased more than 30-fold 2-5 h post-Hx and was similar in this respect to nonhepatectomized rats. Ornithine prevented the increase in both normal and hepatectomized rats, suggesting that ornithine was rate limiting for the ornithine carbamoyltransferase (OCT) reaction. The orotic acid excretion response to NH4+ was much less 24-27 h post-Hx, indicating that ornithine availability for the OCT reaction may be increased at this time.
To examine the beneficial effect of arginine on ammonia intoxication, rats were injected intraperitoneally with a single dose of NH4Cl (6.75 mmol/kg) with and without arginine (5.0 mmol/kg) or ornithine (5.0 mmol/kg). Arginine or ornithine reduced the blood ammonia nitrogen at 30 min after NH4Cl injection from 3,288 +/- 800 micrograms/dl (mean +/- SE) to 538 +/- 90 and 575 +/- 34 micrograms/dl, respectively. In rats administered this dose of NH4Cl, arginine or ornithine did not increase further the hepatic carbamoyl-phosphate synthetase (EC 6.3.4.16) activation by N-acetylglutamate beyond the effect of NH4Cl. However, arginine or ornithine did increase the hepatic citrulline and urea content as well as the plasma urea concentration in these NH4Cl-injected rats. In rats injected with four doses of NH4Cl (2.5 mmol/kg), arginine or ornithine pretreatment increased the urea excretion and normalized the orotic acid excretion. These results indicate that arginine mitigates ammonia intoxication in the rat by increasing ornithine carbamoyltransferase activity through increased ornithine availability and not via activation of N-acetylglutamate synthetase. By increasing ornithine carbamoyltransferase activity, ornithine enhances the conversion of ammonia to citrulline and urea.
To determine whether the [14C] aminopyrine breath test (ABT) predicts surgical risk in patients with liver disease, it was obtained prior to various surgeries in 38 patients with known or suspected liver disease. A modified Child's classification was also determined. Six of the seven operative deaths (three Child's A, two B, two C) had ABTs less than 2.3%, while 30 of 31 survivors (24 Child's A, seven B) had ABTs greater than 2.3% (p less than 0.000018). Seven of the 16 patients with normal ABTs had biopsy-proven cirrhosis and had postoperative courses indistinguishable from the remainder of the group. We conclude that surgery in patients with ABTs less than 2.3% is associated with extremely high mortality. In addition, cirrhotics with normal ABTs tolerate elective surgery well.
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Low concentrations of thyrotropin-releasing hormone and one of its metabolites, histidyl-proline diketopiperazine, are shown to have an inhibitory effect on the activation of 3-hydroxy-3-methylglutaryl coenzyme A reductase which occurs during organ culture of canine intestinal mucosa. Somatostatin and vasoactive intestinal polypeptide, in contrast, are shown to have no effect. Thyrotropin-releasing hormone, recently shown to be present in gut mucosa, may be a physiological regulator of intestinal cholesterol synthesis. Histidyl-proline diketopiperazine, an active metabolite of the hormone, is possibly the active agent since its inhibitory effect was observed at a concentration as low as 10(-12) M. These observations demonstrate an effect on intestinal metabolism by a neurotransmitter-like hormone at potentially physiologic concentrations.
Hormonal regulation of intestinal cholesterol synthesis was studied both in vitro and in vivo. Cholesterol synthesis rate was determined by measurement of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (EC 1.1.1.34) activity and by incorporation [14C]acetate into sterol. In vitro studies utilized organ culture of canine ileal mucosa. During 6-h culture, reductase activity was stimulated sevenfold. Insulin (10-6 M) augmented this rise to 144 +/- 7% of th control activity, while 10(-8) M glucagon, 10(-3) M adenosine 3',5'-cyclic monophosphate, and 3-isobutyl-1-methylxanthine suppressed activity (final reductase activity was 83 +/- 3%, 75 +/- 4%, and 41 +/- 3%, respectively, of cultured control values). In vivo studies utilized dogs with isolated Thiry-Vella ileal fistulas. In vivo, insulin doubled reductase activity while glucagon led to a 42 +/- 9% suppression. It is concluded that insulin and glucagon may be potential physiological regulators of intestinal cholesterol synthesis. The glucagon effect may be mediated by cyclic nucleotides.
Three cases of carbamazepine-induced granulomatous hepatitis are reported. Each patient had ingested carbamazepine for less than 1 month before presenting with a febrile illness suggestive of biliary tract infection. After withdrawal of carbamazepine, symptoms disappeared rapidly. Histologically, all patients had granulomatous hepatitis. Two patients also had acute cholangitis. Carbamazepine-induced liver injury can be confused clinically and pathologically with biliary tract infection.
A retrospective study was performed to determine the usefulness of the intravenous cholangiogram for evaluation of common bile duct disease. Using interpretations obtained by chart review, 128 intravenous cholangiograms were categorized according to common bile duct visualization. Fifty-five percent of the studies were considered technically adequate for interpretation, while 23% and 22% were suboptimal and nondiagnostic, respectively. The intravenous cholangiogram diagnoses were verified when possible by comparison with the findings of: (a) endoscopic retrograde cholangiography, (b) operative cholangiography, (c) choledochotomy, or (d) autopsy. In verified studies of adequate intravenous cholangiograms, the diagnostic error rate was 40%, largely owing to missed stones. We conclude that the intravenous cholangiogram is usually unreliable for biliary tract evaluation, and should be replaced by alternative studies such as endoscopic or transhepatic cholangiography.
Based on the results of aggressive screening of 20,000 women and an annual average midbreast absorbed dose of 1 rad per year, the authors describe a model for estimating the benefit/risk ratio for mammography in screening populations of asymptomatic, randomly selected women. Benefits in terms of breast-cancer deaths averted over not screening are estimated. The "worst-case" estimate of the benefit/risk ratio for five annual mammographic examinations on randomly selected asymptomatic women age 35-49 at the start of screening is 3.4 +/- 1.1 to 1. The corresponding "most probable" estimate is 8.0 +/- 3.1 to 1.
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