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Biomedical subjects

J M Little

Publications and source records attributed to J M Little.

At least 163 records · Page 9Linked to original sources

A comparison between primary and secondary liver cancer.

Two groups of patients have been compared, one with primary liver cancer, the other with liver secondaries. The groups did not demonstrate major differences in age, sex, ethnic background or treatment methods. Although patients with secondaries showed some survival advantage during the first 6-12 months, any difference had disappeared by 24 months. Patients with potentially 'curable' lesions having hepatic resection fared significantly better than all other patients, whether their tumours were primary or secondary in the liver. For practical purposes, the two groups can be considered as having problems of comparable biological significance.

Actuarial Analysis↗

Lithocholate glucuronide is a cholestatic agent.

Lithocholic acid and its taurine, glycine, and sulfate derivatives are potent cholestatic agents. Lithocholate glucuronide is present in the plasma and urine of patients with cholestatic syndromes, but little is known of its metabolism, excretion, and cholestatic potential. [3 beta-3H]lithocholate 3-O-beta-D-glucuronide was synthesized, and chemical and radiochemical purity were established. The aqueous solubility of lithocholate glucuronide was determined and found to be greater than that of lithocholic acid or several of its derivatives. In the range of concentrations examined, calcium ions precipitated lithocholate glucuronide stoichiometrically. The material was administered to rats prepared with an external biliary fistula. When 17-25 micrograms quantities were administered, 89.1 +/- 4.5% (mean +/- SEM) of the radiolabel was secreted in bile within the first 20 h after administration, the major fraction being secreted in less than 20 min. Four-fifths of the radiolabeled material in bile was the administered unaltered parent compound, while a minor fraction consisted of a more polar derivative(s). We showed that increasing biliary concentrations of more polar derivatives were observed with milligram doses of [3H]lithocholate glucuronide, and with time after the administration of these loading doses. Milligram doses of [3H]lithocholate glucuronide resulted in partial or complete cholestasis. When induced cholestasis was partial, secretion in bile remained the primary excretory route (82.5-105.6% recovery in bile), while, when complete cholestasis was induced, wide tissue distribution of radiolabel was observed. Cholestasis developed rapidly during infusion of [3H]lithocholate glucuronide. Bile flow was diminished within 10-20 min of the start of an infusion of 0.05 mumol, 100 g-1 body weight, minute-1, administered concomitantly with an equimolar infusion of taurocholate. The results establish that lithocholate glucuronide exerts cholestatic effects comparable to those exerted by unconjugated lithocholic acid.

Animals↗

Experience with barbiturate therapy for cerebral protection during carotid endarterectomy.

Carotid endarterectomy was performed 28 times in 27 patients. All but one patient had symptomatic carotid artery disease, 59% had bilateral disease and 59% had associated intracranial disease. Barbiturate therapy was used as a means of cerebral protection during carotid artery cross-clamping. Neurological deficit occurred in two patients, being permanent in one patient (3.5%); both patients had bilateral carotid and intracranial disease and both had carotid stump pressures greater than 55 mmHg. No morbidity could be attributed to barbiturate usage.

Adult↗

Keratoconus and Leber's congenital amaurosis: a clinicopathological correlation.

A 42-year-old man with Leber's congenital amaurosis, cataracts and keratoconus died following abdominal surgery. Postmortem pathological examination of the globes disclosed cone-shaped corneas with unusual central subepithelial scars and a retinopathy consistent with retinitis pigmentosa. A review of the family history revealed two siblings with congenital blindness.

Adult↗

Ocular neurofibromatosis.

A 4 1/2-month-old girl with unilateral congenital glaucoma of the left eye subsequently underwent five surgical procedures that proved to be unsuccessful in controlling the intraocular pressure. Neurofibromatosis was diagnosed at the age of 5 1/2 years when she was found to have a plexiform neuroma of the left eyelids and multiple café au lait spots including in the left temple. Two years later the buphthalmic left globe was enucleated. Histopathologic findings included a diffuse neurofibroma of the ciliary body and choroid, peripheral anterior synechiae, total angle closure, and endothelialization of the iris, all of which probably contributed to the glaucoma. Other interesting features were melanocytic hamartomas of the iris, an anterior subcapsular cataract and ovoid bodies in the diffuse neurofibroma of the choroid.

Child, Preschool↗

Hepatic resection.

In the four years between the beginning of 1979 and the end of 1982, 23 hepatic resections have been carried out for tumours, trauma, biliary access, cystic disease of the liver and spontaneous rupture. There have been four deaths amongst these 23 patients. The 23 resections were performed on 68 patients referred for possible surgery on their hepatic lesions. Right-sided hepatic resections and resections carried out under emergency circumstances were found to carry a significantly higher risk than all other resections. Of the various organ imaging methods available for assessment of hepatic tumours, CT scanning seems to be the most powerful. Liver surgery is probably best done in a limited number of units prepared to implement appropriate protocols of investigation and surgical management.

Adult↗

Chronic pancreatitis: results of a protocol of management.

Thirty-five patients with chronic pancreatitis of varying cause have been treated according to a protocol first introduced in 1979. At the end of a mean follow up time of 2.1 years, only 54% of patients were found to have derived benefit defined by pain relief and improved quality of life. Patients with alcoholic pancreatitis did particularly poorly, and alcoholics who continued to drink almost never benefited. Patients with dilated pancreatic ducts were more likely to do well than those with small ducts, and pancreaticojejunostomy had a satisfactory record of pain relief. Patients with biliary pancreatitis generally did well with cholecystectomy and clearance of the common bile duct. The 40-80% pancreatectomy had a poor record for pain relief, and produced diabetes in the majority of patients in whom it was used. Nothing will reverse the established pathology of chronic pancreatitis, which remains an unsatisfactory condition to treat.

Adult↗

What is meant by the term "bile acid"?

The bile acids are a set of acidic steroids. Many conventional bile acids share a common derivation and have functional characteristics in common. Exceptions exist, however, to virtually all of the rules that can be applied to a definition of bile acids. The term is thus best applied to those steroids with a side chain at C-17, which contains a carboxylic acid group, and to acidic derivatives of such compounds. Naturally occurring bile acids are a more numerous and diverse group than has been generally recognized. The site of origin, synthetic pathways, metabolism, and bioactivity of recently recognized unconventional bile acids are under intensive investigation.

Animals↗

Development of the bile acid pool in rats from neonatal life through puberty to maturity.

The bile acid pools of developing rats were measured by gas-liquid chromatography. From shortly after birth the bile acid pools fell to a nadir on the 10th day of life (0.295 +/- 0.031 mg X g-1 body weight at 2 days to 0.144 +/- 0.012 mg X g-1 body weight at 10 days, p less than 0.001). The pool re-expanded rapidly between the 12th and 15th day. After weaning and during puberty there was a further temporary increase in pool size, during which females had larger pools than males. By adulthood the pool size had returned to the 2-day-old and weanling (15- and 18-day-old) levels, expressed per gramme body weight, and there was no longer a significant sex difference. These results show that changes in pool size are occurring at times when there are major physiological changes in the developing animal. The changes during puberty suggest hormonal control.

Aging↗

Hepatic metabolism of 3 alpha-hydroxy-5 beta-etianic acid (3 alpha-hydroxy-5 beta-androstan-17 beta-carboxylic acid) in the adult rat.

Normal human meconium has been shown to contain short-chain (C20-C22) bile acids and, recently, these compounds have been identified in sera of patients with cholestasis. This suggests that shortchain bile acids may be secreted in bile. We have examined this point by studying the hepatic metabolism and biliary secretion of one naturally occurring C20 bile acid, 3 alpha-hydroxy-5 beta-etianic acid (3 alpha-hydroxy-5 beta-androstan-17 beta-carboxylic acid). [3-3H]-3 alpha-hydroxy-5 beta-etianic acid was prepared and administered intravenously to rats prepared with an external biliary fistula. 85.5 +/- 1.2% of the administered dose was recovered in bile over 20 h with 71.5 +/- 1.3% appearing in the first hour. 11.9 +/- 1.6% of the dose was estimated to be distributed in body water and 0.6 +/- 0.2% was recovered as organic matter in urine. Total recovery of label was 98.0 +/- 2.6%. Administration of milligram quantities of 3 alpha-hydroxy-5 beta-etianic acid produced an increase in bile flow (58.9 +/- 7.1% over basal levels) within 20 min after injection of the steroid. The radiolabeled material in bile was shown by thin-layer chromatography (TLC) to be a polar conjugate which, after beta-glucuronidase hydrolysis, cochromatographed with authentic free 3 alpha-hydroxy-5 beta-etianic acid. After purification, and derivatization, the steroid moiety was proven by gas chromatography-mass spectrometry to be identical to 3 alpha-hydroxy-5 beta-etianic acid. Characterization of the conjugate by TLC and by 3 alpha-hydroxysteroid dehydrogenase assay, before and after beta-glucuronidase hydrolysis, indicated that the steroid was secreted in bile as the 3-O-beta-glucuronide. It is concluded that 3 alpha-hydroxy-5 beta-etianic acid is cleared from the plasma, conjugated with glucuronic acid, and secreted into bile rapidly and in high concentration. The choleretic properties of this shortchain bile acid contrast with the cholestatic effects of lithocholic acid, its C24 analog. Both the form of conjugation of etianic acid and its effect on bile flow suggest that the shortened side chain of this steroid markedly alters its hepatic metabolism and physiology.

Androstanols↗

Diversity of bile acids in the fetus and newborn infant.

The bile acids found in the fetus and newborn are more numerous and diverse than has generally been appreciated. The four conventional bile acids, cholic, chenodeoxycholic, deoxycholic, and lithocholic acids, are found. In addition, however, stereoisomers of the conventional bile acids, bile acids with functional groups at different positions or in greater number than found in conventional bile acids, and "short-chain" and "long-chain" bile acids are found. The site of origin, pathways of synthesis, metabolism, and excretory routes of these unconventional bile acids are largely unknown. Their effects on the function of the liver and other tissues have not yet been established. It is uncertain which of these compounds is peculiar to the fetus and newborn, and which will be found in normal or abnormal adults. This review is an early look at a field bound to advance rapidly in the next several years.

Bile↗

The photopic electroretinogram in congenital stationary night blindness with myopia.

Previous studies have reported that subjects affected with congenital stationary night blindness and myopia demonstrated some photopic (cone) abnormalities in their electroretinogram (ERG). By comparing the photopic ERG elicited with a threshold and a suprathreshold stimulus it was found that, at threshold, no significant differences were noted both in the peak time and in the amplitude of ERGs evoked from CSNB and normal subjects. However, a more powerful stimulus (16 times the threshold) yields a significant difference in the ERGs recorded from the two groups. ERGs recorded from CSNB patients are decreased in amplitude with a b-wave peak time that remains normal. First derivative analysis of the ERG wave along with a selective recording of the oscillatory components of the ERG suggest that the only visible anomaly in the suprathreshold photopic ERG of CSNB patients is an absence of the two oscillations normally seen on the ascending portion of the b-wave. Data obtained on normal subjects are also reported that try to explain the functional significance of these two oscillatory potentials.

Electroretinography↗

Unilateral congenital ptosis and amblyopia.

Amblyopia was detected in 15 of 55 children with unilateral congenital ptosis. Anisometropia was the main cause of the amblyopia in 10 cases, and strabismus alone was the cause in 2 cases. In three cases amblyopia developed after ptosis surgery.

Adolescent↗

Glucagon stimulation of hepatic Na+, K+-ATPase.

In the perfused rat liver administration of glucagon was shown to result in a transiently increased uptake of K+, indicating the possible involvement of the Na+, K+-ATPase. Direct measurement of the activity of Na+, K+-ATPase revealed a two-fold stimulation of the enzyme by glucagon. The effect of glucagon on the activity of the enzyme was immediate. Simultaneously with the increase in the activity of the Na+, K+-ATPase, the activity of Mg2+-ATPase decreased. In order to evaluate whether the activation of the Na+, K+-ATPase by glucagon is related to the metabolic effects of the hormone, experimental conditions known to interfere with the activity of the enzyme were employed and glucagon stimulation of Ca2+-efflux, mitochondrial metabolism and gluconeogenesis were measured. K+-free perfusate, high K+ perfusate or ouabain interfered to varying degrees with the glucagon stimulation of these responses. The combination of K+-free perfusate and ouabain almost completely abolished the glucagon stimulation of all three parameters. These results demonstrate the glucagon stimulation of Na+, K+-ATPase and raise the possibility that the activation of the enzyme by glucagon might be a necessary link for the manifestation of its metabolic effects.

Animals↗

Long-term sequelae of gastrectomy.

The sequelae of gastrectomy are well-known. This paper describes a complicated clinical course which occurred eight years after partial gastrectomy. Initial features included marked weight loss, anaemia, multiple lung and liver abscesses, and cholestatic jaundice. Acalculous cholecystitis with a mucocele of the gallbladder developed later. We emphasise the value of total parenteral nutrition in supporting such critically ill patients.

Abscess↗