Search PubMed⌕ Search

Biomedical subjects

J M Little

Publications and source records attributed to J M Little.

At least 109 records · Page 6Linked to original sources
PubMed1988

Inhibitors of sterol synthesis. Metabolism of 5 alpha-cholest-8(14)-en-3 beta-ol-15-one after intravenous administration to bile duct-cannulated rats.

The metabolism of 5 alpha-cholest-8(14)-en-3 beta-ol-15-one has been studied after intravenous administration to bile duct-cannulated rats. Very rapid and substantial conversion of the 15-ketosterol to polar biliary metabolites was observed in both male and female rats. For example, upon intravenous injection of [4-14C]5 alpha-cholest-8(14)-en-3 beta-ol-15-one to male bile duct-cannulated rats, approximately 86% of the administered 14C was recovered in bile in the first 38 h. Of the total amount of 14C recovered in bile in 38 h, approximately 50% was excreted in bile in the first 70 min and approximately 90% was excreted within 8 h after the injection of the 15-ketosterol. A substantial fraction of the polar biliary metabolites was shown to undergo enterohepatic circulation. Of the radioactivity derived from the labeled 15-ketosterol which was not recovered in bile or other excreta at 48 h after the intravenous administration of the 15-ketosterol, most (approximately 79%) was recovered in the form of cholesterol and cholesteryl esters of blood and the various tissues. The very substantial and rapid biliary excretion of polar metabolites of the 15-ketosterol (or of cholesterol derived from the 15-ketosterol), coupled with inhibition of the intestinal absorption of cholesterol by the 15-ketosterol, may contribute to the overall hypocholesterolemic action of the 15-ketosterol which has been observed in rodents and in nonhuman primates by providing a metabolic pathway(s) wherein a substantial fraction of the absorbed 15-ketosterol is rapidly removed from the body by biliary excretion in the form of polar metabolites.

Animals↗
PubMed1988

Intestinal absorption of bile acid glucuronides in rats.

While the intestinal absorption of taurine, glycine, and sulfate conjugates of bile acids has been studied extensively, nothing is known about the absorption of bile acid glucuronides. In the present study, the intestinal phase of the enterohepatic circulation of two bile acid glucuronides was examined. [3 beta-3H]cholic acid 3-O-beta-D-glucuronide or [3 beta-3H]lithocholic acid 3-O-beta-D-glucuronide was perfused through isolated segments of ileum or jejunum with intact blood supply in rats prepared with a biliary fistula. [14C]Taurocholic acid was perfused simultaneously with each glucuronide to compare glucuronide absorption with that of an actively transported bile acid. Intestinal absorption was determined by measuring the rate of secretion of labeled bile acid in bile. The absorption of [3H]cholic acid glucuronide by the ileum and jejunum was one fortieth and one eighth, respectively, that of [14C]taurocholic acid. Comparison of the two glucuronides show that [3H]lithocholic acid glucuronide absorption was 18 and 10 times greater than [3H]cholic acid glucuronide absorption from the jejunum and ileum, respectively. Collectively, the above observations suggest that glucuronidation of bile acids markedly reduces absorption from the small intestine.

Animals↗
PubMed1988

Long-term canine duct-occluded segmental pancreatic autografts: endocrine function.

This study examines the endocrine function of duct-obliterated canine segmental autografts for periods up to 5 years posttransplant. Overall the response profile of autografted animals was subnormal. After intravenous glucose tolerance tests K-values in transplanted animals (2.8 +/- 0.9%/min) were significantly lower than normal (4.6 +/- 1.2% min, p less than 0.001). After oral glucose stimulation, blood glucose in the autografted dogs reached a mean peak of 10.6 +/- 2.8 mmol/L whereas in normal dogs the peak value was 6.0 +/- 1.0 mmol/L (p less than 0.002). The mean insulin response in autografted dogs showed lower insulin concentrations in the early stages of the test, whereas insulin secretion after glucagon stimulation was significantly reduced in autografted dogs. Intravenous glucose tolerance tests were analyzed by calculating K value or measuring a single blood glucose concentration 40 min after glucose injection. This value had a high correlation with the K value (r = 0.967). No progressive deterioration of graft function up to 5 years was found. Glycosylated hemoglobin levels were measured in autografted (646 +/- 59 pmol/mg) and normal dogs (620 +/- 85 pmol/mg) and no significant difference was found. In conclusion, duct-occluded segmental pancreatic autografts were shown to have a reduced functional capacity but there was no deterioration of function up to 5 years after duct-occlusion and grafting. The degree of metabolic control may be sufficient to prevent diabetic complications.

Animals↗
PubMed1988

Long-term duct-occluded segmental pancreatic autografts. Does fibrosis lead to graft loss?

In clinical pancreas transplantation, duct-occluded segmental allografts are often used. There is concern that fibrosis following duct-occlusion may lead to progressive graft failure. In this study, sequential histology and endocrine function in long-term (up to 5 years) canine autografts were assessed. Segmental pancreatic autografts with residual pancreatectomy were performed, and the pancreatic duct was occluded with cyanoacrylate glue. Serial i.v. glucose tolerance tests (IVGTT) and percutaneous needle-core biopsies of the grafts were performed as long as grafts functioned. Ten dogs were long-term (greater than 18 months) survivors: 8 dogs had functioning grafts for a median of 48 months (range 18-60) after transplantation, and 3 dogs had graft failure at 21, 27, and 60 months. The mean 40-min blood glucose concentration (BGL-40') after i.v. glucose injection did not increase with time up to 5 years after grafting. Graft biopsies showed a universal picture of aggregated islet cells and fibrous replacement of acinar tissue. The total amount of fibrosis did not change with time, but the existing fibrosis became less cellular and more dense. This long-term study showed that in autografted animals, adequate endocrine function was maintained in the majority of cases, and progressive replacement of islet tissue by fibrosis could not be demonstrated in serial biopsies taken between 18 months and 5 years after autotransplantation. We therefore conclude, that while duct-occlusion results in extensive fibrosis, the process is not progressive, and although fibrosis may contribute to late graft failure this is not inevitable.

Animals↗
PubMed1988

Early diagnosis of rejection of canine pancreas allografts by fine-needle aspiration biopsy.

In pancreatic allograft transplantation with bladder exocrine drainage, falls in urinary amylase (UA) levels have been shown to be an earlier marker of rejection than rises in fasting blood glucose levels. Nevertheless, this is often too late for reversal of the rejection process. In an attempt to diagnose rejection earlier, fine-needle aspiration biopsy was correlated with UA and graft histology. Sixteen dogs were given total pancreatic allografts, 10 without immunosuppression and 6 with triple therapy. FNAB and needle-core biopsies were performed on days 0, 2, 4, 7, 9, 24, and 30 and/or at functional rejection, defined as a fasting UA level of less than 5000 IU/L. Cytocentrifuge preparations of the FNABs were evaluated by total corrected increment (TCI) scores. These increased significantly from 1.0 (+/- 0.4; mean +/- SEM) 6 days, to 3.0 (+/- 1.2) 4 days before functional rejection. The increase was due to the presence of blast cells and macrophages. The TCI of healthy immunosuppressed grafts remained below 1.6 for 30 days after transplantation and was greater than 5.0 when pancreatitis or acute rejection was seen on conventional histology. Minimal histologic change had significantly lower TCI scores than both acute rejection (P less than 0.01) and pancreatitis (P less than 0.001). Acute rejection and pancreatitis were distinguished by a significant difference in increments of monocytes/lymphocytes and macrophages. In contrast to FNAB, UA levels did not differentiate minimal change from acute rejection but were a reliable marker of end-stage rejection.

Amylases↗
PubMed1988

Injuries of branches of the aortic arch.

Injuries to the carotid, subclavian, axillary and vertebral arteries have comprised 19.5% of vascular trauma seen at Westmead Hospital during the period 1979-86. The cause of injury was penetrating trauma in 38.5% of cases, and blunt trauma, due mainly to motor vehicle or motor bike accident, in 61.5% of cases. In most cases (77%) the vascular injury was apparent because of large and/or expanding haematoma or overt haemorrhage. There was a large incidence of associated injury with head injury in 46% and brachial plexus injury in 31%. The mortality was high (46%), with most patients dying from the associated head injury, but one patient died from stroke after presenting with a neurological deficit associated with a carotid injury.

Adolescent↗
PubMed1988

EEG monitoring during carotid endarterectomy.

One hundred and thirty-one patients undergoing 142 carotid endarterectomy procedures were randomized to have their operation performed either with or without intra-operative electroencephalographic (EEG) monitoring. Patients with EEG monitoring were shunted if both the internal carotid back pressure (ICBP) was less than 50 mmHg and ipsilateral change was evident on the EEG after clamping. Patients without EEG monitoring were shunted if ICBP was less than 50 mmHg. There one postoperative death (0.7%) with neurological deficits occurring in five patients (3.5%). There were significantly fewer neurological deficits (P = 0.02) in patients with no EEG change (one of 59) compared with those with EEG change (two of 13). There was a highly significant increase (P = 0.005) in incidence of neurological deficit (two of five patients) when ICBP was considered 'adequate' at 50 mmHg or greater but EEG change occurred. No neurological deficit occurred in 14 patients who were not shunted with ICBP less than 50 mmHg but with no EEG change. There was no difference in the incidence of neurological deficit in patients with low and high ICBP when both 50 and 55 mmHg were used as the cut-off points. It is concluded that EEG monitoring is useful in identifying patients requiring shunting during carotid endarterectomy. Use of a shunt is recommended if there is EEG change regardless of ICBP; conversely, if ICBP is low but there is no EEG change it would appear safe to proceed without shunting.

Adult↗
PubMed1988

Monitoring of canine pancreas allograft function with measurements of urinary amylase.

A canine model of whole pancreas transplantation with pancreaticocystostomy was studied for predictability of graft rejection using urinary amylase (UA) monitoring. Six pancreatectomized dogs were transplanted without immunosuppression and with acute rejection occurring at a median of 9.5 days (range 7-12 days). A differential loss of allograft exocrine and endocrine function was demonstrated, with a gradual decrease in UA after transplantation but maintenance of fasting blood glucose levels (FBGL) till the day before complete loss of graft structure. Another 13 dogs treated with cyclosporin (25 mg/kg per day) had prolonged graft survival (P less than 0.01) with an actuarial median survival of 91 days (range 8-159 days). Five allografts were lost because of rejection and eight dogs died with functioning grafts. Fasting spot levels of UA less than 5000 iu/l or less than 10,000 iu/l had a positive predictivity of graft failure of 71% or 31%, respectively. Falls of UA levels of greater than 75% in 24 h and 48 h were seen equally in both rejecting and functioning allografts. This study confirmed the role of UA as an earlier marker of rejection than FBGL. The clinical role of UA will be important, but its use as a predictor of pancreas rejection may be dependent on a fall to a predetermined level rather than the rate of fall.

Amylases↗
PubMed1988

Hepatocellular carcinoma in western Sydney.

All the cases of proven hepatocellular carcinoma seen at Westmead Hospital, Sydney between January 1980 and the end of 1987 were reviewed. Hepatitis B infection was the major predisposing condition. Six patients had taken significant doses of sex steroids. Seventeen of the patients were cirrhotic at the time of diagnosis and in seven of these there was a significant history of alcohol abuse. AFP was elevated in only 15 of the 34 patients. Multiple regression analysis revealed that the single, independent determinant of a raised AFP level was found to be presence of Hepatitis B infection. Resection was possible in 10 patients. In the last ten months, seven patients have been treated by embolisation of the tumour with Adriamycin bonded to lipidol. Survival was influenced by the presence or absence of cirrhosis but not by evidence of Hepatitis B infection. The prognosis for patients with hepatocellular carcinoma in Australia is as dismal as it is in any other country. Although a rare tumour its incidence may well increase as the community now contains relatively greater numbers of immigrants from areas where the risk of developing a hepatocellular carcinoma is higher and because of the number of drug addicts who are frequently exposed to Hepatitis B infection. With the exception of patients with Hepatitis B infection, screening with AFP holds little promise in the Caucasian community.

Biomarkers, Tumor↗
PubMed1988

Subclavian vein catheterisation for parenteral nutrition.

Two hundred and twenty-six central venous catheters were placed in 195 consecutive patients requiring central venous catheterisation for total parenteral nutrition (TPN). Of these 226 catheters, 198 were placed percutaneously into the subclavian vein by the infraclavicular route. In 99 consecutive subclavian catheter insertions, a 12G needle with introducing sheath was used to puncture the vein (Group 1). The Seldinger method of catheterisation was used in another 99 consecutive subclavian catheter insertions (Group 2), the vein being punctured with a 19G needle. Pneumothorax occurred on three occasions (3.0%) in Group 1 but did not occur in Group 2. However, there were two episodes of pleural extravasation in Group 2 (2.0%) which may have been due to guide wire perforation of a central vein; this complication did not occur in Group 1. Although the Seldinger technique of insertion should reduce the incidence of pneumothorax, care should be taken in passage of the guide wire.

Adolescent↗
PubMed1988

Abnormal dark-adapted electroretinogram in Best's vitelliform macular degeneration.

It is generally well accepted that in Best's vitelliform macular degeneration (BVMD) the electroretinogram (ERG) is normal whereas the electro-oculogram (EOG) is markedly abnormal. We describe a patient in whom BVMD was suspected on the basis of the clinical findings, EOG and family history (one of her daughters had the typical vitelliform lesion). However, her dark-adapted ERG was markedly abnormal. Similar anomalies were found in the dark-adapted ERG of the daughter. While the temporal features of the various ERG waves were well preserved, a substantial decrease in the amplitude of specific segments of the ERG signal was observed. A similar decrease in the amplitude of the oscillatory potentials was also found. We believe that this unusual combination of BVMD and abnormal dark-adapted ERG may be due to the reported reduced penetrance and variable expressivity of the BVMD gene(s).

Adult↗