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Biomedical subjects

R Strong

Publications and source records attributed to R Strong.

At least 19 recordsLinked to original sources
PubMed1992

Modulation of tyrosine hydroxylase gene expression in the rat adrenal gland by exercise: effects of age.

Both aging and exercise are associated with alterations in circulating levels of catecholamines. To determine the interactions of age and exercise on tyrosine hydroxylase (TH) activity and TH mRNA, Fischer-344 female rats aged 5 months (young) and 25 months (old) were trained by treadmill running for 10 weeks. The elevation in maximum oxygen consumption in both groups was equivalent following exercise, indicating that training had occurred. In control rats, both TH activity and TH mRNA were greater in the older groups when compared with the younger animals. In young rats, exercise decreased TH activity by 25% and TH mRNA by 27%. In older rats, exercise was not associated with a decrease in TH activity and TH mRNA. Choline acetyltransferase activity (ChAT) was decreased and glutamic acid decarboxylase activity (GAD) was increased by exercise in young rats. The decrease in ChAT activity and increase in GAD activity suggest that trans-synaptic mechanisms play a role in the exercise-induced alteration of TH gene expression. Neither ChAT nor GAD was altered by exercise in older groups. Our data suggest that the previously reported diminution in catecholamines associated with exercise may be due to a decrease in TH mRNA and a resulting decrease in TH activity. There was no effect of exercise in the old rats, supporting previous observations that the plasticity of the sympathoadrenal system diminishes with age.

Acetylcholine↗
PubMed1992

Nutritional support in children with end-stage liver disease: a randomized crossover trial of a branched-chain amino acid supplement.

Malnutrition is common in children with end-stage liver disease (ESLD) awaiting orthotopic liver transplantation (OLT), and nutritional support is assuming an important role in preoperative management. To evaluate preoperative nutritional therapy, 19 children (median age 1.25 y) with ESLD awaiting OLT were prospectively studied. Two high-energy, isoenergetic and isonitrogenous nutritional formulations delivered nasogastrically were compared: a branched-chain amino acid (BCAA)-enriched semielemental formulation and a matched standard semielemental formation. Twelve of 19 patients completed a randomized controlled study before OLT and 10 of 19 completed a full crossover study. Improvements in weight and height occurred during the BCAA supplements, with no statistical change on the standard formulation. Significant increases in total body potassium, midupper arm circumference, and subscapular skinfold thickness occurred during the BCAA supplements, whereas no significant changes occurred during the standard formulation period. Significantly fewer albumin infusions were required during the BCAA supplement. These findings suggest that BCAA-enriched formulas have advantages over standard semielemental formulas in improving nutritional status in children with ESLD, and are deserving of wider application and study.

Albumins↗
PubMed1992

The nature of malnutrition in children with end-stage liver disease awaiting orthotopic liver transplantation.

To evaluate malnutrition in chronic liver disease, and its relationship to nutrient deficiencies and hepatic dysfunction, 27 children with end-stage liver disease were studied. Mean protein-energy intakes were 70% of recommended daily intakes. The patients were underweight and stunted with reduced mean triceps and subscapular skinfold thicknesses and midupper arm circumference. Mean total body potassium was only 63 +/- 18% of that expected for age and sex. Deficiency of essential fatty acids (32%), and low concentrations of fat-soluble vitamins (A, 92%; E, 32%), iron (32%), zinc (42%), and selenium (13%) were common. Serum ammonia concentrations were raised in all patients, and increased methionine, tyrosine, and glutamic acid, and reduced glutamine concentrations were noted. There was no correlation between the degree of malnutrition and the degree of liver synthetic function, the degree of cholestasis, or the degree of liver injury. We suggest that potentially correctable factors in addition to liver failure (eg, inadequate absorbed intake) were important determinants of malnutrition in these patients.

Amino Acids↗
PubMed1992

Piroxicam induced submassive necrosis of the liver.

Several widely used non-steroidal anti-inflammatory drugs have been reported as causing severe hepatitis. Three cases of severe acute hepatitis have been reported in association with piroxicam. A fatal submassive necrosis that occurred in a 68 year old lady who had received piroxicam for 15 months is described. A 48 year old man who developed submassive hepatic necrosis six weeks after beginning piroxicam but was successfully treated with orthotopic liver transplantation is also reported. Piroxicam may induce submassive necrosis of the liver, probably as an idiosyncratic reaction.

Aged↗
PubMed1992

Liver transplantation in the 1990s.

Liver transplantation is now the therapy of choice for advanced, irreversible, progressive liver disease. The authors look at who should have a transplant and explain that the predicted outcomes of surgery depend on the pre-operative disease. A brief overview of post-operative care is given.

Clinical Protocols↗
PubMed1991

Vasoactive intestinal polypeptide induces tyrosine hydroxylase in PC12 cells.

Physiological stress induces tyrosine hydroxylase, the rate-limiting enzyme for catecholamine biosynthesis, via trans-synaptic mechanisms within the adrenal medulla. Previous studies have implicated cAMP as a second messenger capable of inducing tyrosine hydroxylase; however, it is unclear whether any receptor coupled to adenylate cyclase mediates tyrosine hydroxylase induction. Recently, vasoactive intestinal polypeptide, whose receptor is coupled to adenylate cyclase in many tissues, has been shown to meet many of the criteria for a neuromodulator within the adrenal medulla. We therefore undertook a series of studies to determine whether vasoactive intestinal polypeptide may induce tyrosine hydroxylase in PC12 cells, a cell line derived from rat adrenal medulla. Here we report that vasoactive intestinal polypeptide produces a transient, time- and concentration-dependent increase in tyrosine hydroxylase mRNA levels which is followed by a stable increase in tyrosine hydroxylase protein. The increase in tyrosine hydroxylase mRNA does not occur in a mutant PC12 cell line deficient in cAMP-dependent protein kinase activity, indicating that the effect of vasoactive intestinal polypeptide is mediated through the cAMP second messenger pathway. This is the first report demonstrating that a neuromodulator which acts on an adenylate cyclase-coupled receptor can induce tyrosine hydroxylase.

Animals↗
PubMed1991

Degeneration of the cholinergic innervation of the locus ceruleus in Alzheimer's disease.

Choline acetyltransferase (Acetyl-CoA: choline O-acetyltransferase: EC 2.3.1.6) (ChAT) enzyme activity and neuron density were measured in the locus ceruleus (LC) of autopsied brains of neurologically normal individuals and patients who had Alzheimer's disease. Neuron density in the LC of individuals with Alzheimer's was significantly reduced to approximately 50% of normal values. ChAT activity was also reduced by about 50%. Furthermore, the number of pigmented neurons in the LC was highly correlated with presynaptic ChAT activity. These findings were specific for the LC, since deficits in ChAT and neuron density were not found in two adrenergic brainstem nuclei (C1 and C2). We measured mitogen activity in LC extracts in order to determine whether loss of cholinergic afferents to the LC, as evidenced by loss of ChAT, was related to putative trophic factors. Mitogen activity was significantly reduced (50%) in the Alzheimer's group as compared to normals. Mitogen activity was significantly correlated with ChAT activity and the density of neurons in the LC. The loss of cholinergic nerve terminals in the LC in Alzheimer's disease may be functionally significant, since acetylcholine has important effects on LC physiology. The highly significant relationships between ChAT, neuron density and mitogen activity has important implications for our understanding of mechanisms of neurodegeneration in Alzheimer's disease.

Aged↗
PubMed1991

Malnutrition in children with chronic liver disease accepted for liver transplantation: clinical profile and effect on outcome.

The nutritional profiles of 37 children (aged 0.5-14.0 years) with chronic liver disease at the time of acceptance for orthotopic liver transplantation (OLTP) have been evaluated using clinical, biochemical and body composition methods. Nutritional progress while waiting for a donor has been related to outcome, whether transplanted or not. At the time of acceptance, most children were underweight (mean standard deviation (s.d.) weight = -1.4 +/- 0.2) and stunted (mean s.d. height = -2.2 +/- 0.4), had low serum albumin (27/35) and had reduced body fat and depleted body cell mass (measured by total body potassium--mean % expected for age = 58 +/- 5%, n = 15). Mean ad libitum nutrient intake was 63 +/- 5% of recommended daily intake (RDI). Those who died while waiting (n = 8) had significantly lower mean initial s.d. weight compared with those transplanted. The overall actuarial 1 year survival of those who were transplanted (mean waiting time = 75 days) was 81% but those who were initially well nourished (s.d. weight greater than -1.0) had an actuarial 1 year survival of 100%. There were no significant differences in actuarial survival in relationship to age, type of transplant (whole liver or segmental), liver biochemistry or the presence or absence of ascites. Of the total group accepted for OLTP, whether transplanted or not, the overall 1 year survival for those who were relatively well nourished was 88% and for those undernourished (initial s.d. weight less than -1.0) was 38% (P less than 0.003). Declining nutritional status during the waiting period also adversely affected outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Predicting cholangiocarcinoma in patients with primary sclerosing cholangitis before transplantation.

Patients with primary sclerosing cholangitis are at an increased risk of developing cholangiocarcinoma, which is difficult to diagnose because the biliary tree is already distorted. Eleven patients with primary sclerosing cholangitis who underwent orthotopic liver transplantation at this hospital were evaluated. Four patients had coincidental histologically proved cholangiocarcinoma. Patients with cholangiocarcinoma in contrast to patients without tumour presented with rapid onset of persistent jaundice, pruritus, and weight loss associated with an appreciable rise in bilirubin (8x v 2x) and alkaline phosphatase (3.5x v 1.2x) over one year. Cholangiography and computed tomography showed appreciably dilated intrahepatic bile ducts (3/4 v 0/7). The diagnosis of cholangiocarcinoma could only be established before operation in one patient by fine needle aspiration cytology. Tumour was recognised at operation in one other. Histological examination of hepatectomy specimens showed that patients with cholangiocarcinoma had less advanced histological features of primary sclerosing cholangitis. Multiple areas of carcinoembryonic antigen positive epithelial atypia and carcinoma in situ were found in all patients with cholangiocarcinoma. Cholangiocarcinoma recurred in two patients at 14 and 39 months after transplantation. Superimposed cholangiocarcinoma can be predicted in most patients with cholangitis before transplantation, although a definitive diagnosis is difficult to make. Their prognosis after successful transplantation is guarded.

Adenoma, Bile Duct↗
PubMed1990

GABA receptor modulation of tyrosine hydroxylase gene expression in the rat adrenal gland.

Chromaffin cell gamma-aminobutyric acid (GABA) receptors play a role in modulating catecholamine secretion. The present experiments examined the role of GABA receptors in modulation of tyrosine hydroxylase (TH) induction in rat adrenal gland. Administration of bicuculline, a GABA antagonist, had no effect on TH activity or TH mRNA. However, bicuculline potentiated reserpine's effect on TH activity and TH mRNA induction. These data suggest that GABA receptors modulate induction of TH and TH mRNA in the adrenal gland.

Adrenal Glands↗
PubMed1990

Modulation of tyrosine hydroxylase gene expression in the rat adrenal gland by age and reserpine.

Tyrosine hydroxylase (TH), TH messenger RNA (TH mRNA) and dopamine (DA) were measured simultaneously in adrenal glands of individual Fischer 344 rats aged 2, 6, 13 and 23 months. Between 2 and 23 months TH activity rose 2-fold as compared to the youngest group. TH mRNA content of the adrenal gland rose 3-fold between 2 and 23 months. A 3-fold increase in adrenal DA content, the first catecholamine product of TH, provides evidence that the increases in TH gene expression are functionally significant. To determine if mechanisms that regulate gene expression are altered by aging, the effects of reserpine on induction of TH mRNA and TH activity were compared in another group of rats aged 2, 12 and 27 months. Consistent with the results of the first experiment, there were age-related increases in both TH activity and TH mRNA in the age-matched control groups. TH activity rose 2-fold and TH mRNA rose more than 6-fold between 2 and 27 months. The discrepancy in the relative magnitudes of increases in TH mRNA and TH protein suggest an uncoupling of regulation of TH mRNA and TH protein levels. Moreover, there were significant age-related differences with respect to modulation of TH gene expression by reserpine treatment. TH activity was induced by reserpine in the youngest group, but not in the two older age-groups. In contrast, reserpine caused significant induction of TH mRNA in all age groups. These results provide evidence that aging is accompanied by alterations in transcriptional and post-transcriptional mechanisms involved in regulation of TH gene expression.

Adrenal Glands↗
PubMed1990

Improvement in chronic hepatocerebral degeneration following liver transplantation.

Chronic progressive hepatocerebral degeneration with spastic paraparesis, dementia, dysarthria, ataxia, tremor, and neuropsychiatric symptoms follows long-standing portal-systemic shunting, is associated with structural changes in the central nervous system, and does not respond to conventional therapy for hepatic encephalopathy. A case of advanced chronic liver disease with severe, progressive hepatocerebral degeneration after 23 yr of portal-systemic shunting is reported in whom there was significant objective improvement in intellectual function and in the chronic neurological signs 3 mo after orthotopic liver transplantation and further improvement 12 mo after transplantation.

Adult↗
PubMed1990

Baclofen does not protect against cerebral ischemia in rats.

Presynaptic release of glutamate into the extracellular compartment and activation of receptor-operated calcium channels may contribute to ischemic neuronal damage. We evaluated the effect of baclofen, a selective inhibitor of presynaptic glutamate release, on mortality, working memory, and light microscopic hippocampal and cortical damage in the four-vessel occlusion model of cerebral ischemia using 64 male Wistar rats. Baclofen (10 mg/kg i.p.) given 1 hour before and 30-60 minutes after 20 minutes of global ischemia did not lessen mortality, prevent ischemic cellular damage, or significantly improve working memory compared with no treatment. We conclude that preischemic and postischemic administration of baclofen does not protect neurons from ischemic injury.

Animals↗
PubMed1990

Calcium-calmodulin binding in ischemic rat neurons after calcium channel blocker therapy.

Calcium channel blockers such as nicardipine improve outcome after global cerebral ischemia and may attenuate ischemic neuronal injury by preventing calcium influx and binding to calmodulin. We followed the temporal and regional sequence of neuronal calcium-calmodulin binding in normal rats (n = 6), untreated ischemic rats (n = 15), and ischemic rats treated with 0.05 mg/kg/hr s.c. nicardipine (n = 13). After 30 minutes of four-vessel occlusion, 40-microns brain sections were incubated in an anti-calmodulin antibody specific for calmodulin not bound to calcium and brain protein. Light-microscopic sections were examined immediately after ischemia and after 2 and 24 hours of reperfusion. Extensive staining of unbound calmodulin was seen in all hippocampal regions and in the cortex in normal rats. In untreated ischemic control rats, staining was lost, indicating calcium-calmodulin binding immediately after ischemia in all regions. However, after 24 hours, staining returned to normal in the cortex and dentate, and minimal staining returned in CA1 and CA3. Nicardipine-treated animals had significantly less calcium-calmodulin binding in CA1 and in the dentate after 2 hours of reperfusion. This study demonstrates that in clinically relevant doses nicardipine has a limited effect on calcium-calmodulin binding in selectively vulnerable regions after severe ischemia.

Animals↗
PubMed1990

Post-choledochoenterostomy 'sump syndrome'.

The 'sump syndrome' is an uncommon, late complication of a side-to-side choledochoenterostomy. Five patients with this syndrome were encountered over a 5-year period. Pain or cholangitis was the clinical presentation in four patients, whereas one patient presented with secondary septic arthritis and a hepatic abscess. Liver function tests were mildly abnormal in each patient. All patients had a stomal size of less than 1 cm as assessed by forward- or side-viewing endoscopy. Endoscopic retrograde cholangiography revealed either stones or debris in the distal common bile ducts of all patients. Four patients had a surgical clearance of their duct with concurrent closure of the choledochoduodenostomy in three patients and the creation of a Rouxen-Y end-to-side choledochojejunostomy in the fourth patient. The other patient had an endoscopic sphincterotomy performed. After 1-4 years of follow-up, four patients have had a total resolution of symptoms. The other patient with follow-up for 4 years has had one episode of cholangitis which resolved rapidly with antibiotic treatment. The pathogenesis and clinical spectrum of the sump syndrome are reviewed and current management strategies are discussed.

Abdominal Pain↗