Posterior sternoclavicular dislocation: a novel method of external fixation.
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Accidental Falls↗
Biomedical subjects
G J Cooper
Publications and source records attributed to G J Cooper.
Amylin and insulin in rat soleus muscle: dose responses for cosecreted noncompetitive antagonists.
Increasing concentrations of amylin progressively depressed the maximal insulin-stimulated radioglucose incorporation into soleus muscle glycogen, but did not substantively change the EC50 (range 0.78 to 1.52 nM); these findings show noncompetitive, insurmountable antagonism of insulin action by amylin. The results from 36 combinations of different insulin and amylin concentrations were used to construct a response surface that can be used to predict the response for any combination of insulin and amylin concentration. The predicted response to a constant ratio of insulin and amylin concentration is a bell-shaped curve. The experimentally determined response to increasing amounts of an amylin-insulin mixture (molar ratio of 0.14:1, within the range measured for pancreatic secretion and plasma levels) gave a bell-shaped response rather than the sigmoidal response seen with insulin alone. The amylin dose-response relation in the soleus system provides a useful bioassay for amylin agonists. The dose response for highly purified, synthetic human amylin obtained by measuring amylin concentrations by radioimmunoassay in the incubation medium gave an EC50 of 456 pM (+/- 0.18 log units). Human amylin had a potency greater than or equal to that of human insulin in this highly insulin-sensitive preparation.
Amyloid↗
Hyperamylinemia, hyperinsulinemia, and insulin resistance in genetically obese LA/N-cp rats.
The experimental evidence supporting a direct role for hyperinsulinemia as a cause of insulin resistance remains equivocal. Amylin, an islet beta-cell peptide cosecreted with insulin in response to nutrient stimuli, causes insulin resistance when infused into intact animals or applied to isolated skeletal muscles. We compared measures of amylin and insulin gene expression between control and genetically obese, insulin-resistant Lister Albany/NIH-(LA/N-cp) rats. Pancreatic amylin messenger RNA levels were increased 7.8 +/- 0.7-fold (mean +/- SEM), and plasma amylin-like immunoreactive material was increased 10.9 +/- 1.1-fold (LA/N-lean, 14 +/- 4 pM; LA/N-cp, 153 +/- 16 pM; p less than 0.0001) in obese rats. Pancreatic insulin I mRNA levels were increased 7.4 +/- 0.5-fold, and plasma insulin levels 20.0 +/- 5.0-fold, in these rats (LA/N-lean, 308 +/- 84 pM; LA/N-cp 6,120 +/- 1,540 pM; p less than 0.0001). The EC50 for insulin-stimulated incorporation of glucose into glycogen was about fourfold higher in muscles isolated from obese rats. The present results, coupled with previous observations, support the hypothesis that hyperamylinemia, rather than hyperinsulinemia per se, could have directly caused the insulin resistance in the obese LA/N-cp rats. Hyperamylinemia needs to be considered in future experimental studies probing the relation between hyperinsulinemia and insulin resistance.
Amyloid↗
Overcoming perioperative spasm of the internal mammary artery: which is the best vasodilator?
After mobilization, vasospasm often reduces flow through the internal mammary artery. An established method of relaxing the artery and increasing flow is to wrap it in a papaverine-soaked swab. To our knowledge the ability of other topical vasodilators to overcome spasm of the internal mammary artery has not been studied clinically. In 50 patients in whom the left mammary artery was used for myocardial revascularization, we have investigated the effect of five agents on internal mammary artery free flow. The agents investigated were normal saline, papaverine, nifedipine, glyceryl trinitrate, and sodium nitroprusside. Under controlled hemodynamic conditions, free flow was measured before any pharmacologic intervention and a median of 18.5 minutes after the pedicle had been sprayed with one of the five agents. Normal saline produced a small increase in flow from a median of 23 ml/min (range 17 to 88) to 38 ml/min (20 to 84) (not significant), whereas a significant increase occurred with papaverine, from 25 (16 to 78) to 43 ml/min (34 to 112) (p less than 0.01). Nifedipine and glyceryl trinitrate raised free flow by almost threefold, from 23 (14 to 66) to 71 ml/min (45 to 118) and from 23 (14 to 58) to 62 ml/min (46 to 126), respectively (both p less than 0.001). Sodium nitroprusside, however, with an increase in flow from 26 (10 to 58) to 108 ml/min (46 to 196), 250% over control, proved to be more effective than nifedipine and glyceryl trinitrate (p less than 0.05). We therefore recommend the topical use of sodium nitroprusside to relieve perioperative spasm of the internal mammary artery.
Administration, Topical↗
HIV-1 western blot: development and assessment of testing to resolve indeterminate reactivity.
OBJECTIVE: To reduce the number of HIV-1 Western blot (WB)-indeterminates requiring follow-up and the time taken to provide a clear positive or negative result. DESIGN: In the first of two stages, a testing and follow-up strategy was developed to resolve anti-HIV-1 status of WB-indeterminates. In the second stage, implementation of this strategy was assessed. METHODS: After dividing indeterminates into four groups according to WB profile, samples were tested for anti-HIV-1, anti-HIV-2, anti-HTLV-I antibodies, and HIV-1 antigen using the most sensitive assays available. When testing failed to clarify anti-HIV-1 status, follow-up samples were taken to monitor changes in antibody status. RESULTS: Samples in two out of the four indeterminate groups were negative for anti-HIV-1. The other two groups required additional testing and/or follow-up to distinguish reactivity caused by anti-HIV-1 from cross-reactivity. CONCLUSION: Grouping HIV-1 WB-indeterminates according to profile allows a significant percentage to be reported as anti-HIV-1-negative, while additional testing may allow others to be reported as anti-HIV-1-positive. The remainder require a maximum of 3 months' follow-up to resolve anti-HIV-1 status.
AIDS Serodiagnosis↗
Use of disposable skin staplers for bowel anastomosis to reduce laparotomy time in war.
Laparotomy for penetrating wounds to the abdomen is demanding in terms of time, skill and resources. Any modification of existing techniques that will lessen these demands will be of benefit at surgery in forward areas in war. A previous paper (1) compared a method of small bowel anastomosis using disposable skin staplers with a two-layer handsewn anastomosis using fresh pig ileum. The stapled method was both significantly faster to perform and mechanically superior. In two further studies on a total of 12 pigs the stapled method has been compared with a single-layer and a double-layer handsewn small bowel anastomosis. All 12 pigs recovered from laparotomy without complication. Construction times were recorded. The quality of healing of the anastomoses was assessed by clinical observation, post-mortem and histological examination, and tensiometry. The skill required to perform the stapled anastomoses was estimated subjectively. The stapled technique was consistently faster than the handsewn methods. A Kolmogorov two-sample test showed an improvement in times when comparing the stapled method with the single layer, with a significance of P = 0.05. An improvement was also seen when the stapled method was compared with the double layer, with a significance of P = 0.01. There was no statistically significant difference between the construction times for the two handsewn methods. There was no evidence of anastomotic failure or haematoma at post-mortem and no adverse reaction to the metal staples. No features were identified on histology to indicate impaired healing with the stapled method. Tensiometry of the anastomoses showed that the stapled anastomosis is as mechanically reliable as the handsewn anastomosis. The level of skill required to perform the stapled anastomosisis judged to be within the capabilities of relatively junior surgeons once the technique has been mastered in an anastomosis workshop.
Anastomosis, Surgical↗
Prediction of hepatitis C virus infectivity in seropositive Australian blood donors by supplemental immunoassays and detection of viral RNA.
The prevalence of anti-hepatitis C virus (HCV) enzyme immunoassay (EIA)-positive in 167,511 Australian volunteer blood donors from Adelaide, Melbourne, Perth, and Sydney was 0.78%. One thousand two-hundred and eighteen EIA-positive serum samples were assessed by supplemental tests including a blocking EIA and two peptide EIAs corresponding to major epitopes of the HCV C-100-3 antigen. Seven hundred and eighteen samples (59%) were negative by supplemental testing; no evidence of reactivity with other HCV gene products or HCV RNA detected by cDNA polymerase chain reaction was found in selected samples from this group. In contrast, of 43 samples randomly selected from 400 samples (32.8%) positive by supplemental testing, 88% were reactive with HCV 33-C or core antigens and 52% contained HCV RNA, suggesting contact with HCV and infectivity of most donors in this group. Most samples equivocal by supplemental testing reacted only with C-100 and not with other HCV antigens when tested by dot immunoblot assay. Only 21% had detectable HCV RNA. The battery of assays used in this study indicated that approximately 32% of HCV EIA repeatably reactive serum samples were serologically related to HCV, corresponding to a 0.25% prevalence of potentially infectious donors.
Adult↗
Amylin secretion from the perfused pancreas: dissociation from insulin and abnormal elevation in insulin-resistant diabetic rats.
Amylin has been co-secreted from pancreatic islet beta-cells in constant proportion with insulin in some studies. We measured basal and glucose-stimulated amylin and insulin secretion from isolated perfused pancreases of normal and diabetic fatty Zucker rats. Glucose concentrations in the perfusion buffer were increased then decreased in small steps to mimic physiologic changes occurring after a meal. The absolute rate of amylin secretion and the molar ratio of amylin to insulin secreted from diabetic pancreases increased dramatically when infused glucose concentrations fell. Similar changes also occurred in normal pancreases, although the absolute change in amylin secretion was smaller. These studies provide the first evidence that (i) there is a mechanism within the pancreas whereby independent secretion of amylin and insulin can occur; (ii) the molar ratio of amylin to insulin secreted from both normal and diabetic pancreases can vary over a wide range; and (iii) there are important differences in the kinetics of amylin and insulin secretion or their coupling to stimulation by glucose between the isolated pancreases of normal rats and those with genetically transmitted insulin resistance and diabetes mellitus.
Amyloid↗
8-37h-CGRP antagonizes actions of amylin on carbohydrate metabolism in vitro and in vivo.
8-37hCGRP is a potent antagonist at calcitonin gene-related peptide (CGRP) liver membrane receptors; it also blocks vasodilator actions of CGRP and the related peptide, amylin, in intact rats. We now report that 8-37hCGRP antagonizes amylin inhibition of insulin-stimulated labelled glucose uptake into isolated rat soleus muscle, and inhibits amylin-evoked elevation of plasma lactate and glucose in fasted anaesthetized rats. The different relative potencies of the 3 ligands (amylin, CGRP, 8-37hCGRP) on the liver receptor and on the soleus muscle point to distinct CGRP receptors in liver membranes and amylin receptors on muscle cells.
Amino Acid Sequence↗
Amylin injection causes elevated plasma lactate and glucose in the rat.
Intravenous injections of 25.5 nmol rat amylin into fasted anesthetized rats caused a rapid increase in plasma lactate followed by an increase in plasma glucose; there was a transient fall in blood pressure. Subcutaneous injection of 25.5 nmol amylin also caused increases in lactate and glucose but did not change blood pressure. Similar responses were observed during somatostatin infusion and in the absence of changes in catecholamines. These results fit with a scheme in which amylin elicits muscle glycogenolysis, release of lactate, and increased hepatic gluconeogenesis due to increased supply of substrate.
Amyloid↗
Co-secretion of amylin and insulin from cultured islet beta-cells: modulation by nutrient secretagogues, islet hormones and hypoglycemic agents.
Amylin is a pancreatic islet beta-cell peptide hormone which modulates carbohydrate metabolism in skeletal muscle and liver, and could contribute to impaired insulin sensitivity in Type II diabetes. Here we report the first description of amylin secretion from isolated beta-cells. We measured amylin secretion from HIT T15 beta-cells exposed to glucose, arginine, glucagon, somatostatin, tolbutamide, glyburide, or metformin. With the exception of glucagon at concentrations above 1 microM, all compounds induced parallel, dose-dependent changes in secretion of amylin and insulin. We conclude that: 1) insulin and amylin are co-secreted from islet beta-cells; (2) nutrient secretagogues and peptide modulators exert direct effects on beta-cells to alter amylin and insulin secretion; (3) most modulators of islet beta-cell secretion alter amylin and insulin in parallel, but differential secretion can occur; and (4) HIT cell line is a useful model in which to study amylin metabolism.
Amyloid↗
Daily amylin replacement reverses hepatic glycogen depletion in insulin-treated streptozotocin diabetic rats.
In streptozotocin-diabetic rats treated with insulin replacement, liver glycogen is some 35% depleted. Five consecutive daily subcutaneous injections with amylin dose-dependently restored liver glycogen to normal levels. Significant increases over insulin-only therapy occurred with amylin doses of 10, 30 and 100 micrograms/day, representing amylin: insulin ratios of 0.22, 0.75 and 2.79.
Amyloid↗
Peroxovanadates have full insulin-like effects on glycogen synthesis in normal and insulin-resistant skeletal muscle.
1. The insulin-like effects of orthovanadate (10 mM) and peroxides of vanadate (peroxovanadates, at 1 mM) on rates of lactate formation, glucose oxidation and glycogen synthesis were measured in incubated soleus-muscle preparations isolated from non-obese Wistar rats and lean (fa/?) or insulin-resistant obese Zucker (fa/fa) rats. 2. The stimulation of the rates of lactate formation and glucose oxidation by either orthovanadate or peroxovanadates was of similar magnitude to the stimulation by a maximally effective concentration of insulin (1000 microunits/ml). 3. Peroxovanadates, but not orthovanadate, maximally stimulated the rate of glycogen synthesis in incubated soleus muscles isolated from Wistar rats. 4. When soleus-muscle preparations were incubated in the presence of both insulin (1000 microunits/ml) and peroxovanadates (1 mM), this did not result in a synergistic increase in the rate of total glucose utilization as compared with either agent alone. 5. Soleus muscles isolated from obese (fa/fa) Zucker rats exhibited a decrease in response to a physiologically relevant concentration of insulin (100 microunits/ml). Peroxovanadates, at 1 mM, maximally stimulated the rate of glycogen synthesis in soleus muscles isolated from obese (fa/fa) Zucker rats. 6. The findings indicate that peroxovanadates are useful and important agents for investigating the mechanism of action of insulin in skeletal muscle.
Animals↗
Amylin activates glycogen phosphorylase in the isolated soleus muscle of the rat.
The pancreatic beta-cell hormone amylin acts in isolated rat skeletal muscle to decrease insulin-stimulated incorporation of glucose into glycogen. It also increases blood levels of lactate and glucose in fasted rats in vivo. However, it remained uncertain whether amylin exerts direct effects to stimulate muscle glycogenolysis. We now report that amylin caused a dose-dependent increase in activity of muscle glycogen phosphorylase in isolated rat soleus muscle by stimulating phosphorylase a. Insulin inhibited amylin-stimulated activation of phosphorylase. Effects of amylin to stimulate muscle glycogenolysis are consistent with observed effects of amylin in vivo and could be a major mechanism whereby amylin modulates carbohydrate metabolism.
Amyloid↗
Liposarcoma of the esophagus.
Liposarcoma is one of the most common soft tissue sarcomas found in adults, yet it rarely develops in the alimentary tract. This report describes the pathological features and management of a liposarcoma of the esophagus.
Aged↗
The role of stress waves in thoracic visceral injury from blast loading: modification of stress transmission by foams and high-density materials.
Materials have been applied to the thoracic wall of anaesthetised experimental animals exposed to blast overpressure to investigate the coupling of direct stress waves into the thorax and the relative contribution of compressive stress waves and gross thoracic compression to lung injury. The ultimate purpose of the work is to develop effective personal protection from the primary effects of blast overpressure--efficient protection can only be achieved if the injury mechanism is identified and characterized. Foam materials acted as acoustic couplers and resulted in a significant augmentation of the visceral injury; decoupling and elimination of injury were achieved by application of a high acoustic impedance layer on top of the foam. In vitro experiments studying stress wave transmission from air through various layers into an anechoic water chamber showed a significant increase in power transmitted by the foams, principally at high frequencies. Material such as copper or resin bonded Kevlar incorporated as a facing upon the foam achieved substantial decoupling at high frequencies--low frequency transmission was largely unaffected. An acoustic transmission model replicated the coupling of the blast waves into the anechoic water chamber. The studies suggest that direct transmission of stress waves plays a dominant role in lung parenchymal injury from blast loading and that gross thoracic compression is not the primary injury mechanism. Acoustic decoupling principles may therefore be employed to reduce the direct stress coupled into the body and thus reduce the severity of lung injury--the most simple decoupler is a high acoustic impedance material as a facing upon a foam, but decoupling layers may be optimized using acoustic transmission models. Conventional impacts producing high body wall velocities will also lead to stress wave generation and transmission--stress wave effects may dominate the visceral response to the impact with direct compression and shear contributing little to the aetiology of the injury.
Acoustics↗
Amylin and insulin co-replacement therapy for insulin-dependent (type I) diabetes mellitus.
Amylin is a proteinaceous hormone secreted form insulin-producing pancreatic beta-cells following stimulation by food molecules such as glucose and arginine. Amylin decreases insulin-stimulated glucose uptake in skeletal muscle and counteracts the ability of insulin to suppress output of glucose from the liver. Substantial evidence supports the view that maylin is a second glucoregulatory hormone produced from islet beta-cells, which can modulate a number of metabolic processes also regulated by insulin. The islet beta-cell may therefore transmit a dual message to peripheral tissues through the two hormones, insulin and amylin. Like insulin, amylin is deficient in individuals with autoimmune diabetes mellitus. Since amylin can modulate processes of fuel metabolism in key tissues, amylin deficiency could contribute to the clinical course in patients with autoimmune diabetes. Here, I propose that amylin lack plays a significant role to promote the tendency to hypoglycemia and defective glycemic control characteristic of insulin-treated patients with autoimmune diabetes. Treatment of such diabetics with injections of amylin as well as insulin is being evaluated with the aim of lessening the incidence and severity of hypoglycemia and improving glycemic control.
Amino Acid Sequence↗
Metastasis from a granulosa cell tumour of the ovary presenting in the chest but arising below the diaphragm.
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Diaphragm↗