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Biomedical subjects

G J Cooper

Publications and source records attributed to G J Cooper.

At least 145 records · Page 8Linked to original sources

Mitral valve repair: a valuable procedure with good long term results even when performed infrequently.

OBJECTIVE: To assess the results of mitral valve repair in a series with a low frequency of repair despite a policy to conserve the valve whenever possible. DESIGN: Retrospective review of case notes with clinical and echocardiographic examination of survivors. SETTING: Cardiac surgery unit in a university teaching hospital. PATIENTS: 62 consecutive patients undergoing mitral valve repair by one surgeon between 1979 and 1989. INTERVENTIONS: Mitral valve repair according to the criteria and techniques of Carpentier. MAIN OUTCOME MEASURES: Frequency of repair, operative mortality, actuarial survival, freedom from reoperation and thromboembolism, clinical state, and echocardiographic state. RESULTS: The 62 patients, median age 58 years (interquartile range 51 to 64 years), represent 14% (70% confidence interval 12% to 15%) of the 454 mitral valve operations performed in the study period. Operative mortality was 8% (70% CI 5% to 13%). Actuarial survival was 62% (70% CI 43% to 81%) at nine years. At nine years actuarial freedom from reoperation was 91% (70% CI 79% to 102%) and freedom from thromboembolism 91% (70% CI 80% to 102%). At a median follow up of 33 months (interquartile range 21 to 74 months), 38 of 46 survivors had improved functional state. Of 21 patients who underwent echocardiography one had severe mitral regurgitation and one mitral stenosis. CONCLUSION: Although compared with other reports of mitral valve repair the prevalence of repair was low in this series the results are comparable and justify a positive approach to repair in all patients undergoing mitral valve surgery even if this can only be achieved in a small proportion of patients.

Female↗

Field surgery on a future conventional battlefield: strategy and wound management.

Most papers appearing in the surgical literature dealing with wound ballistics concern themselves with wound management in the civilian setting. The pathophysiology of modern war wounds is contrasted with ballistic wounds commonly encountered in peacetime, but it should be noted that even in peacetime the modern terrorist may have access to sophisticated military weaponry, and that patients injured by them may fall within the catchment area of any civilian hospital. Management problems associated with both wound types are highlighted; areas of controversy are discussed. The orthodox military surgical approach to ballistic wounds is expounded and defended.

Anti-Bacterial Agents↗

Assessment of the use of disposable skin staplers in bowel anastomoses to reduce laparotomy time in penetrating ballistic injury to the abdomen.

Laparotomy and anastomosis of the small bowel after penetrating injury to the abdomen is a lengthy procedure. This paper describes the use of skin staplers for bowel anastomosis and presents the results of a short series of experiments upon dead pigs to compare the staple technique with conventional handsewn anastomosis. The time taken to perform each small bowel anastomosis, the integrity of the anastomosis and the skill required were assessed. The staple technique was considerably faster (mean construction time: 5.4 min, range 4-6 min) than the handsewn technique (mean construction time: 12 min, range 10-14 min), at least halving the anastomosis time (Kolmogorov two-sample test P = 0.05). In addition, the stapled anastomosis had a higher intraluminal failure pressure (mean failure pressure: 65 cmH2O, 6.37 kPa, range 30-70 cmH2O) than the handsewn anastomosis (mean failure pressure: 38.6 cmH2O, 3.78 kPa, range 10-70 cmH2O).

Abdominal Injuries↗

Interaction of penetrating missiles with tissues: some common misapprehensions and implications for wound management.

It is apparent from review of published papers and books that misunderstanding and confusion exists in the minds of many authors describing the interaction of penetrating missiles with tissues. These misapprehensions may influence the management of wounds by suggesting didactic approaches based upon a preconceived notion of the nature and severity of the wound for different types of projectiles. This review considers the biophysics of penetrating missile wounds, highlights some of the more common misconceptions and seeks to reconcile the conflicting and confusing management doctrines that are promulgated in the literature-differences that arise not only from two scenarios, peace and war, but also from misapprehensions of the wounding process. Wounds of war and of peacetime differ both in the nature of the wound and in the propensity for wound infection. Additionally, the limitations imposed by war dictate the type of management that may be practised and result in procedures that would be considered inappropriate by some in civilian clinical practice. Many of the procedures described in civilian peacetime settings, such as reliance on antibiotics alone for the control of infection in penetrating wounds, or minimal excision and debridement, can yield good results but would herald disaster if transposed to a war setting.

Anti-Bacterial Agents↗

Prediction of the delayed complications of intestinal and mesenteric injuries following experimental blunt abdominal trauma.

Injuries to the intestine and mesentery are often found in patients undergoing laparotomy for blunt abdominal trauma. Although treatment of perforations is relatively straightforward, the same is not true for contusions. Few guidelines exist at present to aid the surgeon in deciding which injuries require resection in order to avoid the complications of delayed perforation and late stricture formation. The natural history of these non-perforating intestinal and mesenteric injuries has been examined in an experimental model to identify possible criteria on which future management can be based. In the immediate postinjury period peristalsis and local mesenteric pulsation were absent in the majority of injuries which went on to full recovery and these observations are thus of little predictive value in predicting outcome. The initial size of contusion (length of contusion along longitudinal axis of bowel) relative to bowel wall circumference (BWC) was related to complications as follows: contusion less than BWC (n = 47)--one complication; contusion greater than BWC (n = 8)--three complications (P = 0.02). Similarly, six mesenteric injuries which produced an initial ischaemia (assessed by fluorescein) less than twice the BWC did not result in any complications, compared with four complications which occurred in ten cases when the initial ischaemia was greater than twice the BWC. These results go some way towards providing a better understanding of these injuries and in turn may help the emergency surgeon in deciding which injuries require resection.

Abdominal Injuries↗

The role of amylin in the insulin resistance of non-insulin-dependent diabetes mellitus.

Decreased responsiveness of glucose metabolism to insulin in skeletal muscle and the liver (insulin resistance or insensitivity) is characteristic of many conditions, including non-insulin-dependent (type II) diabetes mellitus. Most current work in this area centres on the hypothesis that the primary defect is an impairment of insulin binding and/or transduction of the insulin signal in affected tissues. However, studies imply that defects in the post-insulin receptor signaling pathways are of primary importance in the causation of insulin resistance. Amylin, a novel pancreatic hormone, secreted along with insulin from the pancreatic beta-cells, can modulate insulin effects, to produce insulin resistance in skeletal muscle and liver.

Amyloid↗

Induction of insulin resistance in vivo by amylin and calcitonin gene-related peptide.

During hyperinsulinemic glucose-clamp studies, intravenous infusion of calcitonin gene-related peptide (CGRP) in rats antagonized the ability of insulin to stimulate peripheral glucose disposal by 52% (196 +/- 7.2 vs. 105 +/- 10.5 mumol.kg-1.min-1, P less than 0.05) and to inhibit hepatic glucose output by 54% (P less than 0.01). CGRP also inhibited the in vitro effects of insulin to stimulate hexose uptake in cultured BC3H1 myocytes at all insulin concentrations studied. Amylin is a peptide isolated from amyloid deposits in pancreatic islets of type II (non-insulin-dependent) diabetic subjects, is present in normal beta-cells, and bears a striking homology to CGRP. When synthetic human amylin was infused during clamp studies, it inhibited the ability of insulin to stimulate glucose disposal by 56% (96.9 +/- 9.4 vs. 42.4 +/- 5.0 mumol.kg-1.min-1, P less than 0.05) and to suppress hepatic glucose output by 64%. Therefore, amylin and CGRP can cause insulin resistance in vivo and may be implicated in insulin-resistant states such as type II diabetes mellitus.

Adipose Tissue↗

Amylin and the amylin gene: structure, function and relationship to islet amyloid and to diabetes mellitus.

Amylin, the major peptide component of the islet amyloid commonly found in the pancreases of patients with type 2 (non-insulin-dependent) diabetes mellitus (NIDDM), is a recently discovered islet polypeptide. This peptide has many structural and functional features suggesting that it is a novel hormone, which may control carbohydrate metabolism in partnership with insulin and other glucoregulatory factors. Amylin is synthesised in, and probably secreted from, the beta-cells of the islets of Langerhans, where it has recently been immunolocalised to secretory granules. DNA cloning studies indicate that in the human and the rat, amylin is generated from a precursor, preproamylin, which displays a typical signal peptide followed by a small prohormone-like sequence containing the amylin sequence. The presence of the signal peptide suggests that amylin is secreted and plays a physiological role. Amylin is probably generated by proteolytic processing similar to that for proinsulin and other islet prohormones. The human amylin gene encodes the complete polypeptide precursor in two exons which are separated by an intron of approx. 5 kb, and is located on chromosome 12. Amylin is a potent modulator of glycogen synthesis and glucose uptake in skeletal muscle, and is capable of inducing an insulin-resistant state in this tissue in vitro, and perhaps also in the liver in vivo. In normal metabolism, amylin could act in concert with insulin as a signal for the body to switch the site of carbohydrate disposal from glycogen to longer-term stores in adipose tissue, by making skeletal muscle relatively insulin-resistant, whilst at the same time leaving rates of insulin-stimulated carbohydrate metabolism in adipose tissue unaltered. Several lines of evidence now implicate elevated amylin levels in the pathogenic mechanisms underlying NIDDM, and suggest to us that the obesity which frequently accompanies this syndrome is a result of, rather than a risk factor for, NIDDM. Following the beta-cell destruction which occurs in type 1 (insulin-dependent) diabetes mellitus (IDDM), it is probable that amylin secretion disappears in addition to that of insulin. As patients with insulin-treated IDDM frequently experience problems with hypoglycaemia, and as amylin acts to modulate the action of insulin in various tissues, it is possible that amylin deficiency may contribute to morbidity in insulin-treated IDDM, perhaps through the loss of a natural damping mechanism which guards against hypoglycaemia under conditions of normal physiology.

Amino Acid Sequence↗

Amylin hormone.

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Amyloid↗

Analysis of 828 servicemen killed or injured by explosion in Northern Ireland 1970-84: the Hostile Action Casualty System.

Death and injury due to terrorist bombings continue to exercise civilian and military surgeons alike. In this paper 828 servicemen killed and injured by explosions in Northern Ireland have been studied, using data stored in the Hostile Action Casualty System (HACS). Because of the nature of the conflict in Northern Ireland, the magnitude of each explosion and the distance of the victims from it are quite accurately known. The overpressure (blast loading) to which the victim was exposed can be estimated from the information on the HACS forms and standard tables, giving overpressures for a given change at a known distance. Using the HACS data, the numbers of injuries due to overpressure (primary blast injury), missiles energized by the blast (secondary injury), displacement of the victim by the blast wind (tertiary injury) and flash burn can be determined. Of the 828 servicemen involved in explosions, 216 were killed, most of them before any treatment could be instituted. Of the servicemen in the survey, 90 per cent were wearing body armour. Although body armour affords considerable protection from secondary missiles, it is unlikely to reduce the number of deaths due to primary blast injury.

Blast Injuries↗

The amylin superfamily: a novel grouping of biologically active polypeptides related to the insulin A-chain.

The peptide amylin (previously termed Diabetes Associated Peptide) has recently been isolated and characterised from the amyloid of the pancreatic islets of Langerhans from human type 2 diabetics. Amylin shows about 46% identity in amino acid sequence on comparison with the calcitonin gene-related peptides (CGRPs) and also shows some similarity to insulin. Recent studies have also shown that both amylin and CGRP are potent inhibitors of insulin-stimulated glycogen synthesis in skeletal muscle in vitro. Hormones may be arranged into families, therefore a degree of order exists even though hormone-mediated effects are complex. The polypeptides insulin, insulin-like growth factors (IGFs) and relaxins have been grouped into such a family with similarities both at the protein-structural and genetic levels. We now demonstrate that this insulin-related family, along with amylin and the CGRPs, are members of a peptide superfamily defined by structural similarity in the region corresponding to the A-chain of insulin. In order to distinguish this grouping of small biologically active peptides from the previous one, we have designated it the amylin superfamily. All the members of the previously defined insulin family have a region homologous to the insulin B-chain. Insulin, the IGFs, the relaxins, the CGRPs and amylin are all involved in carbohydrate metabolism and therefore these peptides are functionally as well as structurally related. This grouping of peptides may have important implications for the study of human metabolic disease.

Amino Acid Sequence↗

Biophysics of impact injury to the chest and abdomen.

The physical mechanism of blunt impact injuries to thoracic and abdominal viscera is often conveniently described simply in terms of "crush"--this is an over-simplification. Any impact to the torso does result in the rapid displacement of the body wall which may lacerate and contuse underlying viscera, but this simple explanation does not account for pathology at sites some distance from the contact point and does not adequately describe the dependence of the severity and location of injury upon the rate of energy transfer. Quite minor displacements of the body wall may produce serious injury if the body wall velocity is high. The motion of the body wall generates waves that propagate within the body and transfer energy to internal sites. The nature and properties of these waves are discussed in simple terms and the role of waves in the production of the characteristic injuries resulting from impact to the torso is presented.

Abdominal Injuries↗

Pancreatic amylin and calcitonin gene-related peptide cause resistance to insulin in skeletal muscle in vitro.

Insulin resistance occurs in a variety of conditions, including diabetes, obesity and essential hypertension, but its underlying molecular mechanisms are unclear. In type 2 (non-insulin-dependent) diabetes mellitus, it is insulin-resistance in skeletal muscle, the chief site of insulin-mediated glucose disposal in humans, that predominantly accounts for the low rates of glucose clearance from the blood, and hence for impaired glucose tolerance. Human type 2 diabetes is characterized by a decrease in non-oxidative glucose storage (muscle glycogen synthesis), and by the deposition of amyloid in the islets of Langerhans. Amylin is a 37-amino-acid peptide which is a major component of islet amyloid and has structural similarity to human calcitonin gene-related peptide-2 (CGRP-2; ref. 8). CGRP is a neuropeptide which may be involved in motor activity in skeletal muscle. We now report that human pancreatic amylin and rat CGRP-1 are potent inhibitors of both basal and insulin-stimulated rates of glycogen synthesis in stripped rat soleus muscle in vitro. These results may provide a basis for a new understanding of the molecular mechanisms that cause insulin resistance in skeletal muscle.

Amyloid↗