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Biomedical subjects

G J Cooper

Publications and source records attributed to G J Cooper.

At least 91 records · Page 5Linked to original sources
PubMed1997

Anticoagulant control in the first three months after mechanical heart valve replacement.

To establish the precision of anticoagulant control in the first three months after mechanical heart valve replacement, 53 patients from a consecutive series of 91 were telephoned and asked to read out their anticoagulation record. The levels of international normalised ratio (INR) were analysed by Rosendaal's method. Twenty-nine per cent of patient days were spent with an INR in the recommended range of 3.0-4.5. Warfarin dosage was increased at a median INR of 2.1 (interquartile range 1.7-2.3), unchanged at 2.7 (interquartile range 2.3-3.1) and decreased at 4.3 (interquartile range 3.6-5.1). Anticoagulant control is poor in the first three months after mechanical heart valve replacement. Data on the INR at which warfarin dosage is changed suggest either that recommended guidelines are not being followed or a reluctance to increase the dosage in patients receiving inadequate anticoagulation.

Aged↗
PubMed1996

Role of de novo protein synthesis and calmodulin in rapid activation of Na(+)-H+ exchange of aldosterone in frog diluting segment.

1. In the amphibian early distal tubule aldosterone activates the Na(+)-H+ exchangers, resulting in an increase in intracellular pH (pHi). Since this activation is rapid (within 30 min), it may be mediated by either a genomic or non-genomic pathway. 2. pHi was measured in single microperfused early distal tubule segments using the fluorescent probe 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein (BCECF). 3. A 30 min incubation in aldosterone increased both resting pHi and the setpoint of the Na(+-H+ exchanger. These changes were prevented by the mineralocorticoid receptor antagonist, spironolactone. 4. Actinomycin D and cycloheximide, inhibitors of transcription and translation, respectively, were without effect on resting pHi, but inhibited activation of the Na(+)-H+ exchanger by aldosterone. 5. The effect of aldosterone upon pHi and setpoint was also prevented by the calcium-calmodulin antagonist, W-7. 6. These results indicate that, although the response to aldosterone is rapid, aldosterone binds to a specific mineralocorticoid receptor which then triggers gene activation followed by de novo protein synthesis. Furthermore, since calmodulin is a known activator of the Na(+)-H+ exchanger, and the response is inhibited by W-7, it is suggested that this protein may be calmodulin.

Aldosterone↗
PubMed1996

Arterial and venous conduits for coronary artery bypass. A current review.

Poor long-term patency of saphenous vein grafts limits the long-term success of the coronary artery bypass operation. If this is to be improved, either measures that increase the patency of saphenous vein grafts or alternative conduits are required. The benefits of using the left internal mammary artery as a pedicled graft to the left anterior descending coronary artery have prompted increasing use of arterial grafts to further improve outcome. Concurrently advances in the understanding of the pathological processes underlying saphenous vein graft occlusion raise the possibility of improving vein graft patency. In this paper we review the problem of vein graft occlusion and possible solutions, the theoretical benefits of arterial grafts and the clinical results associated with their use.

Arteries↗
PubMed1996

Distension reduces the vasoreactivity of the internal mammary artery.

Although the vasoreactivity of internal mammary artery grafts is beneficial in the long term, after mobilisation, vasospasm reduces flow through the vessel. This may be overcome and flow improved by distension. To assess the effects of distension on the vasoreactivity of the artery we have measured changes in isometric tension in rings of distended and undistended human internal mammary artery. For an equivalent wall tension, the diameter of the distended artery was 1922 microns (CL 1858 to 1986) and undistended 1684 microns (CL 1628 to 1739), (P < 0.001). In response to 25 mM potassium the increase in isometric tension, as a percent of resting tension, was 35% (CL 31 to 39) in undistended and 5% (CL 3 to 6) in distended segments (P < 0.001), with 10 microM noradrenaline increases were 57% (CL 47 to 66) and 3% (CL 2 to 5), respectively (P < 0.001). The reduction in developed tension in segments contracted with potassium and relaxed with 1 microM acetylcholine was 65% (CL 47 to 83) in undistended, and 15% (CL -1 to 32) in distended (P < 0.01). With 10 microM glyceryl trinitrate relaxation was 96% (CL 87 to 105) and 17% (CL -9 to 43), respectively (P < 0.01). Similarly, after contraction by noradrenaline, with acetylcholine, undistended segments relaxed by 50% (CL 44 to 55) and distended by 14% (CL 8 to 21) (P < 0.01), with glyceryl trinitrate relaxation was 90% (CL 80 to 99) and 7% (CL -4 to 19), respectively (P < 0.001). Distension produces a profound reduction in vasoreactivity of the internal mammary artery which is not due to endothelial damage alone.

Adult↗
PubMed1996

Efficacy of delayed administration of benzylpenicillin in the control of infection in penetrating soft tissue injuries in war.

In war, uncomplicated penetrating injuries to limbs require evacuation to a surgical facility. A delay is inevitable between injury and definitive surgical treatment. This paper describes an experimental model that has been developed to assess the efficacy of antibiotics in such war wounds; the aim is to develop a treatment protocol to prevent the development of infection before casualties reach a surgical facility. The model is described in detail. Its use to determine efficacy of an antibiotic regimen, and the consequences of delay in the initial administration of antibiotic, are summarized. Streptococcus Lancefield Group L (Strep L) is a pig pathogen analogous to the Streptococcus pyogenes Lancefield Group A in man. The latter is perceived as a major threat to the casualty with a neglected penetrating wound. Strep L caused reproducible infection in a low-energy-transfer fragment wound to a pig thigh. When the wound was observed over a period of 7 days, the only other organisms that appeared consistently were pig pathogenic and nonpathogenic staphylococcal species. Despite the site of the wound, fecal organisms were not observed to colonize the wound significantly, neither were they a cause of early wound infection. The treatment regimen studied as benzylpenicillin, 1 megaunit (6 hourly), given intramuscularly. When commenced 1 hour after wounding, this prevented wound infection for 3 days, when Strep L was deliberately inoculated at the time of wounding. If the start of antibiotics was delayed until 6 hours after wounding, antibiotic regimen was less effective; the wound track remained infected at 3 days. In a further series of experiments, Staphylococcus hyicus, a potential pig pathogen (which is penicillin resistant through beta-lactamase production), was introduced in addition to Strep L. The antibiotic regimen remained effective when the Strep L plus 10(3) S. hyicus were inoculated. When 10(4) S. hyicus were introduced, treatment was less effective, but still of some benefit. Inoculation of > 10(5) S. hyicus rendered treatment commencing at 1 hour ineffective. If the start of treatment was delayed to 6 hours after injury, this treatment regimen was adversely affected by the introduction of only 10(3) S. hyicus. In conclusion, an intramuscular benzylpenicillin regimen, commenced 1 hour after wounding, can prevent infection in penetrating soft tissue missile wounds for up to 3 days. A delay of 6 hours renders treatment ineffective.

Animals↗
PubMed1996

Small fragment wounds: biophysics and pathophysiology.

This paper considers the wounding effects of small fragments in modern warfare. Small fragment wounds may be expected to predominate on a future conventional battlefield; however, studies and models of "military" wounds have tended to focus on bullets as the wounding projectile. This paper discusses briefly the types of fragment projectile expected from modern munitions. It goes on to define a model for such projectiles, and describes the interaction with soft tissue simulants. The extent of penetration, temporary cavitation, and contamination by foreign material are all considered. This work with simulants is validated by experimental shots against animal tissue. A wound model in an experimental animal is described. This model was used to investigate the hematologic, biochemical, and histologic effects of a small fragment wound. The effects on skin and skeletal muscle are described. By sampling at various times (up to 1 week) after wounding, the natural progress of these wounds has been ascertained. The results from 28 experimental animals, with untreated fragment wounds, are reported. The most important findings are that the skin damage is very localized and that the muscle damage is limited, with little necrotic tissue in the track. Furthermore, the extent of the muscle damage, peripheral to the wound track, improves with time, healing within a few days, provided the wound remains free from infection. There was no clinical or microbiologic evidence of infection in those animals followed for up to 3 days. However, of eight animals followed to 1 week, three developed infected wounds. This work has implications for the management of soft tissue wounds caused by fragmentation munitions. The conventional military approach has been to treat penetrating war wounds by exploration, debridement, excision of dead tissue, and delayed primary closure; conservative treatment has largely been regarded as inappropriate. The work presented here shows that the potential culture medium within the wound is small and can be removed by the normal bodily responses. There is no need for surgery, provided that infection can be prevented. It may be inferred that if bacterial colonization can be prevented in the early stages by the timely use of antibiotics, surgery may be unnecessary. Further studies are planned to investigate this possibility.

Animals↗
PubMed1996

Pattern and mechanism of traumatic amputation by explosive blast.

The mechanism of traumatic amputation of limbs by explosion is presented. A survey of blast casualties from Northern Ireland revealed that amputations through joints were very uncommon--the principal site was through the shaft of the long bones. Computer modelling of a bone exposed to blast forces reinforced the hypothesis developed from the casualty survey, that the primary mechanism of the bone injury was the direct coupling of the blast wave into the tissues. The fracture occurs from the resulting axial stresses in the bone, prior to limb flailing from the gas flow over the limb. The gas flow completes the amputation. Field trials employing a goat hind limb model have confirmed the hypothesis. Having identified the mechanism, concepts to develop protective clothing may now be proposed.

Amputation, Traumatic↗
PubMed1996

The influence of personal blast protection on the distribution and severity of primary blast gut injury.

Primary blast injuries have been recognized since World War I when the most significant reported injury was to the lung. The prevalence of injury to tissues containing air was underlined by the frequency of gut blast injury in underwater explosions mostly reported during World War II. Gut injury is the most likely cause of mortality after the more immediate effects of pulmonary primary blast injury. Effective protection has been achieved for lungs exposed to short duration external blast waves by the placement of stress wave decouplers on to the thoracoabdominal wall in a pig model, thus modifying the energy coupled into the body. A combination of two densities of glass-reinforced plastic plate and Plastazote foam (GRP/PZ) effectively eliminated pulmonary injury in 17 protected animals, compared with the production of severe blast lung in nine unprotected animals (p < 0.001). Partial pulmonary protection was achieved using a plasticized lead and plastazote foam decoupling combination (PbPVC/PZ) in a further group of 10 animals. Peak incident overpressures were not significantly different in any group. Small bowel contusions were highly significantly reduced in the GRP/PZ groups when compared with unprotected animals and with PbPVC protected animals (both p < 0.001); no significant reduction was observed in the summed colonic contusion size in any protected group. Intestinal perforations were also highly significantly reduced in both GRP/PZ groups (p < 0.001). Primary pulmonary blast injury and probably small bowel injury are caused by the propagation of coupled stress waves within the body. Elimination of these injuries implies prevention of stress wave propagation. Because colonic injury was not prevented by the same protection, a different mechanism for the injury is suggested: transmission and propagation of shear waves. These findings have important implications for blast protection and the clinical management of primary blast casualties.

Animals↗
PubMed1996

Amylin, amyloid and age-related disease.

Amylin, a 37-amino acid peptide, is cosecreted with insulin from the beta-cells of the pancreatic islets in normal response to physiological stimuli. It is the major protein of islet amyloid, which is usually present in the pancreases of people with non-insulin-dependent (type II) diabetes mellitus. Amylin elicits potent effects on carbohydrate metabolism in rodent tissues, causing insulin resistance in skeletal muscle and liver. A close structural relationship exists between amylin and the 2 calcitonin gene-related peptides, which are widely distributed neuropeptides and potent vasodilators. These exert biological effects similar to those of amylin on the organs primarily responsible for the regulation of carbohydrate metabolism. All 3 peptides are thought to cause their biological actions by binding to similar cell surface receptors. This article reviews the field of amylin and its role in the physiological regulation of carbohydrate metabolism, and in disease mechanisms associated with insulin resistance in diabetes mellitus, impaired glucose tolerance and essential hypertension. Potential therapeutic applications are also discussed.

Amyloid↗
PubMed1995

Amylin stimulates osteoblast proliferation and increases mineralized bone volume in adult mice.

Amylin, a 37-amino-acid peptide co-secreted with insulin from the beta-cells of the pancreatic islets, has previously been demonstrated to inhibit bone resorption in vitro. However, its effects on bone formation and bone mass have not been assessed. We report that periphysiological concentrations of amylin stimulate proliferation of fetal rat osteoblasts in vitro. When amylin is injected daily for 5 days over the calvariae of adult mice in vivo, there are substantial increases in histomorphometric indices of bone formation, a reduction in bone resorption, and a significant increase in mineralized bone area. Equimolar doses of calcitonin in this in vivo model produced an inhibition of bone resorption but no significant effect on bone area. These findings support a role for amylin as a physiological regulator of bone and suggest that it should also be evaluated as a potential treatment for osteoporosis.

Amyloid↗
PubMed1995

Direct mechanical assistance of the right ventricle with the Hemopump in a porcine model.

In 6 pigs, a 14F Hemopump was placed through the pulmonary artery into the right ventricle. The pulmonary artery was banded proximal to the outflow port of the Hemopump, and tightening the band increased right ventricular peak systolic pressure by 50%. There were significant falls in right ventricular stroke volume (from 43 +/- 7.3 mL [+/- the standard deviation] to 27 +/- 8.0 mL; p < 0.001) and cardiac output (from 4.94 +/- 0.76 L/min to 3.70 +/- 0.95 L/min; p < 0.01) and increases in right ventricular peak systolic pressure (from 28 +/- 9.7 mm Hg to 42 +/- 17.1 mm Hg; p < 0.01) and end-diastolic pressure (from 2 +/- 0.8 mm Hg to 12 +/- 6.4 mm Hg; p < 0.02). Mean aortic pressure fell (from 65 +/- 29.9 mm Hg to 61 +/- 9.6 mm Hg; p < 0.01), but systemic vascular resistance was unchanged, thus indicating a fall in left ventricular output reflected by a decrease in mixed venous oxygen saturation (from 60% +/- 8.9% to 47% +/- 7.6%; p < 0.01). After 15 minutes with the Hemopump at maximum speed, these variables returned to control levels (stroke volume, 38 +/- 4.5 mL; cardiac output, 4.50 +/- 0.63 L/min; right ventricular peak systolic pressure, 29 +/- 8.3 mm Hg; right ventricular end-diastolic pressure, 4 +/- 2.0 mm Hg; mean aortic pressure, 72 +/- 10.4 mm Hg; mixed venous oxygen saturation, 56% +/- 4.6% [all, p = not significant versus controls]).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Distension produces medial but not endothelial damage in porcine internal mammary artery.

The influence of intraluminal distension on porcine internal mammary artery was studied using adenosine 5'-triphosphate (ATP) concentration and prostacyclin production as biochemical markers of medial and endothelial functional integrity respectively. Distension reduced mean (95% confidence limits) tissue ATP concentrations from 459 (337-581) nmol/g wet weight to 314 (193-435) nmol/g wet weight (n = 10, P < 0.01). Stimulated prostacyclin production was similar in undistended (25.8(15.9-35.9) pg/min per mg wet weight) and distended arteries (33.2(21.4-45.1) pg/min per mg wet weight) (n = 8, not significant). The data demonstrate that distension of the internal mammary artery results in acute medial but not endothelial damage. Distension-induced medial damage is unlikely to be rapidly reversible and might have implications for the early and long-term function of the artery as a bypass graft.

Adenosine Triphosphate↗
PubMed1995

Papaverine injures the endothelium of the internal mammary artery.

Intraluminal injection of papaverine may be employed to dilate the internal mammary artery for use as a coronary artery bypass graft. The biochemical and morphological consequences of exposing the endothelium of the internal mammary artery to papaverine have been investigated. Biochemical injury was assessed by measuring changes in basal and vortex-stimulated prostaglandin I2 production, and morphological damage by scanning electron microscopy. Segments of internal mammary artery from 10 patients were placed in one of three solutions; papaverine (1.5 mg/ml of normal saline), normal saline acidified to the pH of the papaverine solution, and normal saline alone. Basal production of prostaglandin I2 was similar in the three groups but vortex-stimulated production was significantly lower in segments stored in papaverine (18.3 pg/mg) and acidified saline (19.1 pg/mg) compared with that of saline alone (43.6 pg/mg). No consistent morphological difference was found by scanning electron microscopy. It was concluded that the low pH of the papaverine solution injured the endothelium of the internal mammary artery.

6-Ketoprostaglandin F1 alpha↗
PubMed1995

Bridge to transplantation with the wearable Novacor left ventricular assist system: operative technique.

Although the outcome of patients transplanted after univentricular cardiac support is similar to that of conventional patients, death on the device remains a substantial problem. The wearable Novacor left ventricular assist system (LVAS) may offer advantages over console-based systems by improving rehabilitation before transplantation. For these advantages to be realised, however, a smooth perioperative course is necessary. We describe our operative technique, based on minimising blood loss and preserving right ventricular function, and the results in the first three patients to have the wearable Novacor LVAS implanted in this institution.

Cardiac Surgical Procedures↗