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Biomedical subjects

G Clarke

Publications and source records attributed to G Clarke.

At least 91 records · Page 5Linked to original sources

Acute renal failure following surgery for abdominal aortic aneurysm.

Between January 1974 and April 1986, 440 patients underwent elective or emergency repair of abdominal aortic aneurysms at this hospital. Acute renal failure requiring dialysis following repair occurred in 32 patients (7.3%) and form the basis of this report. All were male patients of mean age 69 years; 21 (66%) gave a history of other major medical problems and 19 (59%) used medication for these medical conditions. Twelve patients (37.5%) survived to leave hospital. No differences were observed between survivors and non-survivors with regard to age, previous medical condition, drug therapy, or creatinine value on admission. Mode of presentation, duration of surgery, frequency of hypotension and number of blood transfusions were similar in both groups. Total hospital stay and duration of intensive care were distributed equally between the two groups. Those who survived seemed to require less inotropic support and a shorter duration of ventilation than the non-survivors; the continued need for these support and persistent leucocytosis greater than 15,000/mm3 were associated with little chance of survival.

Acute Kidney Injury↗

Reperfused-viable and reperfused-infarcted myocardium: differentiation with in vivo P-31 MR spectroscopy.

The ability of in vivo phosphorus-31 magnetic resonance (MR) spectroscopy to permit accurate distinction between reperfused-viable and reperfused-infarcted myocardium was examined in a canine model of acute coronary occlusion. In vivo myocardial pH and phosphocreatine, adenosine triphosphate, and inorganic phosphate levels were measured at baseline and for the first 90 minutes after reperfusion of a total coronary artery occlusion producing either predominantly viable (nine animals) or infarcted (nine animals) myocardium in the region of metabolic study. Myocardial viability was assessed in each animal by means of postmortem triphenyltetrazolium chloride staining. Tissue was characterized from the in vivo P-31 MR data by means of logistic regression analysis. The accuracy of using the P-31 MR data for distinguishing reperfused-viable from reperfused-infarcted myocardium was 100% (69 of 69 data points, 18 of 18 animals). Results of the logistic regression procedure indicated that phosphocreatine was the metabolic variable enabling most effective separation of reperfused-viable and reperfused-infarcted myocardium. Thus, metabolic data obtained with P-31 MR spectroscopy permit effective separation of reperfused-viable from reperfused-infarcted myocardium.

Adenosine Triphosphate↗

Effective separation of normal, acutely ischemic, and reperfused myocardium with P-31 MR spectroscopy.

The ability of phosphorus-31 magnetic resonance (MR) spectroscopy to accurately characterize myocardium as normal, ischemic, or reperfused but viable was examined in the canine model of acute coronary artery occlusion. P-31 MR measurements of in vivo myocardial pH, phosphocreatine, adenosine triphosphate, and inorganic phosphate levels were made at baseline and for 6 hours after sustained coronary occlusion (ten animals) or coronary occlusion reperfused after 60 minutes (12 animals). Ten control animals were studied in parallel fashion, without coronary occlusion. Myocardial tissue characterization derived from the P-31 MR spectroscopy data by logistic regression analysis had an overall accuracy of 89%. Overall accuracy was unaffected by duration between coronary occlusion and P-31 MR study. Thus, metabolic data obtained with P-31 MR spectroscopy effectively separate normal, acutely ischemic, and reperfused but viable myocardium.

Adenosine Triphosphate↗

Performance of patients with a "frozen pelvis" in an in vitro fertilization program.

It is now possible to identify and study the performance of different subgroups of patients in in vitro fertilization (IVF) programs. Patients with severe pelvic adhesions due to pelvic inflammatory disease (PID) or endometriosis were classed as having a frozen pelvis if less than or equal to 20% of total ovarian surface was visible and if the rest of the ovary was bound down with significant adhesions. IVF offers the only hope of pregnancy for these patients. Fifty-one treatment cycles in 23 such patients were matched against 51 cycles in 48 patients with adhesion-free ovaries. The study group had a significantly higher number of cancelled oocyte retrievals because of poor estradiol (E2) response. They also had a significantly lower rate of E2 rise and a lower peak value of E2 before and after the administration of human chorionic gonadotropin. These patients took longer to respond to a hyperstimulation regime, and when a response occurred they formed fewer follicles, as measured with the use of ultrasound. Lower numbers of oocytes were obtained from this group, but the fertilization rate of oocytes was the same for both groups. One pregnancy occurred in the study group and 11 in the control group. It is possible that disruption of ovarian blood supply or mechanical factors due to the pressure of significant adhesions prevent a good follicular response in patients with a frozen pelvis.

Adult↗

Intracellular myocardial pH measured in vivo with sustained and reperfused coronary occlusion.

Intracellular pH provides an important measure of the adequacy of local tissue perfusion. The purpose of this study was to measure regional intracellular myocardial pH (impH) in the ischemic zone in vivo during experimental canine coronary occlusion, with and without coronary reperfusion. Twenty adult dogs were studied. Ten dogs underwent permanent ligation of the proximal anterior left descending coronary artery (group L), five dogs had coronary reperfusion after 1 hour of total coronary occlusion (group R), and five dogs did not undergo ligation and served as controls (group C). Intracellular myocardial pH was measured by 31phosphorus nuclear magnetic resonance spectroscopy at baseline and then at 15-minute intervals for 6 hours after coronary occlusion (or after sham occlusion in group C). Baseline impH did not differ among groups (group C, 7.22 +/- 0.12 mean +/- standard error of mean; group L, 7.17 +/- 0.07; group R, 7.22 +/- 0.09). During hour 1 of total occlusion, the impH of both groups L (6.58 +/- 0.05) and R (6.55 +/- 0.08) was significantly reduced as compared with the impH of group C (7.3 +/- 0.12; p less than 0.05). At 0 to 1, 1 to 3, and 3 to 5 hours of reperfusion, the impH of group R (7.34 +/- 0.08, 7.27 +/- 0.07, and 7.29 +/- 0.06, respectively for these times) did not differ from group C (7.26 +/- 0.11, 7.21 +/- 0.07, and 7.25 +/- 0.10). At these same times, the impH of group L (6.47 +/- 0.05, 6.57 +/- 0.04, and 6.75 +/- 0.04) was significantly reduced as compared with both groups R and C (p less than 0.05). Thus a severe, persistent regional intracellular myocardial acidosis occurs in the ischemic zone with coronary occlusion but is rapidly corrected by reperfusion within 1 hour.

Acidosis↗

Dissociation between pancreatic enzyme secretory and synthetic dose-responses to cholecystokinin in man.

The effect of varying the intensity of pancreatic stimulation on the synthesis of human pancreatic enzymes has not previously been studied. We have measured the secretion and synthesis of pancreatic enzymes in response to either secretin alone (1 CU.kg-1.h-1) or secretion plus increasing doses of cholecystokinin (CCK) (0.25, 0.5 or 1.0 IDU.kg-1.h-1). Enzyme synthesis was measured using the incorporation of 75Se-methionine (0.15 mCi (5.6 kBq).kg-1.h-1) into the trichloracetic acid-insoluble fraction of the duodenal aspirate. Outputs of trypsin, chymotrypsin, lipase and protein showed a bell-shaped dose response to increasing doses of cholecystokinin, with maximal outputs occurring in response to secretin plus cholecystokinin 0.5 IDU.kg-1.h-1. The rate of incorporation of 75Se-methionine increased with increasing doses of cholecystokinin and was maximal in response to secretion plus cholecystokinin 1.0 IDU.kg-1.h-1. There was therefore dissociation between the secretory and synthetic responses to increasing doses of cholecystokinin.

Cholecystokinin↗

Effects of porcine relaxin on oxytocin release from the neurohypophysis in the anaesthetized lactating rat.

The effect of relaxin on electrically evoked release of oxytocin from the posterior pituitary was examined by monitoring changes in intramammary pressure in the anaesthetized lactating rat. The amount of oxytocin released by electrical stimulation of the neurohypophysis in vivo was dramatically reduced following i.v. injection of highly purified porcine relaxin (2.5-10 micrograms/rat). Relaxin inhibited oxytocin release in a dose-dependent manner and the onset of inhibition occurred within 6-10 min and lasted for 10-60 min. No effect on the sensitivity of the mammary gland to exogenous oxytocin was observed after relaxin treatment. During the period of inhibition, i.v. injection of the opioid antagonist naloxone chloride (1 mg/kg) completely and immediately restored electrically evoked oxytocin release. The neurohypophysis is known to contain endogenous opioid peptides, therefore the effect of relaxin on electrically stimulated release of oxytocin from the rat isolated neural lobe in vitro was examined. Relaxin (500-2000 ng/ml) failed to inhibit oxytocin release in vitro. The results suggest that relaxin can inhibit the release of oxytocin from terminals in the neurohypophysis, but by an indirect mechanism. This action appears to be mediated through endogenous opioid peptides whose source is not clear. They are unlikely to be of neurohypophysial origin and may probably come from the adrenal medulla, since acute adrenalectomy negated the inhibitory effect of relaxin on oxytocin release.

Animals↗

Smoking in pregnancy: relevance of maternal screening tests on fetal outcome.

A number of laboratory parameters were estimated in 54 pregnant women in order to assess whether changes induced by smoking could reflect weight gain in the fetus. There was a significant correlation between maternal weight gain index, oestriol levels, antithrombin III levels and reticulocyte synthesis with infant and placental weight gain. One or more of these tests was found abnormal in 27% of normal pregnant patients, 72% of light smokers, and 89% of heavy smokers. Several other parameters were found to be significantly altered in smoking compared to non-smoking pregnant patients; however, these bore no relationship to infant and placental parameters. These studies indicate that laboratory assessment of a number of maternal parameters could be of some value in determining the likelihood of depressed weight gain by infants of smoking mothers.

Birth Weight↗

Inhibition of oxytocin secretion by mu and delta receptor selective enkephalin analogues.

The effects on oxytocin release of enkephalin analogues, thought to be highly selective agonists of the mu or delta opioid receptor, were compared. Oxytocin release was evoked in urethane-anaesthetised rats (7-10 days post partum) by intracerebroventricular injection of NaCl (3M) at 15-20 min. intervals and detected by the resultant increase in intramammary pressure. Enkephalin analogues (the mu receptor agonist Tyr-D-Ala-Gly-MePhe-NH (CH2)2OH (DAGO), the delta receptor agonist (D-Ala2-D-Leu5) - enkephalin (DADLE) and metkephamid, which has been reported to be particularly efficacious at the delta receptor) were administered intracerebroventricularly 3-5 min. prior to hypertonic saline. Oxytocin release was inhibited in a dose-dependent, naloxone-reversable manner by DAGO (ED50 : 40ng), DADLE (ED50 : 156ng) and metkephamid (ED50 : 42ng); the mammary gland sensitivity to oxytocin was unaffected. These results suggest that the inhibitory action may be mediated through both mu and delta receptors and provide further evidence in support of a role of enkephalins in the control of oxytocin secretion.

Animals↗

Two new monoclonal antibodies to human monocytes and granulocytes: isolation of membrane antigens and lack of effects of antibodies on leukocyte functions in vitro.

Mice were immunized with purified human monocytes or granulocytes obtained by leukapheresis and isolated on dextran gradients or by countercurrent centrifugation-elutriation. A monoclonal antibody, Mo95, was generated in response to monocytes and was found to react strongly with monocytes, large granular lymphocytes (LGL), granulocytes, eosinophils, and some myelomonocytic leukemia cells, but not with normal T or B lymphocytes, platelets, red cells, or leukemic cell lines. Mo95 is an IgG1 antibody, which precipitated a 95 kD molecular weight antigen. Addition of the Mo95 antibody to monocytes in the absence of complement did not inhibit lysozyme secretion nor did it affect superoxide production, C3b-rosetting, nitrotetrazolium blue reduction, phagocytosis, or chemotactic responses. A second antibody, PMN70, was found to react exclusively with granulocytes and not with monocytes, lymphocytes, LGL, platelets, red cells, or any of the myelomonocytic, T-cell-derived or B-cell-derived leukemic cell lines tested. The PMN70 antibody immunoprecipitated a 70 kD molecular weight antigen found only on mature granulocytes. Mo95 and PMN70 appear to be distinct from five other tested monoclonal antibodies reactive to monocytes and/or granulocytes on the basis of the fluorescent cell sorter and immunoprecipitation studies performed.

Animals↗

A comparison of analgesia and suppression of oxytocin release by opiates.

The potency of opiates for suppressing oxytocin release relative to their potency as analgesics was tested in lactating rats. Oxytocin release was evoked by the sucking of the young in urethane-anaesthetized and unanaesthetized rats, and was detected by the characteristic behaviour of the young and milk yield respectively. The tail-flick test, using noxious radiant heat, was used to assess analgesia. Intraperitoneal injection of morphine (1 mg kg-1 and 5 mg kg-1) significantly reduced milk yield in unanaesthetized rats. Urethane-anaesthetized rats displayed a pattern of reflex milk-ejection responses similar to that found in conscious rats. This reflex was significantly inhibited in a dose-related, naloxone-reversible manner by buprenorphine (ED50 0.18 mg kg-1), meptazinol (ED50: 14.0 mg kg-1), morphine (ED50: 0.67 mg kg-1), pentazocine (ED50: 15.0 mg kg-1) and pethidine (ED50: 7.9 mg kg-1). Although intraperitoneal injection of morphine (5 mg kg-1) abolished the increase in intramammary pressure occurring at reflex milk-ejection, that evoked by intravenous oxytocin (0.5-1 mu) was unaffected. Each opiate also caused significant, dose-related, naloxone-reversible increases in tail-flick latency. The ED50 doses were buprenorphine (ED50: 0.14 mg kg-1), meptazinol (ED50: 12.5 mg kg-1), morphine (ED50: 5.0 mg kg-1), pentazocine (ED50: 12.5 mg kg-1) and pethidine (ED50: 6.1 mg kg-1). The order of potency for analgesia and for suppression of oxytocin release were identical, namely: buprenorphine greater than morphine greater than pethidine greater than meptazinol greater than pentazocine. The results obtained with lactating rats suggest that secretion of the hormone oxytocin is substantially reduced during opiate-induced analgesia.

Analgesia↗

Synovial infection with Mycobacterium kansasii.

Atypical mycobacteria have been recognised as saprophytic organisms for many years, but it was only with the development of better microbiological culture techniques that they became recognised as potentially pathogenic to man. Infections of tendon sheaths and joints by these organisms may present diagnostic problems, and we report here 3 cases in which Mycobacterium kansasii was responsible for disease at the hand and wrist.

Adult↗

Long term effect of a school based antismoking programme.

In the winters of 1977-8 and 1978-9 about 400 children in seven junior schools in northern England were taught the "My Body" health education programme. In the springs of 1980 and of 1982 these children, and an age matched control group, answered a questionnaire about their smoking behaviour, knowledge, and attitudes. Comparison of the two groups suggested that the programme had had a positive effect on the boys but a negligible, or even negative, effect on the girls. Various suggestions as to the reasons for this differential impact are discussed.

Adolescent↗

Differential inhibitory action by morphine on the release of oxytocin and vasopressin from the isolated neural lobe.

Simultaneous release of both oxytocin and vasopressin was evoked by electrically stimulating the isolated neural lobe. Morphine inhibited the electrically evoked release of both oxytocin and vasopressin, but whereas the opiate antagonist naloxone reversed the suppression of oxytocin release it was without effect against the opiate block of vasopressin secretion. Thus, although the secretion of both neurohypophysial hormones can be suppressed by opiates, the mechanisms may involve different types of receptors. We also provide evidence that, at least for the oxytocin neurones, the presence of endogenous opioid peptides in the neural lobe limits the amount of hormone released by electrical stimulation.

Animals↗