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Biomedical subjects

M A Gregory

Publications and source records attributed to M A Gregory.

At least 19 recordsLinked to original sources

Serial morphological changes in primate skeletal myofibres after 3 hours of ischaemia and 24 hours of reperfusion.

The sequential morphological changes occurring in skeletal myofibres after 3 hours' ischaemia and from 3 hours to 24 hours of reperfusion in vervet monkeys are described. Eight vervet monkeys were studied under general anaesthesia. A hind limb was exsanguinated and a tourniquet applied for 3 hours. Open muscle biopsy specimens were obtained from the tibialis anterior muscle before tourniquet application, just before tourniquet release and 3, 6, 12, 18 and 24 hours after tourniquet deflation. All specimens were prepared for transmission electron microscopy. After 3 hours of ischaemia and increasing periods of reperfusion, a small number of fibres showed progressive pathomorphological changes that eventually resulted in myofibre death. After initial glycogen loss and later intermyofibrillar oedema, the majority of myofibres returned to normal, while a group of fibres remained oedematous. The progressive morphological characteristics of reversibly injured myofibres undergoing repair and irreversible injured cells undergoing necrosis are described.

Animals

Alterations in the cytological composition of the juxta-scar villous mucosa after ulcer therapy with sucralfate or cimetidine.

A comparative light-microscopic morphometric analysis of non-metaplastic mucosa obtained from the pretreatment juxta-duodenal ulcer (DU) villous mucosa of 10 patients and from the first part of the duodenum of 5 normal volunteers revealed a significant increase (P less than 0.01) in the number of goblet cells (GCs) per 100 microns of villous mucosa (GC/100 microns). Such an increase was thought to represent a mucoprotective response by the mucosa to the corrosive lumenal factors that may cause or maintain ulceration. A similar morphometric analysis was performed on the endoscopically healed juxta-scar villous mucosa of 11 patients successfully treated for 6 weeks with sucralfate (5 patients) or cimetidine (6 patients). After treatment with cimetidine, GC/100 microns was reduced to near-normal levels, whereas after sucralfate therapy it was significantly raised (P less than 0.05). The difference in GC/100 microns after treatment with either sucralfate or cimetidine was significant at the P less than 0.02 level. The apparent drug-mediated difference in the cytological composition of the healed mucosa was thought to be a function of the pharmacodynamic mechanisms of action of the two drugs in promoting DU healing. It is proposed that the retention of GC hyperplasia after curative therapy with sucralfate may predisposed patients so treated to extended periods of remission.

Cimetidine

Alterations in the morphology of skeletal myofibres after 90 minutes of ischaemia and 3 hours of reperfusion.

Morphometric, light and electron microscopic methods were employed to determine whether skeletal myofibres were damaged by 90 minutes of tourniquet-mediated ischaemia. Open biceps muscle biopsies were obtained before 90 minutes of upper limb tourniquet ischaemia in 5 Chacma baboons. Further biopsies were obtained just before tourniquet release in 2 animals and after 3 hours' reperfusion in the remaining 3 animals. Other than a slight reduction in myofibre diameter and the anaerobic depletion of intermyofibrillar glycogen, no pathological changes were noted in skeletal myofibres after ischaemia. However, after reperfusion there was myofibre enlargement, intermyofibrillar oedema, internalisation of nuclei, myofibrillar and mitochondrial disorganisation and dissolution, and Z-band streaming. These results show that reperfusion injury affects skeletal myofibres after 90 minutes of tourniquet-mediated ischaemia.

Animals

Disposition of propofol infusions for caesarean section.

The disposition of propofol was studied in women undergoing elective Caesarean section. Indices of maternal recovery and neonatal assessment were correlated with venous concentrations of propofol. After induction of anaesthesia with propofol 2.0 mg.kg-1, ten patients received propofol 6 mg.kg-1.hr-1 with nitrous oxide 50 per cent in oxygen (low group) and nine were given propofol 9 mg.kg-1.hr-1 with oxygen 100 per cent (high group). Pharmacokinetic variables were similar between the groups. The mean +/- SD Vss = 2.38 +/- 1.16 L.kg-1, Cl = 39.2 +/- 9.75 ml.min-1.kg-1 and t1/2 beta = 126 +/- 68.7 min. At the time of delivery (8-16 min), the concentration of propofol ranged from 1.91-3.82 micrograms.ml-1 in the maternal vein (MV), 1.00-2.00 micrograms.ml-1 in the umbilical vein (UV) and 0.53-1.66 micrograms.ml-1 in the umbilical artery (UA). Neonates with high UV concentrations of propofol at delivery had lower neurologic and adaptive capacity scores 15 minutes later. The concentrations of propofol were similar between groups during the infusion but they declined at a faster rate in the low group postoperatively. Maternal recovery times did not depend on the total dose of propofol but the concentration of propofol at the time of eye opening was greater in the high group than the low group (1.74 +/- 0.51 vs 1.24 +/- 0.32 micrograms.ml-1, P less than 0.01). The rapid placental transfer of propofol during Caesarean section requires propofol infusions to be given cautiously, especially when induction to delivery times are long.

Adult

A histometric analysis of skeletal myofibers following 90 min of tourniquet ischemia and reperfusion.

Routine tourniquet use causes sublethal hypoxic cellular injury and results in edema formation. Using a histochemical morphometric technique, edema caused by 90 min of tourniquet-induced ischemia and 3 hr of reperfusion is measured in the different muscle fibers of a primate model. The degree of cellular swelling is shown to be related to the fiber's metabolic dependence upon oxygen. After reperfusion, predominantly oxidative type 1 fibers show a 29% increase in diameter, P less than 0.0005, type 2a fibers which are both oxidative and glycolytic increase by 7%, P less than 0.005, and the glycolytic type 2b fibers increase by 5%, P less than 0.01. A 48% increase in interfiber distance occurs with reperfusion, P less than 0.01. By quantifying the different fibers' responses to ischemic injury, this method may be of use in investigating the pathophysiology and prevention of reperfusion injury and the post-tourniquet syndrome.

Animals

Plasma etomidate levels in mother and fetus.

The most commonly used induction agent in anaesthesia for Caesarean section is still thiopentone. The increasing incidence of Caesarean section for delivery of premature babies from a hostile environment may call in question the assumption that the dose of thiopentone received by the neonate will not cause depression in the hours following birth. Previous studies on thiopentone for Caesarean section have shown inconsistency in umbilical vein/maternal vein ratios. We have studied plasma etomidate levels in maternal and umbilical blood at the time of delivery to see whether equilibrium occurs with this agent. We were able to demonstrate an umbilical/maternal vein etomidate ratio of 0.5 (SD 0.18), with no relation to time in the range encountered. Also, the uterine artery/uterine vein etomidate ratio was 0.86 (SD 0.33), suggesting that etomidate uptake into the fetus is effectively complete. Further, in all cases the neonatal plasma etomidate levels were less than half those measured at recovery of consciousness in adults in other studies, despite a larger induction dose than is usually used.

Adult

Propofol infusion anaesthesia for caesarean section.

Two propofol infusion regimens and a standard general anaesthetic were compared in thirty Chinese women undergoing elective Caesarean section. After induction of anaesthesia with propofol 2 mg.kg-1, ten patients received propofol 6 mg.kg-1.hr-1 and nitrous oxide 50 per cent in oxygen while ten were given propofol 9 mg.kg-1.hr-1 with 100 per cent oxygen. The other ten patients received thiopentone 4 mg.kg-1 and nitrous oxide 50 per cent in oxygen with enflurane one per cent. Maternal recovery times and psychomotor performance were recorded. Neonates were assessed by Apgar scores, neurologic and adapative capacity scores (NACS) and umbilical cord blood gas analysis. Haemodynamic changes were similar immediately following induction but the low propofol infusion group had the best haemodynamic stability subsequently. Recovery times were fastest in the low-infusion group but there were no differences in later postbox testing. Neonatal Apgar scores and umbilical blood gas analysis were similar but NACS at two hours were poorer in the high infusion group. A propofol infusion coupled with nitrous oxide appears to be a satisfactory technique for Caesarean section.

Adult

Pharmacokinetics of propofol in women undergoing elective caesarean section.

We have compared the pharmacokinetics of a bolus induction dose of propofol 2 mg kg-1 in 10 Chinese women undergoing elective Caesarean section with those in six non-pregnant Chinese women having laparoscopic sterilization. Blood propofol concentrations were measured using high pressure liquid chromatography with fluorimetric detection. Pharmacokinetic data were analysed by a model independent method based on statistical moment theory. Data from the laparoscopy group also underwent compartmental analysis, which produced similar kinetic results. Non-compartmental analysis estimated that the women undergoing Caesarean section had a similar elimination half-life (mean 81.27 (SD 18.87) min) and apparent volume of distribution at steady state (2.66 (0.63) litre kg-1) as non-obstetric patients (99.45 (29.40) min and 3.36 (1.87) litre kg-1). Clearance was more rapid in the Caesarean section group (39.32 (8.07) ml min-1 kg-1 vs 29.40 (8.72) ml min-1 kg-1) (P less than 0.05). The increased total body clearance may result from blood loss and delivery of the fetus and placenta at operation, although an increase in extrahepatic clearance is also possible.

Adult

Effect of adrenaline on venous plasma concentrations of bupivacaine after interpleural administration.

Bupivacaine 2.5 mg kg-1 (0.5 ml kg-1 of 0.5% solution), with or without adrenaline 5 micrograms ml-1, was administered by interpleural injection to 12 patients after elective cholecystectomy. Noncompartmental analysis indicated that the addition of adrenaline had no effect on total body clearance, apparent volume of distribution at steady state or elimination half-life of bupivacaine. However, peak plasma concentrations were lower in the adrenaline group (mean (SD) [range]: 2.57 (0.61) [1.52-3.11] vs 3.22 (0.27) [2.84-3.53] micrograms ml-1, P less than 0.05) and the time to maximum concentration was delayed (median [range]: 25 [15-30] vs 15 [10-20] min, P less than 0.05). Analgesia was variable and no differences were detected between the two groups. The addition of adrenaline appears prudent to minimize possible bupivacaine toxicity.

Analgesia

Obstetric epidural analgesia with mixtures of bupivacaine, adrenaline and fentanyl.

We performed a double-blind comparison of six solutions for epidural analgesia in 90 healthy Chinese women with uncomplicated pregnancies. Patients were randomly allocated to receive 10 ml bupivacaine 0.125% or 0.25% plain, bupivacaine 0.125% with adrenaline 1.25 micrograms/ml, bupivacaine 0.25% with adrenaline 2.5 micrograms/ml or the latter two solutions with added fentanyl 50 micrograms. Analgesia was unsatisfactory in 30% of the bupivacaine 0.125% groups without fentanyl. The addition of adrenaline, compared with bupivacaine 0.25% plain, gave faster onset and longer duration of analgesia (p less than 0.05) which was similar to that found in both fentanyl groups. There were no differences in method of delivery or neonatal Apgar scores among groups. The least concentrated mixture that gave the best analgesia was the combination of bupivacaine 0.125% with adrenaline 1.25 micrograms/ml and fentanyl 50 micrograms.

Adult

The haemodynamic effects of propofol and thiopentone for induction of caesarean section.

Forty Chinese women for elective caesarean section received either propofol 2 mg.kg-1 or thiopentone 4 mg.kg-1 for induction of general anaesthesia. Systolic, mean and diastolic arterial pressures and heart rate were recorded non-invasively every minute for ten minutes. Post-induction arterial pressures were similar to pre-induction values with no differences between thiopentone and propofol. Following intubation, the rise in systolic arterial pressure was greater in the thiopentone group, 32.1 mmHg (SD 23.7) compared with the propofol group, 17.4 mmHg (SD 23.8), (P less than 0.05). In the thiopentone group, arterial pressures were slower in returning to baseline values. Heart rate was initially elevated in both groups to the same degree. At caesarean section, induction with propofol causes less variation in arterial pressure than thiopentone. Hypotension is probably prevented by the coincident stimulus of rapid sequence induction. Neonatal Apgar scores were similar between the two groups.

Adult

Maternal and fetal levels of propofol at caesarean section.

Twenty women were given a bolus induction of propofol 2.0 mg.kg-1 for elective caesarean section. Induction to delivery times ranged from five to fourteen minutes. At delivery the maternal venous (MV) concentrations of propofol ranged from 0.53 to 1.48 micrograms.ml-1 umbilical vein (UV) 0.39 to 1.4 micrograms.ml-1 and umbilical artery (UA) 0.34 to 0.68 micrograms.ml-1 MV propofol concentrations were always higher than corresponding UV concentrations. The mean (95% confidence interval) UV/MV ratio was 0.65 (0.56-0.74) and the mean UA/UV ratio was 1.07 (0.99-1.15). Neither ratio was shown to be correlated with induction to delivery time. Distribution of propofol is rapid across the placenta and in the fetus. Apgar scores were higher with shorter incision to delivery times but were not correlated to umbilical levels of propofol.

Adult

The addition of fentanyl to epidural bupivacaine in first stage labour.

Epidural analgesia was studied in 100 healthy Chinese women with uncomplicated pregnancies in first stage labour. Patients were randomly allocated to receive 8 ml of one of the following five solutions: bupivacaine 0.125% with fentanyl 50 micrograms or fentanyl 100 micrograms, bupivacaine 0.25% plain, bupivacaine 0.25% with fentanyl 50 micrograms or fentanyl 100 micrograms. There was no difference in quality of analgesia among groups as measured by the reduction of visual analogue pain scores 20 minutes after the epidural dose. The duration of analgesia was similar among groups with the overall median duration being 105 minutes. There was no difference in method of delivery or neonatal Apgar scores. The least concentrated mixture providing good quality analgesia for the first stage of labour was the combination of bupivacaine 0.125% with fentanyl 50 micrograms.

Adult

A morphological control for ventricular pathology in man: a morphometric and morphologic assessment of LV myofibres in secundum ASD.

Ethical considerations preclude the biopsy of normal human myocardium. As a consequence, morphological investigations of diseased human heart muscle are hampered by a lack of suitable normal control tissue. The left ventricular (LV) myocardium of patients with isolated secundum atrial septal defect (ASD) is considered to be normal. This study was designed to investigate the possibility that the fine-structure of LV myofibres in hearts with ASD could be used as normal controls for myofibre pathomorphology. Wedge biopsies from the LV of four adults undergoing elective surgery for the repair of ASD were examined by light and electron microscopy. Bivariant myofibre morphometry showed that the LV myocardium of one specimen was 'normal' while three specimens exhibited varying degrees of hypertrophy. There was a correlation between the diameter (FD) and morphology of individual myofibres within and between specimens. In general, myofibres with FD less than 25 microns were similar in fine-structural appearance to those described as morphologically normal in animal models whereas those with FD greater than 25 microns exhibited hypertrophic features that increased in 'severity' with increase in myofibre size. It is proposed that although the LV myocardium in ASD may be mildly hypertrophied, myofibres with FD less than 25 microns are probably normal and may be used as fine-structural controls for myofibre pathomorphology in hearts suspected of disease.

Adult

Morphometric analysis to detect suspected myocardial disease. A pilot study.

Myofibres in the normal left ventricle (LVs) of 24 healthy young accident victims and the diseased LVs of 10 subjects who died from constrictive pericarditis or congestive (African) cardiomyopathy were subjected to morphometric evaluation. Each myofibre was represented by a pair of measurements: cross-nuclear fibre (FD) and nuclear (ND) diameters. Using a VIDS image analyser interfaced with a light microscope, 150 paired measurements were determined for each of the 34 specimens. The bivariate relationship between FD and ND for each group of specimens were expressed as linear regressions. The limits for the group distribution of normal specimen FD/ND means were calculated and graphically depicted in the form of an ellipse. Disease specimens were plotted for comparison. Of the normal specimens, 23/24 FD/ND coordinates fell within the "normal' ellipse whereas the altered relationship between FD and ND in pathological myocardia caused all 10 specimen means to be plotted outside the ellipse and their regression lines to be displaced from normal. It is suggested that the normal data define the morphometric parameters of LV myofibres in healthy hearts and create a graphic standard by which myofibre pathology in hearts suspected of disease can be detected.

Adolescent

Variations in the morphology of villous epithelial cells within 8 mm of untreated duodenal ulcers.

In order to investigate the bio-mechanics of duodenal ulcerogenesis and compare the 'quality' of drug mediated mucosal healing, it is necessary to define the morphological appearance of ulcerative mucosae. This report describes the morphological appearance of pre-therapy, juxta-duodenal ulcer (DU) villous epithelia. Biopsies made at endoscopy from the first part of the duodenum in four healthy volunteers and 3-8 mm from the edge of the DU in 97 patients were examined by light and electron microscopy. Irrespective of whether biopsies were made from the normal or juxta-DU mucosa, the villous epithelium was populated by one, or more, of six, morphologically identifiable cell types. Control epithelia were populated with normal goblet and absorptive cells. Based on the fine-structural characteristics of the predominant cell type, pathological specimens were divided into two groups: metaplastic (Group 1) and non-metaplastic (Group 2). Group 1 specimens were either exclusively populated with fully differentiated metaplastic gastric surface mucus secreting cells (GMC) (Group 1A), or GMC in various phases of metaplastic differentiation together with abnormal goblet cells (Group 1B). Group 2 specimens were populated with 'pathological' absorptive and normal goblet cells. It is postulated that the group variations in pre-therapy juxta-DU morphology represent various phases in the natural history of duodenal ulcerogenesis and healing.

Duodenal Ulcer