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Biomedical subjects

M S Hickey

Publications and source records attributed to M S Hickey.

At least 19 recordsLinked to original sources

Metabolic and anthropometric factors related to skeletal muscle UCP3 gene expression in healthy human adults.

This cross-sectional investigation sought to determine the relationship between selected metabolic, endocrine, and anthropometric factors and skeletal muscle UCP3 mRNA in healthy adult humans. Twenty-four healthy adults (13 male and 11 female) across a range of aerobic capacity, age, and body composition were studied. Muscle biopsies were obtained from the vastus lateralis, from which UCP3 mRNA was quantified by Northern blot, and fiber type was determined by use of the myosin ATPase staining procedure. In addition, resting energy expenditure and maximum rate of oxygen consumption were determined by indirect calorimetry, body composition was determined by dual-energy X-ray absorptiometry, and fasting plasma leptin and insulin were determined by ELISA. UCP3 mRNA was correlated positively with the percent type I fibers (r = 0.842, P < 0.001), plasma leptin (r = 0.454, P = 0.026), and plasma insulin (r = 0.615, P < 0.001) and inversely to age (r = -0.411, P = 0.046). Stepwise multiple regression analysis determined that percent type I muscle fibers was the best predictor of vastus lateralis UCP3 mRNA, and no other variable entered the equation (model r(2) = 0.66). This study suggests that of the variables measured, UCP3 mRNA is primarily related to skeletal muscle fiber type in healthy adults. The factors that contribute to fiber-specific differences in UCP3 mRNA expression will need to be examined in future studies.

Adult↗

Aspiration of an oropharyngeal airway during nasotracheal intubation.

The oropharyngeal airway (OPA) has been a remarkably safe device since its invention by Guedel in 1933. This plastic device is easily placed in the mouth and used for aiding in mask ventilation. We report a case of the aspiration of an OPA causing near total upper airway obstruction.

Adult↗

Substrate utilization during exercise in formerly morbidly obese women.

The purpose of this study was to compare substrate utilization during fasting and submaximal exercise in morbidly obese women after weight loss (WL) with that in weight-matched controls (C). WL were studied in the weight-stable condition approximately 24 mo after gastric bypass surgery. Energy intake (self-reported) and expenditure ((2)H(2)(18)O) were also compared. The respiratory exchange ratio during exercise at the same absolute (15 W) workload was significantly (P < or = 0.05) elevated in WL vs. C (0.90 +/- 0.02 vs. 0.83 +/- 0.03); this was reflected as lower fat utilization in WL (29.7 +/- 4.8 vs. 53.2 +/- 9.7% of energy from fat). Respiratory exchange ratio during exercise at the same relative (65% of maximal O(2) uptake) intensity was also significantly (P < 0.05) elevated in WL (0.96 +/- 0.01 vs. 0.89 +/- 0.02), and fat use was concomitantly depressed (12.4 +/- 3.0 vs. 34.3 +/- 9.9% of energy from fat). Resting substrate utilization, daily energy expenditure, and self-reported relative macronutrient intake did not differ between groups. These data suggest that lipid oxidation is depressed during physical activity in WL. This defect may, at least in part, contribute to a propensity for the development of morbid obesity.

Adult↗

Plasma leptin and exercise: recent findings.

The cloning of murine and human obese genes in 1994, and the subsequent identification that the product of the obese gene, leptin, is secreted from adipose tissue, stimulated a tremendous amount of interdisciplinary interest in adipose tissue endocrinology and the potential role of this tissue in the regulation of energy balance. Exercise, with concomitant changes in fuel flux, systemic hormone levels and energy expenditure, may contribute to the regulation of plasma leptin levels and presumably, leptin action. The initial work characterising the leptin-exercise relationship was equivocal. Cross-sectional studies provided some mixed evidence regarding the relationship between aerobic capacity or habitual physical activity and plasma leptin. In contrast, studies on acute bouts of exercise and exercise training interventions have, with few exceptions, suggested that exercise does not alter systemic leptin independent of changes in fat mass. In general, these studies did not carefully control for energy balance, and sampled only a single fasting plasma leptin level. Two recent studies utilising experimental designs in which energy balance was controlled and 24-hour profiles of plasma leptin were determined have provided the most compelling evidence to date of the interaction between exercise, energy balance and systemic leptin in humans. These studies provide a clear explanation for the apparent lack of an acute effect of exercise on systemic leptin and underscore the importance of clearly defining the balance between energy intake and energy expenditure when studying the physiology of leptin. The aim of this brief review is to provide an overview of the interaction between energy expenditure during physical activity and systemic leptin level. Special emphasis will be placed on those studies in which energy intake/balance was carefully controlled.

Circadian Rhythm↗

Elective removal of an intramyocardial bullet.

A 26-year-old man had a gunshot wound in the right posterolateral aspect of the chest. A chest radiograph showed the bullet in the region of the cardiac silhouette. The patient was hemodynamically stable and had no complaints of dyspnea or abdominal pain. Echocardiography and computed tomography identified the bullet in the wall of the right ventricle. The surgical management of the injury is discussed in detail.

Adult↗

Residual atrial fibrillation and clinical consequences following postoperative supraventricular arrhythmias.

AIMS: This retrospective study investigated whether the supraventricular arrhythmias (SVA) observed during cardiac surgery are limited to or persist beyond the postoperative period, their clinical consequences and whether they are influenced by preoperative and postoperative factors. METHODS: A total of 375 patients undergoing elective bypass graft surgery over a 15-month period by three surgeons were included. All patients had their preoperative medications continued to the day of surgery and prophylactic anti-arrhythmic medications were not used in any of the cases. Standard anaesthetic techniques were used. Rhythm disturbances were diagnosed by ECG. The arrhythmias were treated medically or by cardioversion. All patients were followed up for 6 months. RESULTS: Postoperative SVA occurred in 25% of patients. The commonest arrhythmia was atrial fibrillation (89.4%), followed by atrial flutter (6.4%) and supraventricular tachycardia (4.2%). In 89. 8% of the cases, the arrhythmias occurred within the first four postoperative days with a maximum incidence on the second day (27. 7%). Atrial fibrillation was still present in 50% of patients at hospital discharge and in 39% at 6 months follow up. Patients with arrhythmias had a prolonged hospital stay (7.7+/-2.6 vs. 6.0+/-2.6 days; P<0.05). There was no hospital mortality in the study and the incidence of postoperative stroke was equal in the sinus rhythm and arrhythmia patients (1.1%). SVA were more frequent when cardioplegia was used to protect the heart (32%) than with intermittent ischaemia (9%; P<0.001). At 6 months follow up, the patients receiving cardioplegia also had a higher prevalence of atrial fibrillation than those operated with intermittent ischaemia (41% vs. 22%; P<0. 05). The incidence of SVA and persistence of atrial fibrillation was unrelated to other preoperative and intraoperative factors. CONCLUSION: Postoperative supraventricular arrhythmias have a long-lasting effect on cardiac rhythm: patients with SVA have a high probability of remaining in atrial fibrillation at hospital discharge and 6 months after surgery. The occurrence of atrial fibrillation seems to be influenced by the type of myocardial protection used but this does not appear to exert harmful effects.

Aged↗

Arterial switch operation: successful bilateral internal thoracic artery grafting.

Internal thoracic artery grafting in arterial switch operations for transposition of great arteries has been reported for salvage of myocardial ischemia after initial coronary transfer. We report a situation where we opted for primary coronary bypass grafting to avoid an obviously difficult coronary transfer, with successful outcome.

Humans↗

Early discharge following coronary bypass surgery: is it safe?

OBJECTIVES: Early discharge has been proposed as a means of containing the escalating cost of health care in cardiac surgery. The aim of this study was to investigate whether shortening the length of hospital stay after coronary artery bypass surgery is safe and cost effective. METHODS: Patients (n=198) undergoing elective bypass surgery by two surgeons for a period of 12 months were prospectively entered into the study but not randomized. The anaesthetic and surgical treatments were identical in all patients with the exception that one of the surgeons used intermittent cold crystalloid cardioplegia ('normal discharge' group; n=119) and the other used intermittent ischaemia without cardioplegia ('early discharge' group; n=79). Previous to the study both surgeons discharged patients on the 7th-8th postoperative day. For the present study, one of the two surgeons adopted the new policy of discharging patients on the 4th postoperative day ('early discharge' group). The criteria for hospital discharge included: presence of sinus rhythm, absence of pyrexia and wound infection, normal routine blood tests, satisfactory chest X-ray and ECG and full mobility. RESULTS: The clinical characteristics were identical in the two groups. The number of grafts per patient was 2.8+/-0.8 and 3.2+/-1.0, and the total ischaemic time 47+/-13 and 46+/-14 min in the normal and early discharge groups, respectively (P=NS in each instance). In the normal discharge group the mean hospital stay was 7.7+/-3.3 days whereas in the early discharge group it was 4.7+/-2.0 days (P<0. 0001) with 73.5% of the patients being discharged within the first 4 days following surgery. The shortening of hospital stay resulted in a mean reduction of costs of pound750/patient. There was no operative mortality (<30 days following surgery) and the incidence of non-fatal perioperative complications were similar in the two groups, with the exception that the incidence of supraventricular arrhythmias was significantly higher in the normal discharge group than in the early discharge group (33% vs. 6.3% respectively; P<0. 0001). These rhythm abnormalities occurred within the first 4 days in 89% of patients following surgery and were the cause of readmission in only one patient in the normal discharge group. There were a total of ten (8.4%) readmissions in the normal discharge group and three (3.8%) in the early discharge group. CONCLUSION: Shortening the postoperative hospital stay to 4 days following elective coronary bypass surgery appears to be safe and can be a means of reducing the cost of care. This in turn may result in a greater availability of resources and in an effective way of reducing waiting lists.

Aged↗

Post infarction ventricular septal defect - can we do better?

OBJECTIVE: To identify predictors of early and late outcome among 117 consecutive patients who underwent postinfarction ventricular septal defect (VSD) repair over a period of 12 years. METHODS: A retrospective analysis of clinical data was performed. Mean age was 65.5+/-7.8. There were 43 females. Full data were obtained in 110 patients. Of these, 76 patients presented with anterior and 34 with posterior VSD. Thirty-three patients were operated in cardiogenic shock. Mean time between myocardial infarction (MI) and VSD development was 5.6+/-7.8 days (median 4) and from VSD to surgery 9. 0+/-28.1 (median 2). Sixty-six patients had intraaortic balloon pump (IABP) inserted, and 15 were ventilated preoperatively. Logistic regression and Cox regression were used for multivariate analysis. RESULTS: Thirty days mortality was 37%. Among 110 patients, in whom complete analysis was possible, 38 died within 30 days (35%). Mortality in the posterior VSD group was 35% and in the anterior VSD group 34% (NS). In 44 patients (40%) a residual shunt was found on postoperative echocardiography. This required reoperation in 13 patients (four deaths). Cardiogenic shock prior to surgery adversely influenced early survival - odds ratio (OR) 5.7 (confidence interval (CI) 2.1-16.0) (P=0.0008). Deterioration of haemodynamic status in between admission and surgery was stronger predictor of mortality than shock on admission - OR 6.0 (CI 1.6-22.6) (P=0.008) vs. 3.1 (CI 1.0-9.3) (P=0.049). A longer time between MI and surgery favoured survival - OR 0.1 (CI 0.03-0.4) (P=0.002). The time period from the infarct to the septal rupture, but not from the rupture to surgery, appeared to be a significant predictor of survival - OR 0.2 (CI 0. 05-0.6) (P=0.008). Five years survival was 46+/-5%. Preoperative cardiogenic shock affected late survival - OR 2.7 (CI 1.5-4.9) (P=0. 001). Of 72 patients who survived 30 postoperative days, 12 (17%) were in New York Heart Association (NYHA) class III or IV and five (6.9%) in Canadian Cardiovascular Soceity (CCS) class III or IV at the last follow-up. CONCLUSIONS: Preoperative cardiogenic shock and early postinfarction septal rupture carry a grave prognosis. Achieving haemodynamic stability prior to surgery may be beneficial but prolonged attempts to improve patients' cardiovascular state are hazardous.

Adult↗

Modulation of immune function by dietary lectins in rheumatoid arthritis.

Despite the almost universal clinical observation that inflammation of the gut is frequently associated with inflammation of the joints and vice versa, the nature of this relationship remains elusive. In the present review, we provide evidence for how the interaction of dietary lectins with enterocytes and lymphocytes may facilitate the translocation of both dietary and gut-derived pathogenic antigens to peripheral tissues, which in turn causes persistent peripheral antigenic stimulation. In genetically susceptible individuals, this antigenic stimulation may ultimately result in the expression of overt rheumatoid arthritis (RA) via molecular mimicry, a process whereby foreign peptides, similar in structure to endogenous peptides, may cause antibodies or T-lymphocytes to cross-react with both foreign and endogenous peptides and thereby break immunological tolerance. By eliminating dietary elements, particularly lectins, which adversely influence both enterocyte and lymphocyte structure and function, it is proposed that the peripheral antigenic stimulus (both pathogenic and dietary) will be reduced and thereby result in a diminution of disease symptoms in certain patients with RA.

Antigens↗

A simple method of treating coronary air embolism after cardiopulmonary bypass.

Coronary air embolism is a potential complication of cardiac operations performed with cardiopulmonary bypass, especially open heart operations. There are many recommended methods described in the literature to treat the sequelae of coronary air embolism, none universally effective. We describe a simple and safe method to treat the condition, which we have found very effective in our practice.

Cardiopulmonary Bypass↗

Effect of short-term exercise training on insulin-stimulated PI 3-kinase activity in human skeletal muscle.

The purpose of this study was to determine if the improvement in insulin sensitivity with exercise training is associated with enhanced phosphatidylinositol 3-kinase (PI 3-kinase) activity. Nine sedentary men were studied before and after 7 days of exercise training (1 h/day, approximately 75% maximal oxygen consumption). Insulin sensitivity was determined with a euglycemic-hyperinsulinemic glucose clamp in the sedentary state and 15-17 h after the final exercise bout. PI 3-kinase activity was determined from samples (vastus lateralis) obtained in the fasted condition and after 60 min of submaximal insulin stimulation during the clamp. After exercise, glucose infusion rate increased (P < 0. 05) significantly (means +/- SE, 7.8 +/- 0.5 vs. 9.8 +/- 0.8 mg. kg(-1). min(-1)), indicating improved insulin sensitivity. Insulin-stimulated (insulin stimulated/fasting) phosphotyrosine immunoprecipitable PI 3-kinase activity also increased significantly (P < 0.05) with exercise (3.1 +/- 0.8-fold) compared with the sedentary condition (1.3 +/- 0.1-fold). There was no change in fasting PI 3-kinase activity. These data suggest that an enhancement of insulin signal transduction in skeletal muscle may contribute to the improvement in insulin action with exercise.

Adult↗

Impact of hyperinsulinemia on myosin heavy chain gene regulation.

The purpose of this study was to determine whether hyperinsulinemia alters myosin heavy chain (MHC) gene expression in human skeletal muscle. A biopsy from the vastus lateralis was obtained in young, lean [age 24.6 +/- 1.0 (SE) yr, body fat 11.9 +/- 1.9%, body mass index 26.1 +/- 1.1 kg/m2; n = 10] men before and after 3 h of hyperinsulinemia (hyperinsulinemic-euglycemic clamp). Muscle was analyzed for mRNA of type I, IIa, and IIx MHC isoforms. Hyperinsulinemia (mean of 1,065.7 +/- 9.8 pmol/l during minutes 20 to 180) did not change (P > 0.05) the mRNA concentration of either the type I MHC or type IIA MHC isoforms. In contrast, type IIX MHC mRNA increased (P < 0.05) with hyperinsulinemia compared with the fasted condition. These data indicate that hyperinsulinemia rapidly increases type IIx MHC mRNA in human skeletal muscle.

Adult↗

A new paradigm for type 2 diabetes mellitus: could it be a disease of the foregut?

SUMMARY BACKGROUND DATA: We previously reported, in a study of 608 patients, that the gastric bypass operation (GB) controls type 2 diabetes mellitus in the morbidly obese patient more effectively than any medical therapy. Further, we showed for the first time that it was possible to reduce the mortality from diabetes; GB reduced the chance of dying from 4.5% per year to 1% per year. This control of diabetes has been ascribed to the weight loss induced by the operation. These studies, in weight-stable women, were designed to determine whether weight loss was really the important factor. METHODS: Fasting plasma insulin, fasting plasma glucose, minimal model-derived insulin sensitivity and leptin levels were measured in carefully matched cohorts: six women who had undergone GB and had been stable at their lowered weight 24 to 30 months after surgery versus a control group of six women who did not undergo surgery and were similarly weight-stable. The two groups were matched in age, percentage of fat, body mass index, waist circumference, and aerobic capacity. RESULTS: Even though the two groups of patients were closely matched in weight, age, percentage of fat, and even aerobic capacity, and with both groups maintaining stable weights, the surgical group demonstrated significantly lower levels of serum leptin, fasting plasma insulin, and fasting plasma glucose compared to the control group. Similarly, minimal model-derived insulin sensitivity was significantly higher in the surgical group. Finally, self-reported food intake was significantly lower in the surgical group. CONCLUSIONS: Weight loss is not the reason why GB controls diabetes mellitus. Instead, bypassing the foregut and reducing food intake produce the profound long-term alterations in glucose metabolism and insulin action. These findings suggest that our current paradigms of type 2 diabetes mellitus deserve review. The critical lesion may lie in abnormal signals from the gut.

Adult↗

Fiber type and citrate synthase activity in the human gastrocnemius and vastus lateralis with aging.

The purpose of this study was to determine whether enzymatic and histochemical characteristics of human skeletal muscle are altered with aging. Tissues from the vastus lateralis (VL) and gastrocnemius were analyzed for citrate synthase (CS) activity and fiber type in 55 sedentary men (age range 18-80 yr). In this population, CS activity in the gastrocnemius was negatively related to age (r = -0. 32, P < 0.05); there was no relationship in the VL. Treadmill-determined maximal oxygen consumption was positively related (r = 0.40, P < 0.05) to CS in the gastrocnemius but not in the VL. CS activity in the gastrocnemius was 24% lower in the oldest (>/=60 yr, n = 10) vs. the youngest (</=30 yr; n = 12) men; there was no change in CS activity in the VL with aging. No changes in fiber type were evident with age in either muscle. These data suggest a reduction in oxidative enzyme activity in human skeletal muscle with the aging process; this relationship may be muscle-group specific.

Adipose Tissue↗

Vanadate stimulation of 2-deoxyglucose transport is not mediated by PI 3-kinase in human skeletal muscle.

Glucose transport in mammalian skeletal muscle is stimulated by insulin, hypoxia and tyrosine protein phosphatase inhibitors such as vanadate. However, it is unknown whether the vanadate signaling mechanism shares a common or separate pathway with insulin or hypoxia. Therefore, experiments were conducted on incubated human muscle strips to compare the effects of vanadate with insulin and hypoxia stimulated 2-deoxyglucose transport (2-DOG). We also used the phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor wortmannin to examine whether PI 3-kinase is a common step by which each stimulate glucose transport. Results demonstrate that whereas the effects of vanadate and hypoxia were additive with insulin stimulated glucose transport, the effect of vanadate plus hypoxia was not. In addition, wortmannin significantly (P < 0.05) reduced insulin but not vanadate or hypoxia stimulated 2-DOG transport. Moreover, PI 3-kinase activity was significantly elevated (P < 0.05) in the presence of insulin but not vanadate. In conclusion, these data suggest that vanadate and hypoxia stimulate glucose transport via a similar signaling pathway which is distinct from insulin and that the vanadate signaling pathway is not mediated by PI 3-kinase in human skeletal muscle.

Analysis of Variance↗