Pregnancy and development of diabetes in First Nations and non-First Nations women in Alberta, Canada.

AIM: To conduct a retrospective population-based study to examine the risk of developing diabetes after delivery in First Nations and non-First Nations women in Alberta. METHODS: Delivery records (1999-2014) were linked to provincial administrative data, which allowed for a maximum follow-up of 16 years after delivery. Prevalence of pregnancy risk factors were compared by First Nations status. Hazard ratios for diabetes after delivery by First Nations status, high pre-pregnancy body weight (≥91 kg) and gestational diabetes status were estimated using the Cox proportional hazards model. RESULTS: Age-adjusted prevalence of gestational diabetes (7.9% vs 4.6%; P<0.0001), high pre-pregnancy body weight (18.8% vs 10.2%; P<0.0001) and diabetes after delivery (3.9% vs 1.1%; P<0.0001) were higher in First Nations women than in non-First Nations women. Development of diabetes after delivery was higher with First Nations status (hazard ratio 3.0, 95% CI 2.6-3.4), high pre-pregnancy body weight (hazard ratio 3.6, 95% CI 3.3-4.0) and gestational diabetes status (hazard ratio 19.2, 95% CI 17.9-20.6). The highest risk was within First Nations women with high pre-pregnancy body weight and gestational diabetes (hazard ratio 54.8, 95% CI 45.2-66.5) compared to women without these three risk factors. Reduced prenatal visits per pregnancy (8.4 vs 10.7; P<0.0001) and delayed first prenatal visit (time to delivery 23.7 vs 26.7 weeks; P<0.0001) were observed in First Nations women compared to non-First Nations women. CONCLUSION: First Nations women are at greater risk of developing diabetes after pregnancy, with gestational diabetes being the strongest predictor. Strategies that target the specific needs of First Nations women before, during and after pregnancy are required.

Breeding biology and the evolution of dynamic sexual dichromatism in frogs.

Dynamic sexual dichromatism is a temporary colour change between the sexes and has evolved independently in a wide range of anurans, many of which are explosive breeders wherein males physically compete for access to females. Behavioural studies in a few species indicate that dynamic dichromatism functions as a visual signal in large breeding aggregations; however, the prevalence of this trait and the social and environmental factors underlying its expression are poorly understood. We compiled a database of 178 anurans with dynamic dichromatism that include representatives from 15 families and subfamilies. Dynamic dichromatism is common in two of the three subfamilies of hylid treefrogs. Phylogenetic comparative analyses of 355 hylid species (of which 95 display dynamic dichromatism) reveal high transition rates between dynamic dichromatism, ontogenetic (permanent) dichromatism and monochromatism reflecting the high evolutionary lability of this trait. Correlated evolution in hylids between dynamic dichromatism and forming large breeding aggregations indicates that the evolution of large breeding aggregations precedes the evolution of dynamic dichromatism. Multivariate phylogenetic logistic regression recovers the interaction between biogeographic distribution and forming breeding aggregations as a significant predictor of dynamic dichromatism in hylids. Accounting for macroecological differences between temperate and tropical regions, such as seasonality and the availability of breeding sites, may improve our understanding of ecological contexts in which dynamic dichromatism is likely to arise in tropical lineages and why it is retained in some temperate species and lost in others.

Influence of prenatal nutrition and obesity on tissue specific fat mass and obesity-associated (FTO) gene expression.

The recent discovery of an association between body composition, energy intake and the fat mass and obesity-associated (FTO) gene represents a promising new therapeutic target in obesity prevention. In a well, pre-established large animal model, we investigated the regulation of FTO gene expression under conditions either leading to obesity or increased risk of obesity related disorders: i) a sedentary 'Western' lifestyle and ii) prenatal exposure to nutrient restriction. Pregnant sheep were either fed to fully meet their nutritional requirements throughout gestation or 50% of this amount from early-to-mid gestation. Following weaning, offspring were either made obese through exposure to a sedentary obesogenic environment or remained lean. A significant positive relationship between placental FTO gene expression and fetal weight was found at 110 days gestation. In both the newborn and adult offspring, the hypothalamus was the major site of FTO gene expression. Hypothalamic FTO gene expression was upregulated by obesity and was further increased by prenatal nutrient restriction. Importantly, we found a strong negative relationship between the hypothalamic FTO gene expression and food intake in lean animals only that may imply FTO as a novel controller of energy intake. In contrast, FTO gene expression in the heart was downregulated in obese offspring born to nutrient restricted mothers. In addition, FTO gene expression was unaffected by obesity or prenatal diet in insulin-dependent tissues, where it changed with age possibly reflecting adaptations in cellular energetic activity. These findings extend information gained from human epidemiology and provide new insights into the regulation of in vivo energy metabolism to prevent obesity.

Improved cardiovascular health following a progressive walking and dietary intervention for type 2 diabetes.

AIM: To examine the impact of two different lifestyle programmes on cardiovascular health and glycaemic control among people with type 2 diabetes. METHODS: A two-phase 24-week randomized trial. During the first phase, participants were to increase daily steps using a pedometer. At week 12, participants were randomly allocated to either an enhanced lifestyle programme (ELP) targeting walking speed or a basic lifestyle programme (BLP) targeting total daily steps. Both programmes focused on increasing the intake of low glycaemic index foods but utilized different goal setting strategies. Clinical measurements were completed at baseline, week 12 and week 24. Principal outcomes were change in resting pulse rate (PR) and glycated haemoglobin A1c (A1c) between week 12 and week 24 compared between groups using analysis of covariance. RESULTS: Forty-one participants [mean +/- s.d. : age = 56.5 +/- 7.2 years, body mass index (BMI) = 32.7 +/- 6.1 kg/m(2)] were randomized. After 12 weeks, we observed an increase in average total daily steps of 1688 (95% confidence interval: 330-3040, [corrected] p = 0.02). Weight, BMI and systolic and diastolic blood pressure improved (p < 0.01 for all). No changes were observed for energy intake. At week 24, those in the ELP had a lower resting PR (71 +/- 12 b.p.m.) compared with those in the BLP (78 +/- 12 b.p.m.) (adjusted p = 0.03), while no group differences for total daily steps or glycaemic control were observed. CONCLUSIONS: Improvements in cardiovascular health can be expected following a pedometer-based lifestyle modification programme that progresses from walking more to walking faster.

Acute effect of metformin on exercise capacity in active males.

AIM: Physical activity and metformin are often used concomitantly in the treatment of diabetes, even though little is known about possible interactions between these treatment modalities. This study was designed to examine the acute effect of metformin on oxygen consumption and lactate concentration during exercise. METHODS: Eleven healthy, active men [mean +/- s.d.: age = 29.9 +/- 3.7 years; body mass index = 25.2 +/- 2.8 kg/m2; maximal oxygen consumption (VO2max) = 53.5 +/- 8.9 ml/kg/min] completed a randomized, double-blind, placebo-controlled, crossover study. The testing protocol consisted of a standardized breakfast with metformin (1000 mg) or placebo. Three hours after breakfast, participants underwent a graded maximal exercise test on a cycle ergometer. Approximately 30 min after this exercise test, participants cycled continuously at an intensity below their ventilatory threshold for 45 min (mean exercise intensity = 69 +/- 5.5% of VO2max). RESULTS: During the graded exercise test, average oxygen consumption was higher for the metformin condition (2.9 vs. 2.8 l/min, p = 0.04); however, there was no treatment effect on VO2max or ventilatory threshold. During continuous exercise, lactate was lower for the metformin condition (4.7 vs. 5.4 mmol/l, p = 0.05). Following a standardized lunch, glucose concentrations were lower in the metformin compared with the placebo condition (5.8 vs. 6.4 mmol/l, p = 0.04). CONCLUSION: A single dose of metformin does not acutely influence maximal oxygen consumption or ventilatory threshold in healthy active males. The lower lactate concentration observed during continuous exercise with metformin was an unexpected finding considering that, in the resting state, metformin has been previously associated with a modest increase in lactate concentrations.

Gender differences in the metabolic response to graded numbers of transplanted islets of Langerhans.

Gender differences after treatment with streptozotocin (STZ) have been previously reported; however, differences in the glucose response to islet transplantation in STZ-induced diabetes in male and female rats after islet transplantation have not been examined. Male and female Wistar-Furth rats were made diabetic using STZ (55 mg/kg BW) and then given an intraportal islet transplant. Control animals received sham injections and sham transplant surgery; diabetic animals received STZ and sham surgery. In male animals, islet grafts contained 0 (diabetic), 250, 500, 1000, 1500, 2000, and 3000 islets; in female rats, grafts were made up of 0, 500 700, 750, 1000, or 2500 islets. STZ treatment had more dramatic effects on male than female rats. During the diabetic phase, body weights of male rats were significantly reduced compared to those of control male animals; this was not observed among females. Although all STZ-treated animals were hyperglycemic, plasma glucose levels in male diabetic rats were significantly higher than those in females during this phase (29.8 +/- 2.1 vs. 24.6 +/- 0.6 mM). After islet transplantation, body weight gain was positively associated with the number of islets transplanted in male rats (r2 = 0.59; P < 0.01), but not in females (r2 = 0.09; P > 0.8). In both male and female rats, animals that received 1000 islets or more were generally normoglycemic by 3 weeks posttransplant (males, 10.8 +/- 2.2 mM; females, 7.1 +/- 0.2 mM). Approximately 60% of male and female animals that received 500 islets achieved a reduction in plasma glucose levels. Mean plasma glucose levels were 17.2 +/- 2.3 in the females and 22.6 +/- 1.0 mM in males. However, a significantly larger proportion of female 500-islet animals (6 of 16) achieved a plasma glucose level of 9.5 mM or less compared with males receiving 500 islets (2 of 30). Multivariate regression analysis suggests that sex and islet number interact to affect glycemic normalization after islet transplantation. Gender differences appear to influence body weight and plasma glucose responses to islet transplantation. This finding may have particular relevance when a marginal number of functional islets are available.

Long-term consequences in offspring of diabetes in pregnancy: studies with syngeneic islet-transplanted streptozotocin-diabetic rats.

To study the long-term effects of exposure to maternal hyperglycemia and insulin deficiency in utero, we used the syngeneic islet transplanted streptozotocin-diabetic rat model of diabetes in pregnancy and examined insulin secretion and action in 6-month-old offspring. Female rats were rendered diabetic with streptozotocin and then transplanted with 2500, 750, or 500 islets. Control animals were also studied, and one group whose islet transplants failed remained diabetic. During pregnancy, plasma glucose levels in the diabetic rats and the groups receiving 500 and 750 islets were 24.7 +/- 1.0, 15.3 +/- 1.4, and 7.9 +/- 0.5 mmol/liter, respectively, all significantly greater than the control value (5.6 +/- 0.3 mmol/liter; P < 0.05). The plasma glucose level in the 2500 islet group was 6.2 +/- 0.2 mmol/liter, which was not significantly higher than the control value. When the offspring were studied at 6 months, there was no significant difference between groups in either glucose or insulin levels after iv glucose, although acute insulin secretion tended to be higher in the offspring of the diabetic animals. A study of insulin action with the euglycemic clamp at two insulin levels showed that insulin sensitivity was reduced in the offspring of diabetic animals vs. controls (1.97 +/- 0.24 vs. 7.58 +/- 0.95 mumol/liter x 100/kg/min.pmol/liter; P < 0.05). Insulin sensitivity was also significantly reduced in the 2500, 750, and 500 islet group offspring (4.81 +/- 0.57, 4.82 +/- 0.64, and 4.01 +/- 0.63 mumol/liter x 100/kg/min.pmol/liter; P < 0.05) compared to that in the control. There were no differences in insulin sensitivity between male and female animals. In summary, animals displaying maternal insulin deficiency have offspring who are insulin resistant without any evidence of iv glucose intolerance or diminished insulin secretion.

Tardive dyskinesia: characterization and prevalence in a statewide system.

The prevalence of tardive dyskinesia in a state-wide mental hospital system was assessed using a new quantitative rating scale and related to demographic, medication, and medical history variables. Twenty-six percent of patients had definite signs of tardive dyskinesia, about 12% moderately severe dyskinesia, and 40% exhibited at least some minimal symptoms. Tardive dyskinesia significantly increased with age, and females had a slightly but significantly greater prevalence rate than males. There was no difference in dyskinesia prevalence between patients on or off neuroleptics at time of rating, but patients on multiple neuroleptic drugs had higher prevalence of moderately severe dyskinesia.

Major hemorrhage following administration of intrapleural streptokinase.

Severe spontaneous bleeding has not been reported to complicate therapy with intrapleural streptokinase (SK). Recent data have demonstrated intrapleural SK to be devoid of systemic fibrinolytic effect. This report presents a patient who suffered major hemorrhage following the administration of 500,000 units of SK intrapleurally.

Prediction of employability in schizophrenic patients.

This study, the third of a series of reports on employability and schizophrenia, investigated the effects of both interview and non-interview variables on employability. Data on 46 chronic schizophrenic inpatients included demographic and illness-related variables, measures of psychopathology and interview-based ratings of employment skill. Latent class analysis using linear structural relations (LISREL) modelling generated the main finding namely, that interview-based measures are the strongest determinants of employability. However, other variables pertaining to illness, prior functioning and negative symptoms, exert an effect on interview performance and hence indirectly influence employability ratings and judgements.

A prospective study of incisional time, blood loss, pain, and healing with carbon dioxide laser, scalpel, and electrosurgery.

Carbon dioxide laser incisions are reported to be less painful, less bloody, and less prone to seroma formation and to heal better than scalpel or electrosurgical incisions. We compared all three modalities in a prospective randomized study of cholecystectomy incisions. Time required for the incision and incisional blood loss was less with electrosurgery than with the carbon dioxide laser or scalpel. Postoperative pain and wound healing, however, were the same for all three techniques. The carbon dioxide laser appears to offer no advantage over conventional means of making a standard incision.

Concentration of melanocyte stimulating hormone (MSH) within specific brain regions in aged squirrel monkeys.

The concentration of MSH per unit protein is reduced on average in several sites within the brains of aged squirrel monkeys. This decrease may account for alterations in CNS functions mediated via MSH but perhaps does not account for reduced fever in these aged subhuman primates.

Laparoscopic fundoplication for symptomatic but physiologic gastroesophageal reflux.

Esophageal pH monitoring identifies some patients who have physiologic amounts of esophageal acid exposure but have a strong correlation between symptoms of esophageal reflux events. These patients with symptomatic physiologic reflux probably have enhanced sensory perception of reflux events and may be difficult to control with acid-suppressive therapy. Little is known about the role of fundoplication in such patients. Patients with no endoscopic evidence of gastroesophageal reflux disease and a normal 24-hour pH composite score (<22.4 in our laboratory), but a symptom index (SI = number of symptoms with pH <4/total number of symptoms) greater than 50% were offered laparoscopic fundoplication if acid-suppressive therapy was unsatisfactory. This group comprised 18 (4%) of 459 patients undergoing fundoplication at our institution. Heartburn, dysphagia, and reflux symptoms were scored on a scale of 0 to 10 with patients on and off medicine preoperatively, and at a mean of 7.2 months (range 1 to 32 months) postoperatively. The 18 patients with symptomatic physiologic reflux (6 males and 12 females) had heartburn as a major complaint. Preoperative response to proton pump inhibitors for heartburn was 72% and for all symptoms was 60%. The group had a mean pH composite score of 14 (range 4 to 22). The symptom used to calculate the symptom index was heartburn in 12 patients, regurgitation in three, chest pain in two, and cough in one. An average of 18 symptoms (range 2 to 56) were recorded. The mean symptom index was 82% (range 50% to 100%). A Nissen fundoplication was performed in nine patients and a Toupet fundoplication in nine. Surgery was successful (>90%) in alleviating reflux symptoms in 14 patients and partially successful (>75%) in three of the remaining four patients. Gas bloat and dysphagia were seen in one patient each. Fundoplication is effective at relieving reflux symptoms in carefully selected patients with symptomatic physiologic reflux, with minimal side effects.

Lethal potency and fractionation of Duvernoy's secretion from the brown tree snake, Boiga irregularis.

The liquid secretion contained only 15% protein and had relatively low proteolytic activity. The reconstituted crude secretion had a murine i.p. LD50 of 10.33 mg/kg and was not hemorrhagic in doses up to 200 micrograms. Fast Protein Liquid Chromatographic (FPLC) cation exchange analysis of reconstituted crude secretion resulted in resolution of 16 peaks. Lethal activity was identified in three peaks. The major lethal fraction was 12.5% of the secretion protein and had a murine i.p. LD50 of 7.3 mg/kg. A pooled fraction containing two lethal peaks which comprised 9.4% of secretion protein had moderate proteolytic activity and produced myoglobinuria in mice. The fraction had an approximate murine i.p. LD50 of 3.7 mg/kg. Microscopic examination of muscle tissue from mice succumbing to this fraction revealed multifocal myofiber degeneration and necrosis. SDS-PAGE indicated that the major lethal fraction contained three proteins with mol. wts of 12,500, 18,000 and 52,000 and the myotoxic fraction contained two proteins with mol. wts of 14,500 and 17,000. While B. irregularis Duvernoy's secretion has a low lethal index, it does contain a myotoxic fraction with moderate lethal potency. These observations and recent data describing clinical envenomation of several infant patients suggest that large specimens may pose a hazard to infants and small children.

Pathologic changes induced by phospholipase A2 isolated from the venom of Collett's snake, Pseudechis colletti: a light and electron microscopic study.

Pseudechis colletti is an Australian elapid snake with a range limited to central Queensland, Australia. The venom of this snake, as well as that of several other Australian elapids, has been shown to contain a phospholipase A2 (PLA2) which can cause a marked myoglobinuria in mice. Few studies have described the histopathologic and ultrastructural changes that result from myotoxic PLA2-induced damage. Our investigation demonstrated that the isolated PLA2 induced myodegeneration and necrosis in myocardium in a dose-related manner, with subsequent myoglobinuria and myoglobinuric nephropathy.

Accuracy and reliability of total body electrical conductivity (TOBEC) for determining body composition of rats in experimental studies.

Total body electrical conductivity (TOBEC) has been promoted as a noninvasive method to estimate body composition in small mammals. Validation of this method has primarily been under normative conditions and has generally been inadequate. This article reports on the reliability and accuracy of TOBEC methodology to assess gradual, physiologically induced changes in body composition in rats under different experimental conditions. Reliability of the index of electrical conductivity (EM number) was assessed by analyzing components of variance. Accuracy was assessed by comparing EM number to actual lean body mass (LBM, from carcass analysis), across different experimental conditions, within a particular experimental condition, and over time for a given set of animals. Reliable measurements were obtained by strictly adhering to a standard protocol. TOBEC was inaccurate across experimental conditions, within experimental conditions, and within a single experimental condition during the course of an experiment. This inaccuracy apparently stemmed from the lack of a direct relationship between EM number and LBM; EM number was more strongly correlated with body weight than with LBM. At the present time, TOBEC cannot be used in place of carcass analysis to accurately predict the body composition of rats during or following the administration of a variety of experimental conditions.

Dietary fiber intakes and insulin requirements in pregnant women with type 1 diabetes.

OBJECTIVE: To determine whether higher dietary fiber intake (water soluble and insoluble) is associated with lower insulin requirements and better glycemic control in pregnant women with type 1 diabetes consuming a self-selected diet. DESIGN: A longitudinal, observational study. SUBJECTS: Pregnant women (n=141) with type 1 diabetes participating in an interdisciplinary program examining the effects of glycemic control on pregnancy outcome (Diabetes and Pregnancy Program, University of Cincinnati Medical Center). MEASUREMENTS: We determined total, water soluble and insoluble fiber intakes from 3-day food records kept each trimester during pregnancy. Outcome measures were insulin dose, pre-meal blood glucose, and glycated hemoglobin concentrations. STATISTICAL ANALYSES: Correlation coefficients, multiple regression, mixed-model analysis of variance. RESULTS: Mean intakes (g/day) of total, water soluble fiber, and insoluble fiber were 14.0 (range, 1.8-33.1), 4.8 (range, 0.6-10.5) and 9.0 (range, 1.1-24.0), respectively. In the second and third trimesters of pregnancy, insulin requirements were inversely associated with total, water soluble, and insoluble fiber intakes; the correlation coefficients ranged from -0.22 to -0.17 (P=.02 to .08). Insulin requirements associated with a higher fiber intake (20.5 g/day) were 16% to 18% lower than for a lower fiber intake (8.1 g/day). These relations remained after adjustment for body weight, disease severity and duration, insulin type, and study year in the second (P=.03 to .10) but not in the third trimester. Pre-meal blood glucose and glycated hemoglobin concentrations were not associated with fiber intake. CONCLUSIONS: Among pregnant women with type 1 diabetes, higher fiber intake is associated with lower daily insulin requirements. Dietary fiber intake should be considered when counseling patients about the management of blood glucose concentrations.

Laparoscopic inguinal hernia repair using an anatomically contoured three-dimensional mesh.

BACKGROUND: Laparoscopic inguinal hernia repair frequently is performed with mechanical fixation of a flat polypropylene mesh. Mechanical fixation is associated with pain syndromes, and mesh migration may occur without fixation of flat prostheses. An anatomically contoured mesh (3D Max; Davol, Cranston, RI, USA) using no or minimal fixation would avoid these problems. METHODS: A retrospective case study reviewed 212 transabdominal preperitoneal herniaplasties with 11 x 16-cm 3D Max mesh in 146 patients. Fixation with three helical tacks at the most was used early or with very large defects. RESULTS: Fixation was used in 19% of the cases, but only for 1 of the last 98 patients. As reported, 94% of the patients returned to normal activities by 3 weeks, 97% returned to unrestricted sports by 6 weeks, and 92% complete recovery from surgery by 9 weeks. Fixation or bilateral repair did not alter recovery. Four patients had minor pain or numbness. Symptomatic recurrence was 0%. One asymptomatic indirect recurrence was noted on examination, during a mean follow-up period of 23 months, yielding a 0.55% hernia rate and a 0.42% patient-year recurrence risk. CONCLUSIONS: An anatomically contoured mesh for transabdominal preperitoneal hernia repair often requires no fixation, with minimal risk of neuropathy and less than a 0.5% patient-year recurrence rate. Recovery is excellent even with bilateral repair or some fixation.

Decision for surgical management of perforation following endoscopic sphincterotomy.

Duodenal perforation resulting from endoscopic sphincterotomy (ES) is a serious complication with a high mortality. Diagnosis is often problematic and the optimum treatment is controversial. Eight proven perforations occurred following 441 ES at University of Colorado Hospital, a rate of 1.8 per cent. Physical and laboratory findings were of little diagnostic value, whereas plain abdominal radiographs showed evidence of perforation in 86 per cent. All patients were operated on promptly after diagnosis of perforation. Delay in diagnosis of perforation beyond 24 hours in six patients was associated with a high morbidity and two deaths. Analysis of published series confirmed that delay in diagnosis and delay in operation after perforation were associated with a higher mortality rate than early diagnosis with or without operation. We recommend operative intervention in all patients with clinical evidence of perforation following ES.