Resistance to diet-induced obesity in mu-opioid receptor-deficient mice: evidence for a "thrifty gene"

Using pharmacological tools, a role for opioid receptors in the regulation of food intake has been documented. However, the involvement of specific receptor subtypes remains questionable, and little information is available regarding a role for opioid receptors in energy metabolism. Using adult male mice lacking the mu-opioid receptor (MOR) gene (MOR-/-), we show that the MOR is not essential for the maintenance of normal levels of ad libitum food intake but does modulate the efficiency of energy storage during high-fat diets through the regulation of energy partitioning. When fed a regular diet, MOR-/- mice displayed only subtle alterations in energy homeostasis, suggesting a relative overuse of fat as a fuel source in the fed state. When fed a high-fat diet, MOR-/- mice were resistant to obesity and impaired glucose tolerance, despite having similar energy intake to wild-type mice. This resistance to obesity was associated with a strong induction of the expression of key mitochondrial enzymes involved in fatty acid oxidation within skeletal muscle. This metabolic role of the MOR, which is consistent with the properties of a "thrifty gene," suggests that the MOR pathway is a potential target for pharmacological intervention in the treatment of obesity associated with the intake of fatty diets.     

Monochorionic and dichorionic twin pregnancies discordant for fetal anencephaly: a systematic review of prenatal management options

The aim of this study was to evaluate the effect of selective feticide (SF) compared to expectant management (EM) on perinatal outcome in dichorionic and monochorionic twins discordant for anencephaly. For this purpose, we conducted a systematic review of literature and added ten unpublished cases. As a result, we found that in dichorionic twins, mean gestational age (GA) at birth in the SF group was 38.0 weeks versus 34.9 weeks (P = 0.0002). Mean birth weight was 2922 g in the SF group versus 2474 g (P = 0.03). In monochorionic twins, mean GA at birth was 35.2 weeks versus 32.7 weeks (P = 0.1). Mean birth weight was 2711 g versus 1667 g (P = 0.0001).We conclude that while SF does not reduce perinatal mortality, it does result in significantly longer gestations and higher birth weight, and appears to be the management of choice in dichorionic twins discordant for anencephaly. In monochorionic twins, SF also increases birth weight, but in view of the complexity of this group, no clear recommendations can be made.     

The burden of mortality of obesity at middle and old age is small. A life table analysis of the US Health and Retirement Survey

The evidence of effect of overweight and obesity on mortality at middle and old age is conflicting. The increased relative risk of cardiovascular disease and diabetes for overweight and obese individuals compared to normal weight is well documented, but the absolute risk of cardiovascular death has decreased spectacularly since the 1980s. We estimate the burden of mortality of obesity among middle and old aged adults in the Health and Retirement Survey (HRS), a US prospective longitudinal study. We calculate univariate and multivariate age-specific probabilities and proportional hazard ratios of death in relation to self-reported body mass index (BMI), smoking and education. The life table translates age specific adjusted event rates in survival times, dependent on risk factor distributions (smoking, levels of education and self reported BMI). 95% confidence intervals are calculated by bootstrapping. The highest life expectancy at age 55 was found in overweight (BMI 25-29.9), highly educated non smokers: 30.7 (29.5-31.9) years (men) and 33.2 (32.1-34.3) (women), slightly higher than a BMI 23-24.9 in both sexes. Smoking decreased the population life expectancy with 3.5 (2.7-4.4) years (men) and 1.8 (1.0-2.5) years (women). Less than optimal education cost men and women respectively 2.8 (2.1-3.6) and 2.6 (1.6-3.6) years. Obesity and low normal weight decreased population life expectancy respectively by 0.8 (0.2-1.3) and 0.8 (0.0-1.5) years for men and women in a contemporary, US population. The burden of mortality of obesity is limited, compared to smoking and low education.     

Identity development, coping, and adjustment in emerging adults with a chronic illness: the sample case of type 1 diabetes

PURPOSE: The present study focused on identity development in emerging adults (aged 18-30 years) with type 1 diabetes. The three study aims were to examine the following: (1) whether identity development was affected by having diabetes, as compared with development in a nondiabetic sample; (2) how identity development was related to depressive symptoms, coping with diabetes, and diabetes-related problems in the diabetic sample; and (3) whether the pathways from identity development to problems with diabetes and depressive symptoms were mediated through coping strategies in the diabetic sample. METHODS: A total of 194 emerging adults with type 1 diabetes and 344 nondiabetic emerging adults participated. RESULTS: First, using analyses of variance, some mean identity differences between the diabetic and comparison samples were found, with emerging adults with diabetes scoring lower on proactive identity exploration. Using cluster analysis, we found that the same identity types or statuses emerged in both the diabetic and nondiabetic samples. Second, in emerging adults with diabetes, these identity statuses were differentially related to diabetes-related problems, depressive symptoms, and illness coping, with the identity statuses representing a strong sense of identity being accompanied by less diabetes-related problems and depressive symptoms and more adequate coping strategies. Third, using structural equation modeling, the pathways from a strong sense of identity to diabetes-related problems and depressive symptoms were mediated through adaptive and maladaptive coping. CONCLUSIONS: Clinicians should be sensitive to the normative task of identity development in emerging adults with diabetes because identity development can function as a resource in coping with and adjusting to diabetes.     

Improved aero-anaerobe recovery from infected prosthetic joint samples taken from 72 patients and collected intraoperatively in Rosenow's broth

INTRODUCTION: Recovery of the bacteria responsible for prosthetic joint infections is a major problem, which is due in part to the alteration of their ability to grow by storage during transportation to the laboratory. METHODS: In this prospective study, we assessed the benefit of inoculating an enriched liquid medium (Rosenow's broth) with intraoperative samples from 72 patients with prosthetic joint revision due to infection. We compared the results of culture of specimens collected in a standard receptacle with the results for specimens collected in Rosenow's broth. RESULTS AND INTERPRETATION: 144 samples were taken by each of the 2 collection methods for subsequent culture. Concordance between standard and Rosenow samples was observed for 52 of the 58 strains cultured on agar and for 42 of the 97 strains (p < 0.001) which grew only in liquid medium. Infection would not have been diagnosed in 26 patients (almost one-third of all patients) without combining sample collection in Rosenow's broth with standard collection. The bacteria that were not recovered from standard samples but which were recovered from those collected in Rosenow's broth included not only strict anaerobes, in particular Propionibacterium acnes, but also coagulase-negative staphylococci and streptococci.     

Influence of obesity on in-hospital and early mortality and morbidity after myocardial revascularization.

OBJECTIVE: Obese patients are thought to have an increased risk for complications in coronary artery bypass surgery. Several risk stratification systems do not identify obesity as a variable for risk adjustment. The aim of this study is to evaluate the in-hospital and early (one year) mortality and morbidity in obese and non-obese patients after a CABG in the UMC St Radboud. METHODS: The data of 1130 patients undergoing a myocardial revascularization from January 2000 to August 2002 were analyzed. Obesity was measured by the body mass index (BMI). A BMI>or=30 kg/m2 was defined as obese. We compared 206 obese patients with 924 non-obese patients. Uni- and multivariate analysis were used to analyze the results. The 1-year survival was analyzed using Kaplan-Meier methods. RESULTS: There were no significant differences between obese and non-obese patients according to postoperative myocardial infarction, re-operation for bleeding, in-hospital mortality, renal complications, neurological complications, pulmonary complications, gastrointestinal complications, re-intubation, re-admission on intensive care, ventilation time, days on intensive care, days in hospital and late mortality. Only the incidence of postoperative wound infections was increased in obese patients, 8.3% in the obese versus 4.4% in the non-obese (P=0.02). Multivariate analysis identified obesity only as risk factor for postoperative for wound infections (P=0.04, odds ratio: 1.97). CONCLUSIONS: Obese patients do not have an increased risk of in-hospital and early (1 year) mortality after CABG. However, obese patients have an increased risk of postoperative wound infections compared to non-obese patients.     

Heparin-level-based anticoagulation management during cardiopulmonary bypass: a pilot investigation on the effects of a half-dose aprotinin protocol on postoperative blood loss and hemostatic activation and inflammatory response

Cardiac surgery involving cardiopulmonary bypass (CPB) leads to activation of the hemostatic/inflammatory system. We compared the influence of a half-dose aprotinin regimen on postoperative blood loss and the activation of the hemostatic/inflammatory system during CPB, when used during a heparin-level-based heparin management for cardiac surgery. Two-hundred patients (n = 100 in each group) were enrolled in this randomized prospective study. In Group I only heparin was given according to the results of the Hepcon HMS Plus. In Group II aprotinin was added with a bolus of 1 x 10(6) kallikrein inhibiting units (KIU) for the patient immediately before initiation of CPB, 1 x 10(6) KIU in the priming solution of the CPB, and a continuous infusion of 250,000 KIU/h during CPB. Postoperative blood loss was determined after 12 h. Heparin and antithrombin activity were evaluated by an anti-Xa assay and measurement of antithrombin III activity. Hemostatic activation was evaluated by adenosine diphosphate-stimulated platelet aggregometry and by measurements of the generation/release of beta-thromboglobulin (beta-TG), soluble P-selectin (sPS), thrombin (TAT), prothrombin 1 and 2 fragments (PTF1+2), factor XIIa (FXIIa), plasmin (PAP), and D-dimers. Inflammatory response was evaluated by measuring complement factors 5b-9 (C5b-9), interleukin (IL)-6, and neutrophil elastase (NE). There were no differences in the pre-CPB values or duration of CPB between the two groups. There were no differences in the post-CPB values for platelet count, platelet aggregation, beta-TG, sPS, TAT, PTF1+2, C5b-9, NE, or IL-6. The additional use of aprotinin resulted in a significant decrease of PAP, D-dimers, and 12 h postoperative blood loss, whereas generation of the contact factor XIIa was increased. The administration of aprotinin significantly reduced postoperative blood loss after cardiac surgery and CPB. This most likely has to be attributed to the antifibrinolytic effects of aprotinin. No effects on thrombin generation, platelet activation, inflammatory response, or clinical outcome were noted. IMPLICATIONS: The use of half-dose aprotinin and heparin-level-based anticoagulation management during cardiopulmonary bypass leads to a significant reduction of postoperative blood loss after cardiac surgery. This effect can most likely be attributed to the antifibrinolytic effects of aprotinin, as we did not observe effects on other variables of activation of the hemostatic/inflammatory system.     

Assessing analgesia in single and repeated administrations of propacetamol for postoperative pain: comparison with morphine after dental surgery

We conducted this double-blinded, randomized study to assess the analgesic effect of repeated administrations of paracetamol, administered as propacetamol, an injectable prodrug formulation of paracetamol, and to compare this with the analgesic effects of morphine. Patients experiencing moderate to severe pain after elective surgical removal of bone-impacted third-molar teeth under general anesthesia were randomly assigned to receive IV propacetamol 2 g (n = 31), IM morphine 10 mg (n = 30), or placebo (n = 34). Five hours later, the treatments were readministered at half of the previous dosages. Standard measures of analgesia were collected repeatedly for 10 h. Propacetamol and morphine were significantly more effective than placebo in all primary measures of analgesia over 5 h after the first administration and globally over 10 h (first and second administrations). After the first dose, 21 of the 34 patients in the placebo group required rescue medication, compared with 6 of the 31 in the propacetamol group (P < 0.0009) and 4 of the 30 in the morphine group (P < 0.0001). No statistically or clinically significant differences were found between propacetamol and morphine for any sum or peak measures of analgesia. No serious adverse events were reported; adverse events were significantly less frequent in the propacetamol group than in the morphine group (P < 0.027). Propacetamol administered IV in repeated doses (2 g followed by 1 g) has a significant analgesic effect that is indistinguishable from that of morphine administered IM (10 mg followed by 5 mg) after dental surgery, with better tolerability. IMPLICATIONS: After moderately painful surgical procedures, IV paracetamol, administered as propacetamol, may be an asset in the control of acute postoperative pain.