Impacts and patterns of disturbed gastrointestinal function in critically ill patients

Disordered upper gastrointestinal tract motility occurs frequently in intensive care unit patients and often represents a substantial treatment challenge. In addition to specific complications such as pulmonary aspiration and diarrhea, abnormal gastrointestinal motility is a limiting factor for delivery and success of enteral nutrition. The pathophysiologies involved are incompletely understood because of the difficulties of making measurements of gastrointestinal function in critically ill patients. With the recent development of techniques that overcome some of these difficulties, the prospects are brighter for significant advances in this field.     

Absence of nitroglycerin-induced heparin resistance in healthy volunteers.

A previously described nitroglycerin-induced heparin resistance could not be verified by in-vitro experiments or in a randomized, double-blind, crossover trial in healthy volunteers. A clinically relevant attenuation of the anticoagulant effect of a heparin bolus (40 U.kg-1) by a concomitant infusion of nitroglycerin (100 micrograms.min-1) was absent. Activated partial thromboplastin time was not significantly different under nitroglycerin infusion as compared to placebo after heparin injection. Concentrations and activities of antithrombin III and heparin cofactor II remained unchanged during nitroglycerin infusion. An interaction of these two frequently combined drugs in patients with active thromboembolic disease or after a prolonged concomitant intravenous administration cannot be ruled out. Since this is of clinical importance, further studies must clarify a possible nitroglycerin-induced heparin resistance.     

Estrogen receptor-alpha and -beta are expressed throughout postnatal development in the rat and rabbit growth plate

Estrogen regulates skeletal growth and promotes epiphyseal fusion. To explore the mechanisms underlying these effects we investigated the expression of estrogen receptor-alpha (ERalpha) and -beta (ERbeta) in rat and rabbit growth plates during postnatal development, using immunohistochemistry. Immunoreactivity for ERalpha and ERbeta was observed in resting zone and proliferative zone chondrocytes at all ages studied for both rat (7, 14, 28 and 70 days of age) and rabbit (1, 7, 28 and 120 days of age). In the rat distal humerus and the rabbit proximal tibia, expression of both receptors in the hypertrophic zone was minimal at early ages, increasing only at the last time point prior to epiphyseal fusion. Expression was rarely seen in the hypertrophic zone of the rat proximal tibia, a growth plate that does not fuse until late in life. Therefore, we conclude that ERalpha and ERbeta are both expressed in the mammalian growth plate. The temporal and anatomical pattern suggests that ER expression in the hypertrophic zone in particular may play a role in epiphyseal fusion.     

Uric Acid and Cardiovascular Events: A Mendelian Randomization Study

Obesity and diets rich in uric acid–raising components appear to account for the increased prevalence of hyperuricemia in Westernized populations. Prevalence rates of hypertension, diabetes mellitus, CKD, and cardiovascular disease are also increasing. We used Mendelian randomization to examine whether uric acid is an independent and causal cardiovascular risk factor. Serum uric acid was measured in 3315 patients of the Ludwigshafen Risk and Cardiovascular Health Study. We calculated a weighted genetic risk score (GRS) for uric acid concentration based on eight uric acid–regulating single nucleotide polymorphisms. Causal odds ratios and causal hazard ratios (HRs) were calculated using a two-stage regression estimate with the GRS as the instrumental variable to examine associations with cardiometabolic phenotypes (cross-sectional) and mortality (prospectively) by logistic regression and Cox regression, respectively. Our GRS was not consistently associated with any biochemical marker except for uric acid, arguing against pleiotropy. Uric acid was associated with a range of prevalent diseases, including coronary artery disease. Uric acid and the GRS were both associated with cardiovascular death and sudden cardiac death. In a multivariate model adjusted for factors including medication, causal HRs corresponding to each 1-mg/dl increase in genetically predicted uric acid concentration were significant for cardiovascular death (HR, 1.77; 95% confidence interval, 1.12 to 2.81) and sudden cardiac death (HR, 2.41; 95% confidence interval, 1.16 to 5.00). These results suggest that high uric acid is causally related to adverse cardiovascular outcomes, especially sudden cardiac death.     

Timescales of developmental toxicity impacting on research and needs for intervention

Much progress has happened in understanding developmental vulnerability to preventable environmental hazards. Along with the improved insight, the perspective has widened, and developmental toxicity now involves latent effects that can result in delayed adverse effects in adults or at old age and additional effects that can be transgenerationally transferred to future generations. Although epidemiology and toxicology to an increasing degree are exploring the adverse effects from developmental exposures in human beings, the improved documentation has resulted in little progress in protection, and few environmental chemicals are currently regulated to protect against developmental toxicity, whether it be neurotoxicity, endocrine disruption or other adverse outcome. The desire to obtain a high degree of certainty and verification of the evidence used for decision‐making must be weighed against the costs and necessary duration of research, as well as the long‐term costs to human health because of delayed protection of vulnerable early‐life stages of human development and, possibly, future generations. Although two‐generation toxicology tests may be useful for initial test purposes, other rapidly emerging tools need to be seriously considered from computational chemistry and metabolomics to CLARITY‐BPA‐type designs, big data and population record linkage approaches that will allow efficient generation of new insight; epigenetic mechanisms may necessitate a set of additional regulatory tests to reveal such effects. As reflected by the Prenatal Programming and Toxicity (PPTOX) VI conference, the current scientific understanding and the timescales involved require an intensified approach to protect against preventable adverse health effects that can harm the next generation and generations to come. While further research is needed, the main emphasis should be on research translation and timely public health intervention to avoid serious, irreversible and perhaps transgenerational harm.     

Die Proktokolektomie bei Colitis ulcerosa

Background

The coloproctomucosectomy (CPM) is the procedure of the choice for the surgical treatment of ulcerative colitis (UC). In cases with pronounced immunosuppression (IS), a 3-step (3S) procedure [i.e., subtotal colectomy and ileal pouch-anal anastomosis (IPAA) and finally ileostomy reconstruction] is often selected. Fewer perioperative complications can be expected compared to the 2-step (2S) procedure; however, an additional in-hospital stay and surgical intervention are necessary. The aim of the present study was to compare both approaches using the clinical outcome of our patients undergoing IPAA to determine efficacy of these two concepts.

Patients and methods

From 1997–2010, a total of 225 patients were operated using a 2S or 3S IPAA procedure. Clinical outcomes were evaluated based on the number of surgical steps for the ileoanal pouch procedure and IPAA. The survey was performed within the scope of prospective study.

Results

Of the 225 patients with CPM, 66 were excluded due to a diagnosis other than UC (familial adenomatous polyposis, indeterminate colitis, Crohn’s disease) and patients with permanent ILS procedures without the possibility or wish for an IPAA (n?=??54). Included were 71 patients with 2S (w?=?30, m?=?41) and 34 patients with 3S procedures (w?=?21, m?=?13). Compared to the 2S procedure, the 3S procedure was shown to have shorter operation times (246 versus 296 min; p??=?0.05), shorter hospital stays (15.5 versus 24.6 days; p?=?0.05), shorter intensive care unit stays (3.3 versus 7.2 days; p?=?0.05), and fewer major complications (5.9?% versus 22.5?%; p?=?0.035). Patients with 3S procedures had a higher BMI (26.2 versus 23.1 kg/m²; p?=?0.05) and fewer required IS (10?% vs. 62?%; p?<?0.05).

Conclusion

The decision for a 3S procedure in UC and pronounced IS is advisable and justified. Using a 3S procedure, immunosuppression and its influence on perioperative morbidity are thus reduced. The IPAA can be performed with shorter operation times, shorter hospital stays and fewer major complications.     

Usefulness of Acarbose and Dietary Modifications to Limit Glycemic Variability Following Roux-en-Y Gastric Bypass as Assessed by Continuous Glucose Monitoring

Abstract Background: About 70% of the patients operated on for a gastric bypass (Roux-en-Y gastric bypass [RYGB]) suffer from dumping syndrome. In these patients, previous studies have demonstrated a high glycemic variability with hypoglycemia and with altered continuous glucose monitoring (CGM) profiles. The aim of this study was to evaluate the effect of treatment with dietary counseling plus acarbose administration on the symptoms and on the characteristics of the CGM profile. Subjects and Methods: Eight consecutive patients with dumping syndrome were given dietary counseling for 6 weeks and also treated with acarbose (50-100?mg three times a day). Their symptoms and the features of the CGM were compared before and after treatment. Results: The symptoms disappeared in seven patients. There was a significant increase in the time to the interstitial glucose (IG) peak and a reduction in the rate of the IG increase after a meal and in the rate of the IG decrease following the peak. The time below 60?mg/dL was significantly decreased, and the minimal IG value was significantly increased. The maximum and mean IG levels and the time above 140?mg/dL were decreased, but not significantly. Six patients spent more than 1% of the time with IG values below 60?mg/dL before treatment, but after treatment this was reduced to one patient. Before treatment only one patient had an IG level neither below 60 or above 140?mg/dL, and after treatment four patients were in this category. Conclusions: Dietary counseling and acarbose treatment eliminated the symptoms and improved the CGM profile of patients suffering from dumping syndrome after RYGB.