Do patients with moderately impaired gastrointestinal function requiring enteral nutrition need a predigested nitrogen source? A prospective crossover controlled clinical trial.

This prospective double blind randomised seven day crossover controlled clinical trial was carried out to determine whether enterally fed patients with moderately impaired gastrointestinal function require a predigested nitrogen (N) source compared with whole protein. Twelve malnourished patients with varying gastrointestinal abnormalities, who required enteral feeding, received 2.25 l of one of two isocaloric isonitrogenous enteral diets (1 kcal/ml, 4.8 g nitrogen/l) containing either predominantly medium chain peptides (tetra or higher peptides) or whole protein as the nitrogen source. Nitrogen absorption and balance were calculated from dietary intake and analysis of 24 hour total urinary and faecal nitrogen for the last five days of each study period. There was no significant difference in either stool weight (110 (SEM) (49) v 111 (32) g/d), nitrogen absorption (91 (2) v 89 (2)%) or nitrogen balance (+1.0 (1.3) v +0.6 (1.4) g nitrogen/d) between the peptide and whole protein nitrogen sources when all patients are considered. There was, however, evidence to suggest a nutritional advantage from administering an enteral diet whose nitrogen source comprises oligopeptides, rather than whole protein, to a subgroup of patients with small bowel disease.     

The Effect of Standard Versus Longer Intestinal Bypass on GLP-1 Regulation and Glucose Metabolism in Patients With Type 2 Diabetes Undergoing Roux-en-Y Gastric Bypass: The Long-Limb Study

OBJECTIVERoux-en-Y gastric bypass (RYGB) characteristically enhances postprandial levels of glucagon-like peptide 1 (GLP-1), a mechanism that contributes to its profound glucose-lowering effects. This enhancement is thought to be triggered by bypass of food to the distal small intestine with higher densities of neuroendocrine L-cells. We hypothesized that if this is the predominant mechanism behind the enhanced secretion of GLP-1, a longer intestinal bypass would potentiate the postprandial peak in GLP-1, translating into higher insulin secretion and, thus, additional improvements in glucose tolerance. To investigate this, we conducted a mechanistic study comparing two variants of RYGB that differ in the length of intestinal bypass.RESEARCH DESIGN AND METHODSA total of 53 patients with type 2 diabetes (T2D) and obesity were randomized to either standard limb RYGB (50-cm biliopancreatic limb) or long limb RYGB (150-cm biliopancreatic limb). They underwent measurements of GLP-1 and insulin secretion following a mixed meal and insulin sensitivity using euglycemic hyperinsulinemic clamps at baseline and 2 weeks and at 20% weight loss after surgery.RESULTSBoth groups exhibited enhancement in postprandial GLP-1 secretion and improvements in glycemia compared with baseline. There were no significant differences in postprandial peak concentrations of GLP-1, time to peak, insulin secretion, and insulin sensitivity.CONCLUSIONSThe findings of this study demonstrate that lengthening of the intestinal bypass in RYGB does not affect GLP-1 secretion. Thus, the characteristic enhancement of GLP-1 response after RYGB might not depend on delivery of nutrients to more distal intestinal segments.     

A Randomized Controlled Trial of High-Intensity Exercise and Executive Functioning in Cognitively Normal Older Adults

BackgroundThere is a paucity of interventional research that systematically assesses the role of exercise intensity and cardiorespiratory fitness, and their relationship with executive function in older adults. To address this limitation, we have examined the effect of a systematically manipulated exercise intervention on executive function.MethodsNinety-nine cognitively normal participants (age = 69.10 ± 5.2 years; n = 54 female) were randomized into either a high-intensity cycle-based exercise, moderate-intensity cycle-based exercise, or no-intervention control group. All participants underwent neuropsychological testing and fitness assessment at baseline (preintervention), 6-month follow-up (postintervention), and 12-month postintervention. Executive function was measured comprehensively, including measures of each subdomain: Shifting, Updating/ Working Memory, Inhibition, Verbal Generativity, and Nonverbal Reasoning. Cardiorespiratory fitness was measured by analysis of peak aerobic capacity; VO₂peak.ResultsFirst, the exercise intervention was found to increase cardiorespiratory fitness (VO₂peak) in the intervention groups, in comparison to the control group (F =10.40, p≤0.01). However, the authors failed to find mean differences in executive function scores between the high-intensity, moderate intensity, or inactive control group. On the basis of change scores, cardiorespiratory fitness was found to associate positively with the executive function (EF) subdomains of Updating/Working Memory (β = 0.37, p = 0.01, r = 0.34) and Verbal Generativity (β = 0.30, p = 0.03, r = 0.28) for intervention, but not control participants.ConclusionAt the aggregate level, the authors failed to find evidence that 6-months of high-intensity aerobic exercise improves EF in older adults. However, it remains possible that individual differences in experimentally induced changes in cardiorespiratory fitness may be associated with changes in Updating/ Working Memory and Verbal Generativity.     

Parental origin of mutation and the risk of breast cancer in a prospective study of women with a BRCA1 or BRCA2 mutation

The objective is to estimate the risk of breast cancer in women who carry a deleterious BRCA1 or BRCA2 mutation, according to parental origin of mutation. We conducted a cohort study of women with a BRCA1 mutation (n = 1523) or BRCA2 mutation (n = 369) who had not been diagnosed with breast or ovarian cancer. For each woman, the pedigree was reviewed and the origin of the mutation was assigned as probable paternal or maternal. The hazard ratio (HR) for developing breast cancer in the follow‐up period was estimated for women with a paternal mutation compared to a maternal mutation. The risk of breast cancer was modestly higher in women with a paternal BRCA1 mutation compared to women with a maternal BRCA1 mutation (HR = 1.46; 95% CI = 0.99–2.16) but the difference was not significant (p = 0.06). The parental mutation origin did not affect the risk in women with a BRCA2 mutation. Our results are consistent with the hypothesis that there is an increased risk of breast cancer among women with a paternally inherited BRCA1 mutation compared to a maternally inherited mutation. However, the data are not sufficiently compelling to justify different screening recommendations for the two subgroups.     

Failure of recombinant human interleukin-3 therapy to induce erythropoiesis in patients with refractory Diamond-Blackfan anemia [see comments]

In two previous studies, we observed that recombinant human interleukin- 3 (IL-3) induced an increase in marrow burst-forming unit-erythroid- derived colonies in vitro in some patients with Diamond-Blackfan anemia (DBA). To determine whether a similar erythropoietic response could be induced in vivo, we treated 13 patients with DBA (aged 4 to 19 years) with two preparations of IL-3. All patients had absent absolute reticulocyte counts and markedly reduced to absent recognizable bone marrow erythroid elements; patients with circulating reticulocytes in the previous 12 months were excluded from study. All patients except 1 had failed steroid therapy and had been transfusion-dependent since infancy; 1 patient was maintained on high-dose prednisone at the time of enrollment. On the first arm of the study, IL-3 (Immunex Corp, Seattle, WA) was administered subcutaneously using a dose escalation regimen of 125 to 500 micrograms/m2/day in divided dosage at 12-hour intervals, coadministered with 1.5 mg/kg/d of oral ferrous sulphate. Of the 13 patients that entered the trial, 4 stopped prematurely because of adverse side effects. In the other 9 evaluable cases, reticulocytes increased transiently in 1 patient from 0 to 65 x 10(9)/L after 35 days of IL-3 therapy at 250 micrograms/m2, but transfusion dependency persisted. One transient peak in absolute reticulocyte count was noted in 6 other patients, but no erythroid response was observed after completion of a full course of IL-3. Oral prednisone at 0.5 mg/kg/d was then coadministered with IL-3 at 500 micrograms/m2 to 5 of the patients without effect, and treatment was stopped. In 2 patients, a second preparation of IL-3 (Sandoz Canada Inc, Dorval, Quebec, Canada) was initiated in a dose escalation regimen of 2.5 to 10 micrograms/kg and was coadministered with ferrous sulphate. No erythroid response was observed in either patient, and in one of the two, alternate-day subcutaneous recombinant erythropoietin at 300 U/kg was administered for 3 weeks in combination with daily IL-3 at 10 micrograms/kg, but no increased erythropoiesis was seen. Significant increases in white blood cell and eosinophil counts during administration of both preparations of IL-3 were observed in all patients. These data show that the response of DBA patients to IL-3 in vivo is heterogeneous and cannot be predicted from in vitro studies. The absence of a corrective effect of IL-3 in these patients with DBA indicates that a deficiency of the cytokine is not central in the pathogenesis of the disorder.