Supplementing a yeast probiotic to pre-weaning Holstein calves: Feed intake, growth and fecal biomarkers of gut health.

Diarrhea, resulting from gastrointestinal infection by pathogens, is a common cause of the high mortality and morbidity of neonatal calves. The objective of this study was to evaluate the effects of supplementing a yeast product in milk replacer (MR) on growth and health of calves, and on fecal populations of some targeted microorganisms related to calf health and growth (i.e., total bacteria, Escherichia coli, Clostridium cluster XIVa, Faecalibacterium prausnitzii and Bifidobacterium spp.). We hypothesized that feeding a Saccharomyces cerevisiae var boulardii (SCB) product would improve gastrointestinal health and growth performance of calves. Forty-two Holstein bull calves (42.6 ± 0.77 kg at birth) were randomly assigned on day 2 of age to either a control or SCB treatment. The SCB was supplemented in MR and fed at 5 g/d per head to supply 10 billion colony-forming units per day. All calves received high quality colostrum (>50 mg/mL of immunoglobulin G) during the first 24 h of life, and were fed with 8 L MR (150 g/L mixed with 40 °C water) daily from day 2-35, and 4 L daily from day 35-42. Calves were also fed calf starter ad libitum from day 7-56. Daily MR and starter offered and refused, daily fecal scores, nasal scores, ear scores, and weekly body weight of calves were recorded. Fecal samples were collected on day 7, 35 and 56 after the first feeding of that day for microbial targets analysis. Overall, there is no serious disease challenge for all the calves during the entire experimental period. No differences were observed in MR intake, starter intake, metabolizable energy (ME) intake, average daily gain, ME intake to gain ratio, fecal score, nasal score, eye score or any targeted microorganisms between treatments throughout the experiment. These results suggest that supplementing SCB in MR has no additive effects on animal growth or fecal biomarkers of gut health when calves do not show deteriorated health status.

Validation of a calf-side ß-hydroxybutyrate test and its utility for estimation of starter intake in dairy calves around weaning.

Recent research suggests that circulating ß-hydroxybutyrate (BHB) levels may be a meaningful indicator of grain intake and rumen development in pre-ruminant calves. As such, BHB levels may be a surrogate measure of rumen function to contribute to minimal weaning stress during the transition from liquid to solid feed. The primary objective of this study was to determine the optimal cut-point of circulating BHB levels that would be predictive of sufficient grain intake and rumen development for a successful transition from liquid to solid feed at the time of weaning. An additional objective was to validate the Precision Xtra (Abbott Diabetes Care, Abingdon, UK) calf-side test for determination of BHB in whole blood in calves around weaning, as compared with the gold standard laboratory method. A total of 20 Holstein female calves were randomly assigned at birth to be weaned at 6 wk (n=10) or 8 wk (n=10) of age. Milk replacer (mixed at 150 g/L) was offered at 1.2kg/calf per d in 2 meals until a 1-wk step down, when milk meals were reduced by 50% 1 wk before weaning. Daily measurements included the intakes of starter grain, chopped straw, and water. Weekly measurements included body weight and blood BHB, until 70 d of life. To assess digestive tract development, rumen fluid samples were taken before and after weaning (d 35, 49, and 63) and analyzed for ruminal short-chain fatty acids. Whole blood was collected by jugular venipuncture, and BHB was determined by the Precision Xtra test at calf-side. In addition, serum was separated from a clotted sample, frozen, and stored until laboratory analysis was performed. Laboratory BHB results were correlated with both the Precision Xtra test (r=0.95) and starter intake over 1 d (r=0.89), a 3-d average (r=0.90), and a 7-d average (r=0.90). Additionally, laboratory BHB results were associated with total ruminal volatile fatty acids (r=0.82), ruminal butyrate (r=0.77), and body weight (r=0.69). A receiver operating characteristic curve was created to plot the true positive rate against the false positive rate at 10µmol/L BHB intervals to determine the optimal cut-point of circulating BHB that is predictive of an average starter intake of 1,000 g/d over a 3-d period. The optimal combination of sensitivity (95.7%) and specificity (96.1%) was at 100µmol of BHB/L of blood. A value of 0.2 mmol/L on the Precision Xtra test yielded a sensitivity and specificity of 84.0 and 97.2%, respectively, over the 3-d average period of starter intake. These results show considerable promise for use of the Precision Xtra whole blood BHB test in the decision-making process of determining sufficient starter grain intake and rumen development for a successful transition from liquid to solid feed, and indicate that this test conducted at calf-side is highly accurate.

Management of Dysphagia in Esophageal Adenocarcinoma Patients Undergoing Neoadjuvant Chemotherapy: Can Invasive Tube Feeding be Avoided?

BACKGROUND: Neoadjuvant chemotherapy is an accepted standard for locally advanced esophagogastric junction adenocarcinoma. However, the dysphagia frequently associated with this condition may interfere with patient tolerance of this treatment. In many centers, invasive tube feeding, placed either endoscopically, radiographically, or surgically, is used to address this issue, but it can cause significant morbidity. We sought to determine if an approach of goal-directed dietary counseling and appropriately timed neoadjuvant chemotherapy could obviate the need for invasive tube feeding. METHODS: Patients with locally advanced (cT3 or N+) esophageal and esophagogastric junction adenocarcinoma undergoing neoadjuvant TCF [Taxotere, cisplatin 5-fluorouracil (5-FU)], ECF (epirubicin, cisplatin, 5-FU), or FLOT (docetaxel, oxaliplatin, leucovorin, and 5-FU) at the McGill University Health Center from March 2007 to September 2012 were identified from a prospective database. All received individualized goal-directed dietary counseling, were monitored for signs/symptoms of malnutrition with serial (baseline/presurgery) body mass index, albumin, and completed serial symptom scores (dysphagia), and quality-of-life questionnaires (Functional Assessment in Cancer Therapy with the esophageal subset, FACT-E). We assessed the response of dysphagia and nutritional status to neoadjuvant chemotherapy and the need for invasive tube feeding. RESULTS: Of 130 patients undergoing neoadjuvant chemotherapy, 78 had severe dysphagia (defined as dysphagia score ≥2 on a 5-point Likert scale), most of whom received TCF (91 %). Overall dysphagia scores improved in 75 (96 %) of 78 patients from a dysphagia score of 3-0, most of which improved after the first cycle of therapy. This was associated with an increase in quality of life (FACT-E scores 117 ± 23 to 140 ± 20). With maintenance of weight (70 ± 22 to 69 ± 24 kg), body mass index (24.5 ± 8 to 23.9 ± 7 kg/m(2)), and serum albumin (40 ± 5 to 37 ± 4 g/L). Only one patient required a stent, and none required jejunostomy or gastrostomy. CONCLUSIONS: Appropriately timed neoadjuvant chemotherapy with a highly effective regimen rapidly restores normal swallowing, maintains nutritional status, and obviates the need for invasive tube feeding in patients with significant dysphagia from esophageal adenocarcinoma.

Weaning age affects growth, feed intake, gastrointestinal development, and behavior in Holstein calves fed an elevated plane of nutrition during the preweaning stage.

Recent research has revealed potential advantages of feeding an elevated plane of nutrition to calves during the preweaning period. However, calves fed more nutrients preweaning may be more susceptible to depressed growth and weaning stress during the transition from liquid to solid feed. The objective of this study was to investigate the relationship between the age of weaning and feed intake, and its influence on growth, gastrointestinal development, and behavioral indicators in dairy calves fed an elevated plane of nutrition during the preweaning period. To meet this objective, 20 female Holstein calves were randomly assigned at birth to be weaned at 6 or 8 wk. Milk replacer (mixed at 150 g/L) was offered at 1.2 kg/calf per day in 2 meals until a 1-wk step-down, when meals were reduced by 50% 1 wk before weaning. Daily starter, chopped oat straw, water intake, and weekly body weights were measured until d 70 of life. To assess digestive tract development, rumen fluid, fecal, and blood samples were taken before and after weaning (d 35, 49, and 63) and analyzed for ruminal short-chain fatty acids, blood ß-hydroxybutyrate, and fecal starch, respectively. Behavioral indicators of weaning stress, including vocalizing and non-nutritive oral behavior, were measured by visual observation for 1 h, 3 times per week, before the second feeding of the day during the period from 2 wk before weaning to 2 wk after weaning. The calves weaned at 8 wk compared with 6 wk had higher average daily gain for the week preweaning (0.79±0.09 vs. 0.34±0.10 kg/d) and postweaning (1.05±0.09 vs. 0.35±0.11 kg/d), and were heavier at d 70 (99.9±1.81 vs. 91.0±2.26 kg). From 5 to 8 wk of age, starter and water intakes were lower in calves weaned at 8 wk of age. However, overall starter intake did not differ during the last week of the experiment. Furthermore, calves weaned at 8 wk compared with 6 wk had higher starter intake for 1 wk preweaning (1.36±0.13 vs. 0.40±0.08 kg/d) and postweaning (2.51±0.20 vs. 1.16±0.15 kg/d). In both treatments, weaning increased ruminal short-chain fatty acids, blood ß-hydroxybutyrate, and fecal starch, yet the differences between the week before and after weaning were greater for calves weaned at 6 wk compared with those weaned at 8 wk. Treatment × week relative to weaning interactions indicated that several behaviors varied between early- and later-weaned calves during the week before weaning; calves weaned at 6 wk tended to exhibit 75% more non-nutritive oral behavior and spent 55% less time ruminating, and 36% less time lying compared with calves weaned at 8 wk. Under the conditions of this study, the results suggest that calves fed an elevated plane of nutrition preweaning have higher starter intakes and average daily gain during the weaning period when weaning is extended from 6 to 8 wk of age.

A virtual look at Epstein-Barr virus infection: simulation mechanism.

Epstein-Barr virus (EBV) is an important human pathogen that establishes a life-long persistent infection and for which no precise animal model exists. In this paper, we describe in detail an agent-based model and computer simulation of EBV infection. Agents representing EBV and sets of B and T lymphocytes move and interact on a three-dimensional grid approximating Waldeyer's ring, together with abstract compartments for lymph and blood. The simulation allows us to explore the development and resolution of virtual infections in a manner not possible in actual human experiments. Specifically, we identify parameters capable of inducing clearance, persistent infection, or death.

Genetic regulation of immunoglobulin and specific antibody levels in twins reared apart.

We studied the effect of the same genetic but different environmental factors on total immunoglobulin and specific antibody levels in twins reared apart. Sera were analyzed from 26 monozygotic (MZ) and 10 dizygotic (DZ) twin pairs, who were separated on average 2 mo after birth and reared apart. Total IgM, IgG, and IgA were measured by single radial diffusion. Specific antibodies of each isotype to tetanus toxoid, and to polyvalent and type 14 pneumococcal capsular polysaccharides were measured by a solid-phase antigen-enzyme-labeled anti-Ig immunoassay. One-way analysis of variance showed intrapair total Ig and antibody levels to be more highly correlated in MZ compared with DZ twins. Our results indicate that genetic factors are more important than environment in regulating these humoral immune responses.

Anorexia nervosa. Treatment efficacy of cyproheptadine and amitriptyline.

Patients with anorexia nervosa have concurrent problems of emaciation and depression. Therefore, treatment with medications affecting both weight gain and depression seemed reasonable. Seventy-two anorectic patients were randomly assigned in a double-blind study to receive cyproheptadine hydrochloride, a weight-inducing drug, amitriptyline hydrochloride, a tricyclic antidepressant, or placebo. Overall, cyproheptadine had a marginal effect on decreasing the number of days necessary to achieve a normal weight. There was a differential drug effect present in the bulimic subgroups of the anorectic patients: cyproheptadine significantly increased treatment efficiency for the nonbulimic patients and significantly impaired treatment efficiency for the bulimic patients when compared with the amitriptyline- and placebo-treated groups. The differential cyproheptadine effect on the anorectic bulimic subgroups is the first pharmacologic evidence of the validity of these subgroups. Cyproheptadine had an anti-depressant effect demonstrated by a significant decrease in the Hamilton depression ratings.

Comorbidity of psychiatric diagnoses in anorexia nervosa.

The comorbidity of psychiatric diagnoses was examined with the Diagnostic Interview Schedule in 62 women who participated in a 10-year follow-up study of anorexia nervosa. Sixty-two age- and sex-matched controls, their parents, and parents of the anorectic probands were also interviewed with the Diagnostic Interview Schedule. There was a statistically significant comorbidity of the affective and anxiety disorders with anorexia nervosa. The first-degree relatives of the anorectic probands had significantly more alcoholism and total number of psychiatric diagnoses compared with the first-degree relatives of controls. There were two mothers with bulimia nervosa, two cases of anorexia nervosa and two of bulimia nervosa in other first-degree relatives of anorectic probands, and no cases of eating disorders in the first-degree relatives of controls.

Bulimia. Its incidence and clinical importance in patients with anorexia nervosa.

Among the various eating patterns encountered in anorexia nervosa, the occurrence of bulimia (rapid consumption of large amounts of food in a short period of time) is a perplexing phenomenon, because its presence contradicts the common belief that patients with anorexia nervosa are always firm in their abstinence from food. We studied the eating habits of 105 hospitalized female patients within the context of a prospective treatment study on anorexia nervosa: 53% had achieved weight loss by consistently fasting, whereas 47% periodically resorted to bulimia. The two groups were contrasted with regard to their developmental and psychosocial history, clinical characteristics, and psychiatric symptomatology. Fasting patients were more introverted, more often denied hunger, and displayed little overt psychic distress. In contrast, bulimic patients were more extroverted, admitted more frequently to a strong appetite and tended to be older. Vomiting was frequent, and kleptomania almost exclusively present in bulimic patients, who manifested greater anxiety, depression, guilt, interpersonal sensitivity, and had more somatic complaints. This association of bulimia with certain personality features and a distinct psychiatric symptomatology suggests that patients with bulimia form a subgroup among patients with anorexia nervosa.

A comparison study of antidepressants and structured intensive group psychotherapy in the treatment of bulimia nervosa.

Previous research on the treatment of outpatients with bulimia nervosa has focused on two treatment strategies: (1) drug therapy, primarily using tricyclic antidepressants, and (2) psychotherapy, often employing behavioral and cognitive behavioral techniques. We report here the short-term treatment outcome of a 12-week comparison trial of bulimic outpatients who were randomly assigned to one of four treatment cells: (1) imipramine hydrochloride treatment, (2) placebo treatment, (3) imipramine treatment combined with intensive group psychotherapy, and (4) placebo treatment combined with intensive group psychotherapy. All three active treatment cells resulted in significant reductions in target-eating behaviors and in a significant improvement in mood relative to placebo treatment. However, the results also suggested that the amount of improvement obtained with the intensive group psychotherapy component was superior to that obtained with antidepressant treatment alone. The addition of antidepressant treatment to the intensive group psychotherapy component did not significantly improve outcome over intensive group psychotherapy combined with placebo treatment in terms of eating behavior, but did result in more improvement in the symptoms of depression and anxiety.

Leukopenia in anorexia nervosa. Lack of increased risk of infection.

To determine whether patients with anorexia nervosa (AN) and leukopenia have an increased risk of infection, we reviewed the incidence of leukopenia and infection in 68 cases of AN and studied the mechanism of profound neutropenia in one. Compared with controls, patients with AN had substantially lower total leukocyte counts and absolute neutrophil, lymphocyte, and monocyte counts. Despite frequent and often severe panleukopenia, the patients with AN had no more infections than did the control subjects. The patient with severe neutropenia ahd a hypocellular bone marrow biopsy specimen showing relative myeloid hyperplasia, normal distribution of neutrophils between the marginal and circulating pools, and normal bone marrow neutrophil reserves as estimated by response to hydrocortisone sodium succinate. We conclude that patients uith AN and associated leukopenia do not have increased infection propensity.

Leptin in anorexia nervosa.

Serum leptin levels are low in untreated anorexia nervosa, but studies of the exact relationship between leptin and body weight and the impact of refeeding in anorectics are limited. Therefore, we studied serum leptin, insulin-like growth factor I, and other endocrine parameters in female anorectics before and after gaining weight and in female normal body weight controls. Leptin levels in untreated anorectics were significantly lower than those in normal body weight controls (3.6 +/- 1.6 vs. 12.0 +/- 6.9 ng/mL; P < 0.001), and they uncoupled from body weight in a nonlinear relationship, suggesting a threshold effect at lowest body weights. Leptin increased significantly with refeeding (5.6 +/- 3.8 ng/mL; P < 0.01). The significant linear correlations of leptin with body mass index in the anorectics after weight gain and in normal body weight controls (r = 0.69; P < 0.001 and r = 0.76; P < 0.001, respectively) are consistent with a normal physiological increase in leptin with weight gain. Leptin and insulin-like growth factor I were highly correlated, even after controlling for body weight (r = 0.63; P = 0.001) during starvation, but were no longer significantly correlated after body weight gain in the anorectics or the normal body weight controls. Further studies are necessary to elucidate the relationship of leptin to neuroendrocrine abnormalities seen in starvation and to determine a possible contribution of leptin to difficulties with weight restoration in anorexia nervosa.

Role of interleukin-6 and transforming growth factor-beta in anorexia nervosa.

Anorexia nervosa is a serious eating disorder characterized by extreme weight loss and abnormalities of the neuroendocrine and immune systems. To determine the potential role of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and transforming growth factor-beta (TGF-beta) in anorexia nervosa, serum concentrations of these cytokines were measured in patients with anorexia nervosa during starvation and after weight gain. Serum IL-6 and TGF-beta concentrations were both significantly elevated during starvation and returned to levels comparable to those of normal-weight controls by the end of therapy. In contrast, serum TNF-alpha levels were undetectable in all patients and controls. Cytokines may play previously unsuspected roles in anorexia nervosa and its complications.

Heritability of substance abuse and antisocial behavior: a study of monozygotic twins reared apart.

Thirty-two sets of monozygotic twins reared apart since shortly after birth (31 pairs and one set of triplets; median age at separation was 0.2 years) were interviewed separately and blindly using the Diagnostic Interview Schedule for presence of DSM-III Axis I psychiatric disorders and antisocial personality. Because the sample was recruited from a nonclinical population, predictably few subjects met criteria for such disorders. However, items counting toward diagnoses were cumulated into four scores: alcohol-related problems, drug-related problems, childhood antisocial behavior, and adult antisocial behavior. The scores showed within-scale cohesion as measured by Cronbach's coefficient alpha. The drug scale and both antisocial scales showed significant heritability (p less than 0.1), but the alcohol scale had an estimated heritability of zero (albeit with a broad confidence interval). There appeared to be substantial commonalities in the genetic factors responsible for these traits.

Elevated pain threshold in anorexia nervosa subjects.

BACKGROUND: Conflicting data have been published regarding pain threshold in subjects with anorexia nervosa (AN), with some studies indicating elevated pain threshold and others indicating normal thresholds. Previous research has indicated the presence of elevated pain threshold in eating disorder subjects with binge-eating behavior. METHODS: In this study pressure pain detection thresholds (PDT) (assessed by a pressure analgesiometer) in binge-eating/purging and restricting subtypes of AN subjects were compared to control subjects. RESULTS: PDT was elevated in AN compared to control subjects at baseline. There was no difference in PDT between the subgroups of AN subjects. CONCLUSIONS: The etiology of elevated PDT in AN subjects is most likely different from the etiology of elevated PDT in bulimia nervosa subjects.

Characteristics of 275 patients with bulimia.

The authors present data on 275 patients who met DSM-III criteria for bulimia. The mean age of the patients was 24.8 years, and the average duration of illness was approximately 7 years. These patients reported a variety of abnormal eating-related behaviors: binge eating (100%), self-induced vomiting (88.1%), laxative abuse (60.6%), diuretic abuse (33.1%), and chewing and spitting out food (64.5%). Over one-third reported a history of problems with alcohol or other drugs and most indicated substantial social impairment.

Maintenance treatment and 6-month outcome for bulimic patients who respond to initial treatment.

Bulimic subjects who responded to intensive group psychotherapy plus imipramine or placebo or to imipramine alone (N = 68) were assigned to 4-month maintenance with weekly support groups and/or medication (placebo or imipramine) and were evaluated 6 months after initial treatment (N = 61). Thirty percent of the subjects relapsed during the 6 months. Initial treatment with group psychotherapy plus placebo or imipramine was associated with a lower relapse rate than initial treatment with imipramine alone. Neither attendance at the maintenance group sessions nor imipramine maintenance was associated with better outcome.

Tourette's disorder in a set of reared-apart triplets: genetic and environmental influences.

Tourette's disorder was diagnosed in triplets reared apart from early infancy and reunited as adults. These data, combined with data on other family members, support the findings of research studies that have demonstrated genetic influences on Tourette's disorder.

Dietary composition and physiologic adaptations to energy restriction.

BACKGROUND: The concept of a body weight set point, determined predominantly by genetic mechanisms, has been proposed to explain the poor long-term results of conventional energy-restricted diets in the treatment of obesity. OBJECTIVE: The objective of this study was to examine whether dietary composition affects hormonal and metabolic adaptations to energy restriction. DESIGN: A randomized, crossover design was used to compare the effects of a high-glycemic-index (high-GI) and a low-glycemic-index (low-GI) energy-restricted diet. The macronutrient composition of the high-GI diet was (as percent of energy) 67% carbohydrate, 15% protein, and 18% fat and that of the low-GI diet was 43% carbohydrate, 27% protein, and 30% fat; the diets had similar total energy, energy density, and fiber contents. The subjects, 10 moderately overweight young men, were studied for 9 d on 2 separate occasions. On days -1 to 0, they consumed self-selected foods ad libitum. On days 1-6, they received an energy-restricted high- or low-GI diet. On days 7-8, the high- or low-GI diets were consumed ad libitum. RESULTS: Serum leptin decreased to a lesser extent from day 0 to day 6 with the high-GI diet than with the low-GI diet. Resting energy expenditure declined by 10.5% during the high-GI diet but by only 4.6% during the low-GI diet (7.38 +/- 0.39 and 7.78 +/- 0.36 MJ/d, respectively, on days 5-6; P = 0.04). Nitrogen balance tended to be more negative, and energy intake from snacks on days 7-8 was greater, with the high-GI than the low-GI diet. CONCLUSION: Diets with identical energy contents can have different effects on leptin concentrations, energy expenditure, voluntary food intake, and nitrogen balance, suggesting that the physiologic adaptations to energy restriction can be modified by dietary composition.

Genetic factors in the electrocardiogram and heart rate of twins reared apart and together.

Important physiologic mechanisms have been thought not to exhibit large amounts of variability, due in part to the assumption that critical biologic functions will have evolved to an evolutionary optimum. The attainment of this optimum would necessarily eliminate individual differences in these variables. Using a sample of monozygotic and dizygotic twins reared apart since birth or early infancy, 12-lead electrocardiographic recordings and vectorcardiograms were obtained. Values of these variables for monozygotic and dizygotic twins reared together were obtained from other studies. Maximum likelihood tests of genetic and environmental components of variation for PR interval, QRS duration, QT interval and ventricular rate indicated a significant contribution of genetic effects (most heritabilities ranged from 30 to 60%), with a negligible contribution from common familial environmental effects.