[Assessment of the state of the small intestine microbiota in children on a long-term dairy-free diet].

An overview of recent outcomes of studies indicates an imbalance in the diet of children. Quantitative and qualitative malnutrition of children is the basis of a number of childhood diseases. The aim of the research was to study the prevalence of small intestine bacterial overgrowth syndrome (SIBO) in children on a long-term dairy-free diet. Material and methods. 40 children aged 7-11 years following a long-term dairy-free diet (average 3 years and 5 months, from 0.5 to 6.3 years) were examined (main group). 30 children who did not follow restrictive diets were consisted control group. In all children, SIBO was determined using a hydrogen breath test with a load of lactulose using a digital analyzer of exhaled hydrogen. Results. The proportion of children with intolerance to dairy products was 32.5%: 10.0% with allergy to cow's milk proteins, and 22.5% with lactose intolerance. 27.5% children followed a dairy-free diet according to an unjustified prescription by physician. 30.0% of children did not consume dairy products because of their unwillingness. 10.0% of children did not consume dairy products due to the unwillingness of their parents. An imbalance in the microbiota of the small intestine during the hydrogen breath test with lactulose loading was detected in 55.0% of children following a long-term dairy-free diet. 22.5% of children complained of recurrent abdominal pain, diarrhea was determined in 10.0%, constipation - in 7.5%, nausea - in 10.0%. In the control group, the SIBO during the hydrogen breath test with lactulose loading was found in 20.0%. Periodic abdominal pain was determined in 10.0%, nausea - in 6.7%, diarrhea - in 10.0%, constipation - in 3.3% children. Conclusion. Thus, among children of primary school age who follow a long-term dairyfree diet, SIBO is significantly more often recorded relative to children who are on a traditional type of diet.

A continuous-time multistate Markov model to describe the occurrence and severity of diarrhea events in metastatic breast cancer patients treated with lumretuzumab in combination with pertuzumab and paclitaxel.

PURPOSE: To inform lumretuzumab and pertuzumab dose modifications in order to decrease the incidence, severity, and duration of the diarrhea events in metastatic breast cancer patients treated with a combination therapy of lumretuzumab (anti-HER3) in combination with pertuzumab (anti-HER2) and paclitaxel using quantitative clinical pharmacology modeling approaches. METHODS: The safety and pharmacokinetic (PK) data from three clinical trials (lumretuzumab monotherapy n = 47, pertuzumab monotherapy n = 78, and the combination therapy of lumretuzumab, pertuzumab and paclitaxel n = 35) were pooled together to develop a continuous-time discrete states Markov model describing the dynamics of the diarrhea events. RESULTS: The model was able to capture the time course of different severities of diarrhea reasonably well. The effect of lumretuzumab and pertuzumab was well described by an Emax function indicating an increased rate of transition from moderate to mild or more severe diarrhea with higher doses. The concentration needed to trigger or worsen diarrhea episodes was estimated to be 120-fold lower in combination therapy compared to monotherapy, suggesting strong synergy between the two monoclonal antibodies. The prophylactic effect of loperamide in a subset of patients was also well captured by the model with a clear tendency to reduce the occurrence of diarrhea events. CONCLUSIONS: This work shows that PK-toxicity modeling provides insight into how the severity of key adverse events evolves over time and highlights the potential use to support decision making in drug development.

Metabolic risk factors in pediatric stone formers: a report from an emerging economy.

The goal of this study was to investigate metabolic risk factors in pediatric stone formers in an emerging economy. A prospective, data collection enrolled 250 children age <1-15 years at our center. Risk factors were evaluated by gender and in age groups <1-5, 6-10 and 11-15 years. Patients were evaluated for demographics, blood and 24 h urine for calcium, magnesium, phosphate, uric acid, electrolytes and additional protein, citrate, ammonia and oxalate in urine. All reported values were two sided and statistical significance was considered at p value ≤0.05. The mean age at diagnosis was 7.50 ± 3.56 years with a male to female ratio of 1.84:1. A family history of urolithiasis was found in 41 (16.4 %), urinary tract infection in 18 (7 %) and chronic diarrhea in 75 (30 %). Hypercalcemia was seen in 37 (14.8 %), hyperuricemia in 23 (9.2 %) and hyperphosphatemia in 6 (2.4 %). Urinary metabolic abnormalities were identified in 248 (98 %) of the cases. Hypocitraturia was found in 207 (82.8 %), hyperoxaluria in 62 (26.4 %), hyperuricosuria in 82 (32.8 %), hypercalciuria in 51 (20.4 %), hyperphosphaturia in 46 (18.4 %), hyperammonuria in 10 (4 %), hypocalciuria in 82 (32.8 %), and hypovolemia in 73 (29.2 %). Risk factors were similar between genders except higher rates of hyponatriuria, hypophosphaturia, and hypocalciuria in females. Hyperuricosuria, hyponatriuria, and hypovolemia were highest in 1-5 years (52, 49, 49 %) as compared to (18, 21, 12 %) those in 11-15 years (p < 0.001), respectively. This study shows that careful metabolic analysis can identify risk factors in 98 % of the children where appropriate metaphylaxis can be undertaken both for treatment and prevention of recurrence.

Calcium-sensing receptor: A new target for therapy of diarrhea.

Management of acute diarrhea remains a global challenge, particularly in resource-limiting countries. Oral rehydration solution (ORS), a passive rehydrating therapy developed approximately 40 years ago, remains the mainstay treatment. Although ORS is effective for hydration, since it does not inhibit enterotoxin-mediated excessive secretion, reduced absorption and compromised barrier function - the primary mechanisms of diarrhea, ORS does not offer a rapid relief of diarrhea symptom. There are a few alternative therapies available, yet the use of these drugs is limited by their expense, lack of availability and/or safety concerns. Novel anti-diarrheal therapeutic approaches, particularly those simple affordable therapies, are needed. This article explores intestinal calcium-sensing receptor (CaSR), a newly uncovered target for therapy of diarrhea. Unlike others, targeting this host antidiarrheal receptor system appears "all-inclusive": it is anti-secretory, pro-absorptive, anti-motility, and anti-inflammatory. Thus, activating CaSR reverses changes of both secretory and inflammatory diarrheas. Considering its unique property of using simple nutrients such as calcium, polyamines, and certain amino acids/oligopeptides as activators, it is possible that through targeting of CaSR with a combination of specific nutrients, novel oral rehydrating solutions that are inexpensive and practical to use in all countries may be developed.

Acid-base assessment: when and how to apply the Henderson-Hasselbalch equation and strong ion difference theory.

The Henderson-Hasselbalch equation is probably the most famous equation in biology but is more descriptive than mechanistic. The traditional approach to acid-base assessment using the Henderson-Hasselbalch equation provides a clinically useful and accurate method when plasma protein concentrations are within the reference range. The simplified strong ion approach is a mechanistic acid-base model that can provide new insight into complicated acid-base disturbances. The simplified strong ion approach should be used to evaluate acid-base balance whenever plasma protein concentrations are abnormal.

Construction and validation of a decision tree for treating metabolic acidosis in calves with neonatal diarrhea.

BACKGROUND: The aim of the present prospective study was to investigate whether a decision tree based on basic clinical signs could be used to determine the treatment of metabolic acidosis in calves successfully without expensive laboratory equipment. A total of 121 calves with a diagnosis of neonatal diarrhea admitted to a veterinary teaching hospital were included in the study. The dosages of sodium bicarbonate administered followed simple guidelines based on the results of a previous retrospective analysis. Calves that were neither dehydrated nor assumed to be acidemic received an oral electrolyte solution. In cases in which intravenous correction of acidosis and/or dehydration was deemed necessary, the provided amount of sodium bicarbonate ranged from 250 to 750 mmol (depending on alterations in posture) and infusion volumes from 1 to 6.25 liters (depending on the degree of dehydration). Individual body weights of calves were disregarded. During the 24 hour study period the investigator was blinded to all laboratory findings. RESULTS: After being lifted, many calves were able to stand despite base excess levels below -20 mmol/l. Especially in those calves, metabolic acidosis was undercorrected with the provided amount of 500 mmol sodium bicarbonate, which was intended for calves standing insecurely. In 13 calves metabolic acidosis was not treated successfully as defined by an expected treatment failure or a measured base excess value below -5 mmol/l. By contrast, 24 hours after the initiation of therapy, a metabolic alkalosis was present in 55 calves (base excess levels above +5 mmol/l). However, the clinical status was not affected significantly by the metabolic alkalosis. CONCLUSIONS: Assuming re-evaluation of the calf after 24 hours, the tested decision tree can be recommended for the use in field practice with minor modifications. Calves that stand insecurely and are not able to correct their position if pushed require higher doses of sodium bicarbonate, if there is clinical evidence of a marked D-lactic acidosis. In those calves, determining the degree of loss of the palpebral reflex was identified as a useful decision criterion to provide an additional amount of 250 mmol sodium bicarbonate. This work demonstrates the clinical relevance of the discovery that D-lactate is responsible for most of the clinical signs expressed in neonatal diarrheic calves suffering from metabolic acidosis.

Contribution of enteric infection, altered intestinal barrier function, and maternal malnutrition to infant malnutrition in Bangladesh.

BACKGROUND: Malnourished children are at increased risk for death due to diarrhea. Our goal was to determine the contribution of specific enteric infections to malnutrition-associated diarrhea and to determine the role of enteric infections in the development of malnutrition. METHODS: Children from an urban slum in Bangladesh were followed for the first year of life by every-other-day home visits. Enteropathogens were identified in diarrheal and monthly surveillance stools; intestinal barrier function was measured by serum endocab antibodies; and nutritional status was measured by anthropometry. RESULTS: Diarrhea occurred 4.69 ± 0.19 times per child per year, with the most common infections caused by enteric protozoa (amebiasis, cryptosporidiosis, and giardiasis), rotavirus, astrovirus, and enterotoxigenic Escherichia coli (ETEC). Malnutrition was present in 16.3% of children at birth and 42.4% at 12 months of age. Children malnourished at birth had increased Entamoeba histolytica, Cryptosporidium, and ETEC infections and more severe diarrhea. Children who became malnourished by 12 months of age were more likely to have prolonged diarrhea, intestinal barrier dysfunction, a mother without education, and low family expenditure. CONCLUSIONS: Prospective observation of infants in an urban slum demonstrated that diarrheal diseases were associated with the development of malnutrition that was in turn linked to intestinal barrier disruption and that diarrhea was more severe in already malnourished children. The enteric protozoa were unexpectedly important causes of diarrhea in this setting. This study demonstrates the complex interrelationship of malnutrition and diarrhea in infants in low-income settings and points to the potential for infectious disease interventions in the prevention and treatment of malnutrition.

Total energy expenditure and physical activity in children treated with home parenteral nutrition.

Determining total energy expenditure (TEE) and its components in children treated with home parenteral nutrition (CHPN) under free-living conditions is an important consideration in the assessment of energy requirements and the maintenance of health. The aim of this study was to assess TEE and physical activity in CHPN. Eleven CHPN (three girls and eight boys; median age, 6.0 y; range, 4.5-15.0 y) were compared with 11 healthy children (three girls and eight boys; median age, 6.0 y, range, 4.5-14.0 y) after pairing for sex, age, and weight. Underlying diseases included chronic intractable diarrhea (n = 5), short bowel syndrome (n = 3), and intestinal dysmotility (n = 3). None of these children had inflammatory disease or recent infection when studied. Fat-free mass (FFM), measured by body impedance analysis, fat mass (FM), measured by skinfold thickness, and energy intake were similar between the two groups, suggesting that CHPN had normal body composition and energy intake. Resting energy expenditure (REE), measured by indirect calorimetry, and TEE, assessed by a technique using 24-h heart-rate monitoring calibrated against indirect calorimetry and physical activity using a triaxial accelerometer, were simultaneously recorded and were also similar in the two groups. Sleeping energy expenditure (SEE), expressed per kilogram of FFM, was significantly greater in the CHPN group (median, 0.15; range, 0.10-0.23 kJ/min/kg FFM versus median, 0.12; range, 0.09-0.21 kJ/min/kg FFM for controls; p < 0.05, Wilcoxon rank test). These findings were explained by the high correlation between the energy flow infused by parenteral nutrition and sleeping energy expenditure (p < 0.05, Spearman test) and also-diet induced thermogenesis (p < 0.05 Spearman test). These results suggest that the energy requirements of children on long-term home parenteral nutrition programs do not differ from controls and that cyclic parenteral nutrition does not interfere with physical activity.

Electrolyte economy and its hormonal regulation in congenital chloride diarrhea.

The economy of Cl-, K+, and Mg++, extracellular volume (ECV) and plasma volume, and the role of hyperreninemia and hyperaldosteronism were explored in 22 patients with congenital chloride diarrhea. Stool volume was in significant correlation with its Cl-, Na+ and K+ content, the correlation being significantly better with Cl- content than with the Na+ content. Low fecal Cl- concentrations were seen in chronic hypochloremic contraction, but acute episodes did not cause reduction of fecal Cl- concentration from the basal level of 140--150 mmol/liter. The adequate condition (defined as normal serum electrolyte concentrations and bl;od pH, and presence of Cl- in urine) was associated with high total exchangeable Cl- and ECV. This excess Cl- and ECV roughly equalled the high daily fecal amount of Cl- and volume. Reduced ECV was accompanied by high renin activities and hyperaldosteronism, but in the adequate condition these were normal. Hyperaldosteronism caused a decrease in urinary Na+-K+ ratio and, after the age of 2--6 months, in the fecal Na+-K+ ratio. Total exchangeable K+ was normal in the adequate condition. No Mg++ depletion was present, although the patients lack Mg++ substitution. The adequate condition could be maintained with an oral supplement of NaCl, KCl and water.

[Modification of the caloric intake as a function of energy expenditure in patients with diarrhea]. / Adaptation des apports caloriques en fonction des dépenses énergétiques chez des malades présentant une diarrhée

UNLABELLED: We have compared, using non protein RQ method, energy expenditures of diarrheic patients with intraperitoneal or intraluminal suppuration and feed enterally (group II) or intravenously (group III). Five non suppurative diarrheic patients feed enterally were studied as control (group I). Carbohydrate, protein and fat intakes were not significantly different in the 3 groups of patients. Patients of group II metabolized significantly less of carbohydrate (p less than 0.01) and more of fat (P less than 0.01) than groups I and III patients. Carbohydrate and fat expenditures of patients of groups I and III were not significantly different. CONCLUSION: 1) There is a possible trouble of carbohydrate absorption in suppurative diarrheic patients. 2) Therefore caloric intake must be preferably parenteral in these patients.