Differential impact of lactose/lactase phenotype on colonic microflora

BACKGROUND:

The ability to digest lactose divides the world’s population into two phenotypes that may be risk variability markers for several diseases. Prebiotic effects likely favour lactose maldigesters who experience lactose spilling into their colon.

OBJECTIVE:

To evaluate the effects of fixed-dose lactose solutions on fecal bifidobacteria and lactobacilli in digesters and maldigesters, and to determine whether the concept of a difference in ability to digest lactose is supported.

METHODS:

A four-week study was performed in 23 lactose mal-digesters and 18 digesters. Following two weeks of dairy food withdrawal, subjects ingested 25 g of lactose twice a day for two weeks. Stool bifidobacteria and lactobacilli counts pre- and postintervention were measured as the primary outcome. For secondary outcomes, total anaerobes, Enterobacteriaceae, beta-galactosidase and N-acetyl-beta-D-glucosaminidase activity in stool, as well as breath hydrogen and symptoms following lactose challenge tests, were measured.

RESULTS:

Lactose maldigesters had a mean change difference (0.72 log₁₀ colony forming units/g stool; P=0.04) in bifidobacteria counts compared with lactose digesters. Lactobacilli counts were increased, but not significantly. Nevertheless, reduced breath hydrogen after lactose ingestion correlated with lactobacilli (r=−0.5; P<0.001). Reduced total breath hydrogen and symptom scores together, with a rise in fecal enzymes after intervention, were appropriate, but not significant.

CONCLUSIONS:

Despite failure to achieve full colonic adaptation, the present study provided evidence for a differential impact of lactose on microflora depending on genetic lactase status. A prebiotic effect was evident in lactose maldigesters but not in lactose digesters. This may play a role in modifying the mechanisms of certain disease risks related to dairy food consumption between the two phenotypes.     

Lack of effect of lactose digestion status on baseline fecal microflora

BACKGROUND:

The genetics of intestinal lactase divide the world’s population into two phenotypes: the ability (a dominant trait) or inability (a recessive trait) to digest lactose. A prebiotic effect of lactose may impact the colonic flora of these phenotypes differently.

OBJECTIVE:

To detect and evaluate the effects of lactose on subjects divided according to their ability to digest lactose.

METHODS:

A total of 57 healthy maldigesters (n=30) and digesters (n=27) completed diet questionnaires, genetic and breath hydrogen testing, and quantitative stool analysis for species of bacteria. Log₁₀ transformation of bacterial counts was compared with lactose intake in both groups using multiple regression analysis.

RESULTS:

There was a significant relationship between genetic and breath hydrogen tests. Daily lactose intake was marginally lower in lactose maldigesters (median [interquartile range] 12.2 g [31 g] versus 15 g [29.6 g], respectively). There was no relationship between lactose intake and breath hydrogen tests in either group. There were no differences in bacterial counts between the two groups, nor was there a relationship between bacterial counts and lactose intake in either group.

CONCLUSION:

The differential bacterial effects of lactose were not quantitatively detected in stool samples taken in the present study.     

Prevalence of abnormal lactose breath hydrogen tests in children with functional abdominal pain

Objectives

The study was undertaken to determine the prevalence of abnormal lactose breath hydrogen test in children with non-organic chronic abdominal pain.

Methods

Children with chronic abdominal pain were examined and investigated for organic causes. All children without a known organic cause underwent lactose and glucose breath hydrogen test. After a standard dose of 2 g/kg of lactose to a maximum of 50 g, hydrogen in breath was measured at 15 min intervals for 3 h. A rise of 20 ppm above baseline was considered suggestive of lactose malabsorption.

Results

Of 108 children screened, organic causes were found in 46 children. Sixty-two patients without any organic cause underwent hydrogen breath test. Lactose hydrogen breath test (HBT) was positive in 36 of 62 (58%), while 11 (17%) had positive HBT with glucose suggestive of small intestinal bacterial overgrowth (SIBO). Twenty out of 34 (59%) improved on lactose free diet while 8 out of 11 (72%) children of SIBO improved on antibiotics.

Conclusions

Lactose malabsorption was seen in 58% of children with non-organic chronic abdominal pain.

     

Prevalence of lactose maldigestion

Ninety-eight adults ranging from 20 to 89 years in age (52 blacks, 46 whites; 48 males, 50 females) were tested for lactose maldigestion by breath hydrogen analysis after consuming milk containing 16.5 g lactose (360 ml milk). Older adults (50 years) displayed a significantly higher incidence (46%) of lactose maldigestion than younger adults (<50 years, 26%). In younger adults there were 2.4 times more maldigesters in blacks than in whites, while in older groups this ratio was 3.6. Level of breath hydrogen significantly increased with age up to the age group of 60–69 years. The interaction between age groups and race was highly significant. Of the maldigesters, 63% reported symptoms and 3% of the total sample reported severe symptoms. Results of this study indicate that the prevalance of lactose maldigestion significantly increases with age in blacks compared to whites and that the magnitude of the problem may be greater in black maldigesters than in white maldigesters.     

The Role of Celiac Disease in Severity of Liver Disorders and Effect of a Gluten Free Diet on Diseases Improvement

Context

Celiac disease (CD) is defined as a permanent intolerance to ingested gluten. The intolerance to gluten results in immune-mediated damage of small intestine mucosa manifested by villous atrophy and crypt hyperplasia. These abnormalities resolve with initiationa gluten-free diet.

Evidence Acquisition

PubMed, Ovid, and Google were searched for full text articles published between 1963 and 2012. The associated keywords were used, and papers described particularly the impact of celiac disease on severity of liver disorder were identified.

Results

Recently evidence has emerged revealingthat celiac disease not only is associated with small intestine abnormalities and malabsorption, but is also a multisystem disorder affecting other systems outside gastrointestinal tract, including musculo-skeletal, cardiovascular and nervous systems. Some correlations have been assumed between celiac and liver diseases. In particular, celiac disease is associated with changes in liver biochemistry and linked to alter the prognosis of other disorders. This review will concentrate on the effect of celiac disease and gluten-free diets on the severity of liver disorders.

Conclusions

Although GFD effect on the progression of CD associated liver diseases is not well defined, it seems that GFD improves liver function tests in patients with a hypertransaminasemia.     

Possible therapeutic use of loperamide for symptoms of lactose intolerance.

OBJECTIVES: To examine a potential practical therapeutic use of loperamide (Lo) to decrease the symptoms of lactose intolerance. SUBJECTS AND METHODS: Nineteen (eight men, 11 women) healthy lactose maldigesters (18 of 19 with symptoms) underwent a 25 g lactose challenge on five separate days. Breath hydrogen was measured, areas under the curve (AUC) were calculated for 4 h, and 4 and 12 h symptom scores were recorded. After establishing baseline measurements, test doses of 4 mg, 8 mg and 12 mg Lo were randomly administered without placebo in a double-blind manner. As well, each subject received seven lactase tablets, in a random, unblinded manner. RESULTS: The median AUC and mean oral cecal transit time followed dose response expectations; however, only lactase treatment achieved significance. Nevertheless, 8 mg Lo significantly improved symptom scores, which were statistically indistinguishable from those of lactase. Four subjects complained of delayed constipation and cramps with various doses of Lo. CONCLUSIONS: Lo monotherapy for lactose intolerance is not economical and may have some side effects. However, Lo may be studied further as an adjunctive treatment of lactose intolerance in an effort to reduce the need for complete lactose digestion. Such a manoeuvre may allow rapid colonic adaptation, which in turn may be beneficial for prophylaxis for a number of colonic diseases.     

Quality of Internet-based information on gastrointestinal diseases

BACKGROUND:

The Internet is becoming an increasingly common source of health information for patients.

OBJECTIVE:

To examine the quality of gastrointestinal disease- and symptom-related Internet sites that might be searched by patients.

METHODS:

A total of 120 websites were evaluated from July to November 2009 using the DISCERN instrument to determine the quality of content of health and treatment information.

RESULTS:

There was substantial variability in the quality of Internet resources regarding gastrointestinal diseases and their symptoms. Information-based and institutional websites were rated highest. Resources related to celiac disease, colon cancer and abdominal pain scored the highest.

CONCLUSIONS:

Overall, the quality of web-based resources was variable. Because patient education is important in the management of gastroenterological diseases, the increasing use of the Internet poses new opportunities and challenges for physicians.     

Torsion of the gallbladder: a systematic review

Background

Gallbladder torsion is a rare disease, predominantly affecting elderly women. It is an important differential in the acute surgical abdomen.

Methods

A total of 324 published case reports of torsion of the gallbladder were reviewed. Features in diagnostic imaging suggestive of torsion were reviewed and summarized.

Results

Gallbladder torsion is primarily a disease of elderly people; the median age at presentation is 77 years. It is more common amongst women, occurring at a female : male ratio of 4 : 1, although not in childhood, when it occurs at a male : female ratio of 2.5 : 1.

Conclusions

Improved imaging techniques within the last 20 years have enabled the preoperative diagnosis of one quarter of patients with gallbladder torsion. With prompt surgical intervention, the condition has an excellent prognosis.     

Chronic Stress Improves NO- and Ca2+ Flux-Dependent Vascular Function: A Pharmacological Study

Background

Stress is associated with cardiovascular diseases.

Objective

This study aimed at assessing whether chronic stress induces vascular alterations, and whether these modulations are nitric oxide (NO) and Ca2+ dependent.

Methods

Wistar rats, 30 days of age, were separated into 2 groups: control (C) and Stress (St). Chronic stress consisted of immobilization for 1 hour/day, 5 days/week, 15 weeks. Systolic blood pressure was assessed. Vascular studies on aortic rings were performed. Concentration-effect curves were built for noradrenaline, in the presence of L-NAME or prazosin, acetylcholine, sodium nitroprusside and KCl. In addition, Ca²⁺ flux was also evaluated.

Results

Chronic stress induced hypertension, decreased the vascular response to KCl and to noradrenaline, and increased the vascular response to acetylcholine. L-NAME blunted the difference observed in noradrenaline curves. Furthermore, contractile response to Ca²⁺ was decreased in the aorta of stressed rats.

Conclusion

Our data suggest that the vascular response to chronic stress is an adaptation to its deleterious effects, such as hypertension. In addition, this adaptation is NO- and Ca²⁺-dependent. These data help to clarify the contribution of stress to cardiovascular abnormalities. However, further studies are necessary to better elucidate the mechanisms involved in the cardiovascular dysfunction associated with stressors. (Arq Bras Cardiol. 2014; [online].ahead print, PP.0-0)     

Challenges in the diagnosis and management of autoimmune hepatitis

BACKGROUND:

Autoimmune hepatitis has diverse clinical phenotypes and outcomes that challenge current diagnostic criteria and management algorithms.

OBJECTIVES:

To highlight the major difficulties in diagnosis and management, describe the efforts to ease them and encourage further progress in problem solving.

METHODS:

The MEDLINE database was reviewed for published experiences from 1984 to 2013.

RESULTS:

Acute or acute severe (fulminant) hepatitis, asymptomatic mild disease, and histological findings of centrilobular necrosis or bile duct injury can confound diagnosis and treatment. Continuation of conventional therapy until normal liver test results and liver tissue reduces the frequency of relapse, but does not prevent its occurrence. Problematic patients can be identified using mathematical models, clinical phenotype, serological markers and the speed of improvement after treatment; however, their recognition and treatment are inconsistent. Mycophenolate mofetil can rescue patients with azathioprine intolerance but is less effective for refractory disease. Budesonide in combination with azathioprine can be used frontline, but is effective primarily in noncirrhotic, uncomplicated disease. Molecular and cellular interventions are feasible but largely unevaluated.

DISCUSSION:

Resolution of the current challenges requires revision of diagnostic criteria, characterization of biological markers that reflect pathogenic pathways, development of dynamic indexes based on changes in disease behaviour, and introduction of new pharmacological, molecular and cellular interventions that have undergone rigorous evaluation.

CONCLUSION:

These challenges reflect important remediable deficiencies in current management.     

Bacterial communities in neonatal feces are similar to mothers’ placentae

BACKGROUND:

The gut microbiota plays an important role in human health. It is essential to understand how the composition of the gut microbiota in neonates is established.

OBJECTIVES:

To investigate the nature of the microbial community in the first feces of newborn infants compared with the mothers’ placentae and vaginas.

METHODS:

One infant who was delivered via Cesarean section was compared with an infant who was delivered vaginally. Bar-coded pyro-sequencing of 16S ribosomal RNA genes was used to investigate the bacterial community composition and structure of each site.

RESULTS:

Neonatal feces of both infants had similar bacterial communities, and they were similar to the mother’s placenta regardless of the method of delivery. The vaginal bacterial community differed between the two mothers, but not different sites within the vagina. The bacteria in the neonatal feces and the mothers’ placentae demonstrated considerably higher diversity compared with the vaginas. The family Lactobacillaceae dominated in the vaginal samples, while the most abundant family in the fecal and placental samples was Micrococcineae.

CONCLUSIONS:

These results may provide new directions for the study of infant gut microbial formation.     

Mycophenolate mofetil for the treatment of autoimmune hepatitis in patients refractory or intolerant to conventional therapy

BACKGROUND:

Autoimmune hepatitis is characterized by hepatocellular inflammation often progressing to cirrhosis. Standard treatment consists of corticosteroids and azathioprine. For the 20% of patients with refractory disease or those who are intolerant to medication, there is no standardized treatment.

OBJECTIVE:

To evaluate mycophenolate mofetil (MMF) as an alternative therapy for autoimmune hepatitis.

METHODS:

The present retrospective study identified all patients with autoimmune hepatitis who were treated with MMF over a 10-year period at the Henry Ford Hospital (Michigan, USA). These patients were evaluated for tolerance and response.

RESULTS:

Of the 90 patients participating in the study, 48% had a complete response, 32% experienced relapses and 21% were refractory. MMF was initiated in 21 patients – 12 (57%) for refractory disease and nine (43%) for medication intolerance. Of the 12 patients converted for refractory disease, all showed biochemical improvement but none had a complete response. Of the patients converted due to intolerance, 88% maintained complete remission. For all patients converted to MMF, there was a mean decrease in steroid dose from 18.9 mg/day to 7.8 mg/day (P=0.01).

CONCLUSIONS:

In patients with autoimmune hepatitis who were intolerant to conventional therapy, MMF was well tolerated, with 88% of patients maintained in remission. MMF did not induce remission in those refractory to conventional therapy; however, it resulted in a significant decrease in steroid use. Prospective studies are needed to better assess the role of MMF as an alternative therapy.     

Resilience in Patients with Ischemic Heart Disease

Background

Resilience is a psychosocial factor associated with clinical outcomes in chronic diseases. The relationship between this protective factor and certain diseases, such heart diseases, is still under-explored.

Objective

The present study sought to investigate the frequency of resilience in individuals with ischemic heart disease.

Method

This was a cross-sectional study with 133 patients of both genders, aged between 35 and 65 years, treated at Rio Grande do Sul Cardiology Institute - Cardiology University Foundation, with a diagnosis of ischemic heart disease during the study period. Sixty-seven patients had a history of acute myocardial infarction. The individuals were interviewed and evaluated by the Wagnild & Young resilience scale and a sociodemographic questionnaire.

Results

Eighty-one percent of patients were classified as resilient according to the scale.

Conclusion

In the sample studied, resilience was identified in high proportion among patients with ischemic heart disease.     

Mutation-prone points in KCNQ

BACKGROUND

KCNQ channels play important roles in controlling membrane excitability. A reduction in KCNQ channel activity due to genetic mutation is responsible for various human diseases, including arrhythmia.

METHODS

A combined bioinformatics analysis was performed to study the positions that are at risk for mutation within the amino acid sequence of KCNQ. A new bioinformatics tool, namely GlobPlot, was used.

RESULTS

According to the present study, the positions that are resistant to mutation are predicted.

CONCLUSION

Several mutation-prone positions within the KCNQ sequence are reported.     

Persistent sputum cellularity and neutrophils may predict bronchiectasis

BACKGROUND:

Quantitative cell counts in sputum provide an accurate assessment of the type and severity of bronchitis.

OBJECTIVE:

To examine whether sputum cell counts could identify bronchiectasis in patients with recurrent bronchitis.

METHODS:

A retrospective survey of a clinical database (January 2004 to January 2005) of quantitative cell counts from sputum selected from expectorate in patients with obstructive airways diseases was used to identify predictors of bronchiectasis using ROC curves. This was prospectively evaluated (February 2005 to April 2008) using high-resolution computed tomography scans of thorax that were independently scored by a radiologist who was blinded to the clinical details.

RESULTS:

The retrospective survey identified 41 patients with bronchiectasis among 490 patients with airway diseases. Total cell count of 60×10⁶/g or greater of the selected sputum with predominant neutrophils on two occasions had a sensitivity of 86.7%, a specificity of 87.5%, and positive and negative predictive values of 93% and 78%, respectively, to identify bronchiectasis. In the prospective study, 10 of 14 (71%) patients who met these criteria were identified to have bronchiectasis. Both total cell count and the percentage of neutrophils correlated with radiographic bronchiectasis severity.

CONCLUSIONS:

Persistent or recurrent intense sputum cellularity with neutrophilia is suggestive of bronchiectasis.     

Prevalence of and risk factors for self-reported chronic bronchitis in a Canadian population: The Canadian Community Health Survey, 2007 to 2008

BACKGROUND:

Chronic bronchitis (CB) represents one of the respiratory disease phenotypes that affect the Canadian health care system significantly. Presently, almost 6.5% of total health care costs are related to respiratory diseases.

OBJECTIVE:

To determine the prevalence of self-reported CB and associated risk factors in the Canadian general population.

METHODS:

Data regarding individuals ≥12 years of age from the Canadian Community Health Survey, 2007 to 2008, were analyzed. CB was determined through self-reported health professional diagnosis. Information regarding covariates of importance, such as demographics, lifestyle variables and socioeconomic status, was obtained. A weighted logistic regression analysis was performed with appropriate technique for clustering effects.

RESULTS:

The prevalence of self-reported CB was 2.5%. A greater prevalence of self-reported CB associated with older age, female sex and white ethnic group was found. There were differences in the prevalence of self-reported CB among regions of Canada for household income, educational attainment and smoking status.

CONCLUSION:

The results suggest an association between ethnicity and the prevalence of CB. The associations between self-reported CB prevalence and household income, educational attainment and smoking status varied according to region of Canada.     

Measurement of von Willebrand factor as the marker of endothelial dysfunction in vascular diseases

BACKGROUND:

von Willebrand factor is a blood glycoprotein that is required for normal hemostasis. Its level can be increased by endothelial cell damage.

HYPOTHESIS:

von Willebrand factor is a suitable marker of endothelial dysfunction.

METHODS:

von Willebrand factor activity was determined by ELISA in patients with acute coronary syndromes, acute stroke and chronic vascular diseases, and was compared with the values of healthy controls.

RESULTS:

von Willebrand factor activity of patients in each group was significantly higher (P<0.001) than that of the control group. The values of patients with acute coronary syndrome and acute stroke were significantly higher (P<0.05 and P<0.01, respectively) than those of patients with chronic vascular diseases. von Willebrand factor activity was significantly higher in patients with acute coronary syndrome and acute stroke (P<0.05 and P<0.01, respectively) on the sixth day than on admission.

CONCLUSIONS:

By measuring von Willebrand factor activity, a considerable, significant difference could be found between healthy people and chronic and acute vascular patients. The routine measurement of von Willebrand factor activity in vascular patients as an index of endothelial dysfunction may have clinical importance, because detection of this marker can be a noninvasive way of assisting diagnosis and indicating disease progression.     

Protective Effect of Salep on Liver

Background:

Salep is used for various purposes in food industries and traditional medicine. Therefore, evaluation of its effect on the liver seems to be necessary.

Objectives:

The aim of this study was to assess salep effect on liver.

Materials and Methods:

In this experimental study, various concentrations of Salep were intraperitoneally administered to five groups of Wistar rats (control, placebo and 20, 40 and 80 mg/kg salep). After one month, liver enzymes and liver tissue were evaluated and compared between different groups.

Results:

Significant decreased level of liver enzymes, MDA (Malondialdehyde) and TOC (Total Oxidation Capacity) were found in various concentrations of salep administration. On the other hand, a significant increase was found in TAC (Total Antioxidant Capacity) level with various doses of salep.

Conclusions:

Elevated level of total protein and albumin and decreased level of liver enzyme by salep extract were found in this study. Therefore, this plant may be a useful medicine for patients with liver diseases.     

Effect of a group-based exercise program on balance in elderly

Objective:

To determine the effectiveness of 8-week group functional balance training classes on balance outcomes in community-dwelling veterans at risk for falls.

Design:

Pre-test, post-test using retrospective data.

Setting:

VISN 8 Patient Safety Center at James A. Haley Veterans Hospital in Tampa, FL, USA.

Participants:

Fifty one community living veterans with mean age of 78 at risk for falls.

Intervention:

Participants received a weekly 1-hour functional balance training class for 8 weeks in a small group setting (4–5 participants).

Measurements:

Pre and post intervention measures included Berg Balance Scale, Limits of Stability (LOS) and modified Clinical Test of Sensory Interaction on Balance (mCTSIB).

Results:

Eighty four percent of the participants completed 5 or more weekly classes. Peripheral neuropathy was the most common risk factor among the participants. There was a significant improvement in the Berg (p < 0.0001) and Composite Reaction Time (p < 0.0004) after the intervention.

Conclusion:

An eight week group functional balance training class was safe and effective in improving balance outcomes in a cohort of elderly veterans at risk for falls.     

Association of PNPLA3 I148M Variant With Chronic Viral Hepatitis,Autoimmune Liver Diseases and Outcomes of Liver Transplantation

Context:

The PNPLA3 I148M variant has been recognized as a genetic determinant of liver fat content and a genetic risk factor of liver damage progression associated with steatohepatitis. The I148M variant is associated with many chronic liver diseases. However, its potential association with inflammatory and autoimmune liver diseases has not been established.

Evidence Acquisition:

We systemically reviewed the potential associations of I148M variant with chronic viral hepatitis, autoimmune liver diseases and the outcome of liver transplantation, explored the underlying molecular mechanisms and tried to translate them into more individualized decision-making and personalized medicine.

Results:

There were associations between I148M variant and chronic viral hepatitis and autoimmune liver diseases and differential associations of I148M variant in donors and recipients with post-liver transplant outcomes. I148M variant may activate the development of steatosis caused by host metabolic disorders in chronic viral hepatitis, but few researches were found to illustrate the mechanisms in autoimmune liver diseases. The peripherally mediated mechanism (via extrahepatic adipose tissue) may play a principal role in triglyceride accumulation regardless of adiponutrin activity in the graft liver.

Conclusions:

Evidences have shown the associations between I148M variant and mentioned diseases. I148M variant induced steatosis may be involved in the mechanism of chronic viral hepatitis and genetic considered personalized therapies, especially for PSC male patients. It is also crucial to pay attention to this parameter in donor selection and prognosis estimation in liver transplantation.