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Biomedical subjects

Andrew Szilagyi

Publications and source records attributed to Andrew Szilagyi.

14 recordsLinked to original sources

Comparison of a real-time polymerase chain reaction assay for lactase genetic polymorphism with standard indirect tests for lactose maldigestion.

BACKGROUND & AIMS: There is a discrepancy in outcome between the lactose tolerance and breath hydrogen tests for lactose maldigestion. The availability of a validated genetic test for lactase polymorphism allows a reevaluation of these tests. METHODS: Thirty healthy adults participated in a 50-g lactose challenge test at a university clinic. Blood was drawn for genetic and timed blood glucose testing (2 hours), and breath hydrogen was measured (4.5 hours). Lactase genetic polymorphism was assessed by a real-time polymerase chain reaction assay. Participants completed a diet questionnaire, and symptoms were recorded during the lactose challenge. Sensitivity and specificity were calculated for each indirect test. The 2-way kappa coefficient between these tests was evaluated. Student t test and Wilcoxon rank sum test were used to compare variables. RESULTS: The lactose tolerance test as a standard had an 87.5% sensitivity and 92.7% specificity for genetic status. Only a moderate agreement between lactose tolerance test and breath hydrogen test was observed (2-way kappa coefficient, .53; 95% confidence interval, .22-.83). When genetic status was used as standard, symptoms had a moderate sensitivity and specificity. Lactose tolerance test had very good sensitivity, and the breath test had excellent specificity. CONCLUSIONS: Both indirect tests independently have good to very good sensitivities and specificities for genetic lactase status. The noted disagreement likely reflects variables that affect the tests independently of intestinal lactase status. The value of these tests in the light of the availability of genetic testing is discussed.

Adult↗

Acute symptomatic gastritis due to Helicobacter heilmannii.

Helicobacter heilmannii is a Gram-negative spiral-shaped organism predominantly associated with zoonotic infection. Human pathology has also been described, but acute symptoms with complete resolution have been infrequently reported. We present a 50-year-old man in whom H. heilmannii gastritis presented as an acute febrile illness and was successfully treated with antibiotics and proton pump inhibitor. Epidemiology, diagnosis, and treatment of similar cases are reviewed.

Gastritis↗

Pharmacological therapy of vascular malformations of the gastrointestinal tract.

Vascular malformation (AVM) in the gastrointestinal tract is an uncommon, but not rare, cause of bleeding and iron deficiency anemia, especially in an aging population. While endoscopic coagulative therapy is the method of choice for controlling bleeding, a substantial number of cases require additional therapy. Adjunctive or even primary phamacotherapy may be indicated in recurrent bleeding. However, there is little evidence-based proof of efficacy for any agent. The bulk of support is derived from anecdotal reports or case series. The present review compares the outcome of AVM after no intervention, coagulative therapy or focus on pharmacological agents. Most of the literature encompasses two common AVMs, angiodysplasia and hereditary hemorrhagic telangiectasia. Similarly, the bulk of information evaluates two therapies, hormones (estrogen and progesterone) and the somatostatin analogue octreotide. Of these, the former is the only therapy evaluated in randomized trials, and the results are conflicting without clear guidelines. The latter therapy has been reported only as case reports and case series without prospective trials. In addition, other anecdotally used medications are discussed.

Adrenal Cortex Hormones↗

The effect of lactose maldigestion on the relationship between dairy food intake and colorectal cancer: a systematic review.

Dairy food consumption has been inconsistently shown to protect against colorectal cancer (CRC) in case-based studies, and no clear benefits against recurrent colonic polyps (CRP) have been reported. Based on population-based studies we have hypothesized that dairy food intake may have anti-CRC effects at both low intake lactase non-persistent (LNP) populations and at high intake lactase persistent (LP) subjects. We separately analyse existing case-based studies and divide origins into high LNP (>or= 80% LNP prevalence), low LNP (prevalence <or= 20%) and mid LNP countries (21-79% prevalence), which coincide with low, high, and mid quantity dairy food intake regions, respectively. Odds ratios and relative risks (RR) of highest versus lowest dairy intake within each group are analyzed together for assessment of protection against CRC and CRP. Eighty studies met stipulated criteria. Thirteen analyzed the effect on recurrent polyps. Forest plots from 2 regions, high LNP (low dairy food intake) RR = 0.84 [95% confidence interval (CI) = 0.73-0.97) and low LNP (high dairy food intake) RR = 0.80 (95% CI = 0.73-0.88) demonstrated significant protection against CRC. In mixed LNP/LP populations (mid dairy food intake) nonsignificant protection was found RR = 0.92 (95% CI = 0.79-1.06). Similar regional analysis for CRP failed to show significant protective effect in any region. This meta-analysis supports that the highest level of dairy food consumption protects subjects in both high and low LNP regions but not in areas with significant mixed LNP/LP populations. In both groups, dairy foods had no effect on polyp formation, suggesting it may only protect against CRC at late stages of promotion. These results raise the possibility that LNP/LP status may be partly responsible for the discrepant results with respect to the relationship between dairy food consumption and CRC.

Case-Control Studies↗

Evaluation of relationships among national colorectal cancer mortality rates, genetic lactase non-persistence status, and per capita yearly milk and milk product consumption.

Colorectal cancer (CRC) is one of the leading causes of mortality in Western countries. Its putative pathogenesis revolves around genetic and environmental factors, particularly diet. One of the most studied dietary factors, dairy product intake, is still debated as a protective agent. The role of lactose as a candidate prebiotic (stimulating lactic acid bacteria) and its relation to genetic lactase non-persistence (LNP) status has not been evaluated. We undertook a review and analysis of national per capita dairy product consumption, national LNP prevalence, and national CRC mortality rates (CRCM) to determine whether relationships existed among these variables. Data on these three items were obtained from the available literature. A negative binomial regression model was used to compare national LNP status with national CRCM rates for three time periods. Pearson correlation was used to compare national per capita dairy food intake with national CRCM rates for the approximate midpoint time period of reviewed articles. We found that there was a significant positive correlation between per capita dairy food intake and CRCM rates. However, there was also a significant negative correlation between national LNP prevalence and CRCM rates. Population-based studies supported the suggestion that in both homogeneous high and homogeneous low prevalence LNP countries characterized by low and high dairy food intake respectively, dairy food consumption exerted a protective effect against CRC and CRCM rate. Because some population studies contradict the hypotheses that dairy food intake promotes CRC or that LNP status protects against CRC, we hypothesize that dairy food consumption may operate by two distinct mechanisms--one that operates at low doses in LNP subjects and another in high doses in non-LNP subjects.

Animals↗

Meta-analysis of outcome of cytomegalovirus colitis in immunocompetent hosts.

There are only a few anecdotal reports of cytomegalovirus (CMV) colitis in immunocompetent hosts. The impact of the disease in this patient population remains poorly understood. The aim of this study was to perform a meta-analysis using individual patient data to determine outcomes of CMV colitis in immunocompetent patients and identify risk factors that might influence prognosis. A literature search was performed from 1980 to 2003 looking for immunocompetent patients with CMV colitis. Immunocompetence was defined as absence of congenital or acquired immune deficiency, transplant, or immunosuppressive medication. Patients were divided by age (<55 versus > or =55) and grouped according to coexisting illnesses. Kaplan-Meier curves were plotted to assess survival. Variables included age, sex, site of acquisition of infection, extent of disease, coexisting illnesses, and treatment modality. A total of 44 patients were identified, with an average age of 61.1. Only 10 were free of any comorbidity. The mean follow-up was 13.4 months. Spontaneous remission occurred in 31.8%, mostly individuals <55 years old. Fourteen deaths occurred, all of which were in patients >55. There was a higher mortality rate among male patients > or =55 (56.9%; P = 0.08), patients with immune-modulating diseases (75.2%; P = 0.10), and those having a colectomy (68.9%; P = 0.09). This analysis underlines the rarity of CMV colitis in patients with an intact immune system. Advanced age, male gender, presence of immune-modulating comorbidities, and need for surgical intervention are factors negatively influencing survival. Conversely, young healthy patients have a good prognosis with no intervention.

Age Factors↗

Inverse dose effect of pretest dietary lactose intake on breath hydrogen results and symptoms in lactase nonpersistent subjects.

The aim of this study was to determine a relationship between pretest intake of lactose and outcome of lactose breath hydrogen test. Patients presented at a testing laboratory participated in the study. A 3-hour breath hydrogen, 50-g lactose challenge was carried out. Results were tabulated and patients completed a 3-day recall diet questionnaire. Daily lactose intake was independently calculated and was associated with breath hydrogen and total symptom score. Statistical analysis used Spearman's correlation, Mann-Whitney U-test and chi2 or Fisher exact test. Of 118 patients, 50% were lactose maldigesters. In these patients, measured breath hydrogen and symptom scores were significantly higher in the lowest intake group (< 5 g/d) than in the highest intake group (> 20 g/d) (P < .05). In the presumed lactose digesters, 59% experienced some symptoms during testing for unclear reasons. Pretest dietary intake of lactose inversely affects results of breath hydrogen.

Adolescent↗

Use of prebiotics for inflammatory bowel disease.

The relevance of diet in both the pathogenesis and the therapy of inflammatory bowel disease is an evolving science. Disturbance of intestinal microflora (dysbiosis) is putatively a key element in the environmental component causing inflammatory bowel disease. Prebiotics are among the dietary components used in an attempt to counteract dysbiosis. Such predominantly carbohydrate dietary components exert effects on the luminal environment by physicochemical changes through pH alteration, by production of short chain fatty acids and by selectively promoting putatively 'health-beneficial' bacteria. The present review elaborates on some of the background rationale and mechanisms on the use of prebiotics. Additionally, published animal and human trials are discussed.

Animals↗

Redefining lactose as a conditional prebiotic.

Lactose in dairy products is maldigested by up to 70% to 75% of the world's population and many people may therefore suffer symptoms reminiscent of irritable bowel syndrome. As a result, most research to date has concentrated on ways of improving lactose tolerance to enhance dairy as a source of nutrition. However, research on other possible benefits of lactose and its maldigestion has lagged. In view of an exponential growth in the understanding of intestinal microfloral host interactions and the expanding therapeutical potential of probiotics, a reassessment of the role of lactose as a potential prebiotic in lactase nonpersistent subjects is required. Gibson and Roberfroid introduced the concept of prebiotics and outlined definitive requirements for such a compound. The present article examines scientific and clinical knowledge about the properties of lactose and argues that in lactase nonpersistent subjects, lactose qualifies as a prebiotic.

Animals↗

Failure to improve parameters of lactose maldigestion using the multiprobiotic product VSL3 in lactose maldigesters: a pilot study.

Lactose maldigestion is a common genetic trait in up to 70% of the world's population. In these subjects, the ingestion of lactose may lead to prebiotic effects which can be confirmed by measurement of breath hydrogen. After a period of continuous lactose ingestion, colonic bacterial adaptation is measurable as improved parameters of lactose digestion. There may be inherent benefits in this process of adaptation which may protect against some diseases. We attempt to link therapeutically beneficial probiotics (VSL3, Seaford Pharmaceuticals Inc, Ontario) with improvement in parameters of lactose maldigestion. Two groups of five subjects with maldigestion were fed one or four packets of VSL3 (one packet containing 450 x 10(9) live bacteria) before testing and then 17 days later. A 50 g lactose challenge was carried out before and after feeding. While there was a trend toward increasing rather than reducing of summed breath hydrogen, no statistically significant changes were observed between results from before testing and those from testing 17 days later. The authors conclude that direct consumption of the probiotic VSL3 may not improve parameters of lactose maldigestion without metabolic activation. In its present format, therefore, the test for colonic adaptation cannot be used to demonstrate direct bacterial embedding with VSL3.

Adaptation, Physiological↗

Deadaption and readaptation with lactose, but no cross-adaptation to lactulose: a case of occult colonic bacterial adaptation.

The standard 3 h breath hydrogen (3hBH2) test distinguishes lactose maldigesters from lactose digesters. However, multiple factors impact on BH2 and care is needed to exclude a priori variables. When these factors are controlled, a negative BH2 test implies lactase persistent status or lactase nonpersistent status with colonic adaptation. A case of a Sicilian man who tested negative (lactase persistent status confirmed) on an initial 50 g lactose challenge is described. It was observed that he consumed 28.1 g lactose/day before testing. He subsequently underwent five additional challenge tests in the course of the next 10 months. In four tests the dose intake of lactose was varied upon instruction, and in the fifth test a 30 g lactulose challenge was carried out. It was demonstrated that on radically decreasing lactose intake, a full lactase nonpersistent status was unmasked. Output of 3hBH2 varied inversely with daily lactose intake. Finally, at a time when he was readapted to lactose, there was no discernible adaptation to lactulose challenge. It was concluded that 'occult' colonically adapted subjects may contribute to negative BH2 tests. There is a relationship between variation in lactose intake and the results of BH2 testing. Finally, there was no cross-adaptation to lactulose challenge when lactose was used as the adapting sugar.

Adaptation, Physiological↗

Diminished efficacy of colonic adaptation to lactulose occurs in patients with inflammatory bowel disease in remission.

Lactulose has been proposed to be beneficial in treating inflammatory bowel disease (IBD). The hypothesis is based on the prebiotic potential of lactulose. A practical approach to testing its usefulness is to determine colonic adaptation to tolerable doses in patients with IBD. Our objective was to determine if a 3-week course of lactulose will decrease BH2 and symptoms in response to an acute lactulose challenge test in control subjects and IBD patients. The design was a prospective cohort study. Subjects were given a 30-g lactulose challenge test (test 1), and then ingested 10 g of lactulose twice a day for 3 weeks before being retested (Test 2). A third test was given after a further 5-week washout period. The main outcomes were the change in 4-hr sum of BH2 (sum(4HrBH2)) values obtained every 30 min, peak BH2, and 4-hr sum of symptom score (sum(4HrSS)) during the lactulose challenge test. In addition, we also report the change in self-reported symptoms and diarrhea during the 3-week administration of lactulose. In controls, sum(4HrBH2) decreased from test 1 (380.5 +/- 56.6 ppm) to test 2 (288.6 +/- 57.4 ppm) (P < 0.05), and returned toward test 1 levels by test 3 (307.5 +/- 53.1, P > 0.5). Unlike controls, the sum(4HrBH2) in patients failed to achieve significance between test 1 (444.5 +/- 55.8 ppm), test 2 (366.5 +/- 80.7 ppm, P > 0.2) or test 3 (411.6 +/- 62.5 ppm, P > 0.2). Sum(4HrSS) results in controls followed a pattern similar to sum(4HrBH2), achieving significance only in test 2 (P < 0.02). Symptoms during the intertest periods decreased by the third week in controls (P < 0.05), but not in patients (P > 0.5). Symptoms were lower in patients and varied insignificantly both in challenges and intertest periods. In conclusion, although controls adapt to a 3-week period of lactulose ingestion, IBD patients fail to meet the criteria for adaptation. However, longer studies may be needed to establish whether IBD patients are slower to adapt.

Adaptation, Physiological↗