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Biomedical subjects

A Szilagyi

Publications and source records attributed to A Szilagyi.

At least 19 recordsLinked to original sources

There is no difference in the disease severity of gastro-oesophageal reflux disease between patients infected and not infected with Helicobacter pylori.

BACKGROUND: The role of Helicobacter pylori in gastro-oesophageal reflux disease (GERD) is controversial. AIM: To compare the severity of GERD in infected vs. non-infected patients, as part of an ongoing randomized controlled trial that examines the impact of H. pylori eradication on GERD-related outcomes. METHODS: Consecutive GERD patients underwent urea breath testing and completed validated GERD symptom severity, and quality of life questionnaires as well as, 24-h pH-metry. These parameters, as well as demographics and endoscopic findings were assessed in double-blinded fashion and compared between H. pylori-infected and non-infected subjects. RESULTS: Helicobacter pylori-infected GERD patients (n=50) were significantly older and less educated than non-infected patients (n=51). They also used proton pump inhibitors less often but had no difference in symptoms (as measured with both the Spechler's Activity Index and the Gastrointestinal Symptom Rating Scale), quality of life, endoscopic findings or 24-h pH-metry findings. CONCLUSION: This prospective, double-blind study demonstrates, using excellent GERD quantifying measures including validated symptom severity scores, endoscopy, and 24-h pH-metry, that there exist no clinically significant differences in clinical or laboratory-related GERD manifestations between H. pylori-infected and non-infected GERD patients.

Adolescent↗

Review article: lactose--a potential prebiotic.

Lactose maldigestion, which affects a large majority of the world's population, has been mostly linked with uncomfortable symptoms. In addition, dairy consumption is variably blamed or recommended for a number of ill effects. There is, however, emerging evidence that certain lactic acid-producing bacteria, which selectively consume prebiotics, may be beneficial against some lower intestinal diseases. Lactose maldigestion and lactose should perhaps be re-evaluated as a potential provider of such a prebiotic. This historical and observational review discusses lactose and argues the opinion that it has prebiotic potential. Moreover, in maldigesters, natural ingestion or lack thereof may be relevant in the pathogenesis of diseases such as colorectal cancer and inflammatory bowel diseases.

Dairy Products↗

Improved parameters of lactose maldigestion using lactulose.

Lactulose is a disaccharide derived from lactose. There has been recent rekindling of interest in the possible benefits of pro- and prebiotics: mainly, lactic acid-producing bacteria and lactulose for the lower intestine. Since lactose maldigestion is a common genetic trait, we undertook this study to delineate similar effects between these two disaccharides. Nine healthy lactose maldigesting subjects underwent two separate periods of three weeks adaptation, first with 10 g twice daily lactulose and then 1.5 g twice daily lactose (in milk). Adaptation was defined by reduced breath Hydrogen (BH2) and symptoms after 50 g lactose challenges. In six subjects fecal beta-galactosidase was measured. All subjects consumed some lactose daily. In the first period, eight subjects improved symptoms and reduced BH2 significantly, while in the second period they did not. Fecal beta-galactosidase significantly increased after lactulose. This study supports the notion that lactulose and lactose may have similar clinical effects.

Adaptation, Physiological↗

Systematic review: the use of somatostatin or octreotide in refractory diarrhoea.

BACKGROUND: Somatostatin and octreotide have multiple effects which make them ideal for treating diarrhoea of different aetiologies. Their use in a variety of conditions with refractory diarrhoea, however, is based on a limited number of studies. AIM: We undertook a systematic review of the available English literature to maximize an evidence-based approach to the treatment of refractory diarrhoea. We tested the hypothesis that efficacy is independent of aetiology. METHODS AND RESULTS: A Medline and individual article search from 1965 to 2000 was undertaken on the use of somatostatin and octreotide in diarrhoea. All reports containing at least five subjects were included. The percentage response in case series and randomized controlled trials was compared, and a meta-analysis of randomized controlled trials where patient level data were provided was carried out. There were 30 publications found (18 case series, 12 randomized controlled trials). The response percentage was 73% overall in case series and 64% in randomized controlled trials (not significant). A meta-analysis of nine randomized controlled trials revealed significant heterogeneity despite an overall relative risk of 0.5 (95% confidence interval, 0.27-0.91). Subgroup analysis of the largest aetiological groups showed that acquired immunodeficiency syndrome studies were homogeneous, but somatostatin and octreotide were less effective. Post-chemotherapy studies remained heterogeneous and somatostatin and octreotide were highly effective. CONCLUSIONS: While this review strengthens the consensus guidelines on the use of somatostatin and octreotide for refractory diarrhoea, evidence-based support requires additional studies.

Antidiarrheals↗

Improvement of perinatal outcome in diabetic pregnant women.

Obstetrical and perinatal outcomes in newborns of diabetic pregnant women depend on metabolic control and fetal surveillance during pregnancy. The effects of fetal surveillance on perinatal mortality and morbidity was analyzed in diabetic pregnant women with appropriate glucose control in our regional center for diabetes and pregnancy. 480 deliveries complicated by frank or gestational diabetes occurred in our Department in the period of 1988-1999. Perinatal mortality and morbidity, prevalence of premature deliveries, methods of fetal surveillance, options for respiratory distress syndrome (RDS) profilaxis, cesarean section rate, timing of delivery and its indications and occurrence of malformations have been analyzed. It was found that malformation rate and perinatal mortality may be reduced to even lower level than that of in healthy pregnant women by appropriate glucose control and by using the latest methods of intrauterine fetal surveillance including cardiotocography (non stress test and oxytocin challenge test), doppler fetal artery velocimetry and fetal pulse oximetry. Timing of delivery was needed in 35% of the cases with IDDM and 15% of gestational diabetes due to chronic placental insufficiency. If labour induction was needed before the 38 weeks, amniocentesis was performed to test fetal lung maturity. Direct fetal glucocorticoid administration was used to enhance fetal lung maturation in 14 cases. C-section rate was slightly higher than that of in non diabetic pregnant women. Our perinatal morbidity data (macrosomia, hyperbilirubinemia, hypoglycemia, injuries, infections) are comparable with the data from the literature. Although perinatal mortality with the help of thorough fetal surveillance is even better in diabetic pregnant women than in non diabetic patients, future eye should be focused on factors affecting perinatal morbidity, because it is still higher than in newborns of healthy mothers.

Cesarean Section↗

Use of interferon for prevention of hepatocellular carcinoma in cirrhotic patients with hepatitis B or hepatitis C virus infection.

The incidence of hepatocellular carcinoma in North America is increasing. Current debate focuses on whether interferon administered to cirrhotic patients-with or without biochemical or virologic response-delays or prevents cancer of the liver. Review of the literature revealed several studies that showed improvement in or delay in progression of histologic fibrosis in patients with hepatitis C virus (HCV) infection. In patients with hepatitis B virus (HBV) infection, conversion to the nonreplicative stage may be associated with histologic improvement. However, only 11 studies (6 of HCV, 3 of HBV, and 2 of HCV and HBV) compared development of hepatocellular carcinoma in interferon-treated patients with cirrhosis and cirrhotic patients who were not treated with interferon. Although no firm statistical conclusions could be drawn, the literature suggests that interferon therapy may prevent hepatocellular carcinoma in patients with cirrhosis, particularly those infected with HCV. Interferon treatment cannot be recommended for all persons with cirrhosis and HBV or HCV infection because the current evidence is only suggestive. Long-term randomized, controlled trials may provide definitive data; however, it will be difficult, if not impossible, to conduct such trials because of the improved efficacy of combination therapy with interferon and ribavirin in patients with chronic HCV infection and the development of new therapies for patients with HBV infection.

Antineoplastic Agents↗

Altered colonic environment, a possible predisposition to colorectal cancer and colonic inflammatory bowel disease: rationale of dietary manipulation with emphasis on disaccharides.

A recurrent theme in the schema of pathogenetic mechanisms attributed to colorectal cancer (CRC) and inflammatory bowel disease (IBD) is the interaction between genes and environment. Dietary and other environmental factors, and lower intestinal flora and their chemical interactions occur in the pathogenesis of both. Events at the mucosal surface may be influenced by factors in the luminal environment and by contributions of the host. In addition, both forms of IBD--Crohn's disease (CD) and ulcerative colitis (UC)--have distinctive associated host events. Even within CD and UC, different clinical patterns and prognoses may have different specific host mechanisms. Some of the current putative pathogenetic processes in CRC and IBD are reviewed. Particular attention is given to hypotheses relating to the role of dietetic substances, mainly fibre and dairy products, and how they may affect disease formation. It is argued that within the context of hypotheses proposed for possible beneficial effects of these two dietetic factors, CRC and IBD may be considered together. Further support is lent to arguments that similar and additional hypothetical features ascribed to beneficial effects of fibre may be attributed to disaccharides, lactose and its derivatives, lactulose and lactitol.

Causality↗

Sequence and homology model of 3-isopropylmalate dehydrogenase from the psychrotrophic bacterium Vibrio sp. I5 suggest reasons for thermal instability.

The leuB gene from the psychrotrophic strain Vibrio sp. I5 has been cloned and sequenced. The gene codes for 3-isopropylmalate dehydrogenase, a 360-residue, dimeric enzyme involved in the biosynthesis of leucine. Three recently solved homologous isopropylmalate dehydrogenase (IPMDH) crystal structures from thermophilic and mesophilic organisms have been used to build a homology model for the psychrotrophic IPMDH and to deduce the possible structural reasons for its decreased thermostability. According to our model the psychrotrophic IPMDH contains fewer stabilizing interactions than its mesophilic and thermophilic counterparts. Elements that have been identified as destabilizing in the comparison of the psychrotrophic, mesophilic and thermophilic IPMDHs are a smaller number of salt-bridges, a reduction in aromatic-aromatic interactions, fewer proline residues and longer surface loops. In addition, there are a number of substitutions of otherwise strictly conserved residues that can be linked to thermostability.

3-Isopropylmalate Dehydrogenase↗

Adverse reactions to food constituents: allergy, intolerance, and autoimmunity.

Food allergies and intolerance represent important health concerns to consumers who are predisposed to these illnesses. Unlike many current food safety issues, food sensitivities are complicated by both complex and multiple individual adverse reactions, which can vary from emotional to pathophysiological ailments. In some instances, the underlying mechanisms that result in the development of food allergies or intolerance have marked differences but produce common symptoms. The present-day diagnosis of these disorders can be impeded by intrinsic limitations in generating accurate information from patient history and biochemical, physicochemical, and immunochemical tests. Oral challenge tests represent effective methods for confirming and testing food allergens and food intolerance; however, these procedures are often restricted to clinical trials. It is important to be able to distinguish among food allergy, intolerance, and autoimmune disease in the management of these disorders. The role of food in the development of autoimmune disease may be exemplified by celiac disease, a food-induced enteropathy, requiring exposure to prolamins in wheat, rye, and barley. Various wheat and soy protein sources, including the soy protein isolates used to make infant formulas, have been related to juvenile or insulin-dependent diabetes mellitus (IDDM), a common chronic disease of childhood. Employing food process technologies to eliminate food constituents with potential for intolerance in some individuals is a potentially viable approach for reducing risk to food-related disorders. Finally, the development of food labelling regulations that require the identification of potential food allergens or agents for intolerance in the ingredient declaration on prepackaged food is a positive step toward the prevention of severe adverse reactions in hypersensitive individuals.

Animals↗

Influence of loperamide on lactose handling and oral-caecal transit time.

BACKGROUND: The influence of pharmacologically prolonged oral caecal transit time on lactose handling is examined in the wake of finding improved lactose handling during naturally occurring prolonged oral-caecal transit time. METHODS: Sixteen normal male volunteers with lactose maldigestion were pretreated with 8 and 12 mg loperamide on different days and lactose handling was compared by measuring areas under the curve during lactose breath H2 testing (3 h). The oral-caecal transit time was similarly measured using lactulose and exhaled breath H2. Symptom scores were recorded and, in three subjects, blood sugar was simultaneously measured. RESULTS: The mean +/-S.E.M. baseline oral-caecal transit time was 56.9 +/- 5.9 min. Loperamide significantly prolonged oral-caecal transit time (90.3 +/- 11.1 and 82.1 +/- 13.9 min for 12 and 8 mg loperamide, respectively; P < 0.05). The lactose breath H2 area under the curve with 12 mg loperamide was significantly less than at baseline (7685 +/- 985.6 vs. 10243.1 +/- 1607, respectively; P < 0.05). Significantly fewer symptoms were recorded with both doses of loperamide during the 3 h test but with 12 mg loperamide only on follow-up. There was no significant rise in blood sugar at any time in the three subjects studied. CONCLUSIONS: Loperamide-induced graded prolongation of oral-caecal transit time is associated with significantly improved lactose handling as measured by a reduction of the area under the curve. Symptoms of lactose intolerance may also be improved with loperamide. Prolongation of oral-caecal transit time with loperamide may be useful as adjunctive or primary therapy of carbohydrate intolerance in patients with rapid transit.

Administration, Oral↗

Caco-2 cell disaccharidase activities are unaffected by gestational hormones.

We previously reported that lactose handling was significantly improved during late-phase pregnancy in women with a genetically determined adult-type hypolactasia. However, the adaptive mechanisms underlying the enhanced lactose digestion during pregnancy are not clear. Progesterone therapy has been associated in animals with increased intestinal lactase activity. To investigate the potential role of progesterone and estrogen as modulators of human lactase activity during pregnancy, we employed the human-derived intestinal epithelial Caco-2 cell line. Measurements of lactase and sucrase activities were performed in parallel with DNA content in progesterone- and estrogen-treated cells after 5, 10, and 30 days of confluency. Caco-2 monolayer DNA content was observed to increase with duration of culture to an equivalent extent in both hormone-treated and control cultures. Lactase and sucrase activities were similarly unaltered by incubation with either progesterone or estrogen, at any time point tested. These data demonstrate that gestational hormones do not influence intestinal cell number nor disaccharidase activity in Caco-2 cells, at the doses tested. Although these studies were carried out in a malignant cell line, our data suggest that the improved lactose handling observed during pregnancy is probably related to prolonged intestinal transit.

Caco-2 Cells↗

Determinants of prolonged oral cecal transit time during late phase pregnancy.

We examined the course of delayed oral cecal transit time (OCTT) and the impact of different variables in late pregnancy. Thirty-three women in late trimester were evaluated and 29 were re-tested post partum. Results were compared with 17 controls. A breath hydrogen test was used to measure OCTT. The impact of 3 demographic and 5 biochemical parameters was evaluated. Oral cecal transit time (99.2 +/- 7.8 min) during pregnancy was significantly prolonged compared both with controls (63.5 +/- 8.7 min) (p = 0.0042) and post partum (68.5 +/- 6.4 min) (p < 0.002). However, 40% during pregnancy had a normal OCTT. Post partum, 8 (29.6%) continued to have delayed OCTT. Serum free T4 levels were significantly lower than in controls (p < 0.0001) and post partum (p < 0.001), but did not correlate with OCTT. Gravidity rank correlated with OCTT (p = 0.022). By multivariate analysis, only 17% of the observed variability during pregnancy could be explained by these parameters. In controls, a formula including progesterone and gastrin levels was significant in explaining 54.7% of variability. Application of both formulae to post-partum returnees overpredicted OCTT; however, the one from pregnancy was more accurate. We conclude that in pregnancy multiple factors account for delayed OCTT and these may be different from controls and post partum. Pregnancy may still influence OCTT post partum.

Adult↗

Lactose handling by women with lactose malabsorption is improved during pregnancy.

OBJECTIVE: To evaluate lactose handling among women in late pregnancy and post partum to determine whether lactose handling is altered in pregnancy. DESIGN: Prospective study of lactose intolerance among pregnant women with and without lactose malabsorption. SETTING: Gastroenterology service of the Sir Mortimer B. Davis-Jewish General Hospital, Montreal. PATIENTS: Thirty-three pregnant women, of whom 18 had lactose malabsorption, 12 did not and 3 were excluded. OUTCOME MEASURES: Lactose breath hydrogen (BH2) concentration after ingestion of lactose or lactulose; comparison before and after delivery of area under the curve (AUC) for lactose, oral-cecal transit time (OCTT) for lactulose, lactose-BH2-derived transit time and estimated dietary lactose consumption. RESULTS: After weaning (at a median time of 9 months after delivery), 28 of the women returned for follow-up. Of the 12 who could absorb lactose before delivery, 4 could no longer absorb lactose. Of the other 16 women, lactose intolerance worsened in 12, remained the same in 2 and improved in 2. The AUC was greater (p < 0.005), the maximal BH2 concentration was higher (p = 0.004) and the number of women whose BH2 concentration peaked was fewer (p < 0.025) post partum than before delivery. The women's symptoms during and after lactose BH2 tests were also greater post partum. The OCTT (based on the lactulose BH2 test) was shorter post partum (p = 0.001). Transit time derived from lactose BH2 tests was also shorter, but not significantly so. The OCTT was not inversely correlated with the change in AUC before and after delivery, but the lactose-BH2-derived transit time was inversely correlated. Pregnant women consumed more lactose before delivery than afterward (p < 0.004). CONCLUSIONS: Women with lactose malabsorption handle lactose better than usual in late pregnancy. Slow intestinal transit and bacterial adaptation to increased lactose intake may be primarily responsible.

Breath Tests↗

Clinical and histopathological variation in hepatocellular carcinoma.

OBJECTIVES: To assess clinical and histopathological variation in hepatocellular carcinoma from different endemic zones and to relate such variation to current putative pathogenic mechanisms of carcinogenesis. METHODS: Review of pertinent English language articles with emphasis on regional differences as they relate to our objectives. RESULTS: Clinical presentation of hepatocellular carcinoma is variable in different endemic zones. Such different features may depend on the interaction of different etiological initiators and, probably, promoters that can lead to different genetic aberrations. Similarly, there also may be histopathological variation. However, it is difficult to clearly delineate such differences, in part, because of lack of uniformity in reporting interpretation of histological data in the literature. And, the ethnic origin of patients is not always noted in middle and low endemic zones of hepatocellular carcinoma. CONCLUSIONS: Distinction in clinical and histopathological variation in hepatocellular carcinoma may benefit from delineating the ethnic origin of subjects included in studies and from adoption of clear uniform terminology for benign, indeterminate, and malignant lesions.

Carcinoma, Hepatocellular↗

Episodic thyrotropin (TSH) and prolactin (PRL) secretion during aging in postmenopausal women.

While aging is known to decrease episodic thyrotropin (TSH) secretion in men, no detailed information is available as to age-related alterations in the TSH and prolactin (PRL) release patterns in postmenopausal women (PMW). Accordingly, we compared the TSH and prolactin (PRL) secretory profiles of 6 euthyroid younger PMW (mean age: 53.0 years) with those of 7 euthyroid older PMW (mean age: 80.4 years). In all PMW, blood samples were obtained at 10 minute intervals for 10 hours for serial determinations of TSH and PRL by RIA. While thyroxine (T4) serum concentrations were not different in younger from older PMW, triiodothyronine (T3) levels markedly (p less than 0.05) decreased in older PMW. In both younger and older PMW, TSH and PRL were secreted episodically (by Cluster pulse algorithm), with considerable inter-individual variabilities in either study group. TSH and PRL pulse attributes (interpulse intervals, frequencies, amplitudes) were comparable in younger and older PMW, although a tendency of mean TSH to increase (p = 0.18) was noted for older PMW. Mean TSH and PRL serum concentrations were positively (r = 0.94, p less than 0.01) correlated in older, whereas not in younger PMW. These observations demonstrate that the pulse characteristics of episodic TSH and PRL secretion are preserved in PMW even of old age. However, in view of markedly decreased circulating T3 concentrations and of no substantial change in the TSH pulsatile secretion in older PMW, the negative feedback on the hypothalamic-pituitary unit may be impaired in elderly women.

Aged↗