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T H Iqbal

Publications and source records attributed to T H Iqbal.

18 recordsLinked to original sources
PubMed2005

Coeliac disease in South Asians resident in Britain: comparison with white Caucasian coeliac patients.

BACKGROUND: The catchment population of our hospital is ethnically diverse and we have seen a number of patients of South Asian origin with coeliac disease. We have suspected that there are differences compared with white Caucasian coeliacs, especially with respect to iron-deficiency anaemia and vitamin D deficiency at presentation. AIMS: To compare the clinical and laboratory features of South Asian adult coeliac patients with adult white Caucasian coeliacs. METHODS: We reviewed the notes of patients attending the adult coeliac clinic over the past 10 years. All patients were older than 16 years at diagnosis. There were 40 South Asians and 90 white Caucasians. Symptoms, haematology, biochemistry, endomysial antibody status, HLA alleles and small bowel histology at presentation were compared between the two racial groups. RESULTS: There were significant differences between the racial groups. South Asians were younger at presentation than the Caucasian patients (mean age 27 years compared with 47 years respectively, P<0.0001); they were less likely to have 'irritable bowel syndrome' symptoms (P<0.01), but more likely to have features of vitamin D deficiency (P<0.03). Their haemoglobin (P<0.05), mean cell volume (P<0.0004), serum iron (P<0.01), transferrin saturation (P<0.05), serum 1,25-dihydroxyvitamin D3 (P<0.002), and levels were lower, while serum alkaline phosphatase levels were higher (P<0.04) than in white Caucasian coeliac patients. There were no differences with respect to serum folate, vitamin B12, serum calcium, alanine aminotransferase and small bowel histology. IgA class endomysial antibody positivity was similar in the two groups (88.5% for South Asians compared with 73.5% for white Caucasians). White Caucasian patients were significantly more likely to be DQ2-positive than the South Asian patients (97.2% compared with 83.3%, P=0.02). CONCLUSION: South Asians with coeliac disease are less likely to present with 'irritable bowel syndrome' symptoms, but more likely to have features of vitamin D deficiency and iron deficiency, and have a higher alkaline phosphatase than white Caucasians. The differences in HLA alleles seen in South Asians with coeliac disease compared with white Caucasian patients suggests that among the South Asians, non-HLA regions may play a stronger role in disease susceptibility and presentation.

Adolescent↗
PubMed1999

Reduced cadherin/catenin complex expression in celiac disease can be reproduced in vitro by cytokine stimulation.

Celiac disease is characterized by a chronic immune response to dietary gluten, in which T cell responses result in elevated mucosal levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, interferon (IFN)-gamma, and transforming growth factor (TGF)-beta, which induce profound mucosal remodeling associated with increased enterocyte proliferation, apoptosis, and migration. Reduced intestinal expression of the morphoregulatory cell adhesion molecule E-cadherin, which forms complexes with beta-catenin, can increase enterocyte proliferation and migration. However, its mechanism of action in gastrointestinal inflammatory conditions and any involvement in celiac disease is unknown. In this study, we describe changes in E-cadherin and beta-catenin expression in celiac disease tissue and determine the effect of cytokines on their expression in an in vitro model. We assessed E-cadherin and beta-catenin expression in intestinal biopsies from 24 patients with celiac disease, 12 patients with treated celiac disease, and 10 healthy patients by immunohistochemistry, Western blotting, and confocal microscopy. Using Caco-2 cells, we examined the effect of TNF-alpha, IL-1, IFN-gamma, and TGF-beta on E-cadherin expression. E-cadherin transcription was assessed in both intestinal biopsies and Caco-2 cells by in situ hybridization and RT-PCR, respectively. A marked reduction in protein expression of E-cadherin and beta-catenin that returns to normal levels after treatment was observed in celiac disease; this reduction was associated with reduced levels of E-cadherin mRNA. E-cadherin expression in Caco-2 cells was significantly reduced after TNF-alpha, IL-1, and IFN-gamma stimulation. The effect of TNF-alpha on E-cadherin expression was maximal after stimulation for 48 hours and also induced modest reductions in beta-catenin expression. The action of TNF-alpha on E-cadherin was reversible and was shown to act at the transcriptional level. These results demonstrate the novel findings that E-cadherin and beta-catenin expression are reversibly down-regulated in celiac disease and that such changes in epithelial cadherin/catenin complexes may be mediated by cytokines acting on cadherin transcription.

Base Sequence↗
PubMed1998

Continuous treatment with omeprazole 20 mg daily for up to 6 years in Barrett's oesophagus.

BACKGROUND: Because of the malignant potential of Barrett's oesophagus, an aim of treatment is to cause the columnar epithelium to regress. A logical approach is to decrease acid reflux which is an important aetiological factor in Barrett's oesophagus. Treatment with omeprazole 20-80 mg over 1-3 years has yielded conflicting but largely disappointing results. AIM: To determine if treatment of Barrett's oesophagus with omeprazole 20 mg daily for up to 6 years can cause regression of the Barrett's epithelium. PATIENTS AND METHODS: Forty-seven patients with Barrett's oesophagus were treated in an open prospective study. Nine patients were treated for 2 years, 12 for 3 years, 10 for 4 years, eight for 5 years and eight for 6 years. Patients were endoscoped at 1-2-year intervals and endoscoped at the end of the treatment period. RESULTS: No significant shortening of the length of the Barrett's segment was seen during any treatment period, although omeprazole controlled reflux symptoms and was well tolerated. Macroscopic squamous islands appeared in 55% of patients, mostly in the first 2-3 years although in five patients they appeared later in treatment. CONCLUSION: Treatment of Barrett's oesophagus with omeprazole 20 mg daily for periods of up to 6 years did not cause regression in the length of the Barrett's segment, but it did lead in over half of the patients to partial re-epithelialization in the form of squamous islands.

Adult↗
PubMed1998

Lactase haplotype frequencies in Caucasians: association with the lactase persistence/non-persistence polymorphism.

A genetic polymorphism is responsible for determining that some humans express lactase at high levels throughout their lives and are thus lactose tolerant, while others lose lactase expression during childhood and are lactose intolerant. We have previously shown that this polymorphism is controlled by an element or elements which act in cis to the lactase gene. We have also reported that 7 polymorphisms in the lactase gene are highly associated and lead to only 3 common haplotypes (A, B and C) in individuals of European extraction. Here we report the frequencies of these polymorphisms in Caucasians from north and south Europe and also from the Indian sub-continent, and show that the alleles differ in frequency, the B and C haplotypes being much more common in southern Europe and India. Allelic association studies with lactase persistence and non-persistence phenotypes show suggestive evidence of association of lactase persistence with certain alleles. This association was rather more clear in the analysis of small families, where haplotypes could be determined. Furthermore haplotype and RNA transcript analysis of 11 unrelated lactase persistent individuals shows that the persistence (highly expressed) allele is almost always on the A haplotype background. Non-persistence is found on a variety of haplotypes including A. Thus it appears that lactase persistence arose more recently than the DNA marker polymorphisms used here to define the main Caucasian haplotypes, possibly as a single mutation on the A haplotype background. The high frequency of the A haplotype in northern Europeans is consistent with the high frequency of lactase persistence.

Alleles↗
PubMed1997

An analytical method for the quantitation of mannitol and disaccharides in serum: a potentially useful technique in measuring small intestinal permeability in vivo.

An electrochemical-HPLC method for the determination of mannitol and lactulose is presented which may facilitate routine testing of intestinal permeability by requiring only a single blood sample instead of a 6-hour urine collection. Chromatographic conditions are described which allow separation of the closely related sugars lactulose and the dietary disaccharides lactose and sucrose. Preliminary results in normal controls and patients with untreated coeliac disease are presented.

Adult↗
PubMed1996

Small intestinal lactase status, frequency distribution of enzyme activity and milk intake in a multi-ethnic population.

The aims of the study were to investigate the prevalence of primary lactase deficiency, frequency distribution of lactase activity and the relationship between lactose intake and lactase activity in three ethnic groups resident in Birmingham. Seventy-two white, 103 Indian and 58 Afro-Caribbean adult dyspeptic patients had distal duodenal biopsies taken for disaccharidase assay at endoscopy. Ten percent of whites, 51% Indians and 81% Afro-Caribbeans had primary lactase deficiency (sucrase/lactase ratio > 4). There was a generalized unexplained depression of disaccharidase activities in the Indians. Frequency distribution of lactase activity for the whole population showed a negative skew without evidence of trimodality. Lactose intake and symptoms attributed to lactose were assessed in a subgroup of 20 whites, 20 Indians and 18 Afro-Caribbeans by questionnaire. Lactose intake did not differ between lactase persistent and deficient subjects both within each racial group and between the groups. Diarrhoea, bloating and cramps were not significantly more common in lactase deficient than lactase persistent individuals.

Journal Article↗
PubMed1996

Small intestinal permeability to mannitol and lactulose in the three ethnic groups resident in west Birmingham.

BACKGROUND/AIMS: Asymptomatic residents of tropical countries have differences in small intestinal morphology and permeability compared with residents of temperate zones. The aim of this study was to investigate small intestinal permeability and morphology in three ethnic groups resident in Birmingham, UK. METHODS: 28 white patients, 101 Indian (Indian subcontinent), and 49 Afro-Caribbean adult patients with dyspepsia had endoscopic distal duodenal biopsies and a hyperosmolar lactulose/mannitol permeability test. Twenty normal white subjects had the permeability test. RESULTS: Lactulose/mannitol excretion ratios (LMER) were: white subjects 0.022 (median), white patients 0.022, Indians 0.031, Afro-Caribbeans 0.033. Differences between the immigrant groups and the two white groups were significant (p < 0.001); 33% of Indians and 45% of Afro-Caribbeans had LMER outside the range of the white groups. Afro-Caribbeans born in the UK had significantly lower LMER than those born abroad (p < 0.05); a similar trend was seen in Indians. Villous height/mucosal thickness ratios, calculated from small intestinal biopsy specimens, were lower in the immigrant groups and correlated inversely with LMER (r = 0.28; p < 0.05). Time resident in the tropics also correlated inversely with LMER. CONCLUSIONS: There were significant differences in small intestinal permeability and morphology between immigrants resident in a Western country and the native white population. The data suggested that these differences were related to environmental factors.

Adolescent↗
PubMed1995

Effect of water-loading on the performance of polyethylene glycol as a marker of small intestinal permeability.

1. Polyethylene glycol has been used extensively to measure small intestinal permeability in vivo. However, polyethylene glycol seems to traverse the intestinal mucosa in much greater quantities than sugar molecules of equivalent M(r). In addition, the recovery of the lowest M(r) polymers of administered polyethylene glycol has been found to be both low and unreliable. 2. To compare the behaviour of a range of polyethylene glycol polymers with sugar probes in vivo, a combined polyethylene glycol/mannitol/lactulose probe was administered sequentially to healthy individuals in the fasted state and under conditions of water-loading. Timed hourly urine collections were made for 6 h. 3. Mannitol and lactulose recoveries were all within the normal range and were unaffected by co-administration of water. The lactulose/mannitol recovery ratios did not vary significantly over the 6 h collection period. In contrast, the recovery of total polyethylene glycol was significantly greater when subjects were water-loaded. Furthermore, proportionally greater quantities of polyethylene glycol M(r) 370 than M(r) 854 were recovered towards the end of the collection period than at the start. 4. Our results show that, in contrast to lactulose and mannitol, excretion of low-medium M(r) polyethylene glycol polymers is highly dependent on co-administration of water. Furthermore, the differential rate of excretion of the low compared with the high M(r) polyethylene glycol polymers suggests that the volume of distribution of the individual polymers may vary with M(r), and smaller polyethylene glycol molecules may undergo considerable renal tubular reabsorption.

Adult↗
PubMed1995

Long term continuous omeprazole treatment of patients with Barrett's oesophagus.

BACKGROUND: The metaplastic columnar epithelium in Barrett's oesophagus has malignant potential. AIM: To determine whether decreasing acid reflux leads to regression of Barrett's epithelium. METHOD: Twenty-four patients with Barrett's oesophagus were treated with omeprazole 20 mg o.m. in an open, prospective study; 11 were treated for 12 months, and 13 for 24 months. Another group of 17 patients with Barrett's oesophagus was treated with an H2-receptor antagonist in standard dosage for 12-36 (mean 23) months. Patients were assessed endoscopically. RESULTS: No evidence of significant shortening of the length of Barrett's oesophagus was seen in any patient treated for 12 or 24 months with omeprazole. Similarly, no shortening of the length of Barrett's oesophagus was seen in any patient treated with an H2-receptor antagonist. However, 6 of 11 patients treated with omeprazole for 12 months, and 7 of 13 treated for 24 months, developed macroscopic squamous islands visible below the squamo-columnar junction. This was not seen in any patient treated with an H2-receptor antagonist. CONCLUSION: Although there can be reappearance of squamous epithelium in Barrett's oesophagus of some patients during treatment with omeprazole 20 mg o.m. over 12-24 months, a significant shortening of the columnar lined segment is not seen.

Adult↗
PubMed1995

Symptomatic cardiomyopathy as a presentation in Whipple's disease.

A patient presenting with congestive cardiac failure and anaemia underwent investigation which led to the diagnosis of Whipple's disease, associated with dilated cardiomyopathy. Conventional antibiotic therapy for Whipple's disease resulted in resolution of the traditional features of Whipple's disease and a marked improvement in the patient's heart failure.

Aged↗
PubMed1994

Phytase activity in the human and rat small intestine.

Phytate is the major storage form of phosphorus in seeds and so is a common dietary constituent. Excessive ingestion of undegraded phytates can cause mineral deficiencies in humans. In addition, phytic acid is antineoplastic in animal models of both colon and breast carcinoma. There have been no previous studies quantifying phytase activity in the human small intestine although it is present in animals. Small intestinal phytase and alkaline phosphatase activity and distribution was measured in vitro in mucosal homogenates from two human small intestinal specimens obtained from transplant donors. Rat intestine was also studied for comparison. Phytase activity was found in human small intestine at low values (30 times less than that in rat tissue and 1000-fold lower than alkaline phosphatase in the same tissue). The activity was greatest in the duodenum and lowest in the ileum. In conclusion, the normal human small intestine has very limited ability to digest undegraded phytates. Although this may have adverse nutritional consequences with respect to metabolic cation imbalances, the presence of undigested phytate in the colon may protect against the development of colonic carcinoma.

6-Phytase↗
PubMed1993

Diffusion of polyethylene glycol-400 across lipid barriers in vitro.

1. Polyethylene glycol has been used extensively as a probe to measure passive small-intestinal permeability in vivo. However, there has been some uncertainty as to its suitability for use as an indicator of the permeation of water-soluble molecules across the intestinal wall because it seems to traverse the mucosa in much greater quantities than sugar molecules of equivalent M(r). 2. We have measured the permeation of polyethylene glycol-400 and lactulose from aqueous solution across pure lipid solvents in vitro. We found considerable transport of polyethylene glycol-400 across chloroform (1.03 g h-1 m-2) but no movement across petroleum ether. 3. However, in a separate experiment in which phospholipid (egg lecithin) was dissolved in the petroleum ether, permeation of polyethylene glycol-400 did occur (0.13 g h-1 m2), implying interaction of polyethylene glycol-400 with the phospholipid. No permeation of lactulose was seen in any of the experiments. 4. Our results suggest that, because of its interaction with lipid solvents, polyethylene glycol-400 is unsuitable as a probe to measure passive intestinal permeability in vivo.

Diffusion↗
PubMedDate not supplied

Ethnic differences in cirrhosis of the liver in a British city: alcoholic cirrhosis in South Asian men.

AIMS AND METHODS: We studied the ethnic origin of cirrhotic patients retrospectively over the 14-year period 1987-2000 and compared the ethnic make-up of the cirrhotic patients with the ethnic make-up of the local catchment population. RESULTS AND CONCLUSIONS: Of 381 cirrhotics, 64.1% were white, 29.1% South Asian, 4.7% Afro-Caribbeans and 2.1% other races. These proportions were different from those of the local community in that South Asians were over-represented and Afro-Caribbeans were under-represented. Alcohol was the commonest cause of cirrhosis (60.9%) and South Asian non-Moslem males with alcoholic cirrhosis were over-represented and were younger at diagnosis than white alcoholic cirrhotics.

Adult↗