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Biomedical subjects

F M Stevens

Publications and source records attributed to F M Stevens.

At least 37 records · Page 2Linked to original sources

Alpha 1-antitrypsin phenotypes in coeliac patients and a control population in the west of Ireland.

alpha 1 antitrypsin or protease inhibitor (Pi) phenotyping was carried out on 111 coeliac disease patients (CD) and 250 controls. The Pi MM phenotype was present in 95 (85.6%) of the coeliacs and 225 (90%) of the controls. The groups did not differ significantly with regard to Pi phenotypes. In the CD group the Pi Phenotype did not relate to HLA B8 or DR3 status. Associated diseases in the CD patients did not correlate with Pi phenotype.

Celiac Disease↗

HLA class II frequencies in celiac disease patients in the west of Ireland.

Restriction fragment length polymorphism analysis, using a single restriction enzyme TaqI-multiple-probe system for HLA-DRB1-DQB1 and -DQA1, was used to determine HLA-DR and -DQ frequencies in 56 unrelated celiac patients and 47 unrelated controls from the west of Ireland. In addition, HLA-DPB1 allelic frequencies were determined in the same group of patients and controls by using the technique of enzymatic DNA amplification of the polymorphic second exon of HLA-DPB1 genes in conjunction with sequence-specific oligonucleotide probing. The results suggest that HLA-DQ rather than HLA-DR is more important in conferring susceptibility to celiac disease. Furthermore, no association between HLA-DP and celiac disease was found in this study.

Adolescent↗

Evidence for a dominant gene mechanism underlying coeliac disease in the west of Ireland.

Although coeliac disease (CD) is strongly associated with the HLA alleles B8 and DR3, the genetic basis of this illness remains obscure. Recent studies show that at least two unlinked loci are involved. Most studies agree on recessivity at the HLA-unlinked locus but differ with respect to dominance or recessivity at the HLA-linked disease susceptibility locus. To address this controversy, we examined the association of CD with HLA in 39 families from the West of Ireland. Previous studies have shown that the prevalence of CD and the frequencies of the HLA antigens associated with it are higher in this population than in most others. Analysis of the data revealed a significant excess of concordant sib-pairs with two HLA haplotypes in common and an excess of discordant pairs with no haplotype in common. Chi-square tests confirmed a highly significant association between HLA-B8 and CD. Both heterozygotes and homozygotes for B8 had a significantly increased risk of CD. The risk for homozygotes was slightly higher than for heterozygotes, although not significantly so. The segregation ratio for disease occurrence among sibs of probands was estimated to be 0.185 when neither parent is affected. We estimated a gene frequency of 0.003 for the disease allele (C) at the HLA-linked locus and of 0.648 for the disease allele (d) at the HLA-unlinked locus. Assuming that CCdd homozygotes are always affected and that only carriers of C who are homozygous dd can be affected, the disease was found to be completely penetrant in Ccdd heterozygotes. These results support dominance at the HLA-linked locus conferring susceptibility to CD. Possible reasons for the discrepancy between the West of Ireland and other populations are discussed.

Alleles↗

Gm typing of Irish coeliac patients and controls does not help locate the "second" coeliac gene.

A two gene model has been proposed to explain the inheritance of coeliac disease (CD). One gene is on chromosome 6 in the MHC complex (HLA associated). It has been suggested the second gene is located on chromosome 14, in or near the region encoding for immunoglobulin heavy chain allotypes (Gm types). In a study of 102 unrelated Irish coeliacs and a group of ethnic controls, we have failed to show an association of CD with any particular Gm type or types. There is no evidence to confirm that a gene on chromosome 14 is implicated in the inheritance of CD.

Adolescent↗

Lung cavities in patients with coeliac disease.

The clinical, radiological and pathological features of 7 patients with coeliac disease (CD) who developed lung abscesses or cavities are described. These patients were seen during a 20-year period during which time approximately 600 coeliacs were seen and 50 died. Six of the coeliac patients with lung abscess died. The patients were middle aged. Staphylococcal infection, Klebsiella pneumoniae, bronchial carcinoma and previous pulmonary tuberculosis accounted for the cavities in 4 patients. In the 3 other patients a definite cause could not be identified. Hyposplenism and malnutrition were common. Next to malignancy pulmonary abscess was the commonest cause of death in the coeliac population. The development of respiratory symptoms should be regarded as a potentially serious and a life-threatening event in the middle-aged coeliac patients. Lung abscess should be added to the list of respiratory diseases associated with coeliac disease.

Adult↗

Ulcerative enteritis--atypical features.

A 40 year old man with two month history of vomiting and weight loss, was found to have multiple strictures in his small bowel. Investigations outruled known causes of small bowel ulceration, and the flat bowel mucosa did not respond to a gluten free diet. Treatment with steroids conferred a temporary benefit, however, small bowel ulceration persisted.

Adult↗

Non-attendance at outpatient clinics at the Regional Hospital, Galway, Ireland.

This paper examines the issue of non-attendance at outpatient clinics at the Regional Hospital, Galway, from the viewpoint of the patients who include both urban and rural residents. The results of a questionnaire survey of outpatients attending general and specialist medical and surgical clinics illustrate that very substantial costs are incurred and long periods of time are spent travelling by many patients. Females, and married females in particular, experience special difficulty in keeping appointments. Non-attendance increases as the cost of transport increases but many patients seriously underestimate the real cost of travel. Patients who have been attending over long periods of time have the worst record of non-attendance. It is recommended that any reorganisation of hospital outpatient systems in rural areas such as Western Ireland should take account of the particular needs of widely dispersed populations.

Adult↗

Decreasing incidence of coeliac disease.

Between 1960 and 1974 the incidence of coeliac disease in children under 12 years in County Galway remained fairly constant, but since 1975 it has fallen by 62% and the lowered incidence seems well established. The number of those who were breast fed and the age at which first gluten feeding took place during the 22 years both increased significantly and from the mid-70s total protein content and osmolarity of proprietary cow's milk formulas were reduced. All three factors may be relevant. A negative correlation with the incidence of gastroenteritis was found.

Age Factors↗

Compliance with gluten free diet in coeliac disease.

Fifty two children in whom coeliac disease was confirmed by persistent enteropathy while they were taking gluten were monitored to assess the effects of compliance with a gluten free diet (GFD). Between the ages of 17.8 and 18.5 years height (in 45 patients followed up for a mean of 14.9 years) and weight (in 43 followed up for a mean of 15.2 years) were significantly lower in those complying poorly with a GFD compared with those complying well. Of the 37 patients still attending the clinic after a mean of 25 years, having been followed up for a mean of 18.4 years, 16 who had complied well with the diet had normal or only slightly abnormal mucosal morphology whereas all 10 who had not complied had abnormal morphology. In these 10 lactase, sucrase, and alkaline phosphatase activities were significantly less than values in those who complied well. Mucosal sucrase and alkaline phosphatase activities in those who complied well were no different from those in a control population, whereas lactase activity was significantly lower. It is concluded that failure to comply with a GFD during childhood results in decreased adult stature and in persisting active enteropathy with depressed brush border enzyme activity.

Body Height↗

Coeliac proctitis.

An increased association of ulcerative colitis and coeliac disease has been reported, as have the results of several small-bowel biopsy studies in ulcerative colitis. Forty-two patients from a population of 438 patients with coeliac disease had rectal biopsies. Fourteen of these showed inflammation of various degrees of severity, including three compatible with a diagnosis of ulcerative colitis. The presenting complaint in 34 of these patients was diarrhoea or steatorrhoea. Twenty-seven patients had coeliac disease diagnosed at the same time or after their rectal biopsy. The other 15 were previously diagnosed coeliacs. Twelve of the 14 patients with abnormal rectal biopsy specimens were known to have subtotal/total villous atrophy at the time of rectal biopsy. Proctitis as seen in these coeliac patients had no unique features to differentiate it from proctitis caused by other disorders. The diarrhoea/steatorrhoea stopped in all patients on commencement of a gluten-free diet, except in those with ulcerative colitis. Proctitis is common in patients with coeliac disease presenting with diarrhoea/steatorrhoea. This study supports the finding of an increased association of coeliac disease and ulcerative colitis and is, to our knowledge, the first rectal biopsy study of a coeliac population.

Adult↗

Fatal hepatitis associated with diclofenac.

Non-steroidal anti-inflammatory agents (NSAIDS) are a well recognised cause of hepatotoxicity. Diclofenac, a relatively new NSAID, was first introduced into the UK in 1979. Five cases of hepatitis have recently been reported, principally in the French literature. We report the first fulminant case of hepatitis in the English literature in a patient taking diclofenac and indomethacin.

Chemical and Drug Induced Liver Injury↗

Immunoglobulins in healthy controls: HLA-B8 and sex differences.

Serum immunoglobulins were measured in one hundred and eighty-four healthy controls. One hundred and fifty-nine of these were also HLA typed. IgG levels did not differ with sex or HLA-B8 status. IgM levels did not differ with HLA-B8 status but were significantly higher in females than males. IgA levels were lower in females than males; they were also lower in HLA-B8 positive compared with HLA-B8 negative individuals; the lowest IgA levels were found in HLA-B8 positive females. The IgA variation may be relevant to the higher incidence of certain disorders among HLA-B8 positive individuals and among females.

Adult↗

Influence of splenectomy and the functional hyposplenism of coeliac disease on platelet count and volume.

Platelet count and volume were measured in 84 splenectomised subjects, 142 patients with coeliac disease and 77 healthy subjects. An inverse, non-linear correlation between platelet count and volume was found in healthy subjects and coeliac patients, but was not present in splenectomised subjects who had higher platelet counts (P = 0.0001) and mean platelet volumes (P = 0.0001) than healthy subjects. Platelet counts correlated with splenic function in patients with coeliac disease and were higher in patients with severe hyposplenism than in normosplenic coeliacs (P = 0.0001). Splenic function did not influence the mean platelet volume (MPV) in coeliac disease but normosplenic coeliacs had higher MPV than normal subjects (P = 0.05). Serum iron and red cell folate were not correlated to MPV in coeliac disease. We conclude that splenic function effects platelet count and volume in non-coeliac subjects and platelet count in coeliac disease. However, other unidentified factor(s) influence the MPV in coeliac disease.

Adolescent↗

Genetic influences on splenic function in coeliac disease.

Splenic function was assessed using 'pitted' erythrocyte counts in 61 first degree relatives of patients with coeliac disease. 'Pitted' erythrocyte counts were normal in 12 parents, but were raised in 20% of 49 siblings and/or children of coeliac patients. First degree relatives had higher 'pitted' erythrocyte counts than normal controls (p = 0.002). The counts were lower in coeliac relatives than in age matched coeliacs (p = 0.0001), but no difference was present between the relatives and coeliac patients whose small bowel mucosa was morphologically normal. Considerable interfamily variation was found in 'pitted' erythrocyte counts, both in the coeliac patients and first degree relatives, and the pattern tended to 'run true' within families. The genetic factor influencing splenic function in coeliac disease is not HLA-linked but seems to be associated with a second, probably recessive, gene influencing the inheritance of coeliac disease.

Adolescent↗