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Biomedical subjects

G K Holmes

Publications and source records attributed to G K Holmes.

At least 19 recordsLinked to original sources
PubMed2001

Coeliac disease and Type 1 diabetes mellitus - the case for screening.

AIM: To review the relationship between coeliac disease and Type 1 diabetes mellitus with emphasis on prevalence of coeliac disease, presentation and implications for screening. METHODS: Papers collected over many years by the author have been included in the review and a literature search employing Medline was undertaken to August 2000. Search words used were coeliac disease and diabetes mellitus. RESULTS: Twenty papers exploring the prevalence of coeliac disease by serological screening of Type 1 diabetes in children, eight in adults and two including both groups were found. An additional 48 papers are included and relate to serological screening tests for coeliac disease, expressions and complications of coeliac disease, the value of GFD and the genetics of the two conditions. Unless formal screening studies are undertaken coeliac disease will not be diagnosed because patients are asymptomatic, have atypical symptoms or even in those with symptoms the diagnosis is overlooked. Based on small bowel biopsy, diagnosis the prevalence of coeliac disease in Type 1 diabetes in children is 1:6 to 1:103 and in adults 1:16 to 1:76. Patients may improve following the start of a gluten-free diet (GFD) in terms of symptoms, growth in children, serum antibody levels, haematological and biochemical indices, morphology of the small intestinal mucosa and control of diabetes. CONCLUSION: Coeliac disease commonly occurs in Type 1 diabetes. It is recommended that screening for coeliac disease should be part of the routine investigation and offered to all patients because of the high prevalence and the potential benefits of treatment with a GFD. This includes control of symptoms, stabilization of diabetes and prevention of complications associated with coeliac disease. The cost per patient diagnosed with coeliac disease from the existing population with Type 1 diabetes would be pound860 and for those newly arising pound950.

Adult↗
PubMed2001

Potential and latent coeliac disease.

This case report details a child with coeliac disease and giardiasis. Treatment of the infection without recourse to a gluten-free diet cured the symptoms of diarrhoea and returned the small intestinal morphology to normal. Thus, the patient moved from active to latent coeliac disease. Potential and latent forms of coeliac disease are being increasingly recognized, since markers have become available to identify patients and investigations developed to test for gluten sensitivity in the small intestinal mucosa. This case provides an opportunity to consider potential and latent forms of coeliac disease and how these impact on clinical practice and the wider understanding of the disorder.

Biomarkers↗
PubMed2000

Measles, month of birth, and Crohn's disease.

BACKGROUND: The rise in the incidence of Crohn's disease (CD) suggests the role of an environmental factor in the development of the disease in susceptible individuals. Perinatal exposure to infection has been proposed as such an environmental factor. AIM: To investigate the influence of birth date on the development of CD in later life. PATIENTS AND METHOD: Four registers of patients with CD, diagnosed from 1972 to 1989, were combined, and data from 1624 patients were examined. The birth dates of CD patients were compared with national birth figures for three decades (1941-50, 1951-60, and 1961-70) to avoid temporal changes in birth trends, and year of birth was compared with epidemic measles years between 1951 and 1967. Risk ratios with 95% confidence intervals (CI) and chi(2) tests were performed. RESULTS: There were marginal differences between the birth dates of the CD patients and those predicted from the general population. Further analysis of both season of birth and year halves revealed a very weak association with the first half of the year (relative risk 1.14 (95% CI 1.01-1.30)). There was no association between developing CD and birth during measles epidemics between 1951 and 1967. CONCLUSIONS: In utero or perinatal exposure to seasonal environmental factors are unlikely potential aetiological agents in the later development of CD.

Adult↗
PubMed1999

Weight loss has an independent beneficial effect on symptoms of gastro-oesophageal reflux in patients who are overweight.

BACKGROUND: Weight loss is commonly recommended as part of first-line management of gastrooesophageal reflux disease (GORD) despite the paucity of published clinical trials. The aim of this study was to prospectively assess the independent effect of weight loss on reflux symptoms in overweight individuals with either normal endoscopic findings or grade-I oesophagitis. METHODS: Thirty-four patients were recruited on the basis of a body mass index (BMI) of greater than 23 and symptoms of GORD for at least 6 months. All patients were advised to lose weight. Symptoms of gastro-oesophageal reflux (GOR) were scored, using a modified DeMeester questionnaire at 0, 6, and 26 weeks. Patients who were unable to stop taking all medication for control of symptoms were excluded from the study. Changes in weight and symptom score were analysed by using a paired t test. Correlation between change in weight and symptom score was assessed with the Pearson correlation test. RESULTS: Thirty-four patients were studied (18 men and 16 women) with a mean age of 65 years (range, 24-70 years). The mean weight at recruitment was 83.4 kg (standard deviation (s), 4.5 kg; BMI, 23.5 kg/m2 (s, 2.3 kg/m2). Twenty-seven patients (80% of the total) lost weight with a mean of 4.0 kg (P < 0.01) and improved by a mean reduction of 75% from the initial symptom score (P < 0.001). In nine patients the symptoms disappeared completely. Three patients gained weight and had a deterioration of their symptoms, whereas four patients gained weight but still improved their symptom score. There was a significant direct correlation between weight loss and symptom score (R = 0.548, P < 0.001). CONCLUSIONS: This study has shown a significant association between weight loss and improvement in symptoms of GOR. Patients who are overweight should be encouraged to lose weight as part of the first-line management.

Aged↗
PubMed1998

Laser therapy combined with brachytherapy for the palliation of malignant dysphagia.

BACKGROUND/AIM OF STUDY: Laser therapy is effective in relieving malignant dysphagia, but repeated treatments at 4 to 6 week intervals are usually required. This prospective randomised trial is designed to determine if addition of brachytherapy offers any advantages over laser therapy alone. METHODS: Patients with inoperable carcinoma of the oesophagus were randomised to receive either endoscopic Nd:YAG laser therapy alone, or laser followed by brachytherapy. Patients who developed worsening dysphagia during follow-up were offered further treatment as appropriate. RESULTS: Fourteen patients were randomised to receive laser only, and 12 to receive laser followed by brachytherapy. Of these 12, one was lost to follow-up and four did not receive brachytherapy because they were unfit, had extension into the cardia or had mainly extrinsic compression. These 4 are included on an 'intention-to-treat' basis. The mean therapeutic interval for the brachytherapy group was significantly longer, 83 days compared to 36 days for the laser group (p = 0.026). There were no differences in the degree of dysphagia relief, number of endoscopic procedures or survival times. CONCLUSION: The preliminary results of this trial suggest that brachytherapy in addition to laser therapy prolongs the first therapeutic interval. However, no long-term advantages have been shown.

Aged↗
PubMed1997

Linkage analysis of candidate regions for coeliac disease genes.

A strong HLA association is seen in coeliac disease [specifically to the DQ(alpha1*0501,beta1*0201 heterodimer], but this cannot entirely account for the increased risk seen in relatives of affected cases. One or more genes at HLA-unlinked loci also predispose to coeliac disease and are probably stronger determinants of disease susceptibility than HLA. A recent study has proposed a number of candidate regions on chromosomes 6p23 (distinct from HLA), 6p12, 3q27, 5q33.3, 7q31.3, 11p11, 15q26, 19p13.3, 19q13.1, 19q13.4 and 22cen for the location of a non-HLA linked susceptibility gene. We have examined these regions in 28 coeliac disease families by linkage analysis. There was excess sharing of chromosome 6p markers, but no support for a predisposition locus telomeric to HLA. No significant evidence in favour of linkage to coeliac disease was obtained for chromosomes 3q27, 5q33.3, 7q31.3, 11p11, 19p13.3, 19q13.1, 19q13.4 or 22cen. There was, however, excess sharing close to D15S642. The maximum non-parametric linkage score was 1.99 (P = 0.03). Although the evidence for linkage of coeliac disease to chromosome 15q26 is not strong, the well established association between coeliac disease and insulin dependent diabetes mellitus, together with the mapping of an IDDM susceptibility locus (IDDM3) to chromosome 15q26, provide indirect support for this as a candidate locus conferring susceptibility to coeliac disease in some families.

Celiac Disease↗
PubMed1996

A randomised prospective comparison of percutaneous endoscopic gastrostomy and nasogastric tube feeding after acute dysphagic stroke.

OBJECTIVE: To compare percutaneous endoscopic gastrostomy and nasogastric tube feeding after acute dysphagic stroke. DESIGN: Randomised prospective study of inpatients with acute stroke requiring enteral nutrition. SETTING: One university hospital (Nottingham) and one district general hospital (Derby). SUBJECTS: 30 patients with persisting dysphagia at 14 days after acute stroke: 16 patients were randomised to gastrostomy tube feeding and 14 to nasogastric tube feeding. MAIN OUTCOME MEASURES: Six week mortality; amount of feed administered; change in nutritional state; treatment failure; and length of hospital stay. RESULTS: Mortality at 6 weeks was significantly lower in the gastrostomy group with two deaths (12%) compared with eight deaths (57%) in the nasogastric group (P < 0.05). All gastrostomy fed patients (16) received the total prescribed feed whereas 10/14 (71%) of nasogastric patients lost at least one day's feed. Nasogastric patients received a significantly (P < 0.001) smaller proportion of their prescribed feed (78%; 95% confidence interval 63% to 94%) compared with the gastrostomy group (100%). Patients fed via a gastrostomy tube showed greater improvement in nutritional state, according to several different criteria at six weeks compared with the nasogastric group. In the gastrostomy group the mean albumin concentration increased from 27.1 g/l (24.5 g/l to 29.7 g/l) to 30.1 g/l (28.3 g/l to 31.9 g/l). In contrast, among the nasogastric group there was a reduction from 31.4 g/l (28.6 g/l to 34.2 g/l) to 22.3 g/l (20.7 g/l to 23.9 g/l) (P < 0.003). In addition, there were fewer treatment failures in the gastrostomy group (0/16 versus 3/14). Six patients from the gastrostomy group were discharged from hospital within six weeks of the procedure compared with none from the nasogastric group (P < 0.05). CONCLUSION: This study indicates that early gastrostomy tube feeding is greatly superior to nasogastric tube feeding and should be the nutritional treatment of choice for patients with acute dysphagic stroke.

Acute Disease↗
PubMed1996

Non-malignant complications of coeliac disease.

Patients with coeliac disease are at increased risk of developing complications which increase morbidity and mortality. Emphasis on malignant complications has often overshadowed the non-malignant risks, which have received relatively little attention, although some of these can be very troublesome and even life-threatening. This article points out that a large population of unidentified or neglected coeliac patients is at potential risk. The challenge is to identify this group by case-finding or screening programmes in selected populations, so that they can be offered a gluten-free diet and other treatments which will not only improve general health but may also prevent or reduce the development of health problems. The non-malignant risks are outlined and bone and neuropsychiatric disturbances considered in more detail because of recent developments in these areas.

Adult↗
PubMed1996

Neurological complications of celiac disease: a rare but continuing problem.

Neurological complications are a recognized but unusual manifestation of celiac disease. We present here our experiences with four current cases. Age of patients at presentation with neurological signs varied from 7 to 67 yr. In one patient, the neurological disability developed before the diagnosis of celiac disease, whereas, in the other three, it occurred from months to 16 yr after the diagnosis had been established. One patient died of rapidly progressive neuromyopathy. The other three patients had combinations of cerebellar and posterior and lateral column abnormalities. All four patients developed neurological complications despite a strict gluten-free diet. In three of four patients, there was no improvement in duodenal histology on this diet. Treatment with vitamin B12, folic acid, or vitamin D failed to reverse the changes. No other nutritional deficiencies were found. Vitamin E levels were normal in two of three patients. One patient had no response to treatment with immunosuppressive drugs. The mechanisms responsible for these neurological complications are poorly understood, although patients whose duodenal histology fails to improve on a gluten-free diet may be at greater risk. There have been no real advances in the understanding of this condition since the original description nearly 30 yr ago.

Adult↗
PubMed1994

Blood-group sialyl-Tn antigen is more specific than Tn as a tumor marker in the pancreas.

The aim of this study was to evaluate the expression of blood group Tn and sialyl-Tn antigens in the pancreas to determine whether they could help to interpret histochemically needle biopsies obtained from the pancreas. Lectin and immunohistochemistry was carried out using the biotin-labeled Vicia villosa agglutinin isolectin B4 and the mouse monoclonal antibody MLS102 to detect the Tn and sialyl-Tn blood-group antigens in the pancreas. All the pancreatic ductal adenocarcinomas (11/11) were positively stained by V. villosa agglutinin and MLS102 monoclonal antibody. None of the normals or chronic pancreatitics bound MLS102 monoclonal antibody. The acini of all the normals and chronic pancreatitics were V. villosa agglutinin positive, which was absent in the normal ductal cells and present only sparingly in the chronic pancreatitis ductal tissues (10/16). Thus, both the Tn and the sialyl-Tn blood-group antigens are present in pancreatic ductal tissues that have undergone malignant transformation. MLS102 is superior to V. villosa agglutinin in distinguishing malignant from normal and nonmalignant pancreatic tissues in needle biopsies.

Adenocarcinoma↗
PubMed1994

Coeliac disease in the elderly.

Of 228 patients with adult coeliac disease, 42 (19%) were diagnosed aged 60 years or over. In this series, of 35 patients who did not have dermatitis herpetiformis, 15 had attended family doctors and hospital outpatient departments for an average of 28 years with unexplained symptoms or abnormalities in blood tests but the diagnosis of coeliac disease had been missed. This is unsatisfactory because these patients can both manage and respond to a gluten free diet. Thirty eight patients complied strictly with the diet with resolution of symptoms. Significant improvement in weight, haemoglobin, albumin, calcium, and alkaline phosphatase values after a year on the diet also occurred. Clinicians should be alert to the possibility of coeliac disease in the elderly particularly in patients with non-specific complaints in the presence of unexplained anaemia.

Adolescent↗
PubMed1994

The prevalence of coeliac disease in adult diabetes mellitus.

Coeliac disease occurs more commonly in children with insulin-dependent diabetes mellitus (IDDM) than in the general population, but the prevalence of coeliac disease in adults with diabetes is unknown. We therefore screened an adult hospital-based diabetic population using IgA antigliadin antibody (IgA-AGA) to identify those patients requiring intestinal biopsy. In 1 year, 1789 patients (43% IDDM, 57% NIDDM) were screened, and 73 had raised IgA-AGA. Of these patients, 49 agreed to duodenal biopsy and 13 (10 IDDM) had coeliac disease. Selective IgA deficiency was found in eight patients, one of whom had coeliac disease. Of these 14 patients with newly diagnosed coeliac disease, four had microcytic anaemia, nine a low serum ferritin, and four a low albumin-corrected calcium. Eight patients had symptoms which improved on gluten withdrawal. Dietary compliance was maintained in 6/8 symptomatic patients, but only in 1/6 without symptoms. Included in the 1789 patients were four (all IDDM) with known coeliac disease. The overall prevalence of coeliac disease in adult patients with IDDM was 1:50 compared with 1:340 in NIDDM. Coeliac disease is common in adults with IDDM and may cause malabsorption and ill health. It should be suspected in any IDDM patient with gastrointestinal symptoms or unexplained anaemia.

Adult↗
PubMed1993

Comparison of two sialosyl-Tn binding monoclonal antibodies (MLS102 and B72.3) in detecting pancreatic cancer.

An immunohistochemical study has been carried out to compare and contrast the cellular distribution of two different sialosyl-Tn antigen binding monoclonal antibodies, MLS102 and B72.3, in the pancreas. MLS102 but not B72.3 monoclonal antibody binding increases with the content of the sialosyl-Tn epitopes. It was found that all 13 pancreatic cancer specimens bound both MLS102 and B72.3 monoclonal antibodies. Their cellular distribution in the cancer was virtually identical. Fifteen of 20 (75%) patients with chronic pancreatitis and five of 10 (50%) normal subjects were B72.3 positive, but MLS102 was completely negative in the latter group. Both monoclonal antibodies bound fetal pancreas diffusely. Thus, when pancreatic ductal cells have undergone malignant transformation, like the fetal pancreas, they express cell surface and secreted glycoconjugates with increased sialosyl-Tn epitopes suggesting enhanced 2-6 sialosyltransferase activity. This study shows that MLS102 is an extremely sensitive and specific tumour marker in the pancreas and that it is better than B72.3 in distinguishing pancreatic cancer from normal and chronic pancreatitis.

Adenocarcinoma↗