Biomedical subjects
W T Cooke
Publications and source records attributed to W T Cooke.
Long term prognosis of Crohn's disease with onset in childhood and adolescence.
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Determining disease activity in inflammatory bowel disease.
To provide a stronger relationship between clinical assessment of disease activity and laboratory measurements, we studied hemoglobin concentrations, sedimentation rates, and the serum levels of albumin and of seromucoids in 86 patients; first when seriously ill with either ulcerative colitis or Crohn's disease, and then again when they were well. Only albumin and seromucoids were separated clearly in the two states: hemoglobin and sedimentation rates showed significant overlap. Paired correlation tests between 10 laboratory variables in 149 patients with Crohn's disease of varying severity revealed a highly significant correlation between seromucoids and albumin (r = 0.71). Both variables correlated with six others, but at lower levels. Processing the correlation matrix by factor analysis suggested that the serum levels of albumin and seromucoid are indicators of the same effect--disease activity. A simple index using only hemoglobin, albumin, and seromucoid values, was derived from this analysis, positive values indicating health and negative ill health. Serum levels of albumin and seromucoids provide the essential data to determine disease activity at routine follow-up of inflammatory bowel disease or to indicate the success or failure of therapeutic regimens, overriding any arbitrary clinical assessment.
Nutritional supplements in Crohn's disease.
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Vitamin D deficiency and bone disease in patients with Crohn's disease.
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Lymphoma risk in coeliac disease of later life.
From 314 patients with coeliac disease, 20 patients were found to have developed a lymphoma. The incidence of lymphoma was much greater in the 6th, 7th and 8th decades of life than in the previous two decades. In 12 patients, the lymphoma was diagnosed within 4 years of the diagnosis of their coeliac disease and there were significantly more of these lymphomas appearing in coeliacs diagnosed between 51 and 80 years, who made up 23% of the series, than in those diagnosed between 21 and 50 years. We conclude that lymphoma is particularly a complication of older coeliacs and that coeliacs newly diagnosed at more than 50 years of age should be more closely followed up for they have a 1 in 10 chance of harbouring a lymphoma.
Coeliac disease, fertility, and pregnancy.
The effect of coeliac disease and its treatment on fertility and pregnancy in 74 patients is reported. Those on a normal diet had a shorter reproductive period, were relatively infertile, and had a higher incidence of spontaneous abortions than those on a gluten-free diet. Although maternal health did not appear to be seriously impaired by pregnancy in undiagnosed coeliacs, those on a gluten-free diet had significantly fewer symptoms and had heavier babies.
Factors in the management of Crohn's disease: a discussion paper.
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"Gluten-sensitive diarrhea without evidence of celiac disease".
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Mortality in Crohn's disease.
A series of 513 patients with Crohn's disease, who were followed for 1 to more than 35 yr by one unit, experienced a twofold increased risk of dying compared with a matched group drawn from the general population (102 observed; 51.8 expected; p < 0.001). The overall risk was similar for men and women and was greatest in the younger patients within a few years of diagnosis. The relative risk of dying decreased as the age at diagnosis of their Crohn's disease increased and also fell as the period of time from diagnosis increased. There was a small but significant excess of death from tumors of the digestive organs (9 observed; 4 expected; p < 0.05). There was also a significant excess of deaths from suicide in women (3 observed; 0.4 expected; p < 0.01). The major burden of mortality lay in causes directly attributable to Crohn's disease or to associated complications within the digestive system (46 observed; 1.41 expected; p < 0.001).
Celiac disease and malignancy.
Fifty-five patients with celiac disease and coexistent malignant disease (27 lymphoma, 28 other malignancies) are described. The important clinical features at presentation of lymphoma were weight loss, abdominal pain, diarrhea, profound weakness and fever, associated with anemia, raised ESR, hypoalbuminemia and steatorrhea. There were no specific features to enable earlier diagnosis. Radiology was unhelpful and in no case were malignant cells seen in the jejunal biopsy. Four of the lymphomas were Hodgkin's disease, none of which involved the bowel; the remainder were reticulum cell sarcoma, 17 of which involved the bowel. Definitive diagnosis prior to death was made in only 18 patients, of whom 16 survived from 2 to 226 days (mean, 76 days). Of the remaining two patients, one is still alive, while the other died 26 years after the original diagnosis of Hodgkin's disease. The possibility of lymphoma should be considered in those who present with celiac disease in middle life and in those who deteriorate for no apparent reason after a period of stability on a gluten-free diet. The index of suspicion for lymphoma in celiac disease should be high and early laparotomy be considered in patients with unexplained deterioration. Twenty-eight patients with 29 carcinomas and 3 other tumors are also described. The presentations of these malignancies were no different from their presentations in non-celiac patients, and their development did not provoke a relapse of celiac disease. Considering the whole series of 55 patients, there was little evidence for the view that malignancy itself was the cause of the flat jejunal mucosal appearances seen in these patients.
Crohn's disease: course, treatment and long term prognosis.
The course, treatment and outcome of Crohn's disease affecting 174 patients diagnosed more than 20 years ago and followed for 20 to 45 years are reported. Fifty patients died, 23 related to Crohn's disease, against an expected 33, giving an increased mortality risk of 1.5 for the series. Fistulae of varying type occurring in 38 per cent of patients were successfully treated usually by excision and had no significant adverse effect upon the long term prognosis. The incidence of suicide and dementia appeared to be increased. Amyloid disease, obstructive uropathy and osteomalacia were other important complications. Definitive surgical operations averaged 2.5 per patient and after the first five years following diagnosis varied between 5 and 7 per cent of those at risk each year for the next 20 years. Recurrence rates were similar after any of the first five operations on a patient for the first 10 years after any operation. There was no evidence that the chance of operation was increased or made to recur more frequently by the performance of such an operation. All but two of the 121 living patients (three lost to follow-up) with a mean duration since diagnosis of 28 years were leading a normal life free from physical restrictions from Crohn's disease though three were mentally handicapped, 21 had radiological abnormality (recurrence), mostly longstanding, and 16 had less than 200 cm small intestine remaining. Specific therapy (corticosteroids 58 patients, sulphasalazine 11 patients and azathioprine four patients) was used at some time in only one third of the series so that such treatment did not appear necessary to produce good results in the majority. It is concluded that the indications for corticosteroid therapy are limited and that at present the joint efforts of physician and surgeon with adequate supportive therapy and well timed surgical resection produce the best results. An optimistic attitude to the eventual outcome is justified.
Gluten-sensitive diarrhea without evidence of celiac disease.
Eight adult female patients suffering from abdominal pain and chronic diarrhea which was often incapacitating and frequently nocturnal, had dramatic relief on a gluten-free diet and return of symptoms after gluten challenge. Previous nonspecific measures and a milk-free diet were ineffective. Multiple jejunal biopsies showed minor, but significant changes in cellularity which returned to normal on the gluten-free diet. Apart from a slight increase in jejunal cellularity, no immunological abnormalities were found after gluten challenge. Steatorrhea or other biochemical defects, common in celiac disease, were not found. It was concluded that these patients had a gluten-sensitive diarrhea, but had no evidence of celiac disease.
Diagnosis of dermatitis herpetiformis.
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Serum concentrations of 25-hydroxy vitamin D in Europeans and Asians after oral vitamin D3.
Serum concentrations of 25-hydroxy vitamin D (25-OHD3) were measured in seven Asians of Indian extraction and eight Europeans before and at intervals after taking 1 mg vitamin D3 by mouth. In all subjects the concentrations rose in the 24 hours after ingestion. There was little change over the next nine days in the concentrations in the Europeans but those in the Asians continued to rise until about day 10. Subsequent rates of fall in 25-OHD3 were similar in the two groups. Our observations suggest that the low serum concentrations of 25-OHD3 found in Asians are not caused by either impaired intestinal absorption of vitamin D or rapid clearance of 25-ODH3 from the plasma.
Coeliac disease and immunological disorders.
Out of 314 patients with coeliac disease, 63 had associated disorders of known or suspected immunological cause (excluding aphthous stomatitis and dermatitis herpetiformis). Autoimmune diseases appeared to occur more often in patients with coeliac disease than in the normal population, 52 such diseases being found in 45 patients. Of individual disorders, diabetes mellitus, thyroid diseases, and ulcerative colitis seemed to be more common than expected. Atopy (asthma and eczema) occurred in 7% of the patients. Most of these immunological disorders developed when the patients were on normal diet. A gluten-free diet and virtually normal jejunum did not prevent their development, and the diet had little ameliorating effect on their course apart from an occasional dramatic improvement in atopic patients.
Intestinal lymphoma associated with malabsorption.
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Acid microclimate in coeliac and Crohn's disease: a model for folate malabsorption.
The surface pH of human proximal jejunum was measured in biopsy samples and found to be more acid than the phosphate buffer in which they were incubated. The in vitro jejunal surface pH was 5.93 +/- 0.05 in control subjects and 6.19 +/- 0.09 in treated coeliac patients. A group of untreated coeliac patients with a surface pH of 6.56 +/- 0.14 had a significantly less acid surface pH compared to controls, as did a group of Crohn's patients with a surface pH of 6.21 +/- 0.04. These two groups with a significantly raised surface pH were subdivisible into 'high' and 'low'groups. Surface pH was found to remain low in the treated coeliac and control groups but became more acid over the incubation period reaching almost normal values in the Crohn's group and the untreated coelic initial surface pH. The raised surface pH in untreated coeliac disease and Crohn's disease would alter the amount of a weak acid available for non-ionic diffusion. Therefore the present results may help to explain the folate malabsorption known to occur in untreated coeliac disease and the frequently seen low serum folate levels in Crohn's disease.