PubMed HealthSearch

Biomedical subjects

S P Wilkinson

Publications and source records attributed to S P Wilkinson.

At least 19 recordsLinked to original sources

Endoscopic crescentic fold disease of the sigmoid colon: the clinical and histopathological spectrum of a distinctive endoscopic appearance.

In this paper we describe an endoscopic appearance of the sigmoid colon characterised by mucosal swelling, erythema and haemorrhage strictly localised to the crescentic mucosal folds. In a 5-year period these changes were seen in 34 (1.42%) of 2380 colonoscopies and fibreoptic sigmoidoscopies. The majority of patients were middle-aged or elderly. Diverticular disease was present in most (82%) but the abnormalities were confined to the crescentic mucosal folds with sparing of the diverticular orifices. The majority of patients presented with a history of bleeding per anum. Histologically there was a spectrum of changes varying from minor vascular congestion to florid active inflammatory disease with crypt architectural abnormalities mimicking ulcerative colitis, but rectal biopsies were invariably normal. Three patients later progressed to typical distal ulcerative colitis and two other patients presenting to us with endoscopic crescentic fold disease had a previous histologically documented history of distal ulcerative colitis. In three patients the histological features were of mucosal prolapse. About half the patients required some form of therapy to control their symptoms. Steroids and/or sulphasalazine were of value although two patients subsequently underwent sigmoid resection, one to control bleeding and the second for a diverticulosis-associated stricture. Whilst endoscopic crescentic fold disease represents a specific endoscopic appearance the clinical and histological features indicate a wide spectrum of disease.

Adult

An Eudragit-coated prednisolone preparation for ulcerative colitis: pharmacokinetics and preliminary therapeutic use.

Prednisolone metasulphabenzoate, a steroid with poor colonic absorption, was coated with the pH-dependent acrylic resin Eudragit S, as a means of delivering an orally administered preparation to the proximal colon. The therapeutic potential of delivering this steroid with potentially less systemic side-effects to the proximal colon was assessed in extensive ulcerative colitis. Plasma and urine prednisolone profiles in 6 healthy volunteers confirmed minimal absorption from Eudragit S-coated prednisolone metasulphabenzoate compared to prednisolone acetate: peak plasma prednisolone concentrations 29 +/- 21 ng/ml vs. 570 +/- 185 ng/ml (P less than 0.01), area under curve measurements 204 +/- 214 vs. 2724 +/- 1236 ng.h/ml (P less than 0.01). Prednisolone metasulphabenzoate coated with Eudragit S (30-60 mg daily) was then administered for 12 weeks to 12 patients with colonoscopically proven extensive ulcerative colitis in relapse. Symptoms, sigmoidoscopic appearances and rectal histological abnormalities all improved during therapy. Complete clinical remission occurred in 7 patients, a partial response in 2 patients and no response in 3 patients. Cortisol responses to tetracosactrin demonstrated no significant adrenal suppression following treatment. Eudragit S-coated prednisolone metasulphabenzoate may be a useful treatment for extensive ulcerative colitis, without risk of systemic steroid side-effects.

Acrylic Resins

Use of the SeHCAT test in the investigation of diarrhoea.

The SeHCAT test was used to investigate possible bile acid malabsorption in 166 patients presenting to a district general hospital with chronic diarrhoea of uncertain cause. Eighty-four (51%) patients had impaired SeHCAT retention. These included 23 of 28 patients with a possible type I abnormality (terminal ileal resection or disease, previous pelvic radiotherapy), 20 of 74 with a possible type II abnormality (idiopathic diarrhoea), 32 of 45 with a possible type III abnormality (post-cholecystectomy, post-vagotomy), and 9 of 19 with diarrhoea associated with diabetes. Patients with severe bile acid malabsorption demonstrated a good response to cholestyramine whereas the response in patients with a mildly abnormal SeHCAT retention was variable. Bile acid malabsorption is an important cause of diarrhoea in patients presenting with unexplained chronic diarrhoea.

Adolescent

Urinary steroid profiles and alcohol-related blood pressure elevation.

1. From an earlier cross-sectional survey of 343 public servants, 15 pairs of non-smoking teetotallers and heavy drinkers (alcohol intake more than 350 mL/week) were matched for age and adiposity and utilized for a case-control study of the effects of alcohol on 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) activity and blood pressure. 2. Two successive 24 h urine collections were analysed by radio-immunoassay (RIA) for cortisol excretion, and for the cortisol and cortisone metabolites, tetrahydrocortisol (THC), allo-tetrahydrocortisol (allo-THC) and tetrahydrocortisone (THE), by capillary column gas chromatography. 3. Heavy drinkers had higher systolic and diastolic blood pressure (BP) than teetotallers (132.6 +/- 2.5 vs 123.2 +/- 1.3 and 78.7 +/- 1.6 vs 71.7 +/- 1.4, respectively; unpaired t-test, P less than 0.01). Twenty-four-hour urinary sodium and cortisol excretion were similar in the two groups. 4. The THC plus allo-THC:THE ratio was similar in drinkers and teetotallers (1.81 +/- 0.20 vs 2.03 +/- 0.20), consistent with no effect of alcohol on 11 beta-OHSD activity. The ratio of THC to allo-THC was increased in drinkers compared with teetotallers (1.49 +/- 0.18 vs 1.05 +/- 0.13; unpaired t-test, P less than 0.05), consistent with either a decrease in 5 alpha-reductase activity or an increase in 5 beta-reductase activity. 5. This study provides no evidence for alcohol-related inhibition of 11 beta-OHSD, despite substantially higher blood pressures in heavy drinkers compared to teetotallers. Such an effect is, therefore, unlikely to contribute significantly to the mechanism of alcohol-related hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Long-term follow up of patients with gastritis associated with Helicobacter pylori infection.

The aim of this study was to evaluate the long-term prognosis for patients suffering from gastritis associated with Helicobacter pylori infection, and in particular the proportion of cases progressing to peptic ulcer. The study was carried out in one urban general practice. One hundred and three patients who had presented with dyspepsia over the 1973-80 period and who were found to have a macroscopically normal endoscopy were reassessed between seven and 14 years later. Gastric antral biopsies had been taken routinely at endoscopy and were subsequently re-examined for the presence of H pylori. The patients' medical records were examined to establish their consulting rates over the follow-up period and whether they suffered from any other medical conditions. Patients were interviewed to assess the course of their dyspeptic symptoms. Comparison of patients who were unequivocally H pylori positive with those who were negative revealed no significant differences in the consultation rate for gastroenterological symptoms, in the proportion of patients referred to a hospital consultant or for further gastroenterological investigations or in the proportion reporting that their symptoms had improved. However, a statistically highly significant relationship was found between H pylori infection and hypertension. The results of this study have shown that there is a good prognosis for non-ulcer dyspepsia whether or not H pylori infection is present. The association between H pylori gastritis and hypertension clearly merits further investigation.

Evaluation Studies as Topic

Pyogenic liver abscess in the elderly.

Seventeen patients over the age of 60 years, admitted to the Aberdeen Teaching Hospitals between 1980 and mid-1988, were diagnosed as having pyogenic liver abscess. Eleven were women and the mean age was 73.5 years. The diagnosis of liver abscess was made by needle aspiration in seven patients and was an unexpected finding at laparotomy in three. Six patients were thought to be suffering from advanced malignant disease until autopsy. The overall fatality was 53%. Misleading results from special investigations reduced the chance of a correct diagnosis in several patients. Even in frail elderly patients, a filling defect in the liver should not be attributed to metastatic malignancy when there is no known primary site, until liver abscess has been excluded by aspiration biopsy under ultrasound or computerized tomographic scan guidance. The high fatality of pyogenic liver abscess seems to be at least in part due to a lack of clinical suspicion.

Aged

Comparison of omeprazole and cimetidine in reflux oesophagitis: symptomatic, endoscopic, and histological evaluations.

Symptomatic patients with endoscopically verified reflux oesophagitis were randomised to a double blind trial in which they received either omeprazole (20 mg once daily) or cimetidine (400 mg four times daily) for four, and if necessary, eight weeks. In an 'intention to treat' analysis, oesophagitis was found to have healed after four weeks in 77 of 137 (56%) in the omeprazole group and in 34 of 133 (26%) in the cimetidine group (p less than 0.001). By eight weeks these values were 71% and 35% respectively; p less than 0.001. Histological assessments were available for 73% of the patients. At entry, 63% (66 of 104) in the omeprazole group and 60% (56 of 94) in the cimetidine group (ns) had abnormal histology. After the study, the proportions of patients who initially had had abnormal histology but who then progressed to normal were 67% (44 of 66: omeprazole) and 48% (27 of 56: cimetidine) respectively (p less than 0.001). All patients had reflux symptoms at entry. After four weeks, 46% in the omeprazole group and 22% (p less than 0.001) in the cimetidine group were asymptomatic. Diary cards completed for the first two weeks showed that patients treated with omeprazole experienced fewer reflux symptoms by day and night and used fewer antacids. Omeprazole, 20 mg once a day for four to eight weeks, healed a greater proportion of patients with reflux oesophagitis than cimetidine, 1.6 g per day, assessed endoscopically and histologically, and relieved more patients' symptoms.

Cimetidine

Duodenal ulceration into the cystic artery.

We report two cases of massive gastrointestinal bleeding due to anterior duodenal ulceration into the cystic artery, with gallbladder infarction as a complication. These cases indicate the potential dangers of laser therapy or embolization in bleeding anterior duodenal ulcers penetrating the cystic artery, as such therapy will arrest blood flow through the cystic artery and may precipitate gallbladder infarction.

Aged

"Liver cancer ... or is it?".

There has been a gradual change in the pattern of presentation of pyogenic liver abscess with an increasing incidence in the elderly. At the same time an improvement in mortality with early diagnosis and treatment has been recognised. We describe two patients in whom the diagnosis of liver abscess was not suspected until autopsy in one and aspiration of pus during biopsy of a liver "tumour" in the other.

Aged

The interaction site for tamoxifen aziridine with the bovine estrogen receptor.

Calf uterine estrogen receptor was covalently labeled with [3H]tamoxifen aziridine during affinity chromatography purification. After carboxymethylation, affinity labeled receptor was digested with trypsin under limit conditions and the labeled peptides were fractionated by reversed-phase high performance liquid chromatography into one major and two minor components. Sequence analysis of the dominant labeled fragment indicated the facile cleavage of label during Edman degradation but identified two peptides, both derived from the extreme carboxyl terminus of the steroid-binding domain. The 17 residues of one peptide were fully conserved in all estrogen receptors. This fragment contained five nucleophilic amino acids and was considered as the more favored interaction site for tamoxifen aziridine. A corresponding region of the glucocorticoid receptor has recently been identified as one of three major contact sites for glucocorticoids (Carlstedt-Duke, J., Strömstedt, P.-E., Persson, B., Cederlund, E., Gustafsson, J.-A., and Jörnvall, H. (1988) J. Biol. Chem. 263, 6842-6846). A comparison of amino acid physical characteristics in the hormone-binding domains of human estrogen and glucocorticoid receptors demonstrated an excellent structural correlation between the two regions and delineated elements in the estrogen receptor which may be directly involved in estradiol binding.

Amino Acid Sequence

A prospective randomised controlled trial of tamoxifen and cyproterone acetate in pancreatic carcinoma.

In a prospective controlled clinical trial, 108 patients with pancreatic adenocarcinoma were randomly allocated to receive tamoxifen 20 mg b.d., cyproteron acetate 100 mg t.d.s. or no active treatment. The median survival of those receiving tamoxifen was longer than either of the other two groups (5.25 compared to 4.25 and 3 months, respectively) but this difference did not achieve statistical significance. Cox regression analysis of 12 clinical and biochemical features showed that, for the entire group of patients, survival was significantly longer in younger patients, those undergoing surgical bypass and those with better initial performance status. However, even when adjustment was made to allow for the distribution of these prognostic variables within the three groups, the difference in survival still did not achieve statistical significance. No side-effects attributable to treatment was observed.

Adenocarcinoma

Biologic variation of common hematologic laboratory quantities in the elderly.

Analytic, within-subject, and between-subject biologic variations were estimated for leukocytes, erythrocytes, hemoglobin, hematocrit, mean cell volume (MCV), mean cell hemoglobin (MCH), mean cell hemoglobin content (MCHC), platelets, and a three-component differential count (lymphocytes, monocytes, and granulocytes in terms of both concentration and percentage of leukocytes) in cohorts of 12 male and 12 female healthy elderly subjects. The assays were performed with an Ortho ELT-800 automated analyzer. The estimates of within-subject biologic variation were similar to published data on young subjects, indicating that this aspect of homeostasis is not compromised in the elderly. The data were used to derive objective analytic goals; goals were surpassed except for assays of erythrocytes, hematocrit, and the derived MCV, MCH, and MCHC. The changes required for serial results to be significantly different were determined and found to be generally valid because most quantities have no heterogeneity of within-subject variation. All quantities had significant individuality; in consequence, conventional population-based reference values are of limited utility, and screening using reference limits will not detect latent or early disease in many subjects.

Aged

Symptom relief and duodenal ulcer healing with omeprazole or cimetidine. Opus (Omeprazole Peptic Ulcer Study) Research Group.

In a double-blind parallel-group study, 98 patients with symptomatic duodenal ulcer received omeprazole 20 mg o.m. and 91 cimetidine 800 mg nocte for 2 or, if then not healed, 4 weeks. After 2 weeks the healing rates on an intention-to-treat basis were: for omeprazole 62% and for cimetidine 33% (P less than 0.001), and at 4 weeks 85% and 61%, respectively (P less than 0.001). The proportions symptom-free at 2 weeks were 83% of the omeprazole and 63% of the cimetidine-group (P less than 0.01) and at 4 weeks 84% and 72% (P = 0.01). Patients receiving omeprazole took fewer antacid tablets than those receiving cimetidine. Patient tolerance of both drugs was similar and good. In the treatment of duodenal ulcer, omeprazole 20 mg o.m. gives faster symptom relief than cimetidine 800 mg nocte, as well as healing a greater proportion of ulcers within 2 and 4 weeks.

Adolescent

Randomised, double blind comparison of omeprazole and cimetidine in the treatment of symptomatic gastric ulcer.

In a randomised, double blind, parallel group study in patients with symptomatic gastric ulcer (94% greater than or equal to 5 mm diameter), 102 received omeprazole 20 mg om and 87 cimetidine 400 mg bd. After four weeks 73% and 58% (p less than 0.05) respectively had healed (eight weeks: 84% and 75%, ns). After four weeks, a greater proportion (81%) of omeprazole treated patients was symptom free than of those receiving cimetidine (60%; p less than 0.01). Over the first two weeks, patients receiving omeprazole had less day pain, less night pain and took fewer antacids than those receiving cimetidine (all p less than 0.05). The difference between omeprazole and cimetidine was not appreciably affected by age, smoking, size of the ulcer and trial centre. Tolerability was similar in the two treatment groups. In the treatment of symptomatic gastric ulcer, omeprazole relieves the symptoms more quickly than cimetidine and heals a greater proportion of ulcers within four weeks.

Cimetidine

Detection of Campylobacter pylori by the biopsy urease test: an assessment in 1445 patients.

The presence of C pylori infection was determined in 1445 patients undergoing upper gastrointestinal endoscopy over a 12 month period. The presence of C pylori was detected in gastric mucosal biopsy specimens by the biopsy urease test, microscopy (Gram stained smears and histology) and culture. Two media were used for the biopsy urease test: Christensen's urea broth (for the first 600 patients) and the Christensen's urea broth modified by increasing the concentration of phenol red and omitting the nutrients, glucose and peptone (for the remaining patients). Both the Christensen's urea broth and modified urea broth were almost 100% specific when compared with detection of C pylori by Gram, culture and histopathology. The modified broth was more sensitive (96% sensitivity compared with culture) than the Christensen's broth (92% sensitivity) but this difference was not statistically significant. The modified broth gave significantly more positive results (58%) in less than 30 minutes than the Christensen's broth (48%). Seventy four per cent of positive results were available in less than two hours. Specimens from patients with extensive C pylori infection gave more rapid results: 86% of specimens that yielded a profuse growth of C pylori and 76% that contained numerous organisms on histological sections had a positive urease test in less than one hour. There was no significant difference between the specificity and sensitivity of our modified urea broth and the other modified broths described in the literature. This test is a cheap and rapid alternative to the diagnosis of C pylori by Gram stained smears or culture.

Biopsy

New spiral bacterium in gastric mucosa.

A new spiral bacterium, distinct from Campylobacter pylori, was found in the gastric mucosa of six patients with gastrointestinal symptoms. All patients had chronic active type B gastritis and four had oesophagitis. Culture and microscopy for C pylori infection was negative. These unculturable spiral organisms were probably an incidental finding in patients presenting for upper gastrointestinal endoscopy, but it is not possible to say from this small series whether these organisms cause chronic active gastritis. The organism is helical, 3.5-7.5 microns long and 0.9 micron in diameter with truncated ends flattened at the tips, and up to 12 sheathed flagella 28 nm in diameter at each pole. It is proposed that this spiral bacterium should be called "Gastrospirillum hominis Gen.nov., Sp.nov."

Adult

Protracted systemic illness and interstitial nephritis due to minocycline.

A severe hypersensitivity-like illness with acute renal failure, lymphadenopathy and skin rash is reported following minocycline treatment in a 16 year old male. Following haemodialysis and steroid therapy his illness remitted, only to recur on withdrawal of the steroids. With further steroid treatment he recovered completely. Lymphocyte function tests, performed in an attempt to positively incriminate minocycline, were inconclusive due to a general suppression of the patient's lymphocytes to in vitro stimulation. Hypersensitivity reactions attributed to minocycline include skin rashes, lymphadenopathy and one previous case of acute interstitial nephritis.

Adolescent