Biomedical subjects
Publications and source records attributed to F I Lee.
A 70-year-old woman with no previous gastroesophageal surgery gave a 6-month history of dysphagia. Barium studies suggested a diagnosis of achalasia. Esophageal manometry showed absence of peristalsis and a high lower esophageal sphincter pressure. Endoscopy showed a dilated esophagus with food residue, and Barrett's esophagus was present. The association of Barrett's esophagus and achalasia must be rare.
Two hundred patients received either ranitidine 150 mg or 300 mg at night for 18 months to prevent duodenal ulcer relapse. Recurrence rates were lower in patients receiving the higher dose of ranitidine (3.1% v 9.7%, p = 0.78; 6.5% v 16.7%, p = 0.037; and 8.9% v 17.0%, p = 0.121 at six, 12, and 18 months respectively). In patients receiving ranitidine 150 mg, recurrences were significantly more common in smokers than non-smokers after 12 and 18 months, while in patients receiving ranitidine 300 mg recurrence rates were similar in smokers and non-smokers. Ranitidine 300 mg at night abolishes the adverse effect of smoking observed during maintenance treatment with ranitidine 150 mg at night and may therefore be an appropriate maintenance dose for smokers who relapse during standard dose maintenance treatment.
The occurrence of upper gastrointestinal disease and the relevance of nonsteroidal antiinflammatory drug (NSAID) usage were documented in 511 consecutive patients (321 women, 190 men) over 70 yr old, referred for upper gastrointestinal endoscopy in a district general hospital. The findings were benign esophageal disease (43%), normal (15%), gastric ulcer (11.5%), and duodenal ulcer (11%). Gastric ulcers were more common in women taking NSAIDs (25%) than in NSAID abstainers (7%) p less than 0.001 and male NSAID users (8%) p less than 0.001. Esophagitis and esophageal stricture were not influenced by NSAID usage, but gastric erosions were more common (10% vs. 3%) p less than 0.01. Of 142 patients receiving NSAIDs, 41% presented with hemorrhage, compared with 20.5% of NSAID abstainers (p less than 0.001). Hemorrhage was as common in aspirin takers (15 of 33, 45%) as in standard-dose NANSAID takers (43 of 109, 39%), even though 86% were taking 300 mg of aspirin per day or less. In elderly patients, esophageal disease is common. NSAID use, even low-dose aspirin, is associated with an increased risk of hemorrhage. In females, NSAID usage is associated with gastric ulcer.
Chronic duodenal ulceration is a recurrent disease. Acute exacerbations may be treated effectively with H2-receptor blockers and a variety of other agents. Intermittent treatment may pose risks of recurrence and complication, and these may be greatly reduced by maintenance treatment. Operative management also reduces recurrence rates, which, however, are commoner in patients coming to surgery nowadays. Full-dose maintenance therapy is an effective option for selected patients.
One hundred thirty-six unselected patients with Crohn's disease (43 men, 93 women) were studied for the possibility of psoriasis and questioned regarding their family history, as were 136 controls, matched for age and sex. Psoriasis was present in 13 of the 136 patients with Crohn's disease (9.6%), compared with three of 136 controls (2.2%) (p less than 0.02). Age at onset and anatomical site of Crohn's disease did not influence the result, and there was no difference between the sexes. Fourteen (three with psoriasis) of the 136 Crohn's patients (10%) had a family history of psoriasis in first-degree relatives compared with four of 136 controls (2.9%) (p less than 0.02). Psoriasis is more common in patients with Crohn's disease and their first-degree relatives than in controls, suggesting the possibility of a genetic link. Psoriasis should be included among the extraintestinal manifestations of the condition.
The human gastric fundal mucosa contains a variety of endocrine cells, the most numerous of which are the so-called enterochromaffin-like (ECL) cells. We have studied the variations with age and sex of the ECL cell populations, utilizing an assessment based on multiple endoscopic biopsies from four groups of subjects. Plasma gastrin levels were also determined in these subjects. In males, endocrine cell densities declined with age but the ECL cell numbers in females opposed this trend. ECL cell counts showed no appreciable differences between young and old females. In older females, there was a high rate of gastritis and increased levels of circulating gastrin. Concentrations in older females (29.6 +/- 8.7 pmol/l) were higher than in both younger (less than 45 years) males (5.3 +/- 1.1 pmol/l) and older (greater than 55 years) males (6.3 +/- 0.6 pmol/l) (P less than 0.05). The plasma gastrin level was also higher in older females than in young females (13.1 +/- 4.5 pmol/l), although this difference failed to reach statistical significance. In conclusion, clinically silent gastritis, raised gastrin levels, and maintenance or rise of ECL cells numbers, in opposition to a general decrease in endocrine cells with age, appear to be features of women of more than 55 years of age. The variations in ECL cell populations reported here should be taken into account when evaluating possible pathological alterations of the stomach.
A randomized, double-blind, clinical trial was undertaken to compare 150 mg ranitidine b.d. with 300 mg ranitidine nocte in the treatment of reflux oesophagitis. Endoscopy data were evaluable for 336 patients after 8 weeks of treatment. At this time 75% of patients who received 150 mg ranitidine b.d., and 73% of those who received 300 mg nocte, had healed or showed endoscopic improvement to grade I oesophagitis. At 12 weeks these rates had increased to 89 and 88%, respectively. Oesophageal biopsies from 258 patients at 8 weeks showed histological improvement in 44 and 47% of those treated with 150 mg ranitidine b.d. and 300 mg ranitidine nocte, respectively. After 12 weeks histological improvement was apparent in 57 and 54% of biopsies from each group, respectively. Symptom severity and frequency was reduced to a similar extent by both treatments. Adverse events were reported by 15 patients. A 300-mg bedtime dose of ranitidine was found to be a well-tolerated, effective alternative to twice daily treatment in reflux oesophagitis.
Famotidine (40 mg) and 800 mg cimetidine as single night-time doses were compared in a randomized, double-blind, multicentre study of acute treatment for duodenal ulceration. Fifteen centres recruited 304 patients into the study. Of these, 274 were included for analysis, with 136 receiving famotidine and 138 receiving cimetidine. After 4 weeks, 75% of the patients who received famotidine and 77% of the patients who received cimetidine were healed. At 6 weeks the cumulative healing rates were 91% with famotidine and 87% with cimetidine. Differences between the groups were not significant at 4 or 6 weeks. No significant difference in healing rates between smokers and non-smokers was found. Day and night pain resolved rapidly in both groups. Both treatments were well-tolerated; adverse events were reported in 17 patients on famotidine and 18 on cimetidine, with headache the most frequent event in both groups. Famotidine is effective and well-tolerated in the short-term treatment of duodenal ulcer.
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Enprostil is a new synthetic prostaglandin E2 with antisecretory and mucosal-protective effects. We compared it with ranitidine in the healing of duodenal ulcer and also examined the subsequent relapse rate. Three hundred thirteen patients were recruited in 15 centers in Europe, of whom 158 were treated with enprostil (E) 35 micrograms twice daily and 155 with ranitidine (R) 150 mg twice daily for up to 6 weeks, using a double-blind method. Patients in both groups were of comparable demography. Healing was significantly quicker with ranitidine. Of patients randomized to treatment, healing (intention-to-treat analysis) at 4 weeks was E 47% and R 69%, and at 6 weeks it was E 66% and R 88%. In patients who met all protocol criteria and completed treatment, healing at 4 weeks was E 58% and R 80%, and at 6 weeks it was E 81% and R 92%. Early relief of pain, both during the day and at night, was significantly quicker with ranitidine. Nausea, diarrhea, vomiting, and abdominal pain occurred more often with enprostil. There were no clinically important abnormalities in hematology or biochemistry. Relapse rates were similar. In conclusion, enprostil is not as effective as ranitidine in healing duodenal ulcers.
Between January 1984 and December 1986, 116 patients were found to have columnar-lined esophagus (Barrett's esophagus) during upper gastrointestinal endoscopy. Twenty-eight patients (16 men and 12 women) were found to have peptic ulcer of the esophagus (Barrett's ulcer). In 17 (60%), standard measures and ranitidine 300 mg daily resulted in healing. Two men with resistant ulcers were treated by surgical repair of their hiatus hernia. Nine (six men, three women) in whom healing failed to occur on this regimen after 3-15 months were treated with high dose ranitidine (300 mg bd). In five, healing was complete after 8 wk and one more healed after an additional 4 wk. The three patients with unhealed ulcers after high dose ranitidine received omeprazole 40 mg in the morning. In two of these, ulcers healed after 4 wk; in the third, one of two ulcers persisted after 8 wk, although the remaining ulcer was smaller and more superficial. Pain relief was good, but minor reflux symptoms persisted in both treatment groups. On completion of the study, patients received 300 mg ranitidine at night. Powerful acid-reducing regimens may be required to heal a proportion of Barrett's ulcers.
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In order to characterize the differentiation of endocrine cells present in Barrett's oesophagus and to determine if they express a single or multiple hormonal pattern, endoscopic biopsies were taken from both the lesion and the fundus of 45 patients and studied at the light microscopical level. Conventional histology revealed three different epithelial patterns: gastric atrophic fundic, intestinal and junctional. A mixture of these patterns was present in 28 cases (62%) and the single type was identified in 17 cases (38%). The use of three silver staining methods and antibodies to human chromogranins allowed us to identify numerous endocrine cells in all but 1 case. Eleven sera against all the most common hormones stored in the endocrine cells of the gut were used to identify the main products of the cells. The following immunoreactivities were identified: 5-hydroxytryptamine (5-HT) (in 75% of the studied cases), somatostatin (87%), motilin (31%), pancreatic polypeptide (PP) (20%), glucose-dependent insulinotropic polypeptide (20%), gastrin (15%), glucagon (15%), peptide tyrosine tyrosine (13%), secretin (7%) and neurotensin (2%). No cholecystokinin-immunoreactive cells were identified. Our results indicated that, in Barrett's epithelium, both gastric and intestinal endocrine cells differentiate, in accordance with the variability of differentiation in the non-endocrine cells present in the different types of columnar epithelium. These findings provide support for the conclusion that Barrett's epithelium arises from a pluripotential stem cell capable of both gastric and intestinal differentiation.
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Colchicine (1 mg/day), or an identical placebo, was given to 64 patients with primary biliary cirrhosis in a double-blind controlled trial. Due to a novel, pair-matched trial design, the two groups were exceptionally well matched at entry. In comparison with placebo, colchicine produced a beneficial effect on serum albumin and bilirubin levels at 3 months in patients who had abnormal liver function (bilirubin greater than 20 mumol/l) at entry: (albumin, P = 0.047; bilirubin, P = 0.022). In patients with normal liver function at entry (bilirubin less than 20 mumol/l), beneficial effects were noted on total globulin levels at 3 months (P = 0.013) and on immunoglobulin G levels at 3 and 6 months (P = 0.044 and 0.001, respectively). At 18 months, survival estimate in the colchicine and placebo groups were 84% and 69%, respectively. The difference did not reach significance. Colchicine produced an early improvement in liver function and immunoglobulin levels. Few serious side effects were encountered, and colchicine clearly merits long-term study in the treatment of primary biliary cirrhosis.
A woman developed severe cholestatic jaundice and progressive renal failure secondary to amyloid deposition. The amyloid protein was of AL type, consisting of IgG-related kappa chains. This form of amyloidosis is classified as immunocyte-related, not associated with myeloma.
Fifty five (26%) of two hundred and fifteen patients presenting with Crohn's disease in the Blackpool area over a 15 year period (1969-1983) were over 60 years of age. There were twice as many women as men (38:17). In 60% disease was limited to the large bowel compared to only 29% in the younger age group. Many of these were women with mild distal colitis. Twenty one patients required operative management. In general, the prognosis was good in colonic disease, but in small bowel and ileocolonic disease the necessity for early operative intervention was potentially fatal. Delayed diagnosis, poor nutritional state and associated disease were relevant adverse factors. The majority of patients at the time of review were well and, where necessary, were coping satisfactorily with a stoma.
A randomised double blind clinical trial was undertaken in the UK and Ireland to compare ranitidine 300 mg given as a single bed time tablet with ranitidine 150 mg twice daily in the acute treatment of duodenal ulcers. Of the 594 patients with endoscopically diagnosed duodenal ulcer entered into the trial, 424 patients had complete endoscopic findings on which healing rates at four weeks were determined. By this time 156 of 201 (78%) patients healed with ranitidine 300 mg nocte compared with 186 of 223 (83%) receiving ranitidine 150 mg twice daily (p = 0.28). After eight weeks of treatment 97% of the patients in each group were healed. The healing rates for smokers and non-smokers did not differ significantly at either four or eight weeks. Each regimen was equally effective in reducing day and night-time pain. Adverse events were reported in 23 patients overall; 12 were withdrawn from the trial. Minor abnormalities in liver function tests were noted in three patients. The trial confirmed that a single dose of ranitidine 300 mg given at night is a safe, effective alternative treatment to ranitidine 150 mg bd for the acute treatment of duodenal ulcer.