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Biomedical subjects

D G Colin-Jones

Publications and source records attributed to D G Colin-Jones.

At least 19 recordsLinked to original sources

Oesophageal motor function before and after healing of oesophagitis.

Forty three patients with reflux oesophagitis were studied to investigate the effect of healing on oesophageal function. All patients underwent oesophageal manometry and transit studies before and after complete healing of oesophagitis. Oesophagitis was treated with omeprazole 40 mg/day for a median duration of 12 weeks. Twenty three patients also had an acid clearance test before and after healing. Thirty eight of the 43 patients had 24 hour oesophageal pH monitoring before treatment and this was repeated after healing (while on omeprazole) in 31 of them. Thirty four volunteers served as controls. All volunteers underwent manometry, 33 had oesophageal transit studies, and 23 had acid clearance test. Patients had significantly reduced lower oesophageal sphincter pressures and distal and middle oesophageal amplitudes, longer durations of contraction, and slower velocity of propagation than the controls (16.5 v 22.5 mm Hg; 52 v 92 mm Hg; 46 v 79 mm Hg; 3.1 v 2.7 seconds; and 3.3 v 4.1 cm/second respectively with the corresponding p values = 0.017; 0.0001; 0.0001; 0.017; and 0.006). Patients had significantly longer transit times (9 v 7 and 17 v 11 seconds: p = 0.027 and 0.002 for erect and supine postures respectively). They also had longer acid clearance times (350 v 288 and 536 v 405 seconds: p = 0.044 and 0.016 for sitting and supine postures respectively). There was no significant change in any of the indices of oesophageal function after healing of oesophagitis (lower oesophageal sphincter pressure = 16.5 v 20; distal amplitude = 52 v 60; middle amplitude = 46 v 49; duration of contraction = 3.1 v 3.1; velocity = 3.3 v 3.3; erect transit time = 9 v 9; supine transit time = 17 v 24; acid clearance test (sitting) = 350 v 371; acid clearance test (supine) = 536 v 645). These results indicate that oesophageal motor dysfunction in reflux oesophagitis is a primary phenomenon.

Adult

Postmarketing surveillance of the safety of cimetidine: 10 year mortality report.

A total of 9928 cimetidine users were identified from prescriptions in four centres and followed for 10 years. The 'all-cause' mortality ratio fell from 1.9 in year 1 to 1.0 in years 8 to 10. Most of the early excess in mortality was attributable to cimetidine being given in the late stages of many diseases, often to counter adverse gastric effects of other drugs. Specific causes of mortality during years 5-10 of the study, were generally unremarkable. Significant increases in mortality ratios were apparent, however, for oesophageal cancer (years 5-7, 2.3; years 8-10, 1.9); lung cancer (years 5-7, 1.1; years 8-10, 1.7); diseases of the oesophagus, stomach, and duodenum (years 5-7, 3.3; years 8-10, 2.3); and chronic liver disease (years 5-7, 2.4; years 8-10, 3.3). None of these increases in mortality seems to be attributable to an adverse effect of cimetidine use. Data are also presented for mortality from diseases of the nervous system. Eight deaths (of which one was miscoded) were certified as being from motor neurone disease, representing a mortality ratio of 2.6 for years 2-10 of the study which is of borderline statistical significance. This study confirms that cimetidine is safe. Mortality from some diseases increased over the study period, but selection rather than any adverse effect of the drug is likely to be the explanation.

Cimetidine

Post-cimetidine surveillance for up to ten years: incidence of carcinoma of the stomach and oesophagus.

The long-term effects of cimetidine on the occurrence of gastric and oesophageal cancer were assessed in a prospective cohort study of 9928 patients who had been prescribed cimetidine. They were first identified between 1978 and 1980, and cancer registrations and deaths were identified among them over a period of up to 10 years. One hundred and eleven cancers were identified after the start of cimetidine treatment: 71 were adenocarcinomas of the stomach, 27 were carcinomas of the cardia and/or oesophagus (22 adenocarcinomas, five unknown histology) and the remaining 13 tumours were squamous cell cancers of the oesophagus. Only six patients presented with early gastric cancers. Over a period of eight years the ratio of observed to expected (O/E) gastric cancer deaths has fallen from 10.7 (p < 0.001) to 1.2 (NS). The O/E ratio of oesophageal cancer deaths also fell over the first six years of study, from 5.4 (p < 0.01) to 1.4 (NS) but it has risen slightly in years 7 and 8 to 3.7 (p < 0.05). These findings do not suggest that there is an increased risk of developing oesophageal or gastric cancer from cimetidine treatment, and are generally consistent with cimetidine being used inadvertently to treat the early symptoms of gastric and oesophageal cancer. The slight rise in oesophageal cancer deaths in years 7 and 8 was unexpected and will be the subject of further observation.

Adenocarcinoma

The evaluation of a gastric bile probe.

The purpose of this study was to validate a new technique for measuring duodenogastric bile reflux in the human subject. A custom built cadmium telluride gamma detector (Radiation Monitoring Devices, Mass), small enough to be passed into the oesophagus and stomach, was developed and tested for sensitivity to 99Tcm and 75Se radioisotopes. When immersed in radiolabelled water, the detector was capable of measuring gamma radiation in quantities as low as 0.1 microCi (0.0037 MBq) per ml. Two patients (A and B) with endoscopically proven bile reflux, and three normal volunteers (C, D and E) underwent oesophageal manometry to map the position of the lower oesophageal sphincter (LOS). The gamma probe was passed via the nose, to a position in the gastric fundus, 5 cm below the LOS. Each subject was placed supine under a gamma camera (Siemens LFOV 37 ZLC head), centred on the epigastrium. A 4 mCi (148 MBq) dose of radiolabelled 99Tcm-HIDA was administered intravenously, and simultaneous internal/external scanning was performed for between 45 and 90 min. Internal gamma probe data was transferred by a screened cable to a Memolog 600 portable recorder, using a 5 s counting interval, and from the gamma camera to a Nodecrest Micas III computer, using a 15 s counting interval. Gamma camera counts from a region of interest over the fundus of the stomach were then correlated with counts from the internal probe using a linear regression analysis program on the Nodecrest. The internal gamma probe functioned well at body temperature in the acidic gastric environment. Radiolabelled bile refluxed into the stomach during HIDA scanning in three out of the five subjects (one patient and two normal volunteers). There was a strong correlation between internal and external gamma counts (A, r = +0.79; C, r = +0.53; E, r = +0.54; P greater than 0.01). In the other two cases, there was no bile reflux, but still a significant correlation between internal and external gamma counts (B, r = +0.89; D, r = +0.75; P greater than 0.01). The mean correlation coefficient for the series of five cases was +0.70. We conclude firstly that the newly developed internal gamma detector is capable of measuring the reflux of radiolabelled bile into the human stomach and, secondly, that bile reflux may occur in normal subjects as well as those with upper gastrointestinal pathology.

Aged

Future needs for ERCP: incidence of conditions leading to bile duct obstruction and requirements for diagnostic and therapeutic biliary procedures.

Although the development of endoscopic methods of treatment for biliary obstruction has proceeded rapidly in recent years, endoscopic retrograde cholangiopancreatographic (ERCP) services are patchily distributed. A recent survey by the British Society of Gastroenterology has shown that almost half the district general hospitals questioned did not have a sphincterotomy service available locally. To assess the level of provision required, two investigations have been undertaken. Firstly, an epidemiological study of bile duct obstruction has been carried out in the South Western Region. Secondly, the actual surgical and endoscopic workload in treating obstructive jaundice has been analysed in two health districts. Using present incidence and treatment rates at least 50 ERCPs per 100,000 of the population per year are estimated to be required in the future. Surgical treatment rates can be expected to fall as the number of therapeutic ERCPs increases. The implications of this estimate in equipment and staffing terms are discussed.

Aged

Studies on the pathogenesis of the early dumping syndrome induced by intraduodenal instillation of hypertonic glucose.

A reaction indistinguishable from the early dumping syndrome was induced in four of nine normal volunteers by intraduodenal instillation of a hypertonic glucose meal. Tachycardia and marked peripheral vasodilatation were demonstrated in 'dumpers' by Doppler ultrasound measurements of the arterial blood flow signal. The dumping reaction was not detectably altered by the addition of guar to the meal. Plasma VIP concentration rose and plasma volume fell to a similar degree in 'dumpers' and 'non-dumpers', suggesting that neither event is an integral component of the dumping mechanism. In contrast, the rates of rise of blood glucose and enteroglucagon concentration were markedly greater in 'dumpers'. The results are inconsistent with the conventional explanation that the early dumping syndrome is caused by a large osmotic fluid shift, but are compatible with a mechanism involving an initial period of intestinal hypermotility.

Blood Flow Velocity

Campylobacter pylori. An advance in understanding of dyspepsia and gastritis.

The prevalence of Campylobacter pylori (CP) rises with age, as does gastritis. There is now convincing evidence that CP is causative in the majority of cases of active chronic gastritis and that its eradication substantially improves the severity of the gastritis, even back to normal in some cases. A small minority of people may have other factors causing their gastritis, bile reflux, or anti-inflammatory drugs, for example, CP causes temporary dyspeptic symptoms when an individual receives an acute infection for the first time, but what is much less certain is whether or not CP is responsible for chronic dyspeptic symptoms, and whether eradication of CP will improve dyspepsia. At present the therapeutic trials are too few and too small to be sure, but some individuals may benefit.

Acute Disease

Pharmacological response to cimetidine and healing of duodenal ulceration: effects of high-dose cimetidine and combination of cimetidine with pirenzepine.

Overnight gastric secretion was studied in 32 patients with acute duodenal ulcers before treatment and whilst taking cimetidine 400 mg b.d. After 6 weeks of treatment with cimetidine 400 mg b.d. 13 patients had healed ulcers, seven patients had healed ulcers but a persistent erosive duodenitis, and 12 patients had persisting ulceration. Inhibition of nocturnal gastric secretion by cimetidine 400 mg b.d. was most profound in patients who healed their ulcers completely; a less profound inhibition of nocturnal gastric secretion was seen in the non-healing and duodenitis groups. In patients with persisting ulcers and poor inhibition of nocturnal gastric secretion by cimetidine, gastric secretion could be suppressed by either cimetidine 400 mg b.d. in combination with pirenzepine 50 mg b.d., or by cimetidine 1600 mg nocte, but suppression of nocturnal gastric secretion was more effective with cimetidine 1600 mg than cimetidine with pirenzepine.

Adolescent

When should endoscopy (or radiology) be used in dyspepsia and peptic ulcer disease?

It is now possible readily to investigate dyspeptic symptoms using either a double-contrast barium meal or upper gastrointestinal endoscopy. The accuracy of endoscopy makes it preferable for routine use. As oesophagogastro-duodenoscopy (OGD) is invasive, some risks (albeit very small) are involved. Moreover, this technique has some weaknesses. For these reasons, selection of patients is important. Organic disease is most likely to occur in older patients: anyone presenting with dyspepsia for the first time over the age of 40 years should be investigated automatically. In individuals under 40 years of age, organic disease is less common and some selection criteria should be applied to reduce the number of negative investigations. After age, smoking is probably the single most important adverse factor. For gastric ulcer, endoscopy with biopsy, repeated after a course of therapy, is routine, but for duodenal ulcer repeat examination need not normally be undertaken owing to the effectiveness of modern healing drugs. Methods for improving the diagnostic accuracy of patient histories and clinical examinations need to be developed in order to utilize diagnostic investigations more efficiently for the patients' benefit.

Dyspepsia

Controlled comparison of cimetidine and carbenoxolone sodium in gastric ulcer.

Fifty-four outpatients with endoscopically diagnosed benign gastric ulcer were allocated at random to treatment with either cimetidine 800 mg daily for six weeks or carbenoxolone sodium 300 mg daily for one week then 150 mg daily for five weeks. Ulcers were reassessed by endoscopy at the end of the trial. The endoscopist was unaware of the treatment and did not take part in the clinical care of the patients. Twenty-one of the 27 patients (78%) given cimetidine and 14 of the 27 (52%) given carbenoxolone had healed ulcers. Symptomatic response occurred earlier with cimetidine but was not significantly better. Unwanted effects were more common in the carbenoxolone group: 12 patients developed hypokalaemia, four of whom needed oral potassium supplements. The results suggest that histamine H2-receptor blockade is at least as effective as carbenoxolone sodium for benign gastric ulcer and produces fewer side effects.

Administration, Oral