A trial of a test-and-treat strategy for Helicobacter pylori positive dyspeptic patients in general practice.

Computer models of different strategies for the management of dyspepsia in primary care indicate that a 'test-and-treat' approach is likely to be associated with the lowest costs and acceptable clinical outcomes. We present information on computer modelling studies and report the findings of a randomised trial comparing a Helicobacter pylori test-and-treat strategy with referral to direct access endoscopy in the management of dyspepsia in general practice. We compared costs and clinical outcomes in patients managed for one year in study (test-and-treat) and control (endoscopy) practices in south London. Patients aged less than 45 years presenting with persistent dyspepsia without alarm symptoms (141 study patients, 91 control patients) were studied. In the one-year follow-up period there were 17 endoscopies in the study group: all the control patients underwent initial endoscopy and five further endoscopies were performed. None revealed peptic ulcer or cancer. Forty-three (30%) of the study patients compared with 16 (17%) of the controls were referred to hospital clinics (p < 0.025). The cost of management per patient for one year in the study group was 205.67 Pounds, compared with 404.31 Pounds in the control group (p < 0.0001). Clinical outcomes in both groups at one year were comparable. An H. pylori test-and-treat strategy for dyspeptic patients aged less than 45, employing office-based serology testing, appears to be associated with substantially lower costs than initial endoscopy and with similar clinical outcomes.

Plasma arachidonic acid-rich phospholipids in Crohn's disease: response to treatment.

1. Increased concentrations of plasma polyunsaturated fatty acids have been implicated in the pathogenesis of Crohn's disease. However, it is not known whether there are corresponding changes in circulating phospholipids--the major source of fatty acids in the plasma. 2. Fasting plasma samples were obtained from 17 control subjects and 13 patients with active Crohn's disease [Simple Index of Crohn's Disease Activity (SICDA) > 6] before, and 2 and 8 weeks after, treatment with either a peptide diet or oral prednisolone. 3. Before treatment, the Crohn's disease patients had mildly active disease (SICDA 9.9 +/- 0.8, erythrocyte sedimentation rate 26.4 +/- 6.5 mm/h, serum C-reactive protein 2.8 +/- 0.4 mg/l). The proportions of the polyunsaturated phosphatidylcholine species, 16:0-20:4 (10.0 +/- 0.7%) and 16:0-22:6 (7.1 +/- 0.8%), were both significantly higher than those in healthy controls (7.6 +/- 0.5%, P < 0.01 and 5.3 +/- 0.5%, P < 0.05 respectively). 4. After 2 weeks treatment, the SICDA in the Crohn's disease patients decreased to 3.2 +/- 0.6 (P < 0.0001 compared with the pretreatment value), and there were corresponding falls in the erythrocyte sedimentation rate (to 12.6 +/- 2.7 mm/h, P < 0.05) and C-reactive protein concentration (to 1.7 +/- 0.3 mg/l, P < 0.05)--these improvements being maintained at 8 weeks. There was also a fall to normal values in 16:0-20:4 (to 7.7 +/- 0.6%, P < 0.01 compared with the pretreatment value) and in 16:0-22:6 (to 5.7 +/- 0.5%, P not significant), by week 8. 5. The proportions of polyunsaturated phosphatidylcholine molecular species were increased in the plasma of patients with active Crohn's disease, but fell to normal levels during disease remission. These observations are consistent with the theory that, in active Crohn's disease, the mucosal phospholipids containing polyunsaturated fatty acids are increased, contribute to eicosanoid synthesis and 'spill' into the plasma.

Endoscopy: throat spray or sedation?

Anxious patients tolerate endoscopy poorly. It was proposed that such patients might derive most benefit from sedation, while most non-anxious patients would prefer endoscopy with lignocaine throat spray alone. In a prospective study, 200 outpatients underwent diagnostic endoscopy after receiving one of two detailed information sheets which offered them either the choice between spray or sedation (n = 100) or the same choice but encouraged those who were anxious about endoscopy to choose sedation (n = 100). When given an informed choice, most non-anxious patients prefer not to be sedated most non-anxious patients prefer not to be sedated during diagnostic endoscopy. If patients who are anxious about the procedure are advised to choose sedation, those who nevertheless opt for topical throat spray alone find the endoscopy just as comfortable. If the endoscopy were to be repeated, 73% of the spray group and 77% of the sedation group would make the same choice again. Of 33 patients who chose spray but had been given only sedation for a previous endoscopy, 26 (79%) would choose spray again for a future endoscopy. The choice of spray or sedation should reflect the patient's view as well as that of the endoscopist.

Comparison of simultaneous 99mTc-HMPAO and 111In oxine labelled white cell scans in the assessment of inflammatory bowel disease.

Forty-seven patients, 29 with chronic inflammatory bowel disease (IBD) and 18 with presumed irritable bowel syndrome, including one with uncomplicated diverticular disease, were studied with simultaneous technetium-99m hexamethylpropylene amine oxime and indium-111 oxine labelled leucocyte scans performed at 1, 3 and 24 h. Twenty-seven patients with IBD had active disease as judged by clinical and laboratory criteria and all of these had positive scans with both agents. No false positive studies were obtained. The 1-h 99mTc-HMPAO WBC scans showed the same distribution to disease as the 3-h 111-In WBC scans, with no difference in intensity (P < 0.92); they showed more extensive disease (P < 0.02) and more intense uptake (P < 0.001) than did the 1-h 111-In scans. The 3-h 99mTc-HMPAO WBC scans showed more extensive disease (P < 0.002), with greater intensity (P < 0.0005), than did the 3-h 111In WBC scans. Physiological bowel activity on 3-h 99mTc-HMPAO WBC scans was present in 12 patients but was faint and did not interfere with assessment of disease extent and activity. It is concluded that in terms of isotope availability, radiation dosimetry and image quality, 99mTc-HMPAO is the agent of choice in detecting active IBD, with localization of disease possible at 1-h after re-injection and optimal resolution and definition of disease extent at 3 h. A negative scan reliably excludes active disease.

Detection of an increased incidence of early gastric cancer in patients with intestinal metaplasia type III who are closely followed up.

Because early gastric cancer is associated with a much better prognosis than advanced disease, its diagnosis is important. Over a 12 year period (1976-87), a progressive increase in the incidence of early gastric cancer was observed. Twenty four of the 718 (3.3%) consecutive gastric resections for gastric cancer in this period were in patients with early gastric cancer. Six of the 24 were diagnosed in the first six year period (1976-81) and 18 in the second six year period (1982-87) (p less than 0.01). This increase was observed during the prospective phase of the study, when all patients diagnosed on initial biopsy specimen as showing type III intestinal metaplasia underwent follow up endoscopy and biopsy at six to 12 month intervals. Eleven of the 18 with early gastric cancer detected in this period were diagnosed as a direct result of this follow up. We conclude that early gastric cancer can be diagnosed with increasing frequency if patients with type III intestinal metaplasia are closely followed endoscopically.

Assessment of gastro-esophageal reflux disease: comparison of reflux scintigraphy with endoscopy biopsy and esophageal pH monitoring.

In a study designed to evaluate reflux scintigraphy in 79 patients with gastro-esophageal reflux disease, quantitated reflux scintigraphy was found to have predictive values of 73% in detecting reflux as judged by esophageal pH monitoring, of 63% in detecting esophagitis as judged by esophagoscopy and biopsy, and of 77% in detecting the presence of either esophagitis or reflux. However, its sensitivity was only 48, 58 and 42%, respectively. Gastro-esophageal reflux scanning has little value in the routine clinical diagnosis of mild to moderate gastroesophageal reflux disease, but none of the other tests (biopsy, endoscopic appearances of 24 hour esophageal pH monitoring) were sufficiently specific to be taken as a sole diagnostic criterion ("gold standard"). Investigation of gastro-esophageal reflux disease could probably best be limited to endoscopy (especially to detect ulceration or metaplasia and to exclude neoplasia) with 24 hour pH monitoring in addition for those patients with suspected reflux disease but negative endoscopy.

Fatal phenolphthalein poisoning with fulminant hepatic failure and disseminated intravascular coagulation.

A 32-year-old female ingested an unknown quantity of Nylax tablets containing phenolphthalein. This results in widespread organ involvement, predominantly causing liver damage and disseminated intravascular coagulation. The eventual cause of death was massive liver necrosis. We suggest that phenolphthalein was responsible for the widespread damage.

Tumours of the pancreas as a sequel to abdominal irradiation.

Two cases of tumours arising in or near the pancreatic head are reported in patients previously treated with abdominal irradiation for testicular tumours. These are only the third and fourth such cases to be reported and they suggest that second cancers may develop as a result of abdominal irradiation for malignant disease.

Non-ulcer dyspepsia and short term De-Nol therapy: a placebo controlled trial with particular reference to the role of Campylobacter pylori.

This double blind randomised study tested the effectiveness of colloidal bismuth subcitrate (De-Nol) in non-ulcer dyspepsia (NUD) and if any benefit is associated with clearance of Campylobacter pylori (C pylori) from the gastric mucosa. Sixty six patients with dyspepsic symptoms, normal abdominal ultrasound, and upper GI endoscopy, were randomly allocated to placebo or De-Nol for eight weeks. Antral biopsies were taken for bacteriological and histological examination, and endoscopies and clinical questionnaires were administered before and after treatment. Fifty two patients (25 on De-Nol and 27 on placebo) completed the trial. De-Nol cleared C pylori from 10 of the 12 C pylori positive patients (83.3%), whereas placebo did not clear C pylori from any of the eight C pylori positive patients (p less than 0.01). In patients receiving De-Nol gastritis improved (p less than 0.01) and symptomatic response was better (p less than 0.001) compared with placebo. In the placebo group seven of the 19 C pylori negative patients became positive: this was associated with significant deterioration of symptoms, a phenomenon not seen in the De-Nol treated group.

Ambulatory esophageal pH recording in gastroesophageal reflux: relevance to the development of esophagitis.

In a group of 60 patients with symptomatic gastroesophageal reflux (GER), we carried out upper gastrointestinal (GI) endoscopy and 24-h ambulatory esophageal pH monitoring to assess the relationship between acid reflux and esophagitis. The results of 24-h pH measurement were compared with those of 15 asymptomatic control subjects who were studied with ambulatory 24-h esophageal pH monitoring only. Thirty-two patients (53.3%) had a normal esophagus macroscopically, and 28 patients (46.7%) had some degree of esophagitis. There was no significant difference between the two groups with and without esophagitis, regarding male:female ratio, age, and duration of symptoms. The group with esophagitis was more symptomatic (p less than 0.001) than the group without, and differed significantly in relation to all pH variables, i.e., number of GER episodes per hour, duration of mucosal exposure to acid (pH less than 4), and number of GER episodes requiring more than 5 min to clear per hour for the upright, supine, and 24-h periods, compared with the control group (p less than 0.001) and the group without esophagitis (p less than 0.001). In the group with esophagitis, comparison of the above pH variables in the upright and supine periods showed significantly higher values in the upright than in the supine period for the total number of reflux episodes per hour (p less than 0.001) and the number of episodes greater than 5 min/h (p less than 0.05). We conclude that the presence of esophagitis is related to both frequency and duration of GER episodes. Our findings also stress the importance of daytime acid exposure in the pathogenesis of esophagitis.

Collagenous colitis with rapid response to sulphasalazine.

A case of collagenous colitis in a young female with a rapid response to sulphasalazine both symptomatically and histologically is reported. This is only the third such response to be reported. In most published accounts, collagenous colitis fails to respond to treatment and runs a very prolonged course.

Bismuth: effects on gastritis and peptic ulcer.

The healing properties of colloidal bismuth subcitrate (CBS) on peptic ulcer are well established and several studies have shown that healing with CBS is associated with a lower relapse rate than that produced by H2-receptor antagonists. The recent observation that CBS is effective against Campylobacter pylori has shed light on this because recent studies have shown that eradication of C. pylori by CBS leads to resolution of the associated gastritis and this may explain the low relapse rates. CBS is also effective in C. pylori positive patients with non ulcer dyspepsia (NUD) in whom clearance of these organisms from the stomach is associated with significant improvement of the associated gastritis and symptoms.

Cricopharyngeal Crohn's disease.

We report a case of Crohn's disease of the cricopharyngeal oesophagus which presented with complete dysphagia and was successfully treated by balloon dilatation. We can find no previous reports of such a case.

In vivo insulin antagonism but evanescent in vitro tissue effect in rats with growth hormone-secreting tumors.

Rats bearing mammosomatotropic tumors have raised insulin but lowered glucose concentrations. To determine if growth hormone (GH) secreted by these tumors causes insulin antagonism, pancreatic suppression tests utilizing infusions (per kg per min) of glucose (8 mg), insulin (200 ng) and somatostatin (1.4 micrograms) for 130 min were performed. Although the steady state plasma glucose and insulin levels (mean of 90, 100, 110, 120 and 130 min samples) were similar in 8 control and 13 tumor-bearing rats, the decrease from the already depressed basal glucose concentration (mmoles/l +/- SE) in the tumor animals was less than in the controls (0.90 +/- 0.30 vs. 2.56 +/- 0.040, p less than 0.005). Since the interpretation of these results was not entirely clear, glucose and insulin-glucose tolerance tests were performed. The glucose disappearance rates (%/min +/- SE) in the glucose tolerance test were lower in 17 tumor rats (2.00 +/- 0.13) compared to 17 control animals (2.51 +/- 0.22). This difference just missed statistical significance (t = 2.00, value of 2.04 necessary for p = 0.05). The decrease occurred in the presence of increased insulin (nmoles/l X 16 min) levels (4.29 +/- 0.38 vs. 2.58 +/- 0.29, p less than 0.005) suggesting insulin antagonism. The glucose disappearance rates (%/min +/- SE) in the insulin-glucose tolerance test were less in 12 tumor-bearing rats compared to 11 control animals (2.80 +/- 0.29 vs. 4.12 +/- 0.35, p less than 0.02). Thus, these GH-secreting tumors cause insulin antagonism in vivo. Freshly isolated hepatocytes from these tumor-bearing animals manifest decreased insulin binding and action (Diabetologia 25:60, 1983). In the present study, however, insulin binding and action (net glucose-C14 incorporation into glycogen) were normal after the hepatocytes were cultured for two days. This suggests that the changes induced by GH in vivo that lead to insulin antagonism are short-lived.

Campylobacter pylori and non-ulcer dyspepsia.

Non-ulcer dyspepsia (NUD) is a poorly understood syndrome often present in association with gastritis. Among patients undergoing gastroscopy, some with NUD have a gastric mucosa colonized by the campylobacter-like organism, Campylobacter pylori. We therefore studied prospectively 55 consecutive patients with NUD and 15 normal controls to determine the prevalence of C. pylori organisms, and to investigate their association with histological gastritis, macroscopic evidence of gastritis, sex, smoking, alcohol consumption, and dyspeptic symptoms. We found a 45.4% prevalence in NUD patients which was statistically significantly higher than the 13.33% prevalence in the control group (p less than 0.05). We also found a close association between C. pylori and microscopic evidence of gastritis (p less than 0.001), male sex (p less than 0.001), and postprandial bloating (p less than 0.05). We did not find any significant association between C. pylori and macroscopic evidence of gastritis, smoking, alcohol consumption and other dyspeptic symptoms. Our findings suggest that C. pylori may play a pathogenic role in NUD.

Mefenamic acid enteropathy.

The clinical, radiological, and histological features of two patients with severe intestinal damage induced by mefenamic acid and mimicking coeliac disease are described. Symptoms rapidly reverted on withdrawal of the drug, and in one case, did not relapse during treatment with other non-steroidal anti-inflammatory drugs.