The size dependence of tin oxide atomic cluster nanowire field effect transistors.

Tin oxide (SnO(2)) cluster nanowires have been fabricated using atomic clusters as building blocks. Nanowires with widths of less than 100 nm were defined using electron beam lithography followed by deposition of Sn clusters which were subsequently thermally oxidized. The cluster nanowires were used to fabricate field effect transistors. The transistors were n-type and demonstrated a clear size-dependent behaviour. With zero gate bias the narrowest wires were depleted, both the carrier concentration and the conduction quickly increasing with wire width. This behaviour is attributed to the formation of a surface depletion region caused by Fermi level pinning. The width of the depletion region was estimated using the carrier concentration calculated from the transistor threshold voltages. The change in the wire conductance with UV illumination was also investigated. Illumination with 365 nm light increases the conduction by up to 40 times. This is attributed to a combination of an increase in carriers due to photo-desorption of oxygen from the surface of the wires and an increase in the mobility due to a reduction of inter-grain potential barrier height.

The prevalence of esophagitis in patients with duodenal ulcer or ulcer-like dyspepsia.

OBJECTIVE: It has been reported that 30-72% of patients with duodenal ulcer disease also have esophagitis. However, many of these reports included patients who had severe or complicated ulcer disease, so that the high prevalence may reflect pyloric stenosis or gastric hyper-secretion. The objective of this study was to determine the prevalence of esophagitis in unselected patients with duodenal ulcer disease or ulcer-like dyspepsia. METHOD: A prospective study of endoscopic and histological esophagitis in consecutive patients with either duodenal ulcer disease or with ulcer-like dyspepsia. RESULTS: Of 27 patients with duodenal ulcer disease, 33% had endoscopic esophagitis, 26% had histological esophagitis, and 48% had esophagitis by either criterion. Of 66 patients with ulcer-like dyspepsia, 35% had endoscopic esophagitis, 47% had histological esophagitis, and 62% had esophagitis by either criterion. Esophagitis was independent of patients' Helicobacter pylori status. CONCLUSIONS: Esophagitis is common in patients with duodenal ulcer disease, and the prevalence is similar in patients with ulcer-like dyspepsia. In addition to causing heartburn, esophagitis may also be cause ulcer-like epigastric pain. Concomitant esophagitis may account for the persisting or recurring dyspepsia that has been reported in up to one-third of duodenal ulcer patients after successful eradication of H. pylori.

Pentagastrin increases pepsin secretion without increasing its fractional synthetic rate.

We studied the effects of increasing doses of pentagastrin on gastric secretion of pepsin and on incorporation of L-[1-13C]leucine into gastric aspirate protein as an index of pepsin synthesis. Pentagastrin (0.25-4.0 micrograms.kg-1.h-1) significantly increased pepsin output from basal 76 mg/h to < or = 181 mg/h but did not significantly alter incorporation of L-[1-13C]leucine from the basal fractional synthetic rate of 3.63 +/- 0.05%/h. In four subjects in whom infusion of tracer leucine was continued for > 1 day, aspiration of pepsin between 24 and 27 h demonstrated that plateau 13C labeling of leucine in pepsin had been attained, but at a value that was only 48% of the 13C labeling of plasma alpha-ketoisocaproic acid (alpha-KIC) [0.730 +/- 0.02 (SE) vs. 1.520 +/- 0.14 atoms %excess]. This suggests that actual rates of pepsin synthesis were approximately double those calculated on the basis of alpha-KIC labeling. The results are consistent with an interpretation that increasing doses of pentagastrin cause increased secretion of pepsinogen by recruitment of gastric chief cells, each synthesizing pepsinogen at an unaltered rate. Plateau 13C enrichment of alpha-KIC may not be a valid surrogate for plateau 13C leucine enrichment when fractional synthetic rates of some secreted proteins are calculated.

Helicobacter pylori and refractory duodenal ulcers: cross-over comparison of continued cimetidine with cimetidine plus antimicrobials.

OBJECTIVES: To determine the distribution of Helicobacter pylori in the antral and duodenal mucosa of patients with duodenal ulcers refractory to 12 wk of treatment with cimetidine and to evaluate the effect of adding antimicrobial agents to cimetidine on the healing of refractory duodenal ulcers. METHODS: A randomized crossover comparison of continued 800 mg of cimetidine at night for 4 wk with cimetidine plus 500 mg of amoxycillin three times a day for the first 2 wk and 250 mg of metronidazole three times a day for the second 2 wk. H. pylori status in the gastric antral and duodenal mucosa was evaluated by histology and bacterial culture before and at the end of each treatment period. RESULTS: Forty-eight patients were studied. Upon entry to the study, all patients had antral colonization with H. pylori. In the duodenum, active chronic duodenitis was present in 66%, duodenal gastric metaplasia in 33%, and H. pylori in 50%, similar proportions to patients with nonrefractory duodenal ulcers. Healing occurred in 70% (30 of 43) of patients during treatment with cimetidine plus antimicrobials but in only 21% (6 of 28) during treatment with cimetidine alone (p = 0.0003). In patients who received antimicrobials, neither clearance of H. pylori from the antrum (58% of patients) or duodenum (71% of colonized patients) nor eradication of H. pylori (33%) was significantly correlated with ulcer healing. CONCLUSIONS: The distribution of H. pylori in refractory duodenal ulcers is similar to nonrefractory ulcers, and the combination of amoxycillin and metronidazole with cimetidine increases the proportion of refractory duodenal ulcers, which heals.

Mucosal concentration and excretion of clindamycin by the human stomach.

Each of 12 patients undergoing routine diagnostic upper gastrointestinal endoscopy received a single iv infusion of clindamycin phosphate 300 mg over 10 min. During the endoscopy, mucosal biopsies of the gastric antrum and fundus were obtained at varying times following the infusion. The clindamycin concentrations in the biopsies and in serum samples also taken after the infusion were determined. In addition, six healthy volunteers participated in a cross-over study on two different days. On both days, each subject received a single iv infusion of clindamycin phosphate 300 mg, immediately after which, gastric secretion was stimulated by iv pentagastrin (2 micrograms/kg/h) which was infused continuously over 150 min. On one of the study days, acid secretion by the stomach was inhibited by a slow iv infusion of ranitidine 50 mg. Clindamycin concentrations in gastric aspirates and serum samples collected after the infusion were determined. Concentrations of clindamycin in the fundal mucosa were significantly higher than the simultaneous serum concentrations (median ratio of tissue concentration to serum concentration, 2.0; P < 0.005) while concentrations in the antral mucosa were similar to those in serum (median ratio, 1.2; P = 0.65). Ranitidine significantly inhibited pentagastrin-stimulated acid secretion as demonstrated by a decrease in the volume of gastric aspirate when ranitidine was administered compared with when it was not administered (P < 0.01). Clindamycin concentrations in gastric juice were approximately one and one-half times higher than those in serum samples obtained simultaneously, both during stimulation of gastric acid secretion with pentagastrin and during inhibition of pentagastrin-stimulated acid secretion with ranitidine. Gastric juice concentrations of clindamycin were significantly higher following administration of ranitidine than after stimulation of gastric secretion by pentagastrin alone. Fundal mucosal and gastric juice concentrations of clindamycin exceeded the hypothetical maximum serum concentrations, indicating that accumulation in the stomach occurred against a concentration gradient.

A placebo-controlled investigation of duodenal ulcer recurrence after withdrawal of long-term treatment with ranitidine.

Ninety-two patients with duodenal ulcer disease, who had received long-term continuous treatment with ranitidine for an average of 7.5 years, participated in a double-blind, placebo-controlled study to determine whether stopping ranitidine resulted in ulcer recurrence. Patients were randomized to continue with ranitidine (n = 46) or to receive placebo (n = 46) and were followed up for six months. Treatment failure was defined as the first symptomatic recurrence of ulcer. The occurrence of epigastric pain during the follow-up period was significantly less frequent in the ranitidine group (13%) than in the placebo group (43%) (P = 0.001). At six months, 9% of the ranitidine group had developed ulcer recurrence, compared with 48% in the placebo group (P < 0.001, logrank test). Multivariate analysis using the Cox proportional hazards model showed that younger age (P = 0.041) and a long history of ulcer disease (P = 0.025) were risk factors for ulcer recurrence but gender, smoking and duration or dose of previous ranitidine treatment were not predictive of relapse during treatment with placebo. In conclusion, withdrawal of ranitidine after more than five years of continuous treatment results in almost half of the patients developing symptomatic ulcer recurrence within six months. Thus, long-term continuous therapy does not alter the natural history of duodenal ulcer disease. Younger patients and those with a long history of ulcer disease appear to be at increased risk of developing ulcer recurrence if long-term treatment is withdrawn.

Maintenance therapy in duodenal and gastric ulcer disease: survey of practice amongst British gastroenterologists.

We have used a postal questionnaire to obtain data on the practice of maintenance therapy for peptic ulcer disease by members of the British Society of Gastroenterology. Completed questionnaires were returned by 434 members. Ninety-six per cent used maintenance therapy for patients with duodenal ulcer and 81% for gastric ulcer. Maintenance therapy was considered to be safe (duodenal ulcer 91%; gastric ulcer 78%), acceptable to patients (duodenal ulcer gastric ulcer 89%; gastric ulcer 80%) and to reduce the incidence of ulcer complications (duodenal ulcer 81%; gastric ulcer 68%). There was consensus that increasing age of patient, current use of non-steroidal anti-inflammatory drugs, previous ulcer complications, and ulcer relapse after surgery were relatively strong indications for maintenance therapy. However, the proportion of patients who received maintenance therapy varied widely amongst respondents (from < 10% to > 50%). There was no agreement on the optimal duration of therapy, nor on management of patients who relapsed during maintenance therapy. It appears that the criteria for use of maintenance therapy need to be better defined, and that established knowledge about the practice of maintenance therapy should be better disseminated and acted upon.

Mallory-Weiss tears occurring during endoscopy: a report of seven cases.

Mallory-Weiss tears occurring during the course of upper gastrointestinal endoscopy are apparently rare. The present report describes seven cases of iatrogenic gastro-oesophageal tears encountered during 10,000 endoscopic examinations over a period of six years. Five of the seven patients were female and six patients were aged 75 years or older. Six patients had hiatal hernias. The site of the mucosal tear was similar in all patients, extending from a V-shaped breach at the gastro-oesophageal junction inferiorly along the lesser curve for a variable distance of up to 8 cm. Neither retching nor struggling during the procedure contributed to the development of the lesion in any of the patients. One patient suffered from a haematemesis which required transfusion, and in a further patient the tear resulted in a haematemesis and gastric perforation necessitating laparotomy. The study indicates that Mallory-Weiss tears complicating endoscopy occur especially in elderly, female patients with hiatal hernias. The importance of admitting patients with this complication to hospital for overnight observation is recommended in view of the possible development of haemorrhage or perforation.

Complications associated with ulcer recurrence following gastric surgery for ulcer disease.

The present study is an attempt to assess the risks of the complications associated with recurrent ulcers in patients who have undergone gastric surgery and to determine whether these risks differ from those observed in patients receiving long term maintenance treatment with H2-receptor antagonists for ulcer disease. One hundred and thirty studies reported in the literature during the past three decades have been analysed to determine both the approximate rate of ulcer recurrence and the proportion of patients with recurrent ulcers who have presented with either haemorrhage or perforation following the various types of gastric surgery for ulcer disease. From these data, estimates of the risks of haemorrhage and of perforation during the years following gastric surgery have been calculated. Vagotomy and antrectomy is associated with a low risk of ulcer recurrence (less than 1%) and the risk of complications in later years is accordingly very small (less than 0.5%). Partial gastrectomy, although associated with low recurrence rates, has a higher risk of complications (1.3% for haemorrhage, 0.3% for perforation) because the proportion of recurrent ulcers that present with haemorrhage or perforation is high (33% and 8%, respectively). Truncal vagotomy plus drainage (TV + D) and highly selective vagotomy (HSV) are associated with recurrence rates of 9% and 12%, respectively, but ulcer recurrences following these operations are less frequently accompanied by complications then recurrences after gastric resection and, as a result, the risks of haemorrhage (1.7% for TV + D; 1.3% for HSV) are similar to the risks after gastric resection. During long term (five years or more) maintenance treatment with H2-receptor antagonists, the risks of haemorrhage and perforation are less than 2% and less than 0.5%, respectively. It appears, therefore, that the likelihood of developing haemorrhage or perforation following gastric surgery is of the same order as that during maintenance treatment with H2-receptor antagonists, at least during the first decade of follow-up.

Nocturnal gastric secretion in duodenal ulcer patients and healthy controls. Ranges and reproducibility.

The nocturnal gastric acid secretion of 22 male duodenal ulcer patients was compared with that of 47 healthy male volunteers. Median nocturnal acid output was greater in duodenal ulcer patients (55 mmol versus 33 mmol 10 h-1; p = 0.013), but there was almost complete overlap of the ranges. Five duodenal ulcer patients and three volunteers had nocturnal outputs of acid previously considered to be pathognomonic of the Zollinger-Ellison syndrome in the absence of other evidence of a gastrinoma. Nineteen healthy volunteers underwent a repeat study to assess the reproducibility of nocturnal gastric acid output. Median intraindividual variability (+/- distribution-free 95% confidence limits) was 23% (-34% to +72%). Studies of nocturnal gastric secretion are of no diagnostic value, and their variability should be taken into consideration when evaluating gastric antisecretory drugs.

Is the fluorescein dilaurate test suitable for monitoring the effectiveness of pancreatic enzyme replacement therapy?

We have employed an oral test of pancreatic digestive function using fluorescein dilaurate (a substrate for pancreatic cholesterol ester hydrolase), administered together with pancreatic enzyme supplements, in order to test the hypothesis that urinary excretion of fluorescein provides a simple method for determining the optimal dose of oral pancreatic enzymes. Commercially available pancreatic enzyme supplements had negligible cholesterol hydrolase activity in vitro, and did not increase the urinary excretion of fluorescein when administered together with fluorescein dilaurate in 16 patients with pancreatic exocrine insufficiency. Inhibition of gastric secretion by ranitidine resulted in a statistically significant increase in urinary fluorescein excretion during the fluorescein dilaurate test. The fluorescein dilaurate test is not, therefore, suitable for determining the effectiveness of oral pancreatic enzyme replacement therapy. Moreover, the manufacturer's advice to stop oral pancreatic enzyme therapy for 5 days before performing the fluorescein dilaurate test appears unnecessary, since oral pancreatic enzymes do not alter test results.

Hiatal hernial ulcers: clinical features and follow-up.

We describe the clinical features and therapeutic outcome in 49 patients in whom benign gastric ulceration of an hiatal hernia was demonstrated endoscopically. Hiatal hernia ulcers accounted for 10% of all benign gastric ulcers. The typical patient was an elderly female with a history of dyspepsia who was receiving non-steroidal anti-inflammatory drugs. Twenty-seven (55%) patients had evidence of haemorrhage (acute in 15; chronic in 12) from the hiatal hernial ulcer at presentation. In 16 (33%) patients, symptoms attributable to haemorrhage constituted the sole clinical evidence of the hiatal hernial ulcer. Acute haemorrhage from hiatal hernial ulcers was associated with non-steroidal anti-inflammatory drug (NSAID) treatment (P less than 0.05). Chronic blood loss from hiatal hernial ulcers was associated with female gender (P less than 0.005) but not with NSAID treatment. Hiatal hernial ulcers healed slowly in response to medical treatment with H2-receptor antagonists (median time to healing 12 weeks). Surgical treatment may be the therapy of choice for hiatal hernial ulcers because of the high complication rate, poor response to medical therapy, and the apparent predominance of mechanical aetiological factors.

Tissue plasminogen activator release and plasminogen activator inhibitor levels in coronary artery disease.

Unstable angina and Q wave myocardial infarction are associated with intraluminal coronary thrombosis, a process to which impaired fibrinolysis may contribute. The authors examined the extrinsic fibrinolytic system, including tissue plasminogen activator antigen, plasminogen activator inhibitor activity and antigen, and euglobulin clot lysis time before and after venous occlusion in 56 patients undergoing coronary angiography for chest pain syndromes and in 16 healthy controls. Fibrinolysis variables were similar (with greater than 95% confidence) in the patients with thrombus-associated coronary syndromes as compared with those with chest pain syndromes not due to coronary thrombosis. These fibrinolytic variables were also similar to those in patients without coronary artery disease and in healthy controls. Their data suggest that defective fibrinolysis is not involved, at least systemically, in the pathogenesis of thrombus-associated coronary artery syndromes.

Effect of simulated intragastric haemorrhage on gastric acid secretion, gastric motility, and serum gastrin.

The majority of upper gastrointestinal bleeds stop spontaneously despite the low pH and proteolytic activity of gastric juice which inhibit coagulation and platelet aggregation. In order to investigate this paradox six healthy male volunteers received intragastric infusions of 160 ml autologous venous blood or 160 ml egg white acting as control in random order on separate days. Basal acid output was calculated before infusion, net acid secretion and gastric volume emptied were calculated after intragastric infusions. Serum gastrin concentrations were also measured before and after intragastric infusions and expressed as the integrated gastrin response. Basal acid output (mmol/h) was 4.7 (1.9) (mean (SEM)) before egg white infusion and 5.9 (2.6) before venous blood infusion. After egg white infusion net acid secretion (mmol/20 min) increased to 5.6 (3.1) compared with 2.3 (1.3) after venous blood infusion (p less than 0.05). The gastric volume emptied (ml/20 min) was less after venous blood infusion at 105 (28) compared with 321 (66) after egg white infusion (p less than 0.03). Integrated gastrin response was similar after venous blood and egg white infusion. When compared with an equivalent protein meal intragastric blood stimulates less acid secretion and delays gastric emptying. This effect may facilitate haemostasis after gastric bleeding.

Maintenance therapy of duodenal and gastric ulcer with H2-receptor antagonists.

Maintenance therapy with either ranitidine or cimetidine has been administered for up to 5 years to several hundred patients suffering from duodenal or gastric ulcer disease. Maintenance treatment prevented symptomatic ulcer relapse in approximately three-quarters of patients over this period of time. About half of symptomatic ulcer relapses occurred during the 1st year of maintenance therapy, and thereafter the symptomatic recurrence rate was extremely low. Potentially the most important effect of maintenance therapy was to reduce the incidence of ulcer complications, particularly haemorrhage (from 6.2% to 0.4% during the 1st year of duodenal ulcer maintenance). Maintenance therapy is therefore likely to reduce ulcer morbidity and to be cost-beneficial in patients who have previously experienced an ulcer complication and are at an increased risk of the same complication in the future. Maintenance therapy with 300 mg ranitidine daily was more effective than 150 mg ranitidine at night in smokers and may be a useful therapeutic option for smokers who relapse during maintenance therapy with 150 mg ranitidine at night or for smokers in whom it is mandatory to prevent ulcer recurrence because of a previous complication. Asymptomatic ulcers occurring during maintenance therapy are clinically benign, and rehealing such ulcers does not alter the subsequent clinical course. Point prevalences of asymptomatic reulceration should not be used when assessing the clinical value of maintenance therapy.

Acute treatment of reflux oesophagitis: a multicentre trial to compare 150 mg ranitidine b.d. with 300 mg ranitidine q.d.s.

H2-receptor antagonists administered in conventional dosage regimens fail to heal a significant proportion of patients with moderate or severe reflux oesophagitis. We have compared the effects of a higher dose of ranitidine (300 mg q.d.s.) with the currently recommended dosage regimen (150 mg b.d.) in 138 patients suffering from reflux oesophagitis. After 4 weeks of treatment 29% of patients who received 150 mg ranitidine b.d., and 63% of patients who received 300 mg ranitidine q.d.s. had complete endoscopic healing of their lesions (P less than 0.0001). After 8 weeks these proportions had increased to 54% and 75%, respectively (P less than 0.01). After 4 weeks of treatment, compete symptomatic relief had been achieved in 46% of patients who received 150 mg ranitidine b.d. and in 67% of patients who received 300 mg ranitidine q.d.s. (P less than 0.05). After 8 weeks these proportions were 64% and 84%, respectively (P less than 0.05). Both dosage schedules were well-tolerated. We conclude that more rapid symptom relief and healing in reflux oesophagitis can be achieved with 300 mg ranitidine q.d.s. than with 150 mg ranitidine b.d.

Inhibition of gastric secretion and motility by simulated upper gastrointestinal haemorrhage: a response to facilitate haemostasis?

As gastric acid and pepsin inhibit blood coagulation and platelet aggregation it is surprising that most upper GI haemorrhages stop spontaneously. To investigate this paradox we have studied acid and pepsin secretion, gastric motility and GI hormones after simulated upper GI haemorrhage. In seven healthy volunteers intraduodenal infusion of 160 ml autologous blood decreased pentagastrin stimulated submaximal acid secretion (mmol/h) from 30.0 (3.2) (mean (SE] in the hour preceding infusion to 21.4 (3.7) in the hour following infusion (p less than 0.02), representing a mean reduction in acid output of 30%. Pepsin output (mg/h) was also decreased from 207.5 (67.7) (mean (SE] in the hour preceding blood infusion to 135.7 (54.7) in the hour after infusion (p less than 0.02) representing a mean reduction in pepsin output of 43%. In six volunteers gastric emptying of a liquid meal was delayed after intraduodenal blood infusion compared with intubation alone with the emptying time (min) to half volume (t 1/2) being prolonged at 75.0 (8.2) (mean (SE] after blood infusion compared with 35.5 (6.6) after intubation alone (p less than 0.02). Plasma GIP concentrations (ng/l) increased to peak levels of 127.9 (62.7) (mean (SE] after intraduodenal blood infusion compared with the pre-infusion value of 58.3 (2.3) (p less than 0.02). These changes may represent protective physiological responses to facilitate haemostasis.

Hypertrophic gastritis associated with increased gastric mucosal prostaglandin E2 concentrations in a patient with the carcinoid syndrome.

A case of a 69 year old man in whom hypertrophic gastritis was associated with the carcinoid syndrome is reported. Concentrations of prostaglandin E2 were increased in plasma, gastric juice, gastric mucosa and urine. He had marked hypochlorhydria in response to pentagastrin stimulation (Peak acid output (PAO) pg:0.2 mmol/h). After successful hepatic arterial embolisation of the metastases (as indicated by an 85% decrease in 24 h urinary 5-HIAA) the concentrations of prostaglandin E2 decreased in the plasma, gastric juice and gastric mucosa. The gastric mucosal hypertrophy regressed and secretion of acid in response to pentagastrin returned (PAO pg:9.0 mmol/h). These findings suggest that the carcinoid tumour was producing a substance which stimulated increased local synthesis of prostaglandin E2 in the gastric mucosa, with concomitant gastric mucosal hypertrophy and inhibition of gastric acid secretion.