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Biomedical subjects

I N Marks

Publications and source records attributed to I N Marks.

At least 19 recordsLinked to original sources
PubMed1995

Optimizing acid suppression for treatment of acid-related diseases.

Gastric acid is of central importance in the pathogenesis of duodenal ulcer, gastric ulcer, and gastroesophageal reflux disease. Pharmacological reduction of acid secretion is, therefore, the mainstay of current treatment, but the optimal degree of acid suppression remains incompletely understood. This paper considers the ideal ways of assessing and reporting the pharmacological effectiveness of acid-inhibiting drugs and relating such data to clinical efficacy. Twenty-four-hour intragastric pH measurements are widely used for this purpose, although this technique cannot measure secretion quantitatively. Data on suppression of 24-hr intragastric acidity for groups of subjects have been successfully correlated with healing rates for duodenal ulcer, gastric ulcer, and gastroesophageal reflux disease. Three primary determinants of healing have been derived from antisecretory data. These are the degree of suppression of acidity, the duration of suppression of acidity, and the duration of treatment. The order of importance of these determinants varies depending on the disease. Data on 24-hr intragastric acidity should be accompanied whenever possible by data on 24-hr plasma gastrin levels, as the relationship between suppression of acidity and a rise in gastrin varies widely between individuals. It is not possible to predict the plasma gastrin level from the intragastric pH or any other measurement of intragastric acidity. Comparative data sets in groups of subjects may provide useful information. Proton pump inhibitors produce a greater and longer-lasting degree of suppression of acidity than conventional doses of H2-receptor antagonists. For this reason, they are more effective in healing duodenal ulcer and gastric ulcer. However, in view of the importance of duration of treatment, healing rates with the H2-receptor antagonists approach those obtained with proton pump inhibitors if treatment is continued for a longer time. In gastroesophageal reflux disease in particular, although the optimal degree of acid suppression is not yet defined, the consistently superior performance of proton pump inhibitors demonstrates that increased suppression of acidity is clinically beneficial.

Duodenal Ulcer↗
PubMed1995

Helicobacter pylori eradication in the African setting, with special reference to reinfection and duodenal ulcer recurrence.

The aim of this study was to determine the effect of Helicobacter pylori eradication on the natural history of duodenal ulcer disease, and to determine the incidence of reinfection in adult patients where H pylori had been eradicated in a community with a high prevalence of the infection. An investigator blinded study, with 24 month endoscopic follow up, in subjects where H pylori had been eradicated, and similarly treated subjects where it had not been eradicated was conducted at a tertiary referral hospital. The patients consisted of a volunteer sample of 48 patients with endoscopically proved active duodenal ulcer disease. Duodenal ulcers were healed with omeprazole, 20 mg/day. After endoscopically confirmed healing, patients were treated with either one (17 patients) or two weeks (31 patients) of 'triple therapy'. H pylori status (urease reaction, histological tests, and culture of antral biopsy specimens) was determined at entry, four weeks after the finish of triple therapy and six, 12, and 24 months after this, or whenever an endoscopically proved recurrent duodenal ulcer was found. The main outcome measures were the recurrence of duodenal ulceration, over 24 months in the eradicated and non-eradicated groups and the incidence of reinfection by H pylori in the eradicated group during this follow up period. Five patients in the eradicated group experienced a duodenal ulcer relapse, of which only three were unexplained (1 = reinfected, 1 = gastrinoma). Fifteen of 21 patients in the non-eradicated group relapsed over the same period (p < 0.001). Only two of 27 patients in the eradicated group were reinfected during the 24 month follow up period. It is concluded that H pylori eradication is an effective treatment strategy for the longterm treatment of duodenal ulcer disease, even in the high prevalence, African setting. Reinfection is uncommon.

Adult↗
PubMed1995

The prevalence and severity of microvascular complications in pancreatic diabetes and IDDM.

OBJECTIVE: To investigate and compare the prevalence, associations, and severity of retinopathy and nephropathy in patients with pancreatic diabetes (PD) and insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS: Thirty patients with PD due to alcohol-induced chronic pancreatitis were matched for age, sex, and duration of diabetes with 30 patients with IDDM. Retinopathy was assessed by fluorescein angiography using the Wisconsin classification. Renal function was assessed by albumin excretion rates (AERs) in at least two timed overnight urine collections and glomerular filtration rates (GFRs) by single injection of 51Cr-EDTA. Microalbuminuria was defined as AER 20-200 micrograms/min and nephropathy as AER > 200 micrograms/min. RESULTS: Retinopathy was found in 33% of patients with PD and in 40% with IDDM. The spectrum of disease was similar in the two groups. The geometric mean of AER was 15 micrograms/min (range 1-1,541) in the PD group and 24 micrograms/min (2-2,288) in the IDDM group. Nephropathy was found in 7 PD and in 5 IDDM patients, and a reduced GFR was present in 8 (26%) and 4 (13%) of the two groups, respectively. Microalbuminuria occurred in 9 (33%) and hyperfiltration in 3 (10%) in each group. These differences were insignificant. Retinopathy correlated with AER in both groups. Retinopathy and AER correlated with duration of diabetes in the IDDM but not in the PD group. CONCLUSIONS: Microvascular complications are equally common and severe in PD and IDDM, and improved glycemic control should be the goal in both.

Albuminuria↗
PubMed1994

Fat-soluble vitamin concentration in chronic alcohol-induced pancreatitis. Relationship with steatorrhea.

In order to study the fat-soluble vitamin concentration of patients with chronic alcohol-induced pancreatitis (CAIP) we measured vitamins A and E, total lipids, and retinol-binding protein (RBP) in the plasma of 44 patients with CAIP and 83 controls (44 healthy controls; 39 Crohn's disease patients). Mean plasma vitamin E and vitamin E/total lipid ratio were significantly lower in CAIP when compared with either control or Crohn's disease groups. A low vitamin E/total lipid ratio was found in 75% of CAIP patients (91% with steatorrhea) and a ratio less than 1.0 was virtually 100% predictive of steatorrhea. The mean plasma vitamin A level for the CAIP group was significantly lower (overall 16%, 38% with steatorrhea) than in controls. Patients with CAIP show subnormal plasma levels vitamin E more often as compared to vitamin A. Further, the plasma vitamin E/total lipids ratio may be a sensitive and practical means in the detection and follow-up of steatorrhea in these patients.

Adolescent↗
PubMed1994

Effect of buprenorphine on pancreatic enzyme synthesis and secretion in normal rats and rats with acute edematous pancreatitis.

Pancreatic enzyme secretion is inhibited during acute pancreatitis, resulting in an increase in acinar zymogen content. Since the premature activation of zymogens has been assigned a central role in the pathogenesis of acute pancreatitis, minimizing the amount of stored zymogens might lead to less severe acute pancreatitis. Inhibition of enzyme synthesis or stimulation of enzyme secretion would result in reduction of zymogen stores. Opiates have a varying effect on pancreatic secretion, depending on the dosage, site of administration, and presence of pancreatic stimulants. The effect of opiates and acute pancreatitis on individual pancreatic enzyme synthesis is unknown. The following study was undertaken in order to examine the effects of an opiate on pancreatic enzyme secretion and synthesis during experimental acute pancreatitis. Four groups of rats were studied. Group I received cerulein (25 micrograms/kg); group II received an opiate, buprenorphine (BPN, 0.5 mg/kg); and group III received cerulein and BPN. Drugs were dissolved in gelatin/saline and injected subcutaneously. A control group (group IV) received only gelatin/saline. Rats were sacrificed 4 hr after injection, and pancreatic mass was measured. Pancreatic acini were prepared and assayed for amylase and DNA content. Amylase, trypsinogen, chymotrypsinogen and lipase synthesis, and amylase secretion were measured for 2 hr. Results showed that, compared to controls, acini of rats with AP had increased amylase content, a finding consistent with decreased in vivo amylase secretion. Total protein and individual enzyme synthesis rates were significantly lower in the acini of the rats with AP than in those of the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1993

Duodenal juice total protein and pancreatic enzyme synthesis, turnover, and secretion in patients after acute pancreatitis.

It is controversial whether acute pancreatitis has longterm effects on pancreatic function. Pancreatic enzyme synthesis, turnover, and secretion were measured in 10 patients in clinical remission who had had one or more (one to six) attacks of acute alcoholic pancreatitis. The studies were done between two and 29 months after the most recent attack. A control group included five patients with no evidence of pancreatic disease. A four hour primed/continuous intravenous infusion of [14C]L-leucine tracer was given with secretin (2 U/kg/h) and cholecystokinin (0.5 U/kg/h) and secreted duodenal juice aspirated. Amylase and trypsin were extracted from duodenal juice by affinity chromatography, permitting measurement of the rate of isotope incorporation into total protein, amylase, and trypsin. The results showed non-parallel changes in enzyme synthesis and turnover with decreases in total enzyme protein and amylase synthesis and turnover but preservation of trypsin synthesis and turnover. The low turnover rates may be ascribed to continuing pancreatic cell malfunction after recovery from acute alcoholic pancreatitis and suggest that the decreased amylase secretion rates are partly a consequence of impaired amylase synthesis and not simply because of loss of pancreatic tissue.

Acute Disease↗
PubMed1992

Helicobacter pylori lipopolysaccharide stimulates gastric mucosal pepsinogen secretion.

The effect of Helicobacter pylori lipopolysaccharide on guinea pig gastric mucosal pepsinogen secretion has been examined using an Ussing chamber technique. Luminal addition of H. pylori lipopolysaccharide resulted in a fifty-fold stimulation of pepsinogen secretion compared to a twelve-fold increase with E. coli lipopolysaccharide. Electron microscopy showed marked degranulation of zymogen granules but no evidence of chief cell disruption.

Animals↗
PubMed1992

Changes in nocturnal and peak acid outputs after duodenal ulcer healing with sucralfate or ranitidine.

Changes in basal and stimulated acid secretion after duodenal ulcer healing have been previously shown to be influenced by the nature of the treatment. This study aimed to determine possible changes in nocturnal acid secretion on duodenal ulcer healing in patients treated with sucralfate or ranitidine. Nocturnal acid output and peak acid output in response to pentagastrin stimulation were studied in 20 patients before and after duodenal ulcer healing with sucralfate (n = 9) or ranitidine (n = 11). Details regarding cigarette smoking were obtained from each subject. Median 10 hour nocturnal acid output fell significantly (p less than 0.05) from 82.4 (29.1-188.3) mmol (median range) to 45.2 (14.7-144.4) mmol after healing with sucralfate, and rose significantly (p less than 0.05) from 54.7 (16.8-74.3) mmol to 86.2 (11.7-118.1) mmol after ulcer healing with ranitidine. Peak acid output fell from 39.6 (22.0-52.8) mmol/hour to 27.8 (13.8-38.2) mmol/hour (p less than 0.01) after healing with sucralfate and was unchanged after healing with ranitidine. There was no correlation between smoking and nocturnal acid output. These results provide further evidence that acid secretion decreases with sucralfate healing and remains the same or may even increase after ranitidine healing.

Adult↗
PubMed1992

Triple therapy with sucralfate is as effective as triple therapy containing bismuth in eradicating Helicobacter pylori and reducing duodenal ulcer relapse rates.

Duodenal ulcer relapse rates after therapy with sucralfate or bismuth are lower than those after H2-receptor antagonist therapy. This may be mediated by an antibacterial effect of these drugs on Helicobacter pylori. Bismuth has become an integral part of 'triple therapy' because of its documented anti-H. pylori effect. In vitro and clinical data suggest that sucralfate may also have an anti-H. pylori effect. The aim of this randomized, prospective therapeutic trial was to compare the efficacy of triple therapy containing bismuth with that containing sucralfate and to determine the effect of therapy with these combinations on duodenal ulcer relapse. Forty H. pylori-positive duodenal ulcer patients were healed with omeprazole and randomized to receive either 1 g sucralfate four times daily or 120 mg bismuth compound four times daily. All patients received 400 mg metronidazole three times daily and either 250 or 500 mg tetracycline four times daily for 7-14 days. Thirty-five patients could be analysed. Overall eradication rates did not differ in the treatment groups (10 of 17 eradicated with sucralfate and 11 of 18 with bismuth). Relapse rates were significantly lower in the eradicated group (1 of 21 compared with 8 of 14 in the non-eradicated group) and did not differ between treatment groups in those patients not eradicated. A triple therapy regimen utilizing sucralfate appears to be as effective as the bismuth-containing regimen.

Bismuth↗
PubMed1992

Acid secretion, 1932-92: advances, adaptations, and paradoxes.

This paper reviews the evolution of our understanding of various aspects of gastric acid secretion over the past 60 years. Embryologic aspects and neonatal acid secretion are considered, and the relationship between parietal cell mass and acid secretion and the changing concepts of parietal cell activation are discussed. The effect of aging on acid secretion and the relevance of acid secretion in health and disease are reviewed, and current views on adaptation to therapeutic inhibition of acid secretion presented. The aetiologic link between acid secretion and ulcer disease is re-examined, and the role of pepsin, growth factors, and Helicobacter pylori briefly considered.

Adaptation, Physiological↗
PubMed1991

Acid secretory responses and parietal cell sensitivity following duodenal ulcer healing with omeprazole, sucralfate, and Maalox.

Acid secretory responses and parietal cell sensitivity (PCS) have been studied in 21 duodenal ulcer patients before and after successful treatment with omeprazole (n = 7), sucralfate (n = 7), or Maalox (n = 7). The second study was carried out 3 days after documented healing and withdrawal of treatment in the sucralfate- and Maalox-treated groups and 14 days after documented healing and withdrawal of treatment in the omeprazole-treated patients. Acid output (mmol/hour) was measured as basal secretion, and in response to 0.1 microgram/kg/hour pentagastrin (low-dose) and 6.0 micrograms/kg/hour pentagastrin (high-dose) stimulation. PCS was calculated as the ratio of low dose:high dose acid output (expressed as a percentage). Ulcer healing with sucralfate resulted in significant (p less than 0.05) decreases in low-dose acid output from 36.4% (13.2-51.0) (median [range]) to 8.4% (3.2-45.4) mmol/hour and PCS from 69.1% (44.9-91.4) to 22.0% (16.0-85.6), whereas no significant decreases in any of the measured parameters were noted following ulcer healing with Maalox. Ulcer healing with omeprazole resulted in significant (p less than 0.05) decreases in basal acid output from 6.3 (1.5-22.9) (median [range]) to 2.2 (0-6.9) mmol/hour, and low-dose acid output from 31.0 (6.0-58.0) to 23.0 (1.4-44.8) mmol/hour. These findings suggest that acid secretory responses following ulcer healing vary according to the therapeutic agent used.

Adult↗
PubMed1991

Acid secretory changes and early relapse following duodenal ulcer healing with ranitidine or sucralfate.

Controversial aspects relating to acid secretory changes following duodenal ulcer healing, and the effect of histamine-2 (H2)-receptor blockers on such changes are discussed. Recent studies comparing the effects of ranitidine or sucralfate on changes in the acid secretory responses in the healing of duodenal ulcers are described, and the relevance of these changes to early relapse considered. The duration of therapy and timing of acid-secretory studies and endoscopies are standardized in all studies, but the acid-secretory parameters vary. These comprised acid secretory responses to graded doses of an intravenous infusion of pentagastrin or histamine, sham-feeding responses, and basal and nocturnal acid secretion. In all studies, healing with sucralfate was associated with a significant decrease in the various parameters of acid secretion. In the ranitidine-healed groups, no appreciable decrease was noted and there was, indeed, a significant increase in nocturnal acid secretion. Routine endoscopies performed 4-6 weeks after documented ulcer healing showed a recurrence of 3 of the 32 (9%) sucralfate-healed and in 14 of the 35 (40%) ranitidine-healed ulcers. Increased acid secretory responsiveness following duodenal ulcer healing was strongly correlated with subsequent early relapse.

Clinical Trials as Topic↗
PubMed1991

Reflux esophagitis therapy: sucralfate versus ranitidine in a double blind multicenter trial.

Sucralfate (Sc) suspension 6 g/day and ranitidine (Rn) tablets, 150 mg, were compared in 125 patients in a double-blind, multicenter, endoscopically controlled trial in the treatment of reflux esophagitis. Inclusion criteria were symptomatic reflux (number and severity of attacks) and endoscopic evidence of esophagitis (grades 1 to 4). Clinical assessments were performed on entry, and at 4 and at 8 weeks, and endoscopy was repeated at 8 weeks. Sc suspension and Rn placebo or Sc placebo and Rn tablets were taken on waking and immediately before retiring at night. Of the 125 patients, 27 were withdrawn because of default (Rn = 4; Sc = 14), noncompliance (Rn = 1; Sc = 2), or the development of congestive cardiac failure (Rn = 1), diarrhea (Rn = 1; Sc = 1), nausea (Sc = 1), constipation (Sc = 1), and hematemesis (Sc = 1). Analysis was performed on the remaining 98 patients, 43 of whom had been treated with Sc and 55 with Rn. Heartburn, acid regurgitation, epigastric pain, dysphagia, and chest pain were relieved in 34% vs 40%, 67% vs 72%, 71% vs 57%, and 86% vs 63% for Sc and Rn, respectively. There was no significant difference between the two groups. Endoscopic healing occurred in 47% of the Sc- and in 31% of the Rn-treated patients (chi 2 = 2.50), and healing or improvement was noted in 81% of the Sc- and 64% of the Rn-treated patients. This difference approached statistical significance (chi 2 = 3.73). There was no obvious endoscopic benefit in 8 of the 43 and 20 of the 55 patients in the groups treated with Sc and Rn, respectively. Although the findings with sucralfate and ranitidine in patients with reflux esophagitis completing the trial suggest a benefit of these agents, the absence of a placebo control group and the high default rates, particularly for those receiving sucralfate, preclude any firm conclusions as to relative or specific efficacy of these agents in this condition.

Administration, Oral↗