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Biomedical subjects

I N Marks

Publications and source records attributed to I N Marks.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1991

A comparison of omeprazole and ranitidine for duodenal ulcer in South African patients. A multiracial study.

The study was a multicenter double-blind parallel-group comparison of omeprazole, a proton-pump inhibitor, with the H2-receptor antagonist, ranitidine, in 206 patients with duodenal ulcer. There were 145 men and 62 women of mixed racial origin with an average age of 40 years (range 19-76); 63 of them were white, 7 black, 135 coloured and 1 Asian. Each drug was given for four weeks and ulcer healing rate, symptom relief, and adverse events were recorded and compared between treatment groups. Patients received either 20 mg omeprazole once daily in the morning (N = 104) or ranitidine 300 mg once daily at night (N = 106). Healing rates were significantly higher in the omeprazole group than in the ranitidine group at both two weeks (80% vs 52%, P less than 0.001) and four weeks (95% vs 85%, P less than 0.05), using the "per protocol" approach, and these results were confirmed using the "intention to treat" approach. Omeprazole-treated patients reported significantly less daytime epigastric pain (P = 0.02) and heartburn (P = 0.04) after two weeks than ranitidine-treated patients. By four weeks, there were no significant differences in symptom reporting between groups. Both treatments were well tolerated, and there were no serious adverse events.

Adult↗
PubMed1991

Basal and maximum acid output after continuous overnight gastric aspiration.

Basal and maximum acid outputs were measured on two occasions in a group of 15 duodenal ulcer (DU) patients in remission. The initial study was carried out after a nocturnal acid collection, whereas the second was carried out in the conventional manner without preceding nocturnal aspiration. No difference in the basal acid output, concentration, or volume of secretion was found between the two study days. Maximum acid output on the other hand, was significantly (p less than 0.02) reduced from 30.9 (14.2-41.2) mmol/h, median (+range), to 23.7 (8.1-33.7) mmol/h after overnight aspiration. The reduction in maximum acid output was attributable to a fall in the volume of gastric secretion from 280 (170-371) ml to 230 (142-280) ml. No fall in acid concentration was seen. We conclude that overnight gastric aspiration does not affect basal gastric secretion, but reduces the maximum acid output as a result of a reduced secretory volume.

Adult↗
PubMed1991

Sucralfate--safety and side effects.

The safety of sucralfate in terms of aluminium absorption, excretion, tissue accumulation, and toxicity is discussed, with special reference to the small amount of aluminium absorbed, its ready excretion by the normal kidney, and the hazard of toxicity in patients with advanced renal failure. The various manifestations of aluminium toxicity are described, and the notion that Alzheimer's disease should be included in this category is refuted. The clinical relevance of possible intraluminal binding and drug-drug interactions in patients receiving sucralfate therapy is also considered. Evidence is presented to show that sucralfate reduces the hyperphosphataemia in chronic uraemia, albeit at the risk of raised blood aluminium levels, but has no measurable effect on normal phosphate levels in patients with good renal function. The bioavailability of phenytoin, fluoroquinolone antibiotics, and H2-receptor blockers may be impaired by concomitant dosing with sucralfate, but normal kinetics are restored by administering the drug 2 h before sucralfate.

Biological Availability↗
PubMed1990

Simple closure of perforated duodenal ulcer: a prospective evaluation of a conservative management policy.

One hundred and thirteen consecutive patients admitted with a perforated duodenal ulcer over a 5-year period (1978-82) and treated by simple closure have been followed prospectively over a median period of 43 months. Patients were divided into two categories according to their previous history of dyspepsia; group 1 (66 patients) with a chronic history of more than 3 months and group 2 (47 patients) where there was no history of dyspepsia or a history of less than 3 months duration. The follow-up periods were similar (group 1, 44 months; group 2, 43 months). The overall recurrence rate was 42 per cent and to date only 14 per cent of the total group of 113 patients have required a definitive operation. The incidence of ulcer recurrence was higher in group 1 than in group 2 in terms of total recurrence (group 1, 50 per cent; group 2, 32 per cent) and patients requiring further surgery (group 1, n = 14, 21 per cent; group 2, n = 7, 15 per cent). Five of these 21 patients required an emergency procedure for haemorrhage or reperforation (group 1, n = 2; group 2, n = 3). There were no significant differences between the 5-year predictive recurrence rate or the requirement for definitive surgery between the groups. Five of the 27 patients currently on medical treatment have required maintenance treatment while the remaining patients receive active treatment for a mean of 20 per cent of the time since they developed recurrent ulceration. These results support continuation of our 'wait and see' policy following simple closure of perforated duodenal ulcer, even in patients with a history of chronic dyspepsia.

Adult↗
PubMed1990

Common variable hypogammaglobulinemia. A case report.

We describe a patient with severe common variable hypogammaglobulinemia (CVH) whose clinical course was dominated by resistant giardiasis requiring prolonged hospitalization. The giardiasis was eventually controlled by initial metronidazole and subsequent mepacrine therapy, but side effects necessitated the withdrawal of both of these drugs. Replacement immunoglobulin treatment failed to restore normal serum immunoglobulin levels, but despite this, they appeared to be of value in reducing the liability to recurrent giardiasis. We discuss the use of immunoglobulin supplementation in this condition and the frequent association between CVH and pentagastrinfast achlorhydria.

Agammaglobulinemia↗
PubMed1990

Duodenal ulcer healing and acid secretory responses to modified sham feeding and pentagastrin stimulation.

The effect of duodenal ulcer healing on the acid secretory responses to modified sham feeding and maximal pentagastrin stimulation has been studied in 17 patients treated successfully with ranitidine (n = 9) and sucralfate (n = 8). Parietal cell sensitivity was calculated as the ratio of the modified sham feeding response to the peak pentagastrin response, expressed as a percentage. Ulcer healing after sucralfate therapy resulted in significant falls in modified sham feeding stimulated acid output (P less than 0.02), from 9.4 (1.8-17.0) (median + range) to 3.7 (0.2-9.4) mmol/h; in peak acid output (P less than 0.05) from 42.8 (23.0-61.4) to 27.7 (7.2-51.0) mmol/h; and in the parietal cell sensitivity (P less than 0.05) from 19.2 (4.4-42.6) to 14.3 (2.8-19.7)%. No significant falls in any of these parameters were noted following ulcer healing with ranitidine. Duodenal ulcer healing with sucralfate results in decreased acid secretory responses to vagal and pentagastrin stimulation.

Adult↗
PubMed1989

Sucralfate in the prevention of porcine experimental peptic ulceration.

Sucralfate is the first drug to be shown to prevent ulceration in bile duct-ligated pigs. Usually such ulceration is uniformly fatal. Seven pigs in each of four groups in this study received only saline, or sucralfate (1 g every six hours), famotidine (40 mg per day), or misoprostol (200 micrograms every six hours). A Foley catheter was placed into a gastrectomy after bile duct ligation. Similar groups of sham-operated pigs were also prepared. After 48 hours, all saline-, famotidine-, or misoprostol-treated pigs showed severe macroscopic ulceration, whereas only two of those treated with sucralfate showed minimal macroscopic ulceration. Until now, only highly selective vagotomy has reduced ulceration caused by bile duct ligation. The present results suggest that acid inhibition is not the only important factor in healing bile duct ligation-induced peptic ulceration.

Alprostadil↗
PubMed1989

A maintenance regimen of sucralfate 2 g at night for reduced relapse rate in duodenal ulcer disease. A one-year follow-up study.

One hundred seventeen patients with recently healed duodenal ulcers were entered into a one-year maintenance study. Patients were randomly assigned to treatment with sucralfate 2 g at night, cimetidine 400 mg, or placebo. The sucralfate versus placebo leg of the study was double-blind, whereas the cimetidine leg was single-blind. Endoscopy was repeated on clinical relapse and routinely at six and 12 months. Ninety-six of the 117 patients were followed up for one year or to an endoscopically proven recurrence. The remaining 21 patients were excluded from analysis because of default or protocol violation. The one-year analysis showed by endoscopy that ulcers had recurred in 17 of the 31 sucralfate-treated patients, 19 of the 32 cimetidine-treated patients, and in 28 of the 33 placebo-treated patients. These data included asymptomatic recurrences in four, four, and three patients, respectively. The relapse rate at 24 weeks was greater in patients healed initially with a histamine (H2)-blocker alone than in those healed initially with sucralfate alone, a combination of sucralfate with a H2-blocker or an antacid alone.

Adult↗
PubMed1989

Acid-secretory response and parietal cell sensitivity in patients with duodenal ulcer before and after treatment with sucralfate or ranitidine.

Patients with endoscopically proved duodenal ulcer were randomly assigned to treatment with either ranitidine 300 mg at bedtime or sucralfate 2 g twice daily for six weeks. Acid-secretory studies were performed before commencement and 60 to 84 hours after cessation of treatment and endoscopic healing was confirmed. Patients were randomly assigned to receive a constant infusion of secretory stimulant: either pentagastrin 0.1 and 6.0 micrograms/kg/hour or histamine acid phosphate 4.0 and 40 micrograms/kg/hour. Acid output in mmol/hour was measured for basal, low dose, and high dose output. Parietal cell sensitivity (PCS) was calculated as the ratio of low-dose acid output: high-dose acid output and expressed as a percentage. Values before and after treatment were compared and significance of differences was determined using the Student paired t test. There was an apparent decrease in basal acid output, low-dose acid output, high-dose acid output, and PCS with ulcer healing, regardless of treatment or stimulant used. Basal acid output, low-dose acid output, high-dose acid output, and PCS were significantly lower in the sucralfate-treated group, but only high-dose acid output decreased significantly in the ranitidine-treated group. These differences may be relevant to early duodenal ulcer relapse in ranitidine-treated patients.

Adolescent↗
PubMed1989

Single step affinity chromatographic purification of human alpha-amylase from aspirated duodenal juice and its application in the measurement of pancreatic alpha-amylase synthesis rates in man.

Human alpha-amylase was purified from aspirated duodenal juice to electrophoretic homogeneity in a single step by affinity chromatography with the competitive inhibitor acarbose (IC50 = 1.22 mumol/l) as ligand. Duodenal juice was applied to an agarose resin to which acarbose had been coupled covalently via a 1.9 nm spacer group. Pure alpha-amylase, eluted with free acarbose, had a molecular mass of 55,000, and isoelectrofocusing revealed the presence of six isozymes with pI values of 7.3, 6.8, 6.7, 6.5, 6.4 and 6.3, all of which possessed amylase activity based on positive starch/iodine staining. The potential usefulness of this one-step purification procedure in the measurement of pancreatic alpha-amylase synthesis rates was evaluated in two control patients with non-pancreatic disease. Aspirated duodenal juice was obtained during a pulse/continuous intravenous 4 h infusion of [14C]leucine together with secretin and pancreozymin, and alpha-amylase purified using our protocol. Pancreatic alpha-amylase synthesis rates were determined from the rate of incorporation of [14C]leucine into alpha-amylase; values of 4.4 and 5.1 h were obtained for the two control patients.

Acarbose↗
PubMed1989

Pancreatic enzyme replacement therapy. Importance of gastric acid secretion, H2-antagonists, and enteric coating.

The relative efficacy of three commercial pancreatic enzyme supplements in improving fat absorption was studied using the [14C]triolein breath test in 12 patients with chronic pancreatitis. Two of the supplements were enteric coated. The one nonenteric coated product was studied twice: with and without ranitidine coadministration. Doses complied with the manufacturers recommendations. Baseline studies included pentagastrin-stimulated gastric acids, 72-hr fecal fat excretion, and [14C]triolein absorption while not on supplementation. Acid outputs were variable (BAO: 0.3-4.1 meq/hr; MAO: 3.5-34.6 meq/hr). Three patients had mild steatorrhea (i.e., less than 10 g/day) and the remaining severe fat malabsorption (56.9 +/- 41.5 g/day). Although fat absorption was significantly improved by all three supplements, the nonenteric coated preparation was most effective (P less than 0.001). However, laboratory analysis demonstrated that lipase content was four times greater, ie, 17,000 IU/4 tablets. Pretreatment with ranitidine failed to further improve the absorption in patients given nonenteric supplements but was effective in those found to have high or normal acid outputs (P less than 0.001). Our results suggest that the recommended dosage of enteric coated preparations is insufficient for adult patients with severe chronic pancreatitis. Secondly, the marked variability of acid secretion in such patients possibly accounts for the variability of results obtained by others on the usefulness of coadministration of antacids and H2 antagonists. Routine measurement of gastric acid secretion status may help optimize the choice and form of pancreatic enzyme supplementation.

Adult↗
PubMed1989

Measurement of pancreatic enzyme synthesis in humans. Problems in patients with calcific pancreatitis.

Earlier studies have suggested that the rate of incorporation of labeled amino acids into duodenal juice proteins during pancreatic stimulation may be used to calculate pancreatic enzyme synthesis and function. In the present study, a pulse/4 h continuous intravenous infusion of 14C labeled leucine was used to compare synthesis rates in 6 patients with chronic calcific pancreatis(CP) to 4 controls. Analysis of duodenal juice protein demonstrated a delay of approximately 1 h in the appearance of labeled proteins, followed by a linear increase in specific activity, allowing calculation of synthesis that varied between 2.6-2.8 h in controls and 6-48 h in CP. The protein in controls was representative of enzyme protein, but that of CP was not, since it was heavily contaminated with albumin (up to 50%). The results indicate that enzyme secreted during the first hour of stimulation is derived from pancreatic stores and that the synthesis rate of enzymes secreted thereafter is approximately 2.7 h in normal humans. The method was, however, unable to determine rates in patients with CP owing to heavy contamination of enzymes with exudative proteins.

Adult↗