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Biomedical subjects

S M Sabesin

Publications and source records attributed to S M Sabesin.

At least 19 recordsLinked to original sources
PubMed1995

Treatment of erosive reflux esophagitis resistant to H2-receptor antagonist therapy. Lansoprazole, a new proton pump inhibitor.

Fifty-four patients with endoscopically documented therapy-resistant erosive reflux esophagitis were treated with lansoprazole, a new proton pump inhibitor, for up to 12 weeks. Prior to entry, all had remained unhealed after treatment with at least two histamine2-receptor antagonists, at therapeutic doses or higher, for at least 12 weeks. Patients were randomized to receive either 30 or 60 mg lansoprazole once daily. Endoscopy was performed and symptoms assessed at weeks 2,4,6,8 and 12. Fifty-nine percent of the 50 evaluable patients were healed (ie, no evidence of erosions) after only two weeks of lansoprazole. Cumulative endoscopic healing rates were 82% and 92% by week 4 and week 8, respectively, and the two doses were equally effective in healing. The 30- and 60-mg doses effected a decrease in the overall symptom score from 5.30 and 4.85 to 2.35 and 1.67, respectively, by the final treatment visit (P = 0.001). No clinically significant adverse events or changes in laboratory parameters were observed, and no patients withdrew prematurely from the study. This study demonstrates that lansoprazole therapy is highly effective in healing erosive reflux esophagitis resistant to therapy with histamine H2-receptor antagonists.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1995

Clinical effectiveness and quality of life with ranitidine vs placebo in gastroesophageal reflux disease patients: a clinical experience network (CEN) study.

BACKGROUND: Gastroesophageal reflux disease (GERD), often characterized as heartburn, is a highly common presenting complaint to family physicians. This study is the first large, prospective, nationwide family practice outpatient evaluation of the effectiveness of the histamine (H2)-receptor antagonist ranitidine as medical therapy for this disorder. METHODS: This randomized, double-blind, placebo-controlled, parallel group, 6-week study was designed to evaluate the effect of ranitidine on clinical outcomes and quality of life in patients with GERD. Eligible patients included those who were at least 18 years old and had at least a 3-month history of heartburn or heartburn therapy and a minimum of 4 days with at least one heart-burn episode in the week preceding the baseline visit. Quality-of-life effects were measured using a general health status instrument and a previously validated heartburn-specific questionnaire. RESULTS: Ranitidine treatment conferred clinically and statistically significant reductions in mean heartburn pain scores within the first 24 hours (P < or = .001) and mean number of heartburn episodes within the first 48 hours (P < or = .001). These reductions were maintained throughout the 6-week trial, during both daytime and nighttime. Compared with patients receiving placebo, patients treated with ranitidine also used significantly fewer doses of antacids (P < or = .003). Further, both ranitidine-treated patients' and their physicians' global assessments of decreases in heartburn severity, as well as clinical improvement on ranitidine, proved superior to those of controls (P < or = .001). The rate of adverse events associated with ranitidine and placebo was low and similar. Ranitidine-treated patients had more favorable scores on the general health status dimensions of physical functioning, bodily pain, and vitality (P < .05), and more favorable scores on all dimensions of the heartburn-specific questionnaire (P < .05). CONCLUSIONS: Twice-daily treatment with ranitidine 150 mg is a valuable therapy for GERD in a typical family practice setting. It reduces the frequency and severity of symptoms within the first 24 to 48 hours of treatment and diminishes the use of nonprescription antacids while improving the quality of life as measured by both a general health status instrument and a disease-specific instrument.

Adult↗
PubMed1993

Safety issues relating to long-term treatment with histamine H2-receptor antagonists.

H2-receptor antagonist therapy is associated with a low incidence of adverse reactions. Adverse events reported in clinical trials of ranitidine in daily doses of up to 1200 mg include headache, tiredness and mild gastrointestinal disturbances, but the incidence is similar to or less than that for placebo. High doses of cimetidine (> 5 g/day) can cause reversible impotence or gynaecomastia. While ranitidine exhibits no clinically significant drug-drug interactions, cimetidine interacts with many drugs metabolized by cytochrome P450. In contrast to ranitidine and cimetidine, where safety data are available for up to 10 years of continuous therapy, experience with famotidine and nizatidine is limited. The safety of long-term H2-receptor antagonist therapy needs to be considered in relation to the potential consequences of prolonged acid suppression, including the risk of proliferation of gastric flora and the risk of developing enterochromaffin-like cell hyperplasia, which could in turn, theoretically, lead to gastric malignancy. Such problems have not been observed in patients during long-term therapy at low or full doses of H2-receptor antagonists. Standard doses of currently available H2-receptor antagonists permit acid secretion in response to food and other stimuli, and this daily acid tide prevents persistent bacterial colonization.

Drug Interactions↗
PubMed1992

The effect of sulfasalazine on bovine endothelial cell proliferation and cell cycle phase distribution. Comparison with olsalazine, 5-aminosalicylic acid, and sulfapyridine.

Sulfasalazine is used in the treatment of chronic inflammatory states, for example, in inflammatory bowel disease and to a lesser degree in rheumatoid arthritis. In chronic inflammation, the formation of new blood vessels may play a key role in maintaining the inflammatory state. This process is dependent on the activation and proliferation of the endothelial cells. To investigate the possible role of sulfasalazine and its metabolites, sulfapyridine and 5-aminosalicylic acid, we examined the effect of these drugs on vascular endothelial cell proliferation in vitro. Cultures of bovine aortic endothelial cells were incubated with sulfasalazine and its metabolites. At 24 hours of incubation, sulfasalazine inhibited tritiated thymidine incorporation and cell proliferation and had already slowed S-phase progression at a concentration greater than 0.125 mmol/L. After 3 hours of incubation, sulfasalazine inhibition of tritiated thymidine incorporation into the DNA of endothelial cells was observed. This inhibition was completely reversible 24 hours after the drug was removed. One of the possible mechanisms for the inhibition of endothelial cell proliferation is interference with the de novo synthesis of thymidine that depends on folate-dependent enzymes. The effect of deoxyuridine and tetrahydrofolate on tritiated thymidine incorporation into cellular DNA, as well as release of tritium to water by [5-3H]-labeled deoxyuridine on methylation to thymidine, were used as probes for the de novo synthesis of thymidine. Deoxyuridine and tetrahydrofolate, when added to cells either individually or together for 3 hours, suppressed incorporation of tritiated thymidine into DNA through an increase in de novo thymidine synthesis. Sulfasalazine, but not its metabolites, reduced this suppression.2+ culture is inhibited by sulfasalazine and olsalazine but not by their metabolites. This inhibition appears to depend partly on the reduction of de novo synthesis of thymidine that is folate dependent.

Aminosalicylic Acids↗
PubMed1992

Clinical results of piezoelectric gallstone lithotripsy.

The safety and efficacy of piezoelectric extracorporeal shockwave lithotripsy in the treatment of symptomatic gallbladder stones were evaluated in 53 consecutively treated patients. All treatments were performed as outpatients without anesthesia; over 95 per cent of 109 treatments were performed without analgesia or sedation. Ursodeoxycholic acid was administered post-treatment. Seventy per cent of patients had multiple sessions. Cumulative stone-free rates of 38 per cent at 6 months, 65 per cent at 12 months, and 75 per cent at 15 months were achieved. There was no difference in eventual stone clearance between patients with single stones less than 20 mm diameter, single stones greater than or equal to 20 mm diameter, or multiple (two or three) stones, although patients with single smaller stones required significantly fewer total shocks to become stone-free (P = .02). Stone clearance correlated with estimated stone volume. Biliary pain occurred in 62 per cent of patients after treatment but ceased in stone-free patients. Biliary complications of pancreatitis (7.5%) and choledocholithiasis (3.8%) were successfully treated by endoscopic papillotomy. Nonbiliary complications were virtually nonexistent. Three patients (5.7%) had elective cholecystectomy. Results indicate that piezoelectric lithotripsy is a safe, minimally painful treatment that, in conjunction with oral bile acids, can produce stone-free rates of 75 to 100 per cent in selected patients.

Adult↗
PubMed1991

Famotidine relieves symptoms of gastroesophageal reflux disease and heals erosions and ulcerations. Results of a multicenter, placebo-controlled, dose-ranging study. USA Merck Gastroesophageal Reflux Disease Study Group.

We conducted a double-blind, placebo-controlled, multicenter trial comparing the efficacy of famotidine 40 mg administered at bedtime (HS), 20 mg given twice daily (BID), and placebo to relieve heartburn and to heal endoscopically documented esophageal erosions or ulcerations. A total of 338 patients were randomized: 135 to receive famotidine 40 mg HS, 137 to receive famotidine 20 mg BID, and 66 to receive placebo. In the group given famotidine 20 mg BID, there was a significantly greater proportion of patients with complete relief of daytime heartburn, and both famotidine groups demonstrated statistically significant advantages over placebo in global scores or by successful outcome. Antacid consumption was significantly reduced in the group given famotidine 20 mg BID as compared with placebo. Both famotidine regimens resulted in a significantly greater proportion of patients with complete endoscopic healing than placebo, with the BID dosing being numerically superior to the 40-mg HS dose.

Adult↗
PubMed1990

Liver transplantation. New hope for many patients.

Because of the broad range of physiologic problems and the many potential sources of complications, liver transplantation patients require contributions from virtually the complete spectrum of medical science. The evolving specialty of liver transplantation has eagerly assimilated advances in surgical techniques, anesthetic agents, critical care, nutrition, immunologic manipulation, and tissue preservation. Stimulated by increasingly successful results, the public appears to have slowly accepted the expense of this labor- and technology-intense therapy. The role of workers in this area is to strive not only to improve results but also to control costs.

Graft Rejection↗
PubMed1990

The effect of essential fatty acid deficiency on eicosanoid production in the inflamed rat colonic mucosa.

Eicosanoids are potent mediators of inflammation and are synthesized in increased quantity in active ulcerative colitis. To elucidate the role of prostaglandin E2, thromboxane A2, prostaglandin I2, and leukotriene B2 in acute chemical colitis induced by 4% acetic acid, we utilized an animal model which has a deficiency of arachidonic acid, the precursor of eicosanoids due to an essential fatty acid deficient diet. Forty-eight hours after colitis was induced, mucosal synthesis of the cyclooxygenase products, prostaglandin E2, thromboxane A2, and prostaglandin I2, was significantly decreased in essential fatty acid deficient rats compared to normal controls. However, the 5-lipoxygenase product, leukotriene B4, was not different between groups. The decrease in cyclooxygenase products did not correlate with any change in the severity of colonic inflammation as assessed by gross morphology, histology, or myleoperoxidase activity. Thus inhibition of formation of the cyclooxygenase products of arachidonate metabolism does not appear to improve the degree of inflammation under the experimental conditions employed in this study.

Acetates↗
PubMed1989

Effects of the acute phase response on the concentration and density distribution of plasma lipids and apolipoproteins.

Longitudinal studies were carried out in the rabbit model to determine alterations in the concentration and density distribution of plasma lipids and apolipoproteins during the acute phase response (APR) characterized by elevated levels of C-reactive protein (CRP) and serum amyloid A (SAA). Twelve hr after the intramuscular injection of croton oil, SAA was detectable in high density lipoprotein (HDL). At the height of the response (72 hr), HDL decreased while SAA became the major HDL apoprotein, up to 80% of the proteins in the higher density fractions. The SAA-enriched particles became denser (density of HDL3) but larger (size of HDL2), had slower electrophoretic mobility, and were depleted in apoA-I, cholesterol, triglyceride, and phospholipid. HDL-cholesterol decreased and was redistributed to other fractions while apoA-I disappeared from the circulation. During this time plasma triglycerides increased 6- to 10-fold while plasma cholesterol and phospholipids showed minimal changes. ApoB increased 5- to 6-fold while the apoB-containing particles shifted to higher density resulting in elevated IDL and then LDL during recovery. VLDL (d less than 1.006 g/ml) increased and acquired 30-40% of the plasma triglycerides, cholesterol, phospholipid, and apoB. SAA also increased in VLDL while apoE decreased.

Acute-Phase Reaction↗
PubMed1988

Comparative evaluation of gastrointestinal intolerance produced by plain and tri-buffered aspirin tablets.

Two multi-investigator, double-blind, randomized, placebo-controlled, crossover trials were conducted to determine whether tri-buffered formulations of both regular strength aspirin and extra strength aspirin would be less likely than plain aspirin to provoke subjective gastrointestinal (GI) intolerance. Each trial was divided into two phases, a qualification phase and a test phase. During the qualification phase, subjects with a history of gastrointestinal intolerance to aspirin were randomized to a double-blind crossover treatment with aspirin and placebo (325 mg aspirin per tablet in study 1 and 500 mg aspirin per tablet in study 2), two tablets four times a day for 3 days or until the occurrence of stomach upset. Subjects who reported gastrointestinal symptoms with aspirin and not with placebo qualified to participate in the test phase of the study. They were rerandomized to participate in a three-way crossover study of plain aspirin, tri-buffered aspirin, and placebo in the test phase. Tri-buffered aspirin was associated with an appreciable reduction in the incidence of gastrointestinal upset relative to plain aspirin, 34 percentage points in study 1 (p less than 0.001) and 33 percentage points in study 2 (p less than 0.001). Similar results were obtained in the evaluation of the reduction of the severity of gastrointestinal symptoms.

Adult↗
PubMed1987

Histamine H2-receptor antagonists and high-density lipoproteins.

Epidemiologic evidence has shown that elevated levels of high-density lipoproteins (HDL) protect against the development of coronary heart disease (CHD). These observations have prompted the evaluation of various factors thought to affect HDL and its subspecies, HDL2 and HDL3. Numerous behavioral and physiologic factors have been shown to elevate HDL levels. These are currently being researched as potential tools in preventing CHD. Several pharmacologic agents are known to alter HDL levels. Studies show that patients with peptic ulcer disease treated with the H2-receptor antagonist cimetidine show significant elevations in their HDL, HDL2, and HDL3 profiles. In contrast, ranitidine has no effect, or may even decrease HDL levels. These divergent effects may be related to differences in pharmacologic activity unrelated to H2-receptor blockade. It should be noted that many of the variables affecting HDL levels were not controlled in these studies, and definite conclusions should not be extrapolated to the general population at risk for CHD. Currently, well-controlled trials to study the effect of cimetidine on HDL levels are in progress.

Histamine H2 Antagonists↗
PubMed1987

Inhibition of hepatic triglyceride secretion and exogenous triglyceride clearance in the cholestatic rat.

Extrahepatic biliary obstruction in humans and rats leads to hypertriglyceridemia. The observed hypertriglyceridemia could result from either a defect of plasma triglyceride (TG) catabolism or hepatic over-production of TG. To examine these questions we have used the rat model to determine hepatic TG secretion by the Triton WR-1339 methodology (inhibition of peripheral lipolysis) and exogenous TG clearance (after i.v. injection of Intralipid). Four groups of rats were studied: group OB--48 h post-operative--bile-duct obstructed; group DV--bile diverted; group SC--sham-operated controls; and group FC--48 h fasted, unoperated controls. The hepatic TG secretion rate for group OB rats was a factor of 7 lower than that of either group SC or FC, and 5 times lower than that for group DV. There were no differences between the hepatic TG secretion rates of groups DV and FC or SC. After i.v. injection of Intralipid, plasma TG decreased with first-order kinetics. The rate constant was taken as the exogenous TG clearance rate (ETGCR). Mean ETGCR for group OB was a factor of 3 lower than that for either control group; while the ETGCR for group DV was equivalent to the control groups. Thus biliary diversion does not affect hepatic TG secretion or the ETGCR. The apparent cause of the hypertriglyceridemia of cholestasis in the bile-obstructed rat is impaired plasma TG catabolism.

Animals↗
PubMed1986

Goals of therapy: aggressive or moderate acid suppression?

Healing with moderate acid suppression is increasingly becoming the goal of therapy in patients with peptic ulcer. Comparative trials between cimetidine and other more potent H2-receptor antagonists indicate no difference in efficacy or pain relief despite the higher degree of acid suppression induced by the newer agents. Recent clinical trials with cimetidine have demonstrated that the inhibition of nocturnal acid secretion alone is the most important factor in the healing of peptic ulcer. The results of clinical trials conducted in the United States and Europe demonstrated that 800 mg of cimetidine at bedtime is the optimal dosage regimen, providing rapid pain relief and ulcer healing in approximately 80% of the patients. Furthermore this regimen has the advantages of easy compliance, convenience, and fewer potential drug interactions, as well as providing 24-hour moderate acid suppression with normal daytime gastric acid levels. Thus in ambulatory patients with duodenal ulcer, a single nightly dose of 800 mg of cimetidine is the optimal regimen for moderate acid suppression. This reinforces a basic concept of medicine that the lowest possible dosage of a drug can be used to treat a condition effectively and safely. While moderate acid suppression with nocturnal dosing will accomplish the goal of healing in the ambulatory patient, different objectives of acid-suppression therapy may be needed when treating hospitalized patients in the intensive care unit. For these patients, well-controlled clinical trials indicate the necessity for a more aggressive approach to gastric acid control, with the goal being to maintain the intragastric pH above 4.0.

Cimetidine↗
PubMed1986

Dietary supplementation with Pluronic L-81 modifies hepatic secretion of very low density lipoproteins in the rat.

Supplementation of high fat/cholesterol-enriched diets with polyoxypropylene-polyoxyethylene copolymers containing 90% hydrophobic constituents has been found to impair enteric secretion of chylomicrons, lower plasma levels of very low density (VLDL) and low density (LDL) lipoprotein cholesterol and prevent diet-induced hypercholesterolemia and atherosclerosis. These agents are known to be absorbed from the gastrointestinal tract and excreted in bile. In order to determine whether dietary supplementation with this group of hydrophobic poloxalenes influences hepatic secretion of triglyceride-rich lipoproteins, groups of rats were maintained for 21-34 days on either standard chow, semisynthetic diet containing 10.0% safflower oil/1.0% cholesterol, or each of the above diets supplemented with the hydrophobic poloxalene Pluronic L-81. At the end of the feeding period, newly secreted hepatic VLDL were isolated from 2-hr recirculating liver perfusates, quantitated, and characterized. Compared to perfusions in chow-fed rats, perfusion experiments in rats fed the high fat/cholesterol-enriched semisynthetic diet revealed a 3.1-fold increased net hepatic VLDL secretion rate; enrichment of secretory VLDL in cholesteryl esters and in C18:2 core lipid fatty acids; and a shift in the size distribution of secretory VLDL towards larger particles. When the 0.5% Pluronic L-81 was included in the high fat/cholesterol-enriched semisynthetic diet, the net hepatic VLDL secretion rate fell significantly and the physicochemical properties of secretory VLDL in these rats were found to resemble those of chow-fed animals. Supplementation of the chow diet with L-81 resulted in a significant fall in the net hepatic VLDL secretion rate from that observed in rats fed chow alone. Compared to rats fed chow alone, perfusate VLDL from rats fed each of the other experimental diets contained markedly lower amounts of both apoB molecular weight variants, as analyzed by gradient gel electrophoresis and densitometric gel scanning. Since previous studies have demonstrated that VLDL are the major cholesterol transport lipoproteins following fat/cholesterol feeding; a precursor-product relationship exists between fat/cholesterol-induced hepatic VLDL and plasma VLDL; such particles are capable of delivering cholesterol to the arterial wall; and dietary supplementation with hydrophobic poloxalenes prevents both the increase in plasma VLDL-cholesterol and diet-induced atherosclerosis, it is possible that dietary supplementation with hydrophobic poloxalenes may influence the atherogenic process through direct and/or indirect effects on hepatic VLDL transport.

Alanine Transaminase↗