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Biomedical subjects

A Mezzetti

Publications and source records attributed to A Mezzetti.

At least 73 records · Page 4Linked to original sources

A 31P-nuclear magnetic resonance study of intermittent warm blood cardioplegia.

This study was designed to assess the effects of intermittent warm blood cardioplegia on myocardial energy metabolites, intracellular pH, and contractile function. The isolated blood-perfused pig hearts were divided into three groups. After 30 minutes of control perfusion, the hearts in group 1 (n = 10) received 90 minutes of continuous warm (37 degrees C) blood cardioplegia; the hearts in group 2 (n = 9) received six 5-minute periods of warm blood cardioplegia, interrupted by six 10-minute episodes of ischemia (37 degrees C). The hearts were then reperfused for 30 minutes. The hearts in group 3 underwent 150 minutes of control perfusion without cardioplegia or ischemic episodes. Phosphorus 31-nuclear magnetic resonance spectra showed that a 10-minute interruption of warm blood cardioplegia decreased phosphocreatine levels and intracellular pH by approximately 47% (p < 0.01) and 0.12 unit (p < 0.05), respectively, and increased inorganic phosphate levels by approximately 87%, whereas resumption of cardioplegia for 5 minutes resulted in almost 100% recovery of phosphocreatine and inorganic phosphate levels and intracellular pH. More important, subsequent interruptions did not result in any cumulative changes in phosphocreatine level, inorganic phosphate level, or intracellular pH beyond those changes observed after the initial cardioplegic interruption. Moreover, during reperfusion there were no significant differences in adenosine triphosphate and phosphocreatine levels among the three groups of hearts. Furthermore, hearts from groups 1 and 2 showed comparable recovery of contractile function. These results indicate that six 10-minute interruptions and six 5-minute restorations of warm blood cardioplegia caused only mild and reversible changes in myocardial energy metabolites and intracellular pH and these changes were not cumulative. This study suggests that antegrade intermittent warm blood cardioplegia may provide as much myocardial protection as does antegrade continuous warm blood cardioplegia in the normal heart.

Adenosine Triphosphate↗

Intermittent antegrade warm cardioplegia reduces oxidative stress and improves metabolism of the ischemic-reperfused human myocardium.

The aim of this study was to compare the effect of intermittent antegrade warm blood cardioplegia and intermittent antegrade cold blood cardioplegia on myocardial metabolism and free radical generation of the ischemic-reperfused human myocardium. Thirty patients undergoing mitral valve procedures were randomly allocated to two groups: group 1 (15 patients) received warm blood cardioplegia and group 2 (15 patients), cold blood cardioplegia. Myocardial metabolism was assessed before aortic clamping, 1 minute after crossclamp removal, and after 20 minutes of reperfusion, by collecting blood simultaneously from the radial artery and coronary sinus. All samples were analyzed for lactate, creatine kinase, reduced and oxidized glutathione, ascorbic acid, fluorescent products of lipid peroxidation, and leukocyte activation (elastase). In all patients, early reperfusion was associated with significant coronary sinus lactate release. In group 2, but not in group 1, significant coronary sinus release of reduced and oxidized glutathione, fluorescent products of lipid peroxidation, and creatine kinase was also found; moreover, arterial-coronary sinus difference of ascorbic acid content was increased only in group 2, suggesting a transmyocardial consumption of this antioxidant vitamin. After 20 minutes of reperfusion, coronary sinus lactate release was no longer present in group 1, whereas significant production was still evident in group 2. In this group, significant coronary sinus release of fluorescent products of lipoperoxidation and reduced and oxidized glutathione was also observed at this time. No significant release of elastase from the coronary sinus was noted in the two groups throughout the study. The left ventricular stroke work index measured at the end of the study indicated a better functional recovery in group 1 than in group 2. In conclusion, intermittent antegrade warm blood cardioplegia protects the myocardium from ischemia-reperfusion injury better than intermittent antegrade cold blood cardioplegia; this phenomenon may be partly due to the decreased tissue oxidant burden mediated by intermittent warm blood cardioplegia.

Aged↗

'White-coat' hypertension in patients with newly diagnosed hypertension: evaluation of prevalence by ambulatory monitoring and impact on cost of health care.

To evaluate the prevalence of 'white-coat' hypertension in patients with newly diagnosed hypertension, 255 subjects (131 males and 124 females) underwent 24-h ambulatory blood pressure monitoring. Patients with 24-h systolic and diastolic blood pressure < 135/85 mmHg were classified as white-coat hypertensives and the remaining as sustained hypertensives. On the assumption that white-coat hypertensives may not need to take antihypertensive medication, we evaluated the impact on cost of health care of two strategies based essentially on treating all patients according to casual blood pressure, or ambulatory blood pressure monitoring, followed by drug treatment in sustained hypertensives only. Of the 255 hypertensives studied, 54 (21%), confidence interval 16%, 26%, were classified as white-coat hypertensives. The age, sex-ratio and body mass index did not differ between the white-coat and the sustained hypertensive subjects. The strategy of monitoring all patients and of treating only the sustained hypertensives resulted in a substantial coat saving, which was calculated to be about 110,000 U.S.A. dollars over a period of 6 years. In conclusion, white-coat hypertensives are frequent among patients with newly diagnosed hypertension, and they do not differ from sustained hypertensives as regards demographic data. Ambulatory blood pressure monitoring, when used to decide whether or not to treat pharmacologically, increases the cost-effectiveness of treatment for hypertension and reduces the cost of health care.

Adult↗

Aminophylline: could it act as an antioxidant in vivo?

Potential antioxidant properties of aminophylline and theophylline were investigated. We have found that these drugs, though ineffective against superoxide anion and hydrogen peroxide, are scavengers of hydroxyl radical (OH.). Indeed, second-order rate constants (k) of aminophylline and theophylline with OH. are about 1.9 x 10(10) mol-1 s-1 and 4.5 x 10(9) mol-1 s-1, respectively. Ethylenediamine, which is present in the aminophylline molecule, significantly contributes to this marked OH. scavenging activity, since it is characterized by a high k value, i.e. about 8 x 10(9) mol-1 s-1. However, when using therapeutically relevant concentrations of the methylxanthines (9 and 13 micrograms mL-1), significant antioxidant effects against OH.-induced oxidant injury are evident only with aminophylline. Although all three substances can apparently bind and inactivate iron, only aminophylline is effective at 9 and 13 micrograms mL-1; also this action is favoured by ethylenediamine. Moreover, therapeutic concentrations of aminophylline, but not of theophylline, are capable of antagonizing hypochlorous acid (HOCl); this effect is entirely due to the presence of ethylenediamine. Oxidant species, such as OH. and HOCl, have been implicated in the pathophysiology of asthma; it could be hypothesized, therefore, that some therapeutic effects of aminophylline may be related to its antioxidant properties, which are partly or totally attributable to ethylenediamine, depending on the chemical identity of the prooxidant antagonized (e.g. iron/OH. or HOCl). Aminophylline antioxidant capacity should be taken into account when investigating the lung epithelial lining fluid antioxidant capacity and oxidative stress indices in humans.

Aminophylline↗

Target organ status and serum lipids in patients with white coat hypertension.

Target organ status and serum lipids were investigated in white coat hypertension in comparison with sustained hypertension and normotension. We selected three groups balanced for sex, age, body mass index, and smoking habit: 50 sustained hypertensives (clinical hypertension and 24-hour ambulatory blood pressure > 135/85 mm Hg, a cutoff limit obtained from a normotensive population), 25 white coat hypertensives (clinical hypertension and 24-hour ambulatory blood pressure < 135/85 mm Hg), and normotensives. Subjects underwent echocardiographic examinations to assess left ventricular mass index, carotid ultrasonography to evaluate intima-media thickness and atherosclerotic plaques, venous occlusion plethysmography to record minimum forearm vascular resistance, and determinations of serum lipid profile and 24-hour urinary albumin excretion. Compared with sustained hypertensives, the white coat hypertensives had significantly lower values of left ventricular mass index (125.9 +/- 20 versus 97.6 +/- 11.5 g/m2, P < .05, intima-media thickness (0.85 +/- 0.18 versus 0.71 +/- 0.15 mm, P < .05), minimum forearm vascular resistance (2.33 +/- 0.11 versus 2.04 +/- 0.08 resistance units, P < .05), urinary albumin excretion values (15.1 +/- 13.8 versus 4.45 +/- 1.48 mg per 24 hours, P < .0001), prevalence of left ventricular hypertrophy (versus 4%, P < .002), intima-media thickening 28% versus 4%, P < .015), and microalbuminuria (22% versus 0%, P < .015). No significant difference, however, was observed between the white coat hypertensives and the normotensives. Serum lipid profile was similar in the white coat hypertensives and in the normotensives.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Cigarette smoke, ferritin, and lipid peroxidation.

Gas and tar phases of commercially available filter cigarettes were tested for ferritin-iron-releasing effects and polyunsaturated-fatty-acid oxidant capacity in vitro. A vacuum pump-dependent apparatus with Cambridge filters was used to separate gas and tar; the former was directly smoked into reaction mixtures, while the latter was extracted from Cambridge filters in aqueous medium and freshly used at 40 to 80% final concentrations. Both phases induced ferritin iron release, which was not antagonized by superoxide dismutase (SOD). In specific experiments, we have also shown that gas and tar extracts could cross an organic (i.e., chloroform)-phospholipid layer before mobilizing ferritin iron. Once delocalized from ferritin, iron could trigger lipid peroxidation; however, a marked prooxidant effect (inhibited by 20 microM deferoxamine mesylate and significantly decreased by 40 microM vitamin E) was observed only with gas, whereas tar extracts showed antioxidant effects. Accordingly, tar extracts could also antagonize lipid peroxidation driven by non-chelated iron or by peroxyl radicals. In the absence of ferritin, gas-induced lipid peroxidation was very low, and tar extracts were apparently ineffective. Thus, the intrinsic lipoperoxidative capacity of cigarette smoke is low and is due to gas; however, when smoke interacts with ferritin, a marked iron-driven peroxidation becomes manifest essentially with gas, tar components acting as antioxidants. The present data suggest that cigarette-smoke-mediated iron mobilization from ferritin may represent a specific prooxidant mechanism related to cigarette smoking in vivo.

Atmosphere Exposure Chambers↗

Impaired left ventricular diastolic function and vascular postischemic vasodilation associated with microalbuminuria in IDDM patients.

OBJECTIVE: Microalbuminuria is considered an important predictor of cardiovascular events in diabetic patients. In this study, a possible association of microalbuminuria with significant changes in left ventricular (LV) morphology and function and generalized vascular dysfunction was analyzed in insulin-dependent diabetes mellitus (IDDM) patients without hypertension, coronary artery disease, or autonomic dysfunction. RESEARCH DESIGN AND METHODS: Thirty-four young long-term IDDM patients, 16 with and 18 without microalbuminuria, and 20 control subjects were studied. LV systolic function and wall thickness were evaluated by M-mode echocardiography. LV diastolic function was studied using a combined echo-Doppler and phonocardiographic technique. The hyperemic response to forearm ischemia was measured by strain-gauge plethysmography. All patients underwent 24-h ambulatory blood pressure monitoring. RESULTS: LV mass index and wall thickness:radius ratio were significantly higher in microalbuminuric patients. LV relaxation was significantly impaired in both diabetic groups compared with control subjects; moreover, this impairment was significantly greater in microalbuminuric than in normoalbuminuric patients. In microalbuminuric patients, forearm postischemic vasodilation was also significantly lower and mean awake diastolic blood pressure (dBP) was significantly higher than in the other two groups. CONCLUSIONS: Our data suggest that microalbuminuria is associated with significant changes in LV morphology, a more severe impairment of cardiac diastolic function, altered vascular dilatory capacity, and higher daytime dBP. Therefore, microalbuminuric patients should be considered to have a higher risk of cardiovascular complications and be kept under closer surveillance.

Adult↗

Vascular changes in hypertensive patients with different left ventricular geometry.

OBJECTIVE: To evaluate vascular structural changes in hypertensive patients with different patterns of left ventricular geometry. DESIGN AND METHODS: From 250 untreated hypertensive patients who underwent ambulatory blood pressure monitoring and echocardiographic study, we selected four groups matched for sex, age, body mass index, smoking habits and serum lipid values: 25 hypertensive subjects with normal left ventricular geometry, 16 with concentric left ventricular remodeling, 26 with concentric left ventricular hypertrophy and 18 with eccentric non-dilated left ventricular hypertrophy. These patients underwent carotid ultrasonography to evaluate the intimal-medial thickness and lumen diameter, and venous occlusion plethysmography to record minimum forearm vascular resistance (an index of arteriolar structural changes). RESULTS: The intimal-medial thickness and minimum forearm vascular resistance were significantly higher (both P<0.05) in hypertensive subjects with concentric left ventricular remodeling (0.95 mm, 2.68 RU) and concentric left ventricular hypertrophy (0.96 mm, 2.71 RU) than in those with eccentric non-dilated left ventricular hypertrophy (0.81 mm, 2.36 RU) and normal left ventricular geometry (0.71 mm, 2.15 RU). There was no difference between hypertensive patients with concentric left ventricular remodeling and concentric left ventricular hypertrophy. The intimal-medial thickness and minimum forearm vascular resistance tended to be higher in hypertensive subjects with eccentric non-dilated left ventricular hypertrophy than in those with normal left ventricular geometry, but this difference did not attain statistical significance. CONCLUSIONS: This study shows that the spectrum of cardiac adaptation to hypertension is associated with a spectrum of vascular adaptation which might be related both to hemodynamic stimuli and differences in the expression or activity of vascular growth factors.

Blood Flow Velocity↗

Transmural distribution of antioxidant defences and lipid peroxidation in the rabbit left ventricular myocardium.

The left ventricular subendocardial and subepicardial layers of six perfused rabbit hearts were tested for enzymatic and non-enzymatic antioxidant defences and for lipid peroxidation. The subendocardium showed significantly lower catalase activity and contents of non-protein thiol compounds and vitamin E associated with a higher degree of lipid peroxidation. The activities of Cu,Zn- and Mn-superoxide dismutases, glutathione reductase, gamma-glutamylcysteine synthetase and gamma-glutamyl transpeptidase showed no significant transmural differences, and Se-independent glutathione peroxidase activity was not detectable in either layer. Comparable results were observed in another group of six unperfused rabbit hearts. In five H2O2-perfused rabbit hearts, lipid peroxidation was higher, and myocardial creatine phosphokinase activity lower, in the subendocardium than in the subepicardium. In this group, only the subendocardium had significantly higher lipid peroxidation levels than the control hearts. Thus, a lower antioxidant capacity and a greater oxidative stress are present in the rabbit subendocardium. These findings could provide insight into the problem of subendocardial vulnerability to free radical-mediated processes, such as occurs in ischaemia-reperfusion injury.

Animals↗

Blood cardioplegia reduces oxidant burden in the ischemic and reperfused human myocardium.

In 20 patients receiving cold crystalloid cardioplegia (n = 10) or cold blood cardioplegia (n = 10) during elective coronary artery bypass grafting, the atrial myocardium was tested for glutathione-related antioxidant defenses and lipid peroxidation. In both groups, ischemia and reperfusion induced a significant increase in lipid peroxidation values (p < 0.05) that was associated with a depression of nonprotein thiol compound levels (p < 0.05). Compared with the cold crystalloid cardioplegia-treated patients, the cold blood cardioplegia-treated patients showed a lower lipid peroxidation (p < 0.05) and higher values of nonprotein thiol compounds (p < 0.05). Moreover, a significant ischemia and reperfusion-dependent activation of glutathione transferase was observed only in the cold crystalloid cardioplegia-treated patients. Selenium-dependent glutathione peroxidase and glutathione reductase activities did not change after release of the aortic cross-clamp and did not differ between the two groups. The highest postoperative plasma level of the myocardial-specific isoenzyme of creatine kinase was significantly more elevated in the cold crystalloid cardioplegia patients. Overall, these tissue biochemical features indicate a lower oxidant burden in the myocardium of cold blood cardioplegia-treated patients, a finding suggesting superior protection for the ischemic and reperfused human myocardium also through antioxidant-type mechanisms, apparently medicated by the antioxidant capacity of erythrocytes and specific plasma molecules.

Blood↗

Omeprazole, bismuth and clarithromycin in the sequential treatment of Helicobacter pylori infection.

AIMS: To assess the therapeutic potential of clarithromycin, a new macrolide with high anti-Helicobacter pylori activity, given with bismuth salts and omeprazole in different regimens aimed at simplifying the treatment of H. pylori-related gastritis. METHODS: Eighty-eight patients with proven H. pylori infection and gastritis were treated with one of the following four regimens: omeprazole 40 mg/day for one week (group A, n = 14); omeprazole 40 mg/day for one week followed by clarithromycin 1 g/day for 2 weeks (group B, n = 26); omeprazole 40 mg/day for one week followed by tripotassium dicitrato bismuthate 480 mg/day and clarithromycin 1 g/day, both for two weeks (group C, n = 26); and tripotassium dicitrato bismuthate 480 mg/day and clarithromycin 1 g/day for two weeks (group D, n = 22). Presence of H. pylori, histology and electron microscopy were assessed at entry and four weeks after the end of each treatment. RESULTS: Omeprazole alone had no effect on H. pylori status. The highest eradication rate was obtained in group C patients (81%), a proportion significantly greater than that observed in group B (50%, P < 0.03) or group D patients (55%, P < 0.05). CONCLUSION: Sequential treatment may be a useful option in the treatment of H. pylori-related gastritis.

Adult↗

H2-receptor antagonists are scavengers of oxygen radicals.

Potential oxygen radical scavenging properties of the H2-receptor antagonists cimetidine, ranitidine and famotidine were investigated. These drugs, although ineffective against superoxide anion and hydrogen peroxide, can scavenge hydroxyl radical (OH.) with a very high rate constant, which is about tenfold higher than that of the specific scavenger mannitol for famotidine (1.7 x 10(10) mol-1 s-1) and cimetidine (1.6 x 10(10) mol-1 s-1), ranitidine displaying a rate constant of 7.5 x 10(9) mol-1 s-1. These OH. savenging effects are significant beginning from 10, 28 and 100 mumol l-1 concentration for famotidine, cimetidine and ranitidine, respectively, thus suggesting that the drugs may effectively act as OH. scavengers in vivo especially in the gastric lumen. Only cimetidine can apparently bind and inactivate iron, which further emphasizes its antioxidant capacity. Moreover, all drugs, even at 10 mumol l-1 concentration, show powerful scavenging effects on hypochlorous acid and monochloramine, which are cytotoxic oxidants arising from inflammatory cells, such as neutrophils. These data suggest that some therapeutical effects of H2-receptor antagonists in peptic ulcer may also be related to their antiradical-antioxidant capacity, and that these drugs could potentially be used in other disease entities characterized by free radical-mediated oxidative stress in vivo.

Chloramines↗

Antiproliferative effect of desferrioxamine on vascular smooth muscle cells in vitro and in vivo.

Vascular smooth muscle cell (VSMC) growth is a primary component of accelerated and spontaneous atherosclerosis. Previous studies have shown that iron may be involved in the control of enzymatic activities that modulate DNA synthesis in human cells. In this study the effects of the iron chelator desferrioxamine on in vitro and in vivo VSMC proliferation were tested. Rat VSMCs in culture and a rabbit model of carotid artery balloon injury were used. Desferrioxamine showed a significant inhibitory effect on [3H]thymidine incorporation in cell cultures that was antagonized by iron supplementation. Desferrioxamine also provided effective preventive myointimal VSMC proliferation as assessed by bromodeoxyuridine labeling and morphometric analysis of endoluminal stenosis. These experiments suggested that iron may be involved in the control of VSMC proliferation and that desferrioxamine may have a role in preventing VSMC growth and myointimal proliferative lesions.

Animals↗

Hypochlorous acid-induced zinc release from thiolate bonds: a potential protective mechanism towards biomolecules oxidant damage during inflammation.

It has been proposed that metalloprotein zinc mobilization mediated by hypochlorous acid (HOCl) may induce cell injury (see H. Fliss and M. Ménard (1991), Archives of Biochemistry and Biophysics, 287, 175-179). In the present paper, we have demonstrated using a dimercaptopropanol-zinc complex that, once released from thiolate bonds by HOCl, zinc can exert a significant antioxidant effect on both linolenic acid and deoxyribose oxidation induced by iron. In these experimental conditions, however, the antagonism towards deoxyribose oxidation is notably less than that towards linolenic acid peroxidation, thus suggesting a more specific inhibitory effect of zinc on iron-mediated oxidant damage when polyunsaturated fatty acids represent the oxidizable substrate. The antioxidant effects of zinc are strictly related to the "free" form; indeed, the dimercaptopropanol-zinc complex per se is stimulatory even on biomolecules oxidant damage, apparently as a result of the prooxidant prooxidant interaction of the thiol compound with iron. In light of these results, it may be proposed that the zinc released from thiolate bonds by HOCl could specifically limit tissue oxidative burden in pathological conditions involving neutrophil accumulation and activation, such as inflammation and ischemia-reperfusion.

Animals↗

Intermittent antegrade cardioplegia: warm blood vs cold crystalloid. A clinical study.

Intermittent antegrade warm blood cardioplegia (IAWBC) is a not usual technique of myocardial protection. We propose a delivery protocol that standardizes the length of ischemic intervals, duration of each cardioplegic dose and K+ amount. Cardioplegia is represented by blood, taken from the oxygenator and injected directly into the aortic root, and K+, added by means of a syringe pump. We reviewed the first 300 patients who underwent elective or urgent coronary artery by-pass procedures (group A) and compared them with the last 300 patients operated on with intermittent antegrade cold crystalloid cardioplegia (group B). The overall mortality in group A was lower than in group B (0.7 vs 3.0, p < 0.05); there was no in-hospital death in patients with poor left ventricle (LVEF < 35%) in group A (0/64 vs 3/39, p < 0.025). Reduction of mortality was due to a drastic fall of morbidity. In group A no patients needed circulatory assistance (13 in group B, p < 0.0005) or intraaortic balloon pumping (9 in group B, p < 0.005) in operating room or in intensive care unit (ICU); only 1 patient had inotropic drug (29 in group B, p < 0.0005) and only 6 needed lignocaine infusion (27 in group B, p < 0.0005). Incidence of postoperative myocardial infarction was lower in group A (4 vs 9 in group B) as well cerebrovascular accidents (4 vs 10 in group B), but difference was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Bacterial mucosal infiltration in Helicobacter pylori-associated gastritis: histological and clinical consequences.

OBJECTIVES: We wished to demonstrate that gastric epithelial cells infiltration by HP is associated with the active inflammatory response and the severity of gastritis in the gastric antrum of patients harboring the bacterium. METHODS: We studied 129 patients with HP-associated gastritis and 60 HP-negative controls with gastritis of different origin. Gastric mucosal biopsies were obtained from all subjects at endoscopy and were examined for histological features of active inflammation and type of gastritis, as well as for electronmicroscopical features of invasion and damage, according to a four-degree classification (range 0-3). RESULTS: At entry, the presence of acute inflammatory activity, defined according to the presence of a polymorphonuclear cell infiltrate, was significantly greater in HP-positive patients than in controls (p < 0.00001) and was well related to the depth of mucosal invasion (p < 0.001). Accordingly, the prevalence of chronic atrophic gastritis was higher in HP-positive patients (p < 0.02 vs. controls) and at grade 3 of invasion (p < 0.04 vs. grade 1 and 2). Peptic ulcers were more frequent in grade 3 patients (p < 0.04). CONCLUSION: Gastric epithelial cell infiltration and damage by HP, as assessed by electron microscopy, is an important feature of HP-associated gastritis due to its histological and clinical correlates.

Female↗

Five-year maintenance treatment with ranitidine: effects on the natural history of duodenal ulcer disease.

In this study, we assessed the effect of a 5-yr maintenance program with ranitidine on the natural history of duodenal ulcer disease both during treatment and after drug withdrawal. Two groups of patients with duodenal ulcer were studied. In group A patients (n = 40), ranitidine (150 mg/day) was given continuously for 5 yr; group B patients (n = 40), received seasonal, 8-wk prophylactic treatment with ranitidine (300 mg/day), in spring and fall. Routine endoscopy was performed every year and whenever ulcer symptoms recurred. After the 5-yr study, the drug was discontinued in both groups, and patients underwent endoscopy after 3, 6, 12, and 18 months. The probability of duodenal ulcer recurrence was significantly lower in patients continuously receiving ranitidine (p < 0.001), and ulcer complications were significantly lesser in group A patients (p < 0.03). In the 18 months of follow-up after drug discontinuation, only 15% (4/26) of patients of group A relapsed, whereas ulcer recurrence was diagnosed in 84% (26/32) of group B patients (p < 0.001). We conclude that low-dose continuous treatment with ranitidine is preferable to seasonal prophylaxis for its ability to modify the natural history of duodenal ulcer disease.

Adult↗