Efficacy and tolerability of pantoprazole versus ranitidine in the treatment of reflux esophagitis and the influence of Helicobacter pylori infection on healing rate.

Patients with reflux esophagitis (grade II or III, Savary-Miller, intention-to-treat, n=256, age range 19-82 years) were randomly assigned to a double-blind, double-dummy treatment with either pantoprazole 40 mg once daily or ranitidine 150 mg twice daily. After 4 weeks, each patient was clinically and endoscopically assessed. Failure to heal required a further 4 weeks of treatment and a new evaluation thereafter. After 4 weeks, healing of lesions was confirmed in 63% (69 out of 109) of patients receiving pantoprazole and in 22% (25 out of 113) receiving ranitidine (P < 0.001, per protocol population). After 8 weeks, the cumulative healing rates were 88% and 46%, respectively (P < 0.001). Complete freedom from esophagitis-related symptoms (acid eructation, heartburn, pain while swallowing) was greater in the pantoprazole than in ranitidine group after 2 and 4 weeks (74% vs. 47%; 87% vs. 52%, respectively, P < 0.001). After 4 weeks, the healing rate was 76% in Helicobacter pylori (Hp)-positive vs. 45% in Hp-negative patients treated with pantoprazole (P < 0.01). The Hp status did not influence healing rates in patients treated with ranitidine. The most frequent adverse events in the pantoprazole group were diarrhea and somnolence (2-3% of patients), and in the ranitidine group, headache, diarrhea, dizziness, increase of liver enzymes and pruritus (2-4% of patients). In conclusion, pantoprazole was more effective than ranitidine in the healing rate and relief from reflux esophagitis-associated symptoms, and Hp infection was associated with higher healing rate during therapy with pantoprazole but not with ranitidine.

Pantoprazole versus ranitidine in the treatment of duodenal ulcer: a multicenter study in Brazil.

OBJECTIVE: The aim of this study was to compare the effectiveness and tolerance of pantoprazole versus ranitidine in the treatment of duodenal ulcers in the Brazilian population. METHODS: A total of 222 patients with active duodenal ulcers (DU) were randomly allocated to a double dummy blind treatment, either with ranitidine (RAN) 300 mg (111, aged from 20-68 yr old, 56 female) or with pantoprazole (PANT) 40 mg (111 patients, 18-70 yr old, 45 female). After a 2-wk course of treatment, each patient was clinically and endoscopically assessed for ulcer healing. Failure to heal required a further 2-wk course of treatment and a new evaluation thereafter. RESULTS: In all, 77 of the 103 patients in the PANT group (74.8%) and 42 of the 94 patients in the RAN group (44.7%) who completed the study had ulcer healing after one 2-wk treatment course, and an additional 23 in the PANT group (22.3%) and 28 in the RAN group (29.8%) after the second 2-wk treatment course, totaling 100 (97.1%) and 70 (74.5%), respectively. Therapeutic gain in favor of pantoprazole was significant both at the end of the first and the second 2-wk treatment course (p<0.001). At 2 wk, symptoms remission was significantly higher in the PANT group (97.6%) than with the RAN group (77.5%) (p<0.001). The Intention-to-treat analysis showed results statistically similar to those observed in the per-protocol analysis. Minor adverse events were reported by four patients in the PANT group and three in the RAN group. No relevant laboratory abnormalities were seen. No patient withdrew from the study due to adverse events. CONCLUSIONS: Our results show that pantoprazole is more effective than ranitidine in the treatment of duodenal ulcer providing faster ulcer healing in most patients (97.1%), in 4 wk. Adverse events were rare and were similar in both groups, and had no influence on the therapeutic outcome.

Intraesophageal balloon distension test in Chagas' disease patients with noncardiac chest pain.

Patients with Chagas' disease often have chest pain as a prominent symptom. The objective of this study was to compare the results of intraesophageal balloon distension in chagasic and nonchagasic patients with chest pain not caused by coronary obstruction. We studied 40 patients with chest pain and angiographically normal coronary arteries, 25 with a positive serologic test for Chagas' disease (Chagas group, 16 women, mean age 53+/-10 years), and 15 with a negative serologic test (control group, 11 women, mean age 46+/-10 years). All patients had radiologic and endoscopic examinations of esophagus, stomach, and duodenum, esophageal manometry with the acid infusion test in the distal esophagus, and intraesophageal balloon distension. None of them had esophageal dilation or any signs of cardiovascular disease. A 25-mm-long latex balloon located 10 cm above the lower esophageal sphincter was inflated and deflated over a period of 10 sec at 1-ml increments of air until the subjects reported chest pain or to a maximum volume of 20 mi. The test caused chest pain in 14 subjects in the control group (93%) and in 12 in the Chagas' disease group (48%, P < 0.05). The mean volume of air that caused chest pain was 10+/-3 ml in the control group and 15+/-4 ml in the Chagas' disease group (mean+/-SD, P < 0.05). The maximum intraesophageal pressure during the examination was higher in Chagas' disease patients with chest pain during balloon distension (60 +/- 21 mm Hg) than in patients who did not have chest pain (37 +/-18 mm Hg, P < 0.05) and did not differ from the control group (48+/-16 mm Hg, P > 0.05). With the other examinations there was no difference between groups or between patients with or without chest pain during the balloon distension test. Although esophagitis was observed in 47% of patients in the control group and in 40% of the Chagas' disease group, the acid infusion test was positive in 27% of patients in the control group and in 4% of patients in the Chagas' disease group. We conclude that, as compared to a group of patients with similar chest pain, chagasic patients are less sensitive to esophageal distension. Thus, it is unlikely that their chest pain is related to esophageal mechanisms.

[A missing name in the history of chagasic megaesophagus: Joseph Cooper Reinhardt (1809/10-1873)]. / Um nome que faltava na história do megaesôfago chagásico: Joseph Cooper Reinhardt (1809/10-1873).

The book entitled "Brazil and the Brasilians", written by the Reverends Kidder and Fletcher and firstly published in the United States in 1857, reports the travels of these two missionaries throughout Brazil and includes a section entitled "A new disease". This section contains data regarding the clinical picture, the natural history and the epidemiology of a commom disease in Brazilian hinterland, which was known as "mal de engasgo". These informations were collected in 1855 by Rev. Fletcher from an anonymous North American physician, who worked in Limeira, State of São Paulo, and is called in the book merely as "Dr.-". The present work reports the results of an investigation carried out aiming at the identification of "Dr.-" and discloses documental evidence that "Dr.-" was actually Dr. Joseph Cooper Reinhardt (1809/10-1883). Dr. Reinhardt worked for many years in the citites of Limeira and Campinas, State of São Paulo, and probably had an extensive knowledge regarding the main features of this particular disease, which would be known, nearly 100 years later, as chagasic megaesophagus. The authors point out that, from now on, any account of the history of chagasic megaesophagus must include the name of Dr. Joseph Cooper Reinhardt.

[Miguel Dias Pimenta (1661-1715) and the history of chagasic megaesophagus and megacolon]. / Miguel Dias Pimenta (1661-1715) e a história do megaesôfago e do megacólon chagásicos.

In the present study an attempt was made to analyse from a clinical viewpoint the descriptions in the book "Noticias do que he o achaque do bicho" by Miguel Dias Pimenta (1661-1715), which are considered by some authors to be the first reference to the chagasic megaesophagus and megacolon that appeared in history. In descriptions considered to refer megaesophagus, although dysphagia, the major symptom of this disease, is not recognized, typical manifestations of a irritating, inflammatory or ulcerative condition are identified, not affecting the esophagus but the stomach. In the description considered to refer to megacolon, the signs and symptoms suggest the diagnostic possibility of hemorrhoids and of the "achaque do bicho" itself, and do not recall the clinical picture of the chagasic megacolon in an absolute manner. On this basis, there is no reason to maintain the book "Noticias do que he o achaque do bicho" within the history of the digestive form of Chagas' disease.

[Small bowel bacterial overgrowth syndrome in chagasic megajejunum: report of 2 cases]. / Síndrome do supercrescimento bacteriano no intestino delgado no megajejuno chagásico: relato de dois casos.

We report two cases of Chagas' disease with megacolon who presented with chronic diarrhea. One of the patients also had evidence of malabsorption, such as steatorrhea and hypocalcemia. Barium meal follow-through showed remarkable dilation of the jejunum in both cases and, in one of them, an associated megaduodenum. Manometric studies of gastrointestinal motility showed abnormally slow propagation of the interdigestive migrating motor complex, which was also excessively prolonged. Cultivation of jejunal aspirates revealed strict anaerobic bacterial growth in both cases. Oral antibiotic therapy led to substantial improvement in symptoms. The two cases herein reported indicate that clinical manifestations of small bowel bacterial overgrowth, possibly caused by motor disturbances associated with megajejunum, may occasionally include the clinical picture of gastrointestinal involvement in Chagas' disease.

[Esophageal origin of precordial pain in chagasic patients with normal subepicardial coronary arteries]. / Origem esofágica de dor precordial em pacientes chagásicos com artérias coronárias subepicárdicas normais.

PURPOSE: To study the chest pain of esophageal origin in chagasic patients (CH) and non-chagasic subjects (NCH) with normal coronary arteries. METHODS: The study comprised 48 patients: 33 CH (age 56 years, 50% male) and 15 NCH (age 47 years, 25 male), with precordial chest pain and normal subepicardial coronary arteries. They were assigned to upper digestive tract radiologic and endoscopic study, esophageal manometric evaluation at baseline and after provocative tests (Bernstein and intravenous edrophonium). RESULTS: Radiologic study: 14 (42%) CH and 4 (27%) NCH had esophageal dilation (p > 0.05). Hiatal hernia was documented in 7 (21%) CH and 6 (40%) NCH (p > 0.05). 2) Digestive endoscopy: In 15 (45%) CH and 6 (40%) NCH distal esophagitis were seen. In the NCH, esophagitis occurred with hiatal hernia; however only 30% of CH with esophagitis had also hiatal hernia while another 30% had esophageal dilation. 3) Esophageal motility disorders (EMD): 11 (33%) CH showed EMD: 8 with inferior esophageal sphincter achalasia (IESA) and 3 with diffuse esophageal spasm. Among NCH, 2 (13%) had IESA (p > 0.05). 4) Bernstein test--a positive test was seen in 5 (15%) CH and 3 (20%) NCH-p > 0.05. CH with esophageal dilation had 14% of positive results, while CH without esophageal dilation had 16%-p > 0.05. 5) Intravenous edrophonium-esophageal contraction amplitude enhancement provoked by the drug infusion was clearly attenuated in the chagasic (6.9 +/- 12.7 mmHg) when compared with the NCH group (18.8 +/- 21.4 mmHg). A positive test (i.e. chest pain) was obtained in only one patient who was NCH. CONCLUSION: Esophageal pain could be elicited at a relatively low and comparable rate in both groups of patients.

Esophageal dysfunction does not always worsen in systemic sclerosis.

Using the manometric method, we studied the progression of esophageal involvement in 17 women with a diagnosis of systemic sclerosis (SSc) and compared the results with those obtained for 14 healthy women. The manometric examination of SSc patients was performed twice, with an interval of 9 to 111 months (median, 40 months). All patients had peristaltic contractions in the proximal esophagus. Eight had peristaltic contractions, and 9 had no contraction in the middle and distal esophagus. The lower esophageal sphincter pressure and the amplitude of contractions in the esophageal body were lower in SSc patients than in controls. The duration of contractions was the same in SSc patients and controls. The velocity of peristaltic contractions did not differ between patients and controls in the distal esophagus, but was higher in SSc patients in the proximal esophagus. In 16 patients, no difference in lower esophageal sphincter (LES) pressure, esophageal contraction amplitude, duration, and velocity was observed between the first and second evaluation. In one patient, the distal esophageal contractions changed from peristaltic to completely absent, and the lower esophageal sphincter pressure changed from 20.2 mm Hg to 5.1 mm Hg. The results suggest that the esophageal involvement of SSc patients was not progressive in all cases.

Cytochrome P450 and glutathione in the liver of rats under exclusive sucrose ingestion.

1. The objective of the present investigation was to study some of the possible mechanisms involved in the protective effect of sucrose ingestion against liver necrosis induced by acetaminophen. Three groups of male Wistar rats (220-260 g) were submitted to the following experimental conditions for a period of 42 h: free access to a balanced commercial diet (Group I), an exclusive sucrose diet (Group II) and fasting (Group III). At the end of the experiment, hepatic cytochrome P450 levels were measured in 11 rats from each group, plasma antipyrine half-life (t1/2) was determined in 40 rats from each group, and hepatic glutathione (GSH) concentration in 10 rats from each group. GSH consumption elicited by a high dose of acetaminophen (ACP, 1.0 g/kg, by gavage) was also determined in 30 rats each from Groups II and III. 2. The liver of Group II rats presented a significant reduction of cytochrome P450 levels in the microsome fraction (range 0.31-0.46, median, 0.37 nmol/mg vs range 0.60-0.93, median 0.74 for group I, and range 0.63-1.22, median 0.91 for group III, reported as nmol/mg microsome protein; range 23.8-48.4, median 40.4 vs 66.6-130, median 81.8 for group I and range 59.0-117.1, median 77.1 for group III, reported as nmol/100 g body weight), and a prolongation of antipyrine half-life (146.4 vs 83.4 min for group I and 93.6 for group III) when compared with the rats of the two other groups. 3. Since the toxicity of acetaminophen depends on the production of a reactive metabolite by the cytochrome P450 system in the liver, we conclude that changes in this system brought about by exclusive sucrose ingestion for 42 h may explain the liver protection against the toxicity of a high dose of the drug even in the presence of a significant concomitant reduction in liver GSH levels.

Cytochrome P450 and glutathione in the liver of rats under exclusive sucrose ingestion

1. The objective of the present investigation was to study some of the possible mechanisms involved in the protective effect of sucrose ingestion against liver necrosis induced by acetaminophen. Three groups of male Wistar rats (220-260 g) were submitted to the following experimental conditions for a period of 42 h: free access to a balanced commercial diet (Group I), an exclusive sucrose diet (Group II) and fasting (Group III). At the end of the experiment, hepatic cytochrome P450 levels were measured in 11 rats from each group, plasma antipyrine half-life (t1/2) was determined in 40 rats from each group, and hepatic glutathione (GSH) concentration in 10 rats from each group. GSH consumption elicited by a high dose of acetaminophen (ACP, 1.0 g/kg, by gavage) was also determined in 30 rats each from Groups II and III. 2. The liver of Group II rats presented a significant reduction of cytochrome P450 levels in the microsome fraction (range 0.31-0.46, median, 0.37 nmol/mg vs range 0.60-0.93, median 0.74 for group I, and range 0.63-1.22, median 0.91 for group III, reported as nmol/mg microsome protein; range 23.8-48.4, median 40.4 vs 66.6-130, median 81.8 for group I and range 59.0-117.1, median 77.1 for group III, reported as nmol/100 g body weight), and a prolongation of antipyrine half-life (146.4 vs 83.4 min for group I and 93.6 for group III) when compared with the rats of the two other groups. 3. Since the toxicity of acetaminophen depends on the production of a reactive metabolite by the cytochrome P450 system in the liver, we conclude that changes in this system brought about by exclusive sucrose ingestion for 42 h may explain the liver protection against the toxicity of a high dose of the drug even in the presence of a significant concomitant reduction in liver GSH levels

Achalasia occurring years after acute poliomyelitis.

We present a case of a 19 year old female patient with dysphagia for 4 months. Radiologic, endoscopy and manometric examinations were compatible with the diagnosis of idiopathic achalasia. Clinical, epidemiologic and serologic investigation was negative for Chagas' disease. When she was three years old she had acute poliomyelitis that left muscular atrophy in her left leg. It is possible that lower esophageal sphincter achalasia was the consequence of lesion in the dorsal motor nucleus of the vagus nerve caused by poliomyelitis. The association between poliomyelitis and achalasia supports the infective hypothesis as the cause of achalasia.

Abnormalities of the interdigestive migrating motor complex in a patient with carcinoid syndrome.

Intraluminal pressures of the gastric antrum, duodenum and jejunum were recorded for 206 min after a 12 h fast in a patient with carcinoid syndrome due to neoplasia of enterochromaffin cells of the ileum and with hepatic metastases. The most conspicuous alteration was a tachyrrhythmia of 16 waves/min predominating in the activity fronts of both duodenum and jejunum. Periods of 11-12 waves/min frequency appeared irregularly and the simultaneous occurrence of frequencies of 11 waves/min and 16 waves/min was also recorded. The gastric antrum was fully quiescent throughout the study. The alterations observed are presumed to be produced by substances secreted by the carcinoid tumor.

Polycystic hydatid disease (Echinococcus vogeli). Treatment with albendazole.

Six patients with polycystic hydatid disease (PHD) were treated with 10 mg kg-1 day-1 albendazole. One patient was treated continuously for eight months and another for three months. In three other patients treatment was discontinuous, consisting of a series of at least three 30-day cycles separated by 15 days without treatment. The last patient was treated continuously with 12 mg kg-1 day-1 albendazole for 51 days and then with three 30-day cycles of treatment with 10 mg kg-1 day-1 separated by 15-day drug-free intervals. Follow-up ranged from 10-30 months. Considerable clinical improvement and cyst reduction or disappearance occurred in four patients. Clinical improvement, but no changes in the hepatic alterations detected by computerized tomography, occurred in the other two patients, although a pulmonary cyst disappeared in one of them. Adverse effects were proteinuria, alopecia, leucopenia, itching and discrete elevation in aspartate transaminase, all of them reversed after the end of treatment. These results indicate that albendazole is effective for the treatment of PHD.

Polycystic hydatid disease (Echinococcus vogeli). Clinical, laboratory and morphological findings in nine Brazilian patients.

Polycystic hydatid disease occurs in neotropical zones and is caused by Echinococcus vogeli. The paca, a wild rodent, is the intermediate host and the final host is the dog. Seven cases of polycystic hydatid disease autochthonous to the Brazilian Amazon region are described. The disease was polycystic in all cases and diagnosis was based on anatomopathological findings. E. vogeli was identified by the shape and dimensions of the rostellar hooks. The liver was the organ most often involved (6/7), followed by the lungs (2/7) and mesentery (2/7), spleen (1/7) and pancreas (1/7). The main clinical manifestations were abdominal pain, hepatomegaly, jaundice, weight loss, anemia, fever, hemoptysis, palpable abdominal masses and signs of portal hypertension. Hepatic calcifications were detected in four cases. Two cases from the hinterland of the State of São Paulo are also reported. Both had calcified round structures in the liver, highly suggestive of calcified polycystic hydatids. The aim of the present report was to report on this relatively unknown hydatid disorder of Tropical America and to disseminate its clinical, ultrasound and radiological features.

[Kinetics of jejunal glucose transport in niacin deficient rats]. / Cinética do transporte jejunal de glicose em ratos com deficiência de niacina.

The kinetic of jejunal glucose transport was studied using perfused rat jejunum in vivo. Ninety rats were fed a diet deficient in niacin and 90 a control diet. The jejunal loops of 7 groups of animal were infused each group with one of following solutions of glucose: 5, 10, 20, 40, 80, 160 and 300 mM/l. The Vmax and Km values were determined. The results showed that the vitamin-deficient rats absorbed less glucose independently of the amount infused and these animals had lower Vmax (133.7 microM/15 min/15 cm) and Km (192.1 mM/l) than control groups (294.1 microM/15 min/15 cm and 171.8 mM/l, respectively). In conclusion one can assume that niacin deficiency leads to a decreased glucose absorption in the jejunal loops, when tested as in our experimental model.

[Echinococcus vogeli cysts in paca liver (Cuniculus paca) native from the Acre State, Brazil]. / Cistos de Echinococcus vogeli em fígado de paca (Cuniculus paca) originária do Estado do Acre, Brasil.

Four of the patients with polycystic hydatid disease observed by us reported that they were aware of the presence of liver disease in the pacas hunted for food. The viscera of these animals were usually given to domestic dogs. All of our 7 patients reported contact with dogs that had previously ingested viscera of pacas. Examination of the liver considered to be diseased by one of the patients and removed from a paca killed in the same region (State of Acre, Brazil) from which the human cases originated showed the presence of hydatid cysts. The characteristics of the rostellar hooks of the protoscolex indicated that this was the larval form of Echinococcus vogeli. These observations confirm the participation of pacas in the biological cycle of E. vogeli and the pathway through which man may become an alternative intermediate host of this echinococcus.