RESUMEN
Pyoderma gangrenosum (PG) is a neutrophilic dermatosis of unknown etiology characterized by typical skin ulcers. It may be related to systemic disorders but its association with solid tumors is very unusual. In this setting, we describe a patient in whom PG was the first and isolated manifestation of advanced gastric adenocarcinoma.
Asunto(s)
Adenocarcinoma/complicaciones , Adenocarcinoma/diagnóstico , Piodermia Gangrenosa/complicaciones , Piodermia Gangrenosa/diagnóstico , Neoplasias Gástricas/complicaciones , Neoplasias Gástricas/diagnóstico , Adulto , Diagnóstico Diferencial , Resultado Fatal , Gastroscopía , Humanos , MasculinoRESUMEN
AIM: Triple therapy seems more effective in curing Helicobacter pylori infection in patients with peptic ulcer than in those with non-ulcer dyspepsia. It has been suggested that this difference depends on the expression of CagA protein that is more frequent in the former. The objective of this study was to investigate a potential association between serum CagA positivity, severity of gastric mucosal inflammation and eradication success among peptic ulcer and non-ulcer dyspepsia patients. MATERIAL AND METHOD: Patients undergoing upper gastrointestinal endoscopy for investigation of dyspepsia at the Department of Gastroenterology, Hospital Vera Cruz, between March, 2000 and March 2001 were screened. H. pylori positive patients, as diagnosed by rapid urease test and histology were included. Severity of gastric mucosal inflammation was determined and serum CagA positivity was assessed using a commercially available ELISA assay prior to H. pylori 7-day eradication therapy with lansoprazole, clarithromycin and amoxicillin (30 mg, 500 mg and 1 g b.i.d., respectively). Eradication success was determined 8-24 weeks following completion of therapy. RESULTS: Seventy-four patients were included in the study (mean age 40.8, range 18-67, female = 28). CagA positivity was observed in 48% of patients. Gastroduodenal peptic ulceration was found in 54% of patients. Serum CagA positivity was significantly higher among peptic ulcer patients (62.5%), while CagA negativity was significantly higher among non-ulcer dyspepsia patients (67.7%). Lymphocyte and eosinophil infiltration was significantly higher among CagA + patients, despite being comparable when distributed among peptic ulcer and non-ulcer dyspepsia patients. Eradication was successful in 93.2% of patients, regardless of CagA status on a per protocol analysis. Based on a per protocol analysis, eradication success was comparable among peptic ulcer and non-ulcer dyspepsia patients, regardless of CagA status. CONCLUSION: Our results support the concept that CagA positivity is associated to peptic ulcer disease and to a higher severity of lymphocyte and eosinophil infiltration. Efficacy of treatment eradication of H. pylori may not be affected by serum CagA status.
Asunto(s)
Amoxicilina/uso terapéutico , Antibacterianos/uso terapéutico , Antiulcerosos/uso terapéutico , Antígenos Bacterianos/sangre , Proteínas Bacterianas/sangre , Claritromicina/uso terapéutico , Dispepsia/etiología , Gastritis/tratamiento farmacológico , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori/aislamiento & purificación , Omeprazol/análogos & derivados , Úlcera Péptica/etiología , 2-Piridinilmetilsulfinilbencimidazoles , Adolescente , Adulto , Anciano , Amoxicilina/administración & dosificación , Antibacterianos/administración & dosificación , Antiulcerosos/administración & dosificación , Antígenos Bacterianos/genética , Proteínas Bacterianas/genética , Biomarcadores , Claritromicina/administración & dosificación , Quimioterapia Combinada , Dispepsia/microbiología , Ensayo de Inmunoadsorción Enzimática , Eosinofilia/sangre , Eosinofilia/etiología , Eosinofilia/patología , Eosinófilos/patología , Femenino , Mucosa Gástrica/microbiología , Mucosa Gástrica/patología , Gastritis/sangre , Gastritis/complicaciones , Gastritis/microbiología , Gastritis/patología , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/patología , Helicobacter pylori/genética , Humanos , Lansoprazol , Linfocitos/patología , Masculino , Persona de Mediana Edad , Omeprazol/administración & dosificación , Omeprazol/uso terapéutico , Úlcera Péptica/sangre , Úlcera Péptica/microbiología , Úlcera Péptica/patologíaRESUMEN
BACKGROUND: The effects of proton pump inhibitors and Helicobacter pylori infection on the distribution of drugs used for the eradication of the bacteria are poorly understood. AIM: The aim of this study was to investigate the effects of a 7-day administration of 20 mg of omeprazole on the pharmacokinetics of amoxicillin and ampicillin in the plasma, saliva and gastric juice of individuals with and without H. pylori infection. METHODS: Fifty-four healthy volunteers without endoscopic lesions were enrolled. Twenty-six volunteers were included in the amoxicillin study and 28 individuals in the ampicillin study. Each study had an open randomized two-period crossover design and a 21-day washout period between phases. Plasma, saliva and gastric juice concentrations of amoxicillin and ampicillin in subjects with and without omeprazole pre-treatment were measured by reversed-phase HPLC using UV detection. RESULTS: Neither pre-treatment with omeprazole nor H. pylori infection interfered with the plasma bioavailability of amoxicillin or ampicillin, as assessed by the AUC0-2 h. Neither ampicillin nor amoxicillin were detected in saliva or gastric juice in any study phase. CONCLUSION: Short-term treatment with omeprazole does not interfere with the pharmacokinetics of amoxicillin or ampicillin. Our results also exclude the presence of a transfer mechanism for amoxicillin or ampicillin from the plasma to the gastric lumen.
Asunto(s)
Amoxicilina/farmacocinética , Ampicilina/farmacocinética , Inhibidores Enzimáticos/farmacología , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori/patogenicidad , Omeprazol/farmacología , Penicilinas/farmacocinética , Inhibidores de la Bomba de Protones , Adulto , Amoxicilina/administración & dosificación , Ampicilina/administración & dosificación , Área Bajo la Curva , Disponibilidad Biológica , Cromatografía Líquida de Alta Presión , Estudios Cruzados , Femenino , Jugo Gástrico/química , Humanos , Masculino , Penicilinas/administración & dosificación , Saliva/químicaRESUMEN
OBJECTIVE: To evaluate the efficacy of two commonly employed treatments for Helicobacter pylori infection and the impact of bacterial resistance to antibiotics on eradication rate. METHODS: Ninety-two consecutive H. pylori-positive patients with active peptic ulcer disease were randomly enrolled to receive a 7-day treatment with either lansoprazole 30 mg plus amoxicillin 1 g and clarithromycin 500 mg [all twice a day (b.i.d.), Group A, n = 46]; or bismuth subcitrate 125 mg four times a day (q.i.d.) plus tetracycline 500 mg q.i.d and furazolidone 200 mg b.i.d. (Group B, n = 46) H. pylori status was reassessed 30 days after completion of the therapy and bacterial resistance to the antibiotics was investigated using an in vitro assay. RESULTS: Five patients from each study group were lost to follow up. Both treatments resulted in similar H. pylori eradication rate: 66-60% (per protocol), 59-52% (intention-to-treat) in Groups A and B, respectively (non significant). However, eradication improved to 79% in the absence of H. pylori resistance to clarithromycin or amoxicillin. CONCLUSION: Primary resistance to clarithromycin or amoxicillin may underscore a potentially serious problem for the eradication of H. pylori infection. Testing for bacterial resistance may become necessary to improve therapeutic efficacy.
Asunto(s)
Antibacterianos/farmacología , Farmacorresistencia Bacteriana , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori/efectos de los fármacos , Úlcera Péptica/tratamiento farmacológico , Adulto , Anciano , Antibacterianos/uso terapéutico , Quimioterapia Combinada , Femenino , Infecciones por Helicobacter/microbiología , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Úlcera Péptica/microbiología , Insuficiencia del TratamientoRESUMEN
AIM: To investigate the presence of lesions of the upper gastrointestinal tract of asymptomatic, healthy volunteers undergoing clinical pharmacology studies. MATERIAL AND METHODS: A series of 53 volunteers (45 male, 23 Helicobacter pylori negative and 30 Helicobacter pylori positive) underwent upper gastrointestinal endoscopy. Helicobacter pylori status was assessed using two methods (rapid urease test and histology) from antral and corpus biopsies. RESULTS: Peptic lesions were found in 24 (45%) subjects: erosive oesophagitis, gastric/duodenal ulcers and gastric/duodenal erosions were found in 23%, 9% and 36% of these volunteers, respectively. Helicobacter pylori-positive subjects had significantly (p<0.05) more gastroduodenal lesions than Helicobacter pylori negative individuals (12/30 vs 3/23). The presence of peptic ulcers and erosive oesophagitis was similar in Helicobacter pylori-positive and -negative individuals. CONCLUSIONS: The possibility that peptic lesions might exist in otherwise asymptomatic, healthy individuals cannot be ruled out. Helicobacter py lori-positive individuals have a significantly higher incidence of gastric and duodenal lesions than Helicobacter pylori negative subjects.
Asunto(s)
Úlcera Péptica/microbiología , Adolescente , Adulto , Femenino , Infecciones por Helicobacter/epidemiología , Infecciones por Helicobacter/etiología , Helicobacter pylori , Humanos , Masculino , Úlcera Péptica/epidemiología , PrevalenciaRESUMEN
BACKGROUND: The effects of proton-pump inhibitors and Helicobacter pylori infection on the distribution of drugs employed for the eradication of H. pylori are poorly understood. The aim of this study was to investigate the effects of a 7-day oral administration of 20 mg omeprazole on the distribution of clarithromycin in the gastric juice of individuals with H. pylori infection. METHODS: Eighteen H. pylori-infected dyspeptic male volunteers without endoscopic lesions were enrolled in a study with an open, randomized, two-period crossover design and a 21-day washout period between phases. Plasma and gastric juice concentrations of clarithromycin in subjects with and without omeprazole pretreatment were measured by means of liquid chromatography coupled to tandem mass spectrometry. RESULTS: The maximum concentration of clarithromycin (Cmax) and the area under the time-concentration curve from 0 to 2 h (AUC0-2h) were significantly higher in gastric juice than in plasma. Omeprazole treatment further augmented clarithromycin Cmax and AUC0-2h in gastric juice approximately 2-fold (P < 0.05). CONCLUSIONS: Short-term treatment with omeprazole in H. pylori-positive volunteers increases the amount of clarithromycin transferred to the gastric juice, confirming a synergism between these drugs. Our results suggest the presence of an active transport mechanism for clarithromycin from plasma to the gastric lumen, which is influenced by omeprazole.
Asunto(s)
Antibacterianos/farmacocinética , Antiulcerosos/farmacología , Claritromicina/farmacocinética , Jugo Gástrico/química , Infecciones por Helicobacter/metabolismo , Helicobacter pylori , Omeprazol/farmacología , Adulto , Transporte Biológico Activo , Cromatografía Líquida de Alta Presión , Estudios Cruzados , Sinergismo Farmacológico , Humanos , Masculino , Factores de TiempoRESUMEN
1. The aim of the present study was to develop an experimental model of liver cirrhosis in rabbits using CCl4 and phenobarbital. 2. Liver cirrhosis was induced in male New Zealand white rabbits (n = 10) by intragastric administration of CCl4 once weekly starting 14 days after the addition of phenobarbital to the drinking water (50 mg/day). Controls received phenobarbital only (n = 7). Alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), albumin and bilirubin levels were determined throughout CCl4 treatment. The initial dose of CCl4 was 20 microg and subsequent doses were calculated to maintain AST and ALT levels between 400 and 800 IU/L for the duration of treatment (16 weeks). Indocyanine green (ICG) clearance was performed before and at the end of CCl4 treatment. Animals were killed at 16 weeks and three fragments of each liver lobe were processed for histological examination. A semiquantitative score was used to evaluate the development of fibrosis. 3. Cirrhosis developed in 80% of rabbits treated with CCl4. These animals did not gain weight compared with controls (P < 0.05). A significant reduction of ICG clearance was observed in CCl4-treated rabbits compared with controls (P < 0.05). The AST, ALT, bilirubin and gamma-GGT levels were elevated in CCl4-treated rabbits. 4. In conclusion, this model is successful in producing liver cirrhosis and may be useful in studies investigating metabolic, immunological or biochemical changes during the evolution of chronic liver disease.
Asunto(s)
Cirrosis Hepática Experimental/inducido químicamente , Animales , Intoxicación por Tetracloruro de Carbono/metabolismo , Intoxicación por Tetracloruro de Carbono/patología , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Modelos Animales de Enfermedad , Cirrosis Hepática Experimental/metabolismo , Cirrosis Hepática Experimental/patología , Masculino , Fenobarbital , ConejosRESUMEN
BACKGROUND: The effects of Helicobacter pylori infection associated with inhibition of gastric acid secretion on the distribution of medications used for H. pylori eradication are poorly understood. The aim of this study was to investigate the effects of a 7-day administration of 20 mg omeprazole on the transfer of metronidazole from plasma to the gastric juice of individuals with and without H. pylori infection. METHODS: Fourteen H. pylori-positive and 14 H. pylori-negative male volunteers were enrolled in a study with an open, randomized, two-period crossover design with a 21-day washout period between phases. Plasma, salivary, and gastric juice concentrations of metronidazole in subjects with and without omeprazole treatment were measured with reversed-phase high-performance liquid chromatography/liquid chromatography. RESULTS: Metronidazole peak concentration (Cmax) was similar in plasma and saliva and was approximately threefold higher in gastric juice in all groups. Omeprazole treatment increased gastric pH and did not affect metronidazole Cmax or the time required for this to be reached (tmax) in plasma, saliva, or gastric juice. However, omeprazole significantly reduced metronidazole transfer from plasma to gastric juice in H. pylori-positive but not H. pylori-negative subjects, as shown by statistical analysis of AUC(0-2 h). CONCLUSION: Short-term treatment with omeprazole in H. pylori- positive volunteers reduces the amount of metronidazole transferred from plasma to gastric juice. This seems to occur in a pH-independent form.
Asunto(s)
Antibacterianos/farmacocinética , Jugo Gástrico/química , Infecciones por Helicobacter/metabolismo , Helicobacter pylori , Metronidazol/farmacocinética , Adulto , Antibacterianos/uso terapéutico , Cromatografía Líquida de Alta Presión , Estudios Cruzados , Infecciones por Helicobacter/tratamiento farmacológico , Humanos , Masculino , Metronidazol/uso terapéutico , Saliva/químicaRESUMEN
BACKGROUND: Endoscopic sclerotherapy is widely accepted as an effective treatment for the eradication of esophageal varices in patients with portal hypertension and a history of upper gastrointestinal bleeding. The objective of this study was to assess the effectiveness and safety of absolute ethanol as an alternative sclerosing agent to the commonly used 5% ethanolamine oleate. METHODS: One hundred fifty-seven patients with portal hypertension and a history of variceal bleeding were randomly assigned to sclerotherapy with absolute ethanol (n = 66) or 5% ethanolamine oleate (n = 91) between January 1992 and July 1994. Once eradication was achieved, these patients were prospectively followed until September 1998. RESULTS: Sclerotherapy with both sclerosants resulted in similar eradication rates (approximately 90%), with comparable numbers of sessions required for eradication (5.4 and 5.9 sessions for absolute ethanol and 5% ethanolamine oleate, respectively). Similar complication and recurrent bleeding rates were observed among both groups. CONCLUSION: Sclerotherapy with absolute ethanol is as effective as with 5% ethanolamine oleate in preventing further bleeding in patients with portal hypertension.
Asunto(s)
Várices Esofágicas y Gástricas/terapia , Etanol/administración & dosificación , Etanolamina/administración & dosificación , Escleroterapia , Adulto , Anciano , Várices Esofágicas y Gástricas/etiología , Femenino , Estudios de Seguimiento , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/terapia , Humanos , Hipertensión Portal/complicaciones , Hipertensión Portal/etiología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , RetratamientoRESUMEN
AIMS: To evaluate the usefulness of plasma hydroxy-metronidazole/metronidazole (OH-MET/MET) ratios as a dynamic liver function test in ethanol abusers with or without liver cirrhosis. METHODS: Metronidazole was administered intravenously for 20 min to healthy volunteers, and to patients with alcohol-induced, non-cirrhotic hepatopathy and liver cirrhosis. Plasma concentrations of metronidazole and hydroxy-metronidazole were measured by high performance liquid chromatography in samples collected 5, 10, 20 and 30 min after the metronidazole infusion. RESULTS: Patients with non-cirrhotic alcoholic hepatopathy had significantly elevated aminotransferase levels compared to healthy volunteers and Child A patients. Child-Pugh C patients had significantly prolonged prothrombin times when compared to healthy volunteers and patients with non-cirrhotic hepatopathy. Metronidazole metabolism, as measured by the OH-MET/MET ratio following the intravenous administration of 500 mg of the drug, was significantly impaired in all ethanol-abusing individuals, including patients with non-cirrhotic alcoholic hepatopathy. CONCLUSIONS: Metronidazole metabolism was impaired in ethanol abusers, even in the absence of liver cirrhosis, indicating that ethanol was capable of affecting liver function in the early stages of alcohol-induced liver disease.
Asunto(s)
Consumo de Bebidas Alcohólicas/sangre , Antiinfecciosos/sangre , Cirrosis Hepática Alcohólica/fisiopatología , Hepatopatías/fisiopatología , Metronidazol/análogos & derivados , Metronidazol/sangre , Adolescente , Adulto , Anciano , Antiinfecciosos/administración & dosificación , Cromatografía Líquida de Alta Presión , Humanos , Cirrosis Hepática Alcohólica/sangre , Hepatopatías/sangre , Hepatopatías/etiología , Pruebas de Función Hepática , Masculino , Metronidazol/administración & dosificación , Persona de Mediana EdadRESUMEN
BACKGROUND: Management of Barrett's esophagus requires reduction of gastric acid secretion and screening for the development of adenocarcinoma. However, the current therapeutic options are ineffective in reducing the Barrett's mucosa. The aim of this study was to evaluate the effectiveness of endoscopic thermal coagulation of Barrett's mucosa as an alternative therapeutic approach and the recurrence of the disease in the long term. METHODS: Fourteen patients (11 men, 3 women; mean age 45.7 years) with Barrett's esophagus participated in the study. They underwent laparoscopic fundoplication and were symptom free with no defective fundoplication wraps before therapeutic endoscopy. Endoscopic thermocoagulation was performed with a flexible videoendoscope and a bipolar probe. Mucosal areas were treated once a month until the Barrett's mucosa disappeared. Endoscopy was performed 1 and 7 months after completion of the treatments and once a year thereafter. RESULTS: The mean follow-up period was 21.6 months (range 18 to 30 months). The mean length of Barrett's esophagus was 4.8 cm. Successful ablation of the columnar epithelium was achieved in 3.7 sessions, as defined by demonstration of normal squamous epithelium at histologic examination of biopsy samples collected after completion of the treatments and at follow-up evaluations. Three patients experienced short-term (10 days) odynophagia or dysphagia. All patients were symptom free with no evidence of Barrett's esophagus at the end of the study. CONCLUSIONS: Bipolar electrocoagulation after antireflux operations is effective in promoting regression of Barrett's esophagus and has few complications. Endoscopic thermal coagulation might reduce risk for adenocarcinoma among these patients.
Asunto(s)
Esófago de Barrett/cirugía , Electrocoagulación , Endoscopía , Esofagitis Péptica/cirugía , Esofagoscopía , Fundoplicación , Laparoscopía , Adolescente , Adulto , Anciano , Esófago de Barrett/patología , Biopsia , Epitelio/patología , Esofagitis Péptica/patología , Esófago/patología , Esófago/cirugía , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Reoperación , Resultado del TratamientoRESUMEN
AIMS: To evaluate plasma hydroxy-metronidazole/metronidazole ratio as a dynamic liver function test in HCV-infected individuals with/without liver disease, in the absence of liver cirrhosis. METHODS: Metronidazole was administered intravenously in healthy volunteers, asymptomatic anti-HCV-positive blood donors, and in chronic hepatitis C patients. Serology to HCV was determined by a second generation assay and confirmed by gelatin particle agglutination test using recombinant antigens C22-3 and C200. Plasma concentration of metronidazole and hydroxy-metronidazole was measured by high performance liquid chromatography in samples collected 5, 10, 20 and 30 min following the end of metronidazole infusion. RESULTS: Chronic hepatitis C patients had abnormal liver enzymes, while healthy volunteers and anti-HCV-positive blood donors had normal liver biochemistry tests. Plasma metronidazole concentration was similar in all groups studied. Plasma hydroxy-metronidazole/metronidazole ratio was significantly reduced in HCV-infected subjects, an effect observed 10 min after the end of drug infusion. CONCLUSIONS: Metronidazole clearance is impaired in anti-HCV-positive blood donors and chronic hepatitis C patients, indicating that HCV is capable of affecting liver function at early stages of the disease. The metronidazole clearance test can detect impaired liver function in HCV-infected individuals even in the absence of liver cirrhosis.
Asunto(s)
Hepacivirus , Hepatitis C/sangre , Hígado/metabolismo , Metronidazol , Adulto , Femenino , Hepacivirus/inmunología , Hepatitis C/diagnóstico , Hepatitis C/inmunología , Humanos , Pruebas de Función Hepática , Masculino , Metronidazol/sangre , Metronidazol/metabolismo , Persona de Mediana EdadRESUMEN
BACKGROUND: The addition of omeprazole to classical triple therapy for eradication of H. pylori may enhance compliance through reducing ulcer symptoms and side-effects. The aim of this study was to investigate the effects of a 5-day administration of omeprazole on metronidazole pharmacokinetics. METHODS: Fourteen healthy male volunteers were selected. The study had an open, randomized, two-period crossover design with a 21-day washout period between the phases. Plasma concentrations of metronidazole and its hydroxy-metabolite were measured by reversed-phase HPLC with ultraviolet detection. RESULTS: Administration of omeprazole did not affect the pharmacokinetic parameters of orally administered metronidazole. CONCLUSION: Our results indicate that short-term treatment with omeprazole in healthy volunteers does not alter the extent or the rate of metronidazole absorption, and does not affect metronidazole clearance.
Asunto(s)
Antiulcerosos/farmacología , Antitricomonas/farmacocinética , Ácido Gástrico/metabolismo , Metronidazol/farmacocinética , Omeprazol/farmacología , Administración Oral , Adulto , Antiulcerosos/administración & dosificación , Antiulcerosos/uso terapéutico , Antitricomonas/efectos adversos , Antitricomonas/uso terapéutico , Disponibilidad Biológica , Estudios Cruzados , Interacciones Farmacológicas , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori , Humanos , Masculino , Metronidazol/efectos adversos , Metronidazol/uso terapéutico , Omeprazol/administración & dosificación , Omeprazol/uso terapéuticoRESUMEN
OBJECTIVE: To evaluate whether the addition of bismuth subnitrate to a dual oral therapy regimen with omeprazole plus amoxycillin could improve Helicobacter pylori eradication. METHODS: Fifty consecutive Helicobacter pylori-positive patients were randomly enrolled to receive either (A) bismuth subnitrate (300 mg q.d.s.), omeprazole (20 mg b.d.) and amoxycillin (500 mg q.d.s.), or (B) omeprazole (20 mg b.d.) and amoxycillin (500 mg q.d.s.). Both groups (n=25 each) received the medication for 14 days. H. pylori status was reassessed 30 days after completion of the therapy in order to evaluate eradication rates. RESULTS: Six patients were lost to follow-up and therefore excluded from the study (three patients from each group). One patient from Group B withdrew from the study because of side-effects. The addition of bismuth subnitrate to omeprazole and amoxycillin significantly improved its efficacy in eradicating H. pylori, with 72% (18/25) eradication in Group A and 52% (13/25) in Group B (P=0.027). The addition of bismuth subnitrate to dual oral therapy was also capable of improving the healing of peptic ulcers when compared with dual oral therapy alone (100%, 8/8 vs. 58%, 4/7; P=0.021). CONCLUSION: Our results demonstrate that the addition of bismuth subnitrate to dual oral therapy enhances H. pylori eradication, and improves healing of peptic ulcers.
Asunto(s)
Amoxicilina/uso terapéutico , Antiulcerosos/uso terapéutico , Bismuto/uso terapéutico , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori , Omeprazol/uso terapéutico , Penicilinas/uso terapéutico , Ranitidina/análogos & derivados , Úlcera Gástrica/tratamiento farmacológico , Adulto , Anciano , Amoxicilina/administración & dosificación , Amoxicilina/efectos adversos , Antiulcerosos/administración & dosificación , Antiulcerosos/efectos adversos , Bismuto/administración & dosificación , Bismuto/efectos adversos , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Gastroscopía , Infecciones por Helicobacter/microbiología , Humanos , Masculino , Persona de Mediana Edad , Omeprazol/administración & dosificación , Omeprazol/efectos adversos , Penicilinas/administración & dosificación , Penicilinas/efectos adversos , Ranitidina/administración & dosificación , Ranitidina/efectos adversos , Ranitidina/uso terapéutico , Úlcera Gástrica/microbiologíaRESUMEN
The authors report a case of a 13-year-old girl with Barrett's esophagus who underwent antireflux surgery and was subsequently treated with endoscopic thermal coagulation using bipolar electrocoagulation. Follow-up endoscopy 15 months after completion of the endoscopic therapy showed normal esophageal mucosa without intestinal metaplasia. Longer follow-up is needed to assess the long-term effects of endoscopic treatment of the Barrett's mucosa with thermal coagulation, and this procedure should still be considered under investigation.
Asunto(s)
Esófago de Barrett/cirugía , Electrocoagulación/métodos , Fundoplicación , Adolescente , Esófago de Barrett/patología , Biopsia con Aguja , Terapia Combinada , Endoscopía/métodos , Femenino , Estudios de Seguimiento , Humanos , Membrana Mucosa/patología , Membrana Mucosa/cirugía , Inducción de RemisiónRESUMEN
Ethanol can affect the regulation of liver hemodynamics through the release of vasoactive mediators such as nitric oxide and endothelins (ETs). The purpose of this study was to investigate the effects of ethanol on the changes in arterial and portal perfusion pressure induced by ET receptor activation. Ethanol significantly reduced portal, but not arterial perfusion pressure. ET-1 and norepinephrine (used as an ET receptor-independent vasoconstrictor) induced changes in hepatic arterial or portal inflow resistance that were not affected by ethanol treatment. However, an IRL 1620-induced increase in portal, but not arterial, inflow resistance was significantly reduced in ethanol-perfused preparations, an effect observed after either intra-arterial or intraportal administration of the agonist. These results suggest that ethanol can diminish the responsiveness of the portal vascular bed of the canine liver to ETB receptor activation.
Asunto(s)
Depresores del Sistema Nervioso Central/farmacología , Antagonistas de los Receptores de Endotelina , Etanol/farmacología , Circulación Hepática/efectos de los fármacos , Presión Portal/efectos de los fármacos , Resistencia Vascular/efectos de los fármacos , Agonistas alfa-Adrenérgicos/farmacología , Animales , Perros , Endotelina-1/farmacología , Endotelinas/farmacología , Norepinefrina/farmacología , Fragmentos de Péptidos/farmacología , Receptor de Endotelina A , Receptor de Endotelina B , Receptores de Endotelina/agonistasRESUMEN
At present, there is no information on endothelin-1 (ET-1)-mediated vascular effects in the human spleen. The objectives of this study were to investigate the in vitro vascular responses to ET-1 using pharmacologic probes (selective ET receptor agonists/antagonists) and to characterize the ET receptor population in the human spleen. Spleens (n = 6) were removed from patients for treatment of underlying disease. The organs were perfused with warmed (37 degrees C), oxygenated (95% O2/5% CO2) Krebs solution at constant flow, with continuous recording of splenic arterial perfusion pressure (SAPP). The increases in SAPP caused by injection of ET-1 (ETA/ETB agonist) were markedly reduced in the presence of the selective ETA antagonist FR-139317, whereas those induced by IRL-1620 (an ETB agonist) and norepinephrine (NE) were unchanged. The increases in SAPP induced by intra-arterial bolus injections of NE and ET-1 were significantly (p < 0.05) potentiated by indomethacin [INDO; a cyclo-oxygenase (COX) inhibitor] alone and the responses to both peptides (ET-1 and IRL-1620) were significantly (p < 0.05) potentiated by INDO and L-NAME [a nitric oxide (NO) synthase inhibitor] together. We conclude that ET-1 contributes to the regulation of vascular tone in human spleen through activation of both ETA and ETB receptors and that these responses are modulated by concomitant release of prostaglandins and NO.
Asunto(s)
Receptores de Endotelina/metabolismo , Bazo/metabolismo , Adulto , Azepinas/farmacología , Inhibidores de la Ciclooxigenasa/farmacología , Antagonistas de los Receptores de Endotelina , Endotelinas/farmacología , Inhibidores Enzimáticos/farmacología , Humanos , Técnicas In Vitro , Indoles/farmacología , Indometacina/farmacología , Persona de Mediana Edad , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico Sintasa/antagonistas & inhibidores , Fragmentos de Péptidos/farmacología , Perfusión , Receptor de Endotelina A , Receptor de Endotelina B , Receptores de Endotelina/agonistas , Bazo/químicaRESUMEN
Gastric mucosal lesions are frequently observed in patients with liver cirrhosis and portal hypertension. Similar lesions can be observed in experimental portal hypertension. This review summarizes our current knowledge of the pathophysiology of portal hypertensive gastropathy, with a particular focus on the microcirculatory disturbances that characterize this condition. The stomach of cirrhotic patients exhibits an increased susceptibility to injury induced by several irritants. Similarly, the stomach of portal hypertensive animals is less resistant to injury. One of the most important factors contributing to the increased susceptibility to damage is an impaired hyperemic response when the epithelium is exposed to irritants. This appears to be related to a reduction in mucosal prostaglandin production and to altered microcirculatory responsiveness to nitric oxide. Nitric oxide overproduction in portal hypertension may have direct effects on gastric blood flow regulation. Elevated production of tumor necrosis factor-alpha by gastric mucosa in portal hypertensive rats has also been shown to contribute to mucosal injury. A better understanding of the pathogenesis of portal hypertensive gastropathy may lead to development of specific therapeutic interventions for this condition.
Asunto(s)
Hipertensión Portal/complicaciones , Gastropatías/etiología , Animales , Mucosa Gástrica/irrigación sanguínea , Mucosa Gástrica/metabolismo , Humanos , Hipertensión Portal/fisiopatología , Cirrosis Hepática/complicaciones , Cirrosis Hepática/fisiopatología , Cirrosis Hepática Experimental/complicaciones , Cirrosis Hepática Experimental/fisiopatología , Óxido Nítrico/metabolismo , Prostaglandinas/metabolismo , Ratas , Gastropatías/fisiopatología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Metronidazole pharmacokinetics were studied in patients with different degrees of liver cirrhosis, classified according to the Child-Pugh algorithm (A, B or C, as liver disease severity increases) and in schistosomic patients. Metronidazole (500 mg) was administered i.v. as a slow infusion over 20 min, and blood samples were collected at set intervals after the end of the infusion. The plasma concentrations of metronidazole and its main metabolite hydroxy-metronidazole were quantified by reversed-phase h.p.l.c. with u.v. detection. The metronidazole and hydroxy-metronidazole areas under the curve from 0 to 24 h (AUC0,24h), the metronidazole terminal elimination half-life (t1/2), the total clearance (CL), the metronidazole volume of distribution (V) values and the hydroxy-metronidazole/metronidazole concentration ratios as a function of time were calculated for each group. Comparison of the metronidazole AUC0,24h, t1/2 and CL values revealed that metronidazole metabolism is progressively impaired as the severity of liver disease increases. There were no variations in these parameters between the schistosomic and Child-Pugh A groups. In addition, there were no differences in the V and hydroxy-metronidazole AUC0,24h among the various groups studied. However, metronidazole metabolism was delayed in patients with hepatic disease, as illustrated by the hydroxy-metronidazole/metronidazole ratio 10 min after the end of metronidazole infusion. These results indicate that the clinical assessment of liver disease is paralleled by an impairment of metronidazole metabolism. Of the studied variables, we propose the hydroxy-metronidazole/metronidazole ratio 10 min after metronidazole infusion as a suitable and practical index for liver function evaluation.
Asunto(s)
Cirrosis Hepática/fisiopatología , Metronidazol/farmacocinética , Esquistosomiasis mansoni/fisiopatología , Adulto , Biotransformación , Femenino , Semivida , Humanos , Cirrosis Hepática/sangre , Pruebas de Función Hepática , Masculino , Metronidazol/análogos & derivados , Metronidazol/sangre , Persona de Mediana Edad , Esquistosomiasis mansoni/sangreRESUMEN
OBJECTIVES: The most used therapeutic schedule to eradicate Helicobacter pylori is the "triple therapy," which is based on the simultaneous use of a bismuth salt and two antibiotics. Sucralfate, a basic aluminum salt of sucrose sulfate, is supposed to have an antibacterial activity and is said to reduce the bacterial density of H. pylori. This randomized, prospective clinical trial compares the efficacy of an alternative oral triple therapy consisting of sucralfate, tinidazol, and tetracycline with a conventional therapy using ranitidine, with respect to H. pylori eradication and duodenal ulcer healing and recurrence in a 12-month follow-up. METHODS: Forty-three patients with active duodenal ulcers diagnosed at endoscopy were enrolled to receive either 1 g of sucralfate four times daily for 30 days, 500 mg of tetracycline four times daily, and 500 mg of tinidazol three times daily, for 10 days (group A; n = 23) or 150 mg of ranitidine twice daily for 30 days (group B; n = 20). The groups were age- and sex-matched and balanced for tobacco use and H. pylori status. Compliance assessed by post-treatment interviews was considered high (all patients declared that they had ingested at least 80% of the drugs). RESULTS: Both therapies were efficient in healing ulcers (group A, 95%; group B, 90%), the relapse rates were high in both groups (group A, 77%; group B, 89%), and the alternative triple therapy eradicated H. pylori in only 4% of the patients. CONCLUSION: Alternative oral triple therapy presented no significant advantage over ranitidine treatment of active ulcer disease.