RESUMO
In the treatment of Zollinger-Ellison syndrome patients with severe disease and acid hypersecretion, proton pump inhibitors are the drugs of choice. Data have now been accumulated on lansoprazole treatment of 41 patients (21 treated at the National Institutes of Health [NIH], Bethesda, Maryland, USA, and 20 treated at the Bichat-Claude Bernard Hospital, Paris, France). Short-term studies of the inhibitory action of lansoprazole on acid secretion have been carried out in both institutions. Our group first performed a dose-response analysis of the efficacy of lansoprazole in reducing basal acid output (BAO) in four patients with severe Zollinger-Ellison syndrome (mean BAO 52 +/- 9 [SD] mmol H+/h) who had previously been treated with a mean omeprazole dosage of 75 mg/day. The maximum acid inhibitory effect was obtained with lansoprazole 60-90 mg/day. The 40-hour duration of action of lansoprazole appears equivalent to that of omeprazole. In a second study at the Bichat-Claude Bernard Hospital, nine Zollinger-Ellison syndrome patients underwent 24-hour intragastric pH monitoring while receiving lansoprazole (mean dosage 80 mg/day, range 30-165 mg/day) or omeprazole (mean dosage 75 mg/day, range 20-180 mg/day). The acid inhibitory activity of the two drugs was comparable. Those patients are currently receiving long-term maintenance treatment with lansoprazole, and satisfactory clinical and biological secretory control has been achieved. The long-term safety and efficacy of lansoprazole administration were studied in the 21 patients followed at the NIH. In those patients the initial maintenance dose was determined using acid inhibition studies; in all patients lansoprazole controlled gastric acid hypersecretion and peptic symptoms in both the short and long term. The mean initial maintenance dose was 60 mg QID, except for two patients who required 60 mg BID. During long-term treatment (mean duration 31 months, range 1-43 months), six patients required a dosage increase within the first year, while the lansoprazole dose could be reduced in six others. The safety profile of lansoprazole has been excellent. Comparable results have been noted in nine Zollinger-Ellison syndrome patients during an ongoing evaluation in our institution. These studies indicate that lansoprazole is an efficacious, well-tolerated antisecretory agent in patients with Zollinger-Ellison syndrome.
Assuntos
Omeprazol/análogos & derivados , Síndrome de Zollinger-Ellison/tratamento farmacológico , 2-Piridinilmetilsulfinilbenzimidazóis , Adulto , Idoso , Antiulcerosos/efeitos adversos , Antiulcerosos/uso terapêutico , Ensaios Clínicos como Assunto , Feminino , Ácido Gástrico/metabolismo , Humanos , Lansoprazol , Masculino , Pessoa de Meia-Idade , Omeprazol/efeitos adversos , Omeprazol/uso terapêutico , Inibidores da Bomba de PrótonsRESUMO
Platelet activating factor (PAF) is a phospholipid mediator known as potent ulcerogenic agent but its physiological role is still unknown in the gastrointestinal tract. Lyso PAF the immediate PAF procursor has no deleterious effect in the gastrointestinal tract. We have previously reported that lyso PAF is produced by gastric mucosa in basal condition and in response to gastrin in healthy men. Helicobacter pylori metabolises lyso PAF to produce PAF. The aim was to study the effect of PAF on the gastric acid secretion. Isolated rabbit glands were used as a model and acid secretion was assessed by (14C) Aminopyrine (AP) uptake. PAF and histamine stimulated AP accumulation time- and dose-dependently. PAF-induced AP accumulation was supressed by omeprazole and Fura 2. BN50727 a specific PAF antagonist inhibited PAF-induced AP accumulation. The presence of a PAF receptor transcript was investigated by reverse transcriptase polymerase chain reaction (RT-PCR) from total mRNA using two primers in which oligonucleotides were synthetized from the human leucocyte PAF receptor cDNA. A single RT-PCR band of the transcript with expected size was detected in the crude isolated cell fraction. These results and others from our laboratory suggest that PAF stimulates gastric acid secretion via specific receptor on the parietal cells and H. pylori produces PAF which may induce mucosal injury directly or indirectly via acid pathway.
Assuntos
Aminopirina/metabolismo , Ácido Gástrico/metabolismo , Mucosa Gástrica/efeitos dos fármacos , Fator de Ativação de Plaquetas/farmacologia , Receptores de Superfície Celular , Receptores Acoplados a Proteínas G , Animais , Antiulcerosos/farmacologia , Azepinas/farmacologia , Relação Dose-Resposta a Droga , Mucosa Gástrica/metabolismo , Infecções por Helicobacter/metabolismo , Helicobacter pylori/metabolismo , Masculino , Omeprazol/farmacologia , Glicoproteínas da Membrana de Plaquetas/genética , Reação em Cadeia da Polimerase , RNA Mensageiro , Coelhos , Tienopiridinas , Triazóis/farmacologiaRESUMO
OBJECTIVES: To evaluate the evolution of fundic argyrophil cell density and hyperplasia grading, fundic chronic gastritis grading and serum gastrin levels in patients treated with proton pump inhibitors. METHODS: Thirty-two patients treated with proton pump inhibitors for gastroesophageal reflux and/or duodenal ulcer were studied. No patient had a gastric ulcer. The studied parameters were serum gastrin levels, fundic argyrophil cell density, the degree of fundic argyrophil cell hyperplasia, the grade of fundic atrophic gastritis and the presence of Helicobacter pylori. The first point of the study was 7 months (range: 0-42 months) and the last point 33 months (range: 7-72 months) after the beginning of the treatment. RESULTS: Serum gastrin levels significantly increased with treatment. Fundic argyrophil cell density did not change significantly. In 3 patients (9%), serum gastrin levels were twice the normal upper limit. The highest serum gastrin levels (249 and 665 pg/mL) were noted in the 2 patients treated with the highest doses of proton pump inhibitors. Micronodular hyperplasia of the fundic argyrophil cells was observed in 2 patients treated with omeprazole 20 mg/d for 4 years and lansoprazole 90 mg/d for 6 years, respectively. Non active superficial chronic gastritis was noted in 2 patients. Serum gastrin levels were significantly correlated with cell densities. CONCLUSION: There were minor modifications of fundic argyrophil cell population and of gastrinaemia during the study period. They were not related to chronic atrophic gastritis. However, survey is mandatory in patients treated with high dose proton pump inhibitors, in those in whom gastrinaemia is elevated and when treatment duration is longer than 5 years.
Assuntos
Úlcera Duodenal/sangue , Inibidores Enzimáticos/uso terapêutico , Fundo Gástrico/patologia , Gastrinas/análise , Refluxo Gastroesofágico/sangue , Inibidores da Bomba de Prótons , 2-Piridinilmetilsulfinilbenzimidazóis , Adulto , Idoso , Idoso de 80 Anos ou mais , Úlcera Duodenal/tratamento farmacológico , Feminino , Fundo Gástrico/microbiologia , Refluxo Gastroesofágico/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Helicobacter pylori/isolamento & purificação , Humanos , Lansoprazol , Masculino , Pessoa de Meia-Idade , Omeprazol/análogos & derivados , Omeprazol/uso terapêutico , Estudos Prospectivos , Fatores de TempoRESUMO
OBJECTIVES: The aim of this prospective study was to confirm the efficacy and safety of lansoprazole in patients with Zollinger-Ellison syndrome (ZES). METHODS: Fourteen patients (5 W, 9 M) with ZES, age (mean +/- SD) 55.5 +/- 12.8 years, were included in the study. STUDY DESIGN: initially and at 1, 3 and 6 months thereafter the following items were assessed: clinical signs, fasting serum gastrin (FSG), basal acid output (BAO) before next dose of lansoprazole. BAO < 10 mmol H+/h was considered as efficient. Initially and at 6 months, laboratory tests (hematology, liver, renal and hormonal), endoscopy and histological enterochromaffin-like cell and gastrin cell density assessments were performed. Lansoprazole initial dose was adjusted according to clinical symptoms and secretory studies. RESULTS: At 6 months, lansoprazole doses of 60, 90, 120 and 180 mg/d maintained BAO < 10 mmol H+/h in 9, 2, 1 and 1 patient, respectively. No significant changes in FSG, endocrine cells densities and biological parameters were noted during treatment. Neither adverse events nor carcinoid tumors were observed. We conclude that lansoprazole is efficient and well tolerated in patients with ZES.
Assuntos
Inibidores Enzimáticos/uso terapêutico , Omeprazol/análogos & derivados , Inibidores da Bomba de Prótons , Síndrome de Zollinger-Ellison/tratamento farmacológico , 2-Piridinilmetilsulfinilbenzimidazóis , Adulto , Idoso , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/efeitos adversos , Feminino , Ácido Gástrico/metabolismo , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Humanos , Lansoprazol , Masculino , Pessoa de Meia-Idade , Omeprazol/efeitos adversos , Omeprazol/uso terapêutico , Taxa Secretória/efeitos dos fármacosRESUMO
We describe a patient with dysphagia. The results of endoscopy, CT scan and echoendoscopy were normal. High-resolution manometry (HRM) showed esogastric junction dysfunction and hypercontractile peristaltic disorder. These HRM abnormalities completely disappeared after pneumatic esophageal dilatation. We discuss the treatment options and recovery of peristalsis after balloon dilatation.
Assuntos
Úlcera Duodenal/fisiopatologia , Ácido Gástrico/metabolismo , Gastrinas/metabolismo , Infecções por Helicobacter/fisiopatologia , Helicobacter pylori/isolamento & purificação , Úlcera Gástrica/fisiopatologia , Doença Crônica , Úlcera Duodenal/sangue , Úlcera Duodenal/microbiologia , Infecções por Helicobacter/sangue , Infecções por Helicobacter/microbiologia , Humanos , Úlcera Gástrica/sangue , Úlcera Gástrica/microbiologiaRESUMO
After a short presentation of the etiopathogenesis of this parasitosis, the authors report their observations on 35 cases of strongyloidiasis followed in the recent years. On the basis of the epidemiologic and clinical analyses of these cases, the authors show that some data, i.e. those on the environment to which the patients belong, or their occupation, and also some clinical manifestations (clinical polymorphism) may suggest the diagnosis of strongyloidiasis in the immunosuppressed in about 30% of the cases. An associated blood eosinophilia may be a more possible for the diagnosis of strongyloidiasis. The positive diagnosis has to take into consideration, beside the repeated diet exam, the method of cultures and also jejunal biopsies, which may also verify the efficiency of the treatment recommended. The authors recommend the treatment with Mintezol and, with lower results, Vermigal and Mebendazol.
Assuntos
Hospitalização , Enteropatias Parasitárias/diagnóstico , Estrongiloidíase/diagnóstico , Adulto , Animais , Anti-Helmínticos/uso terapêutico , Fezes/parasitologia , Feminino , Gastroenterologia , Departamentos Hospitalares , Humanos , Enteropatias Parasitárias/tratamento farmacológico , Enteropatias Parasitárias/parasitologia , Masculino , Pessoa de Meia-Idade , Romênia , Strongyloides/isolamento & purificação , Estrongiloidíase/tratamento farmacológico , Estrongiloidíase/parasitologiaRESUMO
The two categories of anti-albumin antibodies (AAA), namely precipitins (AA-P) and agglutinins (AA-Aggl), were investigated in 260 patients with morphologically diagnosed chronic liver diseases (CLD). A parallelism was observed between AA-P titre and the severity of chronic hepatitis as revealed by clinical diagnosis. Thus, significant differences in AA-P titre were noticed between chronic persistent hepatitis (CPH) and chronic aggressive hepatitis (CAH) and between CAH and liver cirrhosis (LC). No correlation was found between AA-P positivity and either HBsAg presence or disease activity, maximum AA-P values being registered in decompensated, inactive LC. AA-P positivity was found associated with a higher degree of liver cell dysfunction. In every category of CLD a striking association was also observed between AA-P positivity and raised serum aspartate transaminase and bilirubin levels, thus suggesting a common pathogenic substrate, namely liver cell membrane damage. These correlations were also observed after immunosuppressive therapy which would argue for the maintenance of AA-P diagnostic value. AA-Aggl showed raised incidences and titres in CAH patients, the values decreasing in LC. Therefore, the main diagnostic value is attributed to AA-P.
Assuntos
Aglutininas/imunologia , Anticorpos Anti-Idiotípicos/análise , Imunossupressores/uso terapêutico , Hepatopatias/imunologia , Precipitinas/imunologia , Doença Crônica , Hepatite/imunologia , Antígenos de Superfície da Hepatite B/análise , Humanos , Cirrose Hepática Alcoólica/imunologia , Hepatopatias/tratamento farmacológicoRESUMO
Neurotensin receptor expression was studied in 19 human colon cancer cell lines and normal human colon by i) binding experiments using [125I-Tyr3]-neurotensin; ii) RT-PCR analysis. The following data were obtained: 1) A single class of receptor (Kd ranging from 0.23 to 1.21 nM) was found in 9 out of 19 cell lines but not in normal colonic epithelium; 2) The Bmax was in the range between 1000 and 85 fmoles/mg protein with SW48 > WiDR > Cl 19A > HCT116 > SW480 > SW620 > Cl 16E > Cl 27H > HT-29. No specific binding was measurable in Caco-2, FRI, CBS, EB, HCT-8, 320HRS, 320DM and LS174T cell lines; 3) A single RT-PCR product was observed in HT-29, SW48, WIDR, Cl 19A, SW480, Cl 16E, Cl 27H, SW620 and HCT116, but not in other cell lines or in normal human colon. It is concluded that the expression of neurotensin receptors in human colon cancer cells is regulated at the mRNA level and occurs upon malignancy in > 40% of colon cancer cell lines.
Assuntos
Colo/metabolismo , Expressão Gênica , Reação em Cadeia da Polimerase/métodos , Receptores de Neurotensina/biossíntese , Sequência de Bases , Linhagem Celular , Membrana Celular/metabolismo , Células Cultivadas , Neoplasias do Colo/metabolismo , Primers do DNA , Epitélio/metabolismo , Humanos , Dados de Sequência Molecular , Neurotensina/metabolismo , Oligonucleotídeos Antissenso , RNA Mensageiro/biossíntese , DNA Polimerase Dirigida por RNA , Transcrição Gênica , Células Tumorais CultivadasRESUMO
We retrospectively assessed the clinical course in four patients with long-standing Crohn's disease who became infected with human immunodeficiency virus (HIV). The duration of active Crohn's disease was 21, 10, 4, and 4 years in our four patients. They experienced a stable remission of Crohn's disease symptoms after HIV infection. In three patients Crohn's disease was in stable remission for 5, 8, and 8 years after HIV infection and all three died from acquired immunodeficiency syndrome-related disease. One patient was still alive without recurrence of Crohn's disease symptoms 7 years following HIV detection. Our observations of a spontaneous improvement in the clinical course of Crohn's disease after HIV infection, suggests that the integrity of the immune response, especially that of CD4 T cells, plays a major role in the tissue injury mechanism in Crohn's disease.