RESUMEN
BACKGROUND: The success rate of current anti-Helicobacter pylori triple therapies in now generally 80% or less. Sequential therapy has proved superior. AIM: To test a new sequential therapy for H. pylori eradication. METHODS: This was a pilot study of a sequential therapy consisting of 40 mg of esomeprazole and 1 g amoxicillin t.d.s., for 12 days. On days 6 through 12 gatifloxacin (400 mg in the morning) was added. Outcome was accessed 4 or more weeks after ending antibiotic therapy. Both naive and treatment failures were eligible. RESULTS: Thirty patients were entered in the study. One was lost to follow-up and one stopped early because of side effects. The success rate intention-to-treat was 80% (95% CI: 61-92%). The per-protocol eradication rate was 85.7% (95% CI: 67-95%); two of the four failures had pre-treatment gatifloxacin-resistant H. pylori. Side effects were reported by 13 patients (46%) and were generally mild with diarrhoea being most common (n = 6). Only one patient stopped medicine because of side effects of dizziness (severe) and diarrhoea (mild). CONCLUSIONS: Sequential therapy using the combination of a high dose of proton-pump inhibitor and amoxicillin followed gatifloxacin was effective, but pre-treatment susceptibility testing may become necessary as fluoroquinolone resistance increases.
Asunto(s)
Amoxicilina/administración & dosificación , Antiinfecciosos/administración & dosificación , Esomeprazol/administración & dosificación , Fluoroquinolonas/administración & dosificación , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori/efectos de los fármacos , Amoxicilina/efectos adversos , Antiinfecciosos/efectos adversos , Protocolos Clínicos , Esquema de Medicación , Quimioterapia Combinada , Inhibidores Enzimáticos/administración & dosificación , Inhibidores Enzimáticos/efectos adversos , Esomeprazol/efectos adversos , Femenino , Fluoroquinolonas/efectos adversos , Gatifloxacina , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios Prospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Antibiotic resistance and duration of therapy influence the success of proton-pump inhibitor-containing Helicobacter pylori eradication therapy. Clarithromycin resistance is associated with treatment failure. AIM: To examine the success of a 7-day rabeprazole-clarithromycin-amoxicillin therapy in the study population. METHODS: Adults from Ciudad Juarez with H. pylori infections identified by culture or histology received rabeprazole 20 mg, clarithromycin 0.5 g and amoxicillin 1 g, each b.d. for 7 days. Outcome was assessed by 13C-urea breath test carried out 4+ weeks after treatment. RESULTS: A total of 111 patients were enrolled and evaluated by urea breath test; 102 completed the full 7 days therapy. Two deviated from protocol, and five stopped because of adverse events. The cure rate (intention-to-treat) was 85% (95% CI: 78-91%); the per-protocol cure rate was 85% (95% CI: 78-91%). Side-effects were not serious and only 6.6% of those with adverse events stopped medication. Only three isolates were clarithromycin-resistant and none was cured. Compliance explained most of the successes. CONCLUSIONS: In the study population a 7-day rabeprazole triple eradication therapy was both effective and well-tolerated. Clarithromycin resistance was uncommon. We observed a slightly better outcome but consistent with results from recent large studies in US populations.
Asunto(s)
Amoxicilina/uso terapéutico , Antibacterianos/uso terapéutico , Bencimidazoles/uso terapéutico , Claritromicina/uso terapéutico , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori/efectos de los fármacos , Omeprazol/análogos & derivados , 2-Piridinilmetilsulfinilbencimidazoles , Adolescente , Adulto , Amoxicilina/efectos adversos , Antibacterianos/efectos adversos , Bencimidazoles/efectos adversos , Claritromicina/efectos adversos , Farmacorresistencia Bacteriana , Quimioterapia Combinada , Inhibidores Enzimáticos/efectos adversos , Inhibidores Enzimáticos/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Omeprazol/efectos adversos , Omeprazol/uso terapéutico , Cooperación del Paciente , Proyectos Piloto , Rabeprazol , Insuficiencia del Tratamiento , Resultado del TratamientoRESUMEN
Plants and probiotics have a long history in the treatment of gastrointestinal ailments. Our aim was to evaluate the effectiveness of Tibetan yogurt and fresh broccoli tips in Helicobacter pylori- (H. pylori) infected volunteers, using the urea breath test (UBT) to assess the effect on H. pylori. Clinical trials consisted of ingestion of approximately 135 g of fresh, finely minced juvenile broccoli tips (var. Emperor) in commercial plain yogurt t.i.d, for ten servings (3.3 days) or ingestion of freshly made Tibetan yogurt whey (120 ml) given twice a day for 3.5 days. Urea breath testing was done before and after the natural therapies. Five volunteers received broccoli tips and seven received Tibetan yogurt. No trend for a beneficial effect was seen; the UBT results (delta over baseline) before and after yogurt (35.5+/-12.8 vs. 40.7+/-12.2) (p=0.76) or broccoli (15.8 vs. 19.4) (p=1.0) were unchanged. Antimicrobial end products derived from Tibetan yogurt or broccoli tips have little or no anti-H. pylori effect in vivo. It appears that the gastric mucosal microenvironment apparently shielded H. pylori. In vitro studies suggesting anti-H. pylori activity of compounds should be considered as hypotheses to be tested.
Asunto(s)
Brassica , Infecciones por Helicobacter/dietoterapia , Helicobacter pylori , Probióticos , Yogur , Adulto , Brassica/química , Pruebas Respiratorias , Femenino , Humanos , Masculino , Persona de Mediana Edad , Urea/metabolismo , Yogur/microbiologíaRESUMEN
BACKGROUND: The mechanism of citric acid-enhanced Helicobacter pylori urease activity remains unclear. AIM: To compare ascorbic, citric and malic acid given at the same concentration and pH on intragastric urease activity. METHODS: Volunteers received 40 mg of famotidine the evening prior to breath testing. After an overnight fast volunteers were randomized to receive 100 mL of water or 100 mm citric, malic, or ascorbic acid, pH 2.3 containing 75 mg of 13C-urea. At 15 min a second 100 mL solution of one of the test solutions was taken without added urea. RESULTS: Twelve volunteers were studied (eight men, four women, age 19-57, median 50.7) in a randomized-crossover study. The mean breath test result at 30 min with ascorbic (17.5 +/- 5), malic (25.8 +/- 5) and citric acid (29.5 +/- 5) were all significantly greater than with water (9.5 +/- 3). Citric and malic acid were similar (P = 0.699) and significantly greater than ascorbic acid (P < 0.02). When the ascorbic acid was followed by citric acid, the result was similar to that with citrate alone (25.8 +/- 4) and greater than with ascorbic then ascorbic (P = 0.026). CONCLUSIONS: Enhancement of H. pylori urease activity is not strictly a function of the pH. We propose the effect is related to differential effects of the availability of nickel, which is required for urease activity. Citric acid and malic acid were essentially equivalent such that malic acid could substitute for citric acid in the UBT; ascorbic acid would be a poor choice.
Asunto(s)
Ácido Ascórbico/farmacología , Ácido Cítrico/farmacología , Malatos/farmacología , Gastropatías/enzimología , Ureasa/metabolismo , Adulto , Femenino , Infecciones por Helicobacter/enzimología , Helicobacter pylori/enzimología , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Gastropatías/microbiologíaRESUMEN
BACKGROUND: Current anti-Helicobacter pylori treatment regimens are costly and because of the increasing antibiotic resistance, are becoming ineffective. AIM: To evaluate a triple-layer tablet containing 100 mg bismuth subcitrate, 250 mg metronidazole, and 250 mg tetracycline in a single triple-layer tablet. METHODS: H. pylori-infected adult patients received bismuth-metronidazole-tetracycline (two tablets, t.d.s.) and ranitidine (300 mg) once daily for 14 days. Efficacy was determined using 13C-urea breath testing. RESULTS: Thirty-three of 35 enrolled patients were available for evaluation; using the protocol-specified modified intention-to-treat analysis, five failed treatment, two were lost to follow-up (cure rate per-protocol = 85.7%, intention-to-treat = 78.7%). The cure rate among metronidazole-susceptible strains was 100% (22 of 22) (95% confidence interval 84-100%) compared with 55% (five of nine intention-to-treat) (95% confidence interval 21-86%) among metronidazole-resistant strains. In four cases, therapy was truncated at 4-7 days because of side-effects; yet the treatment was effective in three. The three metronidazole-susceptible but clarithromycin-resistant infections were cured. CONCLUSION: This novel triple-layer tablet combination therapy was effective in all patients with metronidazole-susceptible H. pylori and many of those with resistant organisms. A greater degree of acid suppression may further improve effectiveness.
Asunto(s)
Antiácidos/administración & dosificación , Antiinfecciosos/administración & dosificación , Antiulcerosos/administración & dosificación , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori , Compuestos Organometálicos/administración & dosificación , Ranitidina/administración & dosificación , Adolescente , Adulto , Anciano , Antiácidos/efectos adversos , Farmacorresistencia Bacteriana , Quimioterapia Combinada , Femenino , Humanos , Masculino , Metronidazol/administración & dosificación , Metronidazol/efectos adversos , Persona de Mediana Edad , Compuestos Organometálicos/efectos adversos , Cooperación del Paciente , Proyectos Piloto , Ranitidina/efectos adversos , Comprimidos , Tetraciclina/administración & dosificación , Tetraciclina/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: A reliable challenge model is needed to evaluate Helicobacter pylori vaccine candidates. METHODS: A cag pathogenicity island negative, OipA positive, multiple antibiotic susceptible strain of H pylori obtained from an individual with mild gastritis (Baylor strain 100) was used to challenge volunteers. Volunteers received 40 mg of famotidine at bedtime and 10(4)-10(10) cfu of H pylori in beef broth the next morning. Infection was confirmed by (13)C urea breath test ((13)C-UBT), culture, and histology. Eradication therapy was given four or 12 weeks post challenge and eradication was confirmed by at least two separate UBTs, as well as culture and histology. RESULTS: Twenty subjects (nine women and 11 men; aged 23-33 years) received a H pylori challenge. Eighteen (90%) became infected. Mild to moderate dyspeptic symptoms occurred, peaked between days 9 and 12, and resolved. Vomitus from one subject contained >10(3) viable/ml H pylori. By two weeks post challenge gastric histology showed typical chronic H pylori gastritis with intense acute and chronic inflammation. The density of H pylori (as assessed by cfu/biopsy) was similarly independent of the challenge dose. A minimal infectious dose was not found. Gastric mucosal interleukin 8 levels increased more than 20-fold by two weeks after the challenge. CONCLUSION: Challenge reliably resulted in H pylori infection. Infection was associated with typical H pylori gastritis with intense polymorphonuclear cell infiltration and interleukin 8 induction in gastric mucosa, despite absence of the cag pathogenicity island. Experimental H pylori infection is one of the viable approaches to evaluate vaccine candidates.
Asunto(s)
Gastritis/microbiología , Infecciones por Helicobacter/patología , Helicobacter pylori/patogenicidad , Experimentación Humana no Terapéutica , Adolescente , Adulto , Antibacterianos/uso terapéutico , Vacunas Bacterianas , Dispepsia/microbiología , Femenino , Estudios de Seguimiento , Determinación de la Acidez Gástrica , Gastritis/inmunología , Gastritis/patología , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/inmunología , Infecciones por Helicobacter/microbiología , Helicobacter pylori/efectos de los fármacos , Humanos , Concentración de Iones de Hidrógeno , Interleucinas/biosíntesis , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , VirulenciaRESUMEN
BACKGROUND: Antisecretory therapy may exacerbate Helicobacter pylori corpus gastritis. The rate and mechanism(s) remain unknown. AIM: To investigate the early events in proton pump inhibitor therapy on antral and corpus H. pylori gastritis. METHODS: Nine H. pylori-infected volunteers underwent gastric biopsy with jumbo forceps for culture and histology. Histology was scored in the range 0-5 using a visual analogue scale. The depth of inflammation in gastric pits was scored in the range 1-3 (superficial or less than one-third, one-third to two-thirds and greater than two-thirds of the gastric pit, respectively). Tissue interleukin-1 beta and interleukin-8 levels were measured by enzyme-linked immunoabsorbent assay. Omeprazole, 20 mg b.d., was given for 6.5 days and biopsies were repeated on day 7. RESULTS: Proton pump inhibitor therapy resulted in a fall in H. pylori density in the antrum and corpus. Inflammation and tissue levels of interleukin-8 and interleukin-1 beta decreased in the antrum and increased in the corpus mucosa. There was a significant increase in the depth of inflammation to include the proliferative zone in the corpus. CONCLUSIONS: Within 1 week of starting proton pump inhibitor therapy, there was a marked extension of corpus inflammation into the gastric pit and an increase in corpus mucosal interleukin-1 beta and interleukin-8 levels. H. pylori eradication should be considered for all patients receiving long-term antisecretory therapy.
Asunto(s)
Antiulcerosos/efectos adversos , Gastritis/inducido químicamente , Infecciones por Helicobacter , Helicobacter pylori , Omeprazol/efectos adversos , Inhibidores de la Bomba de Protones , Adulto , Femenino , Gastritis/microbiología , Humanos , MasculinoRESUMEN
BACKGROUND: Sirolimus (Rapamune, rapamycin, RAPA) is a potent immunosuppressive drug that has reduced the rate of acute rejection episodes by more than 40% in phase III trials when added to an immunosuppression regimen of cyclosporine (CsA) and prednisone. However, RAPA treatment tends to increase lipid levels, particularly among patients with pre-existing hyperlipidemia. METHODS: To identify the metabolic pathway(s) leading to RAPA-mediated hyperlipidemia, five patients with renal transplants maintained on CsA+/-prednisone+/- azathioprine (AZA) were studied before and after 6 weeks of treatment with RAPA (off RAPA and on RAPA, respectively). Each study patient was infused with a single bolus of [2H4]-lysine to derive metabolic parameters for apoB100-containing lipoproteins by using kinetic analysis based upon quantitation of isotopic enrichment by gas chromatography-mass spectrometry. RESULTS: Serial lipid measurements revealed that four patients displayed increased plasma triglyceride levels after RAPA treatment, which coincided with significantly higher plasma VLDL-apoB100 concentrations (21.7+/-12.1 mg/dl off RAPA vs. 38.7+/-14.8 mg/dl on RAPA, mean+/-SD, P<0.05). Kinetic analysis showed that the RAPA-induced increase in VLDL-apoB100 concentrations was due to a significant reduction in the fractional catabolic rate (FCR) of very low-density lipoprotein (VLDL) apoB100 (0.83+/-0.65 off RAPA vs. 0.24+/-0.10 on RAPA, mean+/-SD, P<0.05), rather than an enhanced VLDL-apoB100 synthesis. In one patient, RAPA treatment induced hypercholesterolemia but not hypertriglyceridemia. This hypercholesterolemia was due to elevated low-density lipoprotein (LDL) cholesterol levels, which coincided with a decreased FCR of LDL-apoB100. Heparin-induced lipoprotein lipase activity was significantly lower in the immunosuppressed hyperlipidemic patients than in normolipidemic controls. However, RAPA treatment did not significantly alter basal lipoprotein lipase activity in renal transplant patients in this study. CONCLUSIONS: This study indicates that for renal transplant patients in whom RAPA treatment induces hyperlipidemia, this effect is the result of reduced catabolism of apoB100-containing lipoproteins.
Asunto(s)
Apolipoproteínas B/metabolismo , Inmunosupresores/uso terapéutico , Trasplante de Riñón , Lipoproteínas/metabolismo , Sirolimus/uso terapéutico , Apolipoproteína B-100 , Humanos , Hiperlipidemias/etiología , Hiperlipidemias/metabolismo , Inmunosupresores/efectos adversos , Lipoproteínas VLDL/sangre , Lipoproteínas VLDL/metabolismo , Modelos Biológicos , Sirolimus/efectos adversosRESUMEN
BACKGROUND: Acquisition of the Helicobacter pylori infection usually occurs in childhood. The prevalence of infection differs among ethnic groups and in adults is inversely related to the socioeconomic status of the individual's family during childhood. This study investigates the seroprevalence of H. pylori infection in children of different ethnic groups in relation to socioeconomic class and investigates the prevalence of acute H. pylori infection among children who have had recent onset of abdominal pain. METHODS: Serum samples were collected from 797 children, aged 6 months to 18 years, of various socioeconomic and ethnic backgrounds, at a large urban children's hospital. H. pylori status was determined by an anti-H. pylori immunoglobulin (Ig)G enzyme-linked immunosorbent assay (ELISA) validated for pediatric use. To determine the prevalence of acute H. pylori infection, children brought to the emergency center with abdominal symptoms without diarrhea and overt signs of acute abdomen were evaluated with both serology and the 13C-urea breath test. Acute H. pylori was defined as a positive 13C-urea breath test result and negative IgG serology for H. pylori. RESULTS: The overall seroprevalence of H. pylori was 12.2% and increased with age (e.g., 8.3% at 6-11.9 months and 17.9% at 13 years). The prevalence was inversely related to socioeconomic status (6.6%, moderate to high vs. 15%, low socioeconomic status). The difference in seroprevalence among blacks (16.8%), Hispanics (13.3%), and whites (8.3%; P < 0.01) could be accounted for by differences in socioeconomic status. Eighteen percent of children who were evaluated at the emergency center for recent-onset abdominal pain had acute H. pylori infections. CONCLUSIONS: Socioeconomic status, not ethnic group, is the more important risk factor for acquisition of H. pylori infection during childhood. Acute H. pylori infection was a relatively common cause of recent-onset, nonsurgical abdominal pain.
Asunto(s)
Dolor Abdominal/etiología , Infecciones por Helicobacter/epidemiología , Helicobacter pylori/aislamiento & purificación , Inmunoglobulina G/sangre , Enfermedad Aguda , Factores de Edad , Anticuerpos Antibacterianos/sangre , Pruebas Respiratorias , Niño , Preescolar , Ensayo de Inmunoadsorción Enzimática , Femenino , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/etnología , Helicobacter pylori/inmunología , Humanos , Lactante , Masculino , Factores de Riesgo , Estudios Seroepidemiológicos , Factores Socioeconómicos , Texas/epidemiologíaRESUMEN
BACKGROUND: Ursodeoxycholic acid (UDCA) has been shown to be beneficial in reducing disease activity in adult patients with primary sclerosing cholangitis (PSC). However, there has been little published regarding PSC in children and no studies investigating the efficacy of UDCA as a treatment for PSC. METHODS: This retrospective study included 10 children who were found to have the diagnosis of PSC during the past 15 years at the Texas Children's Hospital and Herman Hospital, both in Houston, Texas. The male:female ratio was 8:2, the median age of onset was 12 years (range, 1-17 years), and eight patients had coexistent inflammatory bowel disease (IBD; six ulcerative colitis, one Crohn's disease, one unspecified). At the time of diagnosis, five patients were asymptomatic, all of whom had IBD with elevated liver enzymes and three of whom had hepatomegaly. Nine patients were treated with UDCA. The one patient who did not receive UDCA was lost to follow-up soon after diagnosis. The mean dose of UDCA was 17 mg/kg with the doses ranging from 9 to 37 mg/kg. RESULTS: There were no side effects from the medication recorded for any of the patients. These patients showed a significant reduction in alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase at 1, 3, 6, 15, and 20 months after treatment. CONCLUSIONS: This study demonstrates that children with PSC treated with UDCA have significant improvements in liver biochemical indices. However, the long-term effect of UDCA on clinical outcome is unknown.
Asunto(s)
Colangitis Esclerosante/tratamiento farmacológico , Ácido Ursodesoxicólico/uso terapéutico , Adolescente , Alanina Transaminasa/sangre , Fosfatasa Alcalina/sangre , Aspartato Aminotransferasas/sangre , Biopsia , Niño , Preescolar , Colangitis Esclerosante/diagnóstico , Colangitis Esclerosante/epidemiología , Femenino , Humanos , Lactante , Hígado/enzimología , Hígado/patología , Masculino , Estudios Retrospectivos , Factores de Tiempo , Ácido Ursodesoxicólico/efectos adversos , gamma-Glutamiltransferasa/sangreRESUMEN
BACKGROUND: Metronidazole remains a key component of H. pylori infection therapy. It has been suggested that despite resistance, metronidazole may be effective when given at high dose with bismuth, tetracycline, and a proton pump inhibitor (quadruple therapy). AIM: To prospectively evaluate metronidazole quadruple therapy for treatment of metronidazole resistant H. pylori infection in the United States. METHODS: Patients infected with metronidazole resistant H. pylori were prospectively prescribed 14 days of quadruple therapy consisting of metronidazole 500 mg t.d.s., tetracycline 500 mg q.d.s., two bismuth subsalicylate tablets q.d.s., and omeprazole 20 mg o.d. RESULTS: A total of 26 patients were entered into the study; 22 for their first treatment and four as re-treatment for failed therapy. Of the 26 patients, 24 were cured (cure rate 92%; 95% CI: 78-99%). Both treatment failures reported full compliance to 14 days of therapy. Side-effects were common and resulted in premature discontinuation of therapy in 31%. Premature discontinuation did not reduce the cure rate. CONCLUSION: Quadruple metronidazole combination therapy is effective despite the presence of metronidazole resistance and should be considered as either first line therapy or for failures of twice-a-day combination therapies.
Asunto(s)
Antibacterianos/farmacología , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori , Metronidazol/farmacología , Anciano , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Antiulcerosos/administración & dosificación , Bismuto , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Resistencia a Medicamentos , Quimioterapia Combinada , Femenino , Helicobacter pylori/efectos de los fármacos , Humanos , Masculino , Metronidazol/administración & dosificación , Metronidazol/uso terapéutico , Omeprazol/administración & dosificación , Compuestos Organometálicos , Cooperación del Paciente , Estudios Prospectivos , Salicilatos , Tetraciclina/administración & dosificación , Resultado del TratamientoRESUMEN
Human caliciviruses (HuCVs) are the major cause of outbreaks of acute nonbacterial gastroenteritis throughout the world. An increasing recognition of the clinical significance of these viruses as human pathogens causing foodborne and waterborne disease indicates that an effective vaccine would be useful. This article reviews the current challenges that exist for the development of a vaccine for the HuCVs as well as the status of development of a candidate vaccine. HuCVs are viruses that exhibit a restricted tropism for infection of the gastrointestinal tract of humans, and a volunteer model of infection and disease is available. As pathogens with a restricted host range, the HuCVs are excellent models for understanding the mechanisms that mediate and regulate viral infection of the gastrointestinal tract and mucosal immunity in humans.
Asunto(s)
Virus Norwalk/inmunología , Vacunas Virales/inmunología , Infecciones por Caliciviridae/prevención & control , Humanos , Inmunidad Mucosa , Vacunas Sintéticas/inmunologíaRESUMEN
BACKGROUND: Antibiotic resistance has begun to impair the ability to cure Helicobacter pylori infection. AIM: To evaluate furazolidone as a component of combination therapies for treatment of H. pylori infection in the United States. METHODS: Patients with active H. pylori infection received furazolidone combination therapy for 14 days (furazolidone 100 mg and tetracycline 500 mg t.d.s.; omeprazole 20 mg o.d. in the morning and, depending on the pre-treatment antimicrobial susceptibility pattern, 500 mg of metronidazole or clarithromycin t.d.s.). RESULTS: A total of 27 patients received the metronidazole containing combination (cure rate 100%) and seven received the clarithromycin combination (cure rate 86%). Overall the cure rates for intention-to-treat was 97% (95% CI: 85% to 100%). The single failure took the clarithromycin containing combination for only 2 days (per protocol cure rate = 100%). Side-effects were common and led to discontinuation of therapy in 26% of patients. An attempt to eliminate metronidazole and clarithromycin and use furazolidone, tetracycline, and lansoprazole b.d. produced an unsatisfactory cure rate of 72%. CONCLUSION: Furazolidone combination therapy appears to be effective. Additional studies with different antimicrobial combinations and duration of therapy are warranted.
Asunto(s)
Antiulcerosos/uso terapéutico , Quimioterapia Combinada/uso terapéutico , Furazolidona/administración & dosificación , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori , Antiulcerosos/administración & dosificación , Antiulcerosos/efectos adversos , Claritromicina/administración & dosificación , Claritromicina/efectos adversos , Claritromicina/uso terapéutico , Farmacorresistencia Microbiana/fisiología , Femenino , Furazolidona/efectos adversos , Furazolidona/uso terapéutico , Humanos , Masculino , Metronidazol/administración & dosificación , Metronidazol/efectos adversos , Metronidazol/uso terapéutico , Persona de Mediana Edad , Omeprazol/administración & dosificación , Omeprazol/efectos adversos , Omeprazol/uso terapéutico , Estudios Prospectivos , Tetraciclina/administración & dosificación , Tetraciclina/efectos adversos , Tetraciclina/uso terapéutico , Factores de Tiempo , Estados UnidosRESUMEN
BACKGROUND & AIMS: Norwalk virus (NV) is a major cause of epidemic gastroenteritis. The NV capsid is composed of a single protein that forms recombinant (rNV) virus-like particles (VLPs). In mice, these VLPs are immunogenic when administered orally without adjuvant, and they elicit serum immunoglobulin (Ig) G and intestinal IgA responses. The aim of this study was to evaluate the safety and immunogenicity of rNV VLPs in healthy volunteers. METHODS: Twenty antibody-positive adults were orally administered rNV VLPs in sterile Milli-Q water on days 1 and 21. Vaccine safety and serum rNV-specific total and subclass IgG and IgA antibody responses were monitored. The immune response induced by the VLPs was compared with the response elicited by replicating virus. RESULTS: No side effects were observed or reported by the volunteers. Serum IgG responses to rNV VLPs were dose-dependent, and all vaccinees given 250 microgram of rNV VLPs responded with >/=4-fold increases in serum IgG titers. Most of the volunteers (83%; 15 of 18) responded after the first rNV VLP dose and showed no increase in serum IgG titer after the second dose. CONCLUSIONS: Orally administered rNV VLPs are safe and immunogenic in healthy adults when administered without adjuvant and are useful to test the mucosal delivery of immunogens.
Asunto(s)
Virus Norwalk/inmunología , Virión/inmunología , Administración Oral , Adolescente , Adulto , Anticuerpos/inmunología , Formación de Anticuerpos/fisiología , Femenino , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina G/inmunología , Masculino , Persona de Mediana Edad , Recombinación Genética , Replicación Viral/fisiologíaRESUMEN
BACKGROUND: Increasing antibiotic resistance has begun to impair our ability to cure Helicobacter pylori infection. AIM: To evaluate orally administered novel therapies for the treatment of H. pylori infection. METHODS: Healthy H. pylori infected volunteers received: (a) hyperimmune bovine colostral immune globulins, (b) an oligosaccharide containing an H. pylori adhesion target, Neu5Aca2-3Galb1-4Glc-(3'-sialyllactose), or (c) recombinant human lactoferrin. Outcome was assessed by urea breath test or histological assessment of the number of H. pylori present. RESULTS: None of the novel therapies appeared effective and no adverse events occurred. CONCLUSION: Although in vitro data appeared promising, in vivo results were disappointing. Higher doses, longer duration of therapy, adjunctive acid suppression, or a combination could possibly yield better results.
Asunto(s)
Adyuvantes Inmunológicos/uso terapéutico , Antiulcerosos/uso terapéutico , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori , Inmunoglobulina G/uso terapéutico , Lactoferrina/uso terapéutico , Lactosa/análogos & derivados , Ácidos Siálicos/uso terapéutico , Administración Oral , Adulto , Anciano , Animales , Pruebas Respiratorias/métodos , Bovinos , Calostro/inmunología , Femenino , Helicobacter pylori/inmunología , Humanos , Lactosa/uso terapéutico , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/uso terapéutico , Resultado del Tratamiento , UreaRESUMEN
Simian virus 40 (SV40) is known to have contaminated poliovirus vaccines used between 1955 and 1963. Accumulating reports have described the presence of SV40 DNA in human tumors and normal tissues, although the significance of human infections by SV40 is unknown. We investigated whether unselected hospitalized children had evidence of SV40 infections and whether any clinical correlations were apparent. Serum samples were examined for SV40 neutralizing antibody using a specific plaque reduction test; of 337 samples tested, 20 (5.9%) had antibody to SV40. Seropositivity increased with age and was significantly associated with kidney transplants (6 of 15 [40%] positive, P < .001). Many of the antibody-positive patients had impaired immune systems. Molecular assays (polymerase chain reaction and DNA sequence analysis) on archival tissue specimens confirmed the presence of SV40 DNA in 4 of the antibody-positive patients. This study, using 2 independent assays, shows the presence of SV40 infections in children born after 1980. We conclude that SV40 causes natural infections in humans.
Asunto(s)
Hospitalización , Infecciones por Papillomavirus/epidemiología , Virus 40 de los Simios , Infecciones Tumorales por Virus/epidemiología , Adolescente , Anticuerpos Antivirales/sangre , Niño , Preescolar , ADN Viral/análisis , Femenino , Humanos , Lactante , Trasplante de Riñón , Masculino , Infecciones por Papillomavirus/diagnóstico , Reacción en Cadena de la Polimerasa , Poliomavirus/inmunología , Análisis de Secuencia de ADN , Virus 40 de los Simios/genética , Virus 40 de los Simios/inmunología , Infecciones Tumorales por Virus/diagnósticoRESUMEN
BACKGROUND: Choosing the optimum pancreatic enzyme replacement therapy for patients with exocrine insufficiency remains a problem. An enteric coated enzyme microsphere pancreatic enzyme preparation (Pancrease) has been marketed with several levels of lipase activity, implying that there is a dose-response relationship between dose and effectiveness such that the high potency form appears to be the most cost effective. METHODS: In a randomized, single-blind, cross-over study, we evaluated the effectiveness of a commercial enzyme preparation with different amounts of lipase per dosage unit in adults with exocrine pancreatic insufficiency. Patients received a diet comprising 100 g fat each day for 6 days. With each meal (three per day) they received two capsules of either Pancrease MT4 (8000 unit lipase), Pancrease MT10 (20,000 units lipase), Pancrease MT16 (32,000 units lipase) or placebo. A 72-h quantitative faecal collection was carried out for the last 3 days of the 6-day period. RESULTS: There was a reduction in faecal fat excretion with each of the preparations compared to placebo. The difference failed to reach significance with the 8000 units lipase preparation (P > 0.05) but was significant (P = 0.02) with the 20,000 units lipase and the 32,000 units lipase preparations (faecal fat excretion: placebo = 42.1 +/- 29 g, lipase 8000 = 22.1 +/- 7.3 g, lipase 20,000 = 10.2 +/- 4.5 g and lipase 32,000 = 15.8 +/- 12.5 g, P < for 20,000 units and 32,000 units lipase compared to placebo). CONCLUSION: A dose-response relationship between the amount of lipase administered with each meal and a reduction in faecal fat was not evident. The most potent preparation did not provide additional benefits compared to the less expensive lower potency dosage form.
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Enfermedad Celíaca/tratamiento farmacológico , Insuficiencia Pancreática Exocrina/tratamiento farmacológico , Fármacos Gastrointestinales/administración & dosificación , Pancreatina/administración & dosificación , Adulto , Enfermedad Celíaca/etiología , Estudios Cruzados , Relación Dosis-Respuesta a Droga , Insuficiencia Pancreática Exocrina/complicaciones , Heces/química , Humanos , Lipasa/administración & dosificación , Persona de Mediana Edad , Método Simple CiegoRESUMEN
BACKGROUND & AIMS: An association between water sources and the prevalence of Helicobacter pylori infection in Peruvian children was shown previously. The aim of this study was to confirm the presence of H. pylori in drinking water in the same community. METHODS: Forty-eight drinking water samples from different locations in pueblo jovenes (new towns) near Lima were collected. Samples were frozen until technology advanced to the point to the point at which H. pylori might be reliably detected. Immunomagnetic beads coated with anti-H. pylori immunoglobulin Gs were used to concentrate H. pylori, and two polymerase chain reaction assays based on different H. pylori genes were used. One was a polymerase chain reaction for the detection of the H. pylori adhesin subunit encoding gene, and the second was a previously validated H. pylori 16S ribosomal RNA reverse transcriptase-polymerase chain reaction. RESULTS: The expected 375-base pair fragment from the adhesin gene was amplified from 24 water samples. The expected 500-base pair fragment of the 16S ribosomal RNA and the 375-base pair fragment of the adhesin gene were amplified from 11 of the samples. CONCLUSIONS: These results confirm the presence of H. pylori in drinking water in Peru and are consistent with conclusions from a previous epidemiological study of the same population. This provides additional evidence for waterborne transmission of H. pylori in some environments.
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Helicobacter pylori/aislamiento & purificación , Microbiología del Agua , Abastecimiento de Agua , Adhesinas Bacterianas/genética , Secuencia de Bases , Genes Bacterianos , Helicobacter pylori/genética , Helicobacter pylori/metabolismo , Separación Inmunomagnética , Datos de Secuencia Molecular , Hibridación de Ácido Nucleico , Perú , Reacción en Cadena de la Polimerasa , ARN Bacteriano/análisis , ARN Ribosómico 16S/análisis , Sensibilidad y EspecificidadRESUMEN
Viruses that infect cells in the gastrointestinal tract are well suited for examining the immune response to oral delivery of antigen and for exploring the advantages and pitfalls of oral vaccines. Norwalk virus (NV) (family Caliciviridae, genus Calicivirus) causes acute gastroenteritis in all age groups. The NV capsid is composed of 180 copies of a single 58000 molecular weight protein which spontaneously forms virus-like particles (VLPs) that can be purified in extremely high yields (22 mg per 300 ml culture) when produced using the baculovirus expression system. We are testing the potential of these recombinant NV (rNV) particles for use as an oral vaccine by administering them to mice and volunteers. Mice were orally inoculated four times with rNV particles in concentrations ranging from 5 to 500 micrograms in the absence of adjuvant or from 5 to 200 micrograms with 10 micrograms of cholera toxin. Serum IgG and fecal IgA immune responses were monitored. rNV particles were found to be immunogenic when orally given to mice with or without adjuvant. These particles also were safe and immunogenic when orally given to volunteers. These studies show that rNV particles are an excellent model to test the oral delivery of mucosal immunogens in general, and that rNV particles are ideal candidates for vaccine development in particular.
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Gastroenteritis/prevención & control , Virus Norwalk/inmunología , Vacunas Sintéticas/inmunología , Vacunas Virales/inmunología , Administración Oral , Animales , Anticuerpos Antivirales/sangre , Línea Celular , Seguridad de Productos para el Consumidor , Humanos , Ratones , Spodoptera/citología , Virión/inmunologíaRESUMEN
The [13C]aminopyrine breath test measures hepatic mixed function oxidase activity. The cumulative percent dose recovered over 2 hr is a sensitive indicator of hepatic dysfunction; values < or = 7.0% have been shown to indicate severe liver disease. Previous studies have suggested that the test results may be influenced by the use of oral contraceptives steroids. We compared the results from five non-oral contraceptive-using women with those from 31 women whose duration of oral contraceptive steroid usage ranged from 4 to 204 months. The women were taking one of four oral contraceptive formulations that differed in the amounts of estrogen (20, 35, or 50 micrograms with 1 mg progesterone) and progesterone (35 micrograms estrogen with stepped levels of progesterone of 0.5, 0.75, and 1.0 mg). The [13C]aminopyrine breath test was performed on days 21 and 28 of the menstrual cycle. Cumulative percent dose recovery values among the normal menstrual cycle of non-oral contraceptive steroid-using women were 12.1 +/- 1.6 and 11.8 +/- 1.5% (mean +/- SD). In contrast, oral contraceptive steroid users showed a marked reduction in cumulative percent dose recovery at 21 days, averaging 6.1 +/- 2.3% (P < 0.001), and returned to normal values (10.2 +/- 3.5%) at 28 days in most women(seven days after oral contraceptive steroid usage was paused). The adverse impact on hepatic mixed function oxidase by oral contraceptive formulations did not differ on the basis of estrogen or progesterone content. The adverse impact of oral contraceptive usage on the mixed function oxidase activity measured by the [13C]aminopyrine breath test must be considered for women of childbearing potential.