Helicobacter pylori pathogenicity and primary antimicrobial resistance in Northern Spain.

BACKGROUND: Helicobacter pylori infection is associated with chronic gastritis, ulcers and gastric cancer. Antimicrobial resistance has increased worldwide affecting the efficacy of current treatments. Most guidelines recommend implementation of regional surveillance of primary antibiotic resistance of H pylori. Only a fraction of individuals infected with H pylori develop gastric diseases which are related to virulence factors of the bacteria. The aims of the study were to determine the primary antimicrobial resistance rates of H pylori and to know the virulence factors prevalence of strains circulating in Southern Europe. MATERIALS AND METHODS: Susceptibility testing by Etest to clarithromycin, levofloxacin, metronidazole, amoxicillin and tetracycline was performed in 102 isolates (99 naïve patients). The prevalence of virulence factors (cagA, vacA, oipA, babA and dupA) was evaluated in 102 H pylori isolates from patients with mild-disease symptoms and in 22 isolates from patients with severe-disease symptoms. RESULTS: Primary resistance rates were 12.1% to clarithromycin, 13.1% to levofloxacin, 24.2% to metronidazole and 0% to amoxicillin and tetracycline. Combined resistance to clarithromycin and levofloxacin was 3% and to clarithromycin and metronidazole 4%. Prevalence of virulence factors in the mild- and severe-disease group was 35.3% and 81.8% for cagA, 20.6% and 54.5% for cagA/vacAs1m1, 94.1% and 95.4% for babA2, 78.4% and 100% for oipA and 30.4% and 18.2% for dupA. CONCLUSIONS: Primary antimicrobial resistance rates were under 15% for clarithromycin and levofloxacin. The prevalence of H pylori carrying the virulent genotype cagA/vacAs1m1 was higher than 20% in the mild-disease and 54% in the severe-disease symptom group.

Helicobacter pylori antimicrobial resistance during a 5-year period (2013-2017) in northern Spain and its relationship with the eradication therapies.

BACKGROUND: Antibiotic resistance is the main cause for Helicobacter pylori therapy failure. Frequently, empirical regimens have been recommended in patients with various H. pylori eradication failures. In patients with H. pylori-resistant to various families of antibiotics, the treatment guided by antimicrobial susceptibility testing allows the achievement of good eradication rates. AIM: To evaluate the effectiveness of susceptibility-guided antimicrobial treatment for H. pylori infection in patients with resistance to one or various families of antibiotics. METHODS: A total of 3170 consecutive patients infected by H. pylori during 2013-2017 were tested for antimicrobial susceptibility. 66.6% patients showed resistance to one antimicrobial, 18.9% to two, and 2.4% to three families of antibiotics. A cohort of 162 H. pylori-positive patients were enrolled in this study. Forty-three with single H. pylori resistance to clarithromycin (CLR) were treated with omeprazole (PPI), amoxicillin (AMX), and levofloxacin (LVX)-OAL (31 subjects) or omeprazole, AMX, and metronidazole (MTZ)-OAM (12 patients) and 77 patients with dual H. pylori resistance (51 to CLR and MTZ, 12 to CLR plus LVX, and 14 to MTZ plus LVX) received OAL or OBTM (PPI, bismuth subcitrate, tetracycline, and MTZ), OAM, and OAC, respectively. Other 42 patients with triple H. pylori resistance (CLR, LVX, and MTZ) were treated with PPI, AMX, and rifabutin-OAR (18 subjects), PPI, AMX, and doxycycline-OAD (8), OADB (7), OBTM (6), and ODBR (3). All subjects received standard doses for 10 days. Eradication rate was confirmed by 13 C-UBT. Adverse events were assessed by a questionnaire. RESULTS: Intention-to-treat analysis demonstrates that eradication rates using triple therapies in patients with H. pylori resistance to one and to two families of antibiotics were 93% and 94.8%, respectively. In subjects with H. pylori-resistant to three families of antibiotics, cure rate was higher in naïve patients treated with OAR-10 days compared to those treated with bismuth-containing quadruple therapies (90% vs 75%). Adverse events were limited (18 of 162, 11.1%), all of them mild-moderate. CONCLUSIONS: The implementation of susceptibility-guided triple therapy for 10 days leads to eradication rate ≥95% in naïve patients with H. pylori resistance to one or two families of antimicrobials. In naïve patients with H. pylori resistance to three families, OAR treatment achieved a 90% of eradication.

Genetic variation analysis in a follow-up study of gastric cancer precursor lesions confirms the association of MUC2 variants with the evolution of the lesions and identifies a significant association with NFKB1 and CD14.

Gastric carcinogenesis proceeds through a series of gastric cancer precursor lesions (GCPLs) leading to gastric cancer (GC) development. Although Helicobacter pylori infection initiates this process, genetic factors also play a role. We previously reported that genetic variability in MUC2 is associated with the evolution of GCPLs. In order to replicate previous results in an independent sample series and to explore whether genetic variability in other candidate genes plays a role in the evolution of GCPL, genomic DNA from 559 patients with GCPLs, recruited from 9 Spanish hospitals and followed for a mean of 12 years, was genotyped for 141 SNPs in 29 genes. After follow-up, 45.5% of the lesions remained stable, 37% regressed and 17.5% progressed to a more severe lesion. Genetic association with the evolution of the lesions (progression or regression) was analyzed by multinomial and binomial logistic regression. After correction for multiple comparisons, the results obtained confirmed the inverse association between MUC2 variants and the regression of the lesions. A significant association was also observed between NFKB1 and CD14 variants and the evolution of the lesions; interestingly, this association was with both progression and regression in the same direction, which could reflect the dual role of inflammation in cancer. Stratified analyses according to H. pylori virulence factors indicated some significant and differential effects but none of them passed the FDR test. These results confirm that genetic variability in MUC2, NFKB1 and CD14 may have a role in the evolution of the GCPLs along time and in gastric carcinogenesis.

Antimicrobial Susceptibility-Guided Therapy Versus Empirical Concomitant Therapy for Eradication of Helicobacter pylori in a Region with High Rate of Clarithromycin Resistance.

BACKGROUND: Nonbismuth quadruple (concomitant) regimen is recommended for first-line empirical Helicobacter pylori (HP) eradication treatment when clarithromycin resistance is more than 15-20%. Our objective was to evaluate the efficacy and tolerability of concomitant versus antimicrobial susceptibility-guided treatment in an area with high rates of clarithromycin resistance. METHODS: Three hundred consecutive HP-infected patients received antimicrobial susceptibility-guided therapy or empirical concomitant therapy for 10 days. The concomitant regimen was omeprazole (20 mg/12 hour), amoxicillin (1 g/12 hour), clarithromycin (500 mg/12 hour), and metronidazole (500 mg/12 hour) (OACM). Patients diagnosed by culture received one of three combinations of antibiotics based on susceptibility results: omeprazole, amoxicillin, and clarithromycin (OAC); omeprazole, amoxicillin, and levofloxacin (OAL); or omeprazole, amoxicillin, and metronidazole (OAM), at the aforementioned doses (and 500 mg/12 hour in the case of levofloxacin). Eradication was confirmed with a (13)C urea breath test, 6 weeks after treatment. Adverse events and adherence were assessed with questionnaires and reviewing medication sachets. RESULTS: The mean age was 50 years, 59% were women, and 14% had peptic ulcers. Concomitant and antimicrobial susceptibility-guided eradication rates were, respectively, 87% and 94% by intention-to-treat (p = .08) and 89% and 95% (p = .08) per protocol per-protocol analysis. Adverse effects were reported in 31% of patients on OACM and 15% of those on susceptibility-guided therapy (p < .05). CONCLUSIONS: For HP eradication in a region with high rates of multiple drug resistance, antimicrobial susceptibility-guided therapy is more effective than empirical concomitant therapy.

Helicobacter pylori first-line and rescue treatments in the presence of penicillin allergy.

BACKGROUND: Helicobacter pylori eradication is a challenge in penicillin allergy. AIM: To assess the efficacy and safety of first-line and rescue treatments in patients allergic to penicillin. METHODS: Prospective multicenter study. Patients allergic to penicillin were given a first-line treatment comprising (a) 7-day omeprazole-clarithromycin-metronidazole and (b) 10-day omeprazole-bismuth-tetracycline-metronidazole. Rescue treatments were as follows: (a) bismuth quadruple therapy; (b) 10-day PPI-clarithromycin-levofloxacin; and (c) 10-day PPI-clarithromycin-rifabutin. Eradication was confirmed by (13)C-urea breath test. Compliance was determined through questioning and recovery of empty medication envelopes. Adverse effects were evaluated by questionnaires. RESULTS: In total, 267 consecutive treatments were included. (1) First-line treatment: Per-protocol and intention-to-treat eradication rates with omeprazole-clarithromycin-metronidazole were 59 % (62/105; 95 % CI 49-62 %) and 57 % (64/112; 95 % CI 47-67 %). Respective figures for PPI-bismuth-tetracycline-metronidazole were 75 % (37/49; 95 % CI 62-89 %) and 74 % (37/50; 95 % CI (61-87 %) (p < 0.05). Compliance with treatment was 94 and 98 %, respectively. Adverse events were reported in 14 % with both regimens (all mild). (2) Second-line treatment: Intention-to-treat eradication rate with omeprazole-clarithromycin-levofloxacin was 64 % both after triple and quadruple failure; compliance was 88-100 %, with 23-29 % adverse effects (all mild). (3) Third-/fourth-line treatment: Intention-to-treat eradication rate with PPI-clarithromycin-rifabutin was 22 %. CONCLUSION: In allergic to penicillin patients, a first-line treatment with a bismuth-containing quadruple therapy (PPI-bismuth-tetracycline-metronidazole) seems to be a better option than the triple PPI-clarithromycin-metronidazole regimen. A levofloxacin-based regimen (together with a PPI and clarithromycin) represents a second-line rescue option in the presence of penicillin allergy.

Second-line therapy with levofloxacin after failure of treatment to eradicate helicobacter pylori infection: time trends in a Spanish Multicenter Study of 1000 patients.

BACKGROUND: Second-line bismuth-containing quadruple therapy is complex and frequently induces adverse effects. A triple rescue regimen containing levofloxacin is a potential alternative; however, resistance to quinolones is rapidly increasing. AIM: To evaluate the efficacy and tolerability of a second-line triple-regimen-containing levofloxacin in patients whose Helicobacter pylori eradication treatment failed and to assess whether the efficacy of the regimen decreases with time. DESIGN: Prospective multicenter study. PATIENTS: In whom treatment with a regimen comprising a proton-pump inhibitor, clarithromycin, and amoxicillin had failed. INTERVENTION: Levofloxacin (500 mg bid), amoxicillin (1 g bid), and omeprazole (20 mg bid) for 10 days. OUTCOME: Eradication was confirmed using the C-urea breath test 4 to 8 weeks after therapy. Compliance/tolerance: Compliance was determined through questioning and recovery of empty medication envelopes. Incidence of adverse effects was evaluated by means of a questionnaire. RESULTS: The study sample comprised 1000 consecutive patients (mean age, 49 ± 15 y, 42% men, 33% peptic ulcer) of whom 97% took all medications correctly. Per-protocol and intention-to-treat eradication rates were 75.1% (95% confidence interval, 72%-78%) and 73.8% (95% confidence interval, 71%-77%). Efficacy (intention-to-treat) was 76% in the year 2006, 68% in 2007, 70% in 2008, 76% in 2009, 74% in 2010, and 81% in 2011. In the multivariate analysis, none of the studied variables (including diagnosis and year of treatment) were associated with success of eradication. Adverse effects were reported in 20% of patients, most commonly nausea (7.9%), metallic taste (3.9%), myalgia (3.1%), and abdominal pain (2.9%). CONCLUSIONS: Ten-day levofloxacin-containing therapy is an encouraging second-line strategy, providing a safe and simple alternative to quadruple therapy in patients whose previous standard triple therapy has failed. The efficacy of this regimen remains stable with time.

Susceptibility genetic variants associated with early-onset colorectal cancer.

Colorectal cancer (CRC) is the second most common cancer in Western countries. Hereditary forms only correspond to 5% of CRC burden. Recently, genome-wide association studies have identified common low-penetrant CRC genetic susceptibility loci. Early-onset CRC (CRC<50 years old) is especially suggestive of hereditary predisposition although 85-90% of heritability still remains unidentified. CRC<50 patients (n = 191) were compared with a late-onset CRC group (CRC>65 years old) (n = 1264). CRC susceptibility variants at 8q23.3 (rs16892766), 8q24.21 (rs6983267), 10p14 (rs10795668), 11q23.1 (rs3802842), 15q13.3 (rs4779584), 18q21 (rs4939827), 14q22.2 (rs4444235), 16q22.1 (rs9929218), 19q13.1 (rs10411210) and 20p12.3 (rs961253) were genotyped in all DNA samples. A genotype-phenotype correlation with clinical and pathological characteristics in both groups was performed. Risk allele carriers for rs3802842 [Odds ratio (OR) = 1.5, 95% confidence interval (CI) 1.1-2.05, P = 0.0096, dominant model) and rs4779584 (OR = 1.39, 95% CI 1.02-1.9, P = 0.0396, dominant model) were more frequent in the CRC<50 group, whereas homozygotes for rs10795668 risk allele were also more frequent in the early-onset CRC (P = 0.02, codominant model). Regarding early-onset cases, 14q22 (rs4444235), 11q23 (rs3802842) and 20p12 (rs961253) variants were more associated with family history of CRC or tumors of the Lynch syndrome spectrum excluding CRC. In our entire cohort, sum of risk alleles was significantly higher in patients with a CRC family history (OR = 1.40, 95% CI 1.06-1.85, P = 0.01). In conclusion, variants at 10p14 (rs10795668), 11q23.1 (rs3802842) and 15q13.3 (rs4779584) may have a predominant role in predisposition to early-onset CRC. Association of CRC susceptibility variants with some patient's familiar and personal features could be relevant for screening and surveillance strategies in this high-risk group and it should be explored in further studies.

Clinical patterns and outcomes of ischaemic colitis: results of the Working Group for the Study of Ischaemic Colitis in Spain (CIE study).

BACKGROUND: There is a lack of prospective studies evaluating the natural history of colonic ischaemia (CI). We performed such a study to evaluate the clinical presentation, outcome, and mortality as well as clinical variables associated with poor prognosis. METHODS: An open, prospective, and multicentre study was conducted in 24 Spanish hospitals serving a population of 3.5 million people. The study included only patients who met criteria for definitive or probable CI. A website (www.colitisisquemica.org) provided logistical support. RESULTS: A total of 364 patients met criteria for inclusion. CI was suspected clinically in only 24.2% of cases. The distribution of clinical patterns was as follows: reversible colopathy (26.1%), transient colitis (43.7%), gangrenous colitis (9.9%), fulminant pancolitis (2.5%), and chronic segmental colitis (17.9%). A total of 47 patients (12.9%) had an unfavorable outcome as defined by mortality and/or the need for surgery. Multivariate analysis identified the following signs as independent risk factors for an unfavorable outcome: abdominal pain without rectal bleeding [odds ratio (OR) 3.9; 95% confidence interval (CI) = 1.6-9.3], non-bloody diarrhoea (OR 10; 95% CI = 3.7-27.4), and peritoneal signs (OR 7.3; 95% CI = 2.7-19.6). Unfavorable outcomes also were more frequent in isolated right colon ischaemia (IRCI) compared with non-IRCI (40.9 vs. 10.3%, respectively; p < 0.0001). The overall mortality rate was 7.7%. CONCLUSIONS: The clinical presentation of CI is very heterogeneous, perhaps explaining why clinical suspicion of this disease is so low. The presence of IRCI, and occurrence of peritoneal signs or onset of CI as severe abdominal pain without bleeding, should alert the physician to a potentially unfavorable course.

Diagnosis of Whipple's disease using molecular biology techniques.

The diagnosis of Whipple's disease (WD) is based on the existence of clinical signs and symptoms compatible with the disease and in the presence of PAS-positive diastase-resistant granules in the macrophages of the small intestine. If there is suspicion of the disease but no histological findings or only isolated extraintestinal manifestations, species-specific PCR using different sequences of the T. whippleii genome from different tissue types and biological fluids is recommended.This study reports two cases: the first patient had diarrhea and the disease was suspected after an endoscopic examination of the ileum, while the second patient had multi-systemic manifestations,particularly abdominal, thoracic, and peripheral lymphadenopathies. In both cases, the diagnosis was confirmed using molecular biology techniques to samples from the small intestine or from a retroperineal lymph node, respectively.

Antibiotic Resistance Prevalence and Trends in Patients Infected with Helicobacter pylori in the Period 2013-2020: Results of the European Registry on H. pylori Management (Hp-EuReg).

Background: Bacterial antibiotic resistance changes over time depending on multiple factors; therefore, it is essential to monitor the susceptibility trends to reduce the resistance impact on the effectiveness of various treatments. Objective: To conduct a time-trend analysis of Helicobacter pylori resistance to antibiotics in Europe. Methods: The international prospective European Registry on Helicobacter pylori Management (Hp-EuReg) collected data on all infected adult patients diagnosed with culture and antimicrobial susceptibility testing positive results that were registered at AEG-REDCap e-CRF until December 2020. Results: Overall, 41,562 patients were included in the Hp-EuReg. Culture and antimicrobial susceptibility testing were performed on gastric biopsies of 3974 (9.5%) patients, of whom 2852 (7%) were naive cases included for analysis. The number of positive cultures decreased by 35% from the period 2013-2016 to 2017-2020. Concerning naïve patients, no antibiotic resistance was found in 48% of the cases. The most frequent resistances were reported against metronidazole (30%), clarithromycin (25%), and levofloxacin (20%), whereas resistances to tetracycline and amoxicillin were below 1%. Dual and triple resistances were found in 13% and 6% of the cases, respectively. A decrease (p < 0.001) in the metronidazole resistance rate was observed between the 2013-2016 (33%) and 2017-2020 (24%) periods. Conclusion: Culture and antimicrobial susceptibility testing for Helicobacter pylori are scarcely performed (<10%) in Europe. In naïve patients, Helicobacter pylori resistance to clarithromycin remained above 15% throughout the period 2013-2020 and resistance to levofloxacin, as well as dual or triple resistances, were high. A progressive decrease in metronidazole resistance was observed.

Follow-Up Study Confirms the Presence of Gastric Cancer DNA Methylation Hallmarks in High-Risk Precursor Lesions.

To adopt prevention strategies in gastric cancer, it is imperative to develop robust biomarkers with acceptable costs and feasibility in clinical practice to stratified populations according to risk scores. With this aim, we applied an unbiased genome-wide CpG methylation approach to a discovery cohort composed of gastric cancer (n = 24), and non-malignant precursor lesions (n = 64). Then, candidate-methylation approaches were performed in a validation cohort of precursor lesions obtained from an observational longitudinal study (n = 264), with a 12-year follow-up to identify repression or progression cases. H. pylori stratification and histology were considered to determine their influence on the methylation dynamics. As a result, we ascertained that intestinal metaplasia partially recapitulates patterns of aberrant methylation of intestinal type of gastric cancer, independently of the H. pylori status. Two epigenetically regulated genes in cancer, RPRM and ZNF793, consistently showed increased methylation in intestinal metaplasia with respect to earlier precursor lesions. In summary, our result supports the need to investigate the practical utilities of the quantification of DNA methylation in candidate genes as a marker for disease progression. In addition, the H. pylori-dependent methylation in intestinal metaplasia suggests that pharmacological treatments aimed at H. pylori eradication in the late stages of precursor lesions do not prevent epigenome reprogramming toward a cancer signature.

[Plasma levels of folate and vitamin B(12) in patients with chronic liver disease]. / Niveles plasmáticos de la vitamina B(12) y ácido fólico en pacientes con hepatopatía crónica.

BACKGROUND: Patients with liver disease frequently experience changes in their nutritional status. OBJECTIVE: To determine changes in vitamin B12 and folic acid plasma levels in patients with chronic cirrhosis and to assess whether these parameters may be useful in the etiologic diagnosis of this disease. PATIENTS AND METHODS: Thirty-nine patients admitted for decompensated cirrhosis (29 with alcoholic etiology and 10 with non-alcoholic etiology) and 35 controls were prospectively studied. Plasma levels of vitamin B(12), folate acid, mean corpuscular volume (MCV), aspartate aminotransferase (AST), alanine aminotransferase (ALT), AST/ALT ratio, and gamma-glutamyltransferase (GGT), among other parameters, were measured. RESULTS: Vitamin B(12) levels were 1151+/-568pg/ml in patients with decompensated cirrhosis and 440+/-133pg/ml in controls (p<0.05). Plasma folate levels were 8.57+/-3.8ng/ml in controls and 6.68+/-2.74ng/ml in patients with cirrhosis (p<0.05). Folate levels were lower in patients with alcoholic cirrhosis (mean value, 5.7+/-2.1) than in those with non-alcoholic cirrhosis (9.3+/-2.6; p<0.0005). The vitamin B(12)/folate ratio discriminated alcoholic etiology better than other parameters such as AST, ALT, MCV, AST/ALT ratio and GGT. CONCLUSIONS: Plasma levels of vitamin B12 in patients with decompensated chronic liver disease are high, whereas plasma folate levels are low. The ratio between vitamin B12 and folic acid may be useful in the differential diagnosis of the etiology of chronic liver disease.

European Registry on Helicobacter pylori Management: Effectiveness of First and Second-Line Treatment in Spain.

The management of Helicobacter pylori infection has to rely on previous local effectiveness due to the geographical variability of antibiotic resistance. The aim of this study was to evaluate the effectiveness of first and second-line H. pylori treatment in Spain, where the empirical prescription is recommended. A multicentre prospective non-interventional registry of the clinical practice of European gastroenterologists concerning H. pylori infection (Hp-EuReg) was developed, including patients from 2013 until June 2019. Effectiveness was evaluated descriptively and through a multivariate analysis concerning age, gender, presence of ulcer, proton-pump inhibitor (PPI) dose, therapy duration and compliance. Overall, 53 Spanish hospitals were included, and 10,267 patients received a first-line therapy. The best results were obtained with the 10-day bismuth single-capsule therapy (95% cure rate by intention-to-treat) and with both the 14-day bismuth-clarithromycin quadruple (PPI-bismuth-clarithromycin-amoxicillin, 91%) and the 14-day non-bismuth quadruple concomitant (PPI-clarithromycin-amoxicillin-metronidazole, 92%) therapies. Second-line therapies were prescribed to 2448 patients, with most-effective therapies being the triple quinolone (PPI-amoxicillin-levofloxacin/moxifloxacin) and the bismuth-levofloxacin quadruple schemes (PPI-bismuth-levofloxacin-amoxicillin) prescribed for 14 days (92%, 89% and 90% effectiveness, respectively), and the bismuth single-capsule (10 days, 88.5%). Compliance, longer duration and higher acid inhibition were associated with higher effectiveness. "Optimized" H. pylori therapies achieve over 90% success in Spain.

[Clinicopathological characteristics and survival outcome of esophageal cancer. Results from a series of 200 patients]. / Características clinicopatológicas y supervivencia de los pacientes con cáncer de esófago. Resultados de 200 casos consecutivos.

BACKGROUND AND OBJECTIVE: The esophageal cancer (EC) is a slightly frequent but serious disease. Our aim is to describe the characteristics of the patients with EC in our Hospital. PATIENTS AND METHOD: We included 200 patients consecutively diagnosed and/or treated for CE between between January, 2003 and December, 2007. The location of the tumor was analyzed, the histological type, the proofs realized for to establish the classification, the treatments, the survival and the morbi-mortality of the surgery. RESULTS: The endoscopic ultrasonography (EUS) modified the therapeutic strategy in 12% of the patients. The survival to the year, 3 years and 5 years was 48%, 25% and 21%, respectively. 74 (32%) patients were operated, 48 (65%) of them was treated with neoadjuvant chemoradiotherapy. The postsurgical mortality was 8% (6 patients) and the morbidity was 57% (114 patients). In multivariate analysis, after adjustment for traditional risk factors, were the location in the average third ( [HR, hazard ratio]=2.3; confidence interval [IC] of 95%, 1.3-4.1) and not accomplishment of surgery after the chemotherapy and radiotherapy (HR=1.9; IC to 95%, 1.15-3). CONCLUSIONS: The diagnosis is realized very later. The EUS has contributed a better therapeutic strategy to our patients. The mortality continues being high.

[Clostridium-difficile-associated diarrhea]. / Diarrea asociada a Clostridium difficile.

Clostridium difficile is the most frequent cause of nosocomial diarrhea and is a significant cause of morbidity among hospitalized patients. The inflammation is produced as a result of a non-specific response to toxins. In the last few years, a hypervirulent strain, NAP1/BI/027, has been reported. Symptoms usually consist of abdominal pain and diarrhea. The diagnosis should be suspected in any patient who develops diarrhea during antibiotic therapy or 6-8 weeks after treatment. Diagnosis should be confirmed by the detection of CD toxin in stool and by colonoscopy in special situations. The treatment of choice is metronidazole or vancomycin. In some patients who do not respond to this therapy or who have complications, subtotal colectomy may be required. Relapse is frequent and must be distinguished from reinfection. Prevention and control in healthcare settings requires careful attention.

Resveratrol inhibits nonalcoholic fatty liver disease in rats.

BACKGROUND: The prevalence of nonalcoholic fatty liver disease (NAFLD) is high. NAFLD is linked to obesity, diabetes mellitus, and hypertriglyceridemia. Approximately 20% of patients with NAFLD will eventually develop cirrhosis. Our purpose was to investigate whether resveratrol decreased hepatic steatosis in an animal model of steatosis, and whether this therapeutic approach resulted in a decrease in tumor necrosis factor alpha (TNF-alpha) production, lipid peroxidation and oxidative stress. METHODS: Male Wistar CRL: Wi (Han) (225 g) rats were randomized into three groups. A control group (n = 12) was given free access to regular dry rat chow for 4 weeks. The steatosis (n = 12) and resveratrol (n = 12) groups were given free access to feed (a high carbohydrate-fat free modified diet) and water 4 days per week, and fasted for the remaining 3 days for 4 weeks. Rats in the resveratrol group were given resveratrol 10 mg daily by the oral route. All rats were killed at 4 weeks and assessed for fatty infiltration and bacterial translocation. Levels of TNF-alpha in serum, hepatic malondialdehyde (MDA), oxidative stress (superoxide dismutase, glutathione peroxidase, catalase and nitric oxide synthase) and biochemical parameters were measured. RESULTS: Fat deposition was decreased in the resveratrol group as compared to the steatosis group (Grade 1 vs Grade 3, P < 0.05). TNF-alpha and MDA levels were significantly increased in the steatosis group (TNF-alpha; 33.4 +/- 5.2 vs 26.24 +/- 3.47 pg/ml and MDA; 9.08 +/- 0.8 vs 3.17 +/- 1.45 muM respectively, P < 0.05). This was accompanied by increased superoxide dismutase, glutathione peroxidase and catalase and decreased nitric oxide synthase in the liver of resveratrol group significantly (P < 0.05 vs steatosis group). Bacterial translocation was not found in any of the groups. Glucose levels were decreased in the group of rats given resveratrol (P < 0.05). CONCLUSION: Resveratrol decreased NAFLD severity in rats. This effect was mediated, at least in part, by TNF-alpha inhibition and antioxidant activities.

[Molecular and clinical characteristics of a family with Alagille syndrome]. / Características clínicas y moleculares de una familia con síndrome de Alagille.

BACKGROUND AND OBJECTIVE: The Alagille syndrome (AS) is characterized by biliary ductopenia and abnormalities of heart, eyes, face, bones, kidneys and brain with a dominant inheritability. Mutations of Jagged 1 gene are observed in individuals with the full syndrome and/or relatives with little or no phenotypic features. Prognosis of patients depends on the hepatic and cardiovascular involvement. PATIENTS AND METHOD: We present the cases of a woman and her 2 male nephews with AS. We performed a molecular study of the Jagged 1 gene in family members with and without the syndrome. RESULTS: The molecular study detected mutations in the position 2785+2 of TAAG (intron 19) of the Jagged 1 gene in 3 relatives with the full syndrome and in 2 other members with a partial syndrome. Other relatives, without mutation, have some of the phenotypic features of it. CONCLUSIONS: We comment on the clinical forms of AS in this family and the detected mutation. Molecular diagnosis allows to make a genetic counsel.