S-adenosylmethionine treatment prevents carbon tetrachloride-induced S-adenosylmethionine synthetase inactivation and attenuates liver injury.

Administration of carbon tetrachloride to rats resulted in induction of hepatic fibrosis and a 60% reduction of hepatic S-adenosylmethionine synthetase activity without producing any significant modification of hepatic levels of S-adenosylmethionine synthetase messenger RNA. The reduction of S-adenosylmethionine synthetase activity was corrected by treatment with S-adenosylmethionine (3 mg/kg/day, intramuscularly). Administration of carbon tetrachloride also produced a 45% depletion of liver glutathione (reduced form) that was corrected by S-adenosylmethionine treatment. After the rats received carbon tetrachloride, a 2.3-fold increase in liver collagen was observed; prolyl hydroxylase activity was 2.5 times greater than that seen in controls. These increases were attenuated in animals treated with carbon tetrachloride and S-adenosylmethionine. The attenuation by S-adenosylmethionine treatment of the fibrogenic effect of carbon tetrachloride was associated with a decrease in the number of rats in which cirrhosis developed.     

Evaluation of 5 versus 10 granulocyteaphaeresis sessions in steroid-dependent ulcerative colitis： A pilot, prospective, multicenter, randomized study

AIM： To evaluate the efficacy of 5 compared to ：tO granulocyteaphaeresis sessions in patients with active steroid-dependent ulcerative colitis.
METHODS： In this pilot, prospective, multicenter randomized trial, 20 patients with moderately active steroid-dependent ulcerative colitis were randomized to 5 or 10 granulocyteaphaeresis sessions. The primary objective was clinical remission at wk 17. Secondary measures included endoscopic remission and steroid consumption.
RESULTS： Nine patients were randomized to 5 granulocyteaphaeresis sessions （group 1） and 11 patients to 10 granulocyteaphaeresis sessions （group 2）. At wk 17, 37.5% of patients in group 1 and 45.45% of patients in group 2 were in clinical remission. Clinical remission was accompanied by endoscopic remission in all cases. Eighty-six percent of patients achieving remission were steroid-free at wk 17. Daily steroid requirements were significantly lower in group 2. Eighty-nine per cent of patients remained in remission during a one year follow-up. One serious adverse event, not related to the study therapy, was reported.
CONCLUSION： Granulocyteaphaeresis is safe and effective for the treatment of steroid-dependent ulcerative colitis. In this population, increasing the number of aphaeresis sessions is not associated with higher remission rates, but affords a significant steroid-sparing effect.     

Comparison of stool immunoassay with standard methods for detection of Helicobacter pylori infection in patients with upper-gastrointestinal bleeding of peptic origin

OBJECTIVE: To assess the accuracy of the determination of Helicobacter pylori infection by a stool immunoassay in patients with upper-gastrointestinal bleeding (UGB) of peptic origin, in comparison with the routine histological study, serology, rapid urease and 13C-breath tests. METHODS: Sixty-eight patients with endoscopically proven UGB of peptic origin were included. The presence of H. pylori was considered when observed on histology or, if negative, by the positive indications of two of the remaining tests (serology, rapid urease,13C-breath test). The accuracy of stool immunoassay was estimated according to results obtained with other diagnostic methods. RESULTS: Lesions causing gastrointestinal bleeding were 49 duodenal ulcers, 11 gastric ulcers, six pyloric channel ulcers, 13 acute lesions of the gastric mucosa, and 16 erosive duodenitis. H. pylori infection was present in 59 (86.76%) patients. Forty-one patients had received nonsteroidal anti-inflammatory drugs. The sensitivity and specificity of the diagnostic methods were 47.5% and 100% for the rapid urease test, 93% and 87.5% for the breath test, 86.4% and 77.7% for serology, 89.4% and 100% for histology, and 96.6% and 33.3% for the stool test. CONCLUSIONS: The detection of H. pylori antigen in stools in patients with UGB of peptic origin has a good sensitivity (96.6%) but a low specificity (33.3%) for the diagnosis of H. pylori infection, which probably makes this test an inadequate tool in this setting if utilized alone.     

Mismatch repair status in the prediction of benefit from adjuvant fluorouracil chemotherapy in colorectal cancer

AIM: Some retrospective studies have shown a lack of benefit of 5-fluorouracil (5-FU) adjuvant chemotherapy in patients with mismatch repair (MMR) deficient colorectal cancer. Our aim was to assess if this molecular marker can predict benefit from 5-FU adjuvant chemotherapy. A second objective was to determine if MMR status influences short term survival. METHODS: We included 754 patients with a median follow up of 728.5 days (range 1-1097). A total of 260 patients with stage II or III tumours received 5-FU adjuvant chemotherapy, according to standard clinical criteria and irrespective of their MMR status. A tumour was considered MMR deficient when either BAT-26 showed instability or there was loss of MLH1 or MSH2 protein expression. RESULTS: At the end of the follow up period, 206 patients died and 120 presented with tumour recurrence. Sixty six (8.8%) patients had MMR deficient tumours. There were no significant differences in overall survival (MMR competent 72.1%; MMR deficient 78.8%; p = 0.3) or disease free survival (MMR competent 61.3%; MMR deficient 72.3%; p = 0.08). In patients with stage II and III tumours, benefit from 5-FU adjuvant chemotherapy was restricted to patients with MMR competent tumours (overall survival: chemotherapy 87.1%; non-chemotherapy 73.5%; log rank, p = 0.00001). Patients with MMR deficient tumours did not benefit from adjuvant chemotherapy (overall survival: chemotherapy 89.5%; non-chemotherapy 82.4%; log rank, p = 0.4). CONCLUSIONS: Benefit from 5-FU adjuvant chemotherapy depends on the MMR status of tumours in patients with colorectal cancer. 5-FU adjuvant chemotherapy improves survival in patients with MMR competent tumours but this benefit from chemotherapy cannot be extended to patients with MMR deficient tumours.     

On the primary structures of lysozyme, cecropins and attacins from Hyalophora cecropia

Diapausing pupae of Cecropia respond to a bacterial infection by the selective synthesis of RNA and 15-20 hemolymph proteins. Of these we have purified lysozyme and two classes of antibacterial proteins called cecropins and attacins. The primary structure has been determined for the lysozyme, one attacin and five cecropins. We have also prepared a cDNA bank, isolated and sequenced clones corresponding to the lysozyme, the two main attacins and one cecropin. The results of these structural studies are briefly summarized. Finally we review the solid phase synthesis of cecropin A and B and 9 analogs of cecropin A.     

Detection of Metachronous Neoplasms in Colorectal Cancer Patients: Identification of Risk Factors

Purpose Patients with colorectal cancer have a high risk of developing metachronous neoplasms. Identification of predictive factors associated with such conditions would allow individualized follow-up strategies in these patients. This study was designed to identify individual and familial factors associated with the development of metachronous colorectal neoplasms in patients with colorectal cancer. Methods In the context of a prospective, multicenter, general population-based study—the EPICOLON project—all patients with colorectal cancer attended in ten Spanish hospitals during a one-year period were included. Patients with familial adenomatous polyposis or inflammatory bowel disease were excluded. All patients were monitored by colonoscopy within two years of the diagnoses. Demographic, clinical, pathologic, molecular (microsatellite instability status and immunohistochemistry for MSH2 and MLH1), and familial characteristics (fulfillment of Amsterdam I or II criteria, and revised Bethesda guidelines) were analyzed. Results A total of 353 patients were included in the study. At two years of follow-up, colonoscopy revealed the presence of adenomas in 89 (25 percent) patients and colorectal cancer in 14 (3.9 percent) patients, in 7 cases restricted to anastomosis. Univariate analysis demonstrated that development of metachronous neoplasm (adenoma or colorectal cancer) was associated with personal history of previous colorectal cancer (odds ratio, 5.58; 95 percent confidence interval, 1.01–31.01), and presence of previous or synchronous adenomas (odds ratio, 1.77; 95 percent confidence interval, 1.21–3.17). Although nonstatistical significance was achieved, metachronisms were associated with gender (P < 0.09) and differentiation degree (P < 0.08). Multivariate analysis identified previous or synchronous adenomas (odds ratio, 1.98; 95 percent confidence interval, 1.16–3.38) as independent predictive factor. Neither presence of tumor DNA microsatellite instability nor family history correlated with the presence of metachronous neoplasms. Conclusions Patients with previous or synchronous colorectal adenoma have an increased risk of developing metachronous colorectal neoplasms. Accordingly, this subgroup of patients may benefit from specific surveillance strategies. Supported by grants from the Red Nacional de Investigación en Hepatología y Gastroenterología (Instituto de Salud Carlos III, C03/02) and from Fondo de Investigaciones Sanitarias (FIS PI061384). Xavier Llor is a recipient of a Ramon y Cajal grant form Ministerio de Ciencia y Tecnología of the Spanish government Presented at the meeting of the United European Gastroenterology, Copenhagen, Denmark, October 15 to 19, 2005.     

Diagnosis and prognosis of atheroembolic disease

Atheroembolic disease is recognized as an iatrogenic complication from an invasive vascular procedure, such as manipulation of the aorta during angiography or vascular surgery, and after anticoagulant and fibrinolytic therapy. Cholesterol crystal embolism is caused by showers of cholesterol crystals from an atherosclerotic aorta that occlude small arteries. The kidney is a frequent target organ for cholesterol emboli because of proximity of the renal arteries to abdominal aorta and it receive an enormous amount of blood flows. We describe the epidemiologic agents of 19 cases that were diagnosed by histologic sections of the affected tissues; the eosinophilia and the renal failure are the clinical features that guide to the diagnosis, in patients with ischemic nephropathy and general atherosclerosis. 53% among patients had a previous invasive procedure and 26% occurred spontaneously. We remark the importance of the kidney's biopsy in diagnosis of the atheroembolic disease and their bad prognosis with 63% of death rate in 18 months of average follow-up. We report patients with the multiple cholesterol emboli syndrome mimicking systemic vasculitis: they died by multivisceral acute failure. The subacute presentation of atheroembolic disease with progressive renal failure treated with hemodialysis is a sign of bad prognosis. The knowledge of the disease and their prevention are the better treatment.