Ofatumumab monotherapy in rituximab-refractory follicular lymphoma: results from a multicenter study

New treatments are required for rituximab-refractory follicular lymphoma (FL). In the present study, patients with rituximab-refractory FL received 8 weekly infusions of ofatumumab (CD20 mAb; dose 1, 300 mg and doses 2-8, 500 or 1000 mg; N = 116). The median age of these patients was 61 years, 47% had high-risk Follicular Lymphoma International Prognostic Index scores, 65% were chemotherapy-refractory, and the median number of prior therapies was 4. The overall response rate was 13% and 10% for the 500-mg and 1000-mg arms, respectively. Among 27 patients refractory to rituximab monotherapy, the overall response rate was 22%. The median progression-free survival was 5.8 months. Forty-six percent of patients demonstrated tumor reduction 3 months after therapy initiation, and the median progression-free survival for these patients was 9.1 months. The most common adverse events included infections, rash, urticaria, fatigue, and pruritus. Three patients experienced grade 3 infusion-related reactions, none of which were considered serious events. Grade 3-4 neutropenia, leukopenia, anemia, and thrombocytopenia occurred in a subset of patients. Ofatumumab was well tolerated and modestly active in this heavily pretreated, rituximab-refractory population and is therefore now being studied in less refractory FL and in combination with other agents in various B-cell neoplasms. The present study was registered at www.clinicaltrials.gov as NCT00394836.     

Cellular hypersensitivity to gluten derived peptides in coeliac disease.

Wheat gluten derived antigens have been tested for their ability to inhibit the migration of leucocytes from healthy subjects and patients with coeliac disease. Three preparations of a water soluble fraction (Frazer's fraction III, FIII) of partial peptic tryptic digests of wheat gluten had different effects in a direct (one stage) assay. Subfractions B and B2 caused migration inhibition of leucocytes from patients with treated coeliac disease but not of leucocytes from healthy volunteers or patients with Crohn's disease or ulcerative colitis. This migration inhibition seems to be specific for gluten fractions because maize zein fraction B, beta-lactoglobulin and ovalbumin did not cause it. The sensitivity of coeliac leucocytes to fraction B is not related to factors present in coeliac serum as the migration of leucocytes from healthy individuals preincubated with coeliac sera was not inhibited. Puromycin diminished inhibition by fraction B, which was active at 1.2 micrograms/ml in an indirect (two stage) migration inhibition assay; this is consistent with a process involving elaboration of lymphokine(s). More highly purified fractions of B2, P1-P4 were prepared by reverse phase high performance liquid chromatography (HPLC) and showed differing potency in direct and indirect assays, with P4 being the most active fraction. Inhibition of migration by gluten derived peptides appears to result from the release of lymphokine by leucocytes specifically from coeliac patients.     

Genetic markers may predict disease behavior in patients with ulcerative colitis

BACKGROUND & AIMS: Recent studies have suggested that HLA DRB1*0103 and allele 2 of the interleukin 1 receptor antagonist (IL-1RA) gene predict severe and extensive ulcerative colitis, respectively. The aim of this study was to test these hypotheses in patients undergoing surgery for their colitis. METHODS: HLA DRB1 and DQB1 genotyping was performed in 99 patients and 472 controls. Genotyping for polymorphisms of genes encoding tumor necrosis factor alpha and IL-1RA was performed in 107 patients and 89 controls. Measurement of antineutrophil cytoplasmic antibody (ANCA) was performed in 72 patients and 58 healthy subjects by fixed neutrophil enzyme-linked immunosorbent assay and indirect immunofluorescence. RESULTS: The DRB1*0103 allele was increased in patients (14.1% vs. 3.2% in controls; P < 1 x 10[-5]). This association was greatest in patients with extensive disease (15.8%; P < 0.0001) or extraintestinal manifestations (22.8%; P < 0.0001): mouth ulcers (25.8%; P < 0.0001), arthritis (27.2%; P < 0.0001), and uveitis (35.7%; P < 0.0001). The DRB1*04 alleles were reduced in patients (P = 0.005). Differences were noted between extensive and distal disease in the frequency of allele 2 of IL-1RA (10.9% in distal vs. 28.6% in extensive; P = 0.01) and allele 2 homozygosity. ANCA was detected in 76.4% of patients. Carriage of IL-1RA allele 2 and tumor necrosis factor 2 allele was increased in ANCA-positive patients. CONCLUSIONS: Genetic markers may predict disease behavior in ulcerative colitis. (Gastroenterology 1997 Jun;112(6):1845-53)     

Posttraumatic Stress Disorder and One‐Year Outcome in Methadone Maintenance Treatment

Background: Although opiate use may be associated with posttraumatic stress disorder (PTSD), it is not clear whether PTSD is associated with retention in methadone maintenance. Objectives: To evaluate among those receiving methadone maintenance at an urban methadone maintenance clinic the frequency of life‐time traumatic experiences, the predictors and prevalence of current PTSD, and whether PTSD affects retention at 1 year. Methods: Eighty‐nine people participated in the study. The Post Traumatic Diagnostic Scale was used to determine the prevalence of PTSD. The Life Stressor Checklist Revised was used to evaluate trauma history. Logistic regression analyses examined associations between demographic characteristics, substance use, trauma‐related variables, and PTSD. Similar logistic regression analyses were used to examine retention in methadone maintenance at 1 year. Results: The mean number of reported lifetime stressful events was 8.0 (SD = 3.7). Twenty‐seven percent were diagnosed with PTSD. Nearly 92% of those with PTSD had co‐occurring depressive symptoms. Female gender (adjusted odds ratio [AOR][95% CI]; 3.89 [1.07–14.01]), number of traumatic events (AOR [95% CI]; 1.34 [1.13–1.61]), and less education (AOR [95% CI]; 4.13 [1.14–14.98]) were significantly associated with PTSD. Those with a toxicology positive screen were 80% less likely to remaine in methadone maintenance at 1 year (OR [95% CI]; 0.20 [0.07–0.52]). PTSD diagnosis was not significantly associated with treatment retention at 1 year (OR [95% CI]; 0.61 [0.23–1.64]). Conclusions and Scientific Significance: Future studies are needed to determine if treatment of PTSD that is integrated into methadone maintenance programs may impact continued substance abuse use and thereby improve retention in care. (Am J Addict 2012;21:524–530)     

Glycosylation and sulphation of colonic mucus glycoproteins in patients with ulcerative colitis and in healthy subjects.

Studies have been made of mucus glycoprotein biosynthesis in different regions of the lower gastrointestinal tract in normal patients and those with ulcerative colitis (UC), active or inactive, by means of 3H-glucosamine (3H-GlcNH2)--35S-sulphate double labelling of epithelial biopsy specimens under culture conditions. The time based rate of 3H-GlcNH2 labelling of mucus in rectal tissue was similar to that in active or inactive UC whereas the rate of 35SO4(2) labelling was significantly increased in active disease. The 3H specific activities measuring the amount of isotopic incorporation into surface and tissue mucus glycoproteins were increased in patients with active UC compared with normal or inactive subjects. The 35S specific activities did not differ significantly between patients with active UC and those in remission. In the rectum, glycosylation of mucus glycoproteins decreases with the increasing age of the patient. Regional differences in 3H-labelling of mucus components are reported for ascending colon, transverse colon, sigmoid colon, and rectum. Sulphation (35S-labelling) was higher in all parts of the colon in left sided UC. Results point to accelerated glycosylation of core proteins in the active phase of UC.     

Analysis of the IBD5 locus and potential gene-gene interactions in Crohn's disease

BACKGROUND AND AIMS: Genetic variation in the chromosome 5q31 cytokine cluster (IBD5 risk haplotype) has been associated with Crohn's disease (CD) in a Canadian population. We studied the IBD5 risk haplotype in both British and Japanese cohorts. Disease associations have also been reported for CARD15/NOD2 and TNF variants. Complex interactions between susceptibility loci have been shown in animal models, and we tested for potential gene-gene interactions between the three CD associated loci. METHODS: Family based association analyses were performed in 457 British families (252 ulcerative colitis, 282 CD trios) genotyped for the IBD5 haplotype, common CARD15, and TNF-857 variants. To test for possible epistatic interactions between variants, transmission disequilibrium test analyses were further stratified by genotype at other loci, and novel log linear analyses were performed using the haplotype relative risk model. Case control association analyses were performed in 178 Japanese CD patients and 156 healthy controls genotyped for the IBD5 haplotype. RESULTS: The IBD5 haplotype was associated with CD (p=0.007), but not with UC, in the British Caucasian population. The CARD15 variants and IBD5 haplotype showed additive main effects, and in particular no evidence for epistatic interactions was found. Variants from the IBD5 haplotype were extremely rare in the Japanese. CONCLUSIONS: The IBD5 risk haplotype is associated with British CD. Genetic variants predisposing to CD show heterogeneity and population specific differences.     

Liver regeneration requires Yap1-TGFβ-dependent epithelial-mesenchymal transition in hepatocytes

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Image-guided surgery of small breast cancers.

BACKGROUND: Widespread screening mammography has resulted in detection of many breast cancers smaller than one cm. Image-guided percutaneous needle sampling provides accurate diagnostic and prognostic information for adjuvant therapy. Less invasive methods based on imaging techniques are emerging as an alternative to wire localization and lumpectomy. DATA SOURCES: Information presented in this overview was provided by seven investigators from five medical centers in the United States. These researchers are currently developing various techniques of image-guided percutaneous therapy of small (Tis, 1) breast cancers. CONCLUSIONS: Several percutaneous treatment modalities for treatment of early breast cancer, either excisional or in-situ ablative, are described in this overview and their potential applications are discussed.     

《中华男科学》杂志2000～2002年载文及引文分析

目的 :评价《中华男科学》杂志的地位和社会影响力。　方法 :用文献计量学方法对 2 0 0 0～ 2 0 0 2年《中华男科学》杂志载文及其引文情况进行统计分析。　结果 :除综述性文献和译文外 ,3年 16期共载文 34 3篇 ,其中333篇文献有引文 ,占载文总数的 97.0 8%;论著共计 183篇 ,占 5 3.35 %;基金项目论文 6 2篇 ,占总载文量的18.0 8%;载文量与基金项目论文篇数逐年增加 ;分布在全国 30个省及直辖市 ,作者中 43.37%为高级职称 ,拥有博士、硕士学位的占 40 .80 %;期刊与作者平均自引率为 6 .30 %、3.39%;文献发表 5年内被引用的频率最高 ,普赖斯指数为 5 6 .0 3%;引文语种以英文文献为主 ,期刊占引文总数的 83.0 2 %。　结论 :该刊拥有一批优秀的作者群体 ,具有很强的社会影响力以及广阔的发展前景 ,是一高质量的学术期刊。