Single nucleotide polymorphisms in TNFSF15 confer susceptibility to Crohn's disease

The inflammatory bowel diseases (IBDs), Crohn's disease (CD) and ulcerative colitis, are chronic inflammatory disorders of the digestive tract. The pathogenesis of IBD is complicated, and it is widely accepted that immunologic, environmental and genetic components contribute to its etiology. To identify genetic susceptibility factors in CD, we performed a genome-wide association study in Japanese patients and controls using nearly 80,000 gene-based single nucleotide polymorphism (SNP) markers and investigated the haplotype structure of the candidate locus in Japanese and European patients. We identified highly significant associations (P = 1.71 x 10(-14) with odds ratio of 2.17) of SNPs and haplotypes within the TNFSF15 (the gene encoding tumor necrosis factor superfamily, member 15) genes in Japanese CD patients. The association was confirmed in the study of two European IBD cohorts. Interestingly, a core TNFSF15 haplotype showing association with increased risk to the disease was common in the two ethnic groups. Our results suggest that the genetic variations in the TNFSF15 gene contribute to the susceptibility to IBD in the Japanese and European populations.     

Bulimia and depression

In recent years several lines of evidence have emerged suggesting that eating disorders in general, and bulimia in particular, are in some way linked to affective illness. However, there are few data on the frequency of affective syndromes among patients who have anorexia nervosa or bulimia. This report describes the results of semistructured interviews using the Schedule for Affective Disorders and Schizophrenia (SADS) to evaluate the frequency of the current and lifetime diagnoses of affective illness among 50 female patients meeting DSM-III criteria for bulimia. Seventy percent of the patients had, at some time during their lives, met Research Diagnostic Criteria (RDC) for an episode of major depression and 88% had met RDC at some time during their lives for some affective disturbance. The implications of this high frequency of affective disturbance among patients with bulimia are discussed.     

Utilization of the 2017 diagnostic criteria for hEDS by the Toronto GoodHope Ehlers–Danlos syndrome clinic: A retrospective review

The new 2017 diagnostic criteria for hypermobile Ehlers–Danlos Syndrome (hEDS) provide a framework for diagnosing hEDS but are more stringent than the previous Villefranche criteria. Our clinical experience at the GoodHope EDS clinic was that the 2017 criteria left many highly symptomatic patients without a diagnosis of hEDS. We conducted a retrospective cohort study to confirm our clinic experience and assess the accuracy of the 2017 diagnostic criteria for hEDS in patients who had a previous hEDS diagnosis based on the Villefranche criteria. Our study found that 15% (n = 20 of 131) of patients with a prior diagnosis of hEDS met the 2017 diagnostic criteria, and many of the traits used to distinguish hEDS were not significantly more frequent in patients who met 2017 criteria versus those who did not. In both groups objective systemic manifestations were found less frequently than subjective systemic manifestations. Beighton score (BS) as assessed by primary care practitioner was found to be higher than assessment by EDS practitioner in 81% (n = 74 of 91) of cases. Generalized joint hypermobility was confirmed in only 46% (n = 51 of 111) of patients who had a previous diagnosis of hEDS. Higher BS did not correlate with increased number of systemic manifestations in our cohort. Common comorbidities of hEDS were found with similar frequency in those who met 2017 criteria and those who did not. Based on our cohort, the 2017 hEDS diagnostic criteria require refinement to improve its diagnostic accuracy.     

Comparison of magnetic resonance imaging and ultrasonography in staging early prostate cancer. Results of a multi-institutional cooperative trial

BACKGROUND. In 1987, a cooperative study group consisting of five institutions was formed to determine the relative benefits of magnetic resonance imaging (MRI) and endorectal (transrectal) ultrasonography in evaluating patients with clinically localized prostate cancer (stage Ta or Tb). METHODS. Over a period of 15 months, 230 patients were entered into the study and evaluated with identical imaging techniques. We compared imaging results with information obtained at the time of surgery and on pathological analysis. RESULTS. MRI correctly staged 77 percent of cases of advanced disease and 57 percent of cases of localized disease; the corresponding figures for ultrasonography were 66 and 46 percent (P not significant). These figures did not vary significantly between readers; moreover, simultaneous interpretation of MRI and ultrasound scans did not improve accuracy. In terms of detecting and localizing lesions, MRI identified only 60 percent of all malignant tumors measuring more than 5 mm on pathological analysis and ultrasonography identified only 59 percent. CONCLUSIONS. The MRI and ultrasonography equipment that is currently available is not highly accurate in staging early prostate cancer, mainly because neither technique has the ability to identify microscopic spread of disease. Further evaluation with improved equipment may improve the accuracy of these techniques.     

Surgery in the treatment of varicose veins

To identify variables which might influence the results of varicose vein surgery, a ten-year retrospective study was carried out on 612 patients undergoing varicose vein surgery. Patient symptomatology, type of venous insufficiency and operator experience were examined and correlated with the results of surgery. The female-to-male ratio was 2:1. The mean age was 47 years for women, 45 years for men. A family history of varicose veins was recorded in 74% of patients. A history of previous deep venous thrombosis was reported in 5% of cases, but in the sub-group of patients with stasis ulceration, the incidence was 9%. Cosmetic appearance was the commonest presenting complaint (54%), while ulceration was relatively infrequent (14%). There was moderate-to-marked improvement in 86% of cases at one year. This was sustained in 79% at three years, in 75% at five years and in 74% at ten years. There was no correlation between the type of venous insufficiency or the presenting complaint, and the result of surgery. Operator experience had the most significant effect on the outcome of surgery (P less than 0.001). Our findings indicate that varicose vein surgery offers most patients a satisfactory result. The only significant variable was operator experience. We strongly recommend closer supervision of junior staff performing this type of surgery, particularly as a large proportion of these patients (25% in this study) are operated on by the more junior staff.     

Reduction of morbidity and mortality rates for neonatal group B streptococcal disease through early diagnosis and chemoprophylaxis.

Pregnant women, part of the term service population at Orlando Regional Medical Center, were screened for group B streptococci (GBS), using Lim Group B Strep Broth (GIBCO Laboratories, Madison, Wis.) and the Phadebact Strep B Test (Pharmacia Diagnostics, Piscataway, N.J.). Of the 803 women screened, 173 were confirmed as colonized with GBS at the time of admission in labor. Eighty of these women were treated with ampicillin at least 6 h prior to delivery. The remaining 93 women received no ampicillin. None of the infants born to the treated women was colonized with GBS at surface culture sites. Forty-three of the infants born to untreated women were colonized. Rapid identification of GBS colonization in women, combined with ampicillin chemoprophylaxis, significantly reduced vertical transmission of GBS.     

Dysferlin is a plasma membrane protein and is expressed early in human development

Recently, a single gene, DYSF, has been identified which is mutated in patients with limb-girdle muscular dystrophy type 2B (LGMD2B) and with Miyoshi myopathy (MM). This is of interest because these diseases have been considered as two distinct clinical conditions since different muscle groups are the initial targets. Dysferlin, the protein product of the gene, is a novel molecule without homology to any known mammalian protein. We have now raised a monoclonal antibody to dysferlin and report on the expression of this new protein: immunolabelling with the antibody (designated NCL-hamlet) demonstrated a polypeptide of approximately 230 kDa on western blots of skeletal muscle, with localization to the muscle fibre membrane by microscopy at both the light and electron microscopic level. A specific loss of dysferlin labelling was observed in patients with mutations in the LGMD2B/MM gene. Furthermore, patients with two different frameshifting mutations demonstrated very low levels of immunoreactive protein in a manner reminiscent of the dystrophin expressed in many Duchenne patients. Analysis of human fetal tissue showed that dysferlin was expressed at the earliest stages of development examined, at Carnegie stage 15 or 16 (embryonic age 5-6 weeks). Dysferlin is present, therefore, at a time when the limbs start to show regional differentiation. Lack of dysferlin at this critical time may contribute to the pattern of muscle involvement that develops later, with the onset of a muscular dystrophy primarily affecting proximal or distal muscles.     

Effect of age and preexisting antibody on serum antibody response of infants and children to the F and G glycoproteins during respiratory syncytial virus infection.

The serum antibody response of 50 infants and children infected with respiratory syncytial virus (RSV) was determined by a glycoprotein-specific enzyme-linked immunosorbent assay, and the effects of age and preexisting antibody titer at the time of RSV infection on response to the G and F glycoproteins of RSV were examined. The immune response to the G and F glycoproteins was assessed with anti-human immunoglobulin A to permit measurement of the response of young infants in the presence of maternally derived immunoglobulin G. The findings suggested that age primarily affects the response to the F glycoprotein and that preexisting antibody titer affects the response to the G glycoprotein.     

Germinal center and activated b-cell profiles separate Burkitt lymphoma and diffuse large B-cell lymphoma in AIDS and non-AIDS cases

Morphologic features of Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) overlap. No single phenotypic marker or molecular abnormality is pathognomonic. We tested a panel of 8 germinal center (GC) and activated B-cell (ABC) markers for their ability to separate BL and DLBCL. We diagnosed 16 BL and 39 DLBCL cases from 21 patients with AIDS and 34 without AIDS based on traditional morphologic criteria, Ki-67 proliferative index, and c-myc rearrangement (fluorescence in situ hybridization). After immunohistochemically staining tissue microarrays of BL and DLBCL for markers of GC (bcl-6, CD10, cyclin H) and ABC (MUM1, CD138, PAK1, CD44, bcl-2), we scored each case for the percentage of positive cells. Hierarchical clustering yielded 2 major clusters significantly associated with morphologic diagnosis (P < .001). For comparison, we plotted the sum of the GC scores and ABC scores for each case as x and y data points. This revealed a high-GC/low-ABC group and a low-GC/high-ABC group that were associated significantly with morphologic diagnosis (P < .001). Protein expression of multiple GC and ABC markers can separate BL and DLBCL.