A major non-HLA locus in celiac disease maps to chromosome 19

BACKGROUND AND AIMS: The pathogenesis of celiac disease is still unknown despite its well-known association with human leukocyte antigen (HLA)-DQ2 and DQ8. It is clear that non-HLA genes contribute to celiac disease development as well, but none of the previous genome-wide screens in celiac disease have resulted in identification of these genes. METHODS: We, therefore, performed a 2-stage, genome-wide screen in 101 affected sibpairs from 82 Dutch families who met strict diagnostic criteria. The small intestinal biopsy samples, on which the original celiac disease diagnoses had been based, showed a Marsh III lesion in all patients on reevaluation by 1 pathologist. For association analysis of markers in regions linked to celiac disease, 216 independent MIII patients and 216 age- and sex-matched controls were available. RESULTS: As expected, highly significant linkage to the HLA-region was detected (multipoint maximum lod score [MMLS] = 8.14). More importantly, significant linkage was also present at 19p13.1 (MMLS = 4.31), with the peak at marker D19S899. Moreover, this marker was also significantly associated with celiac disease in the case-control study (corrected P = 0.016). Furthermore, we identified suggestive linkage to 6q21-22, which is approximately 70 cM downstream from the HLA region (MMLS = 3.10). CONCLUSIONS: Significant linkage of celiac disease to chromosome region 19p13.1 was detected in our genome-wide screen. These results were confirmed by the association of D19S899 to celiac disease in an independent case-control cohort. Furthermore, we identified a possible second celiac disease locus on chromosome region 6q21-22.     

Remodelling of the sacrum in high-grade spondylolisthesis: a report of two cases

Two young patients are described, who were operated on for high-grade spondylolisthesis. A good posterolateral fusion was achieved, without decompression and without reduction. The clinical course was favourable, the tight hamstring syndrome resolved. Disappearance of the posterior-superior part of the sacrum and of the posterior part of the L5-S1 disc was observed on comparing pre- and postoperative magnetic resonance (MR) images. This resulted in normalisation of the width of the spinal canal. Around the L5 nerve roots in the L5-S1 foramina some fat reappeared. These anatomical changes on MRI could play a role in the disappearance of clinical symptoms.     

Mechanical properties,bone mineral content,and bone composition (collagen,osteocalcin, IGF-I) of the rat femur: Influence of ovariectomy and nandrolone decanoate (anabolic steroid) treatment

Summary Nandrolone decanoate (ND) is an anabolic steroid with a positive effect on bone mass in osteoporotic patients. The mechanism of action, (i.e., reduction of bone resorption and/or Stimulation of bone formation), the ultimate effect on mechanical properties, and the most effective dosage are not yet clear. To address these issues, dose-related effects of the long-term effect of ND on Serum and bone biochemistry, bone mineral content, and bone mechanical properties in ovariectomized (OVX) rats (12 weeks old at the Start of the experiment) were Studied for 6 months. The results were compared with those obtained in agematched, intact, and OVX rats. OVX caused in the femur a significant increase in net periosteal bone formation and net endosteal bone resorption of bone collagen content and torsional strength, and of Serum alkaline phosphatase, osteocalcin, and insulin-like growth factor-I (IGF-I) levels, whereas cortical bone density and calcium/creatinine and phosphorus/creatinine in 24-hour urine were Significantly reduced.Treatment of OVX rats with 1 mg ND/14 days resulted in a Significant increase in periosteal bone formation, femur length, cortical and trabecular bone mineral content and density, torsion stiffness and Strength, and bone IGF-I content, and a decrease in Serum osteocalcin, urinary calcium/creatinine levels, and bone collagen content compared with OVX controls. The higher ND dosage of 2.5 mg/14 days did not improve the results. ND treatment did not reverse all changes induced by OVX to the level of the intact controls.These results indicate that ND acts as an antiresorptive drug and as a bone formation Stimulating drug. Furthermore, the increased bone mass and bone mineral density is associated with improved bone Strength and stiffness and the presence of an increased amount of IGF-I. IGF-I is a growth factor considered to play a role in the maintenance of normal skeletal balance by a paracrine or autocrine mechanism.     

Randomized clinical trial comparing two options for postoperative incisional care to prevent poststernotomy surgical site infections

Surgical site infection (SSI) remains an important complication of cardiac surgery. Prevention is important, as SSI is associated with high mortality and morbidity rates. Incisional care is an important daily issue for surgeons. However, there is still scant scientific evidence on which guidelines can be based. A randomized clinical trial was performed to compare two options for postoperative incisional care. Patients undergoing sternotomy for cardiothoracic surgery were eligible. To protect an incision from exogenous contamination or direct inoculation by endogenous pathogens, the study group received an adhesive drape, impermeable to water and air. The control group was treated with a water- and air-permeable absorbent dressing. Primary outcome measure was SSI. Between March 2003 and January 2005, 1,185 patients were included. Both groups were comparable for base-line characteristics. No significant difference was found in the incidence of sternal SSI between groups (2.6 vs. 3.3%). In our study, an incisional-care program using a sterile, impermeable adhesive drape did not perform better than an absorbent dressing in reducing SSI after cardiothoracic surgery. In our view, future studies in the field of prevention of SSI should concentrate on other areas of interest.     

Underreporting of Meningococcal Disease Incidence in the Netherlands: Results from a Capture–Recapture Analysis Based on Three Registration Sources with Correction for False Positive Diagnoses

In order to come to a reliable evaluation of the effectiveness of the chosen vaccination policy regarding meningococcal disease, the completeness of registrations on meningococcal disease in the Netherlands was estimated with the capture–recapture method. Data over 1993–1998 were collected from (A) mandatory notifications (n = 2926); (B) hospital registration (n = 3968); (C) laboratory surveillance (n = 3484). As the standard capture–recapture method does not take into account false positive diagnoses, we developed a model to adjust for the lack of specificity of our sources. We estimated that 1363 cases were not registered in any of the three sources in the period of study. The completeness of the three sources was therefore estimated at 49% for source A, 67% for source B and 58% for source C. After adjustment for false positive diagnoses, the completeness of source A, B, and C was estimated as 52%, 70% and 62%, respectively. The capture–recapture methods offer an attractive approach to estimate the completeness of surveillance sources and hence contribute to a more accurate estimate of the disease burden under study. However, the method does not account for higher-order interactions or presence of false positive diagnoses. Being aware of these limitations, the capture–recapture method still elucidates the (in)completeness of sources and gives a rough estimate of this (in)completeness. This makes a more accurate monitoring of disease incidence possible and hence attributes to a more reliable foundation for the design and evaluation of health interventions such as vaccination programs.     

Extensive genetic diversity within the Dutch clinical Cryptococcus neoformans population

A set of 300 Dutch Cryptococcus neoformans isolates, obtained from 237 patients during 1977 to 2007, was investigated by determining the mating type, serotype, and AFLP and microsatellite genotype and susceptibility to seven antifungal compounds. Almost half of the studied cases were from HIV-infected patients, followed by a patient group of individuals with other underlying diseases and immunocompetent individuals. The majority of the isolates were mating type α and serotype A, followed by αD isolates and other minor categories. The most frequently observed genotype was AFLP1, distantly followed by AFLP2 and AFLP3. Microsatellite typing revealed a high genetic diversity among serotype A isolates but a lower diversity within the serotype D set of isolates. One patient was infected by multiple AFLP genotypes. Fluconazole and flucytosine had the highest geometric mean MICs of 2.9 and 3.5 μg/ml, respectively, while amphotericin B (0.24 μg/ml), itraconazole (0.08 μg/ml), voriconazole (0.07 μg/ml), posaconazole (0.06 μg/ml), and isavuconazole (0.03 μg/ml) had much lower geometric mean MICs. One isolate had a high flucytosine MIC (>64 μg/ml), while decreased susceptibility (≥16 μg/ml) for flucytosine and fluconazole was found in 9 and 10 C. neoformans isolates, respectively.     

Juvenile polyposis syndrome

Juvenile polyposis syndrome is a rare autosomal dominant syndrome characterized by multiple distinct juvenile polyps in the gastrointestinal tract and an increased risk of colorectal cancer.The cumulative life-time risk of colorectal cancer is 39% and the relative risk is 34.Juvenile polyps have a distinctive histology characterized by an abundance of edematous lamina propria with inflammatory cells and cystically dilated glands lined by cuboidal to columnar epithelium with reactive changes.Clinically,juven...     

Hyperglycemia in bacterial meningitis: a prospective cohort study

Background  

Hyperglycemia has been associated with unfavorable outcome in several disorders, but few data are available in bacterial meningitis. We assessed the incidence and significance of hyperglycemia in adults with bacterial meningitis.