HLA-DQB1*0602 homozygosity increases relative risk for narcolepsy but not disease severity in two ethnic groups

Abstract: Narcolepsy is a neurological disorder known to be tightly associated with HLA-DQA1*0102 and DQB1*0602. In this study, we have examined if homozygosity for DQB1*0602 increases disease susceptibility and/ or severity. Patients diagnosed at Stanford University ( n =160) or enrolled in a multicenter clinical trial ( n =509) were included in this analysis. In both African-Americans and Caucasian-Americans with or without cataplexy, a significantly higher than expected number of subjects were DQB1*0602 homozygotes. Relative risks were 2–4 times higher in DQB1*0602 homozy-gotes vs heterozygotes across all patient groups. In contrast, symptom severity did not differ between DQB1*0602 homozygous and heterozygous subjects. These results indicate that HLA-DQB1*0602 homozygosity increases susceptibility to narcolepsy but does not appear to influence disease severity.     

Increased levels of hyaluronan and albumin after intestinal challenge in adult patients with cow's milk intolerance

Background The mechanisms for adverse reactions to foods in the gastrointestinal tract are poorly understood. Presently, only hmited possibilities are available for identification of adverse immunological reactions to different foods.
Objective The intestinal inflammatory reactions in adult patients with a history of milk-related gastrointestinal symptoms were studied after intestinal challenges by a jejunal perfusion technique and compared with the reactions in a control group. Methods Five skin-prick test and radioallergosorbent test negative and lactose tolerant patients with a history of milk-related gastrointestinal symptoms, verified by double-blind placebo-controlled challenge, and eight healthy controls were investigated. Perfusions were performed allowing analyses of a well-defined 'closed' jejunal segment. Milk perfusions were performed in patients and controls after an overnight fast. Ten millilitres of milk were administered to the segment at 3 mL/min, The jejunal fluid levels of hyaluronan (hyaluronic acid) and albumin were measured.
Results In the five patients the milk challenges induced as a mean fivefold increased levels of hyaluronan compared with prcstitnulation values, whereas no such increases were seen in the control subjects. Albumin, as a marker of plasma leakage, was also increased in the patients but not in the control subjects.
Conclusion The underlying mechanisms for locally increased levels of hyaluronan and also albutnin in the intestinal lumen may be secretion of lymph rich in hyaluronan and reflect the mucosal oedetna. This capacity of the intestinal mucosa to react with lymph leakage towards a locally infused allergen may be a possible way lo delineate gastrointestinal reactions in food-related disorders.     

Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology

In the United States, colorectal cancer (CRC) is the third most common cancer diagnosed among men and women and the second leading cause of death from cancer. CRC largely can be prevented by the detection and removal of adenomatous polyps, and survival is significantly better when CRC is diagnosed while still localized. In 2006 to 2007, the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology came together to develop consensus guidelines for the detection of adenomatous polyps and CRC in asymptomatic average-risk adults. In this update of each organization's guidelines, screening tests are grouped into those that primarily detect cancer early and those that can detect cancer early and also can detect adenomatous polyps, thus providing a greater potential for prevention through polypectomy. When possible, clinicians should make patients aware of the full range of screening options, but at a minimum they should be prepared to offer patients a choice between a screening test that primarily is effective at early cancer detection and a screening test that is effective at both early cancer detection and cancer prevention through the detection and removal of polyps. It is the strong opinion of these 3 organizations that colon cancer prevention should be the primary goal of screening.     

Results of a phase II multicenter trial of weekly docetaxel and gemcitabine as first-line therapy for patients with advanced non-small cell lung cancer

PURPOSE: Standard treatment for advanced non-small cell lung cancer (NSCLC) consists of platinum based combination chemotherapy but efficacy is limited and treatment can be toxic. This trial evaluated a weekly regimen of docetaxel and gemcitabine for advanced NSCLC. The primary endpoint was objective response rate. Other endpoints were 1-year survival, median survival, median duration of response, median disease-free progression, safety, and quality of life. PATIENTS AND METHODS: Fifty patients with advanced NSCLC were treated. Patients received docetaxel (1 per week, 36 mg/m(2)) weeks 1-6 and gemcitabine (1 per week, 900 mg/m(2)) weeks 1, 2, 4, and 5. Each 8-week cycle was repeated for a total of three cycles. Patients completed quality of life surveys (FACT-L) before each cycle. RESULTS: The median age was 68.5 years; 74% were >60 years old. In the intent-to-treat (ITT) analysis of response, 10 patients had a partial response (20%) and five patients had stable disease (10%). The 1-year survival was 32%; median survival for all patients was 6.9 months (range, <1-26.2) and the median progression-free survival was 5.1 months (range, <1-25.5). Toxicities (> grade 3) included neutropenia, thrombocytopenia, GI disorders (nausea, vomiting, dehydration, diarrhea, stomach pain), and asthenia; 10 patients experienced hematological toxicities that were > grade 3. Quality of life decreased during the study. CONCLUSIONS: This study demonstrated that the nonplatinum doublet (docetaxel + gemcitabine) given on a weekly schedule for advanced NSCLC had efficacy similar to that reported with other regimens and was well tolerated. Therefore, this non-platinum based regimen appears promising and warrants further evaluation.     

Clonality of Streptococcus pneumoniae serotype 1 isolates from pediatric patients in the United States

We compared Streptococcus pneumoniae serotype 1 isolates causing disease among children in six geographic regions of the United States to determine genetic relatedness. Genomic fingerprints were determined by repetitive element polymorphism PCR (Rep-PCR). Multilocus sequence type characterization was performed on selected isolates. Four different genomic banding patterns were identified by Rep-PCR. One profile (clone 1) was predominant and matched sequence type 227.     

The HLA Dictionary 2004: a summary of HLA-A, -B, -C, -DRB1/3/4/5 and -DQB1 alleles and their association with serologically defined HLA-A, -B, -C, -DR and -DQ antigens

This report presents serologic equivalents of human leucocyte antigen (HLA)-A, -B, -C, -DRB1, -DRB3, -DRB4, -DRB5 and -DQB1 alleles. The dictionary is an update of the one published in 2001. The data summarize equivalents obtained by the World Health Organization Nomenclature Committee for factors of the HLA System, the International Cell Exchange, the National Marrow Donor Program, recent publications and individual laboratories. This latest update of the dictionary is enhanced by the inclusion of results from studies performed during the 13th International Histocompatibility Workshop and from neural network analyses. A summary of the data as recommended serologic equivalents is presented as expert assigned types. The tables include remarks for alleles, which are or may be expressed as antigens with serologic reaction patterns that differ from the well-established HLA specificities. The equivalents provided will be useful in guiding searches for unrelated hematopoietic stem cell donors in which patients and/or potential donors are typed by either serology or DNA-based methods. The serological DNA equivalent dictionary will also aid in typing and matching procedures for organ transplant programs whose waiting lists of potential donors and recipients comprise of mixtures of serologic and DNA-based typings. The tables with HLA equivalents and a questionnaire for submission of serologic reaction patterns for poorly identified allelic products will be made available through the WMDA web page: www.worldmarrow.org. and in the near future also in a searchable form on the IMGT/HLA database.     

Which information locations in covered entities under HIPAA must be secured first? A multi-criteria decision-making approach

Creating adequate safeguards for physical and online locations (e.g., desktop computers, network servers) where protected health information (PHI) may be breached is critical for management within entities compliant with the Health Information Portability and Accountability Act (HIPAA). With the increasing complexity of cyber breaches and budgetary issues, prioritizing which locations require the most immediate attention by top management through a data-driven model is more important than ever. Using CORAS threat modeling and five methods for multi-criteria decision-making, these locations were ranked from greatest to least risk of data breaches. Statistical methods were subsequently used for consistency and robustness checks. The findings illustrate that each type of covered entity under HIPAA must prioritize a different set of locations to safeguard first: health care providers must focus on the security of network servers, other portable electronic devices, and category of others (i.e., miscellaneous locations); health plans must focus on the security of paper and films, network servers, and others; and business associates must focus on the security of category of others, network servers, and other portable electronic devices. Combined with data on the source of the breaches (external vs. internal) and type of threats (e.g., hacking, theft), these findings provide recommendations for risk identification for privacy officers across health care.