Evidence for the genetic role of human leukocyte antigens in low frequency DRB1*1501 multiple sclerosis patients in Israel

A strong association exists between multiple sclerosis (MS) and the DRB1*1501 haplotype, in most populations. Linkage of Multiple Sclerosis (MS) with the MHC or HLA region on chromosome 6p21 has previously been observed in DRB1*1501 positive MS families. A group of 13 Israeli multiplex MS families with a very low frequency of DRB1*1501 haplotype were examined in this study. Association and a linkage test were performed in order to identify a non-DRB1*1501 effect of HLA on susceptibility for MS. MS multiplex families and healthy controls were molecularly typed for six highly polymorphic markers located within the MHC region: DRB1, DQA1 and DQB1, BAT-2, MIB and D6S248. Data analyses included: (a) an association study comparing the patient group with both healthy relative, and healthy control groups (b) a transmission test for linkage disequilibrium (TDT) of the MS-associated alleles in the multiplex families, and (c) multipoint non-parametric linkage (NPL) and parametric LOD score analyses using the GENEHUNTER program. The DRB1*1303 allele was significantly more frequent among the MS patients. There was a trend towards transmission disequilibrium of DRB1*1303, but was not statistically significant. Allele sharing and LOD score analyses revealed no evidence for linkage. The high frequency of DRB1*1303 observed in our family patients provides evidence to support the association with this allele that previously described in sporadic non-Ashkenazi MS patients. Thus, DRB1*1303 may serve as genetic risk factor for MS. Our study exemplifies the genetic heterogeneity in MS as there is a genetic effect of HLA on MS susceptibility in our low frequency DRB1*1501 patients.     

Immunogenicity of peptides derived from a fibronectin-binding protein of S. aureus expressed on two different plant viruses

The D2 peptide derived from an S. aureus fibronectin-binding protein (FnBP) was expressed on the surface of the icosahedral cowpea mosaic virus (amino acids 1-30 of D2) or on the rod-shaped potato virus X (amino acids 1-38 of D2), termed CPMV-MAST1 and PVX-MAST8, respectively. Mice and rats were immunized subcutaneously with CPMV-MAST1 and mice with PVX-MAST8 in adjuvant and high titres of FnBP-specific antibody were obtained. The mouse IgG was predominantly of the IgG2a and IgG2b isotypes, which strongly bound complement component C1q, suggesting a TH1-bias in the peptide-specific responses. Sera from mice and rats immunized with CPMV-MAST1 and from mice immunized with PVX-MAST8 were shown to completely inhibit the binding of fibronectin to immobilised recombinant FnBP and rat sera against CPMV-MAST1 were able to block adherence of S. aureus to fibronectin. These studies demonstrate that the D2 peptide is highly immunogenic when expressed on 2 different plant viruses and highlight the potential of plant virus-based vaccines to protect against S. aureus infections.     

Time preferences and preventive health behavior: acceptance of the influenza vaccine.

BACKGROUND: Many preventive health behaviors involve immediate costs and delayed benefits. Time preference is the extent to which decision makers value future outcomes relative to immediate ones. Consequently, people with future-oriented time preferences should be more likely to adopt preventive measures. The relationship between time preferences and acceptance of a free influenza vaccination was examined. SAMPLE: The participants were 412 corporate employees who were offered free influenza vaccinations at their workplace. MEASURES: Participants' time preferences were measured in each of two domains: money and health. They also reported on whether they had accepted the influenza vaccination and their beliefs and attitudes about the vaccine. RESULTS: There was a small (OR = 2.38) relationship of vaccination acceptance to monetary time preferences but not to the health time-preference measures. Other variables, such as perceived effectiveness of the vaccine, were more predictive. CONCLUSION: This study provides some evidence of a small relationship between time preferences and preventive health behavior.     

Are more options always better? The attraction effect in physicians' decisions about medications.

Consumer choice research has shown that, contrary to normative theory, the introduction of an inferior alternative to an existing choice set can increase the likelihood that one of the original alternatives will be chosen. This phenomenon, the attraction effect, is relevant to physician decision making, particularly when the physician is in the role of a consumer who must make decisions about prescribing medications when a number of alternatives are available. To investigate the attraction effect in physician decision making, 40 internal medicine residents reviewed three patient cases (concerning depression, sinusitis, and vaginitis) and then chose the most appropriate medication for each patient. In some versions of the cases, two medication options were available. Other versions included a third medication (the decoy) that was inferior in every way to one of the original options (the target) but not to the other (the competitor). The results showed that addition of the "decoy" medication increased the likelihood of choosing the target medication. That is, the attraction effect does occur in physicians' decisions about medications. Physicians should be aware of this bias when evaluating or suggesting several similarly attractive medications or treatment options for the same medical condition.     

A randomized trial of 72- versus 24-hour intravenous tubing set changes in newborns receiving lipid therapy.

OBJECTIVE: To compare the microbial contamination rate of infusate in the intravenous tubing of newborns receiving lipid therapy, replacing the intravenous delivery system at 72-hour versus 24-hour intervals. DESIGN: Infants requiring intravenous lipid therapy were randomly assigned to have intravenous sets changed on a 72- or a 24-hour schedule, in a 3:1 ratio, in order to compare the infusate contamination rates in an equivalent number of tubing sets. SETTING: A 35-bed, teaching, referral, neonatal intensive-care unit (NICU). PARTICIPANTS: All neonates admitted to the NICU for whom intravenous lipid was ordered. METHODS: Patients were randomized in pharmacy, on receipt of the order for intravenous lipid therapy, to either 72- or 24-hour administration set changes, and followed until 1 week after discontinuation of lipids or discharge from the NICU. Microbial contamination of the infusate was assessed in both groups at the time of administration set changes. Contamination rates were analyzed separately for the lipid and amino acid-glucose tubing sets. Patient charts were reviewed for clinical and epidemiological data, including birth weight, gestational age, gender, age at start of lipid therapy, duration of parenteral nutrition, and type of intravenous access. RESULTS: During the study period, 1,101 and 1,112 sets were sampled in the 72- and 24-hour groups, respectively. Microbial contamination rates were higher in the 72-hour group than the 24-hour group for lipid infusions (39/1,101 [3.54%] vs 15/1,112 [1.35%]; P=.001) and for amino acid infusions (12/1,093 [1.10%] vs 4/1,103 [0.36%]; P=.076). Logistic regression analysis controlling for birth weight, gestational age, and type of venous access showed that only the tubing change interval was significantly associated with lipid set contaminations (odds ratio, 2.69; P=.0013). The rate of blood cultures ordered was higher in the 72- versus the 24-hour group (6.11 vs 4.99 per 100 patient days of total parenteral nutrition; P=.017), and a higher proportion of infants randomized to the 72-hour group died (8% vs 4%; P=.05), although the excess deaths could not clearly be attributed to bacteremia. CONCLUSION: Microbial contamination of infusion sets is significantly more frequent with 72- than with 24-hour set changes in neonates receiving lipid solutions. This may be associated with an increased mortality rate.     

Effects of vitamin D3 metabolites on bone cell calcium transport

Summary The vitamin D₃ metabolite, 25-hydroxycholecalciferol, at concentrations of 0.01 to 10.0 g/ml, decreased calcium uptake by isolated bone cells. The effect occurred within 1 min after the simultaneous addition of metabolite and⁴⁵Ca. Lactic acid and ATP production by the cells was not affected. 24(R), 25-dihydroxycholecalciferol produced a similar decrease in calcium uptake. Vitamin D₃ had no effect at concentrations from 0.01 to 10.0 g/ml. No effect of 1,25-dihydroxycholecalciferol on calcium uptake was observed with concentrations from 0.1 to 100 ng/ml and various preincubation periods extending to 2 h. None of the agents had any effect on calcium efflux. The effects of 25-hydroxycholecalciferol and 24(R), 25-dihydroxycholecalciferol on calcium uptake were not seen in isolated fetal rat skin cell preparations.     

Quality assurance in a children's psychiatric hospital

The use of short-term isolation (STI) in a children's psychiatric hospital was examined using the Joint Commission on Accreditation of Hospitals (JCAH) quality assurance mode. A Clinical Care Evaluation addressed two questions: Are we providing quality use of STI? And are we adequately documenting its use? A medical record audit of 78 discharged patients and a review of unit records provided hospital staff with utilization and demographic statistics; structured interviews with staff and inpatients were conducted that provided information about their opinions of STI. The data gathered served as the basis for recommendations that led to planned, informed program changes.     

It's better by day

Day surgery has had a slow record f growth in the UK, despite the benefits it offers. Robert Chapman explains the advantages of planning a dedicated unit.