Cholesteryl Ester Transfer Protein (CETP) Genetic Variation and Early Onset of Non‐Fatal Myocardial Infarction

Although Cholesteryl Ester Transfer Protein (CETP) mediates the transfer of cholesteryl esters and triglycerides between lipoprotein particles and thus plays a crucial role in reverse cholesterol transport, the association of variations in the CETP gene with acute myocardial infarction (MI) remains unclear. In this study we examined whether common genetic variation in the CETP gene is related to early‐onset non‐fatal MI risk in a population‐based case‐control study from western Washington State. Genotyping for the CETP ?2708 G/A, ?971 A/G, ?629 A/C, Intron‐I TaqI G/A and exon‐14 A/G (I405V) SNPs was performed in 578 cases with first acute non‐fatal MI and in 666 demographically similar controls, free of clinical cardiovascular disease, identified randomly from the community. In‐person interviews and non‐fasting blood specimens provided data on coronary heart disease risk factors. In men, there was little evidence for an association between single SNPs and MI risk, but in women the age‐ and race‐adjusted OR was found to be significant in 4 out of the 5 CETP single variants. Haplotype analysis revealed two haplotypes associated with MI risk among men. As compared to men homozygous for the most common haplotype D (?2708 G, ?971 G, ?629 C, TaqI G and exon‐14 A), the fully‐adjusted multiplicative model identified haplotype G (?2708 G, ?971 A, ?629 A, TaqI G and exon‐14 G) was associated with a 4.0‐6.0‐fold increased risk of MI for each additional copy; [95%CI 2.4–14.8] and haplotype B (?2708 G, ?971 G, ?629 A, TaqI A and exon‐14 A) showed a significant decreased risk for early onset MI [OR = 0.18; 95%CI 0.04 – 0.75]. An evolutionary‐based haplotype analysis indicated that the two haplotypes associated with the MI risk are most evolutionarily divergent from the other haplotypes. Variation at the CETP gene locus is associated with the risk of early‐onset non‐fatal MI. This association was found to be independent of HDL‐C levels. These data and the sex‐specific findings require confirmation in other populations.     

Adolescent and parent alliance and treatment outcome in multidimensional family therapy

In this study, the authors examined the relation between adolescent and parent therapeutic alliances and treatment outcome among 65 substance-abusing adolescents receiving multidimensional family therapy. Observer ratings of parent alliance predicted premature termination from treatment. Observer ratings, but not self-report, of adolescent alliance predicted adolescents' substance abuse and dependency symptoms at posttreatment, as well as days of cannabis use at 3-month follow-up. The association between adolescent alliance and substance abuse and dependency symptoms at posttreatment was moderated by the strength of the parent alliance. Results reveal the unique and interactive effects of the 2 alliances on treatment outcome and emphasize the need for a systemic and well-articulated approach to developing and maintaining the multiple alliances inherent to family therapy.     

Familial Mediterranean fever (FMF)-response to TNF-blockers used for treatment of FMF patients with concurrent inflammatory diseases

ObjectiveFamilial Mediterranean fever (FMF) is the most common interleukin 1 (IL-1)-driven monogenic autoinflammatory disease. Yet published data also suggest that tumor necrosis factor (TNF) may have a role in the pathogenesis of FMF and may serve as a target for treatment. In the present study we evaluate this hypothesis.MethodsTo this goal, we studied the incidental effect on FMF of TNF-directed treatment, administered to colchicine-refractory FMF patients for the management of a concurrent inflammatory disease. The rates of FMF patients and of treatments with complete or nearly complete FMF response were determined, based on the number of FMF attacks during TNF-blocker exposures. The possible effect of various FMF and non-FMF features on the outcome was determined using comparative analysis. Patients were identified and data were retrieved using electronic files from the FMF clinic.ResultsTwenty-six patients were identified, each receiving ≥ 1 of four TNF-blockers for a mean duration of 27.6 ± 16.4 months. The TNF-blockers were found to induce complete or nearly complete FMF response in 10 (38.5%) of the patients, and in 13 of 50 (26%) exposures. No clinical, genetic, demographic, or therapeutic feature could predict which FMF patient would respond favorably to TNF-blocker therapy.ConclusionThis study suggests that TNF-blockers may be beneficial for a small proportion of colchicine-resistant FMF patients.     

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.     

Elevated levels of antibody to myelin oligodendrocyte glycoprotein is not specific for patients with multiple sclerosis

OBJECTIVE: To evaluate the presence and specificity of anti-myelin oligodendrocyte glycoprotein (MOG) antibody in the cerebrospinal fluid and plasma of patients with multiple sclerosis (MS). DESIGN: Case-control study of patients with clinically definite MS compared with patients with other neurologic diseases (ONDs) of the central nervous system and control subjects. SETTING: Referral center in the Department of Neurology of Hadassah University Hospital, greater Jerusalem area, Israel. PARTICIPANTS: Consecutive cerebrospinal fluid samples from 31 patients with MS, 31 patients with ONDs, and 28 healthy controls; and plasma samples from 33 patients with MS, 28 patients with ONDs, and 31 healthy controls were taken from the cerebrospinal fluid and plasma bank of the Department of Neurology, Hadassah University Hospital. MAIN OUTCOME MEASURES: Levels and frequencies of anti-MOG antibody in patients with MS, as defined by enzyme-linked immunosorbent assay. RESULTS: Cerebrospinal fluid levels of antibodies to MOG and to myelin basic protein were significantly higher in patients with MS (P<.001 and P = .001, respectively) and patients with ONDs (P = .005 and P = .03, respectively) compared with controls; frequency of antibodies to MOG, but not to myelin basic protein, was higher in patients with MS and patients with ONDs (P = .01 and P = .003, respectively, for the frequency of anti-MOG antibody, and P = .65 and P = .41, respectively, for the frequency of anti-myelin basic protein antibody). Plasma levels of antibodies to MOG and to myelin basic protein were higher in patients with MS compared with patients with ONDs (P = .003 for both comparisons) and with controls (P = .03 and P = .04, respectively); however, the frequency of antibodies to MOG and myelin basic protein was similar in patients with MS, patients with ONDs (P=.54 and P = .82, respectively), and controls (P = .50 and P = .14, respectively). CONCLUSIONS: The elevated presence of anti-MOG antibody is not specific for MS because a similar appearance was also demonstrated in patients with ONDs. Therefore, it is not clear whether this antibody is pathogenic in MS or, on the contrary, has a defensive role against further immune-mediated damage after myelin breakdown.     

Developing interdisciplinary courses for allied health students: a retrospective view

Innovative interdisciplinary education in allied health has been developed in order to give students insight into role competencies of other professionals, improve the quality of health care while reducing costs, and facilitate the interdependent functioning of allied health care providers in meeting patient or client needs. The process of interdisciplinary course development requires the same communication and needs identification by faculty as is necessary for the provision of team care by practitioners. A retrospective account of interdisciplinary course development in a major health sciences center, together with materials developed for class presentation, may serve to encourage this type of activity elsewhere.