Suggestive evidence for association of two potassium channel genes with different idiopathic generalised epilepsy syndromes.

Several potassium channel genes have been implicated in epilepsy. We have investigated three such genes, KCNJ3, KCNJ6 and KCNQ2, by association studies using a broad sample of idiopathic generalised epilepsy (IGE) unselected by syndrome. One of the two single nucleotide polymorphisms (SNPs) examined in one of the inward rectifying potassium channel genes, KCNJ3, was associated with IGE by genotype (P=0.0097), while its association by allele was of borderline significance (P=0.051). Analysis of the different clinical subgroups within the IGE sample showed more significant association with the presence of absence seizures (P=0.0041) and which is still significant after correction for multiple testing. Neither SNP in the other rectifying potassium channel gene, KCNJ6, was associated with IGE or any subgroup. None of the three SNPs in the voltage-gated potassium channel gene, KCNQ2, was associated with IGE. However, one SNP was associated with epilepsy with generalised tonic clonic seizures only (P=0.016), as was an SNP approximately 56 kb distant in the closely linked nicotinic acetylcholine gene CHRNA4 (P=0.014). These two SNPs were not in linkage disequilibrium with each other, suggesting that if they are not true associations they have independently occurred by chance. Neither association remains significant after correcting for multiple testing.

Association of mu-opioid receptor subunit gene and idiopathic generalized epilepsy.

OBJECTIVE: To replicate and extend the previously reported association between the opioid receptor mu subunit gene (OPRM1) and idiopathic absence epilepsy (IAE), using a sample of 230 probands with idiopathic generalized epilepsy (IGE). BACKGROUND: In humans and in animal models, several lines of evidence implicate opioid receptors with seizures. The G118 allele of OPRM1 was associated with IAE (p = 0.019). METHODS: Three single nucleotide polymorphisms (SNP) of OPRM1 were investigated by association studies with IGE using a case/control design, one of which also used a within-family design. RESULTS: Association was found for G118 with IGE (p = 0.00027, odds ratio [OR] = 1.86), replicating the previous association. Within-family tests of linkage and association (haplotype-based haplotype relative risk and transmission disequilibrium test) confirmed this result. Further evidence for involvement of OPRM1 in IGE was provided by an association with G-172T, located in the 5' untranslated region (p = 0.0015, OR = 2.36). Haplotypes of the two SNPs were associated with IGE with a greater level of significance (p = 0.000087) suggesting that both SNPs might be in linkage disequilibrium with a single functional variant. Analysis of the results by subgroups of IGE showed association with all subgroups tested. CONCLUSIONS: These results confirm the previous association and support the hypothesis of a role for OPRM1 in IGE, including absence syndromes. However, the authors found no evidence for a specific association between OPRM1 and idiopathic absence epilepsy. The data suggest that the functional variant predisposing to IGE is located within 60kb of exon 1.

Current medicolegal and confidentiality issues in large, multicenter research programs.

The convenience of fast computers and the Internet have encouraged large collaborative research efforts by allowing transfers of data from multiple sites to a single data repository; however, standards for managing data security are needed to protect the confidentiality of participants. Through Dartmouth Medical School, in 1996-1998, the authors conducted a medicolegal analysis of federal laws, state statutes, and institutional policies in eight states and three different types of health care settings, which are part of a breast cancer surveillance consortium contributing data electronically to a centralized data repository. They learned that a variety of state and federal laws are available to protect confidentiality of professional and lay research participants. The strongest protection available is the Federal Certificate of Confidentiality, which supersedes state statutory protection, has been tested in court, and extends protection from forced disclosure (in litigation) to health care providers as well as patients. This paper describes the careful planning necessary to ensure adequate legal protection and data security, which must include a comprehensive understanding of state and federal protections applicable to medical research. Researchers must also develop rules or guidelines to ensure appropriate collection, use, and sharing of data. Finally, systems for the storage of both paper and electronic records must be as secure as possible.

Mortality among women with ductal carcinoma in situ of the breast in the population-based surveillance, epidemiology and end results program.

BACKGROUND: Over 14% of breast cancers diagnosed in the United States annually are ductal carcinomas in situ (DCIS). There are no published population-based reports of the likelihood of breast cancer death among US women with DCIS. METHODS: We used data from the Surveillance, Epidemiology and End Results program to determine the likelihood of breast cancer death at 5 and 10 years among US women aged 40 and older diagnosed with DCIS from 1978 to 1983 (before screening mammography was common; n = 1525) and from 1984 to 1989 (when screening mammography became common; n = 5547). We also calculated standardized mortality ratios (SMRs) to compare observed deaths from breast cancer, cardiovascular disease, and all causes combined among women with DCIS with deaths expected based on general population mortality rates. RESULTS: Among women diagnosed with DCIS from 1978 to 1983, 1.5% died of breast cancer within 5 years and 3.4% within 10 years. Among women diagnosed from 1984 to 1989, 0.7% died of breast cancer within 5 years and 1.9% within 10 years. Relative to the general population, risk of breast cancer death was greater for women diagnosed from 1978 to 1983 (SMR, 3.4; 95% confidence interval [CI], 2.5-4.5) than for women diagnosed from 1984 to 1989 (10-year SMR, 1.9; 95% CI, 1.5-2.3). Women diagnosed from 1984 to 1989 were significantly less likely than women in the general population to have died of cardiovascular diseases (10-year SMR, 0.6; 95% CI, 0.5-0.7) or of all causes combined (SMR, 0.8; 95% CI, 0.7-0.8). CONCLUSIONS: Among women diagnosed with DCIS, risk of death from breast cancer was low, at least within the 10 years following diagnosis. This may reflect the effectiveness of treatment for DCIS, the "benign" nature of DCIS, or both. At 10 years, women diagnosed from 1984 to 1989 were less likely than women diagnosed from 1978 to 1983 to have died of breast cancer, and their risk of dying of all causes combined was lower than that in the general population.

A comparison of two methods to teach smoking-cessation techniques to medical students.

PURPOSE: To evaluate two smoking-cessation practice exercises, one using standardized patients (SPs), the other using role playing by medical students. METHOD: In the spring of 1994 all 120 first-year University of California, San Francisco, School of Medicine Students were given lectures on the health effects of smoking and how physicians can help patients quit. Afterward some of the students were randomly assigned to two groups in which to practice counseling patients: Group 1 (n = 35) used SPs, Group 2 (n = 37) used role playing. Each of the Group 1 students practiced smoking-cessation techniques with an SP; the SP evaluated the student on cognitive and communication skills, assigned an overall rating, and provide feedback using a standardized form. The Group 2 students (as well as the 48 students not assigned to a group) role-played in pairs and used the same form to provide feedback. All the students evaluated their respective practice practices. Two weeks later 24 Group 1 and 31 Group 2 students participated in a clinic-skills-assessment exercise using SPs. As in the Group 1 practice exercise, each student was evaluated by an SP on cognitive and communication skills and assigned an overall rating. Data were analyzed through a number of statistical methods. The cost of the SP program was determined. RESULTS: The Group 1 students rated their practice exercise much more favorably than did the Group 2 students. However, there was no significant difference between the groups in their ratings by the SPs on the clinical-skills-assessment exercise. The use of SPs cost a great deal more than did the use of role playing. CONCLUSION: Although the students rated the SPs higher than they did the role playing, the two tools produced similar levels of skills attainment. The data suggest that having students practice smoking-cessation techniques through role playing may be as effective as using the more extensive SPs.

Family of origin genograms: evaluation of a teaching program for medical students.

BACKGROUND: The use of family genograms is an important component in family practice, yet little has been written about curriculum for teaching genograms in medical school. Since 1981, the Department of Family and Community Medicine at the University of California, San Francisco, has conducted a behavioral science seminar for fourth-year students on their required 8-week ambulatory care clerkship. At one site, this seminar includes presentation of the students' personal genograms. This report describes the curriculum and a study to determine whether students understood genograms or used them in clinical settings. METHODS: We compared students' perceptions of the usefulness of genograms and genogram documentation in new patient assessments. Students at two sites were given pre- and postclerkship questionnaires, and a random sample of charts was reviewed for documentation of genograms. RESULTS: Students in the genogram demonstration group increased significantly in their stated use of genograms. Surprisingly, the group of students not exposed to the genogram curriculum were more likely to have genograms with more details recorded in the patients' charts. CONCLUSION: These results imply that there were initial differences in the two groups and that didactic teaching must be complemented with clinical supervision. Also, the results have implications for specific areas in need of faculty development.

A Caribbean diet for the management of renal failure

Dietary management is recognized as being cardinal for the conservative management of chronic renal failure. Special proprietary dietitic foods are not widely used because they may be costly, not available nor culturally acceptable. In the absence of data about the chemical composition of foods, the dietary management of renal failure is beset with difficulties. We set out to devise a therapeutic diet based upon locally available, relatively cheap and culturally acceptable foods, to fulfill the accepted goals of low protein 24 - 27 gm/d, high energy, 2,691 - 2,879, kcals/d, low sodium, 14 - 16mEq/d and low potassium, 26 - 35mEq/d. To do this, 75 raw, prepared and cooked foods were analysed for nitrogen, gross energy, sodium and potassium contents. Of the 31 recipes devised or modified, 16 were adjudged palatable by taste panels. Using the results of the chemical analyses and the recipes developed, we devised meal plans which met the therapeutic goals. Proteins of high biological value, eggs and milk, contributed 71 - 78 percent of the total daily allowance. (AU)