Homozygosity mapping of achromatopsia to chromosome 2 using DNA pooling

Achromatopsia is an autosomal recessive disease of the retina, characterized clinically by an inability to distinguish colors, impaired visual acuity, nystagmus and photophobia. A genome-wide search for linkage was performed using an inbred Jewish kindred from Iran. To facilitate the genome-wide search, we utilized a DNA pooling strategy which takes advantage of the likelihood that the disease in this inbred kindred is inherited by all affected individuals from a common founder. Equal molar amounts of DNA from all affected individuals were pooled and used as the PCR template for short tandem repeat polymorphic markers (STRPs). Pooled DNA from unaffected members of the kindred was used as a control. A reduction in the number of alleles in the affected versus control pool was observed at several loci. Upon genotyping of individual family members, significant linkage was established between the disease phenotype and markers localized on chromosome 2. The highest LOD score observed was 5.4 (theta = 0). When four additional small unrelated families were genotyped, the combined peak LOD score was 8.2. Analysis of recombinant chromosomes revealed that the disease gene lies within a 30 cM interval which spans the centromere. Additional fine-mapping studies identified a region of homozygosity in all affected individuals, narrowing the region to 14 cM. A candidate gene for achromatopsia was excluded from this disease interval by radiation hybrid mapping. Linkage of achromatopsia to chromosome 2 is an essential first step in the identification of the disease-causing gene.      

Hospitals: to the next millennium

Hospitals are changing. Throughout the OECD the hospital, that enduring and pervasive organization which has delivered the vast majority of acute care services for decades, is being reconceptualized. We briefly analyse trends which clearly indicate that the existing concept of the hospital is rapidly coming to an end. The emerging model consists of a core facility comprising only the most acute services, intensive care, operating theatres and an accident and emergency unit, with all other services and units linked by information technology to each other and to the core facility. We explore some of the management challenges confronting those who will be responsible for taking their organization through the transition to the boundaryless hospital arrangement, discuss a number of the existing problems with today's hospitals which the new model has the propensity to resolve, and deal with some of the emerging issues which it brings with it.     

The efficacy of the ketogenic diet-1998: a prospective evaluation of intervention in 150 children

OBJECTIVE: The ketogenic diet is a high-fat, low-protein, low-carbohydrate diet developed in the 1920s for the treatment of children with difficult to control seizures. Despite advances in both the pharmacotherapy and the surgery of epilepsy, many children continue to have difficult-to-control seizures. This prospective study sought to determine the ketogenic diet's effectiveness and tolerability in children refractory to today's medications. METHODS: One hundred fifty consecutive children, ages 1 to 16 years, virtually all of whom continued to have more than two seizures per week despite adequate therapy with at least two anticonvulsant medications, were prospectively enrolled in this study, treated with the ketogenic diet, and followed for a minimum of 1 year. Seizure frequency was tabulated from patients' daily seizure calendars and seizure reduction calculated as percentage of baseline frequency. Adverse events and reasons for diet discontinuation were recorded. RESULTS: The children (mean age, 5.3 years), averaged 410 seizures per month before the diet, despite an exposure to a mean of 6.2 antiepileptic medications. Three months after diet initiation, 83% of those starting remained on the diet and 34% had >90% decrease in seizures. At 6 months, 71% still remained on the diet and 32% had a >90% decrease in seizures. At 1 year, 55% remained on the diet and 27% had a >90% decrease in seizure frequency. Most of those discontinuing the diet did so because it was either insufficiently effective or too restrictive. Seven percent stopped because of intercurrent illness. CONCLUSIONS: The ketogenic diet should be considered as alternative therapy for children with difficult-to-control seizures. It is more effective than many of the new anticonvulsant medications and is well tolerated by children and families when it is effective.     

In vivo expression of the B7 costimulatory molecule by subsets of antigen-presenting cells and the malignant cells of Hodgkin's disease

The B-lymphocyte/accessory-cell activation antigen B7 (BB1) has been shown in vitro to stimulate T-lymphocyte proliferation and cytokine production via CD28 present on the latter cells. In this study, benign lymphoid tissues, lymphomas, and extralymphoid inflammatory sites were examined immunohistochemically using anti-B7 and other relevant monoclonal antibodies. B7 was expressed by benign transformed germinal center B cells, as it was by B cells of follicular lymphomas. B7 was also expressed by a subpopulation (a mean of 31% to 65%) of macrophages and dendritic cells in a variety of lymphoid tissues. It was present in abundance on all macrophages constituting sarcoid granulomas in lymph nodes. In extralymphoid inflammation, 17% to 35% of macrophages expressed B7 only weakly. Cases of Hodgkin's disease showed expression of B7 by the majority of Reed-Sternberg cells or malignant mononuclear variants, a phenomenon that potentially contributes to the lymphocytic accumulation that is a feature of this condition. CD28+ T cells were seen in all areas where T cells were present. B7+ and CD28+ cells colocalized in, for example, lymphoid follicles, lymph node paracortex, sarcoid granulomas, and Hodgkin's disease tissue, indicating a potential for cellular interaction via these molecules at these sites.     

Educator's Learning Alignment Instrument (ELAI):: A tool to assess aligned learning concepts within college courses

ObjectiveTo report the development and initial testing of a questionnaire designed to assess the concept of learning alignment within chiropractic college courses.MethodsA 36-item questionnaire, Educator''s Learning Alignment Instrument (ELAI), was created to evaluate how learning goals, course activities, and assessments align within a college course. Questionnaire development was informed by learning theories and tested using a 2-phased electronic survey mechanism among a chiropractic college faculty. Phase 1 included completing the ELAI for a currently implemented course. Phase 2 included questions about confidential reports generated from ELAI data.ResultsThirty-one of 46 (67%) respondents completed an ELAI. Twelve (38%) participated in phase 2. Twenty-one (68%) courses demonstrated consistent learning focus across goals, activities, and assessments. Aggregate data from early, middle, and late chiropractic program courses revealed progressive shifts toward higher-level learning. Eighty-seven percent of courses contained 1 or more individual learning areas with potentially misaligned goals, activities, or assessment. Ninety-seven percent of respondents completed ELAI questions within 20 minutes. Most (87%) phase 2 respondents noted the report accurately reflected the course. Sixty-seven percent of phase 2 respondents agreed that confidential reports provided useful information to inform course design.ConclusionThe ELAI is a nonburdensome instrument that can facilitate faculty reflection on how aligned learning concepts are applied in a course and provide novel data to assess general learning focus within college courses and within programs. Results indicate ELAI questions can be revised to improve clarity. Additional research comparing ELAI responses from experts, peer educators, and students is recommended.