Laminin alpha2 muscular dystrophy: genotype/phenotype studies of 22 patients.

OBJECTIVE: To determine the number of primary laminin alpha2 gene mutations and to conduct genotype/phenotype correlation in a cohort of laminin alpha2-deficient congenital muscular dystrophy patients. BACKGROUND: Congenital muscular dystrophies (CMD) are a heterogeneous group of muscle disorders characterized by early onset muscular dystrophy and a variable involvement of the CNS. Laminin alpha2 deficiency has been reported in about 40 to 50% of cases of the occidental, classic type of CMD. Laminin alpha2 is a muscle specific isoform of laminin localized to the basal lamina of muscle fibers, where it is thought to interact with myofiber membrane receptor, such as integrins, and possibly dystrophin-associated glycoproteins. METHODS: Seventy-five CMD patients were tested for laminin alpha2 expression by immunofluorescence and immunoblot. The entire 10 kb laminin alpha2 coding sequence of 22 completely laminin alpha2-deficient patients was screened for causative mutations by reverse transcription (RT)-PCR/single strand conformational polymorphisms (SSCP) analysis and protein truncation test (PTT) analysis followed by automatic sequencing of patient cDNA. Clinical data from the laminin alpha2-deficient patients were collected. RESULTS: Thirty laminin alpha2-negative patients were identified (40% of CMD patients tested) and 22 of them were screened for laminin alpha2 mutations. Clinical features of laminin alpha2-deficient patients were similar, with severe floppiness at birth, delay in achievement of motor milestones, and MRI findings of white matter changes with normal intelligence. Loss-of-function mutations were identified in 95% (21/22) of the patients studied. SSCP analysis detected laminin alpha2 gene mutations in about 50% of the mutant chromosomes; PTT successfully identified 75% of the mutations. A two base pair deletion mutation at position 2,096-2,097 bp was present in 23% of the patients analyzed. CONCLUSIONS: Our data suggest that the large majority of laminin alpha2-deficient patients show laminin alpha2 gene mutations.

Paternal exposures and the question of birth defects.

Compared to maternal exposures, little attention has been paid to the possibility of paternally induced adverse effects on fetal development. There is increasing concern, however, about the potential for male-mediated developmental toxicity brought about by exposure to teratogenic agents. This is evidenced by the number of calls regarding paternal exposures that are received by teratogen information services. In this paper, we report the experience of the state of Florida's Teratogen Information Services regarding questions asked about paternal exposures, and briefly review what is known about the risk of paternal exposure to the 10 agents which are most frequently queried.

Congenital muscular dystrophy with primary laminin alpha2 (merosin) deficiency presenting as inflammatory myopathy.

Ten laminin alpha2-deficient patients were identified by both immunofluorescence and immunoblotting (30% of congenital muscular dystrophy patients tested). Three of the laminin alpha2-deficient patients were carrying a diagnosis of infantile polymyositis prior to immunostaining studies. The clinical features in the 10 merosin-deficient patients were homogeneous, with severe floppiness at birth, delay in achievement of motor milestones, and magnetic resonance imaging findings of white matter changes with normal intelligence. The 10-kb laminin alpha2-coding sequence was screened for causative mutations by reverse transcriptase-polymerase chain reaction/single-stranded conformational polymorphism analysis in muscle biopsy specimens from 5 patients, followed by automatic sequencing of aberrant conformers. Clear loss-of-function deletion mutations were identified in both alleles of 1 patient. Muscle histopathology in this patient showed a striking inflammatory infiltrate of T cells and B cells. Reexamination of biopsy specimens from other laminin alpha2-deficient patients showed minor signs of inflammation in each. Based on these findings and the histological and clinical picture suggesting failure of muscle regeneration, a pathogenesis model for this major subset of congenital muscular dystrophy is proposed. Our data show that muscle histopathology showing a neonatal inflammatory process should be considered consistent with congenital muscular dystrophy.

Addictive behavior of older adults.

Very little is known about addictive alcohol use by older people. In the present paper personal effects reasons for drinking (i.e. drinking for the effects of alcohol) and concerns about drinking were used as indicators of addictive drinking behavior among a sample of 826 people aged 65 and older who participated in survey interviews in their homes. The relationship of addictive drinking behavior to frequency of drinking, quantity of drinks per occasion, and depressant drug use was examined. Alcohol use was higher among males and young-old (aged 65-74), while depressant medication use was higher among females and old-old (aged 75+). However, with the exception of use of over-the-counter medications containing codeine (which was significantly higher among current drinkers), no relationship existed between alcohol use and use of depressant medications. Personal effects reasons for drinking and concerns about drinking were related both to alcohol and depressant medication use. Frequency of drinking was associated with higher endorsement of both personal effects and social reasons, whereas volume of alcohol consumption (drinks per drinking day) was associated only with personal effects drinking. In addition, use of depressant medications by drinkers was significantly related to consuming alcohol for personal effects reasons (but unrelated to consuming for social reasons) and with having concerns about one's own drinking. These results suggest that even within the generally low levels of alcohol consumption of older people, addictive-use patterns emerge. In addition, the results confirm the importance of including depressant medication use in evaluating the drinking behavior of older people.

The purpose of health fairs as perceived by university-based health educators.

The purpose of this study was to assess the attitudes of university-based health educators on the role of health fairs. Ninety-nine health educators from throughout the country completed a three-part survey requesting information regarding local health fairs, demographics of the respondent, and a series of Likert-type questions regarding the role and function of health fairs. Results indicate that one's level of training and level of involvement played a significant role in determining attitudes regarding the purpose of health fairs. Health educators with doctoral training, when compared to individuals with master's-level training, were less likely to approve of health fairs.

The status of health fairs: perspectives from the health education profession.

This study examined the current status of health fairs throughout the United States. Surveys were sent to all program heads of University Health Education Departments identified in the Eta Sigma Gamma Directory 1985. Information such as number of participating agencies, location of health fairs, and the goals of the health fairs was requested. The results identified 89 health fairs. The majority were held in shopping malls (57%), with schools hosting approximately 21%. The average number of participants consisted of 31 agencies, and the average number of individuals from the community attending the fair was 3000. The average length of health fairs was 1.5 days, with over 88% of identified fairs being held annually. Providing accurate health information and health screenings were ranked as the most important goals for health fairs. Health educators need to become involved with health fairs if such goals are to be realized.

Alcohol education in schools: toward a lifestyle risk-reduction approach.

This article calls for a refocusing of alcohol education to facilitate the adoption of low-risk lifestyle choices regarding decisions about abstinence and quantity and frequency of alcohol use. Five goals are presented as a focal point for lifestyle risk-reduction education about alcohol. It is essential that research and education activities become more focused on the link between the quantity-frequency of alcohol use and alcohol-related problems, and on the information and attitudes that support low-risk versus high-risk A/Q/F choices.