DNA testing for fragile X syndrome in schools for learning difficulties

Fragile X syndrome is the most common inherited cause of mental retardation. Early diagnosis is important not only for appropriate management of individuals but also to identify carriers who are unaware of their high risk of having an affected child. The disorder is associated with a cytogenetically visible fragile site (FRAXA) at Xq27.3, caused by amplification of a (CGG)n repeat sequence within the gene at this locus designated FMR1. Clinical and molecular studies have been undertaken to screen for fragile X syndrome in 154 children with moderate and severe learning difficulties of previously unknown origin. Southern blot analysis of peripheral blood showed the characteristic abnormally large (CGG)n repeat sequence associated with fragile X syndrome in four of the 154 children. The findings were confirmed by cytogenetic observation of the fragile site and by further molecular studies. The families of the affected children were offered genetic counselling and DNA tests to determine their carrier status. These findings show that there are still unrecognised cases of fragile X syndrome. Given the difficulty of making a clinical diagnosis and the implications for families when the diagnosis is missed, screening in high risk populations may be justified. The issues involved in screening all children in special schools for fragile X syndrome are discussed.     

Does age at the start of breast feeding influence infantile diarrhoea morbidity? A case–control study in periurban Guinea–Bissau

Colostrum protects the newborn from intestinal infection by its content of secretory immunoglobulin A and other immediately acting factors. It may also induce maturation of the child's gastrointestinal immune defences, thus contributing to the protection against diarrhoeal disease later in infancy. To test this hypothesis, a case–control study on breast feeding and diarrhoea was carried out in a periurban community in Guinea–Bissau. The child's age at the start of breast feeding was ascertained soon after birth ( n = 279). Subsequent cases of acute diarrhoea ( n = 66) were identified at 3–monthly examinations, and four concurrent controls were randomly selected among attendants. Three separate estimates of association showed that the cases tended to have started breast feeding later after birth than the diarrhoea–free controls, but no single test was statistically significant. Early breast feeding might have consequences for diarrhoeal morbidity after the neonatal period.     

Quality of life after lobectomy for adult liver transplantation

INTRODUCTION: Adult-to-adult living donor liver transplants are being increasingly performed. Although considerable data are available on the quality of life after kidney donation, there is little comparable information on liver donors. METHODS: Between August 1998 and July 2000, 48 adults received liver grafts from living donors. At least 2 months after donation, donors were mailed a structured questionnaire and the standardized Medical Outcomes Study Short-Form Health Survey (SF-36), a generic measure assessing health-related quality of life outcomes using eight scales: mental health, emotional limits, vitality, social function, physical function, physical limits, pain, general health. RESULTS: Thirty donors (62.5%) responded at a mean of 280+/-157 days after donation. Fifteen (50%) of their recipients had major complications (two deaths, four retransplants, nine biliary complications). Regarding overall satisfaction, all said they would donate again. Compared to published U.S. norms (n=2474), our group of donors scored higher than the general population in seven of eight domains on the SF-36. Donors whose recipients had no complications scored significantly higher in mental health (P<0.007) and general health (P<0.008) compared with U.S. norms. Donors whose recipients had major complications scored significantly lower on the mental health scale than those with recipients without major complications. CONCLUSIONS: Donors did not regret their decision to donate; several felt the experience had changed their lives for the better. Donors scored as well as or better than U.S. norms in general health. Quality of life after donation must remain a primary outcome measure when we consider the utility of living-donor liver transplants.     

Avoiding the boomerang: testing the relative effectiveness of antidrug public service announcements before a national campaign

OBJECTIVES: This study examined the relative perceived effectiveness of 30 antidrug public service announcements (PSAs) and assessed the extent to which judgments of effectiveness are related to judgments of realism, amount learned, and positive and negative emotional responses. METHODS: Data were obtained from 3608 students in grades 5 through 12 in 10 schools. The ethnically diverse sample was 50.8% male. Students in 5 experimental conditions viewed sets of 6 antidrug PSAs and filled out a brief evaluation questionnaire following each PSA. Those in the control condition viewed a non-drug-related television program. RESULTS: The relative perceived effectiveness of the 30 PSAs varied considerably. Sixteen were rated as significantly more effective, and 6 as significantly less effective, than the control program. Relative rated effectiveness was highly related to realism (r =.87), amount learned (r =.88), negative emotion (r =.87), and positive emotion (r = -.35). CONCLUSIONS: Evaluative research is necessary to prevent broadcast of PSAs that could have a negative impact. PSAs should point out the negative consequences of drug use behavior rather than telling adolescents to "just say no."     

Job satisfaction and job success as moderators of the self-esteem of people with mental illnesses

This study investigated job satisfaction and job success as moderators of the self-esteem of people with mental illnesses. Prior studies and models had produced contradictory findings so that the appropriateness of self-esteem as an outcome variable for psychiatric rehabilitation employment services was in doubt. Job satisfaction and success measures for 65 employed and 170 unemployed individuals with mental illnesses along with their work status and work status duration measures were combined in a single multiple regression analysis with self-esteem as the criterion. The job satisfaction and success measures were found to be significant and moderate level moderators of self-esteem for the combined sample and separately for the employed and unemployed samples. It appears that self-esteem varies with satisfaction and success with the work status and not with work status alone. These findings suggested that self-esteem was an appropriate and modifiable outcome measure for psychiatric rehabilitation services. Some practical, theoretical, and policy implications of these results were also discussed.     

Demonstration of electrical and anatomic connections between Marshall bundles and left atrium in dogs: implications on the generation of P waves on surface electrocardiogram

INTRODUCTION: The muscle bundles within the ligament of Marshall (LOM) are electrically active. The importance of these muscle bundles (Marshall bundle [MB]) to atrial activation and the generation of the ECG P wave is unclear. METHODS AND RESULTS: We used optical mapping techniques to study epicardial activation patterns in isolated perfused left atrium in four dogs. In another seven dogs, P waves were studied before and after in vivo radiofrequency (RF) ablation of the connection between coronary sinus (CS) and the LOM. Computerized mapping was performed before and after RF ablation. Optical mapping studies showed that CS pacing resulted in broad wavefronts propagating from the middle and distal LOM directly to the adjacent left atrium (LA). Serial sections showed direct connection between MB and LA near the orifice of the left superior pulmonary vein in two dogs. In vivo studies showed that MB potentials were recorded in three dogs. After ablation, the duration of P waves remained unchanged. In the other four dogs, MB potentials were not recorded. Computerized mapping showed that LA wavefronts propagated to the MB region via LA-MB connection and then excited the CS. After ablation, the activation of CS muscle sleeves is delayed, and P wave duration increased from 65.3 +/- 14.9 msec to 70.5 +/- 17.2 msec (P = 0.025). CONCLUSION: In about half of the normal dogs, MB provides an electrical conduit between LA free wall and CS. Severing MB alters the atrial activation and lengthens the P wave. MB contributes to generation of the P wave on surface ECG.     

Mutations in MCT1 cDNA in patients with symptomatic deficiency in lactate transport

We identified 5 patients with subnormal erythrocyte lactate transport plus symptoms and signs of muscle injury on exercise and heat exposure. All had transport rates below the 95% envelope for normals. Three cases had rates 40-50% of mean normal. One was found to have a missense mutation in monocarboxylate transporter 1 (MCT1), the gene for the red cell lactate transporter (also expressed in skeletal muscle), at a conserved site, which was not mutated in a cohort of 90 normal humans. The other 2 cases had a different missense mutation (at a nonconserved site), which was also not mutated in the normal cohort. All 3 patients were heterozygotes. We presume that these mutations are responsible for their subnormal lactate transport, and hence their muscle injury under environmental stress; homozygous patients should be more seriously compromised. The other 2 cases had lactate transport rates 60-65% of mean normal, and their MCT1 revealed a third mutation, which proved to be a common polymorphism in the normal cohort. These 2 patients may be physiologic outliers in lactate transport, with their muscle damage arising from some other genetic defect.