Sleep symptoms and their clinical correlates in Machado-Joseph disease.

OBJECTIVE: To evaluate the presence of sleep symptoms in Machado-Joseph disease/spinocerebellar ataxia type 3 (MJD/SCA3). SUBJECTS/METHODS: We used a sleep questionnaire and the Epworth Sleepiness Scale to compare 53 patients with MJD/SCA3 and 106 controls. RESULTS: Patients with MJD/SCA3 reported more symptoms of insomnia, restless leg syndrome and REM sleep behavior disorder as well as nocturnal cramps, snoring and nocturnal apnea. Insomnia was the most frequently reported sleep-related complaint in the MJD/SCA3 group. CONCLUSIONS: Our results indicate that sleep disorders are common in patients with MJD/SCA3 and probably have a multifactorial etiology, with components of a primary sleep disorder in addition to sleep-disrupting symptoms such as nocturia and cramps.

Enterostomy tube placement in children with spinal muscular atrophy type 1.

OBJECTIVE: To determine the major complication rate in the first 30 days after enterostomy tube insertion in infants with spinal muscular atrophy (SMA) type 1. STUDY DESIGN: A retrospective case review of all children with SMA type 1 who had a gastrostomy or gastrojejunostomy tube placed by the image-guided technique at the Hospital for Sick Children from 1994-2004. Major complications were classified as peritonitis, aspiration pneumonia, respiratory failure, nonelective admission to the pediatric intensive care unit, and death. RESULTS: Twelve children were identified as having SMA type 1 with an enterostomy tube insertion. The median age at tube insertion was 6.1 months (range 2.2 to 15.8 months). Major complications in the first 30 days after the procedure included aspiration pneumonia (5/12 patients [41.6%]), respiratory failure requiring admission to the pediatric intensive care unit (4/12 [33%]), and death (2/12 [16.7%]). Children with development of aspiration pneumonia were significantly older at time of tube insertion (P < .05) than those with no aspiration. CONCLUSIONS: Major complications including death are seen in children with SMA type 1 in the first 30 days after enterostomy tube insertion.

Survival in infants with Down syndrome, Metropolitan Atlanta, 1979-1998.

OBJECTIVE: Factors influencing survival among persons with Down syndrome (DS) are not well understood. We sought to evaluate survival of infants with DS and potential prognostic factors. STUDY DESIGN: Infants with DS who were born alive during 1979 to 1998 were identified using the Metropolitan Atlanta Congenital Defects Program (MACDP), a population-based surveillance system. To document vital status, we used data from hospital records, the National Death Index (NDI), and Georgia vital records. We estimated survival probability using the Kaplan-Meier product limit method and hazard ratios using a Cox proportional hazards model. RESULTS: Survival probability to 1 year was 92.9% (95% CI: 90.9-94.9) and to 10 years was 88.6% (95% CI: 85.0-92.2). Univariate analysis demonstrated that black maternal race, low birth weight, preterm birth, lower paternal education, presence of heart defects, and presence of other major congenital anomalies were important prognostic factors. After multivariate analysis, maternal race, presence of heart defects, low birth weight, and an interaction between maternal race and presence of heart defects were significantly associated with mortality risk. CONCLUSIONS: A racial disparity is apparent in survival for children with Down syndrome. Further study is needed to elucidate possible reasons for the racial disparity.

Timing of voiding cystourethrogram in the investigation of urinary tract infections in children.

OBJECTIVE: To determine whether the detection of vesicoureteral reflux (VUR) in children with a urinary tract infection (UTI) is more likely if the voiding cystourethrogram (VCUG) is performed early (within the first 7 days after diagnosis) or late (>7 days after diagnosis). STUDY DESIGN: We conducted a retrospective case review of children <5 years of age admitted with a first episode of UTI to a tertiary care pediatric hospital over a 2-year period. Timing of the VCUG was at the discretion of the attending pediatrician. Differences in age, sex, mean time to performing the VCUG, and incidence of VUR between the 2 groups (VCUG performed early vs late) were compared by using Student t test (for age) and chi(2) test (for sex and incidence of VUR). Potential confounders (age and sex) were included in a multiple logistic regression analysis. RESULTS: A total of 162 patients were eligible for inclusion. Mean age was 181 days, and 43.8% were female. The incidence of VUR was 21.6%. The early group consisted of 82 patients, and the late group consisted of 80. No significant difference was found for age or sex or for the incidence of reflux (17.1% vs 26.3%, P =.219), with a crude odds ratio of.59 (95% CI 0.3-1.2, P >.05). CONCLUSION: The rate of detection of VUR in children with a first episode of UTI does not increase when the VCUG is done early (within the first 7 days of diagnosis) rather than later.

Comparison of self-reported and observed water contact in an S. mansoni endemic village in Brazil.

Estimates of exposure are critical for immuno-epidemiologic and intervention studies in human schistosomiasis. Direct observation of human water contact patterns is both costly and time consuming. To address these issues, we determined whether individuals residing in a Schistosoma mansoni endemic village in Brazil could accurately self-report their water contact patterns. We compared the results of a water contact questionnaire to the present gold standard, direct observation of water contact in 86 volunteers, aged 8--29. We administered a survey to estimate volunteers' frequency and type of water contact and directly measured each volunteers' water contact patterns during 5 weeks of detailed water contact observations. We found a poor correlation between self reported frequency of contact and directly observed exposure (rho=0.119, P=NS). The questionnaire data was supplemented by information about average body surface area of exposure and duration of contact for specific activities derived from observations of this cohort. This 'supplemented questionnaire' data was significantly correlated with their exposure index (rho=0.227, P=0.05). It provides a starting point from which questionnaires may develop to provide a more cost-effective and less labor intensive method of assessing water contact exposure at the level of the individual.

Long-acting diltiazem CD is safe and effective in a hypertensive Mexican-American population.

STUDY OBJECTIVE: To evaluate the safety and effectiveness of diltiazem CD for reducing blood pressure in Mexican-American patients with mild to moderate hypertension. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Twelve clinical sites in the United States. PATIENTS: Patients with baseline diastolic blood pressures between 95 and 115 mm Hg. INTERVENTIONS: Patients were treated with an average daily dose of diltiazem CD 246 mg (60 patients) or placebo (58 patients) to achieve a trough diastolic blood pressure below 90 mm Hg. MEASUREMENTS AND MAIN RESULTS: Diltiazem CD significantly reduced mean diastolic blood pressure compared with placebo, -8.2 versus -4.1 mm Hg, respectively (p=0.0025). Diastolic blood pressure below 90 mm Hg or a reduction of 10 mm Hg or more was achieved by 57% of diltiazem CD versus 28% of placebo recipients. Systolic blood pressure and heart rate were also reduced with diltiazem CD. Adverse events were mild, with similar frequency for diltiazem CD (15%) and placebo (19%). CONCLUSION: Diltiazem CD is safe and effective in hypertensive Mexican-Americans, and diastolic blood pressure reductions compare with those in non-Hispanic white patients.

Role of acetylated gangliosides on neurite extension.

We have investigated the role of 9-O-acetylated gangliosides identified by the Jones monoclonal antibody (Jones mAb) in the elongation of neurites extended by neurons of embryonic rat dorsal root ganglia (DRG) explants grown on laminin substratum. The behavior of individual growth cones was recorded using a time-lapse video-enhanced imaging system before and after the addition of antibodies that recognize specific gangliosides known to be expressed on these growth cones. It was possible to demonstrate that the advance of growth cones on laminin was halted in the presence of Jones mAb. The onset of effects was rapid and signaled by an immediate cessation of elongation, a loss of lamellipodia and a retrieval of axoplasm. This effect was partially reverted by washing the explants for several minutes with culture medium. mAb A2B5 which also recognizes gangliosides expressed on these growth cones does not induce any change on the growth rate. Our findings show that 9-O-acetylated gangliosides may play an important role on the extension of growth cones and consequently influence navigation and pathway finding during development.

Hb Montefiore (126(H9)Asp-->Tyr). High oxygen affinity and loss of cooperativity secondary to C-terminal disruption.

Hb Montefiore was found, in the heterozygous state, in a Puerto Rican female who had a slightly elevated total Hb level. Structural analysis revealed that Asp-alpha126 was replaced by Tyr. Hb Montefiore migrates close to HbF (at pH 8.6) and accounts for 20.3% of the hemolysate. Oxygen binding of red blood cells revealed a 40% decrease in the P50 (pH 7.4) and a low n value of 1.6 (normal: 2.6). Depletion of red blood cell 2,3-DPG did not change the results. Stripped Hb Montefiore at pH 7.2 showed an 8-fold reduction in P50 (0.6 versus 4.6 mm Hg) and very low cooperativity (n = 1.2 versus 2.9 for the control). Heterotopic effectors, as 2,3-diphosphoglycerate and inositol hexaphosphate had a normal effect and in addition, they increased cooperativity. The chloride ion effect and the Bohr effect were moderately reduced. A bezafibrate derivative (L345), known to bind alpha126, increases the P50 of HbA by 9-fold, but only by 1. 5-fold that of Hb Montefiore. Combining these functional studies with intrinsic fluorescence and Resonance Raman spectroscopy, we interpret the very low n value and the high oxygen affinity for Hb Montefiore as a result of both a destabilized T state that switches to R upon ligand binding and a deoxy T state that binds ligands with higher affinity than that of deoxy HbA. Hb Montefiore still binds ligands cooperatively, but the difference in ligand binding properties of the two quaternary states has been drastically reduced.

Biochemical abnormalities in rhizomelic chondrodysplasia punctata.

Biochemical studies with emphasis on peroxisomal functions were conducted in six patients with well-documented rhizomelic chondrodysplasia punctata (RCDP) and compared with findings in patients with Zellweger syndrome and neonatal adrenoleukodystrophy (ALD). Patients with RCDP had three characteristic biochemical abnormalities: (1) profound defect in plasmalogen (ether lipid) synthesis, which is significantly greater than the analogous defect in Zellweger syndrome or neonatal ALD; (2) reduction of phytanic acid oxidation activity to 1% to 5% of control, similar to that observed in Refsum disease, Zellweger syndrome, and neonatal ALD; (3) presence of the unprocessed form of peroxisomal 3-oxoacyl-coenzyme A thiolase in the postmortem liver of two patients. Other peroxisomal functions were normal, including levels of very long chain fatty acids, pipecolic acid, and bile acid intermediates, and immunoblot studies of peroxisomal acyl-CoA oxidase and bifunctional enzyme in postmortem liver. Unlike what is observed in Zellweger syndrome and neonatal ALD, catalase activity in cultured skin fibroblasts was sedimentable, indicating that peroxisome structure is not grossly deficient in RCDP. The biochemical abnormalities in RCDP were consistent and set it apart from all the other known peroxisomal disorders.

Family planning practices among Anglo and Hispanic women in U.S. counties bordering Mexico.

PIP: The US Center for Disease Control surveyed women of reproductive age living on the US side of the Mexican border as to contraceptive use and source of care. It found that overall contraceptive practice is quite similar among married Hispanic and Anglo (white, non-Hispanic) women: 75% of Anglo and 66% of Hispanics use some method. Among never marrieds however, Anglos are twice as likely as Hispanics to use a method. About 22% of Anglo and 12% of Hispanic women are protected from pregnancy by contraceptive sterilization of themselves or partners, the difference almost entirely attributable to a very low incidence of vasectomy among Hispanic males. The pill is the most popular reversible method among both groups. Hispanic women are more likely to go to Planned Parenthood or health department clinics, Anglo women to go to private physicians or clinics. Unmet need is much higher among Hispanics: about 4 times the proportion of married Hispanic women as comparable Anglo women were at risk of unintended pregnancy and were using no method.^ieng

Saethre-Chotzen syndrome: a broad and variable pattern of skeletal malformations.

A family is described in which 15 persons in five generations are affected with a complex of skeletal malformations which variably includes peculiar asymmetric facies, delayed closure of large fontanels, brachycephaly, acrocephaly, brachydactyly, cutaneous syndactyly, broad great toes, and mild shortness of stature. Although craniosynostosis is either lacking or relatively mild in the members of this family, their features are otherwise strikingly similar to those of patients with the Saethre-Chotzen syndrome. We believe the findings in this family indicate that the Saethre-Chotzen syndrome comprises a broad pattern of carniofacial and other skeletal malformations in which craniosynostosis may sometimes occur.