Improved testing for CMT1A and HNPP using multiplex ligation-dependent probe amplification (MLPA) with rapid DNA preparations: comparison with the interphase FISH method

Charcot-Marie-Tooth disease type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP) are the two most common peripheral neuropathies, with incidences of about 1 in 2,500. Several techniques can be used to detect the typical 1.5-Mb duplication or deletion associated with these respective conditions, but none combines simplicity with high sensitivity. MLPA is a new technique for measuring sequence dosage. We have assessed its performance for the detection of the specific 1.5-Mb duplication/deletion by prospectively testing 50 patients referred with differential diagnoses of CMT or HNPP. Probes were designed to evaluate the TEKT3, PMP22, and COX10 genes within the CMT1A/HNPP region. We have compared the results with our existing fluorescence in situ hybridization (FISH) assay, which was performed in parallel. There was concordance of results for 49 patients. Of note, one patient showed an intermediate multiplex ligation-dependent probe amplification (MLPA) result with an abnormal FISH result, which is consistent with mosaicism. The assay works equally well with either purified DNA or rapid DNA preparations made by direct cell lysis. The use of the latter significantly reduces the cost of the assay. MLPA is a sensitive, specific, robust, and cost-effective technique suitable for fast, high-throughput testing and offers distinct advantages over other testing methods.     

Assessing the relationship between locus of control and social competence in pediatric burn survivors attending summer cAMP

Previous research suggests that children with burn injuries often exhibit psychological and social difficulties. The areas of functioning that are affected most often include level of anxiety, social competence, and self-esteem. Those children having an internal locus of control (LOC) have been shown to react more positively to physical disorders and to have better psychological responding in nonburn populations. The purpose of this study was to determine whether there is a relationship between LOC and social competence in pediatric burn survivors. Participants were children aged 8 to 18 years who had been treated for a burn injury and attended a 1-week summer camp for pediatric burn survivors. Results indicated that the type of LOC was not a predictor of the overall level of social competence, as reported on three different measures of social competence. However, LOC significantly accounted for variability in the child's cooperation level, according to parent report. Other results are discussed, as well as implications for future research and clinical work in this area.     

Cardiac abnormalities in diabetic patients with neuropathy: effects of aldose reductase inhibitor administration

OBJECTIVE: The goal of this study was to determine whether treatment with an aldose reductase inhibitor (ARI) has beneficial effects on asymptomatic cardiac abnormalities in diabetic patients with neuropathy. RESEARCH DESIGN AND METHODS: Diabetic subjects with neuropathy (n = 81) with either a low diastolic peak filling rate or impaired augmentation of left ventricular (LV) ejection fraction (LVEF) during maximal bicycle exercise were identified by gated radionuclide ventriculography. Coronary artery disease, left ventricular hypertrophy, and valvular heart disease were excluded by clinical evaluation, myocardial perfusion imaging, and echocardiography. Subjects were randomized to receive blinded treatment with either the placebo or the ARI zopolrestat 500 or 1,000 mg daily for 1 year. RESULTS: After 1 year of ARI treatment, there were increases in resting LVEF (P < 0.02), cardiac output (P < 0.03), LV stroke volume (P < 0.004), and exercise LVEF (P < 0.001). In placebo-treated subjects, there were decreases in exercise cardiac output (P < 0.03), stroke volume (P < 0.02), and end diastolic volume (P < 0.04). Exercise LVEF increased with ARI treatment independent of blood pressure, insulin use, or the presence of baseline abnormal heart rate variability. There was no change in resting diastolic filling rates in either group. CONCLUSIONS: Diabetic patients with neuropathy have LV abnormalities that can be stabilized and partially reversed by ARI treatment.     

Relation between physical activity and energy expenditure in a representative sample of young children

BACKGROUND: Strategies for the prevention and treatment of childhood obesity require a better understanding of the relation between the pattern of free-living physical activity and total energy expenditure (TEE). OBJECTIVE: We assessed the relations between TEE and physical activity level (PAL) during engagement in different intensities of physical activity. DESIGN: We used a cross-sectional study of 104 children (median age: 5.4 y) in Scotland. TEE was measured with use of doubly labeled water (DLW), and resting energy expenditure was predicted to determine PAL. Time spent sedentary and in light-intensity activity and in moderate- and vigorous-intensity physical activity (MVPA) was assessed by accelerometry concurrent with DLW measurements. Correlation and regression were used to assess the relations between measures of sedentary behavior, intensities of activity, and PAL as the dependent variable. RESULTS: Time spent sedentary was negatively correlated with PAL (r = -0.33, P < 0.01), and time spent in light-intensity activity was positively correlated with PAL (r = 0.31, P < 0.01). In multiple regression analyses, both time spent sedentary and in light-intensity activities were significantly associated with PAL. Time spent in MVPA was not associated with PAL; engagement in MVPA was limited in this sample (median: 3% of waking hours; range: 0-14%). PAL was significantly higher in boys than in girls. CONCLUSION: In this sample and setting, PAL was not influenced by engagement in MVPA but was influenced by time spent sedentary and in light-intensity activities. This study suggests that in young children, MVPA could make only a minor contribution to free-living TEE and PAL.     

Reduced total energy expenditure and physical activity in cachectic patients with pancreatic cancer can be modulated by an energy and protein dense oral supplement enriched with n-3 fatty acids

The aim of the study was to assess the total energy expenditure (TEE), resting energy expenditure (REE) and physical activity level (PAL) in home-living cachectic patients with advanced pancreatic cancer. The influence of an energy and protein dense oral supplement either enriched with or without the n-3 fatty acid eicosapentaenoic acid (EPA) and administered over an 8-week period was also determined. In total, 24 patients were studied at baseline. The total energy expenditure was measured using doubly labelled water and REE determined by indirect calorimetry. Patients were studied at baseline and then randomised to either oral nutritional supplement. Measurements were repeated at 8 weeks. At baseline, REE was increased compared with predicted values for healthy individuals (1387(42) vs 1268(32) kcal day(-1), P=0.001), but TEE (1732(82) vs 1903(48) kcal day(-1), P=0.023) and PAL (1.24(0.04) vs 1.50) were reduced. After 8 weeks, the REE, TEE and PAL of patients who received the control supplement did not change significantly. In contrast, although REE did not change, TEE and PAL increased significantly in those who received the n-3 (EPA) enriched supplement. In summary, patients with advanced pancreatic cancer were hypermetabolic. However, TEE was reduced and this was secondary to a reduction in physical activity. The control energy and protein dense oral supplement did not influence the physical activity component of TEE. In contrast, administration of the supplement enriched with EPA was associated with an increase in physical activity, which may reflect improved quality of life.     

Proton therapy for prostate cancer: the initial Loma Linda University experience

PURPOSE: We analyzed results of conformal proton radiation therapy for localized prostate cancer, with emphasis on biochemical freedom from relapse. METHODS AND MATERIALS: Analyses were performed for 1255 patients treated between October 1991 and December 1997. Outcomes were measured on primarily in terms of biochemical relapse and toxicity. RESULTS: The overall biochemical disease-free survival rate was 73%, and was 90% in patients with initial PSA 相似文献   

The involvement of progesterone in the onset of human labour

Progesterone is essential for the maintenance of pregnancy, and acts to promote uterine quiescence. In many species progesterone levels fall prior to the onset of labour but no fall has been observed in humans. The concept of 'functional' progesterone withdrawal in association with labour has been proposed and a number of mechanisms have been suggested. Recent potential mechanisms of functional withdrawal include changes in progesterone receptor (PR) isoforms, regulation of PR responsive genes through nuclear factor kappaB (NF-kappaB) promoter sites and the non-genomic effects of progesterone or its metabolites.     

Response without shrinkage in bilateral Wilms tumor: significance of rhabdomyomatous histology

PURPOSE: To test the hypothesis that poor response to chemotherapy in patients with bilateral Wilms tumor may be associated with the appearance of rhabdomyomatous histology, suggesting a differentiation response. METHODS: Twenty-six patients with bilateral Wilms tumor were treated at the authors' hospital between 1985 and 1995. Radiologic response to presurgical chemotherapy was assessed, and postsurgery histology was reviewed. RESULTS: There was a significant association between rhabdomyomatous differentiation in postchemotherapy surgical specimens and poor radiologic response. Poor response did not, however, necessarily mean poor outcome: of 11 patients with rhabdomyomatous differentiation, 7 are alive and disease-free, 2 died of complications, and only 2 died of uncontrolled Wilms tumor. CONCLUSIONS: Rhabdomyomatous differentiation in postchemotherapy bilateral Wilms tumor is associated with poor radiologic response. This observation may indicate a differentiation response rather than an absolute failure of response to chemotherapy. Clinical measures other than tumor volume are needed to distinguish between tumors that respond to chemotherapy but do not shrink, and those that genuinely do not respond.