An eight-week trial investigating the efficacy and tolerability of atorvastatin for children and adolescents with heterozygous familial hypercholesterolemia

This study aimed to assess the efficacy and tolerability of atorvastatin in Tanner stage (TS) 1 patients ages 6 to 10?years and TS ??2 patients ages 10 to <18?years with genetically confirmed heterozygous familial hypercholesterolemia (HeFH) and a low density lipoprotein cholesterol (LDL-C) level of 4?mmol/l (155?mg/dl) or higher. In this open-label, 8-week study, 15 TS 1 children were treated initially with atorvastatin 5?mg/day and 24 TS ??2 children with 10?mg/day. Doses were doubled at week 4 if the LDL-C target (<3.35?mmol/l [130?mg/dl]) was not achieved. The efficacy variables were the percentage change from baseline in LDL-C, total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), very low density lipoprotein cholesterol (VLDL-C), and apolipoprotein (Apo) A-I and Apo B. Safety evaluations included clinical monitoring, subject-reported adverse events (AEs), vital signs, and clinical laboratory tests. The mean values for LDL-C, TC, VLDL-C, and Apo B decreased by week 2 among all TS 1 and TS ??2 patients, whereas TG, HDL-C, and Apo A-I varied considerably from week to week. After 8?weeks, the mean reduction in LDL-C was ?40.7%?±?8.4 for the TS 1 children and ?39.7%?±?10.3 for the TS ??2 children. For the TS 1 patients, the mean reductions were ?34.1%?±?6.9 for TC and ?6.0%?±?32.1 for TG. The corresponding changes for the TS ??2 patients were ?35.6%?±?9.5 for TC and ?21.1%?±?29.7 for TG. Four patients experienced mild to moderate treatment-related AEs. No serious AEs or discontinuations were reported. Overall, no difference in safety or tolerability was observed between the younger and older cohorts. Across the range of exposures after atorvastatin 5 to 10?mg (TS 1) or atorvastatin 10 to 20?mg (TS ??2) doses for 8?weeks, clinically meaningful reductions in LDL-C, TC, VLDL-C, and Apo were observed with atorvastatin in pediatric patients who had HeFH. Atorvastatin also was well tolerated in this population.     

Differential methylation of CpG sites in two isoforms of myosin binding protein C,an important hypertrophic cardiomyopathy gene

Hypertrophic cardiomyopathy (HCM) is a common form of cardiac disease. Over 400 causative mutations have been identified in 20 sarcomere and myofilament related genes. The high density of mutations found in genes associated with HCM may suggest that mechanisms promoting increased mutability play a role in disease prevalence. The objective of this study was to evaluate the CpG methylation level of the exonic regions of the cardiac myosin binding protein C gene (MYBPC3), a common causal gene for HCM. To determine if the methylation level is gene specific and possibly involved with gene mutability, we also evaluated the methylation of the CpGs within the exonic regions of the skeletal muscle isoform of the myosin binding protein C gene (MYBPC2); there are no known mutations that lead to the development of familial human disease within this gene. We determined that although the mean number of CG sites was identical within the coding region of each gene, the mean methylation level of CpGs was significantly higher in MYBPC3 than MYBPC2 (P < 0.0001). The results of this study suggest that there are unique aspects of this cardiac gene or its epigenetic environment which may result in increased genetic mutability. Evaluation of the methylation levels of additional causal cardiomyopathic genes is warranted. Environ. Mol. Mutagen., 2011. © 2010 Wiley‐Liss, Inc.     

Factors associated with lower quality of life among patients receiving palliative care

Title.  Factors associated with lower quality of life among patients receiving palliative care.
Aim.  This paper is a report of a study conducted to (1) assess the quality of life (QoL) and physical functioning status of patients diagnosed with advanced cancer and receiving palliative care; (2) determine if there was a statistically significant relationship between their physical functioning and QoL and (3) identify the demographic and disease-related variables related to their QoL.
Background.  Achieving the best possible QoL is a major goal in palliative care. However, research findings about the relationship between QoL and demographic variables have been inconsistent.
Method.  Three hundred patients with advanced cancer were recruited from four district hospitals in Hong Kong between February 2005 and July 2006. Their QoL and physical functioning status were assessed by face-to-face interview, using the McGill Quality of Life Questionnaire (Hong Kong version) and the Palliative Performance Scale respectively.
Results.  Participants reported reduced ambulation, inability to perform hobbies or housework, and the need for occasional assistance in self-care (mean: 64·6 out of 100, sd : 19·3, range: 20–100). QoL was fair (mean: 6·2 out of 10, sd : 1·5, range: 0·9–10). There was a weak positive association between physical functioning and QoL scores. Multiple regression analysis showed that patients who were older, female, had ever been married, or had higher physical functioning tended to have better QoL.
Conclusion.  More could be done in symptom and psychosocial management to improve patients' QoL, in particular for those who are younger, male or single, or who have lower physical functioning.     

Caspase-3 is required for apoptosis-associated DNA fragmentation but not for cell death in neurons deprived of potassium

Caspases are crucial effectors of the cell death pathway activated by virtually all apoptosis-inducing stimuli within neurons and nonneuronal cells. Among the caspases, caspase-3 (CPP32) appears to play a pivotal role and has been found to be necessary for developmentally regulated cell death in the brain. We have used mice lacking caspase-3 (-/-CPP32) to examine its involvement in cultured cerebellar granule neurons induced to undergo apoptosis by potassium deprivation (K+). We find that, following K+ deprivation, neurons from -/-CPP32 mice die to the same extent as those from normal (+/+) mice. Although a small delay in the induction of cell death is observed in -/-CPP32 neurons, the rate of cell death is generally comparable to that of +/+ cultures. Though not critical for neuronal death, caspase-3 is required for DNA fragmentation and chromatin condensation as judged by the absence of these apoptotic features in -/-CPP32 neurons. Boc.Asp.fmk, a pan caspase inhibitor, partially protects +/+ neurons from low-K+-mediated cell death and does so to the same extent in -/-CPP32 cultures, suggesting the involvement of a caspase other than caspase-3 in cell death. However, the protective effect of boc.Asp.fmk is not seen beyond 24 hr, suggesting that the effect of caspase inhibition is one of delaying rather than preventing apoptosis. The more selective caspase inhibitors DEVD.fmk, IETD.fmk, and VEID.fmk fail to affect cell death, indicating that members inhibited by these agents (such as caspases - 6 ,7, 8, 9 and 10) are also not involved in low-K+-mediated apoptosis.     

Severe vitreous hemorrhage associated with closed-globe injury

Background The presence of marked vitreous hemorrhage is associated with poor visual prognosis in ocular trauma involving the posterior segment. The purpose of this study was to investigate the clinical features, prognostic factors, and visual outcomes in such eyes after closed-globe injury. Methods Retrospective chart review of patients with severe vitreous hemorrhage after closed-globe injury between January 2000 and December 2002. Results The study included 33 eyes in 32 patients with a mean age of 41.5 (range, 3–78 years) and a median follow-up period of 12 (range, 3–50 months). Presenting visual acuity was between 4/200, and there was light perception in 32 eyes (97%) and no light perception in one eye (3%). Fifteen eyes (45%) had one or more posterior segment pathologies beneath the vitreous hemorrhage. There were retinal tears in six eyes (18%), retinal detachment in six (18%), submacular hemorrhage in six (15%), choroidal rupture in three (9%), macular pucker in three (9%), retinal dialysis in one (3%), macular hole in one (3%), and retinal vessels occlusion in one (3%). Seven eyes (21%) had final visual acuity 20/40 or better, and 18 eyes (54%) had less than 20/200. Poor prognostic factors included presenting visual acuity of light perception or lower (p=0.032), hyphema (p=0.007), traumatic cataract (p=0.027), and age 55 years or younger (p=0.039). The most common cause of poor visual outcome was macular scar. Conclusion The visual prognosis of severe vitreous hemorrhage after closed-globe injury was guarded. This was frequently associated with various anterior and posterior segment pathologies. In order to provide early visual rehabilitation and management of any potentially treatable posterior pathology, early vitrectomy may be considered.     

重型颅脑外伤开颅术后二次手术原因及对策

目的：探讨重型颅脑外伤后二次手术的原因、处理及效果。方法：回顾分析我院2001年1月～2006年11月收治的17例重型颅脑损伤二次手术病人的临床资料。结果：根据格拉斯哥治疗结果分级（GOS）评分法，本组17例患者出院时GOS1级（死亡）7例；GOS2级（植物生存）2例；GOS3级（重残）1例；GOS4级（中残）3例；GOS5级（良好）4例。结论：二次手术病人多数有多发损伤，病情危重，致残率、死亡率高；掌握手术时机、正确的手术方式、术后严密监测及妥善处理复合伤可改善病人预后。     

Intraluminal brachytherapy in the treatment of bile duct carcinomas

Patients with carcinoma of the biliary tract have a poor prognosis because the disease is often unresectable at diagnosis. Intraluminal brachytherapy has been reported as an effective treatment for localized cholangiocarcinoma of the biliary tract. The purpose of our study was to analyse the survival of patients treated with brachytherapy and make some recommendations regarding its use. Fifteen patients underwent brachytherapy via a trans-hepatic approach at the Royal Prince Alfred Hospital from 1983 to 1993. Eleven patients had low-dose rate brachytherapy and four patients had high-dose rate treatment. There were nine males and six females. The median age was 64 years. Other treatment included bypass procedures in two patients, endoscopic stents in 14 patients and external beam irradiation in one patient. The median survival was 12.5 months and 47% of the patients survived 1 year. The only complication reported was cholangitis which was seen in one patient. There did not seem to be any difference in survival or complications between low- and high-dose rate brachytherapy. We conclude that the addition of intraluminal brachytherapy after biliary drainage prolongs survival and is a safe and effective treatment, but patients still have a high rate of local failure, and further studies will be needed to address this problem.     

Prospective evaluation of remote, interactive videoconferencing to enhance urology resident education: the genitourinary teleteaching initiative

PURPOSE: Changes in referral patterns and resource allocation into Centers of Excellence affect the educational experience of urology trainees by altering resident exposure to patients and clinicians, especially at sites where subspecialty deficiencies exist. Access to educators at Centers of Excellence using interactive videoconferencing technology may facilitate residency training objectives and enhance trainees' overall educational experience. We prospectively evaluated the implementation of this technology at tertiary care teaching centers to enhance urology resident education. MATERIALS AND METHODS: Using videoconferencing technology, urology residents at the University of Western Ontario (London, Canada) participated in a series of didactic, interactive pediatric urology teleteaching seminars. These were presented by an expert pediatric urologist from the Hospital for Sick Children, Toronto, Canada. Using a 5-point Likert scale (1-strongly disagree, 5-strongly agree), participants responded to statements pertaining to seminar content, technology and ease of use at the completion of each session. The results were subsequently tabulated and evaluated to determine the effectiveness and accessibility of the program in providing expert pediatric urological education to residents at a remote urology training program. RESULTS: The entire urology resident staff from postgraduate year 1 to 5 participated in the seminar program. The overall acceptance of this medium was high (mean score 4.5). The quality of presentation, as well as picture and sound quality, all received mean scores greater than 4. Participants indicated that their ability to interact with the presenter was not inhibited by using this medium. All participants agreed that they would use this technology in the future (mean score 4.5) and that the presentation would not be improved if the presenter were on-site. Due to preexisting technology at both centers, no direct cost was incurred throughout the study. CONCLUSIONS: Our experience suggests that interactive teleteaching using readily available, existing technology, is a cost-effective and accepted method of providing trainees with an appropriate educational experience. In centers where subspecialty deficiencies exist, this medium may provide residents with the necessary education requirements of their respective programs without the need for costly teacher (or student) travel. Continual improvements in technology as well as the addition of multiple sites will increased this medium's impact in the future.