Quality planning for mental health

This article describes quality improvement theory and its application in planning a major clinical initiative. The experience of the Harvard Community Health Plan in redesigning its mental health program is used to describe how theory can be translated into practice. A formal process is involved which relies heavily on the use of data in designing the program as well as evaluating its success.     

The prophylactic value of clean intermittent catheterization and anticholinergic medication in newborns and infants with myelodysplasia at risk of developing urinary tract deterioration.

OBJECTIVE--To determine if prophylactic use of clean intermittent catheterization and oxybutynin chloride is effective in preventing urinary tract deterioration in myelodysplastic children with high bladder pressure and detrusor-sphincter dyssynergia. DESIGN--Sequential, nonrandomized trial. SETTING--Referral-based urodynamics facility and myelodysplasia program at a major city pediatric hospital. PARTICIPANTS--Twenty-six of 71 consecutive newborns with myelodysplasia who exhibited these urodynamic findings were treated prophylactically over 5 years, whereas 56 of 105 consecutive newborns with the same findings treated during the previous 7 years were treated expectantly. INTERVENTION--Clean intermittent catheterization and oxybutynin therapy were begun when these specific urodynamic findings were detected. MEASUREMENTS AND RESULTS--Follow-up urodynamic studies and roentgenographic assessment of the urinary tract were performed periodically over 5 years. Oxybutynin eliminated uninhibited contractions in two of 14 newborns and lowered peak contractile pressure in the remaining 12. Oxybutynin also lowered bladder-filling pressure at capacity in all 12 additional neonates with only hypertonicity. Twenty-four (92%) of 26 children had normal kidney function and drainage during the observation period, two (8%) developed hydroureteronephrosis, and one of these two had vesicoureteral reflux. In a prior study of children similarly at risk who were treated expectantly, the roentgenographic appearance of the upper urinary tract had changed in 48%. Minimal side effects were noted with oxybutynin, and no adverse effects of clean intermittent catheterization were detected. CONCLUSIONS--Oxybutynin effectively reduces uninhibited contractions and lowers detrusor filling pressure, while clean intermittent catheterization allows bladder emptying at low pressures with no measurable side effects in these neonates. The overall effect maintains the integrity of the upper urinary tract in almost all myelodysplastic children at risk of urinary tract deterioration. Expectant therapy can no longer be advocated when these "at risk" children are identified because prophylactic treatment is so effective.     

Radiologically placed temporary hepatic artery catheter for treatment of liver cancer

Hepatic artery infusion (HAI) chemotherapy is associated with higher response rates compared to systemic chemotherapy in those patients with unresectable liver malignancies. Operative hepatic artery catheter (HAC) insertion has significant morbidity and mortality, especially in patients with high‐volume disease, some of whom may not respond to HAI chemotherapy. We report our experience in 45 patients with high‐volume liver disease who were initially treated with HAI chemotherapy via a radiologically placed temporary HAC to try to select the responders who then went on to have an operative HAC. In these 45 patients who had 62 radiologically placed HAC, we found very few major complications, and certainly no complications such as cholecystitis, vascular or malperfusion problems.     

Genomic analysis of inherited breast cancer among Palestinian women: Genetic heterogeneity and a founder mutation in TP53

Breast cancer among Palestinian women has lower incidence than in Europe or North America, yet is very frequently familial. We studied genetic causes of this familial clustering in a consecutive hospital‐based series of 875 Palestinian patients with invasive breast cancer, including 453 women with diagnosis by age 40, or with breast or ovarian cancer in a mother, sister, grandmother or aunt (“discovery series”); and 422 women diagnosed after age 40 and with negative family history (“older‐onset sporadic patient series”). Genomic DNA from women in the discovery series was sequenced for all known breast cancer genes, revealing a pathogenic mutation in 13% (61/453) of patients. These mutations were screened in all patients and in 300 Palestinian female controls, revealing 1.0% (4/422) carriers among older, nonfamilial patients and two carriers among controls. The mutational spectrum was highly heterogeneous, including pathogenic mutations in 11 different genes: BRCA1, BRCA2, TP53, ATM, CHEK2, BARD1, BRIP1, PALB2, MRE11A, PTEN and XRCC2. BRCA1 carriers were significantly more likely than other patients to have triple negative tumors (p = 0.03). The single most frequent mutation was TP53 p.R181C, which was significantly enriched in the discovery series compared to controls (p = 0.01) and was responsible for 15% of breast cancers among young onset or familial patients. TP53 p.R181C predisposed specifically to breast cancer with incomplete penetrance, and not to other Li‐Fraumeni cancers. Palestinian women with young onset or familial breast cancer and their families would benefit from genetic analysis and counseling.     

家兔失神经支配腓肠肌肌纤维退行性变与修复性再生的超微结构观察

目的:观察家兔腓肠肌失神经支配后肌纤维在退行性变与修复性再生过程中超微结构的变化,探讨失神经支配骨骼肌修复性再生障碍的机制。方法:实验于2005-04/2006-04在南方医科大学中心实验室完成。选择成年新西兰大白兔20只,切断一侧胫神经腓肠肌肌支,术后1,4,8,12,16周分别采用耳缘静脉注射空气处死4只。取实验侧和对照侧腓肠肌内侧头肌组织少许,用于制备超薄切片标本,透射电镜观察各时间点兔失神经腓肠肌肌纤维形态。结果:纳入动物20只,均进入结果分析。①正常家兔腓肠肌肌原纤维排列整齐,肌小节和Z线清晰,线粒体均匀分布在肌原纤维之间,排列规则,细胞核位于质膜周边,未见溶酶体。②失神经支配1周,肌原纤维排列基本整齐,线粒体增多,无明显肿胀。③失神经支配4周,线粒体明显增多肿胀,部分线粒体空泡样变,溶酶体增多,Z线模糊,肌原纤维间隙增大。④失神经支配8周,肌纤维明显萎缩退行性变,大部分肌原纤维消失,残留的肌原纤维变得模糊,间隙增大,肌小结丧失正常的结构,胞浆内含有大量空泡变性的细胞器,可发现畸形核,染色质浓缩、边集,肌细胞膜极度皱缩。镜下发现较多的位于基膜下活化的肌卫星细胞,细胞内含有发达的粗面内质网和丰富的胞浆。一些肌卫星细胞直接与肌纤维融合。同时在间质中可发现一些形态上很象成纤维细胞的细胞,不过这些细胞含有大量的粗面内质网,胞浆内有颗粒和微丝,少量的圆形的线粒体。在退行性变的肌纤维基膜下也可发现肌管样结构的再生肌细胞,在这些肌管内一些肌丝在一起聚集成束,没有组装成肌原纤维,没有正常的肌小结结构。在它们周围有细小的空肌管样结构,可能是以往再生的肌细胞退行性变后的残余体。在间质中可发现一些细小的肌纤维。⑤失神经支配12周,大部分肌纤维萎缩退行性变,但是仍可发现没有萎缩的肌纤维,这些肌纤维细胞核位于周边,有良好的收缩系统,纤维排列规则,Z线清晰,有完整的肌膜。⑥失神经支配16周,肌卫星细胞的数量明显减少,并可发现大量细小的肌纤维,多分布在较大的肌纤维附近,肌膜完整平滑,无皱褶。可发现核位于中央的肌纤维,胞浆内肌原纤维结构清楚,但是肌原纤维的排列远不如核位于周边的肌纤维整齐,说明其收缩系统发育不良。结论:失神经支配后肌细胞退行性变和修复性再生同时存在,再生的肌细胞不能,化发育为成熟的肌纤维,进而发生退行性变。长时间失神经支配,肌卫星细胞的耗竭是失神经支配骨骼肌晚期的主要超微结构变化。