家族性高胆固醇血症纯合子患者低密度脂蛋白受体缺陷的研究

目的：研究家族性高胆固醇血症纯合子患者的发病机理。方法：在临床研究和家系调查的基础上, 培养患者皮肤成纤维细胞, 采用放射性配体结合受体分析技术研究其低密度脂蛋白受体。结果：患者低密度脂蛋白受体对低密度脂蛋白的高亲和性结合为正常人的７８．２％，高亲和性内移和降解则分别为正常人的３．６％和１．７％。结论：本例家族性高胆固醇血症纯合子患者的发病机制为低密度脂蛋白受体内移功能障碍。     

Rare adipose disorders (RADs) masquerading as obesity

Rare adipose disorders (RADs) including multiple symmetric lipomatosis (MSL), lipedema and Dercum''s disease (DD) may be misdiagnosed as obesity. Lifestyle changes, such as reduced caloric intake and increased physical activity are standard care for obesity. Although lifestyle changes and bariatric surgery work effectively for the obesity component of RADs, these treatments do not routinely reduce the abnormal subcutaneous adipose tissue (SAT) of RADs. RAD SAT likely results from the growth of a brown stem cell population with secondary lymphatic dysfunction in MSL, or by primary vascular and lymphatic dysfunction in lipedema and DD. People with RADs do not lose SAT from caloric limitation and increased energy expenditure alone. In order to improve recognition of RADs apart from obesity, the diagnostic criteria, histology and pathophysiology of RADs are presented and contrasted to familial partial lipodystrophies, acquired partial lipodystrophies and obesity with which they may be confused. Treatment recommendations focus on evidence-based data and include lymphatic decongestive therapy, medications and supplements that support loss of RAD SAT. Associated RAD conditions including depression, anxiety and pain will improve as healthcare providers learn to identify and adopt alternative treatment regimens for the abnormal SAT component of RADs. Effective dietary and exercise regimens are needed in RAD populations to improve quality of life and construct advanced treatment regimens for future generations.     

RESTORATIVE PROCTOCOLECTOMY WITH ILEAL POUCH–ANAL ANASTOMOSIS IN 203 PATIENTS: THE AUCKLAND EXPERIENCE

Background : Restorative proctocolectomy with ileal pouch–anal anastomosis (IPAA) has become an established operation for patients with ulcerative colitis and familial adenomatous polyposis (FAP). The results of a 15-year experience with IPAA are reported. Methods : Between September 1982 and June 1997, 203 patients had IPAA surgery. From a review of the charts, data were collected on the surgical procedure, the diagnosis and early and late complications. Pouch function was assessed by means of a postal questionnaire. Results : Of the 201 patients (median age of 32 years; 89 women) with complete records, 122 had J pouches, 65 had W pouches and 14 S pouches were constructed. The pre-operative diagnosis in 88% was ulcerative colitis and in 10% it was FAP. During a median follow-up time of 6.1 years the diagnoses were changed for 8% of the patients; in 4% the diagnosis was changed to Crohn’s disease. The overall mortality was 1.5% (early = 2, late = 1) The overall morbidity was 62% (early = 17%, late = 52%). The pouch was removed or was non-functional in 9%. All patients with a final diagnosis of Crohn’s disease have had their pouch excised. The median stool frequency was 4.0 (range 1.3–8.7) during the day, and 0.7 (range 0–2.1) during the night. The fewer night-time stools (J = 1.0 ± 0.6; W = 0.4 ± 0.5 P < 0.0001) and the reduced requirement of the W-pouch patients for anti-diarrhoeals (P = 0.004) were offset by the need for two W-pouch patients to pass a catheter to empty their pouches. Conclusions : The type of patients who present for IPAA surgery and the outcomes observed in this series of Auckland patients are similar to those reported from major centres elsewhere.     

Sporadic and familial myoclonic dystonia: Report of three cases and review of literature

Myoclonic dystonia refers to a clinical syndrome characterized by rapid jerky movements along with dystonic posturing of the limbs. Clinically, it is characterized by sudden, brief, electric shock-like movements, mostly involving the upper extremities, shoulders, neck and trunk. Characteristically, the movements wane with consumption of small dose of alcohol in about 50% of cases. Additionally, dystonic contractions are observed in most of the patients in the affected body parts and some patients may exhibit cervical dystonia or graphospasm as well. It may manifest as an autosomal dominant condition or sometimes, as a sporadic entity, though there are doubts whether these represent cases with reduced penetrance. The condition is usually treated with a combination of an anticholinergic agent like, benztropine, pimozide and tetrabenazine. We report one sporadic case and one familial case where the father and the son are affected. The cases were collected from the Movement Disorders Clinic of Bangur Institute of Neurosciences, Kolkata, West Bengal in a period of ten months. Myoclonic dystonia is a rare condition and to the best of our knowledge, this series is the first one reported from our country. Videos of the patients are also provided with the article.     

腹腔镜辅助下回肠储袋与直肠肌管吻合术治疗家族性腺瘤性息肉病的临床体会

目的:探讨腹腔镜辅助下回肠储袋与直肠肌管吻合术治疗家族性腺瘤性息肉病(familial adenomatous polyposis,FAP)的临床价值。方法:回顾分析2006～2011年为13例FAP患者分别行腹腔镜辅助回肠储袋与直肠肌管吻合术及回肠储袋与肛管吻合术的临床资料,并进行对比分析。结果:两组患者手术时间、术中出血量、术后切口长度、进食时间、住院时间、住院费用差异均无统计学意义。术后6个月随访,腹腔镜辅助下回肠储袋与直肠肌管吻合术较回肠储袋肛管吻合术后患者排便次数明显减少,肛管静息压及最大收缩压明显增高。结论:与传统回肠储袋肛管吻合术相比,回肠储袋直肠肌管吻合手术保留了部分直肠肌管,不仅有效减少了盆底肌肉损伤的可能性,而且很好地保护了肛门括约肌,因而可更好地保留患者的控排便功能。     

丁苯酞注射液联合依达拉奉对老年急性脑梗死患者 神经功能及血清hs-CRP、NSE 水平的影响

目的 观察丁苯酞注射液联合依达拉奉对老年急性脑梗死（ACI）患者神经功能及血清超敏C- 反应蛋白（hs-CRP）、神经元特异性烯醇化酶（NSE）水平的影响。方法 选取2015 年1 月—2017 年12 月 在浙江新安国际医院治疗的82 例ACI 患者,按照住院顺序分为联合组和对照组,每组41 例。对照组使用依 达拉奉治疗;联合组在对照组基础上使用丁苯酞注射液。两组疗程均为2 周,比较两组临床疗效、治疗前 后神经功能及血清hs-CRP 和NSE 的变化。结果 联合组患者治疗有效率高于对照组（97.56% VS 87.80%） （P <0.05）;两组患者治疗后6、12、24、48 及72 h 的美国国立卫生研究院卒中量表（NIHSS）评分比较, 采用重复测量设计的方差分析：①不同时间点的NIHSS 评分有差别（F =13.246,P =0.000）;②两组间的 NIHSS 评分有差别（F =22.331,P =0.000）,联合组NIHSS 评分较对照组低;③两组NIHSS 评分变化趋势 有差别（F =16.371,P =0.000）。联合组治疗前后血清hs-CRP、NSE 水平变化差值高于对照组（P <0.05）。 结论 在依达拉奉基础上,联合运用丁苯酞注射液治疗ACI 的效果更佳,能减轻神经功能损伤,有效控制机 体的炎症反应,且不会对患者造成不适,安全性更高,值得临床推广。     

Enamel and dentin mineralization in familial hypophosphatemic rickets: a micro-CT study

Objectives:

The aim of the present study was to analyse the mineralization pattern of enamel and dentin in patients affected by X-linked hypophosphatemic rickets (XLHR) using micro-CT (µCT), and to associate enamel and dentin mineralization in primary and permanent teeth with tooth position, gender and the presence/absence of this disease.

Methods:

19 teeth were collected from 5 individuals from the same family, 1 non-affected by XLHR and 4 affected by XLHR. Gender, age, tooth position (anterior/posterior) and tooth type (deciduous/permanent) were recorded for each patient. Following collection, teeth were placed in 0.1% thymol solution until µCT scan. Projection images were reconstructed and analysed. A plot profile describing the greyscale distance relationship in µCT images was achieved through a line bisecting each tooth in a region with the presence of enamel and dentin. The enamel and dentin mineralization densities were measured and compared. Univariate ANOVA and post hoc Tukey tests were used for all comparisons.

Results:

Teeth of all affected patients presented dentin with a different mineralization pattern compared with the teeth of healthy patients with dentin defects observed next to the pulp chambers. Highly significant differences were found for gray values between anterior and posterior teeth (p < 0.05), affected and non-affected (p < 0.05), as well as when position and disease status were considered (p < 0.05).

Conclusions:

In conclusion, the mineralization patterns of dentin differed when comparing teeth from patients with and without FHR, mainly next to pulp chambers where areas with porosity and consequently lower mineral density and dentin defects were found.     

Liver transplantation in a subject with familial hypercholesterolemia carrying the homozygous p.W577R LDL-receptor gene mutation

Mutations within the low density lipoprotein (LDL)-receptor gene result in familial hypercholesterolemia, an autosomal dominant inherited disease. Clinical homozygous affected subjects die of premature coronary artery disease as early as in early childhood. We identified a girl at the age of five yr with clinical homozygous familial hypercholesterolemia presenting with achilles tendon xanthomas and arcus lipoides. Her total cholesterol reached up to 1050 mg/dL. Molecular characterization of the LDL-receptor gene revealed a homozygous p.W577R mutation. Despite intensive treatment interventions with the combination of diet, statins, colestipol, and LDL-apheresis, the patient developed symptomatic coronary artery disease at the age of 16 yr. Subsequently, orthotopic liver transplantation was performed to cure the defective LDL-receptor gene. Clinical follow-up for almost nine yr post-transplantation revealed excellent liver function, normal liver enzymes, normal LDL-cholesterol, and regression of both tendon xanthomas and symptomatic coronary artery disease. In conclusion, liver transplantation can effectively reduce LDL-cholesterol in a familial hypercholesterolemia recipient with subsequent regression of xanthomas and atherosclerosis. Timing is extremely important in these exceptional cases to exclude the demand for heart transplantation due to severe coronary artery disease. In addition, the identification of the LDL-receptor as etiology of clinical homozygous hypercholesterolemia is a prerequisite once liver transplantation is considered as therapeutic option.     

Partial external biliary diversion for the treatment of intractable pruritus in children with progressive familial intrahepatic cholestasis: Report of two cases

Progressive familial intrahepatic cholestasis (PFIC) is a cholestatic liver disease of childhood. Pruritus secondary to increased bile salts in the serum may not respond to medical treatment. Partial external biliary diversion (PEBD), which reduces the serum bile salt level in the enterohepatic cycle, is used in the treatment of this symptom. In this study, our experience in performing this technique and the early promising results of PEBD in two children with PFIC are reported along with a review of the current literature. Partial external biliary diversion was performed by interposing a 15-cm jejunum between the gallbladder and abdominal wall. Biliary drainage through a stoma began in the fi rst postoperative day and reached 120-200 ml/day. Pruritus improved and then stopped on the 15th postoperative day, while the serum bile acid concentration also decreased. Partial external biliary diversion by jejunal interposition provides an excellent control of pruritus in children with PFIC with no adverse effects. A cholecystectomy should therefore be avoided in patients with PFIC.     

Characterization of a large Lebanese family segregating IgA nephropathy.

BACKGROUND: Familial aggregation of IgA nephropathy (IgAN) suggests that genetic factors contribute to the development of this trait. Because clinical manifestations in IgAN families are often limited to episodic haematuria, large kindreds tractable to linkage analysis have been difficult to identify. METHODS: We identified a large Lebanese-Druze kindred ascertained via an index case with biopsy-documented IgAN. We performed systematic screening of 38 family members and tested linkage to reported IgAN loci. RESULTS: Screening of this family identified 16 affected individuals, including 2 individuals with biopsy-documented IgAN and 14 with chronic renal failure or abnormal urinalyses on at least three separate occasions. This kindred spanned five generations and contained five consanguineous unions. Multigenerational inheritance suggested that autosomal dominant inheritance was most likely. Phenotypic manifestations among affected individuals varied from isolated haematuria to advanced renal failure necessitating transplantation; one instance of IgAN recurrence after transplantation was also documented. Older age was associated with greater severity of disease and higher incidence of renal failure. Parametric and non-parametric analyses with 33 microsatellite markers did not reveal any evidence of linkage to reported IgAN loci on chromosomes 6q22-23, 2q36 and 4q22-31. CONCLUSIONS: We describe one of the largest multigenerational IgAN kindreds reported to date. The high incidence of renal failure among older generations suggests a significant risk of progression to renal failure. We found no evidence of linkage to known loci, suggesting that familial IgAN encompasses multiple subtypes that will require distinction based on genetic or biomarker data.