The Dutch founder mutation SDHD.D92Y shows a reduced penetrance for the development of paragangliomas in a large multigenerational family

Germline mutations in SDHD predispose to the development of head and neck paragangliomas, and phaeochromocytomas. The risk of developing a tumor depends on the sex of the parent who transmits the mutation: paragangliomas only arise upon paternal transmission. In this study, both the risk of paraganglioma and phaeochromocytoma formation, and the risk of developing associated symptoms were investigated in 243 family members with the SDHD.D92Y founder mutation. By using the Kaplan–Meier method, age-specific penetrance was calculated separately for paraganglioma formation as defined by magnetic resonance imaging (MRI) and for paraganglioma-related signs and symptoms. Evaluating clinical signs and symptoms alone, the penetrance reached a maximum of 57% by the age of 47 years. When MRI detection of occult paragangliomas was included, penetrance was estimated to be 54% by the age of 40 years, 68% by the age of 60 years and 87% by the age of 70 years. Multiple tumors were found in 65% and phaeochromocytomas were diagnosed in 8% of paraganglioma patients. Malignant paraganglioma was diagnosed in one patient (3%). Although the majority of carriers of a paternally inherited SDHD mutation will eventually develop head and neck paragangliomas, we find a lower penetrance than previous estimates from studies based on predominantly index cases. The family-based study described here emphasizes the importance of the identification and inclusion of clinically unaffected mutation carriers in all estimates of penetrance. This finding will allow a more accurate genetic counseling and warrants a ‘wait and scan'' policy for asymptomatic paragangliomas, combined with biochemical screening for catecholamine excess in SDHD-linked patients.     

Using therapeutic mammoplasty to extend the role of breast-conserving surgery in women with larger or ptotic breasts

Introduction

The equivalence of breast-conserving surgery followed by postoperative radiotherapy against mastectomy is now firmly established in patients with early breast cancer. The results of surgery in large-breasted women can be poor, with radiation-induced fibrosis, chronic pain and poor cosmesis contributing to long-term psychological and physical morbidity. Therapeutic mammoplasty offers an alternative management strategy to both enhance the role of breast-conserving surgery and provide better outcomes.

Methods

A retrospective note review was undertaken of all patients undergoing therapeutic mammoplasty for breast malignancy between 2007 and 2011. All cases were performed using a Wise pattern-reduction technique. Histology and pathological outcomes were assessed. Postoperative outcomes reviewed included wound infection, seroma and need for further intervention.

Results

During the study period, 20 patients underwent therapeutic mammoplasty with a mean follow-up duration of 36 months. The mean weight of the lumpectomy specimen was 330g. The average cancer size was 34mm, with a mean margin clearance of 7mm. There was one episode of wound infection and three of delayed wound healing at the T-junction. One patient required a mastectomy for involved margins. There were no recurrences at the most recent follow-up visit.

Conclusions

Therapeutic mammoplasty offers a tailored approach to women with larger breasts and early breast cancers with good cosmetic results and oncological outcomes.     

重组人骨形成蛋白2诱导颅神经嵴细胞向肾上腺能神经元分化的研究

目的：研究重组人骨形成蛋白2(rhBMP2)诱导小鼠颅神经嵴细胞(CNCC)分化后所产生的神经元类型是否为肾上腺能神经元。方法：用50ng／ml rhBMP2诱导CNCC分化为神经元。提取诱导前后细胞内的总RNA,用反转录聚合酶链反应(RT-PCR)分别检测细胞中酪氨酸羟化酶(TH)和γ-氨基丁酸受体(GABAAR)亚单位的表达情况。结果：诱导前的CNCC中，TH和GABAAR亚单位均无mRNA水平的表达，诱导后二者均有表达，但表达的量均低于脑组织中的表达。结论：rhBMP2诱导CNCC后所分化的神经元为肾上腺能神经元，但在功能上可能弱于正常的肾上腺能神经元。     

经口腔机器人手术治疗头颈癌的初步经验

该文旨在研究经口腔机器人手术（TORS）治疗头颈部恶性肿瘤的技术可行性、安全性及有效性。对应用daVinci外科机器人治疗的20例患者进行前瞻性研究。纳入标准为成年患者的早期头颈癌，包括口腔癌、口咽癌、下咽癌及喉癌。结果，2例无法充分达到手术部位，手术终止。其他18例术后手术切缘阴性。8例行组织重建。10行单侧颈淋巴清扫，5例行双侧颈清，未行气管切开，术中、术后无并发症。     

Science behind cisplatin-induced nephrotoxicity in humans: A clinical study

Objective

To investigate the relationship between serum electrolyte changes and cisplatin induced nephrotoxicity.

Methods

We collected data from 18 patients undergoing cisplatin chemotherapy including serum electrolytes, creatinine, blood urea nitrogen (BUN) and urine potassium, sodium and pH levels before and after the cisplatin chemotherapy. All the patients had cancer and were treated with 40-50 mg/day cisplatin. Renal injury was assessed by measuring serum electrolytes, creatinine, BUN levels and urine potassium, sodium and pH levels.

Results

The five cycles of cisplatin based chemotherapy resulted in hypomagnesia (P=0.029), hypocalcaemia (P=0.001*), hypophosphatemia (P=0.003*), hypokalemia (P=0.001*) and increased serum creatinine (P=0.001*) and BUN (P=0.292*) levels. In urine analysis, decrease in potassium (P=0.024*) was found, except potassium there was no significant changes in sodium and urine pH.

Conclusions

The present study demonstrates that, acute nephrotoxicity was observed in patients with different types of cancers undergoing cisplatin based chemotherapy due to electrolyte disturbances, when no corrective measures were initiated.     

Hepatoprotective activity of Hepax-A polyherbal formulation

Objective

To evaluate the hepatoprotective potential of Hepax, a polyherbal formulation, against three experimentally induced hepatotoxicity models in rats.

Methods

Hepatoprotective activity of Hepax was studied against three experimentally induced hepatotoxicity models, namely, carbon tetrachloride (CCl₄), paracetamol and thiocetamide induced hepatotoxicity in rats.

Results

Administration of hepatotoxins (CCl₄, paracetamol and thiocetamide) showed significant morphological, biochemical and histological deteriorations in the liver of experimental animals. Pretreatment with Hepax had significant protection against hepatic damage by maintaining the morphological parameters (liver weight and liver weight to organ weight ratio) within normal range and normalizing the elevated levels of biochemical parameters (SGPT, SGOT, ALP and total bilirubin), which were evidently showed in histopathological study.

Conclusions

The Hepax has highly significant hepatoprotective effect at 100 and 200 mg/kg, p.o. on the liver of all the three experimental animal models.     

Biotinylated erythrocytes: in vivo survival and in vitro recovery

Rabbit erythrocytes were biotinylated by reaction with N- hydroxysuccinimidobiotin; the average level of biotinylation was 25,000 molecules per erythrocyte. These biotinylated cells exhibited a normal survival rate when reinfused into rabbits. Two studies demonstrated that the biotin label was stable in vivo. The first was a double- labeling experiment where the biotinylated erythrocytes were also labeled with 14C-cyanate; on reinfusion, the loss of biotinylated erythrocytes and 14C-cyanate label occurred in unison. The second study demonstrated that biotinylated erythrocytes that had been reinfused into rabbits could later be selectively isolated by attachment to an avidin support. This technique will facilitate a variety of studies that require the ability to label a specific cohort of cells in vitro and then reisolate those same cells after in vivo recirculation.