Thrombotic microangiopathic nephropathy, pulmonary hypertension and nephromegaly: case report of a patient treated with endothelin receptor antagonist

The coexistence of thrombotic microangiopathic nephropathy and pulmonary hypertension has only been described in association with malignancy and its treatment. Here we describe a 14-year-old boy with no prior medical history who presented with hypertension, proteinuria and nephromegaly, and then developed progressive pulmonary hypertension. Renal histology showed lesions consistent with glomerulopathy due to thrombotic microangiopathy (TMA). Pulmonary hypertension was controlled by the use of an oral endothelin receptor antagonist (bosentan). Although renal function deteriorated at the onset of pulmonary hypertension, an improvement was observed after the bosentan treatment. Nephromegaly persisted, but current creatinine clearance values are within the normal range. While this case exemplifies how thrombotic microangiopathic nephropathy may be associated with pulmonary hypertension, a therapeutic role of endothelin antagonists is suggested, not only for pulmonary hypertension but also for microangiopathic nephropathy.     

A microRNA signature defines chemoresistance in ovarian cancer through modulation of angiogenesis

Epithelial ovarian cancer is the most lethal gynecologic malignancy; it is highly aggressive and causes almost 125,000 deaths yearly. Despite advances in detection and cytotoxic therapies, a low percentage of patients with advanced stage disease survive 5 y after the initial diagnosis. The high mortality of this disease is mainly caused by resistance to the available therapies. Here, we profiled microRNA (miR) expression in serous epithelial ovarian carcinomas to assess the possibility of a miR signature associated with chemoresistance. We analyzed tumor samples from 198 patients (86 patients as a training set and 112 patients as a validation set) for human miRs. A signature of 23 miRs associated with chemoresistance was generated by array analysis in the training set. Quantitative RT-PCR in the validation set confirmed that three miRs (miR-484, -642, and -217) were able to predict chemoresistance of these tumors. Additional analysis of miR-484 revealed that the sensitive phenotype is caused by a modulation of tumor vasculature through the regulation of the VEGFB and VEGFR2 pathways. We present compelling evidence that three miRs can classify the response to chemotherapy of ovarian cancer patients in a large multicenter cohort and that one of these three miRs is involved in the control of tumor angiogenesis, indicating an option in the treatment of these patients. Our results suggest, in fact, that blockage of VEGF through the use of an anti-VEGFA antibody may not be sufficient to improve survival in ovarian cancer patients unless VEGFB signaling is also blocked.Ovarian cancer is the leading cause of gynecological cancer-related death in the developed world (1). Although progress has been made in its treatment by improved debulking surgery and the introduction of platinum–taxane regimens (2), the overall 5-y survival is only 29% in advanced stage disease (1), mostly because of diagnosis at an advanced stage and intrinsic and acquired resistance to platinum-based chemotherapy. Identifying molecular markers of ovarian cancer chemoresistance is, therefore, of crucial importance. Successful translation of findings at the molecular level will lead to individualized treatment regimens, improved chemotherapeutic response rates, and avoidance of unnecessary treatments.MicroRNAs (miRs) are a class of small noncoding RNAs that modulate gene expression by causing translational repression, mRNA cleavage, or destabilization (3). They are involved in numerous physiological cellular processes (4–7). Most importantly, accumulating evidence indicates that many miRs are aberrantly expressed in human cancers (8–10), and their expression profiles can classify stage, subtype, and prognosis of some cancers (11–14).In this report, we describe an miR signature that defines chemoresistant ovarian carcinoma. We show that some miRs are deregulated in most patients with resistant ovarian carcinomas, and we show that miR-484 exerts its action through the regulation of angiogenic factors. We postulate that this miR signature of drug resistance could be used to develop strategies for targeted therapies in chemorefractive ovarian carcinoma patients.     

Use of healthcare a long time after severe burn injury; relation to perceived health and personality characteristics

Purpose.?The aim of the study was to evaluate which factors are associated with the use of healthcare a long time after severe burn injury.

Method.?After a review process based on clinical reasoning, 69 former burn patients out of a consecutive group treated at the Uppsala Burn Unit from 1980?–?1995 were visited in their homes and their use of care and support was assessed in a semi-structured interview. Post-burn health was assessed with the Burn-Specific Health Scale-Brief (BSHS-B) and personality was assessed with the Swedish universities Scales of Personality (SSP).

Results.?The participants were injured on average eight years previously. Thirty-four had current contact with healthcare due to their burn injury and had significantly lower scores on three BSHS-B-domains: Simple Abilities, Work and Hand function, and significantly higher scores for the SSP-domain Neuroticism and the SSP-scales Stress Susceptibility, Lack of Assertiveness, and lower scores for Social Desirability. There was no relation to age, gender, time since injury, length of stay, or to the surface area burned.

Conclusions.?A routine screening of personality traits as a supplement to long-term follow-ups may help in identifying the patient's need for care.     

薄层扫描法测定熊胆引流物中胆汁酸含量

熊胆向以贵重药材闻名,被称之为稀有药品,为开发熊胆资源,解决熊胆奇缺问题,我校解剖教研室已成功地完成了人工引流熊胆汁技术,可随时进行人工引流获取熊胆汁。为了确定胆汁的质量指标,了解其主要成分,我们进行了引流胆汁与天然熊胆的分析。文献报道,熊胆中主要含熊去氧胆酸(ursodesoxycholic acid,UDCA)、鹅去氧胆酸(cheno desoxycholic acid,CDCA)、胆酸(cholic acid,CA)、去氧胆酸(deoxycholic,acid DCA)等。     

Magnetic resonance imaging: absence of in vitro cytogenetic damage

Human lymphocytes and Chinese hamster ovary (CHO) cells in culture were exposed for 12 1/2 hours to a magnetic resonance imaging apparatus with a 2.35-Tesla magnet and 100-MHz radio frequency emission. The cells were examined for cytogenetic damage manifested either as chromosome aberrations or sister chromatid exchanges (SCEs), which constitute very sensitive measures of genetic and cellular damage. In either unstimulated or stimulated human lymphocytes, as well as in exponentially growing CHO cells, no increase in either chromosome aberrations or SCEs was found as a result of exposure to these MR conditions. The data indicate that long-term exposure to MR imaging conditions far exceeding those to be found in the clinical situation does not cause cytogenetic damage.