Prenatal diagnosis of metachromatic leukodystrophy in a family with pseudo arylsulfatase A deficiency by the cerebroside sulfate loading test

Prenatal diagnosis was requested by a family at risk for metachromatic leukodystrophy (MLD). An examination of the family leukocyte arylsulfatase A profile revealed that the mother had pseudo arylsulfatase A deficiency. Cultured amniotic fluid cells were deficient in arylsulfatase A, so two possibilities were indicated: the fetus was affected with MLD or had the pseudodeficiency phenotype. The only known biochemical test to differentiate the two enzyme deficient phenotypes is cerebroside sulfate loading of growing fibroblasts. The pseudodeficient cells hydrolyze the incorporated sulfatide as efficiently as control cells, whereas MLD cells show no hydrolysis. Application of this test to the at risk cultured amniotic fluid cells resulted in appreciable uptake of the sulfolipid, but no hydrolysis. Control amniotic fluid cell cultures hydrolyzed 82 to 95% of the incorporated sulfatide. Therefore, an affected fetus was indicated. Fibroblasts derived from the aborted fetus showed a deficiency of arylsulfatase A and a similar inability to hydrolyze cerebroside sulfate in the loading test. The loading technique allowed the prenatal diagnosis of MLD when the arylsulfatase A analysis was equivocal.     

TRANSFER FACTOR IN CHRONIC AND RECURRENT RESPIRATORY TRACT INFECTIONS IN CHILDREN

Abstract Gröhn, P. (The Institute of Biomedical Sciences, School of Medicine, University of Tampere, and the Children's Department, Tampere Central Hospital, Tampere, Finland). Transfer factor in chronic and recurrent respiratory tract infections in children. Acta Paediatr Scand, 66:211, 1977.—Five cases with abnormal sensitivity to respiratory tract infections are described. The cases showed a marked impairment in their cell mediated immunity state. Administration of a chromatographically purified transfer factor component increased the skin test sensitivity to common recall antigens. Interestingly, a similar effect in skin reactivity was observed with repeated skin tests alone, when antigen concentrations, initially high enough to cause a positive reaction, were used. Neither the administration of transfer factor nor skin testing with high antigen concentrations had an effect on blast transformation percentages. The therapy with chromatographically purified transfer factor appeared promising on the clinical condition of the patients.     

小肠部分切除大鼠术后一氧化氮代谢途径干预对葡萄糖代谢的影响

目的：观察小肠部分切除大鼠术后一氧化氮代谢途径干预对大鼠术后葡萄糖代谢的影响，寻找解决术后胰岛素抵抗的方法。方法：实验于2005—01／2006—08在解放军第四军医大学第二附属医院中心实验室完成。实验分组：96只大鼠随机数字表法分为4组，正常对照组，L-硝基-精氨酸甲酯处理组，L-精氨酸处理组，L-精氨酸＋L-硝基-精氨酸甲酯处理组，每组24只。实验干预：建立大鼠小肠部分切除模型，各干预组分别尾静脉注射1mg／kg L-硝基-精氨酸甲酯、100mg／kg L-精氨酸处理、0．5mg／kg L-硝基-精氨酸甲酯＋50mg／kg L-精氨酸处理进行一氧化氮代谢途径干预。正常对照组只注射1mL生理盐水。实验评估：①给药后2，8，12，24，48h取血，测定血清中一氧化氮含量及血糖检测。②给药后24h，48h，1周后采用胰岛素敏感性实验计算每公斤代谢体质量每分钟代谢葡萄糖的量。结果：96只大鼠均进入结果分析。①血清一氧化氮含量：L-硝基-精氨酸甲酯处理组各时间点血清一氧化氮含量低于正常对照组（P〈0、05），而L-精氨酸处理组各时间点血清一氧化氮含量高于正常对照组（P〈0．05）；L-精氨酸＋L-硝基-精氨酸甲酯处理组与正常对照组比较差异无显著性（P〉0．1）。②空腹血糖：给药后8，12，24，48h L-硝基-精氨酸甲酯处理组高于正常对照组（P〈0．05）。给药后8，12，24，48h L-精氨酸处理组低于正常对照组（P〈0．05）；L-精氨酸＋L-硝基-精氨酸甲酯处理组与正常对照组比较差异无显著性（P〉0．1）。③稳态情况下每千克代谢体质量每分钟代谢葡萄糖的量：L-硝基-精氨酸甲酯处理组显著低于正常对照组（P〈0．05），而L-精氨酸处理组则显著高于正常对照组（P〈0．05）；L-精氨酸＋L-硝基-精氨酸甲酯处理组与正常对照组比较差异无显著性（P〉0．1）。结论：小肠部分切除大鼠术后一氧化氮代谢途径在葡萄糖转运和胰岛素活性方面可能起着重要作用，提示其可能是解决术后胰岛素抵抗的一种方法。     

TEACHING FUNCTIONING,DISABILITY AND REHABILITATION TO FIRST YEAR MEDICAL STUDENTS

BackgroundMany patients have disabilities; it is therefore essential that medical education includes comprehensive teaching on disability and rehabilitation. In 2006, Hannover Medical School implemented an introductory course in the curriculum for medical students, on how to communicate with persons with disability and on the need for rehabilitation. The course, entitled “Introduction to medicine”, has the main goals of teaching the strategy and systematic approach of medicine to solving patients’ problems.MethodsThis paper describes the content, methods and outcomes of 1 of the 4 main themes of the “Introduction to medicine” course; the theme “Pain and disability”, which is covered in the second week of the course.ResultsEvaluation of the “Pain and disability” module found that students’ ratings for the category “patient involvement” were very high (93%), whereas their ratings for the category “examination of student knowledge” were low. The overall rating of the module was “good” (10.8 out of 15 points), but not “very good”.CONCLUSIONThe concept of the “Pain and disability” module is feasible and successful, even though it is scheduled early in the first year of the curriculum and approximately 350 students participate. Factors related to this success are: a mixture of teaching knowledge, supporting students’ understanding, and applying communication and physical examination skills.LAY ABSTRACTAs every medical doctor will be confronted with persons with disabilities, medical students should learn about disability and rehabilitation topics. Within a comprehensive concept of teaching disability and rehabilitation topics, in Hannover Medical School, a propaedeutic teaching course has been implemented to sensitize the students to how to communicate with persons with disability and to raise awareness about the need for rehabilitation.The survey of the students showed good acceptance of the new course, and the involvement of patients in the lessons was especially appreciated.Key words: teaching, medical school, persons with disabilities, undergraduate medical training, pain, disability, rehabilitation

Disability is defined as the interaction of a person with a health condition and/or impairment and the environment (1, 2). This definition of disability includes persons with congenital conditions (e.g. cerebral palsy, spina bifida, chromosomal aberrations, etc.) and those with acquired impairments (e.g. traumatic brain injury, spinal cord injury, limb amputation, etc.). The definition also includes persons with chronic diseases, cancer, infectious diseases, and others who may experience disability related to a disease and its consequences (e.g. loss of physical performance, need for oxygen, diabetic feet, etc.). In addition, mental health disorders and learning disabilities often result in disability. For medical doctors, and other professions in medicine, education on functioning, disability and rehabilitation must be addressed in the undergraduate curriculum, since:

• in practice, all medical doctors will treat patients with disabilities;
• many persons with disabilities, including those with chronic health conditions, require rehabilitation, including assistive devices;
• in long-term care persons with disabilities may have specific health needs that are treated by medical doctors
• communication with persons with disabilities may be challenging and result in uncertainty and communication barriers on both sides, reducing the quality of medical treatment.

Medical students should therefore learn about the main factors causing disabilities, based on theoretical models, as early as possible in their education, and become competent in communicating with persons with disabilities and creating an appropriate atmosphere during conversation and examination.Rehabilitation is one of 4 main health strategies, together with preventive, curative and supportive strategies (3–5). It is the strategy that “based on the World Health Organization’s (WHO’s) integrative model of human functioning and disability applies and integrates biomedical and engineering approaches to optimize a person’s capacity. This strategy build on and strengthen the resources of the person approaches which provide a facilitating environment. It should help to develop a person’s performance in the interaction with their environment with the goal to enable people with health conditions experiencing or likely to experience disability to achieve and maintain optimal functioning in interaction with the environment” (6). Thus, it is crucial that all physicians understand the principles of rehabilitation, the indications and contraindications for rehabilitation, rehabilitation interventions, and complex rehabilitation concepts. Based on federal regulations in Germany rehabilitation is taught together with physical medicine and naturopathy in a so-called cross-sectional field. However, the content and the academic leadership of this field in German medical faculties is very diverse (7, 8). Currently, the bodies responsible are updating the content of the curriculum (with rehabilitation as an independent field of learning in the course examination) and introducing more rehabilitation topics into the catalogue of learning goals (9).Hannover Medical School has implemented a teaching course to impart basic knowledge about disability and rehabilitation, teach medical students to how to communicate with persons with disability, and raise awareness of the need for rehabilitation. This course is integrated into the initial teaching block on the principles of clinical work (the so-called Propädeutikum), which is delivered at the start of the first year medical student curriculum (10). The course has the following teaching/learning goals:

• provide an insight into a systematic pathway of the medical problem-solving process (“from the patient’s problems to diagnosis”), demonstrated using patient cases;
• understanding pain as symptom and/or disease;
• understanding disability and the main principles of rehabilitation;
• acquiring basic skills in clinical examination and understanding the physician’s role

     

Relationship between mechanical dyssynchrony and intra-operative electrical delay times in patients undergoing cardiac resynchronization therapy

Background

It is important to understand the relationship between electrical and mechanical ventricular activation in CRT patients. By measuring local electrical activation at multiple locations within the coronary veins and myocardial contraction at the same locations in the left ventricle, we determined the relationship between electrical and mechanical activation at potential left ventricular pacing locations.

Methods

In this study, mechanical contraction times were computed using high temporal resolution cine cardiovascular magnetic resonance (CMR) data, while electrical activation times were derived from intra-procedural local electrograms.

Results

In our cohort, there was a strong correlation between electrical and mechanical delay times within each patient (R² = 0.78 ± 0.23). Additionally, the latest electrically activated location corresponded with the latest mechanically contracting location in 91% of patients.

Conclusions

This study provides initial evidence that our method of obtaining non-invasive mechanical activation patterns accurately reflects the underlying electromechanical substrate of intraventricular dyssynchrony.     

Prognostic value of adenosine stress cardiovascular magnetic resonance and dobutamine stress echocardiography in patients with low-risk chest pain

Excluding obstructive coronary artery disease (CAD) as the etiology of acute chest pain in patients without diagnostic electrocardiographic changes or elevated serum cardiac biomarkers is challenging. Stress testing is a valuable risk-stratifying technique reserved for the subset of these patients with low-risk chest pain who have an intermediate clinical probability of obstructive CAD. Given the risks of radiation inherent to nuclear and computed tomography imaging, both adenosine stress cardiovascular magnetic resonance (AS-CMR) imaging and dobutamine stress echocardiography (DSE) are attractive alternative stress modalities. An essential characteristic of stress modalities is their negative prognostic value; as one must exclude clinically-relevant CAD such that patients can be discharged safely. Therefore, the aim of this study was to validate a favorable negative prognostic value for both AS-CMR and DSE in patients presenting with low-risk acute chest pain. This retrospective study included 255 patients with low-risk acute chest pain and no prior history of CAD presenting to the emergency department at our institution, with 89 patients evaluated by AS-CMR and 166 by DSE. Median follow-up was 292?days, and consisted of medical record review. The primary end-point was the composite of cardiac death, nonfatal acute myocardial infarction, obstructive CAD on invasive coronary angiography (ICA) or recurrent chest pain requiring hospital admission. Test characteristics such as sensitivity and specificity could not be evaluated as patients were not routinely evaluated with ICA. All patients completed the stress protocol without adverse events during testing. 82/89 patients (92.1%) and 164/166 patients (98.8%) had negative AS-CMR and DSE studies, respectively. Both AS-CMR and DSE had excellent negative prognostic values for the primary endpoint, 100 and 99%, respectively. Both AS-CMR and DSE are effective stress modalities for excluding clinically significant coronary artery disease in patients presenting acute low-risk chest pain. Patients without findings to suggest ischemia have an excellent intermediate-term prognosis.     

Locally advanced cervix cancer: Chemotherapy prior to definitive surgery or radiotherapy. A single institutional experience

Primary or neoadjuvant chemotherapy prior to definitive local therapy has potential advantages for locally advanced cervix cancer. It can downstage a cancer and allow definitive local therapy to be technically possible (surgery), or potentially more effective (radiotherapy). It can also eradicate subclinical systemic metastases. This report reviews a single institution’s experience of neoadjuvant chemotherapy prior to definitive local therapy for cervix cancer over a 13‐year period. One hundred and six patients were treated with this intent. The patients were analysed for their response to chemotherapy, treatment received, survival, relapse and toxicity. The chemotherapy was feasible and the majority of patients had a complete or partial response (58.5%). Eight patients did not proceed to local treatment. Forty‐six patients had definitive surgery and 52 had definitive radiotherapy. The 5‐year overall survival was 27% and the majority of patients died with disease. The first site of relapse was usually in the pelvis (46.2%). Late complications that required ongoing medical therapy (n = 6) or surgical intervention (n = 2) were recorded in eight patients (7.5%). On univariate analysis stage (P = 0.04), tumour size (P = 0.01), lymph node status (P = 0.003), response to chemotherapy (P = 0.045) and treatment (P = 0.003) were all significant predictors of survival. On multivariate analysis, tumour size (P < 0.0001) and nodal status (P = 0.02) were significant predictors of survival. Despite the impressive responses to chemotherapy of advanced cervix cancer, there is evidence from randomized trials that it does not improve or compromise survival prior to radiotherapy. As its role prior to surgery remains unclear, it should not be used in this setting outside a prospective randomized trial.     

新疆医科大学维汉青年颞下颌关节紊乱病的流行病学调查

目的：探讨颞下颌关节紊乱病（TMD）在新疆医科大学维汉青年人中的患病情况。方法：对新疆医科大学812名在读维汉医学生（年龄17～28岁）进行了TMD患病状况及咬合情况调查。按照Helkimo指数进行分析,包括既往功能紊乱指数和临床检查功能紊乱指数。采用SPSS13．0软件包对数据进行χ^2检验。结果：无既往功能紊乱者（Ai0）占73．40％,既往功能紊乱者（AiⅠ＋Ⅱ）占26．60％,无临床检查功能紊乱者（DiO）占60．50％,临床检查功能紊乱者（DiⅠ～Ⅲ）占39．50％。结论：TMD的患病率为39．50％,男女患病率无显著差异,异常猞组发病率显著高于正常袷组,TMD的发生与夜磨牙、偏侧咀嚼有关。     

房间隔缺损介入封堵术并发症的预防及护理

1临床资料2003-12/2005-01收治房间隔缺损(ASD)24(男15,女9)例,年龄2～68岁,体质量10～72 kg.经心脏X线三位片、心电图、彩色多普勒超声心动图确诊为继发型ASD.经彩色多普勒超声心动图显示ASD直径为4～32 mm,选择的封堵器直径为10～42 mm.结果: 1例术中因封堵器脱落经外科手术抢救治疗无效死亡,1例术后2 d出现Ⅱ度Ⅱ型房室传导阻滞,经药物治疗7 d痊愈,余22例封堵器置入治疗患者无并发症发生,疗效满意.