复合杂合parkin基因突变家族的不同表型

背景：Parkin基因（PRKN）突变可导致常染色体隐性遗传性早发帕金森病（EOPD）。目的：探讨EOPD白人家族PRKN突变的表现和基因型-表型关系。设计：对EOPD家族的3代20例成员进行基因分析，该家族有4例患者。应用直接基因组DNA测序、半定量聚合酶链反应、实时定量聚合酶链反应以及逆转录酶聚合酶链反应分析以确定PRKN突变。结果：4例早发患者（年龄30—38岁）被确定有PRKN复合杂合突变（T240M和EX5_6缺失），虽然PRKN的杂合T240M和纯合EX5_6缺失突变已有描述，但是据悉，本文为上述复合杂合突变的首次报道。患者的表型为典型常染色体隐性遗传性EOPD的表现，其特征是对左旋多巴治疗有效、相对缓慢的进展和运动障碍。所有杂合突变的基因携带者（T240M或EX5_6缺失）和1例56岁的复合杂合突变女性携带者（T240M和EX5_6缺失）无任何神经系统症状。结论：研究发现，PRKN基因复合杂合突变（T240M和EX5_6缺失）导致一个大的白人家族中4例成员发生常染色体隐性遗传性EOPD。另外1例成员具有相同的突变，比4例患者的平均发病年龄大10岁，并且无本病的临床表现。不完全的外显率对遗传咨询具有暗示作用，并且提示复杂的基因一环境交互作用在PRKN相关EOPD的发病机制中发挥作用。     

The effect of nadroparine on coagulation mechanisms: ultrastructural analysis.

Low molecular weight heparins are widely used in the prophylaxis and treatment of thrombotic disorders. The effect of low molecular weight heparins on coagulation was examined ultrastructurally in an animal model. A test and a control group was formed, each consisting of five rabbits. Nadroparine (225 Institute of Chaoy Unit/kg twice daily) was applied to the test group for 10 days. The control group received 1 ml saline solution subcutaneously. Blood and vascular tissue samples collected at the end of the 10th day were evaluated under a JEM 100 B electron microscope. Platelet degranulation and agglutination was observed in the control group. Fibrin materials were detected in the cytoplasms and surroundings of degranulated platelets. Erythrocyte accumulation was remarkable on the vascular endothelium with intact coagulation periods. In the test group, outer membranes of platelets, hyalomere, and granular structures in the granulomeres were detected to be nearly intact. There were rare erythrocytes in the large vascular lumens. The aggregation phase had occurred but no agglutination was detected. Nadroparine seems to preserve consistency of lipoprotein membranes of platelets and granular structures containing enzymes, which contribute to the coagulation mechanisms.     

Case Report: Second case of a successful pregnancy in maternal isovaleric acidaemia

Summary: A female patient with isovaleric acidaemia had a successful outcome from pregnancy.     

Denervation pattern of three mimic muscles in Bell's palsy.

OBJECTIVE: To explore the presence and grade of denervation in three mimic muscles in facial nerve palsy. METHODS: The frontalis, orbicularis oculi (OO), and mentalis muscles were explored in 54 patients with Bell's palsy, after 30 days from the beginning of symptoms. Concentric needle electromyography, including fibrillation detection, was performed in the three muscles on the affected side. Compound muscle action potentials (CMAP) were recorded on both sides and a CMAP ratio was calculated from each muscle. The House-Brackman scale was used to assess the initial clinical evaluation and the follow-up until recovery. RESULTS: Fibrillation was recorded in 32 patients on the 30th day after the onset and was present in 100% of mentalis and in 90% of frontalis, but in only 34% of OO, a statistically significant difference. The grade of fibrillation in OO was also statistically lower from those in the other two muscles. The 32 patients were grouped according to the presence (A) or not (B) of fibrillation in OO. In group A, CMAP ratios (affected/normal side) did not differ significantly among the three muscles. However, in group B they were significantly greater in OO and frontalis than in mentalis. In between-group comparison, group B muscles had significantly higher CMAP ratios, lower degree of fibrillation, and better functional recovery. CONCLUSION: In facial palsy, the presence and grade of fibrillation in OO are lower than in frontalis and mentalis muscles and prognosis is more favorable for the non-fibrillating OO group of patients.     

27-jähriger Reiserückkehrer mit hohem Fieber und septischem Schock im Verlauf

A 27-year-old man was admitted with high fever and shivers eleven days after returning from vacation in Indonesia. Physical examination, laboratory values, abdominal ultrasound, and chest x-ray were not conclusive. All blood cultures yielded growth of Salmonella enterica serovar Typhi, and typhoid fever was diagnosed. Subsequently, the patient developed septic shock and pulmonary edema.In this case report epidemiological, clinical, and therapeutic aspects of typhoid fever are discussed with special emphasis on criteria for severe typhoid fever, which is treated with additional glucocorticoids.     

Hippocampal damage and cytoskeletal disruption resulting from impaired energy metabolism

To determine if impaired energy metabolism might contribute to some aspects of Alzheimer disease (AD), including the vulnerability of the CA1 region of the hippocampal formation and the altered cytoskeleton evident in neurofibrillary tangles, we examined the effects of metabolic poisons on neuronal damage and cytoskeletal disruption in the hippocampal formation. Intrahippocampal injection of 3-nitropropionic acid (3-NP) and malonic acid resulted in neuronal death, particularly in CA1. Cytoskeletal disruption included loss of dendritic MAP2, but sparing of axonal τ. MK-801 (a noncompetitive NMDA receptor antagonist) did not atenuate the lesions produced by intrahippocampal injection of malonate. MK-801, however, was effective against intrastriatal malonate. Acute systemic 3-NP resulted in neuronal damage and cytoskeletal disruption in the CA1 region of the hippocampal formation, including an extensive loss of MAP2 immuno-reactivity, but sparing of τ. The neuronal loss in CA1 was delayed as compared to striatum. Chronic intraventricular infusion of 3-NP produced a different pattern of neuronal damage. Loss of τ-1 immuno-reactivity was observed in CA3 and CA1 s. oriens, whereas MAP2 immunostaining was preserved. These results demonstrate that chronic and acute administration of metabolic inhibitors produce distinct patterns of neuronal damage and cytoskeletal disruption. The results further suggest a differential involvement of the NMDA receptor in malonate-induced neuronal damage in striatum as compared to the hippocampus. The pattern of neuronal damage and cytoskeletal disruption observed following acute metabolic impairment resembled some aspects of neurofibrillary pathology in AD, but did not result in τ hyperphosphorylation.     

Effects of poor glucose handling on arterial stiffness and left ventricular mass in normal children.

AIM: Cardiovascular risk factors can be present in children and young adults. We previously found abnormal microvascular function in children who had glucose intolerance and insulin resistance. The aim of the present study was to investigate whether they also have abnormalities in left ventricular mass (LVM) and arterial stiffness. METHODS: We measured heart dimensions and LVM using echocardiography, and arterial stiffness using pulse wave analysis in 23 children with good glucose handling (postfeeding glucose: 3.9 to 5 mmol/L) and 21 with poor glucose handling (7.7 to 11.4 mmol/L). RESULTS: The time to pulse reflection was slightly shorter in the poorer glucose handlers (mean+/-SD: 143+/-10 vs 153+/-20 ms, P=0.04), suggestive of increased arterial stiffness. Also in this group, there were significant relationships between intraventricular septal thickness, blood pressure and body mass index, but not in the normal glucose handlers. CONCLUSIONS: We have found that normal children who are in the lowest quintile of glucose tolerance in comparison with their peers are exhibiting the first signs of arterial stiffening. In addition, we have seen the beginnings of a relationship between blood pressure, body mass index and left ventricular enlargement in this group. While these changes may not yet be clinically significant, their emergence might be further evidence of early predisposition to cardiovascular disease.