内源性硫化氢的中枢心血管效应与KATP通道开放机制有关

背景:硫化氢具有舒张离体血管平滑肌、促进下丘脑促肾上腺皮质激素释放激素和细胞膜超极化的作用.中枢内硫化氢是否参与心血管活动的调节目前尚未得到充分的研究.目的:观察中枢内源性硫化氢的心血管效应及其机制.设计、时间及地点:随机对照动物实验,于2007-10/2008-10在解放军第一医院检验科完成.材料:清洁级雄性SD大鼠40只,体质量200～250 g;S-腺苷蛋氨酸,KATP通道阻断剂格列苯脲为Sigma公司产品.方法:40只大鼠随机被分为6组:①对照组6只,注射人工脑脊液.②S-腺苷蛋氨酸低剂量组6只注射S-腺苷蛋氨酸5 μmol、中剂量组5只注射S腺苷蛋氨酸10 μmol、高剂量组7只注射S-腺苷蛋氨酸20 μmol.③预先注射人工脑脊液8只或格列苯脲格列苯脲8只,40 min后注射10 pmol S-腺苷蛋氨酸.将大鼠固定于立体定位仪,进行侧脑室注射.主要观察指标:①侧脑室注射不同剂量S-腺苷蛋氨酸后对血压及心率的影响.②侧脑室注射KATP通道阻断剂格列苯脲对侧脑室注射S-腺苷蛋氨酸中枢心血管效应的影响.结果:侧脑室注射S-腺苷蛋氨酸能够显著降低麻醉大鼠的血压,减慢大鼠的心率.侧脑室注射人工脑脊液不影响麻醉大鼠的血压和心率.格列苯脲预处理能显著减弱侧脑室10 μmol S-腺苷蛋氨酸产生的降低血压效应,与人工脑脊液预处理组比较差异有显著性意义(P＜0.05),格列苯脲+S腺苷蛋氨酸组和对照组比较差异无显著性意义(P＞0.05).结论:侧脑室注射S-腺苷蛋氨酸增加内源性硫化氢产生的中枢性降低血压、减慢心率的作用可能与KATP通道开放有关.     

Clinical and biochemical characteristics of patients with ornithine transcarbamylase deficiency

BackgroundOrnithine transcarbamylase deficiency (OTCD) is pleomorphic congenital hyperammonemia, in which the prognosis of the patient is determined both by genotype and environmental factors. This study investigated the clinical and biochemical characteristics of OTCD patients with different prognosis.MethodOf 35 OTCD patients, six males deceased at the first disease-onset, 17 males survived and had controllable ammonia levels after treatment, and 12 females survived through the first disease-onset but had intractable hyperammonemia and high mortality. Fasting blood samples from patients collected at three disease stages were used for the analysis of amino acid (AA) profile, acylcarnitine profile, and micronutrients. Differences in profiles between patients and healthy controls and within patient groups were studied.ResultsAll OTCD patients had accumulation of glutamine, homocitrulline, lysine, glutamate, cystathionine, and pipecolic acid, as well as deficiency of citrulline, tryptophan, threonine, and carnitine. For male non-survivors, most other AAs and long-chain acylcarnitines were elevated at disease onset, of which the levels of creatine, N-acetylaspartic acid, and homoarginine were remarkably high. Male survivors and female patients had most other AAs at low to normal levels. Compared with male survivors, female patients had much lower protein-intolerance, as indicated by significantly lower levels of protein consumption indicators, including essential AAs, 1-methylhistidine, acylcarnitines et al., but high levels of ammonia. Female patients still had significantly higher levels of citrulline, homocitrulline, and citrulline/arginine compared to male survivors.ConclusionUnique profiles were observed in each group of OTCD patients, indicating specific physiological changes that happened to them.     

Effects of hypoglycemia on developmental outcome in children with congenital hyperinsulinism

Children with congenital hyperinsulinism are at risk for recurring, severe episodes of hypoglycemia that can cause seizures, brain damage, and developmental delay. To assess the frequency of permanent brain damage in this disorder, we carried out a telephone survey of 68 children who presented to The Children's Hospital of Philadelphia between 1980 and 2000. One third of the group had some degree of developmental delay. Those presenting in the first week of life and those with medically unresponsive hyperinsulinism were more likely to have delays. Early recognition and control of hypoglycemia are essential for preventing developmental delay in these children.     

Sonographic characteristics of congenital uterine abnormalities and associated pregnancy

Faulty development of the mullerian duct system results in various uterine, vaginal, and renal abnormalities. Complete or partial absence of mullerian duct fusion and/or canalization results in septate, bicornuate, or double uterus; the specific anomaly depends upon the degree of fusion and canalization. Unilateral renal agenesis is frequently associated. Three cases of uterine anomalies associated with pregnancy are presented. When a pregnancy occurs in one side of a double uterus, the nonpregnant side may simulate a solid pelvic mass, such as a leiomyoma. In anomalies where there is a communication between two uterine cavities, the nonpregnant side may require the appearance of a cystic mass. Pregnancy associated with uterine anomalies carries significant morbidity.     

Clinical characteristics and mechanisms of stroke after polytrauma

OBJECTIVES: To describe the clinical characteristics of acute stroke attributable to trauma and to analyze the mechanisms and effect of stroke on outcome in patients with polytrauma. PATIENTS AND METHODS: We retrospectively reviewed the medical records of patients with polytrauma complicated by stroke at the Mayo Clinic in Rochester, Minn. The diagnosis of stroke was matched with trauma for the period between January 1, 1985, and December 31, 2001. Polytrauma was defined as at least 2 injuries that involve at least 1 vital organ (eg, lung or liver) and necessitate patient admission to a trauma intensive care unit. RESULTS: We identified 14 patients with polytrauma who had experienced a stroke (13 ischemic and 1 hemorrhagic). Craniocervical artery dissection was the most common mechanism (7 patients), and skull or facial fractures were a possible marker for this (5 of 7 patients). There were frequent delays in identifying stroke, with limb fracture on the side of the paresis (5 of 6 patients) being a possible factor. Four patients died of postischemic brain swelling, and 5 had major neurologic impairment. CONCLUSIONS: Stroke after polytrauma is due to various mechanisms, is frequently difficult to recognize early, and profoundly affects patient outcome.     

伴有嗜酸粒细胞增多的血液病临床和实验研究

目的 探讨伴有嗜酸粒细胞增多的血液病患者的临床和分子、细胞遗传学特征.方法 对44例伴有嗜酸粒细胞增多血液病患者的骨髓标本,经直接法和24 h短期培养后按常规方法制备染色体,采用R显带技术进行细胞遗传学分析;分别应用PDGFRα、PDGFRβ、FGFR1基因探针,进行荧光原位杂交(FISH)检测.结果 44例患者骨髓细胞经常规染色体核型分析,异常核型检出率为13.64%(44例中6例),而应用FISH技术分析,异常克隆检出率为29.55%(44例中13例),其中7例(15.91%)伴有FIP1L1-PDGFRα(简称F/P)融合基因,3例(6.82%)PDGFRα基因重排,2例(4.55%)PDGFRβ基因异常,1例(2.27%)FGFR1基因重排.将患者分为PDGFRα、PDGFRβ或FGFR1基因重排阳性(13例)与阴性(31例)组,阳性组患者的皮肤、心血管、脾脏、肺脏等器官受累程度以及WBC、PLT、HGB等血液学指标与阴性组患者无明显差异;与阴性组比较,阳性组患者胃肠道症状表现较为突出,且绝大多数患者外周血白细胞分类可见嗜酸粒细胞重度增高(绝对值＞5×109/L)以及骨髓中出现幼稚嗜酸粒细胞(P值均＜0.05).结论 伴有嗜酸粒细胞增多的血液病患者具有独特的临床和血液学特征.染色体核型分析与FISH方法结合具有较高的异常克隆(特别是PDGFRα基因异常)检出率,有助于鉴别疾病的良、恶性本质,判断预后及选择合理的治疗方案.

Abstract：

Objective To analyze the clinical and laboratory characteristics of hematological diseases associated with eosinophilia. Methods Karyotype analysis was performed by direct method and/or short-time culture of bone marrow cells for R-banding. Fluorescence in situ hybridization ( FISH ) was performed using PDGFRα, PDGFRβ and FGFR1 break-apart probes. Results The clinical and hematological findings of 44 patients were diagnosed as hematological diseases associated with eosinophilia. Abnormal karyotypes were detected in 6 cases ( 13.64% ) with karyotyping. The efficiency of the detection of abnormal clone was markedly increased to 29. 55% ( 13/44 ) with FISH techniques, including 7 cases with FIP1 L1-PDGFRα ( F/P,15.91% ), 3(6. 82% ) PDGFRα rearrangement, 2 (4. 55% ) aberrant PDGFRβ gene and 1 (2. 27% )FGFR1 rearrangement. Patients being PDGFRα, PDGFRβ or FGFR1 positive ( 13 cases) or negative (31 cases) showed predominant difference in clinical and laboratory features. The incidence of gut involvement, the absolute count of eosinophils in peripheral blood and the percentage of immature eosinophils in bone marrow were significantly increased in positive patients (P ＜ 0.05 ). Conclusions The hematological diseases associated with eosinophilia are characterized by unique clinical and laboratory features. Karyotyping should be a routine approach to detect the abnormal clone in these diseases. Screening for PDGFRα, PDGFRβ and FGFR1 gene with FISH can provide more genetic information.     

Clinical, biochemical, and morphological characteristics of chronic hepatitis with various etiology

AIM: To investigate clinicomorphological features in patients with chronic diffuse lesions of the liver with consideration of the etiological factor. MATERIAL AND METHODS: Clinical, laboratory, serological and pathohistological examinations were performed in 67 patients with chronic hepatitis (CH). RESULTS: Out of 48 patients with chronic viral hepatitis (CVH), 32(66.6%) demonstrated association of hepatic lesion with alcohol or drug abuse. Knodell activity in the liver was prevalent in drug abusers with CVH. Fat dystrophy and high de Ritis index were typical for alcoholics. CONCLUSION: Viral hepatic lesions associated neither with alcohol nor drug abuse occur only in 1/3 of patients with CH.     

Clinical and biochemical characteristics of biliferous tract diseases in patients with diabetes mellitus

The aim of the study was to investigate manifestations of biliferous tract diseases in patients with diabetes mellitus (DM) and to measure concentrations and the ratio of lipids in gall-bladder and liver bile in these patients. 125patients with DM and biliferous tract diseases were examined. Patients with chronic cholecystitis (CC), cholelithiasis, and biliary dyskinesia underwent clinical examination as well as biochemical and instrumental tests. The control group included 87 healthy individuals of comparable age and gender. CC was diagnosed in 35.2% of DM patients, cholelithiasis - in 17.6% patients. In liver and gall-bladder bile samples taken from patients with CC and cholelithiasis, fatty acids concentrations was not significantly different, cholesterol level was significantly higher, and phospholipids level was lower than in the control group. Thus, indices of cholesterol saturation in liver and gall-bladder bile portions were higher in patients with cholelithiasis than in the control group. The study revealed high biliferous tract diseases morbidity in patients with DM. Thomas-Hofmann index, which characterizes bile saturation with cholesterol, is significantly higher in patients with cholelithiasis and DM, then in healthy individuals.     

非酮症高血糖相关性舞蹈症临床特征分析

目的 总结非酮症高血糖相关性舞蹈症患者的临床特征、影像学表现,探讨该症的可能发病机制及诊治方法。方法 回顾性分析我院近期收治的3例非酮症高血糖相关性舞蹈症患者病例资料,此3例患者分别就诊于我院内分泌科、神经内科、神经外科并分别收入院治疗,同时查阅国内外相关文献进行学习。结果 非酮症高血糖相关性舞蹈症通常表现为非酮症性高血糖、偏侧舞蹈症以及头MRI或CT典型的影像学表现三联征,但表现不尽相同,影像学特征也可出现差异,临床呈现多样化趋势。对3例患者均给予降糖,联合或不联合控制舞蹈症症状药物后,均好转。结论 快速的判断及识别出此症是重中之重,及时而正确的调控血糖是治疗的关键,必要时应用多巴胺受体拮抗剂联合治疗可加速患者临床症状的好转,此症预后良好。     

Clinical and biochemical characteristics of patients with urea cycle disorders in a developing country

ObjectivesTo report the clinical and laboratory characteristics of urea cycle disorder (UCD) patients at a tertiary care center in a developing country.Design and methodsRetrospective study of clinical and laboratory data of UCD patients.ResultsThirty-seven UCD patients were studied, 31 symptomatic (high risk) patients (15 neonatal onset, 16 late onset) and 6 with positive neonatal screening. Argininosuccinate synthetase deficiency was the most frequent disease (17/37, 46%), followed by ornithine transcarbamylase (10/37, 27%), arginase (7/37, 19%), and argininosuccinate lyase (3/37, 8%) deficiencies. Mortality of symptomatic patients was 38% (10/26), neonatal onset had the worst outcome, with 50% of survival.ConclusionsIn Mexico, the mortality of the UCD patients is higher than those reported in other countries, and neurological sequels are frequent and severe. It is essential to implement practice guidelines for the professional management of these patients.     

Clinical factor associated with congenital cytomegalovirus infection in pregnant women with non-primary infection

The aim of this nested case-control study was to evaluate clinical factors associated with the occurrence of congenital cytomegalovirus (CMV) infection in pregnant women with non-primary CMV infection. In a cohort study of CMV screening for 2193 pregnant women and their newborns, seven newborns with congenital CMV infection were identified among 1287 pregnant women with non-primary CMV infection that was defined as negative IgM and positive IgG with IgG avidity index >45%. In the 1287 women with non-primary CMV infection, clinical findings and complications were compared between pregnancies with and without congenital CMV infection. Clinical factors associated with the occurrence of congenital CMV infection were evaluated. The birth weight of newborns with congenital CMV infection was less than that of newborns without congenital infection (p < 0.05). Univariate logistic regression analyses demonstrated that threatened premature delivery (OR 10.6, 95%CI 2.0–55.0; p < 0.01) and multiple pregnancy (OR 7.1, 95%CI 1.4–37.4; p < 0.05) were associated with congenital infection. Multivariable logistic regression analyses demonstrated that threatened premature delivery (OR 8.4, 95%CI 1.5–48.1; p < 0.05) was a single risk factor for congenital CMV infection in pregnant women with non-primary CMV infection. This study revealed for the first time that threatened premature delivery was associated with the occurrence of congenital CMV infection in pregnant women with non-primary CMV infection, the pathophysiology of which may be closely associated with CMV reactivation during pregnancy.     

Clinical, biochemical and enzymatic studies in type I hyperprolinemia associated with chromosomal abnormality

A severe mentally retarded infant with type I hyperprolinemia associated with chromosomal abnormality is reported. The patient had a characteristic facial appearance of hyperprolinemia and suffered from convulsions after the age of 10 months. The child developed severe mental and motor retardation. The karyotype of the patient revealed partial duplication of the short arm in chromosome 10 using G banding techniques. The patient and her mother showed a fasting hyperprolinemia and an abnormal clearance curve after the proline load in the serum. The proline oxidase activities of the liver tissues obtained by biopsy in the patient was about 9% of those of controls. Kinetic studies and mixed experiments of the enzyme were with normal limits. Restriction of dietary proline at the age of 12 months revealed a prompt fall of the plasma levels of proline to the normal range, and a low proline diet was continued until the present time. During the period of dietary treatment, growth was satisfactory, but her mental development did not improve. From the developmental patterns of proline oxidase activities postnataldy, we speculated that restriction of dietary proline intake should be relieved with age.     

系统性红斑狼疮合并多发性骨髓瘤的临床特点分析

目的：系统性红斑狼疮（SLE）合并多发性骨髓瘤（MM）临床上十分少见。本文旨在通过分析SLE合并MM患者的临床特点和诊治经验,以推断SLE和MM二者间的联系。方法本文报道了1例68岁女性同时被诊断为SLE和MM。通过检索PubMed近35年来国外发表的SLE合并MM 的病例共15例,列表和归纳其临床特点。结果文献报道的15例患者中女性明显多于男性（男∶女＝1∶14）,诊断为M M 时中位年龄49岁,明显早于一般人群中MM的诊断年龄。其SLE的症状以关节炎/关节痛、红斑/光敏性皮疹和血液系统损害的发生率较高,分别占80．0％、60．0％和66．7％,与单纯SLE患者的症状发生率无明显差异。有1/3的患者诊断为MM 时其SLE稳定或血清学检查阴性。有12例患者血液中检出M蛋白。结论 SLE患者中可能出现意义未明的单克隆免疫球蛋白病,可能使进展为MM的风险增加。     

Phosphofructokinase deficiency associated with congenital nonspherocytic hemolytic anemia and mild myopathy: biochemical and morphological studies on the muscle

Enzymatic and electron microscopical studies were performed on the muscle of a proband with phosphofructokinase deficiency. Enzymatic studies showed that muscle phosphofructokinase activity of the proband was decreased to about a half of normal. This enzyme was quite thermolabile and had low affinity for fructose 6-phosphate. Electron microscopical studies showed the accumulation of glycogen granules beneath the sarcolemma and between the myofibrils in spite of a lack of accumulation of the intermediates before the step of phosphofructokinase. The proband's clinical symptoms, i.e., hemolytic anemia and myopathy, were considered to be due to the unstable, mutant, muscle-type phosphofructokinase in the red blood cells and muscle.     

Clinical characteristics associated with sentinel headache in patients with unruptured intracranial aneurysms

ObjectiveSentinel headache (SH) is considered as a signal of the impending rupture of an aneurysm. However, it is difficult to diagnose whether the headaches of patients are associated with unstable aneurysms. Therefore, there is some doubt about the importance of headaches in patients with unruptured intracranial aneurysms (UIAs). This study was performed to explore the existence and clinical characteristics of SH associated with aneurysms.MethodsThirty-six patients with a single UIA were collected in this study. Patients were symptomatically categorized into two groups: SH and non-SH. The PHASES scores and patient and aneurysm characteristics were analyzed. Two independent MRI experts who were blinded to the patients’ clinical history conducted the analysis of the SWI results.ResultsThere were 15 patients with sentinel headache. No significant difference was found in patient’s basic information and history. The SH group had a higher PHASES score than the non-SH group (P < 0.05). In univariable analysis, abnormal SWI signals were significantly more frequent in the SH group (P < 0.01) and the inflow angle was significantly lower in the non-SH group (P < 0.05). In multivariable analysis, abnormal signals in SWI were an independent factor associated with SH (P < 0.01).ConclusionsSH exists in patients with UIAs and may indicate a high risk of aneurysm rupture. Abnormal signals on SWI may serve as a clinical feature to identify aneurysm-related SH and be helpful for the formulation of therapeutic strategy. Aneurysm geometry may also be related to SH but need further studies in the future.     

间变性淋巴瘤激酶阳性肺腺癌晚期患者的临床特征

目的分析晚期肺腺癌间变性淋巴瘤激酶(ALK)基因融合患者临床特点。方法收集经组织病理学证实的晚期或局部晚期不能手术的410例肺腺癌患者临床资料,患者均经过增强免疫组织化学(V-IHC)方法检测ALK融合基因表达状态。同时记录患者性别、年龄、初诊时转移部位,ARMs法检测的EGFR基因突变情况等基本资料,总结分析ALK基因融合患者的临床特点,为筛选非小细胞细胞肺癌ALK阳性患者及个体化治疗提供依据。结果 410例晚期肺腺癌患者中Ventana-IHC显示35例ALK阳性,阳性率为8.5%(35/410),同时检测的EGFR突变阳性患者为201例,突变率为49.0%(201/410),ALK基因融合发生率在EGFR阴性肺腺癌患者中占16.7%(35/209)。本组ALK阳性患者年龄在29～78岁,中位年龄52岁;男性15例,女性20例;初发时脑转移6例,肝转移7例,肾转移2例,腹膜转移2例;一线经含培美曲塞化疗18例,其中15例进入二线克唑替尼治疗,克唑替尼有效率46.7%,无进展生存期(PFS) 6.2月;一线克唑替尼治疗17例,有效率63.3%,PFS 10.8月。结论晚期肺腺癌患者ALK基因融合是继EGFR基因突变后的又一驱动基因,其临床发病年龄更轻,更容易出现脑、肝和肾等部位的转移。