Choledocholithiasis: treatment with extracorporeal shock wave lithotripsy

In a patient with choledocholithiasis, a duodenal diverticulum precluded endoscopic retrograde bile duct cannulation. A transhepatic catheter was used to opacify the bile ducts and to guide the endoscopic sphincterotome into the major duodenal papilla. Because limited sphincterotomy did not allow extraction or spontaneous passage of the common duct stones, extracorporeal lithotripsy was performed. Following fragmentation, the stones passed spontaneously and without complications.     

Localization and quantification of mRNA for matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) in human benign and malignant prostatic tissue

BACKGROUND: The family of matrix metalloproteinases (MMPs) has been shown to be involved in proteolytic degradation of the extracellular matrix, which is an essential step in tumor invasion and metastasis. MMPs are tightly regulated by the levels of active enzymes and their inhibitors, the tissue inhibitors of metalloproteinases (TIMPs). MMP-2 and its ratio to TIMP-2 have been associated with tumor recurrence and progression in a number of human malignancies. METHODS: We examined the relationship between MMP-2 and TIMP-2 mRNA expression in 42 men with malignant (n = 32) and benign (n = 10) prostates using nonisotopic in situ hybridization and Northern blot analysis. RESULTS: mRNA for MMP-2 and TIMP-2 was localized to the malignant epithelial cells of both high- and low-grade tumors in the periphery of the glands and in areas of extracapsular involvement, and to the glandular epithelium in the benign prostates. Using Northern blot analysis, the mean MMP-2 to TIMP-2 ratio was approximately one in the benign prostates and low-grade and -stage cancers. The MMP-2 to TIMP-2 ratio increased to 3.3 in the high-grade and 2.8 in the high-stage tumors. CONCLUSIONS: The results suggest a close association between MMP-2/TIMP-2 expression and local tumor invasion, with a disruption in expression of the two genes leading to disease progression. Future studies should focus on the activity of these enzymes and on the ratio of enzyme/inhibitor expression, which may become a useful prognostic marker in prostate cancer.     

Experience with pneumonia in acutely burned patients requiring ventilator support

Acutely burned patients requiring ventilatory support who developed pneumonia while in the hospital were retrospectively reviewed. The Centers for Disease Control and Prevention (CDC) clinical criteria for pneumonia are based on clinical findings, radiographic findings, and culture data. During an 18-month period, 784 burn patients were admitted. Of these, 145 (18.5%) were placed on ventilators for at least 1 day. Fifty-three (36.6%) patients on ventilators developed acute pneumonia based on CDC criteria. Identification of causative organisms was based on positive cultures from blood or endotracheal aspiration within 3 days of the diagnosis of pneumonia. Thirty-nine patients were diagnosed as having inhalation injury. Forty-seven patients were placed on ventilators before or on the day of admission. Ages ranged from 2 to 82 years (mean, 39). Burn size ranged from 2 to 85 per cent (mean, 29.7%) of total body surface area. The total number of ventilator days was 1310 for the 53 patients, with a mean of 27.7 days. Ten patients had positive blood cultures during the period in which pneumonia was present. Thirty-one different organisms were recovered from blood or tracheal aspirates. The most commonly recovered organism was Pseudomonas aeruginosa. In 30 incidences, polymicrobial cultures were encountered. Initiation of appropriate antimicrobial therapy was begun on the basis of clinical impression and current burn unit experience and revised on the basis of the culture data. Of the 53 patients, 13 (25.5%) died, all while still on ventilators. The other 40 patients survived. Thirty-four were weaned off their ventilators, and 6 were transferred while still on ventilator support.     

CYP2D6 mutations and therapeutic outcome in schizophrenic patients

STUDY OBJECTIVE: To investigate whether a relationship exists between the most common known cytochrome P450 (CYP) isozyme 2D6 mutations and schizophrenia. Because most antipsychotic and antidepressant agents interact with CYP2D6, we also investigated clinical outcomes in schizophrenic poor metabolizers (PMs) and extensive metabolizers (EMs). DESIGN: Prospective, observational study. SETTING: Two psychiatric hospitals and a university-affiliated nonpsychiatric hospital. SUBJECTS: Thirty-nine consecutive schizophrenic patients (POP 1), 89 schizophrenics of French Canadian origin (POP 2), and 384 healthy French Canadians (POP 3). INTERVENTION: All study subjects were genotyped for CYP2D6 mutant alleles. POP 1 patients were evaluated before and after 21 or more days of treatment with antipsychotic drugs metabolized at least in part by CYP2D6. MEASUREMENTS AND MAIN RESULTS: Whole blood was collected to determine CYP2D6 alleles *1, *3, *4, *5, *6, and *7 using standard restriction fragment length polymorphisms and polymerase chain reaction techniques. In comparison, CYP2D6 genotypes were determined in POP 2 and POP 3. Twenty-three (59.0%) of 39 patients in POP 1 were genotypically EM homozygotes, 15 (38.4%) were EM heterozygotes, and 1 (2.6%) was a PM. Similar genotype distributions were determined in POP 2 and in POP 3. Genotype distributions for all three populations were in Hardy-Weinberg equilibrium (p>0.05), and there was no significant difference among them (p=0.857). In POP 1, no differences were seen among genotypes in disease symptom severity, number and severity of adverse drug effects, or attitudes toward drug treatment at baseline and at the end of the study. In fact, all patients improved significantly during their hospital stay (all p<0.05), although independent of the CYP2D6 genotype. CONCLUSION: Common CYP2D6 mutant alleles were not associated with schizophrenia or with disease symptoms, antipsychotic-related adverse effects, or attitudes toward treatment.     

Glomerular paramesangial deposits: association with hypocomplementemia in membranoproliferative glomerulonephritis types I and III

Of 22 subjects previously reported with some form of factor H dysfunction, 12 had a glomerulonephritis that appeared to not be of immune complex origin. Factor H dysfunction results in elevated circulating levels of the C3b-dependent C3 convertase, C3b,Bb. Of the 12 cases with glomerulonephritis, the glomerular deposits in the six whose biopsy specimens were studied were predominately subepithelial on the paramesangial portion of the glomerular basement membrane. In a subsequent study, similar deposits were found in patients with membranoproliferative glomerulonephritis (MPGN) type II, also a nephritis that is probably not of immune complex origin. Paramesangial deposits were found in these patients only in biopsy specimens obtained when the C3 level was low, at which time convertase stabilized by nephritic factor would be present in the circulation. This association of paramesangial deposits with circulating convertase was further tested by correlating these deposits with the level of C3 at the time of biopsy in MPGN types I and III. The results in type III MPGN were similar to those in type II; paramesangial deposits were frequently present when the C3 level was low as a result of circulating nephritic factor of the terminal pathway, NFt, and were usually absent when the C3 level was in the upper two thirds of the normal range. Deposits persisted in those patients with C3 levels that had been low but that had increased during the year before biopsy to within the lower one third of the normal range. The persistence of paramesangial deposits in MPGN type III, as compared with MPGN type II, may be related to the differences in composition and function of the two NF stabilized convertases (C3bn,Bb,P,NFt and C3b,Bb,NFa, respectively) that circulate in these two disorders. In contrast to MPGN type III, the hypocomplementemia in MPGN type I is thought to be, for the most part, the result of classical pathway activation, which is not associated with elevated circulating convertase levels. In agreement with this, paramesangial deposits were found in only two of 34 biopsy specimens. At the time of those two biopsies, both patients had a complement profile indicating that the NFt was circulating, as in MPGN type III. In three other cases with profiles compatible with circulating NFt, paramesangial deposits were not found. In all patients with type I MPGN, electron microscopy and immunofluorescence of the glomeruli gave results typical of an immune complex nephritis. Thus, even though the complement profile in MPGN type I may at times indicate the presence of a nephritic factor, circulating immune complexes appear to be basic to pathogenesis. The observations support the hypothesis that elevated levels of the C3b-dependent convertase, as found in the "experiments of nature" with factor H dysfunction and in MPGN types II and III, are associated with paramesangial deposits. The nature of this association and the role of these deposits in producing the nephritis is not clear.     

Ultrasound-guided small-bore Elecath tube insertion for the rapid sclerotherapy of malignant pleural effusion

BACKGROUND: Traditional pleurodesis for malignant pleural effusion is performed by large-bore chest tube insertion with the instillation of sclerosing agents after the compressed lung re-expansion and pleural fluid drainage of 100-150 ml/day. This study was carried out to evaluate the possibility of rapid sclerotherapy for malignant pleural effusions by insertion of a small-bore Elecath tube (12-French) under ultrasound guidance and intrapleural injection of bleomycin 60 IU. METHODS: Twenty-six patients, with 28 cytopathologically proven malignant pleural effusions (two patients had bilateral pleural effusions) and receiving the insertion of the Elecath tube for drainage, were included in our series. This rapid and short-term sclerosing method was performed and completed by intrapleural injection of bleomycin when the pleural effusion had been clearly drained by the small-bore Elecath tube and the compressed lung had fully re-expanded on follow-up chest radiographs. RESULTS: Twenty patients with 22 pleural effusions underwent the intrapleural injection of bleomycin, with the results of pleurodesis being complete response 41% (9/22), partial response 36% (8/22) and failure 23% (5/22). Interestingly, among the 17 successful procedures of pleurodesis (complete response and partial response), 71% (12) procedures could be completed within 2 days (seven within one day and five within 2 days). The remaining unsuccessful procedures carried out on six patients without the injection of bleomycin were due to a non-re-expanded lung (n = 3) and inadequate drainage (n = 3); of these, four patients also received the large-bore chest tube insertion after the removal of the Elecath tube, but the compressed lung still could not re-expand. The complications of the bleomycin injection were fever [77% (17/22)], vomiting [14% (3/22)] and hiccup [5% (1/22)]. CONCLUSION: The method of rapid sclerotherapy for malignant pleural effusions by small-bore Elecath tube is promising, with a success rate achieving 77%, usually within 2 days.      

Neuroimaging and spectroscopy in children with epileptic encephalopathies

AIMS: To investigate the nature of the unifocal cortical abnormalities on FDG positron emission tomography (PET) in children with an epileptic encephalopathy but no focal abnormality on electroencephalogram or standard magnetic resonance imaging (MRI). METHODS: Repeat FDG PET, surface rendered high resolution MRI, and single voxel magnetic resonance proton spectroscopy of the areas of abnormal metabolism compared to the contralateral side in 11 children aged 2 to 12 years. Imaging was repeated after a median of 13 months. RESULTS: Visual analysis of repeat FDG PET revealed similar abnormalities in 10 of 11 children. Semiquantitative analysis revealed similar sited abnormalities in eight children. One child with ictal hypermetabolism initially had an inconsistent second scan. Magnetic resonance spectra in three children showed the N-acetyl-aspartate/choline ratio was lower in the hypometabolic focus than in the reciprocal area on the opposite side, in two children it was higher, and in one child it was equal. Surface rendered MRI was normal in seven of eight children, and showed temporal lobe asymmetry in one. CONCLUSION: In children with established epileptic encephalopathies most hypometabolic areas on FDG PET are stable over time. While focal neuronal loss is likely in these areas in some children, microdysplasias or other focal cortical dysplasias are probable in others.     

骨髓间质干细胞分泌胶质源性神经生长因子及对1-甲基4-苯基吡啶离子诱导PC12细胞凋亡的干预

目的:收集体外培养、纯化的骨髓间质干细胞条件培养液,检测其对多巴胺能神经元有保护作用的胶质源性神经生长因子分泌情况,并观察对1-甲基4-苯基吡啶离子诱导的PC12细胞凋亡的保护作用。方法:实验于2005-05/2006-10在中国医科大学附属一院神经内科实验室完成。①PC12细胞由协和医科大学细胞培养中心提供。1-甲基4-苯基吡啶离子(Sigma,USA,批号3707312)。②选取清洁级SD大鼠20只,麻醉后取股骨和胫骨,去净肌肉取骨髓,按1010L-1接种于含体积分数为0.2胎牛血清的低糖型DMEM培养基中,通过弃悬浮细胞及换液后可得到较纯的骨髓间质干细胞。培养第10天胰蛋白酶消化传代,当第2代细胞扩增至铺满瓶底80%时,改用含体积分数为0.05胎牛血清的低糖型DMEM条件培养液,48h后收集培养液,经超滤浓缩系统(截留分子量为10000)浓缩10倍后过滤除菌。③骨髓间充质干细胞接种于24孔板内,贴壁后多聚甲醛固定,磷酸盐缓冲液漂洗,免疫荧光法鉴定骨髓间充质干细胞表面抗原的表达。骨髓间充质干细胞消化后进行细胞计数,按1×108L-1接种于75cm培养瓶,加入含体积分数为0.2胎牛血清的DMEM培养液20mL,于培养第5,10天采用ELISA法测定细胞培养上清液中的胶质源性神经生长因子含量。④PC12细胞置于RPMI1640培养液中,内含体积分数为0.1的马血清和0.05的胎牛血清,汇集至80%时进行传代接种,液氮罐中贮存备用。实验前首先置换培养液,使血清浓度降至为仅含0.01马血清和0.01胎牛血清,24h后将培养的细胞分为4组:空白对照组,在细胞培养体系中不加入任何药物;骨髓间充质干细胞上清液组,接种后24h在细胞培养体系中分别加入骨髓间充质干细胞上清液30,60,120μL;1-甲基4-苯基吡啶离子组,接种后24h分别加入1-甲基4-苯基吡啶离子,使终浓度分别为100,200,400μmol/L;联合组,接种后24h加入200μmol/L1-甲基4-苯基吡啶离子,24h后再分别给予骨髓间充质干细胞上清液30,60,120μL。⑤各组细胞于给药后24,48h,流式细胞术检测PC12细胞的凋亡率;通过免疫细胞化学法和RT-PCR法检测PC12细胞半胱氨酸天冬氨酸蛋白酶3蛋白和mRNA的表达。结果:①骨髓间充质干细胞表面抗原鉴定:骨髓间充质干细胞可在体外分离扩增,其表面抗原CD45呈阴性,而CD44表达阳性。②骨髓间充质干细胞培养上清液中胶质源性神经生长因子水平检测:第5,10天培养上清液中的胶质源性神经生长因子浓度为(44.57±5.96)ng/L和(45.41±6.33)ng/L,差异无显著性意义(P>0.05)。③PC12细胞凋亡情况:联合组200μmol/L1-甲基4-苯基吡啶离子作用PC12细胞24h后,细胞凋亡率为(42.34±3.21)%;加入30,60,120μL骨髓间充质干细胞上清液处理24h后,细胞凋亡率分别降为(31.96±2.89)%,(17.89±1.78)%,(10.08±0.91)%,差异有显著性意义(P<0.05)。联合组药物作用48h与24h情况相似。④给药后各组半胱氨酸天冬氨酸蛋白酶3蛋白及mRNA的表达:联合组半胱氨酸天冬氨酸蛋白酶3蛋白和mRNA水平均明显低于1-甲基4-苯基吡啶离子组(t=0.05～0.32,P均<0.05)。结论:骨髓间充质干细胞能够分泌胶质源性神经生长因子,对1-甲基4-苯基吡啶离子诱导的PC12细胞凋亡产生保护作用。这种保护作用的强弱与其浓度有关,具体作用机制可能是通过抑制半胱氨酸天冬氨酸蛋白酶3蛋白和mRNA水平实现的。