Altered dimerization of metabotropic glutamate receptor 3 in schizophrenia.

BACKGROUND: Metabotropic glutamate receptors (mGlus) may be involved in the pathophysiology of schizophrenia. Group II mGlus (mGlu2 and mGlu3) have attracted considerable interest since the development of potent specific agonists that exhibit atypical antipsychotic-like activity and reports of a genetic association between the mGlu3 gene and schizophrenia. METHODS: In this postmortem study, mGlu3 protein levels in Brodmann area 10 of prefrontal cortex from schizophrenic (n = 20) and control (n = 35) subjects were analyzed by western immunoblotting using a novel specific mGlu3 antibody and an antibody for the vesicular glutamate transporter 1 (VGluT1). RESULTS: We report a significant decrease in the dimeric/oligomeric forms of mGlu3 in schizophrenic patients compared with control subjects, whereas total mGlu3 and VGluT1 levels were not altered significantly. CONCLUSIONS: This is the first experimental evidence that mGlu3 receptor levels are altered in schizophrenia and supports the hypothesis that neurotransmission involving this particular excitatory amino acid receptor is impaired in schizophrenia.     

Quality assurance, efficiency indicators and cost-utility of the evaluation workup for liver transplantation.

We report the results of a retrospective review of the outpatient pretransplantation workup for United Network for Organ Sharing (UNOS) 3 patients adopted at a liver transplantation (LT) center and illustrate the efficiency indicators used for quality evaluation and cost-analysis. A single-center, pre-LT evaluation workup was performed on an outpatient basis at a cost per patient evaluation of 2,770 Euros (). Objective measures were: the number of patients admitted to and excluded from each phase of the algorithm; the rate of patients admitted to pre-LT evaluation out of the total of referred patients (the referral efficiency rate); the rate of waitlisted patients out of those admitted to pre-LT evaluation (the evaluation efficiency rate); the rate of waitlisted patients out of those referred for LT (the process efficiency rate); and the cost per waitlisted patient, as the ratio of the cost per patient evaluation to the evaluation efficiency rate. From January 1, 1996, to October 1, 2004, 1,837 patients were referred for LT on an outpatient basis. Based on preemptive evaluation of the available clinical data, 412 patients (22.4%) were excluded from pre-LT evaluation and 1,425 (77.6%) were admitted to preliminary consultation. Among these, 603 (42.3%) were excluded from and 822 (57.7%) were admitted to pre-LT evaluation with a referral efficiency rate of 44.7% (822 of 1,837). Out of the patients evaluated for LT, 484 were waitlisted with a cost-utility and evaluation efficiency rate of 58.8% each (484 of 822). Of the 1,837 patients originally addressed for LT 484 were waitlisted, yielding a process efficiency rate of 26.3% (484 of 1,837) and a cost per waitlisted patient of 4,710.8. In conclusion, the 3 indicators allowed monitoring of the efficiency of the pre-LT evaluation algorithm. The current process efficiency rate at our center is low (26.3%), but avoiding early referrals we might increase it to 31.6%, with a 12% net saving on costs per waitlisted patient (from 4,710.8 to 4,165.4).     

Preoperative pulmonary rehabilitation in patients undergoing lung resection for non-small cell lung cancer.

BACKGROUND: The impact of short-term preoperative pulmonary rehabilitation on exercise capacity of patients with chronic obstructive pulmonary disease undergoing lobectomy for non-small cell lung cancer is evaluated. METHODS: A prospective observational study was designed. Inclusion criteria consisted of an indication to lung resection because of a clinical stage I or II non-small cell lung cancer and a chronic obstructive disease on preoperative pulmonary function test. In such conditions, maximal oxygen consumption by a cardio-pulmonary exercise test was evaluated; when this resulted as being < or =15 ml/kg/min a pulmonary rehabilitation programme lasting 4 weeks was considered. Twelve patients fulfilled inclusion criteria, completed the preoperative rehabilitation programme and underwent a new functional evaluation prior to surgery. The postoperative record of these patients was collected. RESULTS: On completion of pulmonary rehabilitation, the resting pulmonary function test and diffuse lung capacity of patients was unchanged, whereas the exercise performance was found to have significantly improved; the mean increase in maximal oxygen consumption proved to be at 2.8 ml/kg/min (p<0.01). Eleven patients underwent lobectomy; no postoperative mortality was noted and mean hospital stay was 17 days. Postoperative pulmonary complication was recorded in 8 patients. CONCLUSIONS: Short-term preoperative pulmonary rehabilitation could improve the exercise capacity of patients with chronic obstructive pulmonary disease who are candidates for lung resection for non-small cell lung cancer.     

术中射频消融后病灶刮除治疗脊柱转移瘤

目的:探讨术中射频消融(RFA)后再行病灶刮除术治疗脊柱转移瘤的可行性及疗效.方法:2004年～2006年,对11例脊柱转移瘤患者术中实施RFA后再行病灶刮除术,将FRA前后病灶标本进行光镜和电镜病理检查,随访患者疼痛缓解情况及肿瘤复发情况.结果:术中未出现脊髓和神经根损伤,RFA后瘤组织固缩,刮除顺利,出血量350～3800ml,平均1024.5ml.全部病例得到6个月以上随访,平均9.8个月,全部患者生存期超过6个月,VAS评分术前平均5.8分,术后6个月时平均1.9分.1例出现局部肿瘤复发.RFA前的标本光、电镜检查均未见肿瘤组织坏死.RFA后光镜检查3例无明显坏死,9例肿瘤细胞完全坏死:电镜检查10例肿瘤细胞完全坏死,1例肿瘤细胞部分坏死,1例无明显坏死.结论:术中RFA后再行病灶刮除治疗脊柱转移瘤安全可行,有利于肿瘤的刮除,减少局部复发的风险.     

Brain-derived neurotrophic factor Val66Met and psychiatric disorders: meta-analysis of case-control studies confirm association to substance-related disorders, eating disorders, and schizophrenia.

BACKGROUND: There is an increasing recognition that the pathophysiology of mental disorders could be the result of deregulation of synaptic plasticity with alterations of neurotrophins. The valine (Val)66-to-methionine (Met) variant, located in the pro brain-derived neurotrophic factor (BDNF) sequence, has been extensively studied through linkage and association approaches in several psychiatric disorders. METHODS: We performed a meta-analysis restricted to individual case-control studies in different categories of mental disorders and BDNF Val66Met polymorphism. We included data from 39 case-control studies encompassing psychiatric phenotypes: eating disorders, substance-related disorders, mood disorders, and schizophrenia, among others. RESULTS: The association of Val66Met was confined to three diagnoses: substance-related disorders, eating disorders, and schizophrenia. The Val/Met and the Met/Met genotypes increase the risk for eating disorders up to 33%, while these same genotypes confer a 21% protective effect in substance-related disorders. The homozygous carriers Met/Met showed a 19% increased risk of schizophrenia with respect to the heterozygous state. CONCLUSIONS: The study confirms the association of Val66Met to substance-related disorders, eating disorders, and schizophrenia. It remains to be determined if other variants in tight linkage disequilibrium with Val66Met could configure an extended functional haplotype that would explain observed discrepancies in risk estimations across studies.     

A new priority policy for patients with hepatocellular carcinoma awaiting liver transplantation within the model for end-stage liver disease system.

The best prioritization of patients with hepatocellular carcinoma (HCC) waiting for liver transplantation under the model for end-stage liver disease (MELD) allocation system is still being debated. We analyzed the impact of a MELD adjustment for HCC, which consisted of the addition of an extra score (based on the HCC stage and waiting time) to the native MELD score. The outcome was analyzed for 301 patients with chronic liver disease listed for liver transplantation between March 1, 2001 and February 28, 2003 [United Network for Organ Sharing (UNOS)-Child-Turcotte-Pugh (CTP) era, 163 patients, 28.8% with HCC] and between March 1, 2003 and February 28, 2004 (HCC-MELD era, 138 patients, 29.7% with HCC). In the HCC-MELD era, the cumulative dropout risk at 6 months was 17.6% for patients with HCC versus 22.3% for those patients without HCC (P = NS), similar to that in the UNOS-CTP era. The cumulative probability of transplantation at 6 months was 70.3% versus 39.0% (P = 0.005), being higher than that in the UNOS-CTP era for patients with HCC (P = 0.02). At the end of the HCC-MELD era, 12 patients with HCC (29.3%) versus 57 without HCC (58.8%) were still on the list (P = 0.001). Both native and adjusted MELD scores were higher (P < 0.05) and progressed more in patients with HCC who dropped out than in those who underwent transplantation or remained on the list (the initial-final native MELD scores were 17.3-23.1, 15.5-15.6, and 12.8-14.1, respectively). The patients without HCC remaining on the list showed stable MELD scores (initial-final: 15.1-15.4). In conclusion, the present data support the strategy of including the native MELD scores in the allocation system for HCC. This model allows the timely transplantation of patients with HCC without severely affecting the outcome of patients without HCC.     

Assessing postoperative discomfort after third molar surgery: a prospective study.

PURPOSE: The purpose of this study was to identify the risk factors for severe discomfort after mandibular third molar surgery and to assess the validity of the Postoperative Symptom Severity (PoSSe) scale. PATIENTS AND METHODS: In a 2-year prospective study, a total of 255 unilateral impacted mandibular third molar teeth were surgically removed under local anesthesia by 3 surgeons. Standardized surgical and analgesic protocols were followed. At the review appointment, 1 week after surgery, all patients returned a completed follow-up questionnaire (PoSSe scale) and were evaluated clinically for postoperative pain (number of painkillers taken) and trismus (differences in mouth opening). Sixteen predictive variables were evaluated using stepwise logistic regression analysis to identify the risk factors associated with severe discomfort. RESULTS: Severe postoperative discomfort was predicted by these independent variables: gender, tobacco use, ramus relationship/space available, and antibiotic prophylaxis. Oral contraceptive use and operation time were not identified as risk factors. The patients' perceptions of the severity of symptoms (PoSSe scale score) was strongly correlated with clinical assessment of trismus (r = 0.54) and pain (r = 0.42). CONCLUSION: The PoSSe scale resulted in a valid and responsive measure of the severity of symptoms after surgical extraction of lower third molars and reflected the clinical severity of the postoperative discomfort. From a patient's perspective, operative factors had little bearing on the quality of life after removal of mandibular third molars.     

One-shot percutaneous ethanol injection of liver tumors under general anesthesia: Preliminary data on efficacy and complications

Purpose: To verify the efficacy of ultrasound (US)-guided injection of large amounts of ethanol into large or multiple liver lesions, in a single session under general anesthesia (one-shot PEI) for percutaneous ablation of hepatic tumors. Methods: Twenty-nine patients (27 with 51 hepatocellular carcinoma (HCC) nodules on cirrhosis, diameter range 1.0<+>–<+>9.0 cm; two patients with a single metastasis from the gastroenteric tract, 5.0 and 9.0 cm, respectively, in diameter) were treated with one-shot PEI. Results: The total volume of alcohol delivered per patient ranged from 16 to 210 ml. Mean ethanol volume in all patients was 49 ml. Dynamic computed tomography (CT) examination showed complete necrosis in 41 of 50 lesions. Two patients died of hypovolemic shock due to massive upper gastrointestinal bleeding, 3 and 7 days, respectively, after the interventional procedure. All the remaining patients are alive (follow-up 5<+>–<+>14 months) except one who died of liver failure 5 months after. New HCC nodules occurred in six patients within 6 months and one intralesional relapse was recorded. Conclusion: In this preliminary experience, one-shot PEI is as effective in inducing liver tumor necrosis as traditional PEI; its advantages are shorter treatment time and the capability of treating larger and multiple liver lesions.