Differential expression of FMR1, FXR1 and FXR2 proteins in human brain and testis

Lack of expression of the fragile X mental retardation protein (FMRP) results in mental retardation and macroorchidism, seen as the major pathological symptoms in fragile X patients. FMRP is a cytoplasmic RNA- binding protein which cosediments with the 60S ribosomal subunit. Recently, two proteins homologous to FMRP were discovered: FXR1 and FXR2. These novel proteins interact with FMRP and with each other and they are also associated with the 60S ribosomal subunit. Here, we studied the expression pattern of the three proteins in brain and testis by immunohistochemistry. In adult brain, FMR1, FXR1 and FXR2 proteins are coexpressed in the cytoplasm of specific differentiated neurons only. However, we observed a different expression pattern in fetal brain as well as in adult and fetal testis, suggesting independent functions for the three proteins in those tissues during embryonic development and adult life.      

A comparative study on neurochemistry of cerebrospinal fluid in advanced Parkinson's disease

This study addresses two issues: (1) the comparative neurochemistry of classic tremor type of Parkinson's disease or PD-A and akinetic type of Parkinson's disease or PD-B; and (2) the neurochemistry of levodopa failure syndrome (LDFS). Cerebrospinal fluid from the lateral ventricle was collected from 50 patients with idiopathic Parkinson's disease of PD-A and PD-B. Levels of monoamine neurotransmitters and metabolites were determined using high performance liquid chromatography. We have found that (1) 5-hydroxylindoleacetic acid (5-HIAA) level is significantly lower in PD-B than in PD-A; (2) 5-HIAA level is inversely associated with score of part one of United Parkinson's Disease Rating Score (UPDRS); (3) 5-HIAA level is inversely associated with score of part four of UPDRS; (4) 3-O-methyldopa (3-OMD) level is positively associated with levodopa failure syndrome (LDFS) assessed by part four of UPDRS and inversely associates with 5-HIAA. From these data, it can be inferred that serotonergic activity is decreased in PD-B to a greater extent than in PD-A and that decreased serotonergic activity plays a role in LDFS.     

Verbal working memory impairment in schizophrenia patients and their first-degree relatives: evidence from the digit span task

OBJECTIVE: The evidence for verbal working memory deficits in schizophrenia has been inconsistent. Few studies have evaluated verbal working memory in the first-degree relatives of schizophrenia patients, who likely share the genetic diathesis for schizophrenia but not the potential confounds associated with chronic mental illness. METHOD: The Wechsler Digit Span Task was used to investigate verbal working memory in 52 schizophrenia patients, 56 of their first-degree relatives, and 73 nonpsychiatric comparison subjects. RESULTS: The nonpsychotic relatives showed no impairment on the forward digit span task, a measure of general attention, but did show impairment on the backward digit span task, a measure of verbal working memory. Schizophrenia patients showed impairment on both the forward and backward digit span tasks. CONCLUSIONS: These results indicate that the forward and backward digit span tasks tap different cognitive abilities that are differentially associated with the diathesis for schizophrenia. Working memory deficits associated with schizophrenia appear to be generalized and not limited to the spatial modality.     

Evaluation of placental protein modifications in normotensive and spontaneously hypertensive rats

Hypertension in pregnancy is often associated to placental deficiency. Therefore several physiopathological modifications occur to sustain fetal well-being through protective mechanisms. Here, we used spontaneously hypertensive rat (SHR) and normotensive Wistar-Kyoto (WKY) counterpart to evaluate in late gestation (d 20) modification of placental proteins involved in adaptation to hypertension. Placenta from WKY and SHR was excised for the evaluation of protein changes by Western blot analysis and zymography. In particular, we showed in SHR placentas an increase in angiotensin receptor type 1 and a decrease in angiotensin converting enzyme. Conversely, inducible nitric oxide synthase expression was increased, while constitutive endothelial nitric oxide synthase was similar in both groups. Placentas from SHR showed a reduced protein expression in both peroxisome proliferators-activated receptors-alpha and -gamma. Pro-metalloproteinase-9 activity was not significantly modified, whereas both pro-metalloproteinase-2 and its active form present a higher activity in SHR placentas. Moreover, at the end of pregnancy, cyclooxygenase-2 expression decreased in SHR placentas. These data may provide new insights into the placental adaptive mechanisms that take place during pregnancy in SHR.     

Risk of Respiratory Complications and Wound Infection in Patients Undergoing Ambulatory Surgery: Smokers versus Nonsmokers

Background: Smoking is considered to be a risk factor for patients undergoing surgery and anesthesia, but it is unclear whether this is applicable to patients undergoing ambulatory surgery. The aim of this study was to determine the risk of respiratory complications and wound infection among smokers.

Methods: The authors studied a random selection of 489 adult patients undergoing ambulatory surgery. Smoking status was determined by self-report and confirmed with end-expired carbon monoxide analysis. The risk of respiratory complications (i.e., desaturation, cough, laryngospasm, bronchospasm, breath-holding, or apnea) and wound infection (i.e., wound redness or discharge +/- positive microbial culture, requiring antibiotic therapy) in smokers versus nonsmokers was ascertained. Odds ratios were estimated from multivariable logistic regression and adjusted for age, gender, body mass index, partner's smoking status, domiciliary smoking exposure, and extent and duration of surgery.

Results: Most smokers continued to smoke up until the day of surgery. Smokers had a higher rate of respiratory complications (32.8%vs. 25.9%; adjusted odds ratio, 1.71; 95% confidence interval, 1.03-2.84;P = 0.038) and wound infection (3.6%vs. 0.6%; odds ratio, 16.3; 95% confidence interval, 1.58-175;P = 0.019). Odds ratios comparing current plus ex-smokers with nonsmokers were of similar magnitude for most of these complications.     

Adenocarcinoma of the Ampulla of Vater: T-Stage,Chromosome 17p Allelic Loss,and Extended Pancreaticoduodenectomy are Relevant Prognostic Factors

Objective To evaluate the prognostic significance of different clinico-pathological and molecular factors, and to compare survival after standard and extended pancreaticoduodenectomy (PD) in ampulla of Vater adenocarcinoma (AVAC). Summary Background Data There are discordant data on factors affecting prognosis, and hence therapeutic choices, in AVAC. Patients and Methods Clinical-pathological factors were evaluated in 59 patients, subjected to PD for AVAC; in 42 subjects information on chromosome 17p and 18q allelic losses (LOH) and microsatellite instability (MSI) was also available. The association between survival and type of PD was investigated in the 25 patients operated between 1990 and 2001 (16 standard and nine extended). Results The overall 5- and 10-year tumor-related survival rates were 46% and 33%, respectively. Sixteen patients had T-stages 1–2, 14 T-stage 3, and 29 T-stage 4 cancers. Chromosome 17p and 18q LOH were detected in 23 (55%) and 15 cases (36%), respectively, and in 12 cases (29%) coexisted. Five cases were MSI-positive (12%). At univariate analysis, poor survival was associated with cancer ulceration (P = 0.051), poor differentiation (P = 0.008), T-stage 4 (P < 0.001), nodal metastases (P = 0.004), chromosome 17p (P < 0.001) and 18q LOH (P = 0.002), and absence of MSI (P = 0.009). At multivariate analysis, only T-stage (P = 0.002) and 17p LOH (P = 0.001) were independent predictors of survival. All patients with MSI-positive cancers were long-survivors (>12 yrs), whereas only 30% of MSI-negative cancer patients survived at 5 years. Extended pancreaticoduodenectomy was associated with a 3-year disease-related survival higher than standard resection (83% vs 31%; P = 0.018). Conclusion MSI and chromosome 17p status allow to better define prognosis within ampullary cancers at the same stage. Surgery alone resulted curative in MSI-positive cancer patients, whereas it was inadequate in patients showing allelic losses, who might benefit from adjuvant therapy. In this observational study, extended PD was associated with increased survival compared to standard procedures. Presented at the 2006 Annual Meeting of the American Hepato-Pancreato-Biliary Association, Miami Beach, Florida, March 9–12, 2006     

Acute Humoral Rejection of Human Lung Allografts and Elevation of C4d in Bronchoalveolar Lavage Fluid

Antibody-mediated rejection is well established for renal allografts but remains controversial for lung allografts. Cardinal features of antibody-mediated rejection in renal allografts include antibodies to donor human leukocyte antigen (HLA) and evidence for antibody action, such as complement activation demonstrated by C4d deposition. We report a lung allograft recipient with circulating antibodies to donor HLA who failed treatment for acute cellular rejection but responded to therapy for humoral rejection. To address the second criteria for antibody-mediated rejection, we determined whether complement activation could be detected by measuring C4d in bronchoalveolar lavage fluid (BALF) by ELISA. Airway allergen challenge of asthmatics activates the complement pathway; therefore, we used BALF from asthmatics pre- and post-allergen challenge to measure C4d. These controls demonstrated that ELISA could detect increases in C4d after allergen challenge. BALF from the index patient had elevated C4d concomitant with graft dysfunction and anti-donor HLA in the absence of infection. Analysis of BALF from 25 additional lung allograft recipients showed that C4d concentrations >100 ng/mL were correlated with anti-HLA antibodies (p = 0.006), but were also observed with infection and in asyptomatic patients. The findings support the occurrence of anti-HLA-mediated lung allograft rejection and suggest that C4d measurement in BALF may be useful in diagnosis.     

Efficacy and safety profile of a novel technique,ThuLEP (Thulium laser enucleation of the prostate) for the treatment of benign prostate hypertrophy. Our experience on 148 patients

Background

Over the past years laser technology has played a predominant role in prostate surgery, for the treatment of benign prostate hypertrophy (BPH). Various laser devices have been introduced in clinical practice, showing good results in terms of complications and urodynamic outcomes efficacy compared with TURP and Open Prostatectomy.

In this study we describe the efficacy and the safety profile of a novel laser technique, ThuLEP (Thulium Laser Enucleation of Prostate) that permits a complete anatomical endoscopic enucleation of prostatic adenoma independently to prostate size.

Methods

148 patients with a mean age of 68.2 years were enrolled between September 2009 and March 2012 (36 months), and treated for BPH with ThuLEP. Every patient was evaluated at base line according to: Digital Rectal Examination (DRE), prostate volume, Post-Voided volume (PVR), International Prostate Symptoms Score (I-PSS), International Index of Erectile Function-5 (IIEF-5), Quality of Life (QoL), PSA values, urine analysis and urine culture, uroflowmetry. The same evaluation was conducted after a 12 month follow-up. ThuLEP was performed by 2 expert surgeons.

Results

Our data showed a better post-operative outcome in terms of catheter removal, blood loss, TURP syndrome, clot retention and residual tissue compared to large series of TURP and OP. Only 1.3% of patients had bladder wall injury during morcellation. I-PSS, Qmax, Prostate Volume, QoL and PVR showed a highly significant improvement at 12 month follow-up in comparison to preoperative assessment.

Conclusion

ThuLEP represent an innovative option in patients with BPH. It is a size independent surgical endoscopic technique and it can be considered the real alternative, at this time, to TURP and even more to Open Prostatectomy for large prostate, with a complete removal of adenoma and with a low complication rate.

     

Parainfluenza Virus Infection in Adult Lung Transplant Recipients: An Emergent Clinical Syndrome with Implications on Allograft Function

Parainfluenza virus is a common cause of seasonal upper respiratory tract infections in children and adults. Studies indicate that parainfluenza virus may play an important role in the etiology of respiratory tract infections in lung transplant recipients with an estimated incidence of 5.3 per 100 patients. Parainfluenza virus type 3 is the most frequent serotype in lung transplant patients. The rate of lower respiratory tract infections with parainfluenza virus among lung transplant recipients is between 10 and 66% of cases. In addition, trans-bronchial biopsy at the time of parainfluenza infection shows signs of acute allograft rejection. Subsequently, 32% of patients have been found to have active bronchiolitis obliterans at a median time of 6 months (range 1-14) postviral infection. These findings indicate that parainfluenza virus infections may have long-term implications for lung transplant recipients. Further studies are required to identify the mechanisms of immunomodulation of parainfluenza virus among these patients. In addition, controlled studies are needed to evaluate the efficacy of aerosolized ribavarin in the treatment of parainfluenza virus infection and to determine whether vaccines may be effective in these high-risk patients.     

Surgical complications in patients with Parkinson's disease after posteroventral pallidotomy

OBJECTIVE: To investigate the potential operative morbidity in posteroventral pallidotomy (PVP) for patients with Parkinson's disease. METHODS: We designed a retrospective study that included 796 consecutive patients (mean age, 64.9 yr; male, 559; female, 237) with Parkinson's disease. All PVPs (simultaneous bilateral PVP, n = 272; sequential bilateral PVP, n = 88; unilateral PVP, n = 436) were performed during a 7-year period. The total number of operations was 884, and the number of PVP procedures was 1156. In 108 patients, ventral intermediate nucleus thalamotomy was performed simultaneously. RESULTS: The overall complication rate, including temporary problems, was 15.3% of 884 operations. Permanent complications occurred in 3.6% of total operations. Intracranial hemorrhage occurred in 24 operations (2.7%). In seven of them, the patients required craniotomy and hematoma evacuation and sustained a disabling motor deficit (0.8%). Intracranial hemorrhage occurred more often in patients who underwent microelectrode recording and had a history of chronic hypertension. Hemiparesis without intracranial hematoma occurred in 12 operations (1.4%). Microelectrode recording was a risk factor for postoperative hemiparesis without hemorrhage. In 19 operations (2.1%), patients developed a partial visual field deficit. Speech disturbance after surgery was observed in 23 operations (2.6%) but resolved in 17 by 1 week after surgery. In 55 operations (6.2%), patients developed postoperative confusion. This occurred more often in elderly patients and those with advanced disease. In 17 operations (1.9%), patients required observation in the intensive care unit because of postoperative hypotension. CONCLUSION: Complications from stereotactic pallidotomy were not frequent. However, the residual symptoms from complications can be serious in many cases.