Evidence that the COMTVal158Met polymorphism moderates subclinical psychotic and affective symptoms in unaffected first-degree relatives of patients with schizophrenia.

OBJECTIVES: Psychotic patients with COMT(Val158Met) Met alleles were recently found to display more intense psychotic and affective responses to daily life stressors. We aimed to test the hypothesis that the Met allele is implicated in the development of affective and psychotic symptomatology in subjects genetically at risk for schizophrenia, by testing if unaffected first-degree relatives of patients with schizophrenia who share a Met allele have greater concordance of symptomatology than relatives not sharing a Met allele. METHODS: Unaffected relatives (n=38) were arranged in as many genetically related pairs as possible (n=26), and Met-sharing between Index Unaffected Subject (IUS) and Related Unaffected Subject (RUS) was assessed. Symptomatology was assessed with the Brief Psychiatric Rating Scale (BPRS) total score. RESULTS: Multilevel regression revealed an interaction between RUS BPRS score and Met-sharing in the model of IUS BPRS score (interaction chi(2)=3.78, p=0.05). Stratified analyses revealed that IUS-RUS total BPRS scores were significantly associated in the case of Met-sharing (B=0.57, 95% CI: 0.22-0.93, p=0.002), but were not when there was no Met-sharing. CONCLUSION: These findings support the hypothesis that the Met allele may be involved in the causation of psychopathology, at least in populations with a genetic predisposition to psychosis.     

Agreement of tricuspid annular systolic excursion measurement between transthoracic and transesophageal echocardiography in the perioperative setting

Objective

The aim of our study was to evaluate the level of agreement between tricuspid annular plane systolic excursion (TAPSE) measured by transthoracic echocardiography (TTE) and TAPSE measured using transesophageal echocardiography (TEE) in anesthetized patients.

Materials and methods

Thirty patients scheduled for elective cardiac surgery were prospectively studied. Shortly after induction of anesthesia before the operation, TAPSE was measured by TTE using M-mode in apical 4chamber view (4CH) and by TEE in six different views: using 2D echocardiography in midesophageal (ME) 4CH view, using M-mode in deep transgastric right ventricle (dTG RV) view at 0° and dTG RV longaxis view (LAX) as well as using anatomical M-mode (AM-mode) in ME 4CH, dTG RV at 0° and dTG RV LAX views.

Results

Bland–Altman analysis showed a good agreement for TAPSE measured using M-mode in TTE and using AM-mode in TEE in the ME 4CH and dTG RV at 0° views (?2.5?±?18 and ?2.2?±?14% respectively). The agreement between TAPSE measured in TTE and TEE using 2D in ME 4CH, using M-mode in dT GRV 0° and using M-mode and AM-mode in dTG RV LAX view showed a significant systematic underestimation of the measurements (?8.8?±?21, ?8.8?±?24, ?17.8?±?28 and ?6.4?±?20%).

Conclusion

Our study showed that the right ventricular function can be accurately and precisely estimated using TAPSE measurement by TEE in the midesophageal four chamber and deep transgastric right ventricle view at 0° using anatomical M-mode.

     

Transforming growth factor-beta1 gene polymorphisms are associated with disease progression in idiopathic pulmonary fibrosis

Transforming growth factor-beta1 (TGF-beta1) is a cytokine that plays a key role in the development of idiopathic pulmonary fibrosis. There have been reports on the presence of two genetic polymorphisms in the DNA sequence encoding the leader sequence of the TGF-beta1 protein, located in codons 10 and 25. The objective of this study was to investigate the association between TGF-beta1 gene polymorphisms in codons 10 and 25 and the susceptibility to idiopathic pulmonary fibrosis and the progression of the disease. Compared with healthy control subjects (n = 140), patients with idiopathic pulmonary fibrosis (n = 128) showed no significant deviations in genotype or allele frequencies. One hundred and ten patients with idiopathic pulmonary fibrosis were followed up for 30.3 +/- 25 months. The presence of a proline allele at codon 10 was independently associated with a significant increase in alveolar arterial oxygen tension difference during follow-up, after controlling for the effect of treatment (coefficient = 0.59; 95% confidence intervals, 0.23 to 0.96; p = 0.002). These findings suggest that (1) TGF-beta1 gene polymorphisms in codons 10 and 25 do not predispose to the development of idiopathic pulmonary fibrosis; and (2) TGF-beta1 gene polymorphisms may affect disease progression in patients with idiopathic pulmonary fibrosis.     

Does epidural versus combined spinal-epidural analgesia prolong labor and increase the risk of instrumental and cesarean delivery in nulliparous women?

Study ObjectiveTo compare duration of labor, mode of delivery, and local anesthetic consumed in women who received labor analgesia with epidural or combined spinal-epidural technique.DesignRetrospective, observational study.SettingDelivery room of a university hospital.Patients788 nulliparous women in labor at term with cervical dilation between three and 5 cm.InterventionsIn Group E (epidural alone), parturients received an epidural solution of 8 mL (levobupivacaine 0.125% with fentanyl 5 μg/mL). In Group CSE (combined spinal-epidural), parturients received a spinal injection of levobupivacaine two mg with fentanyl 15 μg (total volume two mL). Then an epidural catheter was placed in all patients and connected to a patient-controlled analgesia pump (basal infusion rate of 8 mL/hr of 0.1% levobupivacaine and fentanyl two μg/mL, patient-controlled bolus dose of three mL, and lockout time of 30 min).MeasurementsLabor duration, mode of delivery (spontaneous vaginal vs. instrumental delivery vs. cesarean section), and local anesthetic consumed, were recorded.Main ResultsLabor analgesia was performed with an epidural technique in 322 patients (40.9%), and a combined spinal-epidural technique in 466 patients (59.1%), of whom 39 Group E women (12.1%) and 46 Group CSE women (9.9%) required cesarean section (P=ns). No differences in the mode of delivery were observed between the groups. Time from analgesia to delivery (Group E: 217 ± 111 min vs. Group CSE: 213 ± 115 min; P=ns), and epidural local anesthetic consumed (Group E: 35 ± 20 mL vs. Group CSE: 33 ± 20 mL; P=ns), were similar in both groups.ConclusionsNo significant differences were observed between epidural and combined spinal-epidural given for labor analgesia in nulliparous women in duration of labor, mode of delivery, or local anesthetic consumed.     

Characterization of new arylsulfatase A gene mutations reinforces genotype‐phenotype correlation in metachromatic leukodystrophy

Metachromatic Leukodystrophy (MLD) is a rare inherited lysosomal storage disorder caused by the deficiency of Arylsulfatase A (ARSA). The disease manifests itself with a broad spectrum of clinical variants, all characterized by progressive neurodegeneration in the central and peripheral nervous systems. The correlation between mutations in the ARSA gene, residual enzymatic activity associated with the mutated alleles and patients' phenotype, which has been extensively drawn for common ARSA mutations, has recently been expanded to rare ones. In this context, functional studies on the rare allelic variances acquire particular relevance for patients' prognostic evaluation. Here we have characterized eight newly identified ARSA mutations, through lentiviral vector‐based expression studies on cell lines and ARSA defective murine fibroblasts. In each case, the residual activity associated with the new mutant allele correlates well with the patient's phenotype. Therefore, our results confirm the importance of functional characterization of mutant alleles for a precise genotype‐based classification and definition of prognosis in MLD patients, which is particularly relevant for pre‐symptomatic diagnosis. © 2009 Wiley‐Liss, Inc.     

Effects of Short-Term Risedronate on Bone Resorption and Patient Satisfaction in Postmenopausal Osteoporosis Patients

This multicenter, open-label study evaluated the effects of short-term risedronate on bone resorption and patient satisfaction in postmenopausal women with osteoporosis in Brazil. Entry requirements included: osteoporosis of the spine/femoral neck diagnosed by a bone mineral density (BMD) T-score ≤ ?2.5 or radiographic fragility fracture within the last year and no treatment with osteoporosis medication in the preceding 3 mo. Patients were treated with once weekly risedronate of 35 mg for 12 wk. Patients also received 1000 mg calcium carbonate and 400 IU vitamin D. The main outcome was the effect on bone resorption, as assessed by the quantification of serum C-telopeptide of type I collagen (CTX). Of the 556 women screened, 480 women received ≥1 dose of study drug (intent-to-treat [ITT] population), and 390 completed treatment (81%). After 12 wk, CTX decreased in 94% of patients (from 0.419 ± 0.234 to 0.158 ± 0.171 μg/L, p < 0.0001). Mean CTX reduction was 60.6%. Patient satisfaction was good/excellent in 91.7% of patients. A total of 156 adverse events (AEs) were reported by 113 (23.5%) patients in the ITT population. Digestive symptoms emerged or worsened in 7.1% and 3.5%, respectively. Five patients (1.0%) experienced serious AEs, not considered to be related to risedronate. In conclusion, risedronate significantly reduced serum CTX after 12-wk treatment. Almost all patients reported good/excellent satisfaction.