Identification and in silico analysis of 14 novel GJB1, MPZ and PMP22 gene mutations

Duplication within the chromosome 17p11.2 (CMT1Adup), peripheral myelin protein 22 (PMP22), myelin protein zero (MPZ) and gap junction β1-protein (GJB1) gene mutations are frequent causes of the Charcot-Marie-Tooth disease (CMT). A large number of mutations in these genes are listed in databases. Sequence variants identified in patients are frequently reported as mutations without further evaluation. We analyzed 250 consecutively recruited unrelated Austrian CMT patients for CMT1Adup by microsatellite marker typing, real-time PCR or MLPA, and found 79 duplications (31.6%). The coding regions of the PMP22, MPZ and GJB1 genes were analyzed by direct sequencing in the remaining patients; 28 patients showed mutations, 14 of which were novel. We scored the pathogenicity of novel missense mutations by segregation studies and by their exclusion in control samples. Our comprehensive literature study found that up to 60% of the reported mutations in these genes had not been evaluated regarding their pathogenicity, and the PANTHER bioinformatics tool was used to score novel and published missense variants. The PANTHER program scored known polymorphisms as such, but scored ∼82–88% only of the published and novel mutations as most likely deleterious. Mutations associated with axonal CMT were less likely to be classified as deleterious, and the PMP22 S72L mutation repeatedly associated with severe CMT was classified as a polymorphism using default parameters. Our data suggest that this in silico analysis tool could be useful for assessing the functional impact of DNA variations only as a complementary approach. The CMT1Adup, GJB1, MPZ and PMP22 mutation frequencies were in the range of those described in other CMT patient collectives with different ethnical backgrounds.     

The retroperitoneal approach combined with epidural anesthesia reduces morbidity in elective infrarenal aortic aneurysm repair

In elective open infrarenal aortic aneurysm repair the surgical approach and the use of epidural anesthesia (EDA) may determine patients' outcome. Hence we analyzed our results after elective open aneurysm repair in the light of the surgical approach and the use of EDA. Retrospective analysis of a prospective data base. From December 2005 to April 2008, 125 patients with infrarenal aortic aneurysm underwent elective open repair. Patients were divided into four groups: retro- and transperitoneal approach with and without epidural anesthesia (RP+/-EDA and TP+/-EDA). In terms of age, sex, aneurysm diameter, ASA score and clamping time all groups were comparable. In the retroperitoneal groups significantly more tube grafts were implanted (63 vs. 27; P=0.001). The rate of surgical complications did not differ between the groups. The RP+EDA group had the lowest rate of postoperative assisted mechanical ventilation (5.1% vs. 35.7%; P=0.002) and medical complications (17.9% vs. 42.8%; P=0.032). Concerning frequency of surgical complications, the retroperitoneal incision was comparable to the transperitoneal approach in infrarenal aortic reconstruction. Supplementation with EDA resulted in a decreased rate of postoperative assisted mechanical ventilation and in lower morbidity rates.     

Pancreas after living donor kidney transplants in diabetic patients: impact on long-term kidney graft function

Abstract:  In this single-institution study, we compared outcomes in diabetic recipients of living donor (LD) kidney transplants that did vs. did not undergo a subsequent pancreas transplant. Of 307 diabetic recipients who underwent LD kidney transplants from January 1, 1995, through December 31, 2003, a total of 175 underwent a subsequent pancreas after kidney (PAK) transplant; 75 were deemed eligible (E) for, but did not receive (for personal or financial reasons), a PAK, and thus had a kidney transplant alone (KTA); and 57 deemed ineligible (I) for a PAK because of comorbidity also had just a KTA. We analyzed the three groups (PAK, KTA-E, KTA-I) for differences in patient characteristics, glycemic control, renal function, patient and kidney graft survival rates, and causes of death. Kidney graft survival rates (actuarial) were similar in the PAK vs. KTA-E groups at one, five, and 10 yr post-transplant: 98%, 82%, and 67% (PAK) vs. 100%, 84%, and 62% (KTA-E) (p = 0.9). The long-term (greater than four yr post-transplant) estimated glomerular filtration rate (GFR) was higher in the PAK than in the KTA-E group: 53 ± 20 mL/min (PAK) vs. 43 ± 16 mL/min (KTA-E) (p = 0.016). The patient survival rates were also similar for the PAK and KTA-E groups. We conclude that the subsequent transplant of a pancreas after an LD kidney transplant does not adversely affect patient or kidney graft survival rates; in fact, it is associated with better long-term kidney graft function.     

Off-Pump Extraanatomic Bypass from the Ascending to the Descending Aorta for Re-Operation of Interrupted Aortic Arch in an Adolescent

Abstract   The appearance of re-stenosis after repair of an interrupted aortic arch may be a surgical challenge due to adhesions. Here, we describe an approach using off-pump coronary artery bypass grafting techniques to reach the descending aorta through a median sternotomy in a patient with aortic arch stenosis after conduit repair. The 17-year-old patient with diagnoses of interrupted aortic arch and ventricular septal defect presented after two previous operations (one left lateral thoracotomy and one median sternotomy) with a stenosed vascular graft between ascending and descending aorta. Surgery was done via re-sternotomy without cardio-pulmonary bypass. An extraanatomic graft was used to connect ascending and descending aorta. When performing the distal anastomosis, the heart was exposed using a standard suction device. This case demonstrates that the use of modern techniques may facilitate surgical approaches dramatically. In our opinion the above-described technique is the first choice for all patients requiring arch repair following multiple previous operations, performed via sternotomy and thoracotomy.     

Time-dependent hemispheric shift of the cortical control of volitional swallowing

An important part of the cortical processing of swallowing takes place in the sensorimotor cortex, predominantly in the left hemisphere. However, until now, only deglutition related brain activation with low time resolution exceeding a time interval of 1 s has been reported. In this study, we have examined the chronological sequence of cortical swallowing processing in humans by means of high temporal resolution magnetoencephalography (MEG). The cortical MEG activity was recorded during self-paced volitional swallowing in 10 healthy subjects. Data were analyzed using synthetic aperture magnetometry and the group analysis was performed using a permutation test. Swallowing-related muscle activity was recorded by electromyography. Within the time interval of 1 s of the most pronounced muscular swallowing execution, the MEG analysis revealed neural activation in the primary sensorimotor cortex. During the first 600 ms, only left hemispheric activation was found, bihemispheric activation during the next 200 ms and a right hemispheric activation during the last 200 ms. Thus, our results demonstrate a time-dependent shift of neural activation from left to right sensorimotor cortex during deglutition with left hemispheric dominance in the early stage of volitional swallowing and right hemispheric dominance during its later part.     

Differential effects of anxiety and depression on interoceptive accuracy

Background: Feedback from the body is assumed to be altered in depression. Nevertheless, empirical studies investigating this assumed relationship remain sparse. This study aimed to examine interrelations between the ability to perceive heartbeats accurately (interoceptive awareness), depressive symptoms, and anxiety in healthy participants. Methods: A well‐validated heartbeat perception task to measure interoceptive awareness together with two questionnaires indexing anxiety and depression were administered to 119 participants. Results: As main results we observed a negative correlation between heartbeat perception and depression. Only when focussing on high anxiety levels this negative correlation coefficient between depression and interoception remained significant. Conclusions: Our results highlight the possible relationship between depressive symptoms and interoceptive awareness and may have further implications for theoretical models of anxiety disorders and their treatment. Further research is required to examine the potential consequences of altering interoceptive awareness in healthy subjects in relation to depression and anxiety. Depression and Anxiety, 2009. © 2009 Wiley‐Liss, Inc.     

Hematopoietic cell transplantation after reduced-intensity conditioning for older adults with acute myeloid leukemia in complete remission

PURPOSE OF REVIEW: Allogeneic hematopoietic cell transplantation with myeloablative conditioning is a well established therapy for patients with acute myeloid leukemia. Its efficacy depends, in part, on the destruction of recipient acute myeloid leukemia cells by the conditioning regimen and, in part on their removal by donor immune cells contained in the graft (graft-versus-tumor effect). Due to regimen-related toxicities, the use of myeloablative allogeneic hematopoietic cell transplantation has been restricted to younger patients in good condition. More recently, the introduction of allogeneic hematopoietic cell transplantation following reduced-intensity or nonmyeloablative conditioning regimens, which rely mainly on graft-versus-tumor effects for tumor cell eradication, has permitted extending hematopoietic cell transplantation to include older patients and those with medical comorbidities. RECENT FINDINGS: Early results with allogeneic hematopoietic cell transplantation after nonmyeloablative and reduced-intensity conditioning for patients with acute myeloid leukemia in first complete remission are encouraging, with 2-year survivals after hematopoietic cell transplantation ranging from 48 to 79% among studies. Further, retrospective studies have demonstrated similar outcomes in adult patients with acute myeloid leukemia in complete remission given either myeloablative or nonmyeloablative conditioning. SUMMARY: Prospective studies are needed to define the place of allogeneic hematopoietic cell transplantation after nonmyeloablative or reduced-intensity conditioning in patients with acute myeloid leukemia in complete remission, and to determine a role for consolidation chemotherapy before hematopoietic cell transplantation, if any.     

Coordination of strength exertion during the chair-rise movement in very old people

BACKGROUND: Changes in performance of standing up from a chair have been related to measures of strength or power. However, the sit-to-stand (STS) transfer requires that the individual exerts forces with appropriate magnitude and timing. These coordinative aspects have received less attention. This study aims to analyze differences in STS performance in older people based on measures that are derived from ground reaction forces (GRFs) during STS transfer. METHODS: One hundred thirty-five participants (84.5% women; mean age 82.5 years) stood up from a chair as fast as possible. Time of stabilization after reaching an upright position, power, maximum vertical GRF, increase of vertical GRF, overshoot of vertical GRF over body weight, and left-right difference of GRF were measured by a force plate under each foot. To explain variance of total time to stand up, these variables were used as independent variables in a linear regression model. RESULTS: Eighty-one percent of variance of total time to stand up was explained by the independent variables. The strongest predictor of total time was time of stabilization (F = 459.4). Another model of linear regression explained 37% of variance of time to reach an upright position, with increase of GRF as the strongest predictor (F = 38.3). Influence of maximum vertical GRF was weak in both models. CONCLUSIONS: Variables related to coordination of strength, measured during STS transfer, were able to explain a high proportion of variance of time to rise from a chair. Stabilization after reaching an upright position seems to be a parameter worth further investigation.