Shortening the second phase duration of biphasic shocks: effects of class III antiarrhythmic drugs on defibrillation efficacy in humans

INTRODUCTION: The specific waveform providing optimal defibrillation threshold (DFT) is unknown. We compared the defibrillation efficacy of biphasic pulses with second phases (P2) of 2 and 5 msec in a randomized prospective clinical study. METHODS AND RESULTS: Intraoperative DFTs of 62 patients (age 54 +/- 13 years; ejection fraction 43% +/- 17%; amiodarone 47%, d,l-sotalol 13%) were determined in random order using a binary search protocol. Anodal shocks of 60% tilt first phases (P1) and P2 of 2 msec/5 msec were delivered from two 100-microF capacitors between the right ventricular electrode and the test housing of a Phylax 06/XM device. Mean DFT was significantly lower using the shorter P2 (9.5 +/- 4.5 J vs 11.3 +/- 5.2 J; P < 0.0001). According to subgroup analysis, the effect of changing P2 duration was only influenced by antiarrhythmic treatment. DFT decreased markedly using the shorter P2 in patients treated with amiodarone (10.7 +/- 4.9 J vs 13.4 +/- 5.6 J; P < 0.00001) or d,l-sotalol (6.1 +/- 3.3 J vs 9.1 +/- 4.6 J; P < 0.05). The difference in patients not treated with Class III drugs was found to be insignificant. Chronic amiodarone treatment increased DFT only when the longer P2 was used. CONCLUSION: Biphasic shocks with shorter P2 should be used in patients undergoing Class III antiarrhythmic treatment.     

Selective fascicular nerve repair: a rapid method for intraoperative motorsensory differentiation by acetylcholinesterase histochemistry

Summary The selective reunion of motor and sensory fascicles of severed mixed nerves appears indispensible for optimal recovery of the impaired motor function. Procedures available for rapid identification of motor and sensory fascicles rendered ambiguous results. The only highly reliable and simple method marking motor fascicles, namely acetylcholinesterase histochemistry, neccessitated two operations due to its long duration (28 h). In the present study rapid demonstration of acetylcholinesterase activity was accomplished by elevating the temperature and the concentration of 2 constituents of the incubation medium. Now incubation takes 2 h instead of 20 h. Thus, the time necessary for the entire diagnostic procedure could be reduced from 28 h to 4 h. Indeed, intraoperative motorsensory differentiation using acetylcholinesterase activity as a marker appears feasible. The new technique has already been applied to 6 clinical cases of acute nerve injuries of the forearm. The histochemical results obtained are comparable to those of the standard procedure indicating equally high reliability of both methods. Finally, opportunities for further reducing the duration of the modified histochemical procedure and its applicability to fascicular nerve grafting are discussed.     

18F-FDG PET detection of lymph node metastases in medullary thyroid carcinoma.

Postsurgically elevated or increasing serum calcitonin levels strongly suggest the presence of residual or recurrent medullary thyroid carcinoma (MTC). Several imaging modalities (sonography, MRI, CT, scintigraphy with different types of radiolabeled ligands, etc.) are routinely used in an attempt to localize tumorous tissue, but such efforts often fail. In the search for a more reliable method, 18F-FDG PET was applied to detect tumor tissue of residual or recurrent MTC. METHODS: Forty patients with a postoperatively elevated plasma calcitonin level were included. These patients underwent routine diagnostic imaging procedures (CT, MRI, and 131I-metaiodobenzylguanidine [MIBG] whole-body planar scintigraphy or SPECT) and 18F-FDG PET examinations. Two independent experts visually analyzed the images provided by each method to detect pathologic lesions. Lymph nodes of > or = 1 cm in short diameter that were detected by radiologic methods were considered to be pathologic. 18F-FDG accumulation with a sharp contour reported by both independent observers was similarly regarded as pathologic. RESULTS: PET detected 270 foci with a high tracer accumulation, whereas only 116 lesions were detected by MRI and 141 by CT. The numbers of such foci determined by PET, MRI, and CT were 98, 34, and 34, respectively, in the neck; 25, 5, and 6, respectively, in the supraclavicular regions; and 117, 35, and 39, respectively, in the mediastinum. 131I-MIBG scintigraphy findings were positive for only 3 patients. CONCLUSION: For MTC patients with a postoperatively elevated plasma tumor marker level, PET was more sensitive and superior in localizing tumorous lymph node involvement than were the other imaging modalities, especially in the cervical, supraclavicular, and mediastinal lymphatic regions.     

Ultrasound-assisted laparoscopic cryomyolysis: two- and three-dimensional findings before, during and after treatment.

OBJECTIVE: To investigate the role of two- and three-dimensional (2D and 3D) ultrasound and power Doppler before, during and after surgery in monitoring the effects of uterine fibroid laparoscopic cryomyolysis. METHODS: This prospective study involved 10 premenopausal patients with a sonographic diagnosis of a single subserosal and/or intramural uterine myoma, who underwent laparoscopic cryomyolysis. All patients suffered from symptoms due to fibroids (menometrorrhagia, bulk-related symptoms, pelvic pain). During laparoscopy transvaginal sonography was performed to guide the insertion of the cryoprobe, monitor extension of the ice-ball and evaluate the reduction of the blood supply of the myoma. All patients underwent 2D and 3D sonographic and power Doppler imaging evaluation of the myoma 1 week before treatment, during cryomyolysis, and 1, 3 and 6 months after treatment; size, echostructure and vascularization were recorded. RESULTS: With cryomyolysis, we achieved selective vessel and tissue damage within the fibroid alone. Eight patients were free of symptoms and two had improved after 3 months. Progressive shrinkage of the treated myoma was observed during follow-up with a reduction percentage after 1 month of 22.2%, after 3 months of 37.5% and after 6 months of 52.6%. After cryomyolysis a significant reduction in central blood flow of the myoma was observed. 2D and 3D power Doppler evaluation of vascularization did not differ although subjectively findings were best evaluated by 3D images. CONCLUSION: Sonography can aid the safe accomplishment of cryomyolysis by assessing myomata preoperatively, guiding the freezing procedure during laparoscopy, and helping to monitor postoperative progress. The use of ultrasound in this new treatment of fibroids will permit the physician to modulate and individualize treatment.     

Defective insulin secretion and increased susceptibility to experimental diabetes are induced by reduced Akt activity in pancreatic islet beta cells

The insulin and IGF signaling pathways are critical for development and maintenance of pancreatic beta cell mass and function. The serine-threonine kinase Akt is one of several mediators regulated by these pathways. We have studied the role of Akt in pancreatic beta cell physiology by generating transgenic mice expressing a kinase-dead mutant of this enzyme in beta cells. Reduction of Akt activity in transgenic animals resulted in impaired glucose tolerance due to defective insulin secretion. The mechanisms involved in dysregulation of secretion in these mice lie at the level of insulin exocytosis and are not the result of abnormalities in glucose signaling or function of voltage-gated Ca2+ channels. Therefore, transgenic mice showed increased susceptibility to developing glucose intolerance and diabetes following fat feeding. These observations suggest that Akt plays a novel and important role in the regulation of distal components of the secretory pathway and that this enzyme represents a therapeutic target for improvement of beta cell function in diabetes.     

Axial plane dissimilarities of two identical Lenke-type 6C scoliosis cases visualized and analyzed by vertebral vectors

Purpose

The global appearance of scoliosis in the horizontal plane is not really known. Therefore, the aims of this study were to analyze scoliosis in the horizontal plane using vertebral vectors in two patients classified with the same Lenke group, and to highlight the importance of the information obtained from these vertebral vector-based top-view images in clinical practice.

Methods

Two identical cases of scoliosis were selected, based on preoperative full-body standing anteroposterior and lateral radiographs obtained by the EOS? 2D/3D system. Three-dimensional (3D) surface reconstructions of the spinal curves were performed by using sterEOS? 3D software before and after surgery. In both patients, we also determined the vertebral vectors and horizontal plane coordinates for analyzing the curves mathematically before and after surgery.

Results

Despite the identical appearance of spinal curves in the frontal and sagittal planes, the horizontal views seemed to be significantly different. The vertebral vectors in the horizontal plane provided different types of parameters regarding scoliosis and the impact of surgical treatment: reducing lateral deviations, achieving harmony of the curves in the sagittal plane, and reducing rotations in the horizontal plane.

Conclusions

Vertebral vectors allow the evolution of scoliosis curve projections in the horizontal plane before and after surgical treatment, along with representation of the entire spine. The top view in the horizontal plane is essential to completely evaluate the scoliosis curves, because, despite the similar representations in the frontal and sagittal planes, the occurrence of scoliosis in the horizontal plane can be completely different.

Graphical abstract

These slides can be retrieved under Electronic Supplementary Material.

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T-lymphocyte recovery and function after cord blood transplantation

The Szabolcs laboratory is focused on understanding the biology of donor-derived cellular immunity in recipients of allogeneic hematopoietic cell transplantation that can be translated into new immunotherapy strategies. To this end, we are focused on developing novel laboratory approaches to analyze and augment immune recovery for high risk patient cohorts without increasing graft-versus-host disease. Much of our work has focused on unrelated cord blood transplantation as the dominant clinical scenario and laboratory model. Our overarching goal is to minimize transplant-related mortality and morbidity and render HLA-mismatched unrelated cord blood transplant, a widely accepted safe cellular therapy. Donor leukocyte infusions in the allogeneic hematopoietic transplant setting can provide a clinically relevant boost of immunity to reduce opportunistic infections and to increase graft-versus-leukemia activity. Our laboratory has a major focus toward ex vivo expansion of cord blood T cells with anti-apoptotic cytokines and CD3/CD28 co-stimulatory beads. Expanded lymphocytes lack alloreactivity against recipient and other allogeneic cells indicating a favorable safety profile from graft-versus-host disease. Nevertheless, expanded T cells can be primed subsequently against lymphoid and myeloid leukemia cells to generate tumor-specific cytotoxic T cells. These findings offer a major step in fulfilling critical biological requirements to quickly generate a cellular product ex vivo, using a negligible fraction of a cord blood graft that provides a flexible adoptive immunotherapy platform for both children and adults.     

Induction of pluripotent stem cells from autopsy donor-derived somatic cells

Human induced pluripotent stem cells (iPSCs) have become an intriguing approach for neurological disease modeling, because neural lineage-specific cell types that retain the donors’ complex genetics can be established in vitro. The statistical power of these iPSC-based models, however, is dependent on accurate diagnoses of the somatic cell donors; unfortunately, many neurodegenerative diseases are commonly misdiagnosed in live human subjects. Postmortem histopathological examination of a donor's brain, combined with premortem clinical criteria, is often the most robust approach to correctly classify an individual as a disease-specific case or unaffected control. In this study, we describe iPSCs generated from a skin biopsy collected postmortem during the rapid autopsy of a 75-year-old male, whole body donor, defined as an unaffected neurological control by both clinical and histopathological criteria. These iPSCs were established in a feeder-free system by lentiviral transduction of the Yamanaka factors, Oct3/4, Sox2, Klf4, and c-Myc. Selected iPSC clones expressed both nuclear and surface antigens recognized as pluripotency markers of human embryonic stem cells (hESCs) and were able to differentiate in vitro into neurons and glia. Statistical analysis also demonstrated that fibroblast proliferation was significantly affected by biopsy site, but not donor age (within an elderly cohort). These results provide evidence that autopsy donor-derived fibroblasts can be successfully reprogrammed into iPSCs, and may provide an advantageous approach for generating iPSC-based neurological disease models.