Localization of dystonic muscles with 18F-FDG PET/CT in idiopathic cervical dystonia.

The purpose of this study was to investigate whether (18)F-FDG PET/CT is useful for localizing dystonic cervical muscles in patients with idiopathic cervical dystonia (ICD) by comparing disease severity before and disease severity after botulinum toxin (BT) injection into hypermetabolic muscles. METHODS: Six patients with ICD underwent (18)F-FDG PET/CT. Dystonic muscles suitable for BT injection therapy were defined as those showing diffusely increased (18)F-FDG uptake. RESULTS: Hypermetabolic cervical muscles were identified in all 6 patients. In 2 patients who underwent PET/CT both in a supine position and in a sitting position during (18)F-FDG uptake, abnormal hypermetabolic muscles were observed by PET/CT only when patients were in the sitting position with their heads and necks in the adopted abnormal involuntary posture. Symptoms were significantly improved in 4 patients who underwent BT injection therapy guided by PET/CT and who were clinically monitored. CONCLUSION: (18)F-FDG PET/CT is potentially useful for identifying dystonic cervical muscles for BT therapy in patients with ICD.     

The effect of cognitive-behavioral group therapy on the self-esteem, depression, and self-efficacy of runaway adolescents in a shelter in South Korea.

This study examined the effects of cognitive-behavioral group therapy (CBT) on the self-esteem, depression, and self-efficacy of runaway adolescents residing in a shelter in Seoul, South Korea. The study used a control group pretest-posttest design. The experimental group and the control group consisted of 14 and 13 male subjects, respectively, with subjects having been randomly assigned to these groups. The experimental group participated in a CBT that consisted of eight sessions over an 8-week period; the control group did not participate in the program. To examine the effects of the CBT on dependent variables, the Wilcoxon signed rank test was used. The scores on depression decreased significantly (z = -2.325, p = .02) and those on self-efficacy increased significantly (z = -2.098, p = .03) after the intervention in the experimental group. There was no significant change on self-esteem (z = -1.19, p = .23). In the control group, the scores on depression, self-esteem, and self-efficacy did not change significantly after the intervention period. The CBT developed in this study consisted of structured and specific content that could be usefully applied to runaway adolescents residing in a shelter.     

Synergistic effects of Nell-1 and BMP-2 on the osteogenic differentiation of myoblasts.

Osteogenesis is synergistically enhanced by the combined effect of complimentary factors. This study showed that Nell-1 and BMP-2 synergistically enhanced osteogenic differentiation of myoblasts and phosphorylated the JNK MAPK pathway. The findings are important because of the osteochondral specificity of Nell-1 signaling and the potential therapeutic effects of coordinated BMP-2 and Nell-1 delivery. INTRODUCTION: BMPs play an important role in the migration and proliferation of mesenchymal cells and have a unique ability to alter the differentiation of mesenchymal cells toward chondrogenic and osteogenic lineages. Signaling upstream of Cbfa1/Runx2, BMPs effects are not limited to cells of the osteoblast lineage. Thus, additional osteoblast-specific factors that could synergize with BMP-2 would be advantageous for bone regeneration procedures. NELL-1 (NEL-like molecule-1; NEL [a protein strongly expressed in neural tissue encoding epidermal growth factor like domain]) is a novel growth factor believed to preferentially target cells committed to the osteochondral lineage. MATERIALS AND METHODS: C2C12 myoblasts were transduced with AdLacZ, AdNell-1, AdBMP-2, or AdNell-1+AdBMP-2 overexpression viruses. Effects were studied by cell morphology, alkaline phosphatase activity, osteopontin production, and MAPK signaling. Additionally, in a nude mouse model, viruses were injected into leg muscles, and new bone formation was examined after 2 and 8 wk. RESULTS: C2C12 myoblasts co-transduced with AdNell-1+AdBMP-2 showed a synergistic effect on osteogenic differentiation as detected by alkaline phosphatase activity and osteopontin production. Nell-1 stimulation on AdNell-1 + AdBMP-2 preconditioned C2C12 cells revealed significant activation of the non-BMP-2 associated c-Jun N-terminal kinase (JNK) MAPK signaling pathway, but not the p38 or extracellular signal-regulated kinase (ERK1/2) MAPK pathways. Importantly Nell-1 alone did not induce osteogenic differentiation of myoblasts. In a nude mouse model, injection of AdNell-1 alone stimulated no bone formation within muscle; however, injection of AdNell-1+AdBMP-2 stimulated a synergistic increase in bone formation compared with AdBMP-2 alone. CONCLUSIONS: These findings are important because of the confirmed osteochondral specificity of Nell-1 signaling and the potential therapeutic effects of enhanced BMP-2 action with coordinated Nell-1 delivery.     

Fidgetin-like 1 gene inhibited by basic fibroblast growth factor regulates the proliferation and differentiation of osteoblasts.

The FIGNL1 gene was proven to be a new subfamily member of ATPases associated with diverse cellular activities (AAA proteins). In this in vitro study, the AAA proteins inhibited osteoblast proliferation and stimulated osteoblast differentiation. We showed that FIGNL1 may play some regulatory role in osteoblastogenesis. INTRODUCTION: The fidgetin-like 1 (FIGNL1) gene encodes a new subfamily member of ATPases associated with diverse cellular activities (AAA proteins). Although the FIGNL1 protein localizes to both the nucleus and cytoplasm, the function of FIGNL1 remains unknown. In a previous study, we identified several genes that mediate the anabolic effects of basic fibroblast growth factor (bFGF) on bone by using microarray data. FIGNL1 was one of the genes that downregulated >2-fold in MC3T3-E1 cells after treatment with bFGF. Therefore, this study was aimed to identify and confirm the function of FIGNL1 on osteoblastogenesis. MATERIALS AND METHODS: We examined the effect of the FIGNL1 gene on proliferation, differentiation, and apoptosis in mouse osteoblast cells (MC3T3-E1 and mouse primary calvarial cells) using flow cytometry, RT-PCR, cell proliferation assay, and cell death assay. MC3T3-E1 cells and mouse calvarial cells were transfected with small interfering RNA (siRNA) directed against the FIGNL1 or nontargeting control siRNA and examined by cell proliferation and cell death assays. Also, FIGNL1 was fused to enhance green fluorescent protein (EGFP), and the EGFP-fused protein was transiently expressed in MC3T3-E1 cells. RESULTS: Reduced expression of FIGNL1 by bFGF and TGF-beta1 treatment was verified by RT-PCR analysis. Overexpression of FIGNL1 reduced the proliferation of MC3T3-E1 and calvarial cells, more than the mock transfected control cells did. In contrast, siFIGNL1 transfection significantly increased the proliferation of osteoblasts, whereas overexpression of FIGNL1 did not seem to alter apoptosis in osteoblasts. Meanwhile, overexpression of FIGNL1 enhanced the mRNA expression of alkaline phosphatase (ALP) and osteocalcin (OCN) in osteoblasts. In contrast, siFIGNL1 decreased the expression of ALP and OCN. A pEGFP-FIGNL1 transfected into MCT3-E1 cells had an initially ubiquitous distribution and rapidly translocated to the nucleus 1 h after bFGF treatment. CONCLUSIONS: From these results, we proposed that FIGNL1, a subfamily member of the AAA family of proteins, might play some regulatory role in osteoblast proliferation and differentiation. Further analyses of FIGNL1 will be needed to better delineate the mechanisms contributing to the inhibition of proliferation and stimulation of osteoblast differentiation.     

BKV in Simultaneous Pancreas-Kidney Transplant Recipients: A Leading Cause of Renal Graft Loss in First 2 Years Post-Transplant

With the introduction of more potent immunosuppressive agents, rejection has decreased in simultaneous pancreas/kidney transplant (SPK) recipients. However, as a consequence, opportunistic infections have increased. The purpose of this report is to outline the course of SPK patients who developed polyomavirus-associated nephropathy (PVAN). A retrospective review of 146 consecutive SPK recipients from January 1, 1996 to December 31, 2002 was performed. Immunosuppression, rejection and development of PVAN were reviewed. Nine patients were identified. All received induction with either OKT3 or thymoglobulin. Immunosuppression included tacrolimus/cyclosporine, MMF/azathioprine and sirolimus/prednisone. Two patients were treated for kidney rejection prior to the diagnosis of PVAN. Time to diagnosis was an average of 359.3 days post-transplantation. Immunosuppression was decreased but five ultimately lost function. However, none developed pancreatic abnormalities as demonstrated by normal glucose and amylase. Two underwent renal retransplantation after PVAN diagnosis and both have normal kidney function. PVAN was the leading cause of renal loss in SPK patients in the first 2 years after transplantation and is a serious concern for SPK recipients. The pancreas, however, is spared from evidence of infection, and no pancreatic rejection occurred when immunosuppression was decreased.     

Fontan conversion with arrhythmia surgery.

OBJECTIVE: Hemodynamic abnormalities and refractory atrial arrhythmias in patients late after the Fontan operation result in significant morbidity and mortality. We reviewed our experience with Fontan conversion and concomitant arrhythmia surgery. METHODS: Between January 1996 and February 2004, 16 patients underwent Fontan conversion and arrhythmia surgery. Mean age at the initial Fontan operation was 5.1+/-3.5 (range: 2-15) years and mean age at Fontan conversion was 17.0+/-5.8 (range: 6-30). The initial Fontan operations were atriopulmonary connections in 14 patients, extracardiac lateral tunnel in 1, and intracardiac lateral tunnel in 1. The types of arrhythmia included atrial flutter in 10 patients and atrial fibrillation in 3. Fontan conversion operation was performed with intracardiac lateral tunnel in 5 patients and extracardiac conduit in 11. Arrhythmia surgery included isthmus cryoablation in 10 patients and right-sided maze in 3. RESULTS: There has been no mortality. At Fontan conversion operation, 7 patients required permanent pacemaker. All patients have improved to New York Heart Association class I or II. With a mean follow-up of 26.9+/-30.6 (range:1-87) months, 16 patients had sinus rhythm, 2 patients had transient atrial flutter which was well controlled, and 2 patients required permanent pacemaker during follow-up. CONCLUSIONS: Fontan conversion with concomitant arrhythmia surgery and permanent pacemaker placement is safe, improves New York Heart Association functional class, and has a low incidence of recurrent arrhythmias. In most patients, concomitant permanent pacemakers are needed.     

The effect of skin surface warming during anesthesia preparation on preventing redistribution hypothermia in the early operative period of off-pump coronary artery bypass surgery.

OBJECTIVE: Redistribution hypothermia adversely affects hemodynamics and postoperative recovery in patients undergoing cardiac surgery. In off-pump coronary bypass surgery (OPCAB), maintaining the temperature is important because warming by cardiopulmonary bypass is omitted. Pre-warming studies reported earlier showing pre-warming as an effective means of preventing redistribution hypothermia was time consuming since it required at least 1-2h to pre-warm the patients before the surgery. Because pre-warming for such a long time is impractical in clinical practice, this study evaluated the efficacy of active warming during the preanesthetic period for the prevention of redistribution hypothermia in the early operative period of OPCAB. METHODS: After gaining the approval of Institutional Review Board and informed consent from the patients, 40 patients undergoing OPCAB were divided into control and pre-warming groups. The patients in control group (n=20) were managed with warm mattresses and cotton blankets, whereas patients in pre-warming group (n=20) were actively warmed with a forced-air warming device before the induction of anesthesia. Hemodynamic variables and temperature were recorded before anesthesia (Tpre) and at 30 min intervals after anesthesia for 90 min (T30, T60, and T90). RESULTS: Active warming duration was 49.7+/-9.9 min. There were no statistically significant differences in skin temperature, core temperature and hemodynamic variables between the two groups at preinduction period except for mean arterial pressure and central venous pressure. The core temperature at T30, T60, and T90 was statistically higher in pre-warming group than that in control group. Core temperature of six (30%) and seven patients (35%) in control group was reduced below 35 degrees C at T60 and T90, respectively, whereas core temperature of only one patient (5%) in pre-warming group was reduced below 35 degrees C at T90 (P=0.02). CONCLUSIONS: Active warming using forced air blanket before the induction of anesthesia reduced the incidence and degree of redistribution hypothermia in patients undergoing OPCAB. It is a simple method with reasonable cost, which does not delay the induction of anesthesia nor the surgery.