BACKGROUND: Loss-of-function mutations in the KCNJ2 cause approximately 50% of Andersen-Tawil Syndrome (ATS) characterized by a classic triad of periodic paralysis, ventricular arrhythmia, and dysmorphic features. Do KCNJ2 mutations occur in patients lacking this triad and lacking a family history of ATS? OBJECTIVES: The purpose of this study was to identify and characterize mutations in the KCNJ2-encoded inward rectifier potassium channel Kir2.1 from patients referred for genetic arrhythmia testing. METHODS: Mutational analysis of KCNJ2 was performed for 541 unrelated patients. The mutations were made in wild type (WT) and expressed in COS-1 cells and voltage clamped for ion currents. RESULTS: Three novel missense mutations (R67Q, R85W, and T305A) and one known mutation (T75M) were identified in 4/249 (1.6%) patients genotype-negative for other known arrhythmia genes with overall incidence 4/541 (0.74%). They had prominent U-waves, marked ventricular ectopy, and polymorphic ventricular tachycardia but no facial/skeletal abnormalities. Periodic paralysis was present in only one case. Outward current was decreased to less than 5% of WT for all mutants expressed alone. Co-expression with WT (simulating heterozygosity) caused a marked dominant negative effect for T75M and R82W, no dominant negative effect for R67Q, and a novel selective enhancement of inward rectification for T305A. CONCLUSIONS: KCNJ2 loss of function mutations were found in approximately 1% of patients referred for genetic arrhythmia testing that lacked criteria for ATS. Characterization of three new mutations identified a novel dominant negative effect selectively reducing outward current for T305A. These results extend the range of clinical phenotype and molecular phenotype associated with KCNJ2 mutations. 相似文献
Vacuum Assisted Closure brand Negative Pressure Wound Therapy (V.A.C. NPWT) has been shown to be an effective therapeutic option for the treatment of recalcitrant wounds; however, the mechanism of action at the cellular level remains to be elucidated. Here, we examined the effects of negative pressure wound therapy, manifolded with two different dressings, on fibroblast viability, chemotactic signaling, and proliferation in a fibrin clot matrix. Fibroblasts were grown in a three-dimensional fibrin matrix and were treated for 48 hours with either V.A.C. NPWT and GranuFoam Dressing, or with gauze under suction, or as static controls without negative pressure or dressings. Cells treated by gauze under suction showed significantly greater cell death and stimulated less migration and proliferation than static and V.A.C. NPWT-treated cells (p<0.05). Apoptosis was also significantly higher in gauze under suction than in static treatments. These results indicate that the dressing material has a significant effect on cell response following negative pressure wound therapy. The ability to support cell growth, stimulate chemotaxis, and proliferation without increasing apoptosis may provide an insight into the mechanisms of action of V.A.C. NPWT. 相似文献
Our objective was to evaluate the frequency of neoplastic and preneoplastic skin lesions in Parkinson's disease (PD) patients when compared with an aged-matched population. We performed a cross-sectional survey in PD patients and in an age-matched control group. Patients and controls were examined by a movement disorder specialist and a dermatologist. 150 PD patients and 146 controls were included. Thirty-five PD patients (23.3%) presented skin lesions that could be classified as neoplastic or preneoplastic vs. 20 subjects in the control group (13.7%) (OR 95%, CI 1.92 [1.05, 3.51]). However, this difference lost statistical significance when adjusted for gender (recruitment of controls was matched just for age with an over representation of males in the PD group). Twenty-nine PD patients (19%) presented actinic keratosis and basal cell carcinoma was diagnosed in 4 patients (3%). Although nonconclusive, our results are in agreement with previous studies suggesting an increased risk of skin cancer in PD patients. The frequency of actinic keratosis in PD patients and the associated risk to develop melanoma recommends its screening in future epidemiological studies. 相似文献
Caring for a child in a body cast is a stressful situation for most families and many families state they do not receive adequate information on how to care for their child. This paper presents a comprehensive guide on caring for a child in a body cast. It examines the physical care issues, transportation and cast care. An instrument for assessing the family’s ability to cope with caring for a child in a body cast is described, and further resources for parents and nurses are presented. 相似文献
Localized tissue ischemia is a key factor in the development and poor prognosis of chronic wounds. Currently, there are no standardized animal models that provide sufficient tissue to evaluate the effect of modalities that may induce angiogenesis, and in vitro models of angiogenesis do not mimic the complexity of the ischemic wound bed. Therefore, we set out to develop a reproducible ischemic model for use in wound-healing studies. Male Sprague-Dawley rats underwent creation of dorsal bipedicle skin flaps with centrally located excisional wounds. Oxygen tension, wound-breaking strength, wound area, lactate, and wound vascular endothelial growth factor (VEGF) were compared in flaps measuring 2.5 and 2.0 x 11 cm with and without an underlying silicone sheet. We found that the center of the 2.0 cm flap with silicone remains in the critically ischemic range up to 14 days without tissue necrosis (33+/-4 vs. 49+/-6 mmHg in controls). Wound healing and breaking strength were significantly impaired and tissue lactate from the center of this flap was 2.9 times greater than tissue from either nonischemic controls and 2.5 cm flap (0.23+/-0.05 mg/dL/mg sample vs. 0.09+/-0.02 and 0.08+/-0.02, respectively). Vascular endothelial growth factor was 2 times greater than the nonischemic control. This ischemic wound model is relatively inexpensive, easy to perform, reproducible, and reliable. The excisional wounds provide sufficient tissue for biochemical and histologic analysis, and are amenable to the evaluation of topical and systemic therapies that may induce angiogenesis or improve wound healing. 相似文献
Background: Increased carboxyhemoglobin concentrations in patients receiving inhalation anesthetics (desflurane, enflurane, and isoflurane) have been reported. Recent in vitro studies suggest that dry carbon dioxide absorbents may allow the production of carbon monoxide.
Methods: The authors used high fresh oxygen flow (5 or 10 l/min) through a conventional circle breathing system of an anesthesia machine for 24 or 48 h to produce absorbent drying. Initial studies used 10 l/min oxygen flow with the reservoir bag removed or with the reservoir bag left in place during absorbent drying (this increases resistance to gas flow through the canister). A third investigation evaluated a lower flow rate (5 l/min) for absorbent drying. Water content of the absorbent and temperature were measured. Pigs received a 1.0 (human) minimum alveolar concentration desflurane anesthetic (7.5%) for 240 min using a 1 l/min oxygen flow rate with dried absorbent. Carbon monoxide concentrations in the circuit and carboxyhemoglobin concentrations in the pigs were measured.
Results: Pigs anesthetized with desflurane using Baralyme exposed to 48 h of 10 l/min oxygen flow (reservoir bag removed) had extremely high carboxyhemoglobin concentrations (more than 80%). Circuit carbon monoxide concentrations during desflurane anesthesia using absorbents exposed to 10 l/min oxygen flow (reservoir bag, 24 h) reached peak values of 8,800 to 13,600 ppm, depending on the absorbent used. Carboxyhemoglobin concentrations reached peak values of 73% (Baralyme) and 53% (soda lime). The water content of Baralyme decreased from 12.1 +/- 0.3% (mean +/- SEM) to as low as 1.9 +/- 0.4% at the bottom of the lower canister (oxygen flow direction during drying was from bottom to top). Absorbent temperatures in the bottom canister increased to temperatures as high as 50 [degree sign] Celsius. With the reservoir bag in place during drying (10 l/min oxygen flow), water removal from Baralyme was insufficient to produce carbon monoxide (lowest water content = 5.5%). Use of 5 l/min oxygen flow (reservoir bag removed) for 24 h did not reduce water content sufficiently to produce carbon dioxide with desflurane. 相似文献