Sinus node dysfunction in catecholaminergic polymorphic ventricular tachycardia: Risk factor and potential therapeutic target?

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited heart rhythm disorder characterized by the occurrence of potentially life-threatening polymorphic ventricular tachyarrhythmias in conditions of physical or emotional stress. The underlying cause is a dysregulation in intracellular Ca handling due to mutations in the sarcoplasmic reticulum Ca release unit. Recent experimental work suggests that sinus bradycardia, which is sometimes observed in CPVT patients, may be another primary defect caused by CPVT mutations. Herein, we review the pathophysiology of CPVT and discuss the role of sinus node dysfunction as a modulator of arrhythmia risk and potential therapeutic target.     

Assessment of patient's pain-related behavior at physical examination may allow diagnosis of recent osteoporotic vertebral fracture

Background contextAlthough innumerable studies have analyzed the multiple aspects of osteoporotic vertebral fractures, no study has focused on the clinical features related to spine pain in patients with recent osteoporotic vertebral compression fractures (VCFs).PurposeTo determine whether the assessment of pain-related behavior (P-RB) of patients with osteoporotic VCFs of recent onset may allow the fracture to be strongly suspected, or even diagnosed, at physical examination.Study designPain-related behavior of elderly patients attending an outpatient spine clinic was evaluated on the basis of six consecutive movements made on the examining table.Patient sampleFifty-six patients complaining only of lumbar or thoracic pain. The fractured patients (FPs), representing the fracture group (FG), were the 19 who had a recent VCF, whereas the control group (CG) consisted of the remaining 37 patients.MethodsAssessment of P-RB was based on six parameters: grimacing, sighing, clenching or blocking eyelids, gaping or strongly tightening the lips, need for help to take positions, and extreme difficulty to turn in the prone position. A score of 1 or a decimal was assigned to each parameter, the final score to each patient being 0 to 6. Three types of injury, acute (I), subacute (II), or chronic (III), were identified on the basis of the time elapsed from the probable occurrence of the fracture. The diagnosis of recent fracture was based on magnetic resonance images. Patients were videotaped during their movements. An examiner, unaware of the clinical history and diagnosis, gave a P-RB score to all patients and indicated whether they had to be placed in FG or CG, and also their presumable type of fracture. Subsequently, a DVD with the videotapes of all patients was given to three independent examiners, not specifically expert of spine conditions, who were asked to make the same evaluations as the first examiner.ResultsThe mean scores for P-RB given by the first examiner were 4.6 to FG and 0.7 to CG (p<.01). He identified as FPs 89% of those who were in FG. The type of fracture was indicated correctly in 88% of patients identified as FPs. The mean scores for the three types of fracture ranged from 5.4 (Type I) to 3.3 (Type III) (p<.001). The mean scores for P-RB given by the independent examiners to FG and CG were similar to those of the first examiner. The rates of correctness in identifying the type of fracture in patients indicated as FPs varied from 87% to 80%. The mean scores assigned to the patients included in the three types of fracture ranged from 5.4 to 2.8.ConclusionsPain-related behavior evaluation of patients with osteoporotic VCF during their movements on the examining table may allow to suspect, or even diagnose, the presence of a fracture, particularly in the initial 4 to 6 weeks after the occurrence. Even orthopedic surgeons not particularly familiar with spine care may be able to suspect the injury during physical examination.     

Fibrous Dysplasia of the Maxilla: Diagnostic Reliability of the Study Image. Literature Review

Objective Fibrous dysplasia (FD) is a benign bone disorder in facial bones. This study evaluates the possibility of diagnosing fibrous dysplasia on imaging alone, without biopsy of the lesion, which is often burdensome for the patient. Materials and Methods The authors bring their experience of four cases of bone lesions of the maxillofacial region and present a review of published studies. The imaging techniques evaluated are computed tomography (CT) and magnetic resonance imaging (MRI) with and without contrast. Results The literature review demonstrates that it is impossible to make diagnosis of fibrous dysplasia exclusively by imaging. Radiographic images often show a ground-glass appearance, which is characteristic but not pathognomonic of fibrous dysplasia. Conclusion Although CT and MRI images may in many cases suggest a diagnosis of fibrous dysplasia, histological examination or follow-up imaging should follow.     

Notch signaling deregulation in multiple myeloma: A rational molecular target

Despite recent therapeutic advances, multiple myeloma (MM) is still an incurable neoplasia due to intrinsic or acquired resistance to therapy. Myeloma cell localization in the bone marrow milieu allows direct interactions between tumor cells and non-tumor bone marrow cells which promote neoplastic cell growth, survival, bone disease, acquisition of drug resistance and consequent relapse. Twenty percent of MM patients are at high-risk of treatment failure as defined by tumor markers or presentation as plasma cell leukemia. Cumulative evidences indicate a key role of Notch signaling in multiple myeloma onset and progression. Unlike other Notch-related malignancies, where the majority of patients carry gain-of-function mutations in Notch pathway members, in MM cell Notch signaling is aberrantly activated due to an increased expression of Notch receptors and ligands; notably, this also results in the activation of Notch signaling in surrounding stromal cells which contributes to myeloma cell proliferation, survival and migration, as well as to bone disease and intrinsic and acquired pharmacological resistance. Here we review the last findings on the mechanisms and the effects of Notch signaling dysregulation in MM and provide a rationale for a therapeutic strategy aiming at inhibiting Notch signaling, along with a complete overview on the currently available Notch-directed approaches.     

Different effect of statins on platelet oxidized-LDL receptor (CD36 and LOX-1) expression in hypercholesterolemic subjects.

Hydroxymethyl-glutaryl-CoA-reductase inhibitors (statins) reduce cardiovascular mortality by decreasing cholesterol as well as by non-lipid-related actions. Oxidized low-density lipoproteins (ox-LDL) are pro-atherogenic molecules and potent platelet agonists. CD36 and lectin-like ox-LDL receptor-1 (LOX-1) are specific ox-LDL receptors also expressed in platelets. This study was planned to address whether treatment with atorvastatin 10 mg/day, pravastatin 40 mg/day or simvastatin 20 mg/day could affect platelet CD36 and LOX-1 expression. Twenty-four patients for each treatment were evaluated after 3, 6, and 9 days and at 6 weeks for complete lipid profile (chromogenic), ox-LDL (ELISA), platelet P-selectin (P-sel), CD36, LOX-1 (FACS), and intracellular citrullin recovery (iCit) (HPLC). Data show hyperactivated platelets (P-sel absolute values, percent variation in activated cells, all p < 0.001), and CD36 and LOX-1 overexpression (all p < 0.001) in patients at baseline. P-sel, CD36, and LOX-1 were significantly decreased by atorvastatin and simvastatin (all p < 0.01) and related with iCit increase (r = 0.58, p < 0.001) and platelet-associated ox-LDL (r = 0.51, p < 0.01) at 9 days. Pravastatin reduced LOX-1 and P-sel (p < 0.05) at 6 weeks in relation with decreased LDL and ox-LDL (r = 0.39, p < 0.01 and r = 0.37, p < 0.01, respectively). These data suggest that atorvastatin and simvastatin reduce platelet activity by exposure of CD36 and LOX-1 before significant LDL reduction, whereas pravastatin action is detected later and in relation with LDL and ox-LDL lowering. Rapid and consistent reduction of CD36 and LOX-1 could be considered a direct anti-atherothrombotic mechanism related to the role of ox-LDL in platelet activation, platelet-endothelium interactions, and NO synthase activity.