Catecholaminergic polymorphic ventricular tachycardia: successful emergency treatment with intravenous propranolol

Catecholaminergic polymorphic ventricular tachycardia (VT) is a rare arrhythmogenic disorder, which may cause sudden death and whose relationships with mutations in cardiac ryanodine receptor gene have been recently established. The present article reports a catecholaminergic polymorphic VT case of a 9-year-old girl, without any previous history of syncope, who has been found unconscious while playing and referred comatose to pediatric intensive care unit. The electrocardiogram pattern showed runs of bidirectional and polymorphic VT degenerating into ventricular fibrillation, without QT interval abnormalities. Various attempts of cardioversion, lidocaine, and magnesium sulfate intravenous infusions were only partially effective. Owing to catecholaminergic polymorphic VT highly suggesting electrocardiogram pattern, intravenous propranolol was administered, achieving immediate VT interruption. Long-term nadolol therapy effectively prevented further arrhythmias, with no relapses up to 10 months later; a good neurologic recovery was also obtained. Genetic evaluation revealed in this patient-but not in relatives-a mutation in ryanodine receptor gene on chromosome 1.     

Effects of vacuum-assisted closure on central hemodynamics in a sternotomy wound model

Several authors have reported promising results with vacuum-assisted closure therapy in poststernotomy mediastinitis. The aim of this study was to investigate the hemodynamic outcome following the application of six negative pressures on an open sternotomy wound. Six 70-kg pigs underwent median sternotomy followed by vacuum-assisted closure therapy. Six negative pressures (-50, -75, -100, -125, -150, and -175mmHg) were applied to each pig for 30min each while hemodynamic parameters were measured. An increase in cardiac output was observed at -75mmHg when compared to the other five pressures: -50mmHg (P<0.05; CI 0.12-1.13l/min), -100mmHg (P<0.001; CI 0.34-1.32l/min), -125mmHg (P<0.001; CI 0.51-1.52l/min), -150mmHg (P<0.001; CI 0.50-1.47l/min), and -175mmHg (P<0.05; CI 0.13-1.17l/min). A decrease in systemic vascular resistance was observed at -75mmHg when compared to -125mmHg (P<0.01; CI 108-552dyn.s/cm(5)) and -150mmHg (P<0.01; CI 90-543dyn.s/cm(5)), but not compared to the other pressures. No change (P=ns) was observed in heart frequency, mean arterial pressure or central venous pressure. Our data demonstrates that vacuum-assisted closure therapy of -50 to -175mmHg does not impair the central hemodynamics in a porcine sternotomy model.     

Bone loss induced by dietary magnesium reduction to 10% of the nutrient requirement in rats is associated with increased release of substance P and tumor necrosis factor-alpha

Dietary Mg intake has been linked to osteoporosis. Previous studies have demonstrated that severe Mg deficiency [0.04% of nutrient requirement (NR)] results in osteoporosis in rodent models. We assessed the effects of more moderate dietary Mg restriction (10% of NR) on bone and mineral metabolism over a 6-mo experimental period in rats. At 2, 4 and 6 mo, serum Mg, Ca, parathyroid hormone (PTH), 1,25-dihydroxy-vitamin D, alkaline phosphatase, osteocalcin and urine pyridinoline were measured. Femurs and tibiae were collected for measurement of mineral content, microcomputerized tomography, histomorphometry, and immunocytochemical localization. By 2 mo, profound Mg deficiency had developed as assessed by marked hypomagnesemia and up to a 51% reduction in bone Mg content. These features continued through 6 mo of study. Serum Ca was slightly but significantly higher in Mg-deficient rats than in controls at all time points. At 2 mo, serum PTH was elevated in Mg-deficient rats but was significantly decreased at 6 mo in contrast to control rats in which PTH rose. Serum 1,25-dihydroxy-vitamin D was significantly lower than in controls at 4 and 6 mo. A significant fall in both serum alkaline phosphatase and osteocalcin suggested decreased osteoblast activity. Histomorphometry demonstrated decreased bone volume and trabecular thickness. This was confirmed by microcomputerized tomography analysis, which also showed that trabecular volume, thickness and number were significantly lower in Mg-deficient rats. Increased bone resorption was suggested by an increase in osteoclast number over time compared with controls as well as surface of bone covered by osteoclasts and eroded surface, but there was no difference in osteoblast numbers. The increased bone resorption may be due to an increase in TNF-alpha because immunocytochemical localization of TNF-alpha in osteoclasts was 199% greater than in controls at 2 mo, 75% at 4 mo and 194% at 6 mo. The difference in TNF-alpha may be due to substance P, which was 250% greater than in controls in mononuclear cells at 2 mo and 266% at 4 mo. These data demonstrated that a Mg intake of 10% of NR in rats causes bone loss that may be secondary to the increased release of substance P and TNF-alpha.     

Histopathologic examination of axillary sentinel lymph nodes in breast carcinoma patients

The axillary sentinel lymph node biopsy (SLNB) has gained increasing popularity as a novel surgical approach for staging patients with breast carcinoma and for guiding the choice of adjuvant therapy with minimal morbidity. Patients with negative SLNB represent a subset of breast carcinoma patients with definitely better prognosis, because their pN0 status is based on a very thorough examination of the sentinel lymph nodes (SLNs), with a very low risk of missing even small micrometastatic deposits, as compared with routine examination of the 20 or 30 lymph nodes obtained by the traditional axillary clearing. The histopathologic examination of the SLNs may be performed after fixation and embedding in paraffin, or intraoperatively on frozen sections. Whatever is the preferred tracing technique and surgical procedure, the histopathologic examination of each SLN must be particularly accurate, to avoid a false-negative diagnosis. Unfortunately, because of the lack of standardised guidelines or protocols for SLN examination, different institutions still adopt their own working protocols, which differ substantially in the number of sections cut and examined, in the cutting intervals (ranging from 50 to more than 250 microm), and in the more or less extensive use of immunohistochemical assays for the detection of micrometastatic disease. Herein, a very stringent protocol for the examination of the axillary SLN is reported, which is applied either to frozen SLN for the intraoperative diagnosis, and to fixed and embedded SLN as well.     

CardioSEAL/STARflex versus Amplatzer devices for percutaneous closure of small to moderate (up to 18 mm) atrial septal defects

Background

The Amplatzer septal occluder (ASO) allows the percutaneous closure of small to very large atrial septal defects (ASDs). The CardioSEAL/STARflex (CS/SF) can be used only for closure of small to moderate ASDs (stretch size up to 18 mm). These 2 devices are widely used in clinical practice. Therefore, a comparison of their use in the closure of small to moderate ASDs is needed.

Methods

From December 1996 to September 2002, 274 consecutive patients (mean age 20.3 ± 17 years) underwent percutaneous closure of small to moderate ostium secundum ASDs. The CS/SF device was used in 121 patients, and the ASO was used in 153.

Results

There were no differences in age, sex ratio, or pulmonary/systemic flow ratio. Stretch size of the defect was higher in the ASO group (13.6 ± 3.5 mm vs 15.5 ± 3.2 mm, P < .001). Procedure time and fluoroscopy time were shorter in patients treated with the ASO (61 ± 21 vs 75 ± 32 min, P < .0003, and 11.6 ± 9 vs 23.8 ± 17.4 min, P < .0001, respectively). Residual shunt at procedure and discharge was significantly more frequent in the CS/SF group (P < .0001). There were no differences in the complication rate for the 2 groups (CS/SF 4/121 vs ASO 6/153). Length of follow-up was longer in the CS/SF group (24 ± 14 vs 16 ± 9 months, P = .0001). Residual shunting was significantly more frequent in the CS/SF group during follow-up, while closure rate reached 100% after 1 month in ASO group.

Conclusions

The 2 devices are clinically safe and effective in ASD closure. However, percutaneous closure of small to moderate ASDs with ASO is quicker and provides an higher rate of complete occlusion.     

Lack of p38 MAP kinase activation in TRAIL-resistant cells is not related to the resistance to TRAIL-mediated cell death

Activation of MAP kinases is involved in various cellular processes, including immunoregulation, inflammation, cell growth, cell differentiation, and cell death. To investigate the role of p38 MAP kinase activation in the signaling pathway of TRAIL-mediated apoptosis, we compared TRAIL-mediated MAP kinase activation in TRAIL-susceptible human colon cancer cell line DLD1 and TRAIL-resistant DLD1/TRAIL-R cells. TRAIL-mediated activation of ERK occurred in both cell lines. In contrast, both DLD1 and DLD1/TRAIL-R cells showed no obvious JNK activation after treatment with TRAIL. Interestingly, TRAIL-mediated activation of p38 MAP kinases was observed in DLD1 cells but not in DLD1/TRAIL-R cells. However, activation of p38 MAP kinases was observed in both DLD1 and DLD1/TRAIL-R cells after treatment with anisomycin. Furthermore, inhibiting activated p38 MAP kinases with known inhibitors or with an adenovector expressing dominant negative p38alpha did not block TRAIL-mediated cell death in DLD1 cells. Moreover, activation of p38 MAP kinases by adenovectors expressing constitutive MKK3 or MKK6 (Ad/MKK3bE or Ad/MKK6bE) did not induce cell death in either DLD1 or DLD1/TRAIL-R cell lines. Our results suggest that activation of p38 MAP kinases does not play a major role in TRAIL-mediated apoptosis in DLD1 cells and that lack of TRAIL-mediated p38 MAP kinase activation may not be the mechanism of TRAIL-resistance in DLD1/TRAIL-R cells.     

Susceptibilities of simian immunodeficiency virus to protease inhibitors

We used a focal infectivity assay with HeLa H1-JC.37 cells to directly compare susceptibilities of simian immunodeficiency virus (SIV) and human immunodeficiency virus type 1 (HIV-1) to protease inhibitors. SIVmac239 was inhibited by indinavir, saquinavir, and ritonavir, with 50% effective concentrations (means +/- standard deviations) of 39 +/- 8, 55 +/- 3, and 13 +/- 5 nM, respectively. The corresponding values for inhibition of HIV-1 were 66 +/- 4, 47 +/- 10, and 25 +/- 14 nM, respectively.     

Questions about questions: cognitive survey of questionnaire development

OBJECTIVES: Traditional pretests are used in the development of survey items to identify technical and comprehension problems. Cognitive processes involved in answering survey questions are not the object of this kind of test. METHODS: Cognitive survey methods were used here to test a questionnaire screening for rehabilitation needs in people suffering from back pain. Essential techniques of cognitive testing (think-aloud, probing, confidence ratings) are outlined. We applied these techniques to 20 patients suffering from either acute or chronic back pain in order to test the survey. RESULTS: The main goal, i.e., identifying problems in item formulation by means of cognitive testing, was achieved. Almost one third of the survey questions were rephrased according to the results of the study. Some of the improvements of the questionnaire are illustrated. CONCLUSIONS: The increased effort required to perform cognitive testing as compared to traditional pretesting pays off. The two methods have specific pros and cons and cannot replace one another.