Drug-induced torsade de pointes (TdP) is a rare but lethal side effect of many cardiovascular and non-cardiovascular drugs. It has led to black box warnings or even withdrawal of many useful ...compounds from the market and is one of the major stumbling blocks for new drug development. The critical need for a better test that can predict the TdP liability of a candidate drug has led to the development of multiple preclinical models. Each of these models has it own merits and limitations in preclinical testing for TdP liability; however, most of these models have not been adequately validated, so their precise sensitivity and specificity remain largely unknown. Recent blinded validation studies have demonstrated that the rabbit left ventricular wedge preparation can predict drug-induced TdP with an extremely high sensitivity and specificity. As a matter of fact, the wedge technique was initially developed primarily for studying the electrical heterogeneity of myocardium and the cellular basis of QT prolongation and TdP. Naturally then, the electrophysiological data obtained from the wedge takes into account every critical factor associated with the development of TdP. The TdP scores generated using the wedge technique have been shown to assess the torsadogenic potential of the drugs in a predictable fashion. This review elaborates on the current and prospective role of the rabbit left ventricular wedge preparation in preclinical assessment of drug-induced proarrhythmias including but not limited to TdP.
Many solid and hematological malignancies have been associated with different glomerular diseases. Several case reports and case series of cancer-associated glomerular diseases have shown that ...treating the cancer may lead to resolution of the glomerular process. Hence, knowledge and approach to cancer-associated glomerular diseases is important for both the caring nephrologists and the cancer specialists. While membranous nephropathy has been classically associated with solid malignancies, minimal change disease has been commonly described with hematologic malignancies, especially non-Hodgkin's lymphoma. Membranoproliferative glomerulonephritis is increasingly being recognized to be associated with chronic hematologic malignancies such as chronic lymphocytic leukemia. In this article, we review various cancer-associated glomerular diseases and their pathogenesis as well as principles of treatment. In addition, we also review glomerular diseases seen after chemotherapy and hematopoietic stem cell transplantation.
AIM To evaluate the role of albumin at the time of ulcerative colitis(UC) diagnosis in predicting the clinical course of disease.METHODS Nationwide cohort of patients with newly diagnosed UC in the ...Veterans Affairs health care system was identified and divided into two categories: hypoalbuminemia(i.e.,≤ 3.5 gm/dl) or normal albumin levels(i.e.,> 3.5 gm/dl) at the time of UC diagnosis. The exposure of interest was presence of hypoalbuminemia defined asalbumin level ≤ 3.5 g/dl at the time of UC diagnosis. Patients were then followed over time to identify the use of ≥ 2 courses of corticosteroids(CS),thiopurines,anti-TNF medications and requirement of colectomy for UC management. RESULTS The eligible study cohort included 802 patients,but 92(11.4%) patients did not have their albumin levels checked at the time of UC diagnosis,and they were excluded. A total of 710 patients,who had albumin levels checked at time of UC diagnosis,were included in our study. Amongst them,536 patients had a normal albumin level and 174 patients had hypoalbuminemia. Patients with hypoalbuminemia at diagnosis had a higher likelihood of ≥ 2 courses of CS use(adjusted HR = 1.7,95%CI: 1.3-2.3),higher likelihood of thiopurine or anti-TNF use(adjusted HR = 1.72,95%CI: 1.23-2.40) than patients with normal albumin level at diagnosis. There was a trend of higher likelihood of colectomy in hypoalbuminemic patients,but it was not statistically significant(Adjusted HR = 1.7,95%CI: 0.90-3.25).CONCLUSION Hypoalbuminemia at disease diagnosis can serve as a prognostic marker to predict the clinical course of UC at the time of diagnosis.
Aims We investigated the role of ventricular repolarization sequence in ventricular diastolic function. Methods and results Arterially perfused canine left ventricular wedge preparation with ...simultaneous recording of action potentials and isometric contractile force was used to establish the relationship between ventricular repolarization and relaxation sequences. An isolated rabbit working heart model was used to investigate role of ventricular repolarization sequence in ventricular diastolic function. Under controlled conditions, similar to transmural dispersion of repolarization (TDR), there existed a time difference between initiation of epicardial and endocardial relaxation (TREpi–Endo, 47.4 ± 13.9 ms) with epicardium relaxing earlier. There was a strong correlation between TDR and TREpi–Endo (r2 = 0.99, n = 5) and the interventions that changed transmural repolarization sequence led to parallel changes in transmural relaxation sequence. In isolated rabbit working hearts, reversal of the transmural repolarization sequence that manifested as negative T wave was associated with a significant increase in isovolumic relaxation time (from 49.2 ± 19.1 to 76.4 ± 12.1 ms, n = 5, P = 0.001). Conclusion There is a strong correlation between transmural repolarization and relaxation sequences. A positive T wave that denotes transmural repolarization sequence from epicardium to endocardium is essential for normal diastolic function of ventricle and the reversal of such sequence is associated with ventricular diastolic dysfunction.
Hepatitis B virus (HBV) infection is a major cause of acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma. HBV has also been associated with various common and uncommon glomerular ...diseases, including IgA nephropathy (IgAN). We report a patient with chronic HBV infection who presented with atypical features of IgAN with management and long-term follow-up. Much of the data on the treatment of HBV-associated glomerular diseases come from patients with membranous nephropathy, whereas the information on treatment of other glomerulopathies remains largely anecdotal. To the best of our knowledge, treatment of an adult patient with HBV-associated nephrotic syndrome from IgAN with pegylated interferon has not been previously reported. Treatment with pegylated interferon alfa-2b in our patient resulted in complete clinical remission of the nephrotic syndrome as well as a dramatic decrease in HBV viral load. Patient continued to remain in clinical remission 5 years after treatment.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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