Trends in consumption of calcium channel blockers in the Czech Republic during 1993-1999 and comparison with selected countries: drug utilization study

OBJECTIVE: To determine the patterns of consumption in calcium channel blockers (CCB) groups in the Czech Republic between 1992 and 1999 and make a comparison with selected countries. METHODS: This was part of a drug utilization study using WHO methodology [Anatomical Therapeutic Chemical classification/defined daily doses (ATC/DDD)]. The wholesale data collected by drug distributors were used. Utilization was calculated as the DDDs for 1000 inhabitants per day. In focus was the consumption of short-acting nifedipine. Comparison with wholesale data from Finland, Norway, Germany and Australia was made. RESULTS: There was a decreasing tendency to use short-acting nifedipine in the Czech Republic over the period 1993-1999. Four years after publication of warning evidence, short-acting nifedipine still accounted for 23% of all calcium channel blockers in our country. The abundance of second-generation CCBs increased from less than 1% in 1993 to 43% in 1999. The consumption of short-acting nifedipine in the Czech Republic and Germany is probably three times more frequent than in Nordic countries and Australia. CONCLUSIONS: Consumption of short-acting nifedipine in the Czech Republic 4 years after recognition of its risks still remains very high. This suggests that implementation of clinical trial results to clinical practice is very slow and ineffective.     

Potentiometric and viscometric study of the conformational transitions of 2-hydroxyethyl methacrylate-methacrylic acid copolymers

The dependence of the apparent dissociation constant and of intrinsic viscosity on the degree of dissociation of 2-hydroxyethyl methacrylate-methacrylic acid copolymers was investigated. It was found that the conformational transition indicated in the potentiometric titration was distinct only with copolymers containing at least ca. 48 mole% of methacrylic acid. The transition is probably related with the local configurational and conformational structure while being uncorrelated with the transition of the coiled form of the macromolecule into the expanded one.     

The dynamics of plasma transforming growth factor beta 1 (TGF-beta1) level during radiotherapy with or without simultaneous chemotherapy in advanced head and neck cancer

To assess the plasma TGF-beta1 level during radio(chemo)therapy and to test the predictive power of TGF-beta1 for treatment response in patients with advanced head and neck cancer. Twenty nine patients with advanced head and neck cancer were treated with curative radio(chemo)therapy. Plasma TGF-beta1 level was established at the beginning, in the middle and at the end of the therapy. The dynamics of the TGF-beta1 level was assessed separately for patients with and without chemotherapy. Treatment response was correlated to the TGF-beta1 level. Eighteen patients achieved complete remission, eight partial remission and three patients progressed. Patients treated with radiotherapy had significantly higher initial plasma TGF-beta1 level compared to radiochemotherapy patients (p=0.044). During the treatment, there was a significant decrease in patients treated with radiochemotherapy (p=0.008) but not in radiotherapy patients (p=0.34). Tumor burden did not correlate with plasma TGF-beta1 level (p=0.07). TGF-beta1 has no predictive value for treatment response (CR vs. PR and PD, p=0.12). The combination of radiotherapy and chemotherapy significantly decreases plasma TGF-beta1 level in patients with advanced head and neck cancer. Treatment response cannot be predicted using TGF-beta1.     

I/D ACE gene polymorphism in survival of leukemia patients -- hypothesis and pilot study

Angiotensin-I converting enzyme (ACE) is involved not only in intracellular volume regulation but also in proliferation control. Since both ACE gene polymorphism (I/D ACE) and ABO blood group determine ACE level in peripheral blood and probably also in bone marrow, the hypothesis to the interindividual differences in survival of leukemic patients was suggested.The data of 25 patients of both sexes with acute myelogenous (AML), acute lymphatic (ALL), chronic myelogenous (CML) and chronic lymphatic (CLL) leukemia treated by conventional were used for the study.The overall survival (SUR) was estimated as the time from the date of diagnosis to the date of death. The difference between patient's individual SUR (iSUR) and median SUR according to the type of leukemia (mSUR) was calculated. This difference (iSUR-mSUR) varied with I/D ACE genotype (p<0.02) but neither with diagnosis nor with ABO blood group. The regression model for iSUR calculation, from mSUR and I/D ACE genotype, has been suggested.     

Liposomal amphotericin B versus the combination of fluconazole and itraconazole as prophylaxis for invasive fungal infections during induction chemotherapy for patients with acute myelogenous leukemia and myelodysplastic syndrome

BACKGROUND: Fungal infections are a major cause of morbidity and mortality in patients undergoing induction chemotherapy for acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). The authors evaluated the efficacy and toxicity of liposomal amphotericin B (L-AmB) compared with a combination of fluconazole plus itraconazole (F+I) as prophylaxis in this setting. METHODS: Patients with newly diagnosed AML or high-risk MDS who were undergoing initial induction chemotherapy were randomized to receive either F+I (fluconazole 200 mg orally every 12 hours plus itraconazole tablets 200 mg orally every 12 hours) or L-AmB (3 mg/kg intravenously 3 times per week) in this prospective, open-label study. RESULTS: Seventy-two L-AmB-treated patients and 67 F+I-treated patients were enrolled in the study. Of these, 47% of patients completed antifungal prophylaxis without a change in therapy for proven or suspected fungal infection. Three patients in each arm developed a proven fungal infection. Twenty-three percent of the L-AmB-treated patients and 24% of the F+I-treated patients were changed to alternative antifungal therapy because of persistent fever (P value not significant). Nine percent of the L-AmB-treated patients developed pneumonia of unknown etiology compared with 16% of the F+I-treated patients (P value not significant). Increases in serum creatinine levels to > 2 mg/dL (20% for the L-AmB arm vs. 6% for the F+I arm; P = 0.012) and increases in serum bilirubin levels to > 2 mg/dL (43% vs. 22%, respectively; P = 0.021) were more common with L-AmB. Infusion-related reactions were noted in five L-AmB-treated patients. Responses to chemotherapy and induction mortality rates were similar for the two arms. CONCLUSIONS: L-AmB and F+I appear similar in their efficacy as antifungal prophylaxis during induction chemotherapy for patients with AML and MDS. L-AmB was associated with higher rates of increased serum bilirubin and creatinine levels.     

Primary hyperparathyroidism associated with hypocalcemia in a patient presenting with kidney disease

Elevated serum parathyroid hormone (PTH) level together with hypocalcemia in chronic kidney disease usually suggests secondary hyperparathyroidism. However, primary hyperparathyroidism should also be considered, especially if concomitant vitamin D deficiency is suspected. We report a case of parathyroid adenoma associated with hypocalcemia and metabolic bone disease in a patient presenting with kidney disorder. The patient was successfully treated by parathyroidectomy that was preceded and followed by intensive calcium and vitamin D supplementation.     

Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation

Somatic loss-of-function mutations in the ten-eleven translocation 2 (TET2) gene occur in a significant proportion of patients with myeloid malignancies. Although there are extensive genetic data implicating TET2 mutations in myeloid transformation, the consequences of Tet2 loss in hematopoietic development have not been delineated. We report here an animal model of conditional Tet2 loss in the hematopoietic compartment that leads to increased stem cell self-renewal in vivo as assessed by competitive transplant assays. Tet2 loss leads to a progressive enlargement of the hematopoietic stem cell compartment and eventual myeloproliferation in vivo, including splenomegaly, monocytosis, and extramedullary hematopoiesis. In addition, Tet2(+/-) mice also displayed increased stem cell self-renewal and extramedullary hematopoiesis, suggesting that Tet2 haploinsufficiency contributes to hematopoietic transformation in vivo.