The therapeutic efficacy and toxicity of the liposomal form of daunorubicin (Daunoxome) in lymphosarcoma patients

AIM: To evaluate toxicity and efficacy of CDxOP regimen in the treatment of primary non-Hodgkin's lymphoma (PNHL). MATERIAL AND METHODS: The study included 8 males and 6 females who had large B-cell lymphoma (n = 11), follicular lymphoma, predominantly large cell (n = 1), mantle cell lymphoma (n = 1) and peripheral T-cell lymphoma (n = 1). Seven patients were over 60. PNHL stage IV, III and II was diagnosed in 7, 5 and 2 patients, respectively. Daunoxome dose was 80 mg/m2 with an increase up to 100 mg/m2 in case of slow response and good tolerance. The other drugs were used in standard doses. RESULTS: 6 patients achieved complete remission (43%) and 5 patients--partial response (36%), the overall response was 79%. Three patients did not respond to therapy and died. Six patients are still in complete and two in partial remission, median follow-up being 22 months. The rest 3 patients were treated with other modalities, one of them died of infection. As to complications that might be related to daunoxome, there was myelodepression (6% of profound neutropenia < 1000 microl). No patients had deterioration of the left ventricular ejection fraction (ultrasound measurements) or clinical signs of congestive heart failure (median follow-up for 10 patients was 22 months) including those in whom high cumulative doses were used (640-840 mg/m2). One patient with compromised heart function had frequent ventricular extrasystole immediately after daunoxome infusion. CONCLUSION: Tolerance of CDxOP is acceptable. The results of the treatment are comparable with those of standard chemotherapy. Further comparative studies are needed for determination of efficacy and maximal tolerated dose of daunoxome in combination with other drugs and irradiation, of long-term side effects. This drug may be beneficial for elderly patients.     

Use of noninvasive assisted lung ventilation in children in intensive care units

Thirty-six patients aged 2 months to 14 years were observed. Noninvasive assisted ventilation of the lungs (NAVL) was performed through Respironix Inc. masks (USA) with Puritan-Bennet 7200, Bear 1000, and Bear 750 respirators in the SIMV + PS, CPAP + PS modes with manual regulation of the supporting pressure level. Respiratory rate, heart rate, respiratory volume, pO2, pCO2, SpO2, stroke volume, and minute volume of the heart were evaluated. During development of central respiratory failure in the early postoperative period or in case of forced deep medicamentous neuroplegia NAVL normalized the external respiration function and promoted adequate ventilation of the lungs; in the majority of cases with development of restrictive respiratory failure (RF) it improved ventilation of the lungs and therefore no intubation of the trachea and transfer to forced ventilation was needed. NAVL is indicated as a component of multiple-modality treatment for obstructive RF.     

Results of the multicenter controlled study of the hypolipidemic drug polycosanol in Russia

AIM: To compare efficacy and tolerance of polycosanol vs besafibrate in patients with hypercholesterolemia (HCE). MATERIAL AND METHODS: A multicenter controlled double blind randomised trial entered 113 patients with HCE. After 5 weeks of diet the patients were randomised into two groups. 59 patients of group 1 received polycosanol (10 mg/day), 54 patients of group 2 were given besafibrate (400 mg/day) for 8 weeks. RESULTS: The 8-week course of treatment was completed by 103 patients (91%): 57(97%) patients of group 1 and 46(85%) patients of group 2. In group 1 total cholesterol diminished by an average of 15%, LDLP cholesterol fell by 18%, triglycerides by 15%, while in group 2 a respective decrease was 8, 11 and 6%. Side effects in group 1 were mild. CONCLUSION: A hypolipidemic effect of polycosanol in a daily dose 10 mg is superior to that of besafibrate in a daily dose 400 mg.     

Prevalence of cholelithiasis in different regions

The review characterizes the prevalence of cholelithiasis in Russia and other countries taking into account the evolution of diagnostic methods from necropsy to billiary tract ultrasonography. The authors demonstrate the dynamics of cholelithiasis prevalence in different world's regions, climate-geographic zones, urban and rural areas, as well as the growth of cholelithiasis incidence in Russia and the world during the 20th century. The results of clinical and epidemiological studies on the prevalence of cholelithiasis among aborigines and non-aborigines of Chukotka, Republic of Sakha (Yakutia), Khakasia, and North and South America are given.     

Paraneoplastic lymphadenopathy

AIM: To study a spectrum of histologic patterns in patients with paraneoplastic lymphadenopathies, to analyse repeating changes and the causes of diagnostic mistakes. MATERIAL AND METHODS: In a retrospective analysis of 457 patients observed in Hematology Research Center of the RF in 1994-2004, and diagnosed as having non-malignant lymphadenopathies, we identified 40 patients in whom the second or third biopsy showed lymphoma. Nineteen patients (47.5%) had Hodgkin's lymphomas, 11 (27.5%)--B-cell lymphomas and 10 (25%) T-cell lymphomas. RESULTS: In patients subsequently diagnosed with Hodgkin's lymphoma there were 4 repeating histologic patterns in paraneoplastic lymph nodes: sinus histiocytosis (7 patients, 37%), paracortical reaction with numerous plasma cells and macrophages (7 patients, 37%), marked fibrotic changes (4 patients, 21%) and necrotizing lesions (3 patients, 16%). In 15 patients the second biopsy was performed within 4 weeks, while in 4 patients intervals between biopsies were 2, 4, 10 and 24 months. Eight patients (42%) had paraneoplastic changes in lymph nodes located not in the adjacent zones (in 7 patients above the diaphragm, and in 1 patient in both sides of the diaphragm). Amongst patients with B-cell lymphomas 7 had follicular lymphomas, 3--diffuse large B-cell lymphomas and 1--mantle cell lymphoma. In paraneoplastic lymph nodes there were 3 cases of sinus histiocytosis, 1--necrosis. In 5 patients with follicular lymphoma initially diagnosed as having follicular hyperplasia, retrospective analysis and immunohistochemistry showed partial involvement of lymph nodes with lymphoma. In two of them the presence of malignancy was clinically evident at the moment of the first biopsy, while three had a long history of lymphadenopathy (time to diagnostic biopsies were 5, 13 and 34 months). Amongst patients with T-cell lymphomas 5 had undetermined peripheral T-cell lymphomas, 2--anaplastic large cell lymphomas, 1--angioimmunoblastic lymphoma, 1--hepatolienal lymphoma and 1--Lennert's lymphoma. Median of time to the second biopsy was 4 months, range 1-48 months. Five patients (50%) had in the first lymph node sinus histiocytosis, 3 (30%)--paracortical hyperplasia, and 2--granulomatous lesions. Clonal rearrangements of gamma-chain T-cell receptor genes were found in 2 patients from 3 tested. CONCLUSION: Histologic patterns in lymph nodes not involved by lymphomas in patients with lymphomas are not random. While sinus histiocytosis and necrosis are universal findings, some patterns are disease specific. Paracortical hyperplasia is typical for T-cell lymphomas, prominent fibrosis--for Hodgkin's lymphoma. We believe that paraneoplastic changes in lymph nodes are caused by partial tumor involvement, cytokine reaction, or antitumor immune response. From practical point of view, finding of necrosis, prominent sinus histiocytosis, or prominent fibrosis of a lymph node in the absence of a history of chronic lymphadenitis or inflammation in the draining area should be considered as possible indication to second biopsy. Interpretation of such paraneoplastic phenomena as paracortical hyperplasia and formation of epithelioid-cell granulemas is not easy and must consider context of a clinical picture.     

Significance of determining the phenotypes of blood serum haptoglobin in infectious-inflammatory lung diseases

Studies of haptoglobin phenotypes (Hp) by disk electrophoresis in 173 patients with various, infectious inflammatory pulmonary diseases have revealed a growing incidence rate of Hp2-2. This has prompted a conclusion that Hp2-2 may be regarded as a serum genetic marker indicating a high risk of an inflammatory pulmonary disease.     

Determination of the Mode of Radical Termination from Pulsed Laser Polymerization Experiments in the Presence of Retardation and Chain Transfer to Agent

The pulsed laser polymerization–high termination rate limit–size‐exclusion chromatography (PLP–HTRL–SEC) technique is used to estimate the mode of termination (δ) for n‐butyl methacrylate (n‐BMA) polymerization at 30 °C. It is found that molecular mass distributions measured in these experiments are influenced by an unknown side reaction such as retardation or chain transfer that results in a marked decrease of intensity of the PLP peak. A new approach is developed to evaluate δ, with numerical experiments used to demonstrate the robustness of the methodology in the presence of retardation or chain transfer to agent. Application to the experimental n‐BMA polymerization at 30 °C leads to an estimate for δ of 0.60 ± 0.03.

     

c-kit+ precursors support postinfarction myogenesis in the neonatal, but not adult, heart

We examined the myogenic response to infarction in neonatal and adult mice to determine the role of c-kit(+) cardiovascular precursor cells (CPC) that are known to be present in early heart development. Infarction of postnatal day 1-3 c-kit(BAC)-EGFP mouse hearts induced the localized expansion of (c-kit)EGFP(+) cells within the infarct, expression of the c-kit and Nkx2.5 mRNA, myogenesis, and partial regeneration of the infarction, with (c-kit)EGFP(+) cells adopting myogenic and vascular fates. Conversely, infarction of adult mice resulted in a modest induction of (c-kit)EGFP(+) cells within the infarct, which did not express Nkx2.5 or undergo myogenic differentiation, but adopted a vascular fate within the infarction, indicating a lack of authentic CPC. Explantation of infarcted neonatal and adult heart tissue to scid mice, and adoptive transfer of labeled bone marrow, confirmed the cardiac source of myogenic (neonate) and angiogenic (neonate and adult) cells. FACS-purified (c-kit)EGFP(+)/(αMHC)mCherry(-) (noncardiac) cells from microdissected infarcts within 6 h of infarction underwent cardiac differentiation, forming spontaneously beating myocytes in vitro; cre/LoxP fate mapping identified a noncardiac population of (c-kit)EGFP(+) myocytes within infarctions, indicating that the induction of undifferentiated precursors contributes to localized myogenesis. Thus, adult postinfarct myogenic failure is likely not due to a context-dependent restriction of precursor differentiation, and c-kit induction following injury of the adult heart does not define precursor status.     

SAH gene variants revisited in the European Project On Genes in Hypertension

OBJECTIVE: Previous studies found significant association of hypertension and hypertension-related phenotypes with genetic variation in SAH (Spontaneously hypertensive rat-clone A-Hypertension-associated). We sought independent confirmation of these findings in the European Project On Genes in Hypertension. METHODS AND RESULTS: We randomly recruited 2603 relatives from 560 families and 31 unrelated subjects from six European populations (mean age 38.8 +/- 15.7 years; 52.1% women). We measured systolic/diastolic blood pressure (mean, 122.4/76.6 mmHg), body mass index (24.9 kg/m2), triceps skinfold (1.7 cm), waist-to-hip ratio (0.83 units), serum total and high-density lipoprotein (HDL) cholesterol (5.14 and 1.33 mmol/l), serum triglycerides (1.95 mmol/l) and blood glucose (4.90 mmol/l). We genotyped the G-1606A and -962del/ins polymorphisms. In all subjects, the allele frequencies were 11.8 and 29.5% for -1606A and -962del, respectively. Lewontin's D' was 0.97 (P < 0.0001). Haplotype frequencies were 58.8% for -1606G plus -962ins, 29.5% for -1606G plus -962del, and 11.7% for -1606A plus -962ins. Both before and after adjustment for covariates, none of the phenotype-genotype associations approached statistical significance. Our study had 80% power to detect on two-sided tests (P = 0.05), effect sizes of 1.8/1.3 mmHg for systolic/diastolic blood pressure, 0.52 kg/m2 for body mass index, 0.01 units for the waist-to-hip ratio, 0.96 mm for the triceps skinfold, 0.13 and 0.05 mmol/l for total and HDL cholesterol, 0.18 mmol/l for serum triglycerides, and 0.11 mmol/l for blood glucose. The family-based analyses did not reveal population stratification (P > or = 0.67). CONCLUSION: The evidence supporting an association of hypertension or hypertension-related phenotypes with the SAH gene remains equivocal in human studies.