Cytokines and heart rate variability in patients with chronic heart failure

INTRODUCTION: Heart rate variability (HRV) analysis is a non-invasive method of assessment of the autonomic nervous system's effects on heart function. In chronic heart failure (CHF), decreased HRV correlates with the progression of the disease. It is also known that in CHF increased levels of proinflammatory cytokines are present. Because these molecules are believed to influence the nervous system at both the central and peripheral levels, their potential role in HRV reduction in the course of CHF has been proposed. AIM: The study was designed to verify potential relations between cytokines and HRV parameters in CHF patients. The concept of the study was driven by the recognition of controversies in this field and the paucity of published reports. METHODS: Forty-four patients with CHF and stable NYHA class I-IV symptoms and 15 healthy controls were enrolled in the study. Time-domain HRV analysis was performed based on of 24-hour Holter ECG monitoring. Plasma concentrations of soluble TNFalpha receptors sTNF-RI and sTNF-RII and interleukin 6 (IL-6) were measured using commercially available ELISA kits (Quantikine, RD Systems). RESULTS: In patients with CHF, HRV indices included in the analysis were significantly decreased, and the levels of cytokines increased in comparison with the control group. In the whole study population, both in the CHF patients and the control group, significant negative correlations were observed between sTNF-RI level and long-term HRV indices such as SDNN (r=-0.44; p=0.0006), SDANN (r=-0.44; p=0.0005) and short-time index SDNNI (r=-0.37; p=0.004). Similar negative correlations were found between sTNF-RII level and SDNN (r=-0.35; p=0.007), SDANN (r=-0.34; p=0.01), and SDNNI (r=-0.31; p=0.02), as well as between IL-6 level and SDNN (r=-0.41; p=0.001), SDANN (r=-0.44; p=0.0005) and SDNNI (r=-0.34; p=0.009). CONCLUSIONS: Significant negative correlations between TNF-alpha soluble receptors sTNF-RI, sTNF-RII and IL-6 levels and time-domain HRV parameters were observed in the study. Because the results of investigations conducted so far do not elucidate the cause-effect relationship, further studies are needed to clarify the mechanisms of HRV depression in CHF and the role of cytokines in this severe clinical condition.     

Lympho- and myeloproliferative disorders in renal transplant recipients--one center's experience and review of the literature

Recipients of renal transplants have an increased risk of developing secondary malignancies. About 4% of patients who underwent kidney transplantation will develop cancer, and 1% of transplanted patients will develop lymphoproliferative disorders. According to clinical analyses and laboratory data, the main reason for increased risk of developing malignant disease in this group of patients, is their immunocompromised status due to immunosuppressive treatment. So called "strong" immunosuppressive drugs like antilymphocytic globulin (ALG), antithymocytic globulin (ATG), or monoclonal globulin OKT3 seem to favor the development of secondary malignancies much more than other drugs, like: corticosteroids, azathioprine (AZA), or cyclosporine (CsA). Secondary lymphoproliferative disorders are usually connected with reactivation of Ebstein-Barr virus infection. Patients with early onset (<1 year after the transplantation) have a favorable clinical course after withdrawal of immunosuppression. The subset of late-onset (>1 year) has usually much more aggressive clinical course and patients require intensive treatment. The general recommendation in these patients is to stop or to reduce the immunosuppressive treatment and to continue the chemotherapy in full dose. This treatment is often complicated by severe infections, but it offers a chance to achieve remission without worsening the function of transplanted organ. In this paper we are presenting five patients with secondary lympho- or myeloproliferative disorders after kidney transplantation and give an overview of the recent literature in this field.     

Endocrine pancreatic function in patients after acute pancreatitis

BACKGROUND/AIMS: The incidence of carbohydrate tolerance disorders in patients after acute pancreatitis has not been clearly established yet. The aim of the study was to estimate the frequency of endocrine pancreatic function impairment in patients after acute pancreatitis and its correlation with acute pancreatitis etiology and clinical course. METHODOLOGY: 82 patients (27 women and 55 men), aged between 28-65 (mean: 47 +/- 8.3), 1-7 (mean: 4.7 +/- 3.6) years after acute pancreatitis were evaluated. Control group consisted of 15 healthy volunteers. Oral glucose tolerance test with RIA insulin level was performed in all examined patients. Patients with any sign of chronic pancreatitis, based on clinical, functional (stool chymotrypsin test) and imaging (US and CT) findings, were excluded from the study. RESULTS: Impaired glucose tolerance was found in 4 patients (4.9%) and overt diabetes in 13 patients (15.8%) recovered from acute pancreatitis, which was not significantly different from those values in the local general population. Mean insulin values fasting and 30, 60 and 90 min after administration of 75 g glucose were significantly lower in patients after acute pancreatitis than in controls (p < 0.001). Endocrine pancreatic function impairment was found significantly more often in patients after severe acute pancreatitis clinical course (p < 0.0001), than in patients after mild pancreatitis. The frequency of impaired glucose tolerance and diabetes after acute alcoholic pancreatitis was 13 (36%), which was significantly higher (p < 0.05), than in cases of gallstone etiology (14%) and other causes (0%). CONCLUSIONS: Pancreatic endocrine function impairment following acute pancreatitis is associated with the decreased plasma insulin levels fasting and after glucose stimulus. Overall, the incidence of diabetes mellitus in patients after acute pancreatitis is similar to the reported values for the general population in this area. Alcoholic pancreatitis is more often complicated with impaired glucose tolerance and diabetes mellitus as regards to other causes of pancreatitis. Endocrine pancreatic function impairment is significantly more common after severe than after mild acute pancreatitis.     

The Influence of Human Neutrophils on N-nitrosodimethylamine (NDMA) Synthesis

N-nitrozodimethyloamine (NDMA) is a carcinogenic compound that can be formed in vivo. NDMA is synthesized from precursors-amines and nitrosating agents. Nitrosating agents are formed through the reaction of oxide, reactive oxygen species and nitric oxide (NO). Human neutrophils (PMN) are an important source of the most reactive oxygen species as well as of the nitric oxide. The increase in oxygen metabolism of PMN can lead to the increase nitrosating agent and nitroso-forms. Inflammatory process is associated with locally decreased pH that may favor nitrosation reaction.

In the present study, we estimated the NDMA synthesis by LPS-stimulated PMN in the presence of the iNOS inhibitor – N-nitro-L-arginine methyl ester (L-NAME). In the nitrosation reaction dimethylamine (DMA) was used as substrat. The viability of the cells was measured by cytometric method. NDMA concentrations the culture media was measured by GCMS method. NO production was estimated by Griess's method. Expression of iNOS was determined by western blotting.

Results obtained showed that DMA nitrosation is most effective in pH between 3–4.5. Nonstimulated PMN produced lower concentrations of NO than LPS-stimulated cells (1.27 μg/cm³ and 1.57 μg/cm³, respectively). In the culture of nonstimulated PMN supplemented with DMA, there was NDMA (mean – 0.99 ng/cm³). In the culture of LPS-stimulated PMN in the presence of DMA, the concentration of NDMA was higher than in the culture of nonstimulated PMN (median – 1.45 ng/cm³). In the supernatants of cells incubated without DMA and with DMA, LPS and L-NAME, no NDMA was detected. These results indicate that PMN can be one of sources of nitrosating agents and can play a role in endogenous NDMA synthesis. Stimulation of PMN can lead to the increase of NDMA concentration following the increase of NO production. Different pathological conditions associated with PMN activation as well as the decreased pH may favor endogenous NDMA synthesis.     

Masowe badania molekularne dla identyfikacji dawców ze słabą ekspresją antygenu D

One of the basic rules of transfusion is to prevent alloimmunisation by highly immunogenic RhD antigen and not to transfuse RhD negative individuals with RhD positive blood. In some cases the expression of this antigen is so weak that it is undetectable in routine serological tests. The paper presents an algorithm for mass DNA testing with the purpose of identifying donors with low RhD expression. The screening is based on RHD gene detection (absent in RhD negative Caucasians) in DNA isolated from pools of 96 plasma samples from blood donors identified as RhD negative by the routine serological methods in Blood Transfusion Centers. Such procedure substantially reduces the costs. Plasma samples can be brought from the territory of the whole country, stored and accumulated for testing in one selected center. The cost would amount to approximately 25 PLN per donor. The test is performed once for each RhD negative individual. It is estimated that such persons will represent approximately 0.2% of RhD negative donors.     

Inhibitor kinazy Brutona u chorych z nawrotowym lub opornym na leczenie chłoniakiem z komórek płaszcza – wyniki międzynarodowego,wieloośrodkowego,badania II fazy z ibrutynibem (PCI-32765) – EHA Encore

Bruton's tyrosine kinase (BTK) is a central mediator of B-cell receptor (BCR) signaling essential for normal B-cell development. Ibrutinib is an oral BTK inhibitor that induces apoptosis and inhibits migration and adhesion of malignant B-cells. Updated results of this international, multicenter, phase 2 study of single agent ibrutinib in relapsed or refractory MCL will be presented.Ibrutinib 560 mg PO QD was administered continuously until disease progression. Tumor response was assessed every 2 cycles (one cycle = 28 days). The study enrolled 115 patients (65 bortezomib-naïve, 50 bortezomib-exposed); 111 patients were treated; 110 were evaluable for response. Baseline characteristics included: median age 68 years, time since diagnosis 42 months, number of prior treatments 3; bulky disease (>10 cm) 13%, prior stem cell transplant 10%, high risk MIPI 49%.Median time on treatment was 9.2 months; 53% of patients remain on therapy. Median PFS was 13.9 months and DOR has not yet been reached. Responses increased with longer treatment: comparing to previous data described at ASH 2011, the CR rate increased from 16% to 39%, and the ORR increased from 69% to 75%.     

Pain associated with the musculoskeletal system in children from Warsaw schools

Objective

To assess the prevalence of pain in the musculoskeletal system and possible reasons for these complaints among early age children from Warsaw schools.

Material and methods

The study was conducted in 34 randomly selected primary schools in Warsaw in 2011. 2748 survey-questionnaires were given to parents or legal guardians by children. Of these, 1509 surveys were subject to a final analysis. The survey included 66 questions regarding, among other things, pain in the musculoskeletal system in children. Additionally, there were questions about possibly occurring diseases, any postural defects, significant obesity, as well as effects of these complaints on the child''s physical activity. Survey data regarded 6–7-year-old children.

Results

In the group of 1509 respondents, 242 children (16%) complained about pain in the musculoskeletal system. Pain was located most frequently in the knee joints, and more rarely in the spine and joints in the upper extremities. In the group of children who complained about pain, moderate physical activity was statistically significantly limited. According to parents, physicians did not diagnose any medical conditions in 106 children. Joint disease was diagnosed in 33 children. Postural defects were diagnosed in 589 children. In 123 children complaining about pain at least one postural defect was diagnosed. Such defects were diagnosed statistically significantly more rarely (p = 0.011) in 1234 children who did not complain about pain (460 children). Platypodia or other foot deformation was observed in 25% of these children, spinal curvature in 12%, abnormal knee joint position in 11% and uneven hip position in 2% children. Of note, 17% of all children were significantly overweight. In overweight children the prevalence of pain, especially in the knee joints and feet, was significantly higher.

Conclusions

This study aims to underline the problem of musculoskeletal pain in early-age children which limits their physical activity. Also the authors draw attention to the issue of postural defects in a large group of school children. This issue undoubtedly requires more attention and a plan how to create more effective methods of prevention.