Immune reconstitution after haematopoietic cell transplantation in children: immunophenotype analysis with regard to factors affecting the speed of recovery

Immune reconstitution was studied prospectively in 66 children who underwent 77 haematopoietic cell transplantations (HCT): 46 autologous HCTs in 39 patients and 31 allogeneic HCTs in 27 patients. We studied the dynamic analysis of immune recovery with regard to potential factors affecting its speed, including age, type of HCT, diagnosis, graft-versus-host disease (GvHD) and cytomegalovirus (CMV) infection reactivation. Absolute counts of different lymphocyte subsets and immunoglobulin serum levels were determined in peripheral blood of patients on d -7 and +16, and then at various intervals up to 24 months post transplant. Common patterns of immune recovery after both allogeneic and autologous HCT were identified: (i) CD4+CD45RO+ peripheral T-cell expansion on d +16; (ii) inverted CD4+:CD8+ ratio from d +30 onwards; (iii) rapid natural killer (NK) cell (CD16+/-CD56+) count normalization. We observed prolonged T-cell lymphopenia (CD3+, CD3+CD4+, CD4+CD45RA+) until 24 months after autologous HCT, whereas in the allogeneic setting CD3+CD4+ cells, including naive CD45RA+ cells, returned to normal values at 9 months post transplant. Age > 10 years and coexistence of GvHD and CMV reactivation were associated with a substantial delay in T- (CD4+, including CD45RA+) and B-cell recovery after allogeneic HCT. Multidrug GvHD prophylaxis resulted in impaired T- (CD4+, CD4+CD45RA+) and B-cell reconstitution only in the early phase after allogeneic HCT (up to 4 months). Our results demonstrated that T-cell recovery was severely impaired in children after autologous HCT. It should be emphasized that specific approaches to enhance immune reconstitution are necessary to control minimal residual disease and avoid the risk of infectious complications in the autologous setting. Thymic involution after allogeneic HCT seems to be associated with age and coexistence of GvHD and CMV reactivation.     

Negative D-dimers and exclusion of venous thromboembolism--own experience

The assessment of D-dimer concentration has become essential step during diagnostic algorithm of venous thromboembolism (VTE). This test characterizes high sensitivity but limited specificity. Negative D-dimer with high probability excludes VTE. The aim of this study was to assess the percentage of patients treated in Department of Internal Medicine, Endocrinology and Haemostatic Disorders, Medical University of Gdańisk, who in spite of clinical signs of VTE showed normal D-dimer level. Between 2000 and 2004 in our department 57 cases with recent deep vein thrombosis (DVT) were diagnosed, in 2 cases with co-existence of pulmonary embolism (PE). The D-dimer concentration was assessed in patients' plasma with the use of immunoturbidometry. Between 57 cases with VTE, 7 patients (12%) showed normal D-dimer level (<500 microg/ml). This group consisted of 4 men and 3 women, aged from 40 to 82 years (the mean age of 58 years). In all 7 cases DVT was diagnosed, in 2 patients with concomitent PE. The final diagnosis was confirmed by compression ultrasonography and pulmonary scintigraphy. Our analysis underlines the observation that occurrence of VTE and negative d-dimer concentration is possible and may probably be related to methodological limitations. However, the lack of increase of D-dimer could also be caused by fibrinolysis alteration.     

Efficacy and safety of ezetimibe co-administered with simvastatin in thiazolidinedione-treated type 2 diabetic patients

AIM: In patients with type 2 diabetes mellitus (T2DM), combination therapy is usually required to optimize glucose metabolism as well as to help patients achieve aggressive targets for low-density lipoprotein cholesterol (LDL-C) and other lipid parameters associated with cardiovascular risk. The thiazolidinediones (TZDs) are increasingly being used for both their blood glucose-lowering properties and their modest beneficial effects on triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C). Ezetimibe, an intestinal cholesterol absorption inhibitor, has a mechanism of action that differs from that of statins, which inhibit hepatic cholesterol synthesis. We compared the lipid-modifying efficacy and safety of adding ezetimibe to simvastatin, vs. doubling the dose of simvastatin, in TZD-treated T2DM patients. METHODS: This was a randomized, double-blind, parallel group, multicentre study in T2DM patients, 30-75 years of age, who had been on a stable dose of a TZD for at least 3 months and had LDL-C > 2.6 mmol/l (100 mg/dl) prior to study entry. Other antidiabetic medications were also allowed. Following 6 weeks of open-label simvastatin 20 mg/day, patients were randomized to the addition of either blinded ezetimibe 10 mg/day (n = 104) or an additional blinded simvastatin 20 mg/day (total simvastatin 40 mg/day; n = 110) for 24 weeks. Patients were stratified according to TZD type and dose (pioglitazone 15-30 vs. 45 mg/day; rosiglitazone 2-4 vs. 8 mg/day). RESULTS: LDL-C was reduced more (p < 0.001) by adding ezetimibe 10 mg to simvastatin 20 mg (-20.8%) than by doubling the dose of simvastatin to 40 mg (-0.3%). Ezetimibe plus simvastatin 20 mg also produced significant incremental reductions in non-HDL-C (p < 0.001), very low-density lipoprotein cholesterol (p < 0.05) and apolipoprotein B (p < 0.001) relative to simvastatin 40 mg. There were no differences between the groups with respect to changes in TG and HDL-C levels, and both treatments were well tolerated. CONCLUSIONS: Co-administration of ezetimibe with simvastatin, a dual inhibition treatment strategy targeting both cholesterol synthesis and absorption, is well tolerated and provides greater LDL-C-lowering efficacy than increasing the dose of simvastatin in T2DM patients taking TZDs.     

Relationship between peritoneal equilibration test and surface tension of peritoneal effluent in CAPD patients

Surface phenomena resulting from interactions between molecules occur commonly in nature. Peritoneal effluent is a mixture of organic and inorganic substances both macro- and micromolecular. Surfactants present in dialysate affect its surface properties. Among them are: proteins, phospholipids, fatty acids. Our aim in this study was to investigate relationships between peritoneal membrane solute transport characteristics and surface tension of peritoneal effluent. The study was conducted in 40 CAPD patients who were stable, without peritonitis (24 M, 16F), age 51.5 +/- 15.8 (range 30-79) mean CAPD duration 26.4 +/- 20.6 months (range 4-72). Standard peritoneal equilibration test (sPET) was done in all patients. Dialysate surface tension (ST) values after 4 hours dewell were determined using Wilhelmy Plate method. Mean ST values of individual dialysate sample based on 10 measurements were calculated. According to the PET values patients were divided into two groups: group 1 (high/high average transporters, n = 26) and group 2 (low average/low transporters, n = 14). Patients in group 1 had significantly lower ST of dialysate than patients in group 2 (51.2 +/- 4.8 vs 57.9 +/- 1.4 mN/m), p<0.01. The lowest values of ST (48.5 +/- 5 mN/m) were found in patients classified as high transporters (n = 8). Correlation's: significant negative correlation was found between ST and D4/P4 for creatinine (r = -0.45, p<0.005) and significant positive correlation between ST and D4/DO for glucose (r = 0.48, p = 0.003). We conclude that there are significant relationships between peritoneal transport status and surface tension of peritoneal effluent. High transporters have significantly higher concentrations of surfactants in dialysis effluent.     

Multivariate analysis of risk factors for development of duodenal ulcer in Helicobacter pylori-infected patients

BACKGROUND: Although Helicobacter pylori is a significant etiologic factor of peptic ulcer disease, it remains unknown why ulcers develop only in the minority of infected individuals. AIM: The aim of this cross-sectional study was to evaluate the association between the presence of duodenal ulcer in H. pylori-infected patients and different risk factors. METHODS: A total of 122 H. pylori-infected patients were enrolled; 79 had duodenal ulcer and 43 gastritis. Univariate analysis was conducted using either Fisher's exact test or exact Cochrane-Armitage trend test. In multivariate analysis the logistic model was used. RESULTS: Univariate analysis indicated six factors (male sex, smoking, antral H. pylori density, CAGA presence in antrum, and VACA s1a presence in antrum and corpus). Four factors (sex, smoking-alcohol index, H. pylori density index, and CAGA index) were found to be significant in multivariate analysis. The best model predicting duodenal ulcer included male sex, smoking, presence of H. PYLORI on histopathology in antrum and CAGA presence in corpus. CONCLUSION: Although several risk factors were significantly associated with duodenal ulcer, we failed in the identification of either a single risk factor or a set of factors that can unequivocally differentiate patients with ulcer from those with gastritis.     

Percutaneous high-speed rotational atherectomy (Rotablator™) of a restenosed ostial renal artery: A case report

This case report describes the feasibility and potential benefit of the use of a high-speed rotational atherectomy device (the Rotablator?) in the treatment of renovascular hypertension in a patient with a recorded restenosis of an ostial renal artery lesion following standard balloon angioplasty.