Late left ventricular diastolic flow propagation velocity determined by color M-mode Doppler in the assessment of diastolic dysfunction.

BACKGROUND: Early color M-mode Doppler flow propagation (Ep) through the left ventricle (LV) has been proposed as a useful noninvasive index for assessing LV relaxation, whereas data concerning late velocity propagation (Ap) is lacking. METHODS: We studied 51 patients with delayed relaxation (group I) and 50 with pseudonormal filling pattern (group II). Another 51 aged-matched healthy persons served as the control group. RESULTS: Patients showed increased left atrial dimensions, atrial wave of the pulmonary vein flow, and Ap, and reduced LV ejection fraction, Ep, and Ep/Ap ratio compared with the control group. Patients in group II revealed increased left atrial dimensions (P =.001), atrial wave of the pulmonary vein flow (P <.001), and Ep/Ap ratio (P <.001), and reduced LV ejection fraction and Ap (P <.001) compared with group I. Regression analysis showed that the strongest independent variable distinguishing normal from pseudonormal filling pattern was the Ep/Ap ratio. CONCLUSION: Ap evaluation offers a new diagnostic diastolic index, especially in the field of the pseudonormal pattern where the separation from normal is difficult.     

Induction of antigen-specific isotype switching by in vitro immunization of human naive B lymphocytes

The use of in vitro immunization technology for the generation of human antigen-specific antibodies has essentially resulted in low affinity IgM antibodies, resembling an in vivo primary immune response. We now describe a detailed reproducible protocol for a two-step in vitro immunization, which yields isotype switched, antigen-specific human antibodies. The immunizing antigen was a 30aa synthetic peptide, containing both a B (15aa V3 peptide of the HIV-1) and a T helper cell epitope (15aa peptide from tetanus toxin). The immunization protocol includes: (i) a selection procedure of donors with a memory T cell response against tetatus toxoid; (ii) immunization of mature naive peripheral B lymphocytes in two distinct phases, involving a primary and a secondary step. None of the donors which were examined after primary 7immunization showed at any time an IgG anti-V3 specific antibody response, while all the donors showed an IgM response. After the secondary immunization step, anti-V3 antibodies of both IgM and IgG isotypes were detected. The switch frequency event was high among the tested donors (5/8).     

Effect of haemodialysis on serum levels of tumour markers in patients with end-stage renal failure

SUMMARY: We studied the effect of haemodialysis on the serum levels of tumour markers in 78 patients, 49 men and 29 women with a mean age of 61 ± 2 years, who had been undergoing haemodialysis for 39 ± 10 months. No patient had any clinical evidence of malignancy. Serum values of carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), squamous-cell-carcinoma-related antigen (SCC), neuron-specific enolase (NSE), tissue polypeptide antigen (TPA), CA 15-3, CA 19–9, and among males prostate-specific antigen (PSA) were determined before and after dialysis. Postdialysis values, after being corrected for haemoconcentration, were compared with predialysis values. A significant increase of 32% was observed in NSE levels ( P <0.001) and of 21% in CA 15-3 ( P <0.001) after haemodialysis. A lesser, but still statistically significant, increase (8-12%) was observed in SCC, AFP and CEA levels ( P <0.05), while the values of the remaining three markers remained unchanged. In conclusion, an increase in some tumour markers was found in our patients after dialysis, a finding which requires further investigation.     

Plasma lipids and lipoproteins and essential hypertension

In recent years there have been many studies demonstrating a correlation between increased arterial blood pressure and altered lipid profiles, and there has been an especially positive correlation between high cholesterol levels and blood pressure. There are differences between the various reports that are important. In our study the lipid distribution in 105 hypertensive patients with mild or moderate arterial hypertension according to WHO criteria without clinically or ultrasonographically apparent atherosclerosis was compared to the lipid distribution in 65 age-matched healthy persons. On the epidemiological level a significant, positive association was found between LDL serum levels (P 0.001), Apo B serum levels (P 0.001), serum triglyceride levels (P 0.05) and VLDL serum levels (P 0.01) and arterial hypertension. However, in contrast to recent reports, no significant difference was found between total serum cholesterol levels in normotensives and hypertensives, and there was no difference in HDL serum levels. No evidence could be found for a significant increase in lipoprotein (a) serum levels in hypertensives.Abbreviations LDL low density lipoprotein - VLDL very low density lipoprotein - HDL high density lipoprotein - Apo B 100 apolipoprotein B 100 - Apo A I apolipoprotein A I Correspondence to: H. Vetter     

An association study of the cholesteryl ester transfer protein TaqI B polymorphism with late onset Alzheimer's disease

Cholesteryl ester transfer protein (CETP) is reportedly able to affect the amount of cholesterol available for deposition and/or removal from peripheral tissues, in its capacity to mediate the transfer of cholesterol from high density lipoprotein (HDL) to very low density lipoprotein, in exchange for triacylglycerols from the latter. The TaqI B polymorphism of the human CETP gene has been associated with decreased CETP mass and an increase in HDL-cholesterol. While many studies have addressed the atherogenic or anti-atherogenic potential of this polymorphism, little is known about its effect on neurodegeneration, despite the fact that CETP is expressed in the brain and the disturbance of cholesterol homeostasis appears to be an important factor in the pathogenesis of Alzheimer's disease (AD). In this report, we have compared the distribution of the TaqI B polymorphism in an independent population of 102 clinically diagnosed late onset AD patients and a spousal control group of 97 individuals. We have also examined the possible interaction between this polymorphism and two other polymorphisms suspected of affecting cholesterol flux, namely apolipoprotein E APOE epsilon4, and lipoprotein lipase LPLS447X. No statistically significant differences have emerged with respect to either genotype or allele frequencies between the AD and control populations. CETP TaqI B did not interact significantly with either APOE epsilon4 or LPLS447X, in this study.     

Differential assessment of angiogenic activity and of vascular survival ability (VSA) in breast cancer

Recent reports provide evidence that some growth factors behave as inhibitors of the apoptosis of the endothelial cells, bringing forward the concept of vascular survival as a post-angiogenesis process. At least two different vasculature development processes occur within a tumor: the angiogenic (formation of new vessels) and the vascular survival pathway, which is devoted to the preservation of the newly-formed vessels in layers that lose contact with the adjacent normal tissue. We developed a method to assess these processes in tissue samples. We noted that differences among tumors may exist not only in the tumor angiogenic activity (TAA) but also in the vascular survival ability (VSA). One third of the highly angiogenic breast cancer cases examined had a poor ability to maintain high vessel density in inner tumor areas. Both parameters are independently related to prognosis, while VSA was directly related to tumor dimensions and node involvement. Patients with high TAA and VSA had a particularly poor prognosis. It is suggested that although cancer angiogenic activity is important for the local invasion and dissemination into vessels and lymphatics, the VSA may be important for the effective formation of viable tumor foci in lymph nodes or distant organs. Recognition and quantification of the vascular survival ability in human tumors may significantly improve the prognostic value of the assessment of tumor vasculature, and may help to stratify patients for clinical trials with novel anti-angiogenic or angiotoxic drugs. Elucidation of the pathways may provide additional targets for antiangiogenic therapy. This revised version was published online in July 2006 with corrections to the Cover Date.     

CCR2-64I and CXCL12 3'A alleles confer a favorable prognosis to AIDS patients undergoing HAART therapy.

BACKGROUND: The chemokine receptor polymorphisms CCR5Delta32, CXCL12 3'A, CCR2-64I and CCR5-59029 G/A have been demonstrated to affect HIV-1 infection and progression. OBJECTIVE: We studied the impact of the above polymorphisms on the effectiveness of a 30-month treatment with highly active antiretroviral therapy (HAART) in 149 HIV-1 patients. STUDY DESIGN: We stratified the patients according to CD4 CDC criteria and applied Kaplan-Meier analysis using the following end-point criteria: (a) the time from HAART initiation to undetectable viral load (VL) counts (VL<50 copies/ml), (b) the duration of undetectable VL status and (c) the time required for CD4+ T-cell counts to pass over the 500 cells/ml threshold. RESULTS: Our results in the second group (CD4 201-500) revealed that patients with the CCR2-64I allele achieved undetectable VL counts at 3.5+/-0.48 months as compared to 10.26+/-1.42 months in the control group (p=0.018). The VL remained undetectable for 28+/-2 months, in contrast to 20+/-2 months in the control group (p=0.048). Patients carrying CXCL12 3'A restored the CD4 population faster than the control group (9+/-2 and 14+/-2 months, respectively, p=0.023). The CCR5Delta32 and CCR5-59029 G/A alleles did not appear to affect the parameters studied. CONCLUSIONS: Our results suggest that patients carrying either CCR2-64I or CXCL12 3'A have a more favorable prognosis during HAART treatment.     

Integrin expression in correlation to clinicopathological features and prognosis of prostate cancer: A systematic review and meta-analysis

Background: The prompt identification of patients with poor prognosis is essential in order to improve the treatment outcomes in prostate cancer (CaP); as a novel approach, several molecular markers, including integrins, have been discussed as prognostic biomarkers. Our aim was to comprehensively examine aberrant expression of integrins in correlation with clinicopathological features and prognosis in CaP by synthesizing all available evidence, in a systematic review and meta-analysis. Methods: A systematic review and meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. Scientific literature databases (Pubmed, Embase, and Scopus) were systematically searched until May 10, 2020. Random-effects (DerSimonian-Laird) models were used to estimate pooled odds ratios (ORs) for cross-sectional correlations with clinicopathological characteristics and relative risks for longitudinal associations with prognosis. Results: Fourteen studies were included with a total number of 3,194 CaP cases examined (13 cross-sectional and four longitudinal cohort study arms). Correlation of low expression of α₆ (pooled OR = 0.10, 95% confidence interval [CI]: 0.04–0.28, P < 0.001) and β₁ (pooled OR = 0.45; 95% CI: 0.21–1.00, P = 0.049) integrin with high Gleason score was noted. A borderline trend between reduced expression of α₆ integrin and an advanced clinical stage of CaP (pooled OR = 0.48; 95% CI: 0.22-1.03, P = 0.06) was observed. No associations with biochemical recurrence and survival were documented. Conclusions: Evidence on the association of low expression of integrins α₆ and β₁ and more advanced CaP exist, whereas significant results on survival were not documented; further studies are warranted.