Phenotype of endomyocardial biopsy-derived T-lymphocyte cultures and chronic rejection after heart transplantation

Chronic rejection (CR) is a major problem in long-term survival in heart transplantation. We analysed whether the occurrence of CR correlates with the incidence of acute rejections (AR) or with characteristics of endomyocardial biopsy-derived cell cultures. CR was diagnosed by annual angiography and defined as all coronary vascular changes. One year after transplantation 24 of the 63 patients had CR (38%). The incidence of AR in CR + and CR — patients was comparable. The patients in both groups had similar individual median percentages of EMB-yielding cell cultures. During the first year the CR — patients had more cultures in which at least 60% of the cells were CD4 + T cells (50% vs 37%, P = 0.05), due to a stronger CD4 predominance in the first 6 months. In the second year the CD4 predominance in the patients diagnosed as CR + after 1 year tended to be higher (P = 0.08). The patients had comparable percentages of cultures predominated by CD8 + T cells, γδ T cells or NK cells, irrespective of the time interval. These results might indicate that CD4 + T lymphocytes play a dual role in the aetiology of CR.     

In vitro and in vivo effects of BT563, an anti-interleukin-2 receptor monoclonal antibody

Abstract BT563, a murine anti-IL-2R MoAb, was found to be more potent than anti-Tac in inhibiting proliferation in the mixed lymphocyte reaction. Results obtained with 33 B3.1 in these experiments were similar to those with BT563. The anti-IL-2R MoAb 2A3 was shown to be a suitable agent for monitoring the effect of BT563 on peripheral blood. IL-2R-positive cells were not detected in peripheral blood samples from 1 h after the first dose until 8 days after the last dose. Plasma trough levels were measured in patients receiving 5 or 10 mg daily. The administration of BT563 to allograft recipients did not lead to clinically significant side effects.     

Risk of an unintentional pregnancy after only one unprotected coitus; observations concerning today's hormonal postcoital contraceptive agents]

Tietze and Dixon have studied the average chance of getting pregnant after a single act of unprotected coitus. Tietze concluded that the chance lay between 2% and 4%. Dixon calculated that if the coitus occurred 1 day before ovulation the chance was 17.3%, gradually decreasing to zero toward the 9th day before and 6th day after ovulation. The commonly used hormonal postcoital contraceptive methods are 1) the morning-after pill consisting of 5 mg of ethinyl estradiol/day for 5 consecutive days, also called the 5x5 method; and 2) the 2x2 method comprised of taking 50 mg of ethinyl estradiol twice within an 12-hour interval. 3016 women were treated with the 5x5 method, and 17 pregnancies occurred with a failure rate of .6. According to Tietze the real number lay between 60 (2%) and 120 (4%) without treatment yielding a real rate of 14.2-28.4 for these 17 pregnancies. In a group of 1990 women with midcycle coitus, 11 pregnancies occurred yielding a failure rate of 4.9%, although according to Dixon 222 pregnancies were expected. 867 women were also treated with the 2x2 method, 93 women were excluded, and 18 pregnancies occurred, which corresponds to a failure rate of 2.1. According to Tietze the real number was 17 (2%) and 35 (4%), thus the 18 pregnancies yielded a real failure rate of 51.4 and 100. The 5x5 method was found effective in dogs and apes in the doses used, however, neither the method of administration, nor the indications were established for humans, thus at least in 90% of cases women are treated unnecessarily with an outright toxic medicine because of the exorbitantly high doses of synthetic estrogen. The 2x2 method has a high failure rate partly because of deficient instruction by doctors. The effectiveness of the 2x2 method is very meager, thus the medical ethical question arises of deceiving as many as 20,000 women who are prescribed this treatment every year.     

Measurement of thrombin generation intra-operatively and its association with bleeding tendency after cardiac surgery

Introduction

Patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) are susceptible to haemostatic disturbances. Monitoring the haemostatic capacity by conventional clotting tests is challenging.

Materials and Methods

Thrombin generation (TG) by Calibrated Automated Thrombography, clotting tests and tissue factor pathway inhibitor (TFPI) measurements were performed to describe the relationship between haemostatic changes and alterations in these tests. Blood samples were collected before, during and after CPB. Furthermore, it was investigated whether TG measured intraoperatively, is associated with increased risk of bleeding postoperatively.

Results

TG diminished significantly (p < 0.01) after heparinization in the presence and absence of platelets (37% and 50%) compared to baseline. After the start of CPB, TG elevated and persisted till the end of surgery but remained lower than preoperatively. Activated clotting time increased after heparinization and after the start of bypass compared to baseline (400% and 500%). Anti-FXa activity reduced on the start of CPB compared to the level after heparinization, to almost the baseline value following protamine reversal of heparin. The plasma levels of total and free TFPI elevated 9 and 14 fold during bypass and remained after protamine administration higher than preoperatively. Plasma D-dimer levels reduced (p < 0.01) when bypass started. However, a marked elevation was observed in the following time points. TG in platelet-rich plasma measured after heparinization and after the start of CPB associated (p < 0.05) with postoperative blood loss.

Conclusions

TG can be determined during CPB despite the high heparinization level, it reflects the haemostatic capacity better than clotting-based assays and might better predict bleeding when performed intraoperatively.     

Donor-specific CTL frequencies in peripheral blood in relation to graft vascular disease after clinical heart transplantation

Abstract Cellular mechanisms may play a role in the development of graft vascular disease (GVD). We previously demonstrated that GVD correlated with an increase of donor-specific T-helper 1 cytokine production by graft-infiltrating lymphocytes but not by peripheral blood mononuclear cells (PBMC). These T-helper 1 cytokines aid the generation of cytotoxic T-lymphocytes (CTL). In the present report, we investigated whether there is a relationship between the frequency of donor-specific CTL precursors (pCTL) in PBMC and the development of GVD. We tested PBMC samples of five patients with GVD and five patients without GVD in the periods 3–6 months, 1 year, and 3 years after heart transplantation. At all time points, GVD was not related to the number of pCTL. In conclusion, donor-specific cellular tests in peripheral blood could not be related to GVD. Apparently, donor-specific reactions associated with the induction of GVD can only be monitored in the graft.     

Prostate-specific antigen as an estimator of prostate volume in the management of patients with symptomatic benign prostatic hyperplasia

OBJECTIVES: To assess the ability of serum prostate specific antigen (PSA) to estimate prostate volume (PV) to aid in the management of patients with benign prostatic hyperplasia (BPH). METHODS: From 1989 to 2002, data were collected from 2264 patients complaining of lower urinary tract symptoms (LUTS) who visited the Department of Urology of the University Medical Centre Nijmegen, The Netherlands. Baseline PV and serum PSA was determined using standard techniques. All patients who had a baseline PV < or =200 ml, as well as a baseline serum PSA 0-10 ng/ml, were included. Patients with a history of prostate surgery, prostate cancer and conditions other than BPH at baseline were excluded. A log-transformed linear regression model was used to estimate PV. Receiver-operating characteristic (ROC) curves were constructed to evaluate the ability of serum PSA to estimate threshold PVs in men with BPH, and to select the optimal serum PSA cut-off values. RESULTS: The analyses included 1859 patients with a mean age of 63.5 years, mean baseline PV 43.9 ml, and mean baseline PSA value 3.1 ng/ml. PV as well as serum PSA increases with age. Linear regression analyses showed that PV and serum PSA have an age-dependent log-linear relationship, where 42% of the variance of PV can be explained by PSA and age. ROC's area under the curves (AUC) reveal that PSA has a good predictive value for assessing 'prostate enlargement', with AUC around 82% in the overall age groups irrespective of the PV cut-off values. Optimal serum PSA cut-off values for the overall study population irrespective of age are 2.0 ng/ml to detect PV >30 ml and 2.5 ng/ml to detect PV >40 ml. CONCLUSIONS: This study suggests that serum PSA can estimate prostate enlargement sufficiently accurately to be useful for therapeutic, especially medical, management. It is well accepted that the outcome of pharmacotherapy for BPH depends on baseline PV. Therefore, in the absence of reliable direct measurement of PV, serum PSA determination may be used to optimise patient management.     

Recent role of inflammation in prostate diseases: chemoprevention development opportunity

The role of inflammation in prostate diseases is suggested by the presence of inflammatory cells within the Benign Prostatic Hyperplasia (BPH) and Prostate Cancer (PC). Inflammation suggests influence a balance between prostate cell growth and apoptosis by increasing microenvironment around prostate factors such as cytokines, COX-2 and oxidative stress. These factors stimulate proliferation and minimize cell apoptosis. In vitro studies showed an over expression of these inflammatory markers in BPH and PC compared normal tissue. There were also inflammatory marker differences between BPH and PC, which was more severe inflammation process in PC. Another basic difference was a gene polymorphism in PC. Targeting the microenvironment may represent a promising therapeutic approach for prostate disease. Many epidemiological studies showed a beneficial effect of drug that influences inflammation such as non steroidal anti-Inflammatory drugs, antioxidant compound in food or supplements and vitamin D receptor (VDR) agonists. These drugs need more investigation to prove their function as chemoprevention of prostatic disease.