Transrectal ultrasound-guided prostate biopsies in patients taking aspirin for cardiovascular disease: A meta-analysis

Introduction

The management of anti-platelet therapy in the peri-operative period is a source of great concern. The dilemma is between whether to stop these agents peri-operatively in order to reduce the risk of bleeding complications, or to continue them in order not to compromise the protection they afford against the risk of cardiovascular events.

Materials and methods

The aim of this systematic review and meta-analysis was to understand whether continued aspirin therapy is a risk factor for bleeding complications after ultrasound-guided biopsy of the prostate. A bibliographic search covering the period from January 1990 to May 2011 was conducted in PubMed, MEDLINE and EMBASE. We also included our own series in the analysis.

Results

A total of 3218 participants were included. Haematuria was statistically more frequent (P = 0.001) among patients taking aspirin than in the control group with an odds ratio estimate of 1.36 [1.13; 1.64]. This increased risk was, however, due to minor bleeding. The occurrence of rectal bleeding and haematospermia was not statistically increased (P = 0.33 and P = 0.24, respectively) in patients taking aspirin compared to in the control group with odds ratios estimate of 1.24 [0.80; 1.93] and 1.52 [0.75; 3.08], respectively.

Discussion

There is limited information of the relationship between continued use of aspirin and haemorrhagic complications after transrectal ultrasound-guided biopsy of the prostate. This is the first comprehensive analysis on this topic.

Conclusion

Continued use of aspirin does not increase the risk of overall bleeding or moderate and severe haematuria after prostatic biopsy, and thus stopping aspirin before such biopsies is unnecessary.     

Further insights into the anti-aggregating activity of NMDA in human platelets

1. In the present study the effect of N-methyl-D-aspartate (NMDA) on thromboxane B₂ synthesis and on [Ca²⁺]_i was studied in human platelets.
2. NMDA (10⁻⁷ M) completely inhibited the synthesis of thromboxane B₂ from exogenous arachidonic acid (AA), while it did not interfere with the aggregating effect of the thromboxane A₂ receptor agonist U-46619.
3. NMDA (0.1 μM–10 μM) dose-dependently increased intracellular calcium in washed platelets pre-loaded with fura 2 AM, and this effect was not additive with that of AA.
4. NMDA shifted the dose-response curve of AA to the right. At the highest AA concentrations platelet aggregation was not inhibited.
5. The antiaggregating effect of NMDA was not antagonized by N^G-monomethyl-L-arginine (L-NMMA), a nitric oxide synthase (NOS) inhibitor.
6. Finally, NMDA (0.01 nM–100 nM) associated with either aspirin or indomethacin significantly potentiated the antiaggregating activity of both cyclo-oxygenase inhibitors.
7. It was concluded that NMDA is a potent inhibitor of platelet aggregation and thromboxane B₂ synthesis in human platelet rich plasma (PRP).

     

Mimotopes of the hyper variable region 1 of the hepatitis C virus induce cross-reactive antibodies directed against discontinuous epitopes.

Hepatitis C virus (HCV) is a major cause worldwide of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma, and the development of an effective vaccine represents a high priority goal. The hyper variable region 1 (HVR1) of the second envelope protein (E2) of HCV contains a principal neutralizing determinant, but it is highly variable among different isolates and it is involved in the escape from host immune response. To be effective, a vaccine should elicit a cross-reacting humoral response against the majority of viral variants. We show that it is possible to achieve a broadly cross-reactive immune response in rabbits by immunization with mimotopes of the HVR1, selected from a specialized phage library using HCV patients' sera. Some of the cross-reacting anti-mimotope antibodies elicited in rabbits, recognize discontinuous epitopes in a manner similar to those induced by the virus in infected patients.     

Effects of glutathione on red blood cell intracellular magnesium: relation to glucose metabolism.

Recent evidence suggests that the endogenous antioxidant glutathione may play a protective role in cardiovascular disease. To directly investigate the role of glutathione in the regulation of glucose metabolism in hypertension, we studied the acute effects of in vivo infusions of this antioxidant (alone or in combination with insulin) on whole body glucose disposal (WBGD) using euglycemic glucose clamp and the effects on total red blood cell intracellular magnesium (RBC-Mg) in hypertensive (n=20) and normotensive (n=30) subjects. The relationships among WBGD, circulating reduced/oxidized glutathione (GSH/GSSG) levels, and RBC-Mg in both groups were evaluated. The in vitro effects of glutathione (100 micromol/L) on RBC free cytosolic magnesium (Mg(i)) were also studied. In vivo infusions of glutathione (15 mg/minx120 minutes) increased RBC-Mg in both normotensives and hypertensives (1.99+/-0.02 to 2.13+/-0.03 mmol/L, P<0.01, and 1.69+/-0.03 to 1.81+/-0.03 mmol/L, P<0.01, respectively). In vitro GSH but not GSSG increased Mg(i) (179+/-3 to 214+/-5 micromol/L, P<0.01). In basal conditions, RBC-Mg values were related to GSH/GSSG ratios (r=0.84, P<0.0001), and WBGD was directly, significantly, and independently related to both GSH/GSSG ratios (r=0.79, P<0.0001) and RBC-Mg (r=0.89, P<0.0001). This was also true when hypertensive and control groups were analyzed separately. On multivariate analysis, basal RBC-Mg (t=6.81, P<0.001), GSH/GSSG (t=3. 67, P<0.02), and blood pressure (t=2.89, P<0.05) were each independent determinants of WBGD, with RBC-Mg explaining 31% of the variability of WBGD. These data demonstrate a direct action of glutathione both in vivo and in vitro to enhance intracellular magnesium and a clinical linkage between cellular magnesium, GSH/GSSG ratios, and tissue glucose metabolism.     

Lack of association between changes in plasma leptin concentration and in food intake during the menstrual cycle

BACKGROUND: Changes in plasma leptin concentration and food intake occur during the menstrual cycle; because leptin regulates food intake, one could hypothesize that changes in plasma leptin concentration and in food intake are associated throughout the menstrual cycle. However, no data have ever been provided to support such a relationship. The aim of our study was to investigate, during the different phases of the menstrual cycle, (a) the changes in plasma leptin concentration and, if such changes were demonstrated, (b) the potential relationship between the changes in plasma leptin concentration and food intake. DESIGN: The study was designed as an observational study. The plasma leptin concentration was determined in 16 healthy, young women during different phases of the menstrual cycle. At the same time, the basal metabolic rate (BMR), respiratory quotient (RQ) and food intake (FI) were also determined. RESULTS: The plasma leptin concentration increased throughout the menstrual cycle (P < 0.01 for trend) and was significantly correlated with plasma progesterone concentration (r = 0.55, P < 0.007, for follicular phase, r = 0.58, P < 0.02, for the periovulatory period and r = 0.57, P < 0.02, for the luteal phase). No significant differences in BMR and fasting RQ throughout the different phases of the menstrual cycle were found. In contrast, FI significantly declined in the periovulatory phase. No significant correlations between BMR, RQ and FI values and fasting plasma leptin concentration at all menstrual phases were found. CONCLUSION: Changes in plasma leptin concentration and in food intake were found at different phases of the menstrual cycle. Nevertheless, no correlation among those parameters at any phase of the menstrual cycle was observed.     

Thyroid hormones (T3 and T4): dual effect on human cancer cell proliferation

Several findings suggest that the patient's hormonal context plays a crucial role in determining cancer outcome. The exact nature of thyroid hormone action on tumour growth has not been established yet, in fact contrasting data show thyroid hormones have a promotory or an inhibitory action on cancer cell proliferation depending on the case. We hypothesized that not only tissue specificity, but also specific mutations occurring during tumoral development in different thyroid hormone cellular targets are responsible for this dual effect. To test our hypothesis we analysed, by time-course and bromodeoxyuridine assay, thyroid hormone effects on the proliferation of six cancer cell lines originating from the same tissue or organ but carrying different mutations (in phospho-inositide 3 kinase or β-catenin genes). The data obtained in this study show how mutations that affect the balance between degradation and stabilization of β-catenin assume a remarkable importance in determining the cell-specific thyroid hormone effect on cell growth.     

Uterine-sparing surgical management of postpartum hemorrhage: is it always effective?

Purpose  

To further study the efficacy of uterine-sparing procedures based on triple uterine artery ligation (TUAL) possibly complemented with hemostatic multiple square suturing (HMSS) for the management of post-partum hemorrhage (PPH).