Potential Risk Factors for Breast Cancer in Pakistani Women

Background: Breast cancer is the most common female malignancy worldwide and its incidence is on the rise in Pakistan. The aim of this case-control study was to quantify the association of various risk factors with breast cancer risk among Pakistani women. Materials and Methods: A total of 2,246 women were studied, including 1,238 women with histologically confirmed breast cancer patients and age matched control subjects (N1008) without breast cancer and other chronic diseases. Subjects were interviewed using a specifically designed questionnaire. Unconditional logistic regression was applied. Subsequent disease-specific mortality was also measured. Results: In this study, majority of the breast cancer patients (69.59%) were in age ranges of 40s and 50s. BMI greater than 25kg/m2 (OR1.57; 95%CI, 1.26-1.90 and OR1.60; 95%CI, 1.26-2.03), marital status of unmarried (OR2.03; 95%CI, 1.69-2.44), lack of breast feeding, smoking (current or ever), lack of physical activity and post-menopausal status were found to have significant positive associations with breast cancer. It was also observed that increased parity reduced the disease risk. A larger number of cases (58.1%) had their right breast affected while 22.8% had other complications as well. Conclusions: This exploratory analysis indicated a number of risk factors to be associated with increased risk of breast cancer. It was also observed that mean age at diagnosis is a decade earlier than in western countries. It is hoped that our findings will facilitate establishment of adequate evidence-based awareness and preventive measures for Pakistani women.     

4-[18F]fluoroglutamic acid (BAY 85-8050), a new amino acid radiotracer for PET imaging of tumors: synthesis and in vitro characterization

There is a high demand for tumor specific PET tracers in oncology imaging. Besides glucose, certain amino acids also serve as energy sources and anabolic precursors for tumors. Therefore, (18)F-labeled amino acids are interesting probes for tumor specific PET imaging. As glutamine and glutamate play a key role in the adapted intermediary metabolism of tumors, the radiosynthesis of 4-[(18)F]fluoro l-glutamic acid (BAY 85-8050) as a new specific PET tracer was established. Cell-uptake studies revealed specific tumor cell accumulation.     

Special focus on the role of α(1D)-adrenoreceptors in the assessment of renal tubular sodium re-absorptive responses in spontaneously hypertensive rats subjected to high sodium diet

α(1D)-adrenoceptors are involved in the genesis/maintenance of hypertension in spontaneously hypertensive rats (SHR). This study aims to investigate the role of α(1D)-adrenoceptors in the antinatriuretic and antidiuretic responses in SHR subjected to high sodium (SHRHNa) and normal sodium (SHRNNa) intake for six weeks. Renal inulin clearance study was performed in which the antinatriuretic and antidiuretic responses to phenylephrine were examined in the presence and absence of α(?D)-adrenoceptors blocker BMY7378. Data, mean±S.E.M. were subjected to ANOVA with significance at p<0.05. Results show that feeding SHR for six weeks with high salt did not cause any change in blood pressure. SHRHNa had higher (all p<0.05) urine flow rate (UFR), fractional and absolute excretion of sodium (FE(Na) and U(Na)V) compared to SHRNNa. Phenylephrine infusion produced significant reduction in UFR, FE(Na) and U(Na)V in both SHRHNa and SHRNNa. The antidiuretic and antinatriuretic responses to phenylephrine in both groups were attenuated in the presence of BMY7378. Moreover, the antidiuretic and antinatriuretic responses to phenylephrine and BMY7378 were independent on any significant changes in renal and glomerular hemodynamics in both groups. Thus we conclude that high sodium intake did not bring any further increase in blood pressure of SHR, however, it results in exaggerated natriuresis and diuresis in SHRHNa. Irrespective of dietary sodium changes, α?-adrenoceptors are involved in mediating the antinatriuretic and antidiuretic responses to phenylephrine in SHR. Further, high sodium intake did not significantly influence the functionality of α(?D)-adrenoceptors in mediating the adrenergically induced antinatriuresis and antidiuresis.     

Deciding whether to engage the public on health care issues

Health care decision-makers often face calls for greater public participation or see increasing public engagement as part of their organizational mandate. This article identifies six questions decision-makers must consider when deciding whether to formally engage the public or other stakeholders around a particular health care issue. These questions focus on (1) the clarity of the issue for public engagement, (2) the appropriateness of the issue for public engagement, (3) the extent to which there are viable options, (4) the role for the public, (5) whether the public likely want to be involved and (6) consideration of the expected advantages and disadvantages of public engagement.     

Intragraft immunological events associated with EBV DNAemia in liver transplant patients

Epstein-Barr virus (EBV) may cause post-transplant lymphoproliferative disorder, but most EBV infections after liver transplantation (Ltx) are clinically silent reactivations. In this study, we investigated the intragraft immunological events associated with EBV DNAemia. Altogether, 105 adult Ltx patients were monitored for EBV DNAemia. Fourteen (13%) patients developed EBV DNAemia during the first year after transplantation. Liver biopsies obtained associated with EBV DNAemia, without evidence of other herpes or hepatitis viruses or rejection, were available from five patients. The numbers of lymphocytes positive for B-cell marker (CD20), T-cell markers (CD3, CD4 and CD8) and IL-2R, adhesion molecules (ICAM-1, VCAM-1 and ELAM-1) and their ligands [lymphocyte function-associated antigen-1 (LFA-1), very late antigen (VLA-4) and Sialyl Lewis X (sLeX)] were demonstrated in liver biopsies by immunohistochemistry, and zero-biopsies from donor livers were used as controls. EBV DNAemia was associated with increased number of CD20-positive (22±30, p=0.09) and significantly increased numbers of CD3 (80±16, p=0.001)-, CD4 (23±8, p=0.009)- and CD8 (38±8, p=0.001)-positive lymphocytes in the graft. ICAM-1, but not VCAM-1 or ELAM-1, was strongly expressed and the number of LFA-1-positive cells was significantly increased (48±10, p=0.0002). Low-level EBV DNAemia was associated with B- and especially T-cell infiltration of the graft, as well as an increase in ICAM-1 and the number of LFA-1-positive cells. However, EBV DNAemia or these immunological events did not have any effect on the liver transplant.     

Persistent cytomegalovirus infection is associated with increased expression of TGF-beta1, PDGF-AA and ICAM-1 and arterial intimal thickening in kidney allografts.

BACKGROUND: Cytomegalovirus (CMV) is a suggested risk factor for the development of chronic allograft nephropathy. Transforming growth factor-beta (TGF-beta) and platelet-derived growth factor (PDGF) are important molecules in this process. We analysed the impact of persistent CMV infection in kidney allografts on the expression of growth factors, adhesion molecules and inflammation markers. METHODS: In a population of 172 renal transplant recipients, CMV was diagnosed in 82 patients by pp65 antigenaemia test and viral cultures. Biopsies taken after CMV infection were available from 48 of the 82 patients for the demonstration of CMV antigens by immunohistochemistry and in situ DNA hybridization. Biopsy material for further analyses was available from 16 CMV patients. Five patients with no previous CMV infection were used as controls. Biopsy histology was scored according to Banff 97 classification. RESULTS: In 11 out of 16 patients, persistent CMV antigens and/or DNA were demonstrated in the biopsy >2 months after the last positive finding in blood or urine. Increased expression of TGF-beta1 was recorded in tubuli and in arterial endothelium in biopsies with a positive CMV finding compared with controls. Also, the expression of PDGF-AA was increased in tubuli and somewhat in arterial endothelium in CMV-positive biopsies. The expression of intercellular adhesion molecule-1 (ICAM-1) was increased significantly in peritubular capillary endothelium. Vascular intimal thickening was increased in the biopsies with persistent CMV infection. CONCLUSIONS: Persistent CMV infection in kidney allografts was associated with increased vascular changes and increased expression of TGF-beta1, PDGF-AA and ICAM-1.