Is high-sensitivity C-reactive protein an effective screening test for cardiovascular risk?

We evaluate the suggestion that high-sensitivity C-reactive protein testing be used for risk assessment in the primary prevention of cardiovascular disease, using the criteria proposed by the Guide to Clinical Preventive Services developed by the US Preventive Services Task Force. We conclude that at present, none of the 3 major criteria--accuracy, reliability, and likelihood of beneficial intervention--are satisfied.     

Intravenous immunoglobulin and thymoglobulin facilitate kidney transplantation in complement-dependent cytotoxicity B-cell and flow cytometry T- or B-cell crossmatch-positive patients

BACKGROUND: The aim of this study was to investigate the effect of Thymoglobulin and intravenous immunoglobulin (i.v.IG) therapy on the clinical outcome of a putatively high-risk group of kidney transplant recipients who have positive B-cell complement-dependent cytotoxicity (CDC) along with positive T- or B-cell flow cytometry (FC) crossmatch results. METHODS: We prospectively studied the effects of i.v.IG and Thymoglobulin induction treatment in B-cell CDC, and T- or B-cell FC crossmatch-positive kidney transplant recipients (seven women and one man; mean age, 43+/-12 years). RESULTS: Mean peak panel-reactive antibody (PRA) was 47+/-32. Three patients had donor-specific antibody by flow PRA (two anti-DR4 and one anti-A2). Each recipient received induction treatment with i.v.IG 100 mg/kg for 3 days and Thymoglobulin 1.5 mg/kg for 5 days after transplantation. No acute cellular rejections occurred during a median follow-up of 15 months (range, 12-17 months). Only one acute humoral rejection occurred 8 days after transplantation, which responded to plasmapheresis, i.v.IG, and rituximab. One allograft was lost because of polyoma nephritis. Patient survival was 100% and allograft survival was 88%. CONCLUSION: Our results indicate that i.v.IG and Thymoglobulin induction treatment may facilitate kidney transplantation in B-cell CDC and T- or B-cell FC crossmatch-positive patients.     

A monoclonal antibody cytolytic to androgen independent DU145 and PC3 human prostatic carcinoma cells

BACKGROUND: While a range of therapeutic products is available for androgen-dependent prostatic cancer, no specific intervention modality exists for androgen-independent prostatic cancer. The objective of this research was to explore whether epitopes exist on androgen-independent prostatic DU145 cancer cells, which could be susceptible to cytotoxic action of specific antibodies. METHODS: Hybrid cell clones were developed by immunization of mice with DU145 cells and tested for immunoreactivity by solid phase EIA and cytotoxicity in vitro on DU145 in the presence of the complement, employing colorimetric quantitation by MTS (3- (4-, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-(4-sulfophenyl)-2H-tetrazolium). Binding and cytotoxicity studies were also carried out by flow-cytometry. RESULTS: Of 15 stabilized clones immunoreactive with DU145 cells, one monoclonal antibody (mAb 730) manifested cytotoxicity on DU145 cells. Approximately 80% of cells in the DU145 cell line were susceptible to lysis with this antibody at saturating levels. This figure corresponded quantitatively to the number of cells binding with this antibody as determined by Flow-cytometry. Staining with ethidium monoazide bromide (EMA) showed that the cell binding the antibody was also the one killed by the antibody in the presence of the complement. MAb 730 was also cytotoxic to PC3, another androgen-independent human prostatic cancer cell line. This antibody is devoid of classical autoantibody reactivities and does not react with normal human liver, thyroid, kidney, pancreas, and adrenal tissues, as determined by immunofluorescence. Also, it shows negative immuno-reactivity to benign glandular tissue but is observed to positively react with neoplastic prostate tissue. CONCLUSIONS: Epitopes exist on androgen-independent prostatic cancer cells that are susceptible to cytolysis by monoclonal antibodies and these could be investigated for potential immunotherapy.     

Safety of using hepatitis B virus core antibody or surface antigen-positive donors in kidney or pancreas transplantation

Hepatitis B virus core antibody (HBcAb) or surface antigen (HBsAg)-positive organ donors have the potential to transmit infection to transplant recipients. We investigated the safety of using HBcAb(+) or HBsAg(+) donors in kidney or pancreas transplant recipients with 1 yr lamivudine prophylaxis. While HBsAb(-) recipients of HBcAb(+) donors received prophylaxis, HBsAb(+) recipients did not. HBsAg(+) organs were only used in patients who were both HBcAb and HBsAb(+). Forty-six patients received HBcAb(+) and four received HBsAg(+) organs (47 kidney, two pancreas, and one kidney/pancreas). All but one recipient were HBsAg(-), 25 were HBsAb(+), and 19 HBcAb(+). During a median 36 months of follow-up (range 6-66 months), with 43 of a total 50 patients having at least 1 yr follow-up and were off lamivudine, and none of the patients developed hepatitis B viremia or seroconversion to HBsAg or HBsAb(+). These results suggest that HBcAb(+) or HBsAg(+) organs can be used safely in selected recipients with lamivudine prophylaxis without requiring hepatitis B immunglobulin.     

Determination of Optimum Machining Parameters for Face Milling Process of Ti6A14V Metal Matrix Composite

This paper shows the novel approach of Taguchi-Based Grey Relational Analysis of Ti6Al4V Machining parameter. Ti6Al4V metal matrix composite has been fabricated using the powder metallurgy route. Here, all the components of TI6Al4V machining forces, including longitudinal force (F_x), radial force (F_y), tangential force (F_z), surface roughness and material removal rate (MRR) are measured during the facing operation. The effect of three process parameters, cutting speed, tool feed and cutting depth, is being studied on the matching responses. Orthogonal design of experiment (Taguchi L9) has been adopted to execute the process parameters in each level. To validate the process output parameters, the Grey Relational Analysis (GRA) optimization approach was applied. The percentage contribution of machining parameters to the parameter of response performance was interpreted through variance analysis (ANOVA). Through the GRA process, the emphasis was on the fact that for TI6Al4V metal matrix composite among all machining parameters, tool feed serves as the highest contribution to the output responses accompanied by the cutting depth with the cutting speed in addition. From optimal testing, it is found that for minimization of machining forces, maximization of MRR and minimization of Ra, the best combinations of input parameters are the 2nd stage of cutting speed (175 m/min), the 3rd stage of feed (0.25 mm/edge) as well as the 2nd stage of cutting depth (1.2 mm). It is also found that hardness of Ti6Al4V MMC is 59.4 HRA and composition of that material remain the same after milling operation.     

Retention of ovaries and oxidative stress of surgery.

OBJECTIVE: Surgical menopause results in severe menopausal symptoms due to the sudden withdrawal of estrogen. This study evaluated the impact of surgical menopause on oxidant and antioxidant status. METHODS: Thirty eight women who underwent total hysterectomy with or without bilateral salpingo-oophorectomy were included. Oxidant status was assessed by measuring plasma levels of malondialdehyde (MDA) and antioxidant status by assessing glutathione (GSH) and estrogen levels. RESULTS: The levels of MDA were increased in all women, and GSH levels were significantly decreased in women who underwent hysterectomy alone but significantly increased in those who also had oophorectomy. Estrogen levels were increased if the ovaries were retained even in postmenopausal women, while they were decreased in the women who underwent oophorectomy. CONCLUSION: Oxidative stress of surgery, as assessed by increased MDA levels, occurred in all women. After oophorectomy, estrogen levels decreased and GSH levels increased in both premenopausal and postmenopausal women. The ovaries may therefore respond to oxidative stress of surgery by increasing estrogen production, estrogen being a better antioxidant than GSH.