The Broad Spectrum of Quality in Deceased Donor Kidneys

The quality of the deceased donor organ clearly is one of the most crucial factors in determining graft survival and function in recipients of a kidney transplant. There has been considerable effort made towards evaluating these organs culminating in an amendment to allocation policy with the introduction of the expanded criteria donor (ECD) policy.
Our study, from first solitary adult deceased donor transplant recipients from 1996 to 2002 in the National Scientific Transplant Registry database, presents a donor kidney risk grade based on significant donor characteristics, donor–recipient matches and cold ischemia time, generated directly from their risk for graft loss. We investigated the impact of our donor risk grade in a naïve cohort on short- and long-term graft survival, as well as in subgroups of the population.
The projected half-lives for overall graft survival in recipients by donor risk grade were I (10.7 years), II (10.0 years), III (7.9 years), IV (5.7 years) and V (4.5 years). This study indicates that there is great variability in the quality of deceased donor kidneys and that the assessment of risk might be enhanced by this scoring system as compared to the simple two-tiered system of the current ECD classification.     

Long-term results of DeVega tricuspid annuloplasty

DeVega tricuspid annuloplasty was performed in 74 patients undergoing mitral or mitral and aortic valve replacement between January, 1972, and December, 1985. Sixty-two hospital survivors have been followed up for a mean of 85.3 +/- 6.6 months. Actuarial survival at 14 years was 71.5 +/- 8.2%. None of the late deaths was related to the tricuspid annuloplasty. Three patients required tricuspid valve replacement for recurrence of tricuspid regurgitation (0.68% per annum). Eleven asymptomatic patients studied hemodynamically at a mean period of 53 months after the operation showed maintenance of the hemodynamic improvement. We recommend DeVega annuloplasty as the method of choice for moderate to severe tricuspid regurgitation in the absence of an organically diseased or deformed valve.     

Safety and efficacy of atorvastatin in heart transplant recipients.

BACKGROUND: Pravastatin and simvastatin prolong survival and reduce transplant-related coronary vasculopathy, although low-density lipoprotein (LDL) lowering with these agents is only modest. The objective of this study was to assess the safety of moderate dose atorvastatin and its efficacy when prior treatment with another statin had failed to lower LDL to < 100 mg/dl. METHODS: Data from 185 patients were retrospectively evaluated for adverse events, duration of exposure (person-days), and the mean atorvastatin dose exposure. Changes in lipid parameters, and prednisone and cyclosporine doses were determined. RESULTS: Safety: 48 patients received atorvastatin for 24,240 person-days at a mean dose exposure of 21 +/- 10 mg. Rhabdomyolysis, myositis, myalgias, and hepatotoxicity occurred in 0, 2, 2, and 0 patients, respectively. All events occurred at the 10-mg dose, within the first 3 months, and were rapidly reversible with atorvastatin discontinuation. Efficacy: Thirty-four patients evaluable for efficacy analyses had a pre-atorvastatin LDL of 145 +/- 38 mg/dl on the following statins: pravastatin (n = 30, 40 +/- 0mg), fluvastatin (n = 3, 33 +/- 12 mg), simvastatin (n = 1, 40 mg). After atorvastatin (21 +/- 9 mg/day) for 133 +/- 67 days, LDL was reduced to 97 +/- 24 mg/dl (relative reduction 31 +/- 20%, p < 0.0001). At the end of the observation period (418 +/- 229 days, atorvastatin final dose 24 +/- 14 mg/day), LDL was further decreased to 88 +/- 23 mg (relative reduction 37 +/- 17%, p < 0.0001). CONCLUSION: Atorvastatin, when used at moderate doses and with close biochemical and clinical monitoring, appears to be safe and is effective in aggressively lowering LDL in heart transplant recipients when treatment with other statins has failed to achieve LDL goals.     

The predictive value of p16(INK4a) and hybrid capture 2 human papillomavirus testing for high-grade cervical intraepithelial neoplasia

We performed p16(INK4a) immunocytochemical analysis and Hybrid Capture 2 (HC2; Digene, Gaithersburg, MD) high-risk HPV testing on 210 abnormal SurePath (TriPath Imaging, Burlington, NC) Papanicolaou specimens diagnosed as low-grade squamous intraepithelial lesion (LSIL) or high grade squamous intraepithelial lesion (HSIL). The results were compared with 121 follow-up biopsy specimens. p16(INK4a) was positive in 57.9% of women with LSIL compared with 97.1% of women with HSIL. In contrast, HC2 testing was positive in 85.0% of women with LSIL and 86.4% of women with HSIL. The differences in the positive rates for16(INK4a) between LSIL and HSIL was significant (P < .001), whereas, for HC2, it was not (P = .264). In patients who had cervical biopsies following a cytologic diagnosis of LSIL, the positive predictive value (PPV) of p16(INK4a) for a biopsy of cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3; 33.3%) was significantly higher than the PPV of HC2 results (21.2%) (P < .001). Using liquid-based cytology specimens, p16(INK4a) immunocytochemical analysis has a higher PPV than reflex HC2 HPV testing for identifying CIN2/3 among patients with LSIL and might be useful for selecting patients with LSIL for colposcopy.     

Growth of Pakistani children in relation to the 1990 growth standards

This study was designed to compare the growth of Pakistani schoolchildren in the UK with the 1990 UK growth standards. Measurements of height, weight, and sitting height were performed on 785 Pakistani schoolchildren aged 5-14 years with the mean values for each age and sex being plotted on the UK growth standards. The results were expressed as SD scores relative to the 1990 reference data. The mean height for the boys was only 0.2 SD scores below the mean for the new growth standards with the mean height for the girls being 0.4 SD scores below the mean. The mean values for weight and body mass index were 0.3 and 0.5 SD scores less than the mean for boys and girls respectively. This study demonstrates that the growth of Pakistani schoolchildren in the UK is comparable to the 1990 UK growth standards with only minor differences. It is not safe to assume that short stature or low body weight in a Pakistani child is due to his or her ethnic background.     

Determination of malondialdehyde-induced DNA damage in human tissues using an immunoslot blot assay

Malondialdehyde (MDA) is a product of lipid peroxidation and prostaglandin biosynthesis. It is mutagenic and carcinogenic and the major adduct formed by reaction with DNA, a highly fluorescent pyrimidopurinone (M1-dG), has been detected in healthy human liver and leukocyte DNA. Analytical methods used so far for the detection of M1- dG have not been applied to a large number of individuals or variety of samples. Often, only a few microg of DNA from human tissues are available for analysis and a very sensitive assay is needed in order to detect background levels of M1-dG in very small amounts of DNA. In this paper, the development of an immunoslot blot (ISB) assay for the measurement of MI-dG in 1 microg of DNA is described. The limit of detection of the assay is 2.5 adducts per 10(8) bases. A series of human samples were analysed and levels of 5.6-9.5 (n = 8) and 3.1-64.3 (n = 42) of M1-dG per 10(8) normal bases were detected in white blood cell and gastric biopsy DNA, respectively. Results on four human samples were compared with those obtained using an HPLC/32P-post- labelling (HPLC/PPL) method previously developed and indicated a high correlation between M1-dG levels measured by the two assays. The advantages of ISB over other assays including HPLC/PPL, such as the possibility of analysing 1 microg DNA/sample and the fact that it is less time-consuming and laborious, means that it can be more easily used for routine analysis of a large number of samples in biomonitoring studies.      

Laparoscopic donor nephrectomy: impact on an established renal transplant program

The current disparity of viable organs and patients in need of a transplant has been an impetus for innovative measures. Live donor renal transplantation offers significant advantages compared with cadaveric donor transplantation: increased graft and patient survival, diminution in incidence of delayed graft function, acute tubular necrosis (ATN), and reduction in waiting time. Notwithstanding these gains live donors continue to be underutilized and account for only approximately one quarter of all renal transplants performed in the United States. It has been felt that inherent disincentives to live donation have slowed its growth. These include degree and duration of postoperative pain and convalescence, child care concerns, cosmetic concerns, and time until return to full activities and employment. In an attempt to curtail the disincentives to live donation, laparoscopic live donation (laparoscopic donor nephrectomy; LDN) was developed. The purpose of this study was to compare the results of our first 25 laparoscopic nephrectomies (performed over a 10-month period from September 1998 through July 1999) with the previous 25 standard open donor nephrectomies (ODNs) completed over the past 3 years. We conducted a retrospective review of all donor nephrectomies and recipient pairs performed over the past 3 years. End points included sex, operative time, length of stay, immediate and long-term renal function, and willingness to donate. There were no differences in demographics of the ODN versus the LDN group. The average length of stay was 2.48+/-0.72 days for the LDN versus 4.08+/-0.28 days for the ODN. ODN and LDN have comparable short- and long-term function with no delayed graft function and no complications. Growth of living donor transplant has increased from 16 per cent of all kidney transplants performed in 1995 to 23 per cent in 1999. We conclude that LDN is a viable alternative to the standard donor operation. LDN has had a positive impact on the donor pool by minimizing disincentives to live donation. With the initiation of our laparoscopic program the number of LDNs has increased. Presently the live donor pool is the most viable alternative to significantly increase the number of kidneys for transplantation.