Interleukin-6 predicts hypoalbuminemia, hypocholesterolemia, and mortality in hemodialysis patients

Low serum albumin and low serum cholesterol levels are among the most consistent predictors of mortality in patients with end-stage renal disease (ESRD) undergoing hemodialysis. Hypoalbuminemia is often interpreted as a marker of poor nutrition, but serum albumin and cholesterol levels can also be low as part of a cytokine-mediated acute-phase reaction to acute or chronic inflammation. Here we report the results from a 900-day prospective study designed to determine whether tumor necrosis factor-alfa (TNF-alpha) and interleukin-6 (IL-6) predict serum albumin and cholesterol levels and mortality in a group of 90 ambulatory, adult hemodialysis patients with no acute infection, hospitalization or surgery, and no known acquired immunodeficiency syndrome (AIDS), malignancy, or liver disease. Measurable levels of TNF-alpha and/or IL-6 were found in 89 of 90 patients. Significant relationships were found between TNF-alpha and IL-6 and the degree of hypoalbuminemia and dyslipoproteinemia. IL-6 was the strongest predictor of mortality in univariate and multivariate analysis, followed by age, albumin level, and body mass index (BMI). Although the cause of hypercytokinemia was not addressed in this study, the data support the view that hypoalbuminemia and hypocholesterolemia are negative acute-phase responses to inflammatory stimuli. These results suggest that efforts to identify the nature of the stimuli for cytokine production and to lower cytokine levels in hemodialysis patients might be effective in improving the survival of patients undergoing hemodialysis.     

Nonheart-beating kidney donation: current practice and future developments

BACKGROUND: Nonheart-beating kidney donation (NHBD) is gaining acceptance as a method of donor pool expansion. However, a number of practitioners have concerns over rates of delayed graft function, acute rejection, and long-term graft survival. The ethical issues associated with NHBD are complex and may be a further disincentive. Tailored strategies for preservation, viability prediction, and immunosuppression for kidneys from this source have the potential to maximize the number of available organs. This review article presents the current practice of NHBD kidney transplantation, examines the results and draws comparisons with cadaveric kidneys, and explores some areas of potential development. METHODS: A review of the current literature on NHBD kidney donation was performed. RESULTS: The renewed interest in NHBD kidneys is driven by a continuing shortfall in available organs. Those centers involved in NHBD report an increase in kidney transplants of the order of 16% to 40% and there is no evidence that the financial costs are higher with NHBDs. The majority of experience comes from Maastricht category 2 NHBDs, where an estimation of warm time is possible. This is generally limited to 40 minutes. There are variations in the technique for kidney preservation prior to retrieval, but most centers use an aortic balloon catheter. Much work has looked at the ideal technique for kidney preservation prior to implantation. Evidence suggests that machine perfusion produces the best initial function rates, decreased use of adjuvant immunotherapy and fewer haemodialysis sessions than static cold storage. CONCLUSION: Despite being associated with poorer initial graft function, the long-term allograft survival of NHBD kidneys does not differ from the results of transplantation from cadaveric kidneys. Further, serum creatinine levels are generally equivalent. Constant reassessment of the ethical issues is required for donation to be increased while respecting public concerns. Use of viability assessment and tailoring of immune suppression for NHBD kidneys may allow a further increase in donation from this source.     

Cardiovascular risk,obesity, and myocardial blood flow in postmenopausal women

Background. This study was designed to determine whether overweight or obese status is independently associated with myocardial flow reserve (MFR), an established predictor of cardiovascular mortality, in a group of postmenopausal women with no previous cardiovascular disease. Postmenopausal women are the largest group of overweight and physically inactive individuals in the United States. Increased body mass index (BMI) is consistently associated with increased cardiovascular mortality in this population. Whether this is because of obesity itself or the accompanying increase in cardiovascular risk factors (CRFs) remains controversial. Methods. We examined the relationship of myocardial blood flow (MBF), coronary vascular resistance, and MFR to BMI in 60 postmenopausal women with no coronary heart disease. Subjects underwent dynamic N-13 ammonia positron emission tomography for the measurement of MBF and MFR. Baseline demographics, CRF, and hemodynamic parameters were recorded for each subject. Datasets were divided into 3 groups according to BMI: normal (18 to 24), overweight (25 to 29), and obese (≥30). Results. The overweight and obese groups showed significantly higher resting MBF and lower MFR than the normal-weight group (both P<.001), even after adjusting for CRF. A further analysis of subjects without any CRF (n=35) showed that the MFR remained significantly lower in the obese compared with normal-weight subjects (P=.05). Levels of known markers of vascular inflammation (high-sensitivity C-reactive protein and homocysteine) and high-density lipoprotein cholesterol levels correlated with declining MFR. Conclusions. These findings provide a mechanistic link between obesity and coronary heart disease in this population. This study was funded by a Veterans Health Administration MERIT Review Award. C.S.D. is on the Speaker’s Bureau at Pfizer, Inc., and has received grant support from Pfizer, Inc., Eli Lilly & Co., and the Veterans Health Administration.     

Pregnancy after TVT-O: case report and literature review

A 37-year-old woman previously treated with TVT-O developed recurrent symptoms of stress urinary incontinence during pregnancy. Symptoms started to develop later in the second trimester and progressed gradually to affect her quality of life at the end of pregnancy. In the event she had a very quick spontaneous vaginal delivery at 40 weeks’ gestation. Postnatal physiotherapy successfully controlled the incontinence symptoms and urodynamic studies demonstrated no incontinence with a stable bladder and a normal flow rate. The patient remains well 2 years following delivery with no further treatment.     

Enhancement of growth of aerobic, anaerobic, and facultative bacteria in mixed infections with anaerobic and facultative gram-positive cocci

The potential for mutual enhancement of growth of seven strains of anaerobic and facultative gram-positive cocci (AFGPC), seven aerobic and facultative organisms, and two Bacteroides spp. commonly isolated with AFGPC in mixed infection was evaluated. Enhancement was studied by measuring the relative increase in the colony-forming units of the two bacterial components inducing subcutaneous abscesses in mice. Of the 56 combinations, AFGPC were enhanced in 6 and inhibited in 1. The aerobic and facultative bacteria were enhanced in 32 of the 42 combinations and depressed in none. The Bacteroides spp. were enhanced in 12 of the 14 combinations and suppressed in none. The organisms uniformly enhanced by AFGPC were Group A streptococci, Pseudomonas aeruginosa, and Bacteroides fragilis (all seven instances), followed by Escherichia coli (six of seven instances), Bacteroides asaccharolyticus and Klebsiella pneumoniae (five instances each), Staphylococcus aureus (four instances), and Group D streptococci (three instances). It is apparent that in mixed infection with AFGPC the rate of growth of Bacteroides spp. and facultative and aerobic bacteria is enhanced much more than the rate of growth of AFGPC.     

Postnatal corneal transparency, keratocyte cell cycle exit and expression of ALDH1A1

PURPOSE: Recent studies have shown that rabbit corneal keratocytes abundantly express two water-soluble proteins, transketolase (TKT) and aldehyde dehydrogenase class 1A1 (ALDH1A1), in vivo and that these proteins may contribute to corneal transparency at the cellular level. The purpose of this study was to determine the relationship between the expression of these proteins and the development of postnatal corneal transparency. METHODS: Rabbits 1 day to 42 days of postnatal age were evaluated by in vivo confocal microscopy (CM) to measure corneal epithelial thickness, stromal thickness, and corneal haze. Selected corneas were then processed for immunocytochemistry and Western and Northern blot analyses, to determine stromal cell density, cell cycle entry, and expression of ALDH1A1 and TKT. RESULTS: Quantitative measurement of corneal haze showed that the postnatal cornea was hazy after birth and became transparent during the first weeks after eyelid opening. Development of transparency was associated with decreased cytoplasmic light-scattering from postnatal corneal stromal cells, with the appearance of nuclear light-scattering after eyelid opening. Four days after birth, stromal cell density decreased rapidly, and the cells became quiescent, showing decreased staining by Ki67, a cell cycle marker. Whereas expression of TKT showed a gradual increase after birth, ALDH1A1 showed a marked increase after eyelid opening, and the combined expression significantly correlated with the reduction in light-scattering by postnatal stromal cells. CONCLUSIONS: The data suggest that development of postnatal corneal transparency is associated with decreased keratocyte density and quiescence and the expression of TKT/ALDH1A1.     

MR imaging of facial nerve enhancement in Bell palsy or after temporal bone surgery

The authors evaluated magnetic resonance (MR) images obtained with intravenously administered gadolinium in ten patients who had facial paralysis and no facial nerve tumor. In patients with either Bell palsy (four patients) or facial paralysis after temporal bone surgery (six patients), intratemporal facial nerve enhancement was seen. Facial nerve enhancement on MR images proved to be a nonspecific finding.