Spontaneous tumor cytolysis mediated by inflammatory neutrophils: dependence upon divalent cations and reduced oxygen intermediates

The role of divalent cations and reactive products of the respiratory burst were investigated in spontaneous tumor lysis mediated by inflammatory neutrophils (PMNs). Murine peritoneal PMNs, obtained five hours after intraperitoneal injection of bacteria, conjugated and lysed teratocarcinoma cells in chromium release and single-cell cytotoxicity assays. The presence of extracellular magnesium was required and was sufficient for tumor cell binding to PMNs. Postbinding lytic events depended upon the simultaneous presence of extracellular calcium and magnesium. Catalase and superoxide dismutase inhibited postbinding lytic events, indicating that production of reduced oxygen moieties was important. Scavengers of hydroxyl radicals could inhibit tumor cell binding, but none could affect postbinding lytic events. Neither could inhibitors of myeloperoxidase decrease tumor lysis. The ability of conjugating PMNs to lyse their bound targets correlated with their reduction of nitro blue tetrazolium (NBT). Optimal concentrations of phorbol myristate acetate (PMA) markedly increased the NBT positivity of PMNs and the killing of bound tumor cells. Even with optimal stimulation of the respiratory burst, however, there was still a significant number (19%) of bound targets that escaped lysis, suggesting active resistance to oxygen-mediated tumor cell injury.     

Persistent inhibition of Candida albicans biofilm and hyphae growth on titanium by graphene nanocoating

ObjectivesCandida albicanscolonizes biomaterial surfaces and are highly resistant to therapeutics. Graphene nanocoating on titanium compromises initial biofilm formation. However, its sustained antibiofilm potential is unknown. The objective of this study was to investigate the potential of graphene nanocoating to decrease long-term fungal biofilm development and hyphae growth on titanium.MethodsGraphene nanocoating was deposited twice (TiGD) or five times (TiGV) on grade 4 titanium with vacuum assisted technique and characterized with Raman spectroscopy and atomic force microscope. The biofilm formation and hyphae growth of C. albicans was monitored for seven days by CFU, XTT, confocal, mean cell density and scanning electronic microscopy (SEM). Uncoated titanium was the Control. All tests had three independent biological samples and were performed in independent triplicates. Data was analyzed with one- or two-way ANOVA and Tukey's HSD (α = 0.05).ResultsBoth TiGD and TiGV presented less biofilms at all times points compared with Control. The confocal and SEM images revealed few adhered cells on graphene coated samples, absence of hyphae and no features of a mature biofilm architecture. The increase in number of layers of graphene nanocoating did not improve its antibiofilm potential.SignificanceThe graphene nanocoating exerted a long-term persistent inhibitory effect on the biofilm formation on titanium. The fewer cells that were able to attach on graphene coated titanium were scattered and unable to form a mature biofilm with hyphae elements. The findings open opportunities to prevent microbial attachment and proliferation on implantable materials without the use of antibiotics.     

Retrograde Inversion Stripping as a Complication of the Clarivein? Mechanochemical Venous Ablation Procedure

The endovenous revolution has accelerated the development of new techniques and devices for the treatment of varicose veins. The ClariVein^® mechanochemical ablation device offers tumescentless treatment with a rotating ablation tip that can theoretically become stuck in tissue. We present the first report of retrograde stripping of the small saphenous vein without anaesthesia following attempted use of the ClariVein^® device, without adverse sequelae.     

Mycobacterial infections in renal transplant recipients: report of five cases and review of the literature

Five cases of mycobacterial disease in renal transplant recipients at the Hospital of the University of Pennsylvania were studied. In addition, another 42 cases reported in the literature were reviewed. Disseminated tuberculosis was common, accounting for 20 of the 47 cases. Infection with nontuberculous mycobacteria was also common, accounting for 16 cases. In two cases, a tuberculin nonreactor developed tuberculosis after receiving a transplant from a donor who was a reactor; these cases may represent reactivation tuberculosis in the transplanted kidney. A number of cases appeared preventable. For example, two patients at the Hospital of the University of Pennsylvania had evidence of previous tuberculosis but had not received isoniazid prophylaxis. On the basis of a survey of 26 transplantation centers, it was estimated that the minimal tuberculosis rate among renal transplant recipients is 480 cases per 100,000, vs. 13.1 per 100,000 in the general population.     

Human apolipoprotein A-IV metabolism within triglyceride-rich lipoproteins and plasma

In order to investigate the metabolism of apo A-IV within TRL and plasma, we assessed TRL and plasma apo A-IV kinetics in 19 and 4 subjects, respectively, consuming an average US diet for a 6-week period. At the end of this diet study, each subject received a primed-constant infusion of deuterated leucine over a 15 h time period with hourly feeding, and blood samples were drawn at 10 time points. TRL was separated by ultracentrifugation. Apo A-IV was isolated by immunoprecipitation and/or SDS-PAGE. Apo A-IV concentrations were determined by immunoelectrophoresis. Stable isotope tracer/tracee ratios were measured by gas chromatography/mass spectrometry, and the data were analyzed by multicompartmental modeling. The mean concentrations of plasma and TRL apo A-IV during the isotope infusion period were 21.0+/-3.2 and 0.66+/-0.25 mg/dl, respectively, and these values were 11.5 and 30.5% higher than those of fasting samples. The mean TRL and plasma apo A-IV residence times (RT) were 1.97+/-0.57 and 2.71+/-0.65 days, and transport rates (TR) were 0.17+/-0.19 and 3.90+/-1.24 mg/kg per day, respectively. There were significant correlations between TRL apo A-IV concentrations and TR (r(2)=0.79, P<0.001), and between TRL apo A-IV pool size and TRL cholesterol levels (r(2)=0.29, P=0.02). Our data indicated that; (1) TRL apo A-IV has a RT of 1.97 days which is similar to that earlier reported for HDL apo A-IV; (2) Apo A-IV recirculates between TRL and other slowly turning over pools; (3) the primary determinant of TRL apo A-IV levels is its TR; and (4) there is no correlation between TRL apo A-IV and apo B48 fractional catabolism in TRL.     

Hepcidin,a putative mediator of anemia of inflammation,is a type II acute-phase protein

Hepcidin is a liver-made peptide proposed to be a central regulator of intestinal iron absorption and iron recycling by macrophages. In animal models, hepcidin is induced by inflammation and iron loading, but its regulation in humans has not been studied. We report that urinary excretion of hepcidin was greatly increased in patients with iron overload, infections, or inflammatory diseases. Hepcidin excretion correlated well with serum ferritin levels, which are regulated by similar pathologic stimuli. In vitro iron loading of primary human hepatocytes, however, unexpectedly down-regulated hepcidin mRNA, suggesting that in vivo regulation of hepcidin expression by iron stores involves complex indirect effects. Hepcidin mRNA was dramatically induced by interleukin-6 (IL-6) in vitro, but not by IL-1 or tumor necrosis factor alpha (TNF-alpha), demonstrating that human hepcidin is a type II acute-phase reactant. The linkage of hepcidin induction to inflammation in humans supports its proposed role as a key mediator of anemia of inflammation.     

Prevalence and severity of urinary incontinence in elderly Mexican-American women

OBJECTIVES: To measure prevalence and characteristics of urinary incontinence in older Mexican-American women. DESIGN: Cross-sectional analysis of a longitudinal survey of a representative sample of older Mexican Americans. SETTING: Five southwestern states in the United States. PARTICIPANTS: A total of 1589 Mexican-American women, aged 65 and older who were part of the Hispanic Established Population for the Epidemiologic Study of the Elderly. MEASUREMENTS: Self-reported psychosocial, demographic, and health variables; self-reported history of symptoms of urinary incontinence. RESULTS: Two hundred thirty-nine (15%) of the 1589 Mexican-American women reported having urinary incontinence. Almost 33% reported urge incontinence symptoms, 10% reported stress incontinence symptoms, and 42% had symptoms suggestive of mixed incontinence. Thirty-five percent of subjects reported incontinence episodes with moderate to large amounts of urine loss, and 15% reported that their urinary symptoms kept them from engaging in social activities. Age and body mass index were risk factors for incontinence (P=.02 and P=.03, respectively). CONCLUSION: This is the first community-based survey examining rates of urinary incontinence in Mexican-American women. The prevalence of urinary incontinence may be lower in older Mexican-American women than in the general population. They may also have a higher percentage of urge as opposed to stress incontinence symptoms and may suffer from moderate to large volumes of urine loss associated with their incontinence episodes.     

Effect of Physician Delegation to Other Healthcare Providers on the Quality of Care for Geriatric Conditions

The quality of care of older adults in the United States has been consistently shown to be inadequate. This gap between recommended and actual care provides an opportunity to improve the value of health care for older adults. Prior work from the Assessing Care of Vulnerable Elders (ACOVE) investigators first defined, and then sought to improve, clinical practice for common geriatric conditions. A critical component of the ACOVE intervention for practice improvement was an emphasis on the delegation of specific care processes, but the independent effect of delegation on the quality of care has not been evaluated. This study analyzed the pooled results of prior ACOVE projects from 1998 to 2010. Totaled, these studies included 4,776 individuals aged 65 and older of mixed demographic backgrounds and 16,204 ACOVE quality indicators (QIs) for three geriatric conditions: falls, urinary incontinence, and dementia. In unadjusted analyses, QI pass probabilities were 0.36 for physician‐performed tasks, 0.55 for nurse practitioner (NP)‐, physician assistant (PA)‐, and registered nurse (RN)‐performed tasks; and 0.61 for medical assistant– and licensed vocational nurse–performed tasks. In multiply adjusted models, the independent pass‐probability effect of delegation to NPs, PAs, and RNs was 1.37 (P = .05). These findings suggest that delegation of selected tasks to nonphysician healthcare providers is associated with higher quality of care for these geriatric conditions in community practices and supports the value of interdisciplinary team management for common outpatient conditions in older adults.