Home About us Contact
|
Home About us Contact | ||
|
|
||
Baseline Levels (baseline + level)
Selected AbstractsMuscle Strength After Resistance Training Is Inversely Correlated with Baseline Levels of Soluble Tumor Necrosis Factor Receptors in the Oldest OldJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 2 2004Helle Bruunsgaard MD Objectives:, To test the hypothesis that physical exercise induces an antiinflammatory response that is associated with reduced chronic activation of the tumor necrosis factor (TNF)-alpha system in frail elders and that the increase in muscle strength after resistance training is limited by systemic low-grade inflammation. Design:, A 12-week controlled resistance-training study. Setting:, Nursing homes in Copenhagen, Denmark. Participants:, Twenty-one frail nursing home residents aged 86 to 95 completed the study. Intervention:, Ten participants were randomized to a program of resistance training of knee extensors and flexors three times a week for 12 weeks; the remaining 11 participants served as a control group who joined social activities supervised by an occupation therapist. Measurements:, Muscle strength, plasma levels of TNF-,, soluble TNF receptor (sTNFR)-1, and interleukin (IL)-6 were measured before and at the end of the intervention period. Results:, The training program improved muscle strength but did not affect plasma levels of TNF-, and sTNFR-I or IL-6. However, plasma levels of sTNFR-I at baseline were inversely correlated with the increase in muscle strength. Conclusion:, Low-grade activation of the TNF system could limit the increase in muscle strength after resistance training in the oldest old. Furthermore, data suggest that theantiinflammatory response induced by 12 weeks of resistance training is not sufficient to reduce chronic activation of the TNF system, but the small sample size limited this interpretation. [source] Urinary cysteinyl leukotriene E4 significantly increases during pain in children and adults with sickle cell diseaseAMERICAN JOURNAL OF HEMATOLOGY, Issue 4 2009Joshua J. Field Baseline level of the cysteinyl leukotriene (CysLT), leukotriene E4 (LTE4), is associated with an increased pain rate in children and adults with sickle cell disease (SCD). To provide additional evidence for a role of CysLTs in the pathogenesis of vaso-occlusion, we tested the hypothesis that LTE4 levels will increase within an individual during painful episodes compared to baseline. In a cohort of 19 children and adults with SCD, median LTE4 levels increased from 82.36 pg/mg creatinine at baseline to 162.81 pg/mg creatinine during a painful episode (P < 0.001). These data further support a contribution of CysLTs to the process of vaso-occlusion. Am. J. Hematol., 2009. © 2009 Wiley-Liss, Inc. [source] Stress-induced responses of human skin fibroblasts in vitro reflect human longevityAGING CELL, Issue 5 2009Pim Dekker Summary Unlike various model organisms, cellular responses to stress have not been related to human longevity. We investigated cellular responses to stress in skin fibroblasts that were isolated from young and very old subjects, and from offspring of nonagenarian siblings and their partners, representatives of the general population. Fibroblasts were exposed to rotenone and hyperglycemia and assessed for senescence-associated ,-galactosidase (SA-,-gal) activity by flow cytometry. Apoptosis/cell death was measured with the Annexin-V/PI assay and cell-cycle analysis (Sub-G1 content) and growth potential was determined by the colony formation assay. Compared with fibroblasts from young subjects, baseline SA-,-gal activity was higher in fibroblasts from old subjects (P = 0.004) as were stress-induced increases (rotenone: P < 0.001, hyperglycemia: P = 0.027). For measures of apoptosis/cell death, fibroblasts from old subjects showed higher baseline levels (Annexin V+/PI+ cells: P = 0.040, Sub-G1: P = 0.014) and lower stress-induced increases (Sub-G1: P = 0.018) than fibroblasts from young subjects. Numbers and total size of colonies under nonstressed conditions were higher for fibroblasts from young subjects (P = 0.017 and 0.006, respectively). Baseline levels of SA-,-gal activity and apoptosis/cell death were not different between fibroblasts from offspring and partner. Stress-induced increases were lower for SA-,-gal activity (rotenone: P = 0.064, hyperglycemia: P < 0.001) and higher for apoptosis/cell death (Annexin V+/PI, cells: P = 0.041, Annexin V+/PI+ cells: P = 0.008). Numbers and total size of colonies under nonstressed conditions were higher for fibroblasts from offspring (P = 0.001 and 0.024, respectively) whereas rotenone-induced decreases were lower (P = 0.008 and 0.004, respectively). These data provide strong support for the hypothesis that in vitro cellular responses to stress reflect the propensity for human longevity. [source] Tumor necrosis factor- , and transforming growth factor- , reflect severity of liver damage in primary biliary cirrhosisJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 2 2002MANUELA NEUMAN Abstract Background and Aims The pathogenesis of primary biliary cirrhosis (PBC) is unknown. The role of cytokines such as tumor necrosis factor-, (TNF-,) and transforming growth factor-, (,GF-,), and the effect of ursodeoxycholic acid (UDCA) in modifying the cytokine environment in patients with PBC has remained largely unstudied. Our aims were to determine: (i) the relationship between serum levels of TNF-, and TGF-, and the severity of PBC; and (ii) the effects of UDCA therapy on TNF-, and TGF-, levels in patients with PBC. Methods We studied 90 patients who had been treated with UDCA (53 patients) or placebo (37 patients) for 2 years as part of a randomized, double-blind, controlled trial. Patients were divided into histological stage I/II or stage III/IV disease. Serum TNF-, and TGF-, levels were quantified by enzyme-linked immunoabsorbent assay. Results Baseline levels of TNF-, were significantly greater in patients with stage III/IV compared to stage I/II disease. After 2 years of treatment with UDCA, patients showed a significantly greater decrease in TNF-, levels and progression risk score compared to placebo-treated patients. TNF-, and TGF-, levels were significantly reduced compared to baseline levels in the UDCA-treated group after 2 years, while there was no significant change in the levels of placebo-treated patients. Conclusions Serum TNF-, and TGF-, levels may reflect severity of disease in patients with PBC. The beneficial effects of UDCA therapy may be explained by lowering serum levels of these two cytokines. [source] Urotensin II: a novel vasoactive mediator linked to chronic liver disease and portal hypertensionLIVER INTERNATIONAL, Issue 9 2007William Kemp Abstract Background/Aims: Urotensin II (UII) is recognised as the most potent human vasoconstrictor; however, its role in chronic liver disease (CLD) is unknown. Aim: We sought to determine serum UII levels in CLD and explore its relationship with clinical features and outcomes of patients with CLD and portal hypertension. Methods: UII was analysed by radio-immunoassay on cirrhotic patients undergoing hepatic venous pressure gradient (HVPG) determination and age- and sex-matched controls. Follow-up data were prospectively recorded. Results: From 1997 to 2004, 80 patients (male/female: 74/6) underwent a total of 94 HVPG assessments. UII was higher in cirrhotic patients compared with controls (2.05±0.06 and 1.55±0.09 pmol/L, P<0.001) and was correlated with HVPG (r=+0.35, P=0.001) and severity of CLD (r=+0.6, P<0.001). UII was higher in patients who developed refractory ascites (2.45±0.13 vs. 1.7±0.12 pmol/L, P<0.001) and in those who died during the follow-up period (2.27±0.15 pmol/L vs. 1.95±0.08 pmol/L, P<0.05). Conclusion: Serum UII is elevated in patients with CLD, and is associated with the severity of the underlying liver disease and the degree of portal hypertension. Baseline levels can predict future complications such as refractory ascites and patient survival. [source] Foster mother care but not prenatal morphine exposure enhances cocaine self-administration in young adult male and female ratsDEVELOPMENTAL PSYCHOBIOLOGY, Issue 5 2007I. Vathy Abstract The present study was designed to investigate cocaine self-administration in adult male and female rats exposed prenatally to morphine. Pregnant dams were injected two times a day with either saline, analgesic doses of morphine or no drug at all (controls) on gestation Days 11,18. One day after birth, litters were cross-fostered such that control dams were paired with one another and their litters were crossed; saline- and morphine-treated dams were paired and half of each saline litter was crossed with half of each morphine litter. Thus, each mother (control, saline, and morphine) raised half of her own and half of the adopted litter. At the age of 60 days, males and females were trained first to lever press for sucrose pellets and then for cocaine. Once the lever-pressing behavior was learned and baseline level of this activity was established, animals received a cocaine (.5 mg/kg per infusion) reward for each correct response on the active lever during the next 9-day session. The data demonstrate that adult control, saline- and morphine-exposed male rats self-administer cocaine at a similar rate independent of their prenatal treatment. Adult female rats self-administer cocaine at a higher rate than male rats. Further, saline- and morphine-exposed females in diestrus self-administer more than females in proestrus phase of the estrous cycle, while control females show no such differences. In addition, fostering induces increase in cocaine self-administration in all groups of male rats regardless of prenatal drug exposure. In females, the only fostering-induced increase is in prenatally saline-exposed female rats raised by morphine-treated foster mother. Thus, our results suggest that the prenatal drug exposure does not induce changes in lever-pressing behavior for cocaine reward in adult male and female rats, but it sensitizes the animals to postnatal stimuli such as gonadal hormones and/or rearing conditions that result in increased drug self-administration. © 2007 Wiley Periodicals, Inc. Dev Psychobiol 49: 463-473, 2007. [source] Genetic determinants of adult hippocampal neurogenesis correlate with acquisition, but not probe trial performance, in the water maze taskEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2002G. Kempermann Abstract A number of reports have indicated that adult neurogenesis might be involved in hippocampal function. While increases in adult neurogenesis are paralleled by improvements on learning tasks and learning itself can promote the survival of newly generated neurons in the hippocampus, a causal link between learning processes and adult hippocampal neurogenesis is difficult to prove. Here, we addressed the related question of whether the baseline level of adult neurogenesis is predictive of performance on the water maze task as a test of hippocampal function. We used ten strains of recombinant inbred mice, based on C57BL/6, which are good learners and show high baseline levels of neurogenesis, and DBA/2, which are known to be poor learners and which exhibit low levels of adult neurogenesis. Two of these strains, BXD-2 and BXD-8, showed a 26-fold difference in the number of newly generated neurons per hippocampus. Over all strains, including the parental strains, there was a significant correlation between the number of new neurons generated in the dentate gyrus and parameters describing the acquisition of the water maze task (slope of the learning curves). Similar results were seen when the parental strains were not included in the analysis. There was no correlation between adult hippocampal neurogenesis and probe trial performance, performance on the rotarod, overall locomotor activity, and baseline serum corticosterone levels. This result supports the hypothesis that adult neurogenesis is involved in specific aspects of hippocampal function, particularly the acquisition of new information. [source] COSTS OF AN INDUCED IMMUNE RESPONSE ON SEXUAL DISPLAY AND LONGEVITY IN FIELD CRICKETSEVOLUTION, Issue 10 2004Alain Jacot Abstract Immune system activation may benefit hosts by generating resistance to parasites. However, natural resources are usually limited, causing a trade-off between the investment in immunity and that in other life-history or sexually selected traits. Despite its importance for the evolution of host defense, state-dependent fitness costs of immunity received little attention under natural conditions. In a field experiment we manipulated the nutritional condition of male field crickets Gryllus campestris and subsequently investigated the effect of an induced immune response through inoculation of bacterial lipopolysaccharides. Immune system activation caused a condition-dependent reduction in body condition, which was proportional to the condition-gain during the preceding food-supplementation period. Independent of nutritional condition, the immune insult induced an enduring reduction in daily calling rate, whereas control-injected males fully regained their baseline level of sexual signaling following a temporary decline. Since daily calling rate affects female mate choice under natural conditions, this suggests a decline in male mating success as a cost of induced immunity. Food supplementation enhanced male life span, whereas the immune insult reduced longevity, independent of nutritional status. Thus, immune system activation ultimately curtails male fitness due to a combined decline in sexual display and life span. Our field study thus indicates a key role for fitness costs of induced immunity in the evolution of host defense. In particular, costs expressed in sexually selected traits might warrant the honest advertisement of male health status, thus representing an important mechanism in parasite-mediated sexual selection. [source] Serum levels of IL-18 and sIL-2R in patients with alopecia areata receiving combined therapy with oral cyclosporine and steroidsEXPERIMENTAL DERMATOLOGY, Issue 2 2010Deborah Lee Please cite this paper as: Serum levels of IL-18 and sIL-2R in patients with alopecia areata receiving combined therapy with oral cyclosporine and steroids. Experimental Dermatology 2010; 19: 145,147. Abstract:, This study was to determine which immunologic factors contribute to the prognosis of patients with alopecia areata (AA) who were receiving oral cyclosporine A and methylprednisolone. Patients with >25% hair regrowth were defined as responders, and patients exhibiting ,25% regrowth were poor-responders. The serum levels of IL-18 and soluble IL-2 receptor (sIL-2R) were measured at baseline in 21 patients with AA and 22 control subjects. The mean serum level of IL-18 in the patients with extensive AA was significantly higher than that in the control subjects. The mean serum concentration of sIL-2R in the AA patients significantly decreased after 1 month of treatment. The mean basal serum level of IL-18 was highest in the responder, whereas the baseline level of sIL-2R was significantly higher in the poor-responder group than other groups. In conclusion, increased serum sIL-2R level and lower IL-18 level at baseline was associated with a poor prognosis in patients with AA. [source] Glucose-Responsive Bioinorganic Nanohybrid Membrane for Self-Regulated Insulin ReleaseADVANCED FUNCTIONAL MATERIALS, Issue 9 2010Claudia R. Gordijo Abstract A bioinorganic nanohybrid glucose-responsive membrane is developed for self-regulated insulin delivery analogous to a healthy human pancreas. The application of MnO2 nanoparticles as a multifunctional component in a glucose-responsive, protein-based membrane with embedded pH-responsive hydrogel nanoparticles is proposed. The bio-nanohybrid membrane is prepared by crosslinking bovine serum albumin (BSA),MnO2 nanoparticle conjugates with glucose oxidase and catalase in the presence of poly(N -isopropyl acrylamide- co -methacrylic acid) nanoparticles. The preparation and performance of this new nanocomposite material for a glucose-responsive insulin release system is presented. The activity and stability of immobilized glucose oxidase and the morphology and mechanical properties of the membrane are investigated. The enzymatic activity is well preserved in the membranes. The use of MnO2 nanoparticles not only reinforces the mechanical strength and the porous structure of the BSA-based membrane, but enhances the long-term stability of the enzymes. The in vitro release of insulin across the membrane is modulated by changes in glucose concentration mimicking possible fluctuations of blood-glucose level in diabetic patients. A four-fold increase in insulin permeation is observed when the glucose concentration is increased from normal to hyperglycemic levels, which returns to the baseline level when the glucose concentration is reduced to a normal level. [source] Aging per se does not influence postprandial glucose levels in type 2 diabetesGERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 3 2005Yumiko Magata Background: It is well known that postprandial glucose increases with aging in non-diabetic subjects. The question we addressed is whether elderly type 2 diabetic patients with definite fasting hyperglycemia (, 126 mg/dL) also display increased postprandial hyperglycemia relative to their younger counterparts. Methods: Diurnal plasma glucose profiles were measured in 162 overt type 2 diabetic patients treated by diet alone (diet group) or with sulfonylureas as monotherapy (SU group). Plasma glucose concentrations were measured at 08.00 hours (before breakfast), 10.00, 12.00 (before lunch), 14.00, 18.00 (before dinner), 20.00, 24.00, 03.00, 06.00 and 08.00 hours the next morning. The postprandial glucose area under the curve (AUC) from 08.00 to 24.00 hours was calculated above the baseline level equal to the 08.00-hours plasma glucose value, and the relationships with clinical variables, including age, were assessed. Results: There were no differences in diurnal plasma glucose profiles between the middle-aged (< 65 years) and elderly (, 65 years) groups either the diet group or the SU group. Univariate analysis showed that the postprandial glucose area under the curve was related to the 08:00-hours plasma glucose value (R = 0.583, P < 0.001) in the diet alone group and to the duration of diabetes (R = 0.220, P < 0.05), SU dose (R = 0.330, P = 0.001) and urine CPR (R = ,0.229, P < 0.05) in the SU group. In multivariate analysis, postprandial glucose area under the curve was only related to 08.00 hours plasma glucose value in the diet group (R2 of the model = 0.340, P < 0.001) and to the SU dose in SU group (R2 of the model = 0.145, P < 0.001). Conclusion: These results suggest that aging, per se, does not influence postprandial glucose levels in overt type 2 diabetic patients. [source] Changes in TMIG-Index of Competence by subscale in Japanese urban and rural community older populations: Six years prospective studyGERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 2003Yoshinori Fujiwara Objective: To examine the longitudinal changes in higher-level functional capacity in Japanese urban and rural community older populations. Design: Population-based cross-sectional, and prospective cohort studies. Setting: Koganei city in a suburb of Tokyo, and Nangai village, Akita Prefecture, Japan. Participants: One thousand, five hundred and six older persons (793 in Koganei and 713 in Nangai) aged 65,83 years living at home. Main outcome measures: Disability in Instrumental Self-Maintenance (IADL), Intellectual Activity or Social Role, measured by the Tokyo Metropolitan Institute of Gerontology Index of Competence. Results: At baseline, older men and women in the rural area, Nangai, had higher prevalence of disability in Intellectual Activity compared with respective counterparts in the urban area, Koganei. By contrast, disability in Social Role was more prevalent among elderly people in Koganei than in Nangai. In both areas older men and women had lowest prevalence of disability in IADL among three subscales. The six-year longitudinal survey on older persons who had initially no disability in all three subscales demonstrated that in urban Koganei older persons were most likely to be disabled in Social Role with advancing age, followed in turn by Intellectual Activity and IADL. By contrast, elderly people in rural Nangai were most likely to be disabled in Intellectual Activity, followed by Social Role and instrumental ADL. The Cox-proportional hazard model analysis for those who had no IADL disability at baseline revealed that the baseline level of Intellectual Activity or Social Role predicted significantly future onset of IADL disability in both areas even after controlling for sex, age, and chronic medical conditions. Conclusions: In both urban and rural community older populations, disability in Social Role and Intellectual Activity preceded IADL disability, and predicted significantly the future onset of IADL disability. [source] Treatment of refractory fludarabine induced autoimmune haemolytic with the anti-cd20 monoclonal antibody rituximabINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 1 2006R. SWORDS Summary A patient with cold-type autoimmune haemolytic anaemia for 8 years developed progressive B cell chronic lymphocytic leukaemia (CLL). Despite the risk of fludarabine induced exacerbation of haemolysis, he was given aggressive anti-CLL therapy with six courses of FCR (fludarabine 25 mg/m2 D1,3, cyclophosphamide 250 mg/m2 D2,4 and rituximab 375 mg/m2 D1) every 4 weeks. This resulted in a marked acute increase in haemolysis shortly after completing each course of fludarabine. However, haemolysis had settled to its baseline level by the time of subsequent courses of FCR. FCR resulted in complete clinical remission of CLL but residual haemolysis persisted. The patient was then given four weekly infusions of single agent rituximab, resulting in ongoing remission of haemolysis. In this patient, rituximab appears to have controlled fludarabine induced exacerbation of autoimmune haemolysis. In addition, subsequent single agent rituximab therapy resulted in prolonged remission of cold-type autioimmune haemolytic anaemia. It remains to be seen if the addition of rituximab will allow other patients with a positive direct Coomb's test and/or autoimmune haemolysis to receive fludarabine containing chemotherapy without undue risk of life-threatening haemolytic anaemia. [source] To sample or eradicate?JOURNAL OF APPLIED ECOLOGY, Issue 4 2008A cost minimization model for monitoring, managing an invasive species Summary 1Considerable effort is expended by national and local governments to exclude alien species via detection and eradication of invading populations, but these efforts are not necessarily designed in the most economically or biologically efficient manner. 2Using the invasion of the European strain of the gypsy moth Lymantria dispar into the USA as a case study, we develop an analytical model to determine the optimal trap density for detecting isolated infestations. Most models focus on monitoring or eradication costs only; our model considers the costs of both detection and eradication when determining the best monitoring strategy. 3The model assumes that all isolated populations must be located and eradicated by the conclusion of a programme. For programmes lasting longer than 1 year, it is more worthwhile to proactively monitor and manage rather than to wait until the programme is over. 4For a management programme of a given length, optimal trap density is most influenced by the growth rate of the infestation. Optimal trap densities are lowest for infestations with very low growth rates (because they remain small and therefore are less expensive to eradicate) or very high growth rates (because they are easier to detect), and highest for infestations with moderate growth rates (because they are neither inexpensive to eradicate nor easy to detect). 5Our model is useful in setting a baseline level of monitoring for isolated incidents of gypsy moth invasion. Analysis of data in two US states show that actual trap densities are far higher than the optimal densities from the model. The difference suggests risk aversion may play a role in real systems. 6Synthesis and applications. Our model suggests that we can improve the efficiency of detection and eradication programmes for isolated infestations by optimizing detection effort relative to infestation growth rates and management programme duration. It also clearly demonstrates the importance of balancing the costs and benefits of both detection and eradication when developing invasive species monitoring programmes. [source] Immunogenicity and effect of a virosomal influenza vaccine on viral replication and T-cell activation in HIV-infected children receiving highly active antiretroviral therapy,JOURNAL OF MEDICAL VIROLOGY, Issue 4 2006Elisabetta Tanzi Abstract In order to evaluate the immunogenicity and the effect of a virosomal influenza vaccine on viral replication and T-cell activation in HIV-infected children receiving highly active antiretroviral therapy (HAART), 29 children infected with HIV-1 vertically (19 primed with a previous influenza vaccination and 10 who were not been immunized against influenza) were immunized with an intramuscular virosome-adjuvanted influenza vaccine. According to the European Agency for Evaluation of Medical Products (EMEA) criteria, the immunogenicity of the vaccine was adequate against all three influenza strains (A H1N1, A H3N2, and B) in the primed children, and against A H1N1 and A H3N2 in the unprimed children. After in vitro stimulation with vaccine antigens, the IFN-, levels in the peripheral blood mononuclear cells cultures increased significantly from a baseline level of 103.0,±,229.8 pg/ml to a 30-day level of 390.7,±,606.3 pg/ml (P,<,0.05), with concentrations significantly higher (P,<,0.05) in the primed children than in the unprimed children. No increase in plasma HIV-1 RNA or HIV-1 proviral DNA was observed in either subgroup, and the immunophenotype analyses demonstrated that the CD4+ cell counts and percentages, the CD4/CD8 ratio and activated lymphocytes remained stable in either group from baseline to 1 month after each vaccine dose. This study showed that the virosomal influenza vaccine does seem to be immunogenic in the majority of HIV-infected children receiving HAART and does not induce viral replication or T-cell activation. Given the possible influenza-related complications in children infected with HIV, these results support the use of this influenza vaccine in such patients. J. Med. Virol. 78:440,445, 2006. © 2006 Wiley-Liss, Inc. [source] Vitamin K2 treatment for postmenopausal osteoporosis in IndonesiaJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 2 2006Yuditiya Purwosunu Abstract Aim: To investigate the effect of vitamin K2 (menatetrenone) treatment on bone mineral density (BMD) and a bone metabolic marker (osteocalcin) in postmenopausal women with osteoporosis living in Indonesia. Methods: A double-blind randomized placebo-controlled study of 63 postmenopausal women with osteoporosis. The vitamin K2 group (n = 33) received 45 mg menatetrenone and 1500 mg calcium carbonate per day and the control group (n = 30) received placebo and 1500 mg calcium carbonate per day for 48 weeks. BMD of lumbal spine (L2,L4), osteocalcin (OC) and undercarboxylated OC were measured before, 24 and 48 weeks after initiation of the treatment. Results: After 48 weeks of treatment, the mean percentage change of lumbar BMD in the vitamin K2 group was significantly higher (P < 0.05) than that of the control group. The undercarboxylated OC level decreased by 55.9% in the menatetrenone group and 9.3% in the control group compared with the baseline level. The difference between the two groups was significant (P < 0.01). The adverse events were three minor gastrointestinal cases, which subsided after temporary cessation of therapy. Conclusions: Treatment with 45 mg vitamin K2 with 1500 mg calcium per day for postmenopausal women with osteoporosis for 48 weeks resulted in a significant increase in lumbar BMD and a significant decrease in undercarboxylated OC levels. [source] Thrombin induces neoangiogenesis in the chick chorioallantoic membraneJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 10 2003M. Caunt Summary., Most tumors have constitutively active tissue factor on their surface, capable of generating thrombin in the surrounding environment, and thrombosis is associated with cancer. Thrombin is known to induce a malignant phenotype by enhancing tissue adhesion and cell growth in vitro and in vivo in mice. Because tumors require angiogenesis for growth, we examined whether thrombin induces neoangiogenesis in a physiologically intact in vivo model. Thrombin (0.1 U mL,1) induced neoangiogenesis in the chick chorioallantoic membrane over a 24,72-h period by approximately 2,3-fold. This was inhibited by the potent thrombin inhibitor, hirudin and shown to have its mode of action by ligation of the thrombin protease-activated receptor, PAR-1. The thrombin receptor activation peptide, SFLLRNPNDKYEPF (200 µm) also enhanced neoangiogenesis c. 2,3-fold. Thrombin-induced neoangiogenesis was accompanied by the induction of vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2) mRNA at 24,48 h (approximately 2-fold) as determined by semi-quantitative reverse transcriptase-polymerase chain reaction. Thrombin-induced neoangiogenesis was inhibited to baseline level by the specific angiogenesis receptor inhibitors KDR-Fc (vs. VEGF) and Tie-2-Fc (vs. Ang-1 and Ang-2), as well as the non-specific angiogenesis inhibitor thrombospondin-1. Thrombin-induced neoangiogenesis was also inhibited to baseline level by agents known to inhibit thrombin receptor signaling in other cells: G-coupled protein receptor inhibitor, pertussis toxin (40 pg per egg), protein kinase C inhibitor, bisindolylmaleimide (1 µm per egg), MAP kinase inhibitor, PD980598 (10 µm per egg) and PI3 kinase inhibitor, LY294002 (0.25 µm per egg). Thus angiogenesis is stimulated by thrombosis, which could help explain the enhancement of experimental tumorigenesis by thrombin. [source] Influence of extracorporeal porcine liver perfusion on nonhuman primates: Minimizing hemolysis improves subsequent survivalLIVER TRANSPLANTATION, Issue 7 2001Ryuta Nishitai MD The aim of this study is to detect and analyze risk factors of direct cross-circulation between porcine liver and nonhuman primates before a clinical application of extracorporeal liver perfusion (ECLP) as a liver-assist method. Porcine livers were perfused with baboon blood in an ECLP system. Six healthy baboons were directly connected to the ECLP system with continuous prostaglandin E1 administration. Cross-circulation was terminated in the following circumstances: (1) hepatic arterial or portal perfusion pressures elevated to 200 or 60 mm Hg, respectively; (2) massive exudative bleeding from the graft surface; or (3) bile output decreased to less than 5 ,L/h/g of liver weight. In case 1, cross-circulation was continued for 10 hours. Severe macroscopic hemolysis occurred, and serum hemoglobin (s-Hb) concentration reached a peak of 47 mg/dL. The baboon died of acute renal failure 2 days later. Histological study of the perfused porcine liver showed marked microthrombi formation. In 3 of the later 5 cases, cross-circulation was discontinued when mild macroscopic hemolysis was observed. The duration of the 5 cross-circulations was maximally 6 hours (mean, 4.4 ± 1.2 [SD] hours). Mean s-Hb concentration in the 5 cases was elevated to 14.8 ± 5.8 mg/dL at the end of cross-circulation and decreased to the baseline level within 24 hours. These 5 baboons survived without organ dysfunction or immunologic disturbance. When severe hemolysis is avoided, direct cross-circulation using the ECLP system can be achieved without serious complications in nonhuman primates. [source] Effect of renin,angiotensin system inhibitors on prevention of peritoneal fibrosis in peritoneal dialysis patientsNEPHROLOGY, Issue 1 2010SUN JING ABSTRACT: Aim: Long-term peritoneal dialysis (PD) may lead to peritoneal fibrosis and ultrafiltration failure. It had been demonstrated that the renin,angiotensin system (RAS) plays a key role in the regulation of peritoneal function in rats on PD. We investigated the effects of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) on long-term PD patients. Methods: We analyzed data from 66 patients treated with PD therapy at our centre for at least 12 months retrospectively, during which time at least two peritoneal equilibration tests (PET) were performed. Thirty-eight patients were treated with ACE/angiotensin II (AII) inhibitors (ACE/ARB group); the other 28 received none of the above drugs during the entire follow up (control group). The expression of fibronectin, transforming growth factor-,1 (TGF-,1), Aquaporin1 (AQP1) and vascular endothelial growth factor (VEGF) in the overnight effluent were examined by enzyme-linked immunosorbent assay. Results: The demographic data of the two groups showed no difference during the study. No difference between the groups was found with respect to residual renal function (RRF) at the start for both groups by the end of follow up, decreased in the vast majority of patients from both groups (P = 0.014). After 12 months, a significant difference in ultrafiltration was found between the two groups: in the control group it had decreased, while it had not changed in the ACE/ARB group (P < 0.05). In comparison with the baseline level, expression of fibronectin, TGF-,1 and VEGF in dialysate effluent were significantly increased except for AQP1 in the control group (P < 0.05), but not in the ACE/ARB group (P > 0.05). Conclusion: The findings suggest that ACE/AII inhibitors appeared to have a slower rate of decline in ultrafiltration and RRF, effectively protect against peritoneal fibrosis in long-term peritoneal dialysis. Long-term follow up seems to be required to draw more conclusions. [source] Experiences with acute kidney injury complicating non-fulminant hepatitis ANEPHROLOGY, Issue 6 2008HYUN W KIM SUMMARY: Aim: To describe the clinical features and to identify factors related to development of acute kidney injury in acute hepatitis A patients. Methods: The study and control groups consisted of 21 and 425 patients who did or did not develop acute kidney injury, respectively, after acute hepatitis A from January 1997 to May 2007. Results: There were 13 men and eight women; their mean age at diagnosis was 28.8 ± 8.2 years in the study group. Peak values for renal and liver function impairment consisted of a median serum creatinine of 4.6 mg/dL (range, 1.5,15.3 mg/dL) on day 6 (range, days 1,20) and a median total bilirubin of 10.7 mg/dL (range, 2.6,57.5 mg/dL) on day 8 (range, day 1,19). Serum creatinine concentrations returned to baseline level by a median of 16 days and total bilirubin levels returned to normal by a median of 62 days. Six of 21 (29%) patient underwent haemodialysis. Renal biopsies performed in two patients showed acute tubular necrosis and interstitial nephritis, respectively. Logistic regression analysis showed that a lower haematocrit, the presence of coagulopathy and high C-reactive protein concentration on admission, and higher peak bilirubin value during the illness were associated with development of acute kidney injury. Conclusion: Acute hepatitis A should be considered in the differential diagnosis of patients with acute kidney injury, even without fulminant hepatic failure. A lower haematocrit, the presence of coagulopathy and high C-reactive protein level at presentation, and higher peak bilirubin level during the illness were associated with development of acute kidney injury in acute hepatitis A patients. [source] Effects of albumin infusion therapy on total and unbound bilirubin values in term infants with intensive phototherapyPEDIATRICS INTERNATIONAL, Issue 1 2001Shigeharu Hosono Background: The purpose of the present study was to evaluate the effect of intravenous albumin administration on the serum total and unbound bilirubin values in term non-hemolytic hyperbilirubinemic neonates during intensive phototherapy. Methods: Fifty-eight infants (gestational age 39.4~1.4 weeks; birth weight 3245~435 g) were given phototherapy with similar light energy. Twenty infants (control group) received only phototherapy, while 38 others (albumin-treated group) were also given human albumin at 1 g/kg bodyweight, i.v., during the first 2 h of phototherapy. Results: When comparing changes in total and unbound bilirubin values 0, 2, 6 and 24 h after entering the study between the albumin-treated group and the control group, there was a significant reduction in the serum unbound bilirubin values at the end of albumin treatment and at 6 and 24 h. However, there was no significant reduction in total serum bilirubin values during the study period. In the albumin-treated group, the mean serum unbound bilirubin reduction from the baseline level at the end of albumin treatment and at 6 and 24 h was 0.40~0.19, 0.41~0.20 and 0.43~0.20 ,g/dL, respectively. Conclusions: The results suggest that albumin priming may be effective for an immediate reduction in serum unbound bilirubin values, the fraction that is potentially neurotoxic. [source] The relationship between time since registration and measured incidence rates in the General Practice Research Database,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 7 2005James D. Lewis MD, MSCE Abstract Background The General Practice Research Database (GPRD) is widely used to study incidence rates. This study examines whether incidence rates are overestimated during the first year after registration, how long one needs to wait to obtain accurate incidence rates, and whether the time period of overestimation differs among disease types. Methods We measured incidence rates of nine acute, eight chronic, and eight neoplastic outcomes in 3-month intervals through month 36 after enrollment in GPRD. The incidence rates in months 13,36 were used to estimate baseline incidence rates for each diagnosis. Results For patients registering with practices that were already UTS, incidence rates were highest in the first 3 months after registration. In eight of nine acute diagnoses, the incidence rate was within 20% of baseline by months 4,6; and in seven of eight cancers, the incidence rate was within 20% of baseline by months 7,9. For chronic conditions, the incidence rate in months 10,12 differed from baseline by more than 20% for five of the eight outcomes, respectively. For patients registering prior to UTS, incidence rates during the first quarter were within 20% of baseline for all acute and cancer diagnoses and six of eight chronic diagnoses. Conclusions Reported incidence rates are highest in the first 3 months after registration with an UTS practice and decline to baseline over the first year, more quickly for acute conditions than chronic conditions. For patients who registered prior to UTS, incidence rates are near the baseline level at the start of follow-up. Copyright © 2005 John Wiley & Sons, Ltd. [source] Novel Aspects of Intrinsic and Extrinsic Aging of Human Skin: Beneficial Effects of Soy Extract,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 3 2005Kirstin M. Südel ABSTRACT Biochemical and structural changes of dermal connective tissue substantially contribute to the phenotype of aging skin. To study connective tissue metabolism with respect to ultraviolet (UV) exposure, we performed an in vitro (human dermal fibroblasts) and an in vivo complementary DNA array study in combination with protein analysis in young and old volunteers. Several genes of the collagen metabolism such as Collagen I, III and VI as well as heat shock protein 47 and matrix metalloproteinase-1 are expressed differentially, indicating UV-mediated effects on collagen expression, processing and degradation. In particular, Collagen I is time and age dependently reduced after a single UV exposure in human skin in vivo. Moreover, older subjects display a lower baseline level and a shorter UV-mediated increase in hyaluronan (HA) levels. To counteract these age-dependent changes, cultured fibroblasts were treated with a specific soy extract. This treatment resulted in increased collagen and HA synthesis. In a placebo-controlled in vivo study, topical application of an isoflavone-containing emulsion significantly enhanced the number of dermal papillae per area after 2 weeks. Because the flattening of the dermal-epidermal junction is the most reproducible structural change in aged skin, this soy extract appears to rejuvenate the structure of mature skin. [source] Nurse staffing and medication errors: Cross-sectional or longitudinal relationships?,RESEARCH IN NURSING & HEALTH, Issue 1 2009Barbara A. Mark Abstract We used autoregressive latent trajectory (ALT) modeling to examine the relationship between change in nurse staffing and change in medication errors over 6 months in 284 general medical-surgical nursing units. We also investigated the impact of select hospital and nursing unit characteristics on the baseline level and rate of change in medication errors. We found essentially no support for a nurse staffing,medication error relationship either cross-sectionally or longitudinally. Few hospital or nursing unit characteristics had significant relationships to either the baseline level or rate of change in medication errors. However, ALT modeling is a promising technique that can promote a deeper understanding of the theoretically complex relationships that may underlie the nurse staffing,medication error relationship. © 2008 Wiley Periodicals, Inc. Res Nurs Health 32:18,30, 2009 [source] Pathology of the Olfactory Epithelium: Smoking and Ethanol Exposure,THE LARYNGOSCOPE, Issue 8 2004J Vent MD Abstract Objective: To investigate the effects of tobacco smoke on the olfactory epithelium. Cigarette smoking has been associated with hyposmia; however, the pathophysiology is poorly understood. The sense of smell is mediated by olfactory sensory neurons (OSNs) exposed to the nasal airway, rendering them vulnerable to environmental injury and death. As a consequence, a baseline level of apoptotic OSN death has been demonstrated even in the absence of obvious disease. Dead OSNs are replaced by the mitosis and maturation of progenitors to maintain sufficient numbers of neurons into adult life. Disruption of this balance has been suggested as a common cause for clinical smell loss. This current study will evaluate the effects of tobacco smoke on the olfactory mucosa, with emphasis on changes in the degree of OSN apoptosis. Study Design: A rat model was used to assess the olfactory epithelium after exposure to tobacco smoke. Methods: Rats were exposed to tobacco smoke alone (for 12 weeks), smoke plus dietary ethanol (for the final 5 weeks), or to neither (control). Immunohistochemical analysis of the olfactory epithelium was performed using an antibody to the active form of caspase-3. Positive staining for this form of the caspase-3 enzyme indicates a cell undergoing apoptotic proteolysis. Results: Control rats demonstrated a low baseline level of caspase-3 activity in the olfactory epithelium. In contrast, tobacco smoke exposure triggered a dramatic increase in the degree of OSN apoptosis that affected all stages of the neuronal lineage. Conclusions: These results support the following hypothesis: smell loss in smokers is triggered by increased OSN death, which eventually overwhelms the regenerative capacity of the epithelium. [source] IS INFORMED CONSENT IN CARDIAC SURGERY AND PERCUTANEOUS CORONARY INTERVENTION ACHIEVABLE?ANZ JOURNAL OF SURGERY, Issue 7 2007Marco E. Larobina Background: Medical and legal published work regularly discusses informed consent and patient autonomy before medical interventions. Recent discussions have suggested that Cardiothoracic surgeons' risk adjusted mortality data should be published to facilitate the informed consent process. However, as to which aspects of medicine, procedures and the associated risks patients understand is unknown. It is also unclear how well the medical profession understands the concepts of informed consent and medical negligence. The aims of this study were to evaluate patients undergoing coronary artery bypass surgery (CABG) and percutaneous coronary intervention (PCI) to assess their understanding of the risks of interventions and baseline level of understanding of medical concepts and to evaluate the medical staff's understanding of medical negligence and informed consent. Methods: Patients undergoing CABG or PCI at a tertiary hospital were interviewed with questionnaires focusing on the consent process, the patient's understanding of CABG or PCI and associated risks and understanding of medical concepts. Medical staff were questioned on the process of obtaining consent and understanding of medicolegal concepts. Results: Fifty CABG patients, 40 PCI patients and 40 medical staff were interviewed over a 6-month period. No patient identified any of the explained risks as a reason to reconsider having CABG or PCI, but 80% of patients wanted to be informed of all risks of surgery. 80% of patients considered doctors obligated to discuss all risks of surgery. One patient (2%) expressed concern at the prospect of a trainee surgeon carrying out the operation. Stroke (40%) rather than mortality (10%) were the important concerns in patients undergoing CABG and PCI. The purpose of interventions was only partially understood by both groups; PCI patients clearly underestimated the subsequent need for repeat PCI or CABG. Knowledge of medical concepts was poor in both groups: less than 50% of patients understood the cause or consequence of an AMI or stroke and less than 20% of patients correctly identified the ratio equal to 0.5%. One doctor (2.5%) correctly identified the four elements of negligence, eight (20%) the meaning of material risk and four (10%) the meaning of causation. Thirty doctors (75%) believed that all complications of a procedure needed to be explained for informed consent. Less than 10% could recognize landmark legal cases. Conclusion: Patients undergoing both CABG and PCI have a poor understanding of their disease, their intervention, and its complications making the attaining of true informed consent difficult, despite their desire to be informed of all risks. PCI patients particularly were highly optimistic regarding the need for reintervention over time, which requires specific attention during the consent process. Medical staff showed a poor knowledge of the concepts of material risk and medical negligence requiring much improved education of both junior doctors and specialists. [source] Using Conditional Logistic Regression to Fit Proportional Odds Models to Interval Censored DataBIOMETRICS, Issue 2 2000Daniel Rabinowitz Summary. An easily implemented approach to fitting the proportional odds regression model to interval-censored data is presented. The approach is based on using conditional logistic regression routines in standard statistical packages. Using conditional logistic regression allows the practitioner to sidestep complications that attend estimation of the baseline odds ratio function. The approach is applicable both for interval-censored data in settings in which examinations continue regardless of whether the event of interest has occurred and for current status data. The methodology is illustrated through an application to data from an AIDS study of the effect of treatment with ZDV + ddC versus ZDV alone on 50% drop in CD4 cell count from baseline level. Simulations are presented to assess the accuracy of the procedure. [source] Time-dependent clearance and hematological pharmacodynamics upon erythropoietin multiple dosing in ratsBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 5-6 2010Sihem Ait-Oudhia Abstract The pharmacokinetics (PK) and pharmacodynamics (PD) of recombinant human erythropoietin (rHuEPO) upon its repeated administrations were investigated. Two groups (A and B) of normal Wistar rats received rHuEPO intravenously at 450 or 1350,IU/kg thrice weekly for 2 and 6 weeks. PK studies were conducted following days 0 and 4 for group (A) and days 0, 17 and 28 for group (B), then, washout PK were assessed on days 11 and 36 for both groups. Reticulocytes (RET), red blood cells (RBC) and hemoglobin (Hb) were evaluated daily until day 14, then every 2 days until day 30 for group (A) and 59 for group (B). The total clearance CLTotal increased with the dose but decreased over time. Its decay reached 20% and 55% between the first and last full PK in both treatment arms. RET peaked on day 5 and were 77.6% and 87.3% higher than baselines for the two dosing regimen. Their nadirs occurred on days 22 and 55 and were 37.9% and 47.3% below normal values. Hb peaked on days 10 and 34 and was 28.9% and 38.6% above the baseline level, its nadirs occurred on days 25 and 57 and were 13.1% and 16% below baselines. Control animals showed stable baselines over the study but with moderate variability. In conclusion, rHuEPO exhibits a nonlinear PK with a time-dependent decrease of its CLTotal. During exposure, RET, RBC and Hb showed a tolerance effect. After exposure, the rebound was characterized for RET, RBC, but not Hb. Copyright © 2010 John Wiley & Sons, Ltd. [source] Use of radiolabelled iododeoxyuridine as adjuvant treatment for experimental tumours of the liverBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 10 2003J. S. Zager Background The aim of the study was to determine whether hepatic regeneration stimulates growth of tumour residing within the liver, and whether a difference in the rate of DNA synthesis in liver and tumour may be used to target cancer using the radiolabelled thymidine analogue 5-iodo-2,-deoxyuridine (IUdR). Methods Partial hepatectomy was performed on Buffalo rats bearing solitary nodules of syngeneic Morris hepatoma. Liver and tumour DNA synthesis was measured by incorporation of radioactive IUdR. [125I]IUdR was tested as an adjuvant therapy after hepatectomy in Buffalo rats bearing diffuse microscopic Morris hepatomas to simulate the clinical situation. Results Liver regeneration enhanced liver and tumour DNA synthesis as measured by incorporation of radioactive IUdR. Liver DNA synthesis returned to baseline by 7 days, whereas tumour DNA synthesis remained above baseline level. Hepatectomy enhanced the growth of microscopic liver tumours. [125I]IUdR (250 µCi or 1 mCi/kg) administered 4 days after hepatectomy significantly reduced tumour growth without signs of systemic toxicity or liver dysfunction. Conclusion The local environment of the regenerating liver stimulates tumour growth. The thymidine analogue [125I]IUdR may be used preferentially to target tumour DNA synthesis in the regenerating liver, and may prove useful as an adjuvant therapy for hepatic tumours after surgical resection. Copyright © 2003 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] Geranylgeraniol, an Intermediate Product in Mevalonate Pathway, Induces Apoptotic Cell Death in Human Hepatoma Cells: Death Receptor-independent Activation of Caspase-8 with Down-regulation of Bcl-xL ExpressionCANCER SCIENCE, Issue 9 2001Yoshio Takeda Geranylgeraniol (GGOH), an intermediate of mevalonate metabolism, is known to induce apoptosis in various lines of cancer cells. The present study was undertaken to clarify the signaling pathways of apoptosis induced by GGOH in human hepatoma cells. HuH-7 human hepatoma cells were incubated in the absence or presence of GGOH. Activation of caspase-8/-9/-3 in HuH-7 cells was found after 8 h treatment with GGOH, at which tune DNA fragmentation and loss of mitochondrial transmembrane potential (,,m) occurred. HuH-7 cells do not express Bcl-2; however, down-regulation of Bcl-xL expression preceded activation of the caspase cascade in GGOH-treated HuH-7 cells, while Bax expression was not changed by GGOH treatment. Addition of caspase inhibitors restored the decreased cell viability of HuH-7 cells by GGOH, including ,,m, to the baseline level, which indicated that caspase triggers mitochondria-dependent apoptotic pathways in GGOH-treated HuH-7 cells. Similarly, GGOH-mediated apoptosis of HuH-7 cells was clearly prevented by coadministration of ursodeoxycholic acid (UDCA), which led to restoration of the level of Bcl-xL expression. Activation of caspase-8/-9/-3, as well as ,,m, by GGOH treatment was suppressed by addition of UDCA. Our results indicate that activation of the caspase cascade initiating from caspase-8, which could be accelerated by down-regulation of Bcl-xL expression, plays a key role in an apoptotic process induced by GGOH in human hepatoma cells. [source] | |||||||||||||||||||||||||||||||||||||