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Terms modified by ACR Selected AbstractsMicroalbuminuria in Nondiabetic and Nonhypertensive Systolic Heart Failure PatientsCONGESTIVE HEART FAILURE, Issue 5 2008Estêvão L. Figueiredo MD The American Diabetes Association and the National Kidney Foundation define microalbuminuria as an albumin (,g)/creatinine (mg) ratio (ACR) between 30 and 300 ,g/mg regardless of sex. Microalbuminuria is associated with increased cardiovascular risk. The authors evaluated the prevalence of microalbuminuria in nondiabetic and nonhypertensive systolic heart failure (SHF) patients. Twenty-seven SHF patients, 18 years and older, with New York Heart Association functional classes II through IV and left ventricular ejection fraction ,40%, who were nondiabetic and nonhypertensive and not receiving angiotensin-converting enzyme inhibitors, were selected. Twenty-seven healthy individuals, paired according to sex, ethnicity, and age, were used as controls. Early-morning midstream urine was used. Data are expressed as medians. Excretion of albumin in SHF patients (39 ,g/mL urine) was significantly higher than in controls (26 ,g/mL urine). Creatinine excretion was not significantly different between patients and controls. ACR was significantly higher in patients (54 ,g/mg) than in controls (24 ,g/mg). The results indicate that microalbuminuria was significantly present in nondiabetic and nonhypertensive SHF patients. [source] Rate of progression of mild cognitive impairment to dementia , meta-analysis of 41 robust inception cohort studiesACTA PSYCHIATRICA SCANDINAVICA, Issue 4 2009A. J. Mitchell Objective:, To quantify the risk of developing dementia in those with mild cognitive impairment (MCI). Method:, Meta-analysis of inception cohort studies. Results:, Forty-one robust cohort studies were identified. To avoid heterogeneity clinical studies, population studies and clinical trials were analysed separately. Using Mayo defined MCI at baseline and adjusting for sample size, the cumulative proportion who progressed to dementia, to Alzheimer's disease (AD) and to vascular dementia (VaD) was 39.2%, 33.6% and 6.2%, respectively in specialist settings and 21.9%, 28.9% and 5.2%, respectively in population studies. The adjusted annual conversion rate (ACR) from Mayo defined MCI to dementia, AD and VaD was 9.6%, 8.1% and 1.9%, respectively in specialist clinical settings and 4.9%, 6.8% and 1.6% in community studies. Figures from non-Mayo defined MCI and clinical trials are also reported. Conclusion:, The ACR is approximately 5,10% and most people with MCI will not progress to dementia even after 10 years of follow-up. [source] Familial factors in diabetic nephropathy: an offspring studyDIABETIC MEDICINE, Issue 3 2006E. Agius Abstract Aims Familial clustering of diabetic nephropathy in patients with Type 2 diabetes suggests that inherited factors predispose to diabetic nephropathy, but the nature of these factors is uncertain. The aim of the study was to compare the prevalence of known risk factors for nephropathy in non-diabetic offspring of Type 2 diabetic patients with and without nephropathy and in control subjects. Methods Three groups of patients were recruited with 40 or 41 subjects in each group. These were subjects having one Type 2 diabetic parent with nephropathy (DN); subjects having one parent with Type 2 diabetes without nephropathy (DnoN), and non-diabetic unrelated control subjects with no personal or parental history of diabetes (Control subjects). Results The median (interquartile range) albumin/creatinine ratio (ACR) was 1.40 (0.96,2.90) mg/mmol in DN; 0.94 (0.50,1.46) mg/mmol in DnoN and 1.22 (0.66,1.83) mg/mmol in Controls (anova: P = 0.03). ACR was higher in group DN than in DnoN (P < 0.006) and in Control subjects (P < 0.03), but there was no difference between DnoN and Control subjects. Twenty-four-hour ambulatory blood pressure monitoring showed mean daytime systolic blood pressure to be significantly higher in group DN than in DnoN (P < 0.02) or Control subjects (P < 0.01) (anova: P = 0.004). Fasting insulin, HOMA-IR, interleukin-6 (IL-6) and C-reactive protein (CRP) were similar in the three groups. Conclusion Our data provide further evidence that genetic factors are important in determining urinary albumin excretion and renal disease associated with Type 2 diabetes and suggest that genes that affect systemic arterial blood pressure but not those relating to insulin resistance or inflammation are likely to be implicated. [source] The effect of spironolactone, cilazapril and their combination on albuminuria in patients with hypertension and diabetic nephropathy is independent of blood pressure reduction: a randomized controlled studyDIABETIC MEDICINE, Issue 5 2004R. Rachmani Abstract Objective The effect of spironolactone, cilazapril and their combination on albuminuria was examined in a randomized prospective study in female patients with diabetes and hypertension. Patients and methods Sixty female diabetic patients aged 45,70 years with blood pressure (BP) 140,180/90,110 mmHg, serum creatinine (sCr) , 160 µmol/l, HbA1c , 10%, and albuminuria were treated by atenolol 12.5,75 mg/d and hydrochlorothiazide 6.25,25 mg/d. Titration-to-target helped to reach BP values , 135/85 mmHg in 46 patients after 12 weeks. These patients were randomized to spironolactone 100 mg/d or cilazapril 5 mg/d for 24 weeks. Then both groups received spironolactone 50 mg/d and cilazapril 2.5 mg/d for 24 weeks. BP was stabilized by tapering the dose of the initial agents. Urinary albumin/creatinine ratio (ACR), BP, K+. sCr and HbA1c were assessed at baseline and at weeks 12, 16, 36 and 60. Results The average BP at week 12 was 128 ± 4/81 ± 3 mmHg and remained constant, in both groups, throughout the study. ACR declined on spironolactone from a median value (range) of 452 (124,1571) to 216 (64,875) mg/g (P = 0.001), and on cilazapril to 302 (90,975) mg/g (P = 0.001). The difference between spironolactone and cilazapril was significant (P = 0.002). Combined treatment resulted in a further modest decline in ACR. Serum creatinine was unaltered by spironolactone and rose slightly (121 to 126 µmol/l, P = 0.02) on cilazapril. Conclusion At the doses tested, spironolactone was superior to cilazapril in reducing albuminuria. Combined administration was more effective than either drug alone. These effects were independent of BP values. Hyperkalaemia was the main side-effect. [source] Brachial-ankle pulse wave velocity measured automatically by oscillometric method is elevated in diabetic patients with incipient nephropathyDIABETIC MEDICINE, Issue 11 2003H. Yokoyama Abstract Aims To examine whether brachial-ankle pulse wave velocity (baPWV), a possible early marker of atherosclerotic vascular damage, is associated with albuminuria in patients with Type 2 diabetes. Methods BaPWV was measured by automatic oscillometric method in 346 Type 2 diabetic patients with normoalbuminuria (a mean level of three times measurements of albumin-to-creatinine (ACR) < 30 µg/mg creatinine; n = 200), incipient nephropathy (a mean level of ACR , 30 and < 300 µg/mg creatinine; n = 119), and clinical nephropathy (a mean level of ACR , 300 µg/mg creatinine; n = 27), and without peripheral vascular disease. Results BaPWV (cm/s) was significantly higher in patients with incipient nephropathy (1722 ± 382) and clinical nephropathy (1763 ± 322) than in patients with normoalbuminuria (1559 ± 343, P < 0.0001, respectively). By univariate analysis it correlated significantly with age (r = 0.44, P < 0.0001), systolic blood pressure (r = 0.55, P < 0.0001), diastolic blood pressure (r = 0.42, P < 0.0001), albuminuria (r = 0.24, P < 0.0001) and HbA1C (r = 0.11, P < 0.05). Albuminuria revealed an independent significant association with baPWV (P < 0.01) after adjustment for age, sex, smoking, BMI, HbA1C, hyperlipidemia, and hypertension. Multiple regression analysis showed age, diastolic blood pressure and albuminuria were independently associated with baPWV (adjusted R2 = 0.42, P < 0.0001). Conclusions The results might indicate a possible link between the pathogenesis of atherosclerosis and diabetic nephropathy. Future studies are needed to clarify the usefulness and its predictable value. [source] Longitudinal study of urinary albumin excretion in young diabetic patients,-Wessex Diabetic Nephropathy ProjectDIABETIC MEDICINE, Issue 5 2001S. Twyman Summary Aims This study was established to follow changes in albumin/creatinine ratio (ACR) and to determine the prevalence and degree of progression of microalbuminuria (MA) or of clinical proteinuria (CP) in children with Type 1 diabetes. The study has investigated subjects for up to 12 years in establishing the correlation between MA and gender, age, duration of diabetes and glycated haemoglobin (HbA1c). The study has defined clinical cut-offs for MA in daytime clinic urine samples in young diabetic subjects. Methods Three hundred and sixty-one patients were involved in the study, with 221 (61.2%) having over six sets of data. Urine samples were collected at routine annual clinic visits and analysed without prior freezing for ACR. Blood samples were taken for HbA1c measurement. Data including sex, age and duration of diabetes were recorded. Results A random clinic ACR of <,4.5 mg/mmol (males) and 5.2 mg/mmol (females) creatinine was used as the ,clinical cut-off' to define the presence of MA. The presence of MA was independent of HbA1c and duration of diabetes but appeared be associated with the adolescent years (> 10 years). There was little evidence of progression from normoalbuminuria to MA, or from MA to CP. Of patients aged 10,18 years, 30.9% of males and 40.4% of females had one or more episodes of MA. Conclusions Persistent MA and random episodes of MA or CP may be associated with the adolescent years but not with duration of diabetes. Further study will reveal if the substantial increases in ACR sometimes seen during adolescence are predictive of diabetic nephropathy. Clinical cut-offs of <,4.5 and <,5.2 mg/mmol creatinine for males and females, respectively, are suggested for the interpretation of changes in ACR in random urine samples in young people with Type 1 diabetes. [source] Acute-to-chronic species sensitivity distribution extrapolationENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 7 2004Cédric Duboudin Abstract Seeking to make greater use of available data for risk assessment of substances, we constructed, for the situation in which chronic data are limited or even nonexistent but acute data are relatively large, an acute to chronic transformation (ACT) methodology based on the concept of species sensitivity distributions (SSDs). This ACT methodology uses a comparison of acute and chronic SSDs, separately for vertebrate data (with 22 substances) and for invertebrate data (with 15 substances). Rather than comparing an acute toxicity value with a chronic value, as when calculating an acute to chronic ratio (ACR), samples of acute and chronic data corresponding to the same category of species were compared. Starting from a sample of acute data, the ACT methodology showed relationships that enable the creation of a sample of predicted chronic values. This sample can then be used to calculate a predicted chronic hazardous concentration potentially affecting 5% of species (HC5%), just as with a sample of real chronic toxicity values. This ACT approach was tested on 11 substances. For each substance, the real chronic HC5% and the predicted chronic HC5% were calculated and compared. The ratio between chronic HC5% and ACT HC5% was, on average, 1.6 and did not exceed 4.4 for the 11 substances studied. [source] The psychiatrist confronted with a fibromyalgia patientHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue S1 2009Siegfried Kasper Abstract Fibromyalgia is usually treated by rheumatologists but since co-morbid depression and anxiety are frequent, psychiatrists are likely to be confronted with patients suffering from the syndrome. The symptoms associated with fibromyalgia vary from patient to patient but there is one common symptom,they ache all over. In addition to pain, patients report headaches, poor sleep, fatigue, depressed mood and irregular bowel habits, which are also all symptoms of depression. For a formal diagnosis of fibromyalgia, the American College of Rheumatology (ACR) criteria require the patient to have widespread pain for at least 3 months together with tenderness at 11 or more of 18 specific tender points. Treatment of fibromyalgia requires a comprehensive approach involving education, aerobic exercise and cognitive behavioural therapy in addition to pharmacotherapy. The most effective drugs available for the treatment for fibromyalgia, the serotonin noradrenaline reuptake inhibitors, milnacipran and duloxetine and the anti-epileptic, pregabalin, are well known to psychiatrists. Thus the psychiatrist is well placed to initiate treatment in these patients. Copyright © 2009 John Wiley & Sons, Ltd. [source] Irbesartan has no short-term effect on insulin resistance in hypertensive patients with additional cardiometabolic risk factors (i-RESPOND)INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 2 2010K. G. Parhofer Summary Aims:, Intervention studies have shown that angiotensin receptor blockers (ARB) may reduce the incidence of type 2 diabetes mellitus. It is currently unclear whether short-term therapy with ARBs affects metabolic parameters. Methods:, i-RESPOND, a randomised, controlled, multicentre, double-blind study evaluated the effect of 16 weeks of irbesartan vs. hydrochlorothiazide (HCTZ) on insulin resistance as well as on lipid and inflammatory parameters in hypertensive subjects with metabolic syndrome. Patients received irbesartan (150 mg/d; n = 211) or HCTZ (12.5 mg/d; n = 215), titrated to 300 mg/day and 25 mg/day respectively. In a second part of the study (weeks 16,28), patients initially randomised to irbesartan received additional HCTZ and vice versa. Results:, At week 16 both irbesartan and HCTZ had no effect on insulin resistance measured by the Matzuda index and beta-cell function. Similarly, in the second part of the study (week 16,28) no differences between irbesartan and HCTZ with respect to glucose metabolism were observed. However, irbesartan induced beneficial changes in high-sensitivity-C-reactive protein (hs-CRP) (irbesartan: ,5.5 ± 5.2%; HCTZ + 19.9 ± 6.5%, p = 0.0024) and in urinary albumin/creatinine ratio (ACR) (irbesartan: ,13%; HCTZ + 9%; p = 0.0041) compared with HCTZ despite a similar decrease in blood pressure in both treatment groups. Irbesartan and HCTZ were well tolerated and adverse events were comparable. Conclusion:, Irbesartan did not show significant favourable effects on insulin resistance compared with HCTZ in this study; however, may have beneficial effects on inflammation and microalbuminuria in hypertensive patients with metabolic syndrome. [source] DMARD combination therapy in rheumatoid arthritis: 5-year follow-up results in a daily practice settingINTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 1 2006Fereydoun DAVATCHI Abstract Aim:, To evaluate the overall effect of disease modifying anti-rheumatic drug (DMARD) combination therapy in daily practice. Methods:, In a retrospective study, 161 consecutive files of patients who attended regular follow-up sessions, seen from 1998, were analysed. Their data were extracted at baseline, 6 months, 1, 2, 3, 4 and 5 years. American College of Rheumatology ACR70 criteria was chosen for the evaluation of the global result. DMARD combination was methotrexate (7.5,15 mg weekly) and chloroquine (150 mg daily), with low-dose prednisolone (less than 10 mg daily). In cases of remission, methotrexate was gradually tapered, then prednisolone. Chloroquine was discontinued after 1 year if no recurrence occurred at low-dose (150 mg every other day). In cases of recurrence at any stage, the treatment scheme was stepped back. Results:, The data of 161 patients were analysed. One hundred and six were rheumatoid factor positive (RF+) (66%). ACR 70 for all patients at 6 months follow-up was 72.5% (95% CI = 7.0); at 1 year, 75.8% (95% CI = 6.7); at 2 years, 72.2% (95% CI = 7.2); at 3 years, 78.9% (95% CI = 6.6); at 4 years, 78.4% (95% CI = 6.9); and at 5 years, 70.6% (95% CI = 8.5). Conclusion:, The classical DMARD combination therapy, when used with adequate low-dose prednisolone, gave an ACR70 response from 71,79%. The efficacy of the treatment did not fade over time. RF, patients did better than RF+ patients, but the difference was not statistically significant. [source] Protective role of Panax ginseng extract standardized with ginsenoside Rg3 against acrylamide-induced neurotoxicity in ratsJOURNAL OF APPLIED TOXICOLOGY, Issue 3 2006Fathia Mannaa Abstract Acrylamide (ACR) is an industrial neurotoxic chemical that has been recently found in carbohydrate-rich foods cooked at high temperatures. ACR was designated as a probable human carcinogen by IARC (1994) and USEPA (1988). Panax ginseng extract has efficacies such as anticancer, antihypertension, antidiabetes and antinociception. The objective of the current study is to evaluate the protective effects of Panax ginseng extract against ACR-induced toxicity in rats. Sixty adult Sprague Dawley female rats were divided into six groups included a control group, a group treated orally with ACR (50 mg kg,1 body weight; b.w.) for 11 days, a group treated orally with Panax ginseng extract (20 mg kg,1 b.w.) for 11 days and groups treated orally with Panax ginseng for 11 days before, during or after 11 days of ACR treatment. The results indicated that treatment with ACR alone resulted in a significant increase in lipid peroxidation level and LDH activity in brain homogenate as well as in serum CK activity, whereas it caused a significant decrease in SOD activity and a small but statistically insignificant decrease in Na+K+ -ATPase activity in brain homogenate. Serum serotonin, corticosterone, T3, T4, TSH, estradiol, progesterone and plasma adrenaline were significantly decreased in ACR-treated rats. Treatment with Panax ginseng before, during or after ACR treatment reduced or partially antagonized the effects induced by ACR towards the normal values of controls. It could be concluded that Panax ginseng extract exhibited a protective action against ACR toxicity and it is worth noting that treatment with Panax ginseng extract before or at the same time as ACR treatment was more effective than when administered after ACR treatment. Copyright © 2006 John Wiley & Sons, Ltd. [source] Age-dependent telomere-shortening is repressed by phosphorylated ,-tocopherol together with cellular longevity and intracellular oxidative-stress reduction in human brain microvascular endotheliocytesJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 3 2007Yasufumi Tanaka Abstract Cellular life-span of neonatal human brain microvascular endotheliocytes (HBME) was estimated by population doubling levels (PDLs) for serial subcultivations until spontaneous proliferation stoppage, and was 2.4-fold longer for continuous administration with the 6- O -phosphorylated derivative (TocP) of ,-tocopherol (Toc), being bio-available owing to its water-solubility, or TocP plus 2- O -phosphorylated ascorbate (Asc2P), and 1.3-fold longer with Asc2P, at a dose of 150 µM, than for the non-administered control. Enlarged cell diameters indicative of cellular aging were repressed for TocP-administered cells as analyzed with a channelizer. Age-dependent shortening of telomeric DNA length (291 bp/PDL) was slowed markedly for TocP (165 bp/PDL) or TocP plus Asc2P, but slightly for Asc2P. Telomerase activity as assessed by the PCR-based TRAP method was detectable slightly at younger ages but no longer at middle ages for the non-administered cells, but, for TocP-administered cells, was intensely detected at younger ages and appreciably until middle ages. Intracellular TocP amounts were not changed age-dependently in contrast to a marked decrease in Toc which accrued from TocP esterolysis. This may be partly attributed to age-dependent changes in the lipid peroxidation product acrolein (ACR), which was abundant at older ages in non-administered cells, but scarcely in TocP-administered cells. Furthermore, intracellular reactive oxygen species (ROS) such as H2O2 and hydroperoxides as detected using the redox indicator CDCFH-DA was less abundant in TocP-administered cells than in non-administered cells. Thus the telomeric-DNA retention, concurrently with retained telomerase activity, was shown to be correlated with cellular longevity, and may be supported by diminished oxidative stress, in hydrophobic microenvironment, which can be achieved by TocP rather than AscP. J. Cell. Biochem. 102: 689,703, 2007. © 2007 Wiley-Liss, Inc. [source] A retrospective review of the outcome of plasma exchange and aggressive medical therapy in antibody mediated rejection of renal allografts: A single center experienceJOURNAL OF CLINICAL APHERESIS, Issue 6 2008Wisam Al-Badr Abstract Antibody-mediated rejection (AMR) has been recognized as a major cause of renal allograft loss. Protocols using plasma exchange (PE) to reverse rejection have mixed results. Methods: A retrospective chart review was performed to determine the clinical response to PE inpatients with AMR of renal allograft. A good response to treatment was defined as a decline in serum creatinine (SCr) to within 25% above the prerejection value or discontinuation of dialysis with a SCr <2 mg/dl within 3 months of discharge from the hospital and disappearance of donor-specific alloantibodies (DSA). Results: Twenty-two patients, treated with PE for biopsy proven AMR with or without acute-cellular rejection (ACR), were included in the study. Sixty-four percent of patients had concurrent AMR and ACR. Fifty-two percent of all patients had a good response to antirejection therapy, whereas 63% of patients with only AMR and 46% of patients with both AMR and ACR had a good response. Good response to PE did not correlate with the number of plasma volumes exchanged (P = 0.09), but correlated with a shorter period from transplantation to the rejection episode (P = 0.002). Conclusion: Only a shorter interval between transplantation and the acute rejection episode correlated with a good response to PE. J. Clin. Apheresis, 2008. © 2008 Wiley-Liss, Inc. [source] Synchronised therapy and high-dose cyclophosphamide in proliferative lupus nephritisJOURNAL OF CLINICAL APHERESIS, Issue 2 2002Maria Giovanna Danieli Abstract The aim of this open study was to compare the outcomes and side effects of plasmapheresis (PP) in patients with proliferative lupus nephritis treated with cyclophosphamide (Cyc) boluses. The study involved 28 consecutive patients. All of the patients met the ACR modified criteria for SLE and underwent a qualifying renal biopsy. In group I, patients were treated with synchronised therapy (PP, 50 ml/kg, followed by pulse Cyc, 750 mg/m2, repeated monthly for 6 months), whereas in group II, they were given only intermittent Cyc boluses (at the same dosage). The data were collected in the patients' records according to a standardised protocol. Patients were followed-up for a mean of 4 years. The disease-free survival was analysed using Kaplan-Meier estimated survival curves ([S(t)]). At the end of the 6-month treatment period, a statistically significant number of patients in group I (75%) was in complete remission in comparison to group II (31%) (P < 0.02), whereas at long-term follow-up, these percentages were similar (41% vs. 50%, P = n.s.). The main functional and immunological parameters showed a normalisation in both groups. The risk of a poor renal outcome significantly correlated with high serum creatinine levels at the onset of nephritis (P < 0.05). We documented a higher rate of infectious complications in group I. This study reports that synchronised therapy is useful in inducing a faster remission in patients with proliferative lupus nephritis. However, it is not superior to conventional therapy at long term follow-up analysis. Positive results should be reinforced by a long-term maintenance therapy. J. Clin. Apheresis 17:72,77, 2002. © 2002 Wiley-Liss, Inc. [source] Anti-C1q antibodies: association with nephritis and disease activity in systemic lupus erythematosusJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 1 2009Carlos Geraldo Moura Abstract Background: Anti-C1q antibodies have been described in systemic lupus erythematosus (SLE) as well as in other connective tissue diseases. They have been considered as a marker for disease activity and presence of nephritis. Objective: The aim of this study was to determine the prevalence of anti-C1q antibodies in Brazilian lupus patients as well as analyze their association with different clinical and serologic parameters. Methods: Sera from 81 SLE patients, based on the American College of Rheumatology (ACR) criteria, were collected from a lupus referral outpatient clinic in Salvador, Brazil. Antibodies to C1q were detected by an enzyme-linked immunoassay (ELISA) kit and antibodies to other cellular antigens identified by indirect immunofluorescence on HEp-2 cell substrate (ANA), or Crithidia luciliae (dsDNA), and to nucleosome by ELISA. A cutoff of 20,U wasestablished for anti-C1q and antinucleosome assays. Results: Anti-C1q antibodies were detected in 39.5% (32/81) of SLE sera. The presence of anti-C1q antibodies was associated with proteinuria (P=0.028) but not with other laboratory or clinical features, such as antinucleosome or anti-dsDNA antibodies, hematuria, urinary casts or renal failure, leukopenia, pericarditis, pleuritis, malar rash, seizures, and psychosis. There was a positive correlation between the titers of anti-C1q antibodies and the systemic lupuis erythematosus disease activity index (SLEDAI) score (r=0.370; P=0.001). Conclusion: This study in Brazilian SLE patients confirms previous findings of the association of anti-C1q antibodies with nephritis and disease activity. J. Clin. Lab. Anal. 23:19,23, 2009. © 2009 Wiley-Liss, Inc. [source] Reproductive isolation between chromosomal races of the house mouse Mus musculus domesticus in a parapatric contact area revealed by an analysis of multiple unlinked lociJOURNAL OF EVOLUTIONARY BIOLOGY, Issue 2 2008P. FRANCHINI Abstract The house mouse, Mus musculus domesticus, exhibits a high level of chromosomal polymorphism because of the occurrence and fast fixation of Robertsonian fusions between telocentric chromosomes. For this reason, it has been considered a classical speciation model to analyse the role of the chromosomal changes in reproductive isolation. In this study, we analysed a parapatric contact area between two metacentric races in central Italy, the Cittaducale race (CD: 2n = 22) and the Ancarano race (ACR: 2n = 24), to estimate gene flow at the boundary. Hybrids between these two races show high levels of structural heterozygosity and are expected to be highly infertile. A sample of 88 mice from 14 sites was used. The mice were genotyped by means of eight microsatellite loci mapped in four different autosomal arms. The results show clear genetic differentiation between the CD and ACR races, as revealed by differences in allele frequencies, factorial correspondence analysis and indexes of genetic population (e.g. FST and RST) along the contact zone. The genetic differentiation between the races was further highlighted by assignation and clustering analyses, in which all the individuals were correctly assigned by their genotypes to the source chromosomal race. This result is particularly interesting in view of the absence of any geographical or ecological barrier in the parapatric contact zone, which occurs within a village. In these conditions, the observed genetic separation suggests an absence of gene flow between the races. The CD,ACR contact area is a rare example of a final stage of speciation between chromosomal races of rodents because of their chromosomal incompatibility. [source] Immunohistochemical staining of liver grafts with a monoclonal antibody against HCV-Envelope 2 for recurrent hepatitis C after living donor liver transplantationJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 4 2009Hiroshi Sadamori Abstract Aim:, We evaluated the expression of hepatitis C virus (HCV) antigen on liver grafts by immunohistochemical staining (IHS) using IG222 monoclonal antibody (mAb) against HCV-envelope 2 (E2). Methods:, The study material was 84 liver biopsy specimens obtained from 28 patients who underwent living donor liver transplantation (LDLT) for HCV infection. The biopsy samples were examined histopathologically, and by IHS using IG222 mAb against HCV-E2. Serum HCV-RNA level was measured in all patients. The IHS grades were compared among the three groups classified according to the time elapsed from LDLT (at 1,30, 31,179 and ,180 days post-LDLT) and among four post-transplant conditions, including acute cellular rejection (ACR). Results:, Immunoreactivity to IG222 was detected in 78.6% of the specimens obtained during the first month after LDLT, and there were no significant differences on the IHS grades between the three groups classified according to the time elapsed from LDLT. The IHS grades were significantly stronger in definite recurrent HCV (n = 12) and probable recurrent HCV (n = 7) than in definite ACR (n = 7) and other complications (n = 8). There were no significant differences in serum HCV-RNA levels among the four post-transplant conditions. There was no significant correlation between the IHS grades using IG222 mAb and serum HCV-RNA levels when data of 84 liver biopsy specimens were analyzed. Conclusions:, Constant HCV-E2 expression was observed in liver biopsy specimens obtained 1 month or longer. The strong HCV-E2 expression on liver grafts were associated with recurrent hepatitis C after LDLT, but the serum HCV-RNA levels were not. [source] A tandem MS precursor-ion scan approach to identify variable covalent modification of albumin Cys34: a new tool for studying vascular carbonylationJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 11 2008Giancarlo Aldini Abstract We developed a liquid chromatography electrospray ionisation multi-stage mass spectrometry (LC-ESI-MS/MS) approach based on precursor-ion scanning and evaluated it to characterize the covalent modifications of Cys34 human serum albumin (HSA) caused by oxidative stress and reactive carbonyl species (RCS) adduction. HSA was isolated and digested enzymatically to generate a suitable-length peptide (LQQCPF) containing the modified tag residue. The resulting LQQCPF peptides were identified by LC-ESI-MS/MS in precursor-ion scan mode and further characterized in product-ion scan mode. The product ions for precursor-ion scanning were selected by studying the MS/MS fragmentation of a series of LQQCPF derivatives containing Cys34 modified with different ,,,-unsaturated aldehydes and di and ketoaldehydes. We used a Boolean logic to enhance the specificity of the method: this reconstitutes a virtual current trace (vCT) showing the peaks in the three precursor-ion scans, marked by the same parent ion. The method was first evaluated to identify and characterize the Cys34 covalent adducts of HSA incubated with 4-hydroxy-hexenal, 4-hydroxy- trans -2-nonenal (HNE) and acrolein (ACR). Then we studied the Cys34 modification of human plasma incubated with mildly oxidized low-density lipoproteins (LDL), and the method easily identified the LQQCPF adducts with HNE and ACR. In other experiments, plasma was oxidized by 2,2'-azobis(2-amidinopropane) HCl (AAPH) or by Fe2+/H2O2. In both conditions, the sulfinic derivative of LQQCPF was identified and characterized, indicating that the method is suitable not only for studying RCS-modified albumin, but also to check the oxidative state of Cys34 as a marker of oxidative damage. Copyright © 2008 John Wiley & Sons, Ltd. [source] First cosmogenic 10Be constraints on LGM glaciation on New Zealand's North Island: Park Valley, Tararua Range,JOURNAL OF QUATERNARY SCIENCE, Issue 8 2008Martin S. Brook Abstract We report the first direct ages for late Quaternary glaciation on the North Island of New Zealand. Mt Ruapehu, the volcanic massif in the North Island's centre, is currently glaciated and probably sustained glaciers throughout the late Quaternary, yet no numeric ages have been reported for glacial advances anywhere on the North Island. Here, we describe cosmogenic 10Be ages of the surface layers of a glacially transported boulder and glacially polished bedrock from the Tararua Range, part of the axial ranges of the North Island. Results indicate that a limited valley glaciation occurred, culminating in recession at the end of the last glacial coldest period (LGCP, ca. 18,ka). This provides an initial age for deglaciation on the North Island during the last glacial,interglacial transition (LGIT). It appears that glaciation occurred in response to an equilibrium-line altitude (ELA) lowering of ,1400,m below the present-day mean summer freezing level. Ages for glaciation in the Tararua Range correspond closely to exposure ages for the last glacial maximum (LGM) from the lateral moraines of Cascade Valley in the South Island, and in Cobb Valley, in northern South Island. The corollary is that glaciation in the Tararua Range coincided with the phase of maximum cooling during MIS 2, prior to the Antarctic Cold Reversal (ACR), during the LGCP. Copyright © 2008 John Wiley & Sons, Ltd. [source] Spouse Abuse and Alcohol Problems Among White, African American, and Hispanic U.S. Army SoldiersALCOHOLISM, Issue 10 2006Nicole S. Bell Background: Prior studies suggest racial/ethnic differences in the associations between alcohol misuse and spouse abuse. Some studies indicate that drinking patterns are a stronger predictor of spouse abuse for African Americans but not whites or Hispanics, while others report that drinking patterns are a stronger predictor for whites than African Americans or Hispanics. This study extends prior work by exploring associations between heavy drinking, alcohol-related problems, and risk for spouse abuse within racial/ethnic groups as well as variations associated with whether the perpetrator is drinking during the spouse abuse incident. Methods: Cases (N=7,996) were all active-duty male, enlisted Army spouse abusers identified in the Army's Central Registry (ACR) who had also completed an Army Health Risk Appraisal (HRA) Survey between 1991 and 1998. Controls (N=17,821) were matched on gender, rank, and marital and HRA status. Results: We found 3 different patterns of association between alcohol use and domestic violence depending upon both the race/ethnicity of the perpetrator and whether or not alcohol was involved in the spouse abuse event. First, after adjusting for demographic and psychosocial factors, weekly heavy drinking (>14 drinks per week) and alcohol-related problems (yes to 2 or more of 6 alcohol-related problem questions, including the CAGE) were significant predictors of domestic violence among whites and Hispanics only. Also for the white soldiers, the presence of family problems mediated the effect of alcohol-related problems on spouse abuse. Second, alcohol-related problems predicted drinking during a spouse abuse incident for all 3 race groups, but this relation was moderated by typical alcohol consumption patterns in Hispanics and whites only. Finally, alcohol-related problems predicted drinking during a spouse abuse incident, but this was a complex association moderated by different psychosocial or behavioral variables within each race/ethnic group. Conclusion: These findings suggest important cultural/social influences that interact with drinking patterns. [source] Gene expression profiling of acute cellular rejection in rat liver transplantation using DNA microarraysLIVER TRANSPLANTATION, Issue 5 2009Naoki Hama Acute cellular rejection (ACR) is still a major problem in organ transplantation, and its genetic and molecular mechanisms remain poorly understood. We used DNA microarrays to investigate the gene expression profiles in ACR. We hypothesized that changes of gene expression in grafts could also be detected in peripheral blood leukocytes. We first compared the gene expression profiles in liver isografts (Lewis to Lewis) and allografts (Dark Agouti to Lewis) harvested from rats at days 1, 3, 5, and 7 after transplantation. Hierarchical clustering analysis indicated that gene expression started to change on day 3, and 89 differentially expressed genes were extracted from allografts in comparison with isografts at day 3. Most of the up-regulated genes were associated with graft-infiltrating leukocytes. We then confirmed the similarity of gene expression changes in peripheral leukocytes by quantitative real-time polymerase chain reaction. We also investigated the gene expression changes in other inflammatory and liver dysfunction models. Two interferon-gamma inducible genes, interferon regulatory factor 1 and guanylate nucleotide binding protein 2, were overexpressed in both the peripheral leukocytes and liver graft during ACR. Although further studies are necessary, these 2 genes in peripheral leukocytes could be potentially useful markers for rejection or immunosuppression. Liver Transpl 15:509,521, 2009. © 2009 AASLD. [source] Initial steroid bolus injection promotes vigorous CD8+ alloreactive responses toward early graft acceptance immediately after liver transplantation in humansLIVER TRANSPLANTATION, Issue 9 2007Hiroto Egawa We have found that steroid bolus withdrawal prior to graft reperfusion increased the incidence of acute cellular rejection (ACR). This study aims to clarify how initial steroid bolus (ISB) injection at reperfusion influences the kinetics of CD8+ alloreactive immune responses immediately after living donor liver transplantation (LDLT). A total of 49 hepatitis C virus (HCV)-infected recipients were classified into 3 groups according to hierarchical clustering by preoperative CD8+CD45 isoforms. The naive T cell proportion was considerably higher in Group I than in Groups II and III, whereas Group II recipients had the highest effector memory (EM) T cells and Group III the highest effector T cells. The frequency of ACR was significantly higher in recipients without ISB than in those with ISB. In particular, the ACR rates were the highest in Group II without ISB. Following ISB, the proportion of effector T cells was promptly upregulated within 6 hours after graft reperfusion, simultaneously with the upregulation of CD27,CD28, subsets, interferon-gamma (IFN-,), tumor necrosis factor-alpha and perforin expression, which significantly correlated with increasing interleukin (IL)-12 receptor beta 1 cells. These were then downregulated to below preoperative levels by tacrolimus (Tac) administered at 24 hours. These changes did not occur in the absence of ISB. In Group II without ISB, the downregulation of IL-12R,1+ cells was the greatest, consistent with the highest rates of ACR and mortality (60%). In conclusion, ISB must be done in place, especially in Group II with preexisting high EM T cells, to enable the development of early allograft acceptance. Liver Transpl 13:1262,1271, 2007, © 2007 AASLD. [source] Intervention strategies to inhibit protein carbonylation by lipoxidation-derived reactive carbonylsMEDICINAL RESEARCH REVIEWS, Issue 6 2007Giancarlo Aldini Abstract Protein carbonylation induced by reactive carbonyl species (RCS) generated by peroxidation of polyunsaturated fatty acids plays a significant role in the etiology and/or progression of several human diseases, such as cardiovascular (e.g., atherosclerosis, long-term complications of diabetes) and neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, and cerebral ischemia). Most of the biological effects of intermediate RCS, mainly ,,,-unsaturated aldehydes, di-aldehydes, and keto-aldehydes, are due to their capacity to react with the nucleophilic sites of proteins, forming advanced lipoxidation end-products (ALEs). Because of the emerging deleterious role of RCS/protein adducts in several human diseases, different potential therapeutic strategies have been developed in the last few years. This review sheds focus on fundamental studies on lipid-derived RCS generation, their biological effects, and their reactivity with proteins, with particular emphasis to 4-hydroxy- trans -2-nonenal (HNE)-, acrolein (ACR)-, malondialdehyde (MDA)-, and glyoxal (GO)-modified proteins. It also discusses the recently developed pharmacological approaches for the management of chronic diseases in which oxidative stress and RCS formation are massively involved. Inhibition of ALE formation, based on carbonyl-sequestering agents, seems to be the most promising pharmacological tool and is reviewed in detail. © 2006 Wiley Periodicals, Inc. Med Res Rev, 27, No. 6, 817,868, 2007 [source] Association of mast cells and liver allograft rejectionPEDIATRIC TRANSPLANTATION, Issue 3 2008Cigdem Arikan Abstract:, MCs are important effector cells in a broad range of immune responses. Their role in liver allograft rejection is not clear. Twenty-one liver transplant recipients (mean age ± s.d.; 10.2 ± 4.1 yr) who experienced a rejection episode are included in this study. Biopsy specimens from normal livers (allograft biopsy with normal histopathology n = 5 and naïve livers n = 6), transplanted livers with CR (n = 5), and transplanted livers with ACR (n = 26) were studied. The total number of PT in each biopsy specimen was documented, and the number of PT that contained MCs was expressed as a percentage of the total number of PT. MCs, percentage of PT containing MCs and the average number of MCs/PT was significantly higher in rejection specimens than in control biopsy samples. All parameters were significantly higher in CR group than AR groups. Increasing grades of rejection was also associated with progressively more MCs and MC/PT (r = 0.68 p = 0.000; r = 0.58 p = 0.002). Only serum bilirubin level was related to the MCs in AR group. Only MC/PT was detected as an independent predictor of graft survival (p = 0.011, RR 2.87 95% CI 1.3,6.5). Despite the fact that the role of MCs in liver allograft rejection is still unknown; they exist in inflammatory infiltrates during pediatric liver allograft rejection. MC-rich portal infiltrates may distinguish chronic liver rejection from other inflammatory states such as AR, hepatitis and biliary obstruction. [source] Identification of patients with Churg,Strauss syndrome (CSS) using automated dataPHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 10 2004Leslie R. Harrold MD Abstract Purpose Our aim was to identify individuals with Churg,Strauss syndrome (CSS) among asthma drug users, based on patterns of diagnostic and procedural codes (termed ,algorithms') contained in automated claims data. Methods A retrospective study was conducted among patients who had been dispensed asthma drugs at three HMOs. Individuals who received ,3 dispensings of an asthma drug during any consecutive 12-month period beginning 1 January 1994 through 20 June 2000 were identified. Information on patient age, gender, enrollment status, asthma drugs dispensed, inpatient and outpatient diagnoses and procedures were obtained from the HMO automated databases. Twelve combinations of diagnostic and billing codes (,algorithms') were developed using the claims data to identify potential cases of CSS. Chart reviews blinded to drug exposure were performed using a standardized abstraction form. A rheumatologist reviewed abstracted information on all subjects, and those who met two or more American College of Rheumatology (ACR) criteria for CSS were further reviewed by two clinical experts. Cases were classified as unlikely, possible, or probable/definite CSS. Each clinical expert independently rated the cases; disagreements were resolved by consensus. Results A total of 185,604 patients who had been dispensed asthma drugs were identified. Three hundred fifty subjects were selected for chart review, and 15 were classified as having ,probable/definite' CSS. The algorithms that were most successful in identifying patients with CSS were as follows: (1) two or more codes for vasculitis (13 confirmed cases from 129 reviewed; positive predictive value 10%); (2) codes for both vasculitis and neurologic symptoms (6 confirmed cases from 15 reviewed; positive predictive value 40%) and (3) codes for both eosinophilia and vasculitis (4 confirmed cases from 5 reviewed; positive predictive value 80%). Conclusion Automated claims data can be used to identify patients with CSS. This approach can facilitate better epidemiologic study of the risk factors for the condition. Copyright © 2003 John Wiley & Sons, Ltd. [source] Reducing De Novo Donor-Specific Antibody Levels during Acute Rejection Diminishes Renal Allograft LossAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2009M. J. Everly The effect of de novo DSA detected at the time of acute cellular rejection (ACR) and the response of DSA levels to rejection therapy on renal allograft survival were analyzed. Kidney transplant patients with acute rejection underwent DSA testing at rejection diagnosis with DSA levels quantified using Luminex single-antigen beads. Fifty-two patients experienced acute rejection with 16 (31%) testing positive for de novo DSA. Median follow-up was 27.0 ± 17.4 months postacute rejection. Univariate analysis of factors influencing allograft survival demonstrated significance for African American race, DGF, cytotoxic PRA >20% (current) and/or >50% (peak), de novo DSA, C4d and repeat transplantation. Multivariate analysis showed only de novo DSA (6.6-fold increased allograft loss risk, p = 0.017) to be significant. Four-year allograft survival was higher with ACR (without DSA) (100%) than mixed acute rejection (ACR with DSA/C4d) (65%) or antibody-mediated rejection (35%) (p < 0.001). Patients with >50% reduction in DSA within 14 days experienced higher allograft survival (p = 0.039). De novo DSAs detected at rejection are associated with reduced allograft survival, but prompt DSA reduction was associated with improved allograft survival. DSA should be considered a potential new end point for rejection therapy. [source] Incidence and Severity of Acute Cellular Rejection in Recipients Undergoing Adult Living Donor or Deceased Donor Liver Transplantation,AMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2009A. Shaked Living donor liver transplantation (LDLT) may have better immunological outcomes compared to deceased donor liver transplantation (DDLT). The aim of this study was to analyze the incidence of acute cellular rejection (ACR) after LDLT and DDLT. Data from the adult-to-adult living donor liver transplantation (A2ALL) retrospective cohort study on 593 liver transplants done between May 1998 and March 2004 were studied (380 LDLT; 213 DDLT). Median LDLT and DDLT follow-up was 778 and 713 days, respectively. Rates of clinically treated and biopsy-proven ACR were compared. There were 174 (46%) LDLT and 80 (38%) DDLT recipients with ,1 clinically treated episodes of ACR, whereas 103 (27%) LDLT and 58 (27%) DDLT recipients had ,1 biopsy-proven ACR episode. A higher proportion of LDLT recipients had clinically treated ACR (p = 0.052), but this difference was largely attributable to one center. There were similar proportions of biopsy-proven rejection (p = 0.97) and graft loss due to rejection (p = 0.16). Longer cold ischemia time was associated with a higher rate of ACR in both groups despite much shorter median cold ischemia time in LDLT. These data do not show an immunological advantage for LDLT, and therefore do not support the application of unique posttransplant immunosuppression protocols for LDLT recipients. [source] Two Hundred Living Donor Kidney Transplantations Under Alemtuzumab Induction and Tacrolimus Monotherapy: 3-Year Follow-UpAMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2009H. P. Tan Alemtuzumab has been used in off-label studies of solid organ transplantation. We extend our report of the first 200 consecutive living donor solitary kidney transplantations under alemtuzumab pretreatment with tacrolimus monotherapy and subsequent spaced weaning to 3 years of follow-up. We focused especially on the causes of recipient death and graft loss, and the characteristics of rejection. The actuarial 1-, 2- and 3-year patient and graft survivals were 99.0% and 98.0%, 96.4% and 90.8% and 93.3% and 86.3%, respectively. The cumulative incidence of acute cellular rejection (ACR) at the following months was 2%,6, 9.0%,12, 16.5%,18, 19.5%,24, 23.5%,30, 24.0%,36 and 25%,42. The mean serum creatinine (mg/dL) and glomerular filtration rate (mL/min/1.73 m2) at 1 and 3 years were 1.4 ± 0.6 and 58.7 ± 21.6 and 1.5 ± 0.7 and 54.9 ± 20.9, respectively. Fifty (25%) recipients had a total of 89 episodes of ACR. About 88.7% of ACR episodes were Banff 1, and of those, 82% were steroid-sensitive. Nine (4.5%) recipients had antibody-mediated rejection (AMR). About 76.5% were weaned but only 46% are currently on spaced dose (qod or less) tacrolimus monotherapy, and 94.4% remained steroid-free from the time of transplantation. Infectious complications were uncommon. This experience suggests the 3-year efficacy of this approach. [source] Determinants of Poor Graft Outcome in Patients with Antibody-Mediated Acute RejectionAMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2007C. Lefaucheur This study analyzes the incidence and course of antibody-mediated rejection (AMR) in a cohort of 237 renal transplant patients followed for 30 ± 20 months. Among these, 32 patients were considered to be at risk for AMR and received intravenous immunoglobulin (IVIg), either as preconditioning (Group A, n = 18) or at the time of transplant (Group B, n = 14). The prevalence of AMR was 27.8% in Group A, 57.1% in Group B and 3.9% in the remainder of the population. Although graft loss remains greater among AMR than for acute cellular rejection (ACR) or the overall transplant population, we have identified a good outcome group (GFR > 15 mL/min/1.73 m2) (n = 13), whose renal function at the end of follow-up was comparable to that of the general transplant population. The factors associated with bad outcome are: (1) immunologic: presence and/or persistence of donor-specific anti-HLA antibodies post-transplantation and (2) histologic: neutrophilic glomerulitis, peritubular capillary dilatation with neutrophil infiltrates and interstitial edema at the time of first biopsy; and at the time of late biopsy (3,6 months): lesions of vascular rejection, and monocyte/macrophage infiltrates in glomeruli and dilated peritubular capillaries. Persistence of C4d does not predict outcome. This study outlines for the first time the immunologic and histologic profiles of AMR patients with poor prognosis. [source] Acute Cellular Rejection with CD20-Positive Lymphoid Clusters in Kidney Transplant Patients Following Lymphocyte DepletionAMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2007L. K. Kayler Lymphoid clusters (LC) containing CD20-positive B cells in kidney allografts undergoing acute cellular rejection (ACR) have been identified in small studies as a prognostic factor for glucocorticoid resistance and graft loss. Allograft biopsies obtained during the first episode of ACR in 120 recipients were evaluated for LC, immunostained with CD20 antibody, and correlated with conventional histopathologic criteria, response to treatment and outcome. LC were found in 71 (59%) of the 120 biopsies. All contained CD20 positive B cells that accounted for 5,90% of the LC leukocyte content. The incidence of LC was highest in the patients who had no lymphoid depletion or had been treated with Thymoglobulin preconditioning (79% vs. 75%, respectively) compared to 37% in patients pretreated with Campath (p = 0.0001). Banff 1a/1b ACR were more frequent in the LC-positive than the LC-negative group (96% vs. 80%, respectively; p = 0.0051). With a posttransplant follow-up of 953 ± 430 days, no significant differences were detected between LC-postitive and LC-negative groups in time to ACR, steroid resistance, serum creatinine and graft loss. CD20+LC did not portend glucocorticoid resistance or worse short to medium term outcomes. CD20+LC may represent a heterogenous collection in which there may be a small still to be fully defined unfavorable subgroup. [source] | ||||||||||||||||||||||||||||||||||