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2.
Equine Vet J ; 51(6): 825-830, 2019 Nov.
Article in English | MEDLINE | ID: mdl-30866108

ABSTRACT

BACKGROUND: Chemical restraint is often used to perform diagnostic and minor surgical procedures; α2 -adrenoceptor agonists are the most commonly used drugs; however, the combination with an opiate can induce a profound sedation. There is a lack of kinematic studies examining the effects of the combination of these drugs on locomotor patterns. OBJECTIVES: The objective of the study was to evaluate the duration of the effects of sedation with detomidine and detomidine combined with a low dose of butorphanol on the movement patterns of horses. STUDY DESIGN: The study was a controlled, randomised, blinded and crossover experiment. METHODS: Each of six horses was injected intravenously with saline (0.9%) solution (10 mL), detomidine diluted in saline solution (0.01 mg/kg bwt) or a combination of detomidine (0.01 mg/kg bwt) and butorphanol (0.02 mg/kg bwt) diluted in saline solution, in a random order. A single accelerometer positioned at the sacrum was used for gait assessment 15 min before (baseline) and 5, 15, 30, 45, 60, 75, 90, 105 and 120 min after each injection. Eight variables were measured, including speed, stride frequency, stride length, regularity, dorsoventral power, propulsive power, mediolateral power and total power; force of acceleration and the three components of power were calculated. The degree of sedation was measured by the ground-to-lip distance. RESULTS: There were significant differences among groups, with shorter effects after the injection of the combination of drugs, for most parameters. MAIN LIMITATIONS: A small number of horses were involved in the study. CONCLUSIONS: The combination of detomidine and butorphanol produces a shorter effect on almost all accelerometric parameters, probably due to the excitement produced by the opioid drug causing a quicker return to normal values. Accelerometry offers a method of objectively monitoring gait abnormalities in walking sedated horses.


Subject(s)
Butorphanol/pharmacology , Conscious Sedation/veterinary , Horses , Imidazoles/pharmacology , Motor Activity/drug effects , Accelerometry/veterinary , Analgesics, Opioid/administration & dosage , Analgesics, Opioid/pharmacology , Animals , Butorphanol/administration & dosage , Cross-Over Studies , Drug Therapy, Combination , Female , Gait/drug effects , Hypnotics and Sedatives/administration & dosage , Hypnotics and Sedatives/pharmacology , Imidazoles/administration & dosage , Male
4.
Org Biomol Chem ; 16(4): 521-525, 2018 01 24.
Article in English | MEDLINE | ID: mdl-29210413

ABSTRACT

A collection of systematically substituted 3-cyclo-butylcarbamoyl hydantoins was synthesized by a regioselective multicomponent domino process followed by easy coupling reactions. Calculations, NMR studies and X-ray analysis show that these scaffolds are able to project their side chains similar to common secondary structures, such as the α-helix and ß-turn, with favourable enthalpic and entropic profiles.


Subject(s)
Cyclobutanes/chemistry , Hydantoins/chemistry , Peptidomimetics/chemistry , Cyclobutanes/chemical synthesis , Hydantoins/chemical synthesis , Hydrogen Bonding , Models, Chemical , Models, Molecular , Molecular Conformation , Peptidomimetics/chemical synthesis
5.
Br J Cancer ; 112(1): 69-76, 2015 Jan 06.
Article in English | MEDLINE | ID: mdl-25314061

ABSTRACT

BACKGROUND: Surveillance for hepatocellular carcinoma (HCC) is recommended in patients with cirrhosis. As α-fetoprotein (AFP) is considered a poor surveillance test, we tested the performance of its changes over time. METHODS: Eighty patients were diagnosed with HCC (cases) during semiannual surveillance with ultrasonography and AFP measurement were recruited and matched for age, gender, etiology and Child-Pugh class with 160 contemporary cancer-free controls undergoing the same surveillance training group (TG). As a validation group (VG) we considered 36 subsequent patients diagnosed with HCC, matched 1 : 3 with contemporary cancer-free controls. α-Fetoprotein values at the time of HCC diagnosis (T0) and its changes over the 12 (Δ12) and 6 months (Δ6) before cancer detection were considered. RESULTS: In both TG and VG, >80% of HCCs were found at an early stage. In TG, AFP significantly increased over time only in cases. T0 AFP and a positive Δ6 were independently associated with HCC diagnosis (odds ratio: 1.031 and 2.402, respectively). The area under the curve of T0 AFP was 0.76 and its best cutoff (BC) was 10 ng ml(-1) (sensitivity 66.3%, specificity 80.6%). The combination of AFP >10 ng ml(-1) or a positive Δ6 composite α-fetoprotein index (CAI) increased the sensitivity to 80% with a negative predictive value (NPV) of 86.2%. Negative predictive value rose to 99%, considering a cancer prevalence of 3%. In the VG, the AFP-BC was again 10 ng ml(-1) (sensitivity 66.7%, specificity 88.9%), and CAI sensitivity was 80.6% with a NPV value of 90.5%. CONCLUSIONS: CAI achieves adequate sensitivity and NPV as a surveillance test for the early detection of HCC in cirrhosis.


Subject(s)
Carcinoma, Hepatocellular/chemistry , Liver Cirrhosis/diagnosis , Liver Neoplasms/chemistry , alpha-Fetoproteins/analysis , Adult , Aged , Aged, 80 and over , Carcinoma, Hepatocellular/diagnosis , Case-Control Studies , Female , Humans , Liver Neoplasms/diagnosis , Male , Middle Aged , Prospective Studies , Retrospective Studies
6.
Methods Inf Med ; 53(2): 121-36, 2014.
Article in English | MEDLINE | ID: mdl-24573195

ABSTRACT

BACKGROUND: Heart failure (HF) is affecting millions of people every year and it is characterized by impaired ventricular performance, exercise intolerance and shortened life expectancy. Despite significant advancements in drug therapy, mortality of the disease remains excessively high, as heart transplant remains the gold standard treatment for end-stage HF when no contraindications subsist. Traditionally, implanted Ventricular Assist Devices (VADs) have been employed in order to provide circulatory support to patients who cannot survive the waiting time to transplantation, reducing the workload imposed on the heart. In many cases that process could recover its contractility performance. OBJECTIVES: The SensorART platform focuses on the management and remote treatment of patients suffering from HF. It provides an interoperable, extendable and VAD-independent solution, which incorporates various hardware and software components in a holistic approach, in order to improve the quality of the patients' treatment and the workflow of the specialists. This paper focuses on the description and analysis of Specialist's Decision Support System (SDSS), an innovative component of the SensorART platform. METHODS: The SDSS is a Web-based tool that assists specialists on designing the therapy plan for their patients before and after VAD implantation, analyzing patients' data, extracting new knowledge, and making informative decisions. RESULTS: SDSS offers support to medical and VAD experts through the different phases of VAD therapy, incorporating several tools covering all related fields; Statistics, Association Rules, Monitoring, Treatment, Weaning, Speed and Suction Detection. CONCLUSIONS: SDSS and its modules have been tested in a number of patients and the results are encouraging.


Subject(s)
Decision Support Techniques , Heart Failure/therapy , Heart-Assist Devices , Monitoring, Physiologic , Postoperative Care , Remote Consultation , Software , Therapy, Computer-Assisted , Expert Systems , Humans , Internet , Patient Care Planning , Quality Improvement , Workflow
7.
Clin Biochem ; 46(1-2): 94-8, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23103705

ABSTRACT

OBJECTIVES: Neopterin, a marker of inflammation and monocyte activation, is found increased in patients with heart failure (HF). This study investigates whether neopterin levels correlate with left ventricular (LV) remodeling and brain natriuretic peptide (BNP), a marker of cardiac stress, in chronic HF (CHF) patients with different severity of disease. DESIGN AND METHODS: The relationship between neopterin and LV dimensions, NT-proBNP, and pro-inflammatory cytokines were studied in 98 CHF patients, while nineteen healthy subjects were enrolled as controls. Nineteen (19%) patients were in NYHA class I, 38 (39%) in NYHA class II, 27 (28%) in NYHA class III, and 14 (14%) in NYHA class IV. RESULTS: Neopterin levels were higher in CHF patients than in age- and gender-matched healthy controls, and related with indexed LV end-diastolic volume (LVEDVi). Prospectively CHF patients were separated into tertiles of low, medium and high neopterin levels. Among patients, male gender, LVEDVi, diuretic treatment, NYHA class I, NT-proBNP and IL-8 levels were significant determinants of urine neopterin levels by bivariate analysis. Neopterin levels were associated only to LV remodeling, as assessed by LVEDVi, and IL-8 levels, a crucial monocyte chemoattractant, by multivariate ordinal regression analysis. CONCLUSIONS: The relationship between elevated neopterin levels and LV enlargement in CHF patients suggests a crucial role of monocyte activation in the development of cardiac dysfunction in CHF patients. Assessment of neopterin levels is a potential biomarker to evaluate the progression of LV remodeling in CHF patients.


Subject(s)
Heart Failure/blood , Heart Failure/physiopathology , Neopterin/blood , Ventricular Remodeling/physiology , Adult , Biomarkers/blood , Case-Control Studies , Chronic Disease , Female , Humans , Interleukin-8/blood , Male , Middle Aged , Monocytes/physiology , Multivariate Analysis , Natriuretic Peptide, Brain/blood
8.
Peptides ; 36(2): 192-8, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22677787

ABSTRACT

This study aimed to evaluate left ventricular assist device (LVAD) effects on natriuretic peptide (NP) prohormone plasma levels in end-stage heart failure (HF) patients, especially NT-proCNP, in order to better characterize the NP system during hemodynamic recovery by LVAD. HF patients (n=17, NYHA III-IV) undergoing LVAD were studied: 6 died of multi-organ failure syndrome (NS) and 11 survived (S). Total sequential organ failure assessment (t-SOFA) score and blood samples were obtained at admission (T1) and at 24, 72h and 1, 2, 4 weeks (T2-T6) after LVAD. In S, NT-proANP and NT-proCNP significantly increased at 24h after implantation, reaching a reduction to basal levels at 4 weeks following LVAD [NT-proANP: T1 vs. T2 p=0.017, NT-proCNP: T1 vs. T2 p=0.028, T1 vs. T3 p=0.043]. Elevated NT-proBNP plasma levels were observed at all times. In NS, NP plasma levels sustained higher with respect to S. No statistical variation was observed for NT-proCNP and NT-proANP in S and NS while NT-proBNP reached significant differences at T4 in NS. Considering S+NS, only NT-proCNP strongly correlated with t-SOFA score at T1 (rho=0.554, p=0.04) while subdividing patients NT-proCNP positively correlated in NS with t-SOFA score (rho=0.988, p=0.002) only at T4. In NS a correlation between NT-proCNP and NT-proBNP at T1 was observed (rho=-0.900, p=0.037). Both IL-6 and TNF-alpha sustained higher in NS patients than in S; in particular, statistical significance was observed for IL-6. The study of new peptides, such as NT-proCNP, would provide additional information for identifying patients who are more likely to recover.


Subject(s)
Heart Failure/drug therapy , Heart-Assist Devices , Natriuretic Peptide, C-Type/blood , Female , Humans , Male , Middle Aged , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood
9.
J Clin Endocrinol Metab ; 96(7): E1115-9, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21525159

ABSTRACT

CONTEXT: Newborns with congenital hypothyroidism (CH) have an increased risk for congenital heart defects (CHD) due to a common embryonic developmental program between thyroid gland and heart and great vessels. OBJECTIVE: Our objective was to investigate the prevalence and origin of thyroid disorders in young patients with CHD. DESIGN AND SETTING: We conducted a prospective observational study between January 2007 and January 2009 in academic Pediatric Cardiosurgery and Endocrinology. PATIENTS: Patients included 324 children (164 males, 160 females, aged 0.2-15.4 yrs) with CHD. INTERVENTION: Subjects underwent hormonal and genetic screening. MAIN OUTCOME MEASURES: Serum TSH and thyroid hormone levels were assessed. RESULTS: Two CHD patients were diagnosed with CH at the neonatal screening (1:162). Mild hypothyroidism (serum TSH > 4.0 µU/ml) was diagnosed and confirmed 6 months later [TSH = 5.4 ± 1.5 µU/ml; free T(4) = 1.3 ± 0.2 ng/dl (normal values 0.8-1.9)] in 37 children (11.5%) who were negative at neonatal screening. Hypothyroidism was not related to type of CHD, whereas TSH levels positively correlated with serum N-terminal pro-type B natriuretic peptide levels. Biochemical and ultrasound findings consistent with thyroid autoimmunity were present in three of 37 hypothyroid children (8.1%). One patient had hemiagenesis (2.7%). Variations in candidate genes were screened in CHD patients. NKX2.5 coding sequence was normal in all samples. A 3-Mb microdeletion in 22q11.2 was detected in three patients (8.3%), whereas only known polymorphisms were identified in TBX1 coding sequence. CONCLUSIONS: CHD patients have an increased risk for both CH (10-fold higher) and acquired mild hypothyroidism (3-fold higher). Unrecognized mild hypothyroidism may negatively affect the outcome of CHD children, suggesting that thyroid function should be repeatedly checked. Thyroid autoimmunity and 22q11.2 microdeletions account for small percentages of these cases, and still unknown mechanisms underline such a strong association.


Subject(s)
Heart Defects, Congenital/complications , Hypothyroidism/complications , Thyroid Hormones/blood , Adolescent , Child , Child, Preschool , Female , Heart Defects, Congenital/blood , Humans , Hypothyroidism/blood , Hypothyroidism/diagnosis , Infant , Infant, Newborn , Male , Neonatal Screening , Prospective Studies , Risk , Severity of Illness Index
10.
Transplant Proc ; 42(4): 1283-5, 2010 May.
Article in English | MEDLINE | ID: mdl-20534282

ABSTRACT

BACKGROUND: Combined heart-kidney transplantation (HKTx) is an accepted therapeutic option for patients with end-stage heart disease associated with severely impaired renal function. We report our long-term follow-up with this combined procedure. PATIENTS AND METHODS: Between April 1989 to November 2009, nine patients underwent combined simultaneous (HKTx) at our center. Seven patients were males (mean age 45.2 +/- 10.12 years); seven patients were on dialysis at the time of transplantation. RESULTS: Surgical procedures were uneventful in all patients. One patient died in the intensive care unit 41 days after transplantation. During long-term follow-up, three patients died: one due to infection and multiorgan failure 148 months after HKTx, one due to a lung neoplasm after 6 years, and one, a cerebral stroke at 34 months after transplantation. Only one patient experience renal allograft failure secondary to hypertension and cyclosporine nephrotoxicity at 10 years after HKTx with the need for renal replacement therapy. Last estimated glomerular filtration rates of all other patients was 61.3 +/- 17.4 mL/min. CONCLUSIONS: In selected patients, with coexisting end-stage cardiac and renal failure, combined HKTx with an allograft from the same donor proved to give satisfactory short- and long-term results, with a low incidence of both cardiac and renal allograft complications.


Subject(s)
Heart Diseases/surgery , Heart Transplantation/statistics & numerical data , Kidney Diseases/surgery , Kidney Transplantation/statistics & numerical data , Adult , Female , Follow-Up Studies , Graft Rejection , Heart Diseases/complications , Heart Failure/complications , Heart Failure/surgery , Heart Transplantation/pathology , Humans , Hypertension/complications , Hypertension/surgery , Kidney Diseases/complications , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/surgery , Kidney Transplantation/pathology , Male , Middle Aged , Patient Selection , Tissue Donors , Treatment Outcome
11.
Transplant Proc ; 42(4): 1286-90, 2010 May.
Article in English | MEDLINE | ID: mdl-20534283

ABSTRACT

OBJECTIVE: Cardiac allograft vasculopathy represents an accelerated form of obstructive coronary disease. It is the main cause of late death following heart transplantation. Percutaneous coronary intervention is considered a palliative procedure due to high restenosis rates. The aim of this study was to review our experience with percutaneous coronary interventions using stents in cardiac transplant recipients. METHODS: The present analysis included all primary adult heart transplanted patients who had been discharged from the hospital after transplantation, had a clinical follow-up of 12 months and underwent percutaneous coronary intervention (PCI). RESULTS: Seventy heart transplanted patients underwent percutaneous revascularization. Our analysis comprised 85 first-vessel procedures resulting in treatment of 135 lesions. The mean time from heart transplantation to first intervention was 9.3 +/- 4.8 years. Primary success was obtained in 96% lesions; at least 1 recurrent stenosis event occurred in 16 patients with primarily successful PCI. Lesions treated with drug-eluting stents experienced recurrent stenosis in 16% of cases. During a mean follow-up after PCI of 45.2 +/- 41.7 months, 27 deaths (19 cardiac) and 1 late re-transplantation occurred after PCI. CONCLUSION: In cardiac transplant recipients, percutaneous coronary intervention with stents can be performed safely with high rates of primary success. Restenosis rates were higher compared with coronary interventions in native coronary arteries. Drug-eluting stents seemed to favorably impact restenosis compared with bare-metal stents. The clinical benefit from percutaneous coronary intervention may be reduced due to disease progression in untreated coronary segments.


Subject(s)
Angioplasty, Balloon, Coronary/methods , Coronary Disease/surgery , Heart Transplantation/adverse effects , Vascular Diseases/therapy , Adolescent , Adult , Biopsy , Cardiac Catheterization , Coronary Angiography , Coronary Disease/diagnostic imaging , Coronary Disease/etiology , Coronary Disease/pathology , Drug Therapy, Combination , Female , Heart Transplantation/immunology , Heart Transplantation/mortality , Heart Transplantation/pathology , Humans , Immunosuppressive Agents , Male , Middle Aged , Palliative Care , Reoperation/statistics & numerical data , Retrospective Studies , Survival Rate , Transplantation, Homologous/pathology , Vascular Diseases/diagnostic imaging , Vascular Diseases/etiology , Vascular Diseases/pathology
13.
Transplant Proc ; 41(4): 1227-30, 2009 May.
Article in English | MEDLINE | ID: mdl-19460525

ABSTRACT

Given the high prevalence of infection with human herpesvirus type 8, Italy is an area of utmost interest for studying Kaposi sarcoma (KS). We investigated the risk of KS in transplant recipients compared with the general population. A longitudinal study was performed from 1970 to 2006 in 4767 kidney, heart, liver, and lung transplant recipients from 7 Italian transplantation centers. The sample included 72.3% male patients with an overall patient median age of 48 years. Patient-years (PYs) at risk for KS were computed from 30 days posttransplantation to the date of KS, death, last follow-up, or study closure (December 31, 2007). Standardized incidence ratios (SIRs) and 95% confidence intervals were computed to quantify the risk of KS in transplant recipients compared with the general Italian population. Incidence rate ratios were computed to identify risk factors using adjusted Poisson regression. Based on 33,621 PYs, KS was diagnosed in 73 patients (62 men): 31 in kidney recipients, 27 in heart recipients, 8 in liver recipients, and 7 in lung recipients. The overall incidence was 217 cases per 10(5) PYs, with a significantly increased SIR of 125. SIR was particularly high in women (n = 34) and lung recipients (n = 428) but decreased significantly with time posttransplantation. The primary predictors of increased risk of KS were male sex, older age, and lung transplantation. A 5-fold reduction was observed after 18 months posttransplantation. After adjustment, patients born in southern Italy compared with northern Italy demonstrated a significant 2.2-fold increased risk. Our findings confirm that in the early posttransplantation period, Italian patients who have undergone solid-organ transplantation, particularly those from southern Italy and those who are lung recipients, are at greater risk of KS compared with the general population. These findings underscore the need for appropriate models for monitoring transplant recipients for KS, especially those at greater risk and, in particular, in the early postoperative period.


Subject(s)
Organ Transplantation , Postoperative Complications/epidemiology , Adult , Aged , Female , Herpesvirus 8, Human , Humans , Italy/epidemiology , Longitudinal Studies , Male , Middle Aged , Prevalence , Risk Factors , Sarcoma, Kaposi/epidemiology , Sarcoma, Kaposi/virology
14.
AJNR Am J Neuroradiol ; 30(4): 722-7, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19164437

ABSTRACT

BACKGROUND AND PURPOSE: A potential role of perfusion CT (PCT) in selecting patients with stroke for reperfusion therapies has been recently advocated. The purpose of the study was to assess the reliability of PCT in predicting clinical outcome of patients with acute ischemic stroke treated with intra-arterial thrombolysis (IAT). MATERIALS AND METHODS: Twenty-seven patients with acute hemispheric ischemic stroke were investigated with PCT and treated with IAT between 3 and 6 hours of stroke onset. The infarct core was outlined on cerebral blood volume (CBV) maps by using accepted viability thresholds. The penumbra was defined as time-to-peak (TTP)-CBV mismatch. Clinical outcome was assessed by modified Rankin Scale (mRS) scores at 3 months and dichotomized into favorable (mRS score, 0-2) and unfavorable (mRS score, 3-6). Data were retrospectively analyzed by multiple regression to identify predictors of clinical outcome among the following variables: age, sex, National Institutes of Health Stroke Scale score, serum glucose level, thrombolytic agent, infarct core and mismatch size, collateral circulation, time to recanalization, and recanalization rate after IAT. RESULTS: Patients with favorable outcome had smaller cores (P = .03), increased mismatch ratios (P = .03), smaller final infarct sizes (P < .01), higher recanalization rates (P = .03), and reduced infarct growth rates (P < .01), compared with patients with unfavorable outcome. The core size was the strongest predictor of clinical outcome in an "all subset" model search (P = .01; 0.96 point increase in mRS score per any increment of 1 SD; 95% confidence interval, +0.17 to +1.75). CONCLUSIONS: PCT is a reliable tool for the identification of irreversibly damaged brain tissue and for the prediction of clinical outcome of patients with acute stroke treated with IAT.


Subject(s)
Fibrinolytic Agents/administration & dosage , Stroke/diagnostic imaging , Stroke/drug therapy , Thrombolytic Therapy , Tomography, X-Ray Computed/standards , Acute Disease , Adult , Aged , Brain Ischemia/diagnostic imaging , Brain Ischemia/drug therapy , Cerebral Infarction/diagnostic imaging , Cerebral Infarction/drug therapy , Female , Humans , Injections, Intra-Arterial , Male , Middle Aged , Predictive Value of Tests , Regression Analysis , Reproducibility of Results , Retrospective Studies
15.
Eur J Endocrinol ; 160(2): 283-8, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19029225

ABSTRACT

OBJECTIVE: Primary hyperparathyroidism (PHPT) is often complicated by kidney stones. Hypercalciuria and urine oxalate excretion are considered risk factors for urolithiasis in PHPT as well as in idiopathic stone-formers. Recently, the anion-exchanger SLC26A6 has been involved in the oxalate metabolism. DESIGN AND METHODS: We tested the hypothesis that the 206M polymorphic variant of SLC26A6 gene might contribute to the risk of kidney stones in PHPT. DNA samples from 145 PHPT patients and 129 age- and sex-matched healthy subjects were genotyped. RESULTS: The homozygous 206V genotype was the most frequent both in PHPT patients and controls (79.3 and 74.4%), while heterozygosity for the 206M allele was detected in 20.0 and 23.3% respectively. The homozygous 206M genotype was extremely rare, occurring in 0.7 and 2.3% of PHPT and healthy subjects respectively. In the PHPT cohort, the prevalence of urolithiasis did not differ between the V/V and V/M+M/M groups and urine oxalate excretions did not correlate with the genotype. Considering the subset of PHPT stone formers (n=74), calciuria was lower in V/M+M/M patients with respect to V/V stone-formers (4.40+/-1.88 vs 5.92+/-2.62 mg/kg per 24 h; mean+/-s.d., P=0.034). Finally, the SLC26A6 206M alleles were significantly related to the presence of hypertension (73.3 vs 47.8%), showing an OR of 4.8. CONCLUSIONS: Though the SLC26A6 206M polymorphism did not correlate with kidney stone development in PHPT patients, PHPT stone-formers harbouring the M allele had a lower hypercalciuria. This observation and the high prevalence of hypertension associated with the 206M polymorphism need further investigation.


Subject(s)
Hyperparathyroidism, Primary/epidemiology , Hyperparathyroidism, Primary/genetics , Kidney Calculi/epidemiology , Kidney Calculi/genetics , Membrane Transport Proteins/genetics , Aged , Chlorides/metabolism , Female , Gene Frequency , Genetic Predisposition to Disease/epidemiology , Genotype , Humans , Incidence , Italy/epidemiology , Male , Membrane Transport Proteins/metabolism , Middle Aged , Oxalates/metabolism , Polymorphism, Genetic , Prevalence , Risk Factors , Sulfate Transporters
16.
Transplant Proc ; 39(10): 2937-50, 2007 Dec.
Article in English | MEDLINE | ID: mdl-18089298

ABSTRACT

While advances in immunosuppressive therapy have allowed dramatic improvements in the control of acute allograft rejection, there is still a need to improve long-term graft and patient survival rates following renal and heart transplantation. Among the recognized threats to long-term organ survival are chronic allograft dysfunction in the form of chronic allograft nephropathy and cardiac allograft vasculopathy, with long-term patient morbidity and mortality further compromised by higher than normal rates of posttransplant cardiovascular disease, infection, and malignancy. A growing body of evidence finds that the selection and dosing of immunosuppressive therapies can have great influence on long-term transplantation outcomes. Early evidence suggests that the proliferation signal inhibitors (PSIs), everolimus and sirolimus, might offer effective immunosuppressive activity together with antiproliferative effects that may address some of the unmet needs in the long-term therapeutic management of the posttransplant patient. This review summarizes the emerging evidence for employing PSI-based immunosuppression to seek a balance between the goals of maximizing graft and patient survival, while minimizing the risks of adverse events and long-term complications. Based on the proceedings of an international gathering of nephrologists, cardiologists and surgeons at the inaugural PSI Forum meeting "Proliferation signal inhibitors in transplantation: questions at the cutting edge," this paper aims to provide both an evidence base and practical guidance for transplant physicians seeking to optimize their use of PSI treatment and highlights avenues of ongoing research into the clinical potential of this class of immunosuppressive therapy.


Subject(s)
Cell Division/drug effects , Immunosuppressive Agents/therapeutic use , Sirolimus/analogs & derivatives , Transplantation Immunology , Everolimus , Graft Rejection/prevention & control , Humans , Signal Transduction/drug effects , Sirolimus/therapeutic use , Transplantation, Homologous/immunology
17.
J Vet Diagn Invest ; 19(1): 21-7, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17459828

ABSTRACT

The BVDV envelope glycoprotein E(rns)/gp48 and the C terminal 79 amino acids of the capsid protein coding region were expressed in a baculovirus system and antigenically characterized. Western blot assay was used to detect recombinant E(rns) (r-E(rns)) in infected insect cells using specific monoclonal antibodies. The r-E(rns) was then used in an indirect ELISA to detect BVDV specific antibodies in a panel of 540 well-characterized sera. Results of the r-E(rns) ELISA were compared to those obtained with a commercially available competitive ELISA targeting anti-NS2/3 antibodies. A good correlation was observed between the 2 ELISA (kappa = 0.916, 95% C.I.: 0.876, 0.956). Using the commercial NS2/3 ELISA as the reference test, the relative sensitivity of r-E(rns) ELISA was 97.5% (95% C.I.: 94.3%, 99.1%) and the relative specificity was 93.9% (95% C.I.: 89.4%, 96.9%), while relative specificity was 100% (95% C.I.: 97%, 100%) using true negative sera (derived from a negative herd). All but 1 antigen positive animals (n = 36) tested negative in the r-E(rns) ELISA; among them all 22 confirmed PI animals were negative by r-E(rns) ELISA. The ability of r-E(rns) ELISA to identify cattle immunized with inactivated vaccine was also demonstrated in a small group of cattle, compared to an NS2/3 antibody ELISA. Results suggest that r-E(rns) ELISA represents an alternative test for antibody generated by natural infection or BVDV vaccination.


Subject(s)
Antibodies, Viral/analysis , Antibodies, Viral/immunology , Diarrhea Viruses, Bovine Viral/immunology , Enzyme-Linked Immunosorbent Assay/veterinary , Glycoproteins/genetics , Animals , Antibodies, Monoclonal/immunology , Antigens, Viral/immunology , Baculoviridae , Bovine Virus Diarrhea-Mucosal Disease/diagnosis , Bovine Virus Diarrhea-Mucosal Disease/virology , Cattle , Cell Line , Glycoproteins/immunology , Moths/cytology , Recombinant Proteins , Time Factors , Viral Structural Proteins/immunology
18.
Am J Transplant ; 6(6): 1387-97, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16686762

ABSTRACT

We compared efficacy and safety of tacrolimus (Tac)-based vs. cyclosporine (CyA) microemulsion-based immunosuppression in combination with azathioprine (Aza) and corticosteroids in heart transplant recipients. During antibody induction, patients were randomized (1:1) to oral treatment with Tac or CyA. Episodes of acute rejection were assessed by protocol biopsies, which underwent local and blinded central evaluation. The full analysis set comprised 157 patients per group. Patient/graft survival was 92.9% for Tac and 89.8% for CyA at 18 months. The primary end point, incidence of first biopsy proven acute rejection (BPAR) of grade >/= 1B at month 6, was 54.0% for Tac vs. 66.4% for CyA (p = 0.029) according to central assessment. Also, incidence of first BPAR of grade >/= 3A at month 6 was significantly lower for Tac vs. CyA; 28.0% vs. 42.0%, respectively (p = 0.013). Significant differences (p < 0.05) emerged between groups for these clinically relevant adverse events: new-onset diabetes mellitus (20.3% vs. 10.5%); post-transplant arterial hypertension (65.6% vs. 77.7%); and dyslipidemia (28.7% vs. 40.1%) for Tac vs. CyA, respectively. Incidence and pattern of infections over 18 months were comparable between groups, as was renal function. Primary use of Tac during antibody induction resulted in superior prevention of acute rejection without an associated increase in infections.


Subject(s)
Cyclosporine/therapeutic use , Graft Rejection/prevention & control , Heart Transplantation/immunology , Tacrolimus/therapeutic use , Acute Disease , Antilymphocyte Serum/therapeutic use , Biopsy , Blood Pressure , Creatinine/blood , Graft Rejection/drug therapy , Graft Survival , Humans , Immunosuppressive Agents/therapeutic use , Myocardium/pathology , Time Factors
19.
Phys Rev Lett ; 96(6): 061802, 2006 Feb 17.
Article in English | MEDLINE | ID: mdl-16605983

ABSTRACT

We consider type I + II seesaw mechanism, where the exchanges of both right-handed neutrinos and isotriplet Higgs bosons contribute to the neutrino mass. Working in the left-right symmetric framework and assuming the mass matrix of light neutrinos m(v) and the Dirac-type Yukawa couplings to be known, we find the triplet Yukawa coupling matrix f, which carries the information about the masses and mixing of the right-handed neutrinos. We show that in this case there exists a duality: for any solution f, there is a dual solution [symbol: see text] = m(v)/nu(L) - f, where nu(L) is the vacuum expectation value of the triplet Higgs boson. Thus, unlike in pure type I (II) seesaw, there is no unique allowed structure for the matrix f. For n lepton generations the number of solutions is 2(n). We develop an exact analytic method of solving the seesaw nonlinear matrix equation for f.

20.
Article in English | MEDLINE | ID: mdl-16626401

ABSTRACT

Several data from different authors show that Bovine virus diarrhoea virus (BVDV) could be a key component in multiple-etiology diseases, indeed a lower leukocytes number and their impaired functions decrease the resistance to infections. However, most of the information on the impairment of immune function during BVDV infections arise from circumstantial evidence and from experimental infection studies, and few from field data. To assess the effects of BVDV on blood cells parameters, cellular and humoral functions under field conditions, we designed a controlled study in commercial dairy herds, comparing persistent infected (PI) and healthy heifers. A total of 45 heifers were considered, the PI animals were nine, the control animals were 34, while two controls were considered as acute infected animals. The comparison of the mean values in PI calves showed a significant decrease for leukocytes and granulocytes, while platelets showed a significant increase, when compared with control animals. The total number of lymphocytes decreased not significantly in PI animals, while the proportion significantly increased. The number and proportion of monocytes was significantly reduced in PI animals, when compared with controls. The data collected on markers of cellular immunity during our study cannot be compared with the literature because there are no reference values. The presence of a persistent infection affected the cellular enzymes: NAGase, lysozyme and respiratory burst showed a large statistically significant decrease in PI animals when compared with controls. The presence of a persistent infection with BVD virus influenced blood cells number and impaired some blood cell functions. Such impairment confirms that PI animals represent a threat to the herd not only because they could spread BVDV, but also because they are more susceptible to other infectious diseases.


Subject(s)
Bovine Virus Diarrhea-Mucosal Disease/blood , Bovine Virus Diarrhea-Mucosal Disease/immunology , Diarrhea Viruses, Bovine Viral/immunology , Animals , Antibody Formation , Blood Cell Count/veterinary , Cattle , Female , Immunity, Cellular , Leukocytes, Mononuclear/immunology , Lymphocyte Activation/immunology , Random Allocation
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