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Serial Measurements (serial + measurement)
Selected AbstractsSuccessful Renal Transplantation in Factor H Autoantibody Associated HUS with CFHR1 and 3 Deficiency and CFH Variant G2850TAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2010A. M. Waters Factor H (CFH) autoantibodies are associated with atypical hemolytic uremic syndrome (aHUS). Peritransplantation plasma exchange therapy and intensification of immunosuppression, with adjuvant use of anti-CD20 monoclonal antibodies has recently been advocated for cases of CFH-autoantibody associated aHUS. In this report, we describe successful deceased donor renal transplantation in a case of CFH-autoantibody associated aHUS with combined CFHR1 and 3 deficiency in addition to the CFH sequence variant, (cG2850T, pGln950His). CFH-autoantibodies were detected 2 weeks prior to transplantation. Disease recurrence was not observed using basiliximab, an IL2-receptor antagonist and high-dose corticosteroids with mycophenolate mofetil. Adjuvant therapies such as Rituximab nor intensification of plasma therapy were employed. Consequently, careful consideration needs to be given to the use of additional immunosuppression in certain cases of CFH-autoantibody associated aHUS. Serial measurement of CFH-autoantibodies is required in the immediate pre- and posttransplantation period to further clarify their role as a factor in the recurrence of aHUS posttransplantation. Furthermore, delineation of the functional significance of CFH-autoantibodies is warranted in individual cases. [source] Neutrophil gelatinase,associated lipocalin is a predictor of the course of global and renal childhood-onset systemic lupus erythematosus disease activityARTHRITIS & RHEUMATISM, Issue 9 2009Claas H. Hinze Objective To determine whether neutrophil gelatinase,associated lipocalin (NGAL) can predict worsening of global and renal disease activity in childhood-onset systemic lupus erythematosus (SLE). Methods One hundred eleven patients with childhood-onset SLE were enrolled in a longitudinal, prospective study with quarterly study visits and had at least 3 study visits. At each visit, global disease activity was measured using 3 external standards: the numerically converted British Isles Lupus Assessment Group (BILAG) index, the SLE Disease Activity Index 2000 update score, and the physician's assessment of global disease activity. Renal and extrarenal disease activity were measured by the respective domain scores. The disease course over time was categorized at the most recent visit (persistently active, persistently inactive, improved, or worsening). Plasma and urinary NGAL levels were measured by enzyme-linked immunosorbent assay, and urinary NGAL levels were standardized to the urinary creatinine concentration. The longitudinal changes in NGAL levels were compared with the changes in SLE disease activity using mixed-effect models. Results Significant increases in standardized urinary NGAL levels of up to 104% were detected up to 3 months before worsening of lupus nephritis (as measured by all 3 external standards). Plasma NGAL levels increased significantly by as much as 26% up to 3 months before worsening of global SLE disease activity as measured by all 3 external standards. Plasma NGAL levels increased significantly by 26% as early as 3 months prior to worsening of lupus nephritis as measured by the BILAG renal score. Conclusion Serial measurement of urinary and plasma NGAL levels may be valuable in predicting impending worsening of global and renal childhood-onset SLE disease activity. [source] Preliminary evaluation of a scale to assess cognitive function in adults with Down's syndrome: the Prudhoe Cognitive Function TestJOURNAL OF INTELLECTUAL DISABILITY RESEARCH, Issue 3 2003D. W. K. Kay Abstract Background In the clinical diagnosis of dementia in Down's syndrome (DS), it may be difficult to distinguish between cognitive deterioration and the various degrees of pre-existing intellectual disability (ID). Serial measurements of both cognitive function and behaviour are required. The aim of the present study was to evaluate the performance of non-demented adults with DS on a subject-directed instrument, the Prudhoe Cognitive Function Test (PCFT), preliminary to its serial use in a prospective study. Methods From 1985 to 1986, 85 non-demented hospitalized adults with DS were interviewed using the PCFT. The Adaptive Behavior Scale (ABS) was administered to the carers. The subjects' levels of ID (graded from mild through moderate, severe and profound to untestable) were based on their scores on the Stanford,Binet Intelligence Scale, as reported in the medical records, and the relationship between level of disability and performance on the PCFT and ABS, and their respective domains, was examined. Results Both scales produced a wide range of scores and the correlation between them was highly significant. Both scales correlated highly significantly with the degree of ID, but more subjects with high levels (i.e. profound to untestable) of disability obtained very low or zero scores on the PCFT and its domains than on the ABS. Conclusions The PCFT provides a reliable quantitative measure of cognitive function in subjects with DS, and could be a useful adjunct to the diagnosis of dementia in prospective studies. However, the almost uniformly low scores obtained by those with high levels of ID suggests that its power to detect cognitive decline will be limited to those who are less disabled, while the ABS may be more useful than the PCFT in detecting deterioration in people with profound ID. [source] Effects of Variation at the ALDH2 Locus on Alcohol Metabolism, Sensitivity, Consumption, and Dependence in EuropeansALCOHOLISM, Issue 7 2006Peter A. Dickson Background: The low-activity variant of the aldehyde dehydrogenase 2 (ALDH2) gene found in East Asian populations leads to the alcohol flush reaction and reduces alcohol consumption and risk of alcohol dependence (AD). We have tested whether other polymorphisms in the ALDH2 gene have similar effects in people of European ancestry. Methods: Serial measurements of blood and breath alcohol, subjective intoxication, body sway, skin temperature, blood pressure, and pulse were obtained in 412 twins who took part in an alcohol challenge study. Participants provided data on alcohol reactions, alcohol consumption, and symptoms related to AD at the time of the study and subsequently. Haplotypes based on 5 single-nucleotide polymorphisms (SNPs) were used in tests of the effects of variation in the ALDH2 gene on alcohol metabolism and alcohol's effects. Results: The typed SNPs were in strong linkage disequilibrium and 2 complementary haplotypes comprised 83% of those observed. Significant effects of ALDH2 haplotype were observed for breath alcohol concentration, with similar but smaller and nonsignificant effects on blood alcohol. Haplotype-related variation in responses to alcohol, and reported alcohol consumption, was small and not consistently in the direction predicted by the effects on alcohol concentrations. Conclusions: Genetic variation in ALDH2 affects alcohol metabolism in Europeans. However, the data do not support the hypothesis that this leads to effects on alcohol sensitivity, consumption, or risk of dependence. [source] Molecular analysis and patterns of ALT and hepatitis C virus seroconversion in haemodialysis patients with acute hepatitisNEPHROLOGY, Issue 3 2008ELISABETH LAMPE SUMMARY: Background: Haemodialysis (HD) continues to carry the risk of hepatitis C virus (HCV) transmission, with delayed seroconversion and often normal alanine aminotransferase (ALT) values increasing the likelihood of undetected infection and thus uninterrupted spread of HCV. The aim of this study was to identify the characteristic patterns of ALT changes and seroconversion during an outbreak of HCV in a HD unit. We also wanted to establish the relationship between infecting viruses using molecular analysis. Methods: All patients (n = 72) and staff (n = 23) of the HD unit were prospectively followed for 14 months. Serial measurements for ALT, HCV antibody and HCV-RNA were performed besides HCV sequence analysis. Results: The initial screening for anti-HCV and HCV-RNA confirmed chronic infection in 16/72 (22%) subjects and identified three subjects with recent seroconversion. In addition, five cases were reverse transcription-polymerase chain reaction positive alone for a total of eight recent cases. The interval between the initial observation of ALT changes and seroconversion varied from 1 to 8 months, and in several individuals ALT fluctuations only below the upper limit of normal were detected. However, relating each subject's ALT values to ALT at baseline, ALT levels increased between 1.6- and 4.7-fold. Molecular analysis provided evidence for transmission from two chronically infected source patients, probably because of inappropriate infection control measures. Conclusion: Our data highlight the importance of well-implemented safety precautions and regular HCV-RNA testing to prevent the further spread of HCV in this population, and suggest the use of ALT baseline values to identify infections that may remain unnoticed otherwise. [source] Myocardial Contractility and Cardiac Filling Measured by Impedance Cardiography in Patients with Nitroglycerine-Induced Vasovagal SyncopePACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 1 2006PETER MITRO Objective: Increased myocardial contractility and inadequate cardiac filling leading to activation of the Bezold-Jarisch reflex were proposed as possible triggering mechanisms of vasovagal syncope (VVS). In the present study noninvasive hemodynamic measurements were performed in order to examine the role of myocardial contractility and cardiac filling in pathogenesis of VVS. Methods: Hemodynamic parameters were measured during head-up tilt test (HUT) by impedance cardiography in 46 patients with unexplained syncope. Myocardial contractility was measured as index of contractility (IC), acceleration index (ACI), and ejection fraction (EF). Afterload was measured as systemic vascular resistance index (SVRI) and preload was expressed as end-diastolic index (EDI). Serial measurements were done 1 minute before HUT, during HUT at 1-minute intervals, and 1 minute after completion of HUT. Results: HUT was positive in 30 patients (10 men, 20 women, mean age 36 ± 16 years) and negative in 16 patients (8 men, 8 women, mean age 31 ± 14 years). No significant differences were observed between HUT(+) and HUT(,) groups in hemodynamic parameters at supine rest and during HUT until the development of syncope. SVRI was lower in HUT(+) than in HUT(,) group at syncope (122.7 + 66.3 vs 185.6 + 51.4 dyn sec cm,5/m2, P = 0.002) and after syncope (117.0 + 61.1 vs 198.0 + 95.7 dyn sec cm,5/m2, P = 0.007). ACI, IC, EF, and EDI did not differ between groups at syncope. After syncope EF was higher in HUT(+) group compared to HUT(,) group (59.2 + 6.1 vs 52.7 + 9.4%, P = 0.02). Conclusion: The role of increased myocardial contractility and decreased cardiac filling is not confirmed in the present study. [source] Infection of T lymphocytes in Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in children of non-Asian originPEDIATRIC BLOOD & CANCER, Issue 2 2009Karin Beutel MD Abstract Background Epstein-Barr virus (EBV) is one of the most frequent triggers of hemophagocytic lymphohistiocytosis (HLH). EBV-associated HLH (EBV-HLH) and ectopic infection of T cells has been particularly described in patients from Far East Asia. Procedure In a cohort of 12 children with EBV-HLH treated in Germany, the EB viral load was detected by real-time polymerase chain reaction in plasma and peripheral blood mononuclear cells (PBMC). Virological and clinical data were analyzed retrospectively. Results Among the 12 mainly German patients, children with underlying immunodeficiencies as well as otherwise healthy individuals were affected. The clinical course ranged from a steroid-responding to a fatal disease despite intensive treatment. Increased EBV copy numbers in plasma and/or PBMC were found in all patients. Serial measurements reflected the course of the disease. Cell-type specific viral load was determined in seven patients and revealed EBV-infection of T cells in all of them. In contrast to the reported Asian patients a significant viral load was also found in B cells. Conclusions T cell infection appears to be a typical feature of EBV-associated HLH irrespective of patients ethnic background and the clinical course. Evaluation of cell-type specific infection should be considered when targeted therapy is applied. Pediatr Blood Cancer 2009;53:184,190. © 2009 Wiley-Liss, Inc. [source] Erythrocyte concentrations of metabolites or cumulative doses of 6-mercaptopurine and methotrexate do not predict liver changes in children treated for acute lymphoblastic leukemiaPEDIATRIC BLOOD & CANCER, Issue 7 2006Päivi Halonen MD Abstract Background During therapy consisting of 6MP and MTX, metabolites accumulate in the erythrocytes. The erythrocyte levels of metabolites reflect the intensity of therapy. Whether they are associated with hepatotoxicity manifested as histological liver changes is not known. We studied the association of the metabolites and cumulative doses of 6MP and MTX with histological liver disease. Methods Serial measurements of E-TGN, E-MTX, and ALT during maintenance therapy were performed and cumulative doses of 6MP and MTX were calculated as g/m2 in 16 children with ALL. Each subject underwent a percutaneous liver biopsy at the end of therapy to screen for histological liver disease. Results No differences in E-TGN, E-MTX, or cumulative doses of 6MP or MTX were detected in the children with ALL with liver fibrosis compared to those without fibrosis, or in the children with less liver fatty change compared to those with more fatty change. Serum median ALT levels correlated significantly positively with cumulative doses of 6MP during therapy (rS,=,0.527, P,=,0.036), but not with cumulative doses of MTX, or E-TGN, or E-MTX. Conclusions Erythrocyte levels of the metabolites or the cumulative doses of 6MP and MTX do not predict histological liver disease in children treated for ALL. © 2006 Wiley-Liss, Inc. [source] Glucagon is absorbed from the rectum but does not hasten recovery from hypoglycaemia in patients with type 1 diabetesBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 1 2008David R. Parker WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , Patients with type 1 diabetes experience recurrent hypoglycaemia and have abnormal glucose counter regulatory responses with a failure to secrete glucagon. It is unknown if rectal glucagon is absorbed and what effect this may have on counter regulation from hypoglycaemia. WHAT THIS STUDY ADDS , A rectal suppository of glucagon results in a rise in plasma glucagon with metabolic effects in normal subjects. Similarly rectal glucagon results in a rise in plasma glucagon in patients with type 1 diabetes, but 1 mg does not improve recovery rates from experimental hypoglycaemia when compared with placebo. , Larger doses of glucagon per rectum may provide pharmacological circulating concentrations with resulting therapeutic benefit during recovery from hypoglycaemia and deserves further study. AIMS A failure to secrete glucagon during hypoglycaemia is near universal in patients with type 1 diabetes 5 years after disease onset and may contribute to delayed counter-regulation during hypoglycaemia. Rectal glucagon delivery may assist glucose recovery following insulin-induced hypoglycaemia in such patients and has not been previously studied. METHODS Six male patients (age 21,38 years) with type 1 diabetes (median duration 10 years) without microvascular complications, were studied supine after an overnight fast on two separate occasions at least 14 days apart. After omission of their usual morning insulin and 45 min rest, hypoglycaemia was induced by an intravenous insulin infusion which was terminated when capillary glucose concentration reached 2.5 mmol l,1. Subjects were randomized to insert a rectal suppository containing 100 mg indomethacin alone (placebo) or 100 mg indomethacin plus 1 mg glucagon at the hypoglycaemic reaction. Serial measurements were made for 120 min. RESULTS In the two groups, mean (SD) plasma glucose concentrations fell to a similar nadir of 1.8 (0.7) mmol l,1 (placebo) and 2.1 (1.2) mmol l,1 (glucagon). Peak plasma glucagon following hypoglycaemia was higher in the glucagon group; 176 (32) ng l,1vs. 99 (22) ng l,1 after placebo (P = 0.006). However, the glucose recovery rate over 120 min after hypoglycaemia did not differ significantly. CONCLUSIONS Our results provide evidence for the absorption of glucagon from the rectum. They also indicate that 1 mg does not constitute a useful mode of therapy to hasten recovery from hypoglycaemia in patients with type 1 diabetes. [source] Effect of Intravenous Albumin Infusion on Brain Salicylate ConcentrationACADEMIC EMERGENCY MEDICINE, Issue 6 2007Steven C. Curry MD Background:Salicylate poisoning appears to result in death, despite supportive care, once a critical brain salicylate concentration is reached. The binding of salicylate to albumin is saturable; free plasma salicylate concentrations rise disproportionately to total drug levels. Because unbound salicylate distributes into the brain, the authors questioned whether an intravenous (IV) infusion of albumin would cause a redistribution of salicylate from the brain back into the plasma, which might allow enough time for hemodialysis to be instituted. Objectives:To determine if IV albumin infusion would lower brain salicylate concentrations through redistribution in a porcine model of acute salicylate poisoning. Methods:In a randomized controlled trial, 17 swine under anesthesia and controlled ventilation received 400 mg/kg of sodium salicylate IV over 15 minutes. At 60 minutes, nine animals received 1.25 g/kg albumin (25% solution) IV over 15 minutes, while eight control animals received an equal volume of normal saline (5 mL/kg). Arterial pH was maintained between 7.45 and 7.55. Serial measurements of serum albumin as well as free and total salicylate concentrations were obtained, and urine was collected for measurement of total salicylate excretion. At 180 minutes, animals were killed and brains harvested for measurement of brain salicylate concentrations. Results:Average peak serum total salicylate concentrations of 105.5 and 109 mg/dL were achieved in control and albumin-treated animals, respectively. Albumin infusion was accompanied by statistically significant increases in serum total salicylate concentrations (median from 79.5 to 86.9 mg/dL at 75 minutes), while levels decreased slightly in control animals. Serum free salicylate concentrations decreased slightly in albumin-treated animals, but the difference was not statistically significant. Median brain salicylate concentrations were about 14% lower in the albumin treatment group (17.8 mg/100 g brain) compared with controls (20.5 mg/100 g brain); this approached statistical significance (p = 0.075). Median urinary salicylate excretion was higher in the albumin-treated group (0.83 vs. 0.48 g; p = 0.072), with similar urinary pH and volumes in both groups. Conclusions:In this animal model of salicylate poisoning, IV infusion of 1.25 g/kg albumin was accompanied by a 14% decline in median brain salicylate concentrations, which approached statistical significance. [source] Unmasking of central hypothyroidism following growth hormone replacement in adult hypopituitary patientsCLINICAL ENDOCRINOLOGY, Issue 1 2007Amar Agha Summary Background, The effect of GH replacement on thyroid function in hypopituitary patients has hitherto been studied in small groups of children and adults with conflicting results. Objective, We aimed to define the effect and clinical significance of adult GH replacement on thyroid status in a large cohort of GH-deficient patients. Patients and method, We studied 243 patients with severe GH deficiency due to various hypothalamo-pituitary disorders. Before GH treatment, 159 patients had treated central hypothyroidism (treated group) while 84 patients were considered euthyroid (untreated group). GH dose was titrated over 3 months to achieve serum IGF-1 concentration in the upper half of the age-adjusted normal range. Serial measurements of serum T4, T3, TSH and quality of life were made at baseline and at 3 and 6 months after commencing GH replacement. Results, In the untreated group, we observed a significant reduction in serum T4 concentration without a significant increase in serum T3 or TSH concentration; 30/84 patients (36%) became hypothyroid and needed initiation of T4 therapy. Similar but lesser changes were seen in the treated group, 25 of whom (16%) required an increase in T4 dose. Patients who became hypothyroid after GH replacement had lower baseline serum T4 concentration, were more likely to have multiple pituitary hormone deficiencies and showed less improvement in quality of life compared with patients who remained euthyroid. Conclusion, GH deficiency masks central hypothyroidism in a significant proportion of hypopituitary patients and this is exposed after GH replacement. We recommend that hypopituitary patients with GH deficiency and low normal serum T4 concentration should be considered for T4 replacement prior to commencement of GH in order to provide a robust baseline from which to judge the clinical effects of GH replacement. [source] Arsenic trioxide is effective in the treatment of multiple myeloma in SCID miceEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2004Philippe Rousselot Abstract: Objectives :,Pharmacological concentrations of arsenic trioxide (ATO) and organic arsenic melarsoprol induce apoptosis in malignant plasma cells. In an attempt to further document the interest of the arsenic in vivo, we treated severe combined immunodeficient (SCID) mice transplanted with human myeloma cells by ATO or melarsoprol. Methods :,Fifty-two SCID mice were irradiated before intraperitoneal (i.p.) injection of plasma cells from five myeloma patients. Engraftment was assessed by serial measurement of the human monoclonal immunoglobulin G (HuMIgG) concentration in mouse serum. Treatment with ATO (10 ,g/g i.p. 5 d a week), melarsoprol (30 ,g/g i.p. 5 d a week) or phosphate buffer saline was started when a sustained growth of the tumor cells was demonstrated. Results :,Seventeen mice developed the human tumor. A significant decrease in HuMIgG amounts was observed in three of five mice of the ATO group, including two that achieved an apparent complete remission persisting up to 5 months after ATO discontinuation. In these mice, no human plasma cells were detected in tissue samples collected postmortem. Soluble human interleukin-6 receptor amount, measured in mice sera as a surrogate marker of the plasma cell proliferation, varied in parallel with HuMIgG concentration. A significant difference in survival was observed between control and ATO treated mice (113 and 158 d, respectively; P = 0.01) whereas no difference could be evidenced in control and melarsoprol groups. Conclusion :,Present study confirms in vivo the in vitro effects of ATO on myeloma cells. Delayed relapses were observed suggesting that prolonged or maintenance therapy has to be considered in future clinical trials. Whether or not this will translate into clinically relevant effect of the drug in myeloma patients deserves further consideration. [source] Monitoring of cardiac function by serum cardiac troponin T levels, ventricular repolarisation indices, and echocardiography after conditioning with fractionated total body irradiation and high-dose cyclophosphamideEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2002H.W. Auner Abstract:Objectives : Highly differing rates of cardiac complications associated with high-dose cyclophosphamide (CY) have been reported, and only one clinical study has been performed on the cardiotoxic effects of CY monotherapy following total body irradiation (TBI). Patients and methods : We prospectively evaluated the potential cardiotoxic effects of conditioning with fractionated total body irradiation and high-dose cyclophosphamide (TBI/CY) by serial measurement of serum cardiac troponin T (cTnT), assessment of systolic and diastolic echocardiographic parameters and analysis of ventricular repolarisation indices (QT-dispersion and corrected QT-dispersion) in 30 adult patients with haematological malignancies undergoing haematopoietic stem cell transplantation. Results: There was no evidence of pretreatment cardiac dysfunction in any patient. Although cTnT was determined serially for a median of 14 d after completion of conditioning, no elevated levels were observed. Echocardiographic parameters did not show any significant change at a median follow-up of 5 months except for one patient with evidence of impaired diastolic filling. No significant differences for mean values before and after high-dose CY were noted for ventricular repolarisation indices. Two patients had a significant increase in corrected QT-dispersion after CY without any other signs of cardiotoxicity. Congestive heart failure or arrythmias were not observed. Conclusions : These data suggest that TBI/CY is safe with respect to cardiotoxicity in patients without pre-existing cardiac dysfunction. Hitherto unknown synergistic cardiotoxic effects of CY with other cytostatic drugs may constitute the major pathogenic factor of myocardial dysfunction after high-dose chemotherapy. [source] Exposure of the fetus and infant to hens' egg ovalbumin via the placenta and breast milk in relation to maternal intake of dietary eggCLINICAL & EXPERIMENTAL ALLERGY, Issue 10 2005G. H. S. Vance Summary Background Maternally derived allergens may be transferred to the developing infant during pregnancy and lactation. However, it is not known how manipulation of environmental allergen levels might impact on this early-life exposure. Objective To measure dietary egg allergen (ovalbumin (OVA)) in gestation-associated environments, in relation to maternal dietary egg intake. Method OVA was measured by allergen-specific ELISA in maternal blood collected throughout pregnancy, infant blood at birth (umbilical cord) and in breast milk at 3 months post-partum. Samples derived from pregnant women undergoing diagnostic amniocentesis at 16,18 weeks gestation who were not subject to any dietary intervention, and from pregnant women, with personal or partner atopy, randomized to complete dietary egg exclusion or an unmodified healthy diet before 20 weeks gestation as a primary allergy prevention strategy. Maternal dietary egg intake was monitored closely throughout the study period by diary record and serial measurement of OVA-specific immunoglobulin G concentration. Results Circulating OVA was detected throughout pregnancy in 20% of women and correlated with both presence (P<0.001) and concentration (r=0.754, P<0.001) of infant OVA at birth (umbilical cord). At 3 months post-partum OVA was detected in breast milk samples of 35% women, in higher concentrations than measured in blood. Blood and breast milk OVA were not related to maternal dietary intake or atopic pre-disposition. Conclusions Rigorous dietary egg exclusion does not eliminate trans-placental and breast milk egg allergen passage. This early-life exposure could modulate developing immune responses. [source] Serum levels of interferon-,, tumour necrosis factor-,, soluble interleukin-6R and soluble cell activation markers for monitoring response to treatment of leprosy reactionsCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 2 2007A. Iyer Summary Identifying pathogen and host-related laboratory parameters are essential for the early diagnosis of leprosy reactions. The present study aimed to clarify the validity of measuring the profiles of serum cytokines [interleukin (IL)-4, IL-6, IL-10, interferon (IFN)-, and tumour necrosis factor (TNF)-,], the soluble IL-6 receptor (sIL-6R), soluble T cell (sCD27) and macrophage (neopterin) activation markers and Mycobacterium leprae -specific anti-PGL-I IgM antibodies in relation to the leprosy spectrum and reactions. Serum samples from 131 Indonesian leprosy patients (82 non-reactional leprosy patients and 49 reactional) and 112 healthy controls (HC) from the same endemic region were investigated. Forty-four (89·8%) of the reactional patients had erythema nodosum leprosum (ENL) while only five (10·2%) had reversal reaction (RR). Follow-up serum samples after corticosteroid treatment were also obtained from 17 of the patients with ENL and one with RR. A wide variability in cytokine levels was observed in the patient groups. However, IFN-, and sIL-6R were elevated significantly in ENL compared to non-ENL patients. Levels of IFN-,, TNF-, and sIL-6R declined significantly upon corticosteroid treatment of ENL. Thus, although the present study suggests limited applicability of serial measurement of IFN-,, TNF-, and sIL-6R in monitoring treatment efficacy of ENL, reactions it recommends a search for a wider panel of more disease-specific markers in future studies. [source] Efficacy of an individualized written home-management plan in the control of moderate persistent asthma: A randomized, controlled trialACTA PAEDIATRICA, Issue 12 2005Sunil K Agrawal Abstract Background: The management of childhood asthma necessitates a comprehensive approach including pharmacological treatment as well as education about self-evaluation and home management of the condition. Aim: To evaluate the efficacy of adding an individualized written home-management plan in the control of moderate persistent asthma. Methods: Children with moderate persistent asthma were randomized to receive either an individualized written home-management plan or no plan, in addition to standard asthma therapy including education. They were followed up with serial measurement of outcome variables. Results: Children receiving an individualized written home-management plan had fewer acute asthma events, fewer lost school days, lower symptom score and less nocturnal awakening than those who did not receive a written plan. Conclusion: The addition of a written individualized home-management plan improves overall control in children with moderate persistent asthma. [source] Intraoperative Comparison of a Subthreshold Test Pulse with the Standard High-Energy Shock Approach for the Measurement of Defibrillation Lead ImpedanceJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 1 2006ANDREAS SCHUCHERT M.D. There are two methods to measure shocking lead impedance: delivery of high-energy shocks that require patient sedation, and the painless measurement of impedance from subthreshold test pulses. The aim of this study was to compare the two methods. Methods: The study included 131 patients implanted with a standard DR (n = 71) or VR (n = 60) ICD connected to either single-coil (n = 39) or dual-coil (n = 92) defibrillation leads. The noninvasive high-energy impedance test was done using a 17 J shock after induction of ventricular tachyarrhythmias and compared to a 0.4 ,J test pulse used by the ICD for the subthreshold measurements. Results: Defibrillation lead impedance measurements were not significantly different between patients with the same shocking vector configuration. In patients with a single-coil defibrillation lead the impedance was 62 ± 9 , with the high-energy shock and 62 ± 8 , with the subthreshold test pulses (P = 0.13). Patients with a dual-coil configuration recorded average impedances of 40 ± 5 , from both tests (P = 0.44). While there was no difference in values recorded within each lead configuration, there was a significant difference in impedance between the single-coil and the dual-coil patient groups (P = 0.001). Conclusions: There was no significant difference between shocking lead impedances measured with the high-energy shock or the subthreshold test pulses. This offers the possibility of noninvasive, low-energy serial measurements of shocking lead impedance at follow-up visits and removing the need for sedation. [source] CA-125 levels in ruptured and unruptured tubal ectopic pregnanciesJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 4 2006Erdal Malatyalioglu Abstract Aim:, This prospective, single-blind and controlled clinical study aimed to research if CA-125 levels could be a useful test in the differential diagnosis of intact and ruptured tubal ectopic pregnancy. Methods:, Sixty-five women with tubal ectopic pregnancy of 5,10 weeks' duration (27 women with ruptured tubal ectopic pregnancy [REP] and 38 women with unruptured tubal ectopic pregnancy [UREP]) and 65 women with normal intrauterine pregnancy (NIUP) of the same gestational age were studied prospectively. Serum CA-125 levels were measured in all women and these levels were compared among the REP, UREP, and NIUP groups. Results:, The mean CA-125 levels didn't show any significant difference between the REP and NIUP groups (P > 0.05). The mean CA-125 levels of these two groups were higher than that in the UREP group (P < 0.01, P < 0.001, respectively). The dispersion ratios of the CA-125 levels had a statistically significant difference between the REP and UREP groups (,2: 42.44, P < 0.0001). CA-125 levels weren't correlated with gestational weeks in the REP and UREP groups (r: 0.005, P > 0.05; r: 0.008, P > 0.05, respectively). Conclusion:, In intact tubal ectopic pregnancies, expectant or managed with medical treatment, the increase of CA-125 levels in the serial measurements could be a supplementary test for an early diagnosis of tubal rupture. [source] Serial Estimation of Survival Prediction Indices Does Not Improve Outcome Prediction in Critically III Dogs with Naturally Occurring DiseaseJOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue 3 2001DACVECC, DACVIM, Lasely G. King MVB Abstract Objective: The objectives of this study were to test the value of adding serial measurements to the Survival Prediction Index (SPI 2), and to investigate whether time trajectories add predictive information beyond measurements at a single point in time. Design: Prospective clinical trial. Setting: Intensive care unit at a Veterinary Teaching Hospital. Animals: 63 critically ill dogs Interventions: Physiologic data were collected within 24 hours of admission to the ICU (Day 1), and again on Day 3 of hospitalization. Measurements: The first analysis applied the SPI 2 equation on Day 1 and again on Day3. Then a prediction model was re-estimated using Day 1 measurements, and the incremental predictive value of adding Day 1 to Day 3 change scores was evaluated. the third analysis tested the incremental predictive value of change scores in models containing only one prognostic variable. The final analysis compared the re-estimated Day 1 model to an analogously re-estimated Day 3 model. Main Results: Using the SPI 2 equation, the AUC was 7.7% higher using Day 3 measurements than that obtained using Day 1 measurements (P = 0.515). Starting with the re-estimated Day 1 model (AUC = 0.925), forward stepwise addition of the difference score for each variable did not result in an improvement in the AUC. The AUC for the re-estimated Day 1 model was not statistially different from that of the re-estimated model using Day 3 measurements. Conculusion: This study shows no benefit to repeated calculation of the SPI 2 later in hospitalization. [source] Measurement of porto-systemic shunting in mice by novel three-dimensional micro-single photon emission computed tomography imaging enabling longitudinal follow-upLIVER INTERNATIONAL, Issue 8 2010Christophe Van Steenkiste Abstract Background and aims: The reference method for diagnosing porto-systemic shunting (PSS) in experimental portal hypertension involves measuring 51Chrome (51Cr)-labelled microspheres. Unfortunately, this technique necessitates the sacrifice of animals. Alternatively, 99mtechnetium-macroaggregated albumin (99mTc-MAA) has been used; however, planar scintigraphy imaging techniques are not quantitatively accurate and adequate spatial information is not attained. Here, we describe a reliable, minimally invasive and rapid in vivo imaging technique, using three-dimensional single photon emission computed tomography (3D SPECT) modus, that allows more accurate quantification, serial measurements and spatial discrimination. Methodology: Partial portal vein ligation, common bile duct ligation and sham were induced in male mice. A mixture of 51Cr microspheres and 99mTc-macroaggregated albumin particles was injected into the splenic pulpa. All mice were scanned in vivo with ,SPECT (1 mm spatial resolution) and, when mandatory for localisation, a ,SPECT-CT was acquired. A relative quantitative analysis was performed based on the 3D reconstructed datasets. Additionally, 51Cr was measured in the same animals to calculate the correlation coefficient between the 99mTc detection and the gold standard 51Cr. In each measuring modality, the PSS fraction was calculated using the formula: [(lung counts)/(lung counts+liver counts)] × 100. Results: A significant correlation between the 99mTc detection and 51Cr was demonstrated in partial portal vein ligation, common bile duct ligation and sham mice and there was a good agreement between the two modalities. ,SPECT scanning delivers high spatial resolution and 3D image reconstructions. Conclusion: We have demonstrated that quantitative high-resolution ,SPECT imaging with 99mTc-MAA is useful for detecting the extent of PSS in a non-sacrificing set-up. This technology permits serial measurements and high-throughput screening to detect baseline PSS, which is especially important in pharmacological studies. [source] Genetic polymorphism of catechol- O -methyltransferase and levodopa pharmacokinetic,pharmacodynamic pattern in patients with Parkinson's disease,MOVEMENT DISORDERS, Issue 6 2005Manuela Contin PharmD Abstract We explored the potential effect of catechol- O -methyltransferase (COMT) genetic polymorphism on the pharmacokinetics and pharmacodynamics of a standard oral dose of levodopa in patients with Parkinson's disease (PD). We prospectively collected blood samples for COMT genotyping from a population of 104 PD patients. Each patient was examined by a standard oral levodopa/benserazide test, based on simultaneous serial measurements of plasma levodopa concentrations, finger-tapping motor effects and dyskinesia ratings, up to 4 hours after dosing. The main levodopa pharmacokinetic outcome variables were time to peak and peak plasma concentration, plasma elimination half-life, and the area under the plasma concentration,time curve. The main outcome levodopa pharmacodynamic variables were latency, duration, and magnitude of the motor effect elicited by the levodopa test dose, the area under the tapping effect,time curve, and the presence of dyskinesias. Nineteen patients (18%) harbored the low-activity homozygous COMT genotype (A/A), 63 patients (61%) carried the intermediate-activity heterozygous COMT genotype (A/G) and 22 patients (21%) had the high-activity homozygous COMT genotype (G/G). The three groups were comparable for vital and clinical characteristics. No significant difference was found in levodopa main pharmacokinetic,pharmacodynamic variables and dyskinesia incidence among the three subgroups of patients. We failed to identify clinically relevant levodopa pharmacokinetic,pharmacodynamic response patterns associated with the COMT polymorphism in PD patients. © 2005 Movement Disorder Society [source] Prospective evaluation of acute and chronic renal function in children following matched related donor hematopoietic stem cell transplantationPEDIATRIC TRANSPLANTATION, Issue 1 2010Talia Ileri Ileri T, Ertem M, Ozcakar ZB, Ince Unal E, Biyikli Z, Uysal Z, Ekim M, Yalcinkaya F. Prospective evaluation of acute and chronic renal function in children following matched related donor hematopoietic stem cell transplantation. Pediatr Transplantation 2010: 14: 138,144. © 2009 John Wiley & Sons A/S. Abstract:, Acute and chronic renal impairment are important complications after HSCT. A prospective study was conducted to investigate the glomerular renal function in children who received allogeneic HSCT from matched related donors. Non-radiation conditioning regimens were used in all but one patient. CrCl and serial measurements of serum creatinine were evaluated prior to HSCT, within the first 100 days and one yr after. AKI was defined as at least a 1.5-fold rise in pre-HSCT serum creatinine within the first 100 days and classified as grade 1 to 3 according to the new definition criteria proposed by "AKI Network." Fifty-seven patients were enrolled in the study and 24 patients (42%) had AKI. CsA, amphotericin B, and SOS were found as risk factors for AKI. One yr after HSCT five patients (10%) had CKD and none of them required dialysis. None of the parameters were found as a predictor for CKD. We conclude that AKI is an important complication of HSCT. Careful monitoring of renal function, minimizing the use of nephrotoxic medication, prophylaxis, and effective treatment of SOS might be effective preventive measures to decrease the incidence of AKI. [source] Prevention of CMV disease in pediatric kidney transplant recipients: Evaluation of pp67 NASBA-based pre-emptive ganciclovir therapy combined with CMV hyperimmune globulin prophylaxis in high-risk patientsPEDIATRIC TRANSPLANTATION, Issue 4 2008Edith Renoult Abstract:, A new prevention strategy for CMV infection was evaluated in our pediatric kidney transplant unit. This approach comprises a pre-emptive therapy, based upon the monitoring of CMV pp67 mRNA in whole blood by the qualitative NASBA, combined with prophylactic CMV-IG in high risk (R,/D+) children. Thirty-one kidney transplant children were followed for six months with serial measurements of CMV pp67 mRNA in the blood. The R,/D+ patients were given prophylactic CMV-IG for the first 16 wk after transplantation. I.v. ganciclovir was administered upon CMV detection by NASBA and was discontinued after two consecutive negative results. CMV infection, detected by NASBA, developed in 11 (35%) recipients: one (33%) of the R+/D, patients and 10 (72%) of the R,/D+ patients. CMV disease developed in 9.6% of the patients (3/31), exclusively in the R,/D+ group. These three patients presented concurrently with CMV viremia and disease. It is noteworthy that two of the three patients could not receive a complete course of CMV-IG, and one of the latter two subjects had been treated for acute rejection 15 days before CMV infection. Ganciclovir was given for the 11 cases of primary infection, and for three cases of relapsed CMV infection. pp67 NASBA-based pre-emptive ganciclovir therapy, combined with prophylactic CMV-IG in high-risk patients leads to a lower rate of CMV disease, as long as a complete course of CMV-IG has been administered and ganciclovir is given during the period of treatment for acute rejection in high-risk populations. [source] Reference ranges for umbilical vein blood flow in the second half of pregnancy based on longitudinal dataPRENATAL DIAGNOSIS, Issue 2 2005Ganesh Acharya Abstract Objectives To construct new reference ranges for serial measurements of umbilical vein (UV) blood flow. Methods Prospective longitudinal study of blood flow velocities and diameter of the UV measured at four-weekly intervals during 19 to 42 weeks' gestation in 130 low-risk singleton pregnancies. Regression models and multilevel modeling were used to construct the reference ranges. Results On the basis of 511 sets of longitudinal observations, we established new reference percentiles of UV diameter, blood flow velocities, volume flow, and blood flow normalized for fetal weight and abdominal circumference. They reflected some of the developmental patterns of previous cross-sectional studies, but with important differences, particularly near term. The UV blood flow showed a continuous increase until term, whereas the flow normalized per unit fetal weight, a corresponding reduction. Calculating the blood flow on the basis of intensity-weighted mean velocity or 0.5 of the maximum velocity gave almost interchangeable results for most fetuses. Conclusion New reference ranges for UV blood flow based on longitudinal observations appear slightly different from cross-sectional studies, and should be more appropriate for serial evaluation of fetal circulation. Copyright © 2005 John Wiley & Sons, Ltd. [source] Linear Growth Patterns in Prepubertal Children Following Liver TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2009E. M. Alonso Factors impacting linear growth following pediatric liver transplantation (LT) are not well understood. This longitudinal analysis examines predictors of linear growth impairment in prepubertal children included in Studies of Pediatric Liver Transplantation. In 1143 children with serial measurements, mean height scores increased from ,1.55 at LT to ,0.87 and ,0.68 at 24 and 36 months post LT with minimal subsequent catch up growth observed until 60 months. Subgroup analysis of height measurements at 24 months (n = 696), 33.8% were below 10th percentile at 24 months post LT. Multivariate analysis revealed linear growth impairment more likely in patients with metabolic disease (OR 4.4, CI: 1.83,10.59) and >18 months of steroids exposure (OR 3.02, CI: 1.39,6.55). Higher percentiles for weight (OR 0.80, CI: 0.65,0.99) and height (OR 0.62, CI: 0.51,0.77) at LT decreased risk. Less linear catch up was observed in patients with metabolic disease, non-Biliary atresia cholestatic diseases and lower weight and higher height percentiles prior to LT. Prolonged steroid exposure and elevated calculated glomerular filtration rate and ,-Glutamyltransferase following LT were associated with less catch up growth. Linear growth impairment and incomplete linear catch up growth are common following LT and may improve by avoiding advanced growth failure before LT and steroid exposure minimization. [source] Combined antegrade and retrograde endoscopic retroperitoneal bypass of ureteric strictures: a modification of the ,rendezvous' procedureBJU INTERNATIONAL, Issue 7 2010David R. Yates Study Type , Therapy (case series) Level of Evidence 4 OBJECTIVE To evaluate our experience of treating complicated iatrogenic ureteric strictures with a combined antegrade and retrograde endoscopic retroperitoneal bypass technique, a modification of the so-called ,rendezvous' procedure. PATIENTS AND METHODS Seven patients presented to our institution between 2004 and 2008 after developing a complicated iatrogenic ureteric stricture, impassable with solitary antegrade or retrograde stenting techniques. In most cases there was a significant loss of ureteric continuity, with some strictures of up to 10,12 cm. After initial temporizing management with a percutaneous nephrostomy, each patient had a radiological ,rendezvous' procedure to insert a JJ stent and restore ureteric continuity. After 6 months, the JJ stents were removed and the patients evaluated by symptom assessment, serial measurements of serum creatinine and diuretic renography (F-15 mercaptoacetyl triglycine). RESULTS All seven ,rendezvous' procedures were successful and a ureteric stent was inserted across or around the stricture in all cases. Five of seven patients whose follow-up was >6 months had their stent removed successfully. At a median follow-up of 21 months, all patients are alive and none has required subsequent surgery. Six of the seven patients presented with significant symptoms and they are all currently symptom-free, which we consider to be a successful clinical outcome. No patient has developed significant renal impairment (estimated glomerular filtration rate (<30 mL/min) but we could only confirm successful unequivocal renographic drainage in one patient. CONCLUSION Combining antegrade radiological and retrograde endourological techniques, it is possible to restore ureteric continuity with a JJ stent, even in situations with extensive loss of the ureteric lumen. This reduces the need for morbid open surgical repair and offers a long-term solution to patients who might otherwise be consigned to less favourable conservative measures. [source] Randomized controlled trial of acute normovolaemic haemodilution in aortic aneurysm repairBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 4 2001L. Wolowczyk Background: Previous studies have suggested that acute normovolaemic haemodilution (ANH) reduces the need for heterologous blood transfusion in abdominal aortic aneurysm (AAA) surgery and may thus improve postoperative outcome by reducing the systemic inflammatory response. Controlled studies are lacking. The aim of this randomized controlled trial was to evaluate the effects of ANH on the systemic inflammatory response, clinical outcome and use of bank blood after AAA repair. Methods: Patients undergoing elective AAA repair were randomized to ANH (n = 16) or control (n = 18) groups. Intraoperative cell salvage and heterologous blood were used in both groups according to predetermined transfusion triggers. Inflammatory markers in serum and urine were measured to assess the acute-phase response. Clinical outcome was determined using mortality, morbidity and the incidence of the systemic inflammatory response syndrome (SIRS). Results: There was no difference between the ANH and control group in serial measurements of median (range) white cell count (maximum at 2 days after operation: 11·9 (7·7,21·4) versus 10·3 (7·8,20·6) × 109 l,1; P = 0·25), serum C-reactive protein level (maximum at 3 days: 150 (1,274) versus 169 (7,238) mg ml,1; P = 0·76), interleukin 6 level (maximum at 6 h: 142 (32,793) versus 105 (29,509) pg ml,1; P = 0·89), total antioxidant capacity (lowest at 1 h: 0·83 (0·67,1·22) versus 0·83 (0·68,1·23) mmol l,1; P = 0·45) or urinary albumin/creatinine ratio (maximum at 30 min after clamp release: 41 (2,923) versus 124 (4,376) mg ml,1; P = 0·10). SIRS was observed in ten of 16 patients having ANH and in 11 of 18 control patients (P = 0·99). There was no significant difference in mortality and morbidity between the groups. Similarly, there was no difference in median (range) blood loss (ANH 1800 (400,12 000) ml versus control 1600 (500,7500) ml; P = 0·55), use of cell salvage (600 (0,4740) versus 520 (0,2420) ml; P = 0·60) or heterologous blood transfusion (2 (0,32) versus 2 (0,9) units; P = 0·68). Conclusion: In the setting of a randomized controlled trial ANH added no additional benefit, when used in combination with cell salvage, in reducing the requirements for heterologous blood transfusion, and made no impact on systemic inflammatory response and clinical outcome after AAA repair. © 2001 British Journal of Surgery Society Ltd [source] | |||||||||||||||||||||||||