C0 Group Research Articles

Crescent lesions are not a predictive factor in adult-onset Henoch-Schönlein purpura nephritis.

Henoch-Schönlein purpura nephritis (HSPN) is a common secondary glomerulonephritis, and its prognosis mainly depends on the severity of renal impairment. To date, the significance of crescent lesions in adult-onset HSPN is still unclear. Therefore, the purpose of this research was to assess whether crescents could predict the renal outcomes in adult HSPN patients. A total of 188 adult patients with HSPN proven by renal biopsy were enrolled in this prospective study. Patients were divided into three groups based on the proportion of crescents: non-crescent group (C0, n = 110), crescent ≤ 25% group (C1, n = 50) and crescent > 25% group (C2, n = 28). The composited endpoint was defined as eGFR decreased > 50% of baseline level, reached end-stage renal disease and/or death. Among three groups, clinical pathological features, treatment regimens and renal outcomes were compared. During a mean follow-up of 26months, 78 (42.5%) patients had crescent lesions. A total of ten (9.1%) patients in C0 group and five (17.9%) patients in C2 group reached the combined endpoint, but no patients in C1 group reached endpoint. Renal survival analysis indicated patients in C1 group tended to have the best renal outcome, while patients in C2 group had the poorest renal survival. Moreover, Cox regression analysis revealed crescents were not a predictor of poor developing to renal outcome after adjusting potential confounders [hazard ratio (HR) = 0.28, 95% confidence interval (CI) 0.07-1.18, P = 0.083]. Crescent formation is not necessarily a predictive factor of poor renal survival in adult HSPN patients who had small proportions of crescents (crescent ≤ 25%).

Infrahepatic inferior vena cava clamping during liver transection for cholangiocarcinoma: a quasi – experimental study

Introduction: Major hepatectomy is the mainstay of treatment of cholangiocarcinoma. Infrahepatic inferior vena cava (IVC) clamping is effective maneuver for reducing central venous pressure (CVP), may lead to reducing in blood loss during liver transection. The impact of this procedure on major hepatectomy for cholangiocarcinoma is unknown. This study evaluated the effect of infrahepatic IVC clamping on blood loss during liver transection. Method: Clinical and pathological data were retrospectively collected for 116 cholangiocarcinoma patients who underwent major hepatectomy between January 2015 and December 2016, to investigate the benefit of infrahepatic IVC clamping. Two of five surgeons adopt the policy performing infrahepatic IVC clamping during liver transection in all cases. Patients, therefore, were divided into those (n = 39; 33.6%) who received infrahepatic IVC clamping during liver transection (C1) and those (n = 77; 66.4%) who did not (C0). Result: The patient backgrounds, operative parameters, and extent of hepatectomy did not significantly differ between the 2 groups except for gender of patients. A significant lower in blood loss (p=0.028), blood transfusion (p=0.011) and rate of portal clamping (p<0.001) were observed in C1 group. The respective blood loss in C1 group and C0 group was 498.9 (95%CI: 375.8- 622.1) and 685.6 (95%CI:571-800.2) milliliter. Conclusion: The current study found infrahepatic IVC clamping during liver transection reduce blood loss, blood transfusion and rate of portal clamping.

ANALISIS CLUSTERING MENGGUNAKAN ALGORITMA K-MEANS TERHADAP PENJUALAN PRODUK PADAPT BATAMAS NIAGA JAYA

PT Batamas Niaga Jaya was established in 1994 located in Sagulung Mas Indah complex, Sagulung Batu Aji district, Batam. This PT rents out 24 kiosks and 48 counters, in the retail sector, PT has 4 stores, namely BIG supermarket, Department store, Stationary and 7,500 convenience store and 10,000 department stores. 7,500 Convenience Stores and 10,000 Stores PT Batamas Niaga Jaya sells various products including food, beverages, kitchen utensils and equipment, and various daily necessities. Sales transactions for 7,500 convenience stores and 10,000 convenience stores were used as objects for analysis. PT Batamas Niaga Jaya often has problems in product management, the company is unable to classify the best-selling products and is not in demand, so it often lacks selling products and piles of non-salable products. The data used is sales data for the last 3 months (February 2018-April 2018). The data cluster technique uses the K-Means algorithm where the data are grouped into several clusters based on the similarity of the data. The results of the study obtained 2 product groups, namely products that were not in demand with the C0 group and the best-selling product group with the C1 group. The C0 product group that is not in demand consists of 657 products and the C1 group consists of 70 products which are in demand.

Impact of Consolidation Cycles Before Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia in First Complete Remission

BackgroundThe optimal number of high-dose cytarabine (HDAC) consolidation cycles before allogeneic hematopoietic cell transplantation (HCT) for acute myeloid leukemia is not fully standardized. Patients and MethodsThis study evaluated the impact of HDAC consolidation cycles before allogeneic HCT in 194 patients with acute myeloid leukemia in first complete remission between 1998 and 2014. The patients were reclassified into 3 groups—no consolidation (C0, n = 20), 1 consolidation (C1, n = 115), and ≥ 2 consolidations (C2, n = 59)—by pre-HCT consolidation cycle. ResultsThe 3-year relapse-free survival rates was 45.9%, 66.9%, and 73.3% for the C0, C1, and C2 groups, respectively (P = .064), while the 3-year overall survival rates were 35.0%, 55.2%, and 67.5%, respectively (P = .106). The cumulative incidence of acute graft-versus-host disease (GVHD) was higher in the C2 group (38.7%) than in the C0 (22.2%) or C1 (17.7%) group (P = .018). However, the incidence of chronic GVHD showed no difference between the groups. Multivariate analysis for overall survival revealed the following independent factors: adverse cytogenetic risk (hazard ratio [HR] = 1.84, P = .046), C2 versus C0 (HR = 0.41, P = .037), pre-HCT status beyond CR1 versus CR1 (HR = 5.78, P < .001), and presence of chronic GVHD (HR = 0.45, P = .004). ConclusionOne or two cycles of HDAC consolidation therapy led to better subsequent HCT outcomes compared to the no–consolidation therapy group.

A validation study of crescents in predicting ESRD in patients with IgA nephropathy

BackgroundA working group on the Oxford classification of IgA nephropathy (IgAN) recently reported that crescents detected in kidney tissue predicted a worse renal outcome. However, this finding must be validated in independent cohorts before it can be widely applied to clinical practice.MethodsBiopsy-proven IgAN patients were continuously recruited from two large renal centers in China from 1989 to 2014. All patients were followed for more than 1 year unless end stage renal disease (ESRD) occurred within 12 months. Crescents were defined as focal cellular or fibrocellular crescent formations. IgAN patients without detectable crescents were recruited to the C0 group. Patients with crescents in less than or more than 1/4 of all glomeruli were recruited to the C1 or C2 group, respectively. Primary outcome was defined as the time to ESRD, and the secondary outcome was defined as the time to an estimated glomerular filtration rate (eGFR) decline equal to or greater than 50% or to ESRD.ResultsIn total, 1152 IgAN patients were recruited in this study. Among all patients, 53.7% were in the C0 group, 38.8% were in the C1 group, and 7.5% were in the C2 group. Compared to patients in the C0 group, patients in the C1 or C2 group were younger, had more urinary protein excretion and lower eGFR, and presented with more severe mesangial hypercellularity, endocapillary proliferation or tubular atrophy/interstitial fibrosis. After 45 months of follow-up, ESRD had occurred in 80 (12.9%), 46 (10.3%) and 18 (20.9%) of patients in the C0, C1 and C2 groups, respectively. By multivariable Cox regression analysis, inclusion in the C1 (HR = 1.07, 95% CI 0.71–1.63), C2 (HR = 0.84, 95% CI 0.41–1.73), or C1 or C2 group (HR = 1.02, 95% CI 0.68–1.52) was not associated with a higher rate of ESRD than inclusion in the C0 group after adjusting for age, gender, eGFR, mean arterial pressure (MAP), MEST scores, and immunosuppressive treatment. However, in patients with nephrotic-range proteinuria, patients in either the C1 or C2 group had a higher rate of the primary outcome, ESRD (HR = 2.54, 95% CI 1.14–5.66) after adjusting for age, gender, eGFR, MAP, MEST scores, and immunosuppressive treatment. Similar results were found when we evaluated the association between crescents and the secondary outcome.ConclusionsIgAN patients with crescents had more severe clinical and pathological manifestations than those without crescents. However, we failed to replicate the association between crescents and renal function progression in Chinese IgAN patients followed for more than 1 year.

Blood pathway analyses reveal differences between prediabetic subjects with or without dyslipidaemia. The Cardiovascular Risk in Young Finns Study.

Prediabetes often occurs together with dyslipidaemia, which is paradoxically treated with statins predisposing to type 2 diabetes mellitus. We examined peripheral blood pathway profiles in prediabetic subjects with (PRD ) and without dyslipidaemia (PR0 ) and compared these to nonprediabetic controls without dyslipidaemia (C0 ). The participants were from the Cardiovascular Risk in Young Finns Study, including 1240 subjects aged 34 to 49years. Genome-wide expression data of peripheral blood and gene set enrichment analysis were used to investigate the differentially expressed genes and enriched pathways between different subtypes of prediabetes. Pathways for cholesterol synthesis, interleukin-12-mediated signalling events, and downstream signalling in naïve CD8+ T-cells were upregulated in the PR0 group in comparison with controls (C0 ). The upregulation of these pathways was independent of waist circumference, blood pressure, smoking status, and insulin. Adjustment for CRP left the CD8+ T-cell signalling and interleukin-12-mediated signalling event pathway upregulated. The cholesterol synthesis pathway was also upregulated when all prediabetic subjects (PR0 and PRD ) were compared with the nonprediabetic control group. No pathways were upregulated or downregulated when the PRD group was compared with the C0 group. Five genes in the PR0 group and 1 in the PRD group were significantly differentially expressed in comparison with the C0 group. Blood cell gene expression profiles differ significantly between prediabetic subjects with and without dyslipidaemia. Whether this classification may be used in detection of prediabetic individuals at a high risk of cardiovascular complications remains to be examined.

Phylogeographical characterization of H5N8 viruses isolated from poultry and wild birds during 2014-2016 in South Korea.

During 2014–2016 HPAI outbreak in South Korea, H5N8 viruses have been mostly isolated in western areas of the country, which provide wintering habitats for wild birds and have a high density of poultry. Analysis of a total of 101 Korean isolates revealed that primitive H5N8 viruses (C0 group) have evolved into multiple genetic subgroups appearing from various epidemiological sources, namely, the viruses circulating in poultry farms (C1 and C5) and those reintroduced by migratory birds in late 2014 (C2 and C4). No C3 groups were detected. The results may explain the possible reasons of the recent long-term persistence of H5N8 viruses in South Korea, and help to develop the effective measures in controlling HPAI viruses.

A fully discrete BEM–FEM scheme for transient acoustic waves

We study a symmetric BEM–FEM coupling scheme for the scattering of transient acoustic waves by bounded inhomogeneous anisotropic obstacles in a homogeneous field. An incident wave in free space interacts with the obstacles and produces a combination of transmission and scattering. The transmitted part of the wave is discretized in space by finite elements while the scattered wave is reduced to two fields defined on the boundary of the obstacles and is discretized in space with boundary elements. We choose a coupling formulation that leads to a symmetric system of integro-differential equations. The retarded boundary integral equations are discretized in time by Convolution Quadrature, and the interior field is discretized in time with the trapezoidal rule. We show that the scattering problem generates a C0 group of isometries in a Hilbert space, and use associated estimates to derive stability and convergence results. We provide numerical experiments and simulations to validate our results and demonstrate the flexibility of the method.

Short term Efficacy of C0-C1 Mobilization in the Cervical Neutral Position in Upper Cervical Hypomobility: A Randomized Controlled Trial

The purpose of this study is to explore the effects of mobilization of C0-C1 and C7-T1 applied to asymptomatic individuals with reduced upper cervical rotation during the FRT. Design: parallel randomized controlled trial. 48 subjects(38.52 years±15.13) with C1-C2 rotation hypomobility in TFR joined the study and were randomized into three groups(C0, C7, control group). FRT in both directions was measured before and after the intervention. C0 intervention consisted of a dorsal translatoric mobilization of C0-C1 in the cervical neutral position. C7 intervention consisted of a ventral cranial translatoric mobilization of C7- T1 in neutral position and the control group maintained a supine position. C0 group experienced a FRT ROM to the restricted side increase of 17.64。(SD=4.55), that was significantly greater (P<0.001) than 5.95。 (SD=4.81) of the C7 group and 2.45。(SD=5.05) of the control group. The results showed that a dorsal translatoric mobilization of C0-C1 in neutral position restored the physiological FRT mobility in subjects with C1-C2 hypomobility and experienced statistical significant improvement in FRT as compared to a C7-T1 translatoric mobilization and a control group. (Level of evidence: 1b).

Prognostic significance of peritoneal washing cytology in patients with gastric cancer

Positive peritoneal washing cytology is a poor prognostic factor in patients with gastric cancer. The right therapeutic approach for this condition has not been well documented. Patients who underwent surgery for gastric cancer with suspected serosal invasion and peritoneal washing cytology at the Korean National Cancer Centre between May 2001 and December 2009 were included in this retrospective study. Clinicopathological factors and overall survival were analysed with respect to the cytological results and presence of peritoneal metastases. Prognostic factors were analysed in patients with positive cytology but without overt peritoneal metastases. A total of 1072 patients were included in the analysis, of whom 900 had negative cytology (C0 group) and 172 had positive cytology (C1 group). No peritoneal metastases (P0) were found in 830 patients (92·2 per cent) in the C0 group. Peritoneal metastases (P1) were found in 76 patients (44·2 per cent) in the C1 group. Median overall survival times in the P0 C1, P1 C0 and P1 C1 subgroups were 20·0, 14·0 and 10·0 months respectively. Multivariable analysis of the P0 C1 subgroup revealed that clinical N0-2 category and gastric resection were significantly associated with better prognosis (median survival 24·0 versus 13·0 months for N0-2 versus N3, and 21·0 versus 4·0 months for resected versus non-resected). Positive washing cytology in patients with gastric cancer is a negative prognostic factor for patients with, as well as those without, overt peritoneal metastases. Resection is an option in patients with clinical stage N0-2 disease without peritoneal metastases but with a positive washing cytology finding.

Experience with a variety of feed colours reduces feed neophobia in the turkey

When exposed to a new feed, farm birds are commonly reluctant to eat this feed. This phenomenon, called feed neophobia, could be reduced by exposing young animals to a variety of novel feeds. We investigated whether previous experience with a variety of feed colours could reduce food neophobia in turkeys. We hypothesised that both greater variety in visual experience and frequency of changes would increase the acceptance of novel feeds. To test this hypothesis, hatchling turkeys were exposed to a 28-day feeding regime differing in feed colours and frequency of feeding transitions. There were 3 experimental groups: one group was exposed to only one colour of feed (C0 group); the second group was exposed to green and red feeds on alternate weeks (low change rate: LC group) and the third group was exposed to green and red feeds changed randomly each day (high change rate: HC). As the contrast between the novel colour and the familiar feed could also influence bird responses, two subgroups were constituted within each experimental group: one receiving green feed and the other red feed before the novel feed test (i.e. C0 red, C0 green; LC red, LC green; HC red, HC green). From D29 to D31, all birds were exposed to blue, light-green or white novel feeds for 5 min each. Short-term feed intake (5 min) was measured the day before change-over and at each change-over on the three subsequent test-days. All groups were found to eat less of the novel feed than the familiar feed but this difference varied according to the 28-day feeding regime and the feed received immediately prior to testing, suggesting a colour contrast effect. The effect of visual experience with a variety of feed colours on neophobia was observed only when there was a marked contrast of colour with the feed received prior to testing which could be explained by an effect of memory on discrimination. When birds had been exposed to LC schedules, this visual experience resulted in the most significant decrease in neophobia. We conclude that changes in diet colour induce various levels of neophobia in turkeys which depend on the visual contrast between the new diet and that of the previous day, and the alternation rate of the visual experience. These results suggest that in production systems, the use of early visual experience with a variety of feed colours could reduce neophobia problems during change-over.

Validation of a new automatic smoking machine to study the effects of cigarette smoke in newborn lambs

The aim of this study was to describe the characteristics and validate the use of a new, custom-built automatic smoking machine (ASM), primarily designed to study the effects of an environmental tobacco smoke surrogate (ETS surrogate) exposure in animals of various sizes, including large animals. The equipment includes a programmable ASM coupled to a vented whole body chamber, where animals can be exposed to both mainstream and sidestream smoke. The user-friendly interface allows for full programming of puff volume (1-60 mL), time interval between two puffs (1-60 s) and between two cigarettes (1-60 min). Eight newborn lambs were exposed to either 10 (4 lambs, C10 group) or 20 (4 lambs, C20 group) cigarettes, 8 h per day for 15 days. Four additional control, lambs were exposed to air (C0 group). Weight gain was identical in all three groups of lambs. Urinary cotinine/creatinine ratio increased with the number of cigarettes smoked (C0: 11 ± 7 ng/mg; C10: 961 ± 539 ng/mg; C20: 1821 ± 312 ng/mg), with levels in the C10 and C20 groups in keeping with values published in infants exposed to ETS. Overall, results show that our new ASM is especially well suited for ETS surrogate exposure in non-restrained, non-anaesthetized large animals such as sheep.

A anquilose tíbio-társica e sua importância na insuficiência venosa crônica

CONTEXTO: O desenvolvimento de anquilose em pacientes com insuficiência venosa crônica (IVC) pode ser evidenciado em diversos estágios da patologia através de medidas da amplitude de movimento da articulação do tornozelo tomadas com a utilização de um goniômetro. OBJETIVO: Relacionar a diminuição da amplitude de movimento da articulação tíbio-társica na IVC dos membros inferiores (MMII) medida por goniometria com a gravidade da IVC, utilizando-se a classificação CEAP. MÉTODOS: No período de março de 2003 a agosto de 2004, 86 pacientes (67 mulheres e 19 homens) com média de idade de 50,6 anos foram submetidos à goniometria do tornozelo. Os indivíduos foram divididos conforme a gravidade da IVC de seus MMII (121 avaliados) de acordo com a classificação CEAP. Quarenta membros foram caracterizados como C0 (grupo-controle), 40 como C3, e 41 como C4. As medidas obtidas nos diferentes grupos foram comparadas entre si. RESULTADOS: A média da amplitude de movimento da articulação tíbio-társica do grupo C0 foi de 42,4º (variação de 26-54); a do grupo C3 foi de 37,9º (variação de 10-61); e a do grupo C4 foi de 24,5º (variação de 8-50). A diferença das médias de C4 e C3 foi de 36%, e a de C3 comparada com o grupo-controle (C0), de 11%, caracterizando a maior diferença entre C3 e C4. CONCLUSÃO: A goniometria do tornozelo auxilia a graduar a hipertensão venosa crônica, pois demonstra a existência de correlação entre a gravidade da anquilose e a severidade da IVC.

The exploratory about time-share and ranking for right to know the fact and selection of schizophrenic

Objective The best juncturest is exploratory that is to enjoyment right to know the fact and selection for schizophrenic. The best extentest is exploratory that is to enjoyment right to know the fact and selection with different time for schizophrenic. Methods The time was divided for on admission,hospitalization one week,hospitalization tow weeks, hospitalization three weeks and hospitalization four weeks five piece time section (time-share)about enjoymenting right to know the fact and selection of schizophrenic;and to enjoymenting right to know the fact and selection of schizophrenic extent was divided for not to know the fact, mere-know the fact and know the fact (ranking).The pathogenetic condition of schizophrenic were evaluated letting enjoyment identical extent right to know the fact and selection at different time and enjoyment identical time right to know the fact and selection at different extent for PANSS,SI and MAOS. Results The rate of schizophrenic cooperation was that A0 group was 63.64%,B0 group was 45.45%,C0 group was 32.73%,the difference had significance(χ2=21.30,P 0.05). Conclusion The schizophrenic are divided time-share and ranking enjoyment right to know the fact and selection according to patient's condition and the guardian to be stipulated by laws. The schizophrenic time-share and ranking for right to know the fact and selection method procedure simple and agility. The method suit our country. The methods have practical and theory value for actuality clinical work. Key words: Schizophrenic; Right to know the fact; Right to know the selection; Time-share; Ranking

Effects of epidural clonidine pretreatment in epidural patient-controlled analgesia using sufentanil combined with levobupivacaine

To investigate the clinical effects of epidural clonidine pretreatment in epidural patient-controlled analgesia (PCA) using sufentanil combined with levobupivacaine. Sixty patients undergoing abdominal hysterectomy of ASA status I-II were randomly divided into 3 equal groups: C2 group was pretreated with epidural clonidine 2 microg/kg at the L2-3 interspace, 15 min later, epidural anesthesia was performed with 0.5% levobupivacaine, and then 0. 4 microg/ml combined with levobupivacaine 2 mg/ml was given for postoperative epidural patient-controlled analgesia. C4 group was pretreated with epidural clonidine 4 microg/kg, and C0 group was pretreated with normal saline. The analgesic effect, PCA drug dosage, adverse reaction, and visual analog scale (VAS) score were recorded. Anesthesia was clinically satisfactory in all patients. The rate of atropine use of the C4 group was 30%, significantly higher than those of the C2 group (15% ) and C0 group (5%, both P < 0.05). The rate of VAS < or = 3 at rest 24 h postoperatively of the C2 and C4 groups were 88% and 93% respectively, both significantly higher than that of the C0 group (75%, P < 0.01 and P < 0.01). The rate of VAS < or = 3 while coughing 24 h postoperatively of the C2 and C4 groups were 61% and 79% respectively, both significantly higher than that of the C0 group (48%). The dosages of PCA drug of the C2 and C4 groups were significantly lower than that of the C0 group by 11.8% and 22.8% respectively (both P < 0.05). The dosage of PCA drug 0-4 h after operation of the C2 was significantly higher than that of the C4 group. The sedative degree of the C4 group was higher than that of the C0 group. The rate of postoperative vomiting of the C0 group was 40%, significantly higher than that of the C4 group (10%, P < 0.05). Epidural clonidine 2-4 microg/kg pretreatment improves the clinical effects of epidural PCA using sufentanil combined with levobupivacaine.

Efikasnost terapijskog monitoringa ciklosporina odredjivanjem C2 i PIK0−4 tokom prva 24 meseca posle transplantacije bubrega

Cyclosporine (CyA) therapeutic drug monitoring (TDM) through the measurement of drug concentration in blood two hours after the administration (C2), and/or according to the calculated value of the area under the concentration-time curve during the first four hours following administration (AUC(0-4)) shows favourable correlation with clinical manifestations in patients with kidney transplantation (Tx). The aim of this study was to analyze clinical efficiency and usability of TDM CyA through C2 and AUC(0-4) in the group of our kidney transplanted patients during the first 24 months following Tx. The study included 50 patients who had undergone kidney Tx using living donors at the Clinic of Nephrology Military Medical Academy, from 1996 to 2003. The first group (group C2) consisted of 25 patients in whom CyA dose was adjusted according to the target C2 and AUC(0-4) (calculated by the regression formula based on C1, C2 and C3), while the second group (group CO) consisted of 25 "historical" patients in whom the dose of this drug was adjusted according to CO. On the 6th day the average daily dose of CyA in the group C2 was 10.1 +/- 0.8 mg/kg, while in the group CO it was 7.6 +/- 1.6 (p < 0.05). One month following the Tx, daily drug doses were quite similar in the two observed groups (6.2 mg/kg in CO and 6.6 mg/kg in group C2, p = NS). In the group C2, target C2/AUC(0-4) (C2 1700 ng/ml, AUC(0-4) 4400 ng h/ml) on the sixth day was achieved in 36.3%, and on day 14 in 76% of the patients. The target AUC(0-4), in relation with C2, in each observed time interval was reached in the higher number of patients. Maximum CyA concentrations in the group C2 were registered 2 hours following the administration (C2), when compared with the concentrations registered after the first and the third hour (C1 and C3). In relation with C1 and C3, C2 concentration correlated most favorably with AUC(0-4), both on the 6th (r = 0.85) and on the 9th day (r = 0.87). During the first three months following the Tx, in the group CO, 10 episodes (40%) of acute cell rejection (AR) were registered, while in the group C2, two episodes (8%, p = 0.07) were registered; in the observed period covering the first two years, a total of 13 (52%) AR episodes in the group CO and 5 AR episodes (20%) in the group C2 (p = 0.03) were registered. All of five episodes of steroid resistant AR were registered in the group CO. In the group C2, all five patients with AR had lower C2 during AR: the average C2 at the moment of AR was 933.8 ng/ml, and in the patients without rejections was 1364.2 ng/ml (p = 0.008). In the same group, the average C0 at the moment of AR was 263.2 ng/ml, and 240.0 ng/ml (p = 0.486) in the patients without AR. In the C0 group, average C0 concentration at the moment of AR was 227.1 ng/ml, while in the patients without AR it was 227.7 ng/ml (p = 0.95). Totally 68% of the patients showed signs of acute CyA nephrotoxicity during the first year in the group C2, and 52% in the group CO (p = 0.38). In seven patients (28%) of the group C2 and six patients of the group C0 (24%, p = 0.96) in the first two years following Tx, administration of CyA was interrupted due to nephrotoxicity. Overall graft function was good in both groups during the period of two years. One graft was lost in the group CO due to chronic allograft nephropathy. The patients in the group C2 had better early and the same late graft function. Five patients in the group C2 who did not reach the target C2/AUC during the first 30 days, did not have more AR or worse graft function, comparing with the patients who reached the target concentrations. In the patients with CyA TDM through with the C2 and AUC(0-4), AR frequency was considerably lower, and AR episodes had a milder flow than in those with CyA TDM through the CO. The drug concentration in blood two hours after administration (C2) was a good predictor of acute graft rejection, while CO failed to point to the patients with the insufficient drug concentration. Higher drug doses were administered in the group C2 during the first month following Tx, and these patients did not show significantly higher frequency of acute nephrotoxicity and more frequent requirement of the drug use interruption. Graft function in both groups was good during the period of two years. CyA dose determination through C2 and AUC(0-4) is efficient TDM method, relatively simple for use in day to day clinical practice.

Pharmacodynamics of T‐cell function for monitoring immunosuppression

Recent studies show that measuring pharmacodynamic (PD) effects offers a unique possibility to predict immunosuppression. Thus, in this study we have monitored the PD properties of immunosuppressants on diverse T-cell functions in heart transplant (HTx) recipients. PDs and blood concentrations (PK) of three different basis-immunosuppressive drugs were studied: cyclosporin A (CsA); tacrolimus (TRL) and sirolimus (SRL). T-cell function was analysed by expression of proliferating cell nuclear antigen (PCNA) labelling, expression of cytokines (IL-2, IFN-gamma) and surface antigen (for example, CD25) by FACS analysis. In group I, at time points C0 and C2, increased CsA-PK significantly inhibited expression of IL-2, IFN-gamma, PCNA and CD25 (P < 0.05). Correlations (r(2)) at C2 between inhibition of T-cell functions (PD) with PK and with drug doses were: CsA-PK: 0.71-0.91 and CsA-dose: 0.73-0.87. In group II, increased TRL-PK over time did not further inhibit expression of CD25, but inhibited PCNA expression more on day 3, and IL-2 and IFN-gamma expression was significantly higher on days 2 and 3 compared to PD effects of CsA (P < 0.05). Blood SRL concentrations in C0 group III, increased on day 1 and remained stable at days 3 and 4. Expression of PCNA was not altered in the SRL-PK category, whereas expression of CD25 was higher and expression of cytokines was lower than PD effects of CsA. Our results show that PD effects on T-cell function can be used to monitor immunosuppression bringing potential to increase the efficacy and safety of immunosuppressive therapy after HTx.

Stabilization of wave systems with input delay in the boundary control

In the present paper, we consider a wave system that is fixed at one end and a boundary control input possessing a partial time delay of weight (1 � µ) is applied over the other end. Using a simple boundary velocity feedback law, we show that the closed loop system generates a C0 group of linear operators. After a spectral analysis, we show that the closed loop system is a Riesz one, that is, there is a sequence of eigenvectors and generalized eigenvectors that forms a Riesz basis for the state Hilbert space. Furthermore, we show that when the weight µ> 1 , for any time delay, we can choose a suitable feedback gain so that the closed loop system is exponentially stable. When µ = 1 ,w e show that the system is at most asymptotically stable. When µ< 1 , the system is always unstable.

Cyclosporine Profiling With C 2 and C 0 Monitoring Improves Outcomes After Heart Transplantation

Cyclosporine (CsA) level at 2 hours post-dose (C2) is a more sensitive marker for rejection risk than trough (C0) level. A combination of C2 and C0 monitoring may prove optimal. We compared efficacy and safety outcomes among 28 de novo heart transplant patients in whom both C2 and C0 monitoring were undertaken (Group 1), with a single CsA profile at Weeks 2 to 6, versus 28 historic controls monitored by only C0 (Group 2). Patients received anti-thymocyte globulin (ATG) induction with CsA, steroids and azathioprine maintenance therapy. The CsA microemulsion dose was significantly higher in Group 1 than Group 2 up to 3 months post-transplant. Mean C2 values in Group 1 at 3 and 12 months were 1,248 +/- 328 ng/ml and 1,039 +/- 362 ng/ml, respectively. One patient in Group 1 and 7 in Group 2 (25%) discontinued CsA, either due to CsA-related neurotoxicity or two or more episodes of early rejection. At 12 months, graft and patient survival were 100% in both groups. Six patients in Group 1 (21%) and 11 in Group 2 (39%) had at least one episode of biopsy-proven acute rejection (not significant). Over the first 12 months post-transplant, the proportion of biopsies showing Grade 3 rejection was 5% in Group 1 and 11% in Group 2 (p < 0.002). Gloerular filtration rate (GFR) was significantly lower in Group 1 than Group 2 at both 3 and 12 months. Combined use of C2 and C0 monitoring results in improved efficacy versus C0 monitoring alone. Regular measurement of C2 levels should be undertaken in de novo heart transplant recipients.

The group and Riesz basis properties of string systems with time delay and exact controllability with boundary control

The group property of a string system with time delay in boundary and the Riesz basis property of eigenvectors of the system are discussed in the present paper. It is proved that, when the feedback with delay τ > 0, the system also associates a C0 group, and its eigenvectors (generalized eigenvectors) form a Riesz basis in Hilbert space H. This result shows that time delay may destroy the stability of the system, but the group and Riesz basis properties are kept. As a consequence, the exact controllability of the system with boundary control is given.