Modelling and experimental validation of Textile Pockets based active inflatable device.

This paper aims with the mathematical modelling of an active inflatable device. This device is composed of a compressor, an Electro-pneumatic Pressure Converter (EPC) and an Inflatable Textile fabric Pocket (ITP). The later has interesting mechanical properties and is fabricated using Jacquard knitting technique which allows automatic production of unlimited varieties of pattern weaving without any mould. Thanks to these features, these ITPs have provided a better alternative to the classical airbags made by stretchable polymer material. The proposed mathematical model is obtained by combining sub-models of two main parts of the whole system. In this way, a generalised and flexible model is obtained which can easily take into consideration the ITPs of different shapes. The pressure dynamics inside the ITP are considered by taking into account the air flow rate, variation of the volume of ITP and the length of pneumatic lines joining ITP with compressed air source. The parameters of the whole mathematical model are obtained via identification techniques. The effectiveness of the model is assessed through several experimental tests with the help of a servo hydraulic fatigue testing machine.

Epidermolysis bullosa simplex with PLEC mutations: new phenotypes and new mutations.

BACKGROUND: Genetic mutations in the plectin gene (PLEC) cause autosomal recessive forms of epidermolysis bullosa simplex (EBS) associated with either muscular dystrophy (EBS-MD) or pyloric atresia (EBS-PA). Phenotype-genotype analysis has suggested that EBS-MD is due mostly to genetic mutations affecting the central rod domain of plectin, and EBS-PA to mutations outside this domain. OBJECTIVES: This study aimed to describe new phenotypes of patients with EBS-MD and EBS-PA, to identify novel PLEC mutations and to establish genotype-phenotype correlations. METHODS: Seven patients with a suspicion of EBS linked to PLEC mutations were included. A standardized clinical questionnaire was sent to the physicians in charge of each patient. Immunofluorescence studies of skin biopsies followed by molecular analysis of PLEC were performed in all patients. RESULTS: We report the first case of nonlethal EBS-PA improving with age, the first multisystemic involvement in a patient with lethal EBS-PA, and the first patients with EBS-MD with involvement of either the bladder or oesophagus. Eleven novel PLEC mutations are also reported. CONCLUSIONS: Our results confirm that EBS-PA is linked to mutations in the distal exons 1-30 and 32 of PLEC. Long-term survival is possible, with skin improvement, but a delayed onset of MD is probable. While EBS-MD is linked to PLEC mutations in all exons, in most cases one of the mutations affects exon 31. The precocity of MD seems to be linked to the type and localization of the PLEC mutation(s), but no correlation with mucosal involvement has been found.

Evolution of the role of the transplant pharmacist on the multidisciplinary transplant team.

Transplant pharmacists have been recognized as an essential part of the transplant team by their colleagues along with several governing and professional organizations. The specific education, training and responsibilities of the transplant pharmacist have not been clearly delineated in the literature. Various pharmacists across the country have been called upon to serve on the transplant team necessitating standardization of their fundamental and desirable activities. Therefore, the purpose of this manuscript is to describe the training and role of a transplant pharmacist on the patient care team and provide a roadmap to implementation of novel transplant pharmacy services.

Experience with low-dose valganciclovir prophylaxis in adult liver transplant recipients.

Valganciclovir (VGCV) is considered the agent of choice after organ transplant for cytomegalovirus (CMV) prophylaxis. The purpose of this retrospective study was to determine the effectiveness and safety of a low-dose regimen after liver transplant (OLT). Eighty-five patients who underwent OLT between August 2002 and August 2004 were included. All patient data for the first 12 months after transplant were collected. Patients received VGCV 450 mg once daily for 3 months posttransplant. CMV infection was based on detection of CMV virus or viral proteins in blood. CMV disease was defined by the presence of positive antigenemia/viremia and evidence of clinical symptoms and/or tissue findings. Patients were D+R+ (54%) and D-R+ (29%), D+R-(11%) and D-R-(6%). Overall, CMV infection and disease occurred in 13% (11/85). CMV infection and disease occurred in 7% and 6%, respectively. CMV infection and disease occurred in 44% (D+R-), 13% (D+R+), 4% (D-R+) patients. The mean time to onset of CMV infection and disease was 103 days (14 to 312 days). Overall, 82% of patients received antibody therapy. The most common adverse events associated with VGCV were leukopenia (16%), thrombocytopenia (4%), anemia (<1%), and neurotoxicity (<1%). Low-dose VGCV was not an effective means to prevent CMV infection in high-risk (D+R-) patients, especially those who received antibody induction. High-risk patients may require a high-dose regimen, such as 900 mg daily, and/or a longer period of prophylaxis, and/or reduction in the use of potent antibody treatments after liver transplant.

Tacrolimus-induced pain syndrome in a pediatric orthotopic liver transplant patient.

Post-transplant complications are common among patients receiving immunosuppressive medications, including pain syndromes. Recently, a pain syndrome, calcineurin-inhibitor induced pain syndrome (CIPS) has been described. To our knowledge, this article is the second report of tacrolimus-associated CIPS, and the first report in the pediatric setting.

Geometric and postural analysis of mild idiopathic scoliotic patients.

Understanding the aggravation process of mild idiopathic scoliosis is still a challenge. The aim of this study is to investigate the spine and pelvis configuration with regard to gravity line using 3D reconstruction coupled with foot pressure measurements. The distance between each vertebral center and the gravity line is calculated in order to observe the global equilibrium of spine. A protocol has been set and used for 10 mild idiopathic scoliotic patients. 34 asymptomatic volunteers who were previously observed with the same protocol were used as reference for biomechanical comparisons. The first results showed differences between scoliotic and asymptomatic subjects and also among scoliotic patients. The proposed protocol should allow clinicians to follow up scoliotic patients with an innovative and efficient tool.

Determination of mycophenolic acid and its phenol glucuronide metabolite in human plasma and urine by high-performance liquid chromatography.

Simultaneous determination of mycophenolic acid (MPA) and mycophenolate phenol glucuronide (MPAG) in plasma and urine was accomplished by isocratic HPLC with UV detection. Plasma was simply deproteinated with acetonitrile and concentrated, whereas urine was diluted prior to analysis. Linearity was observed from 0.2 to 50 microg/ml for both MPA and MPAG in plasma and from 1 to 50 microg/ml of MPA and 5 to 2000 microg/ml MPAG in urine with extraction recovery from plasma greater than 70%. Detection limits using 0.25 ml plasma were 0.080 and 0.20 microg/ml for MPA and MPAG, respectively. The method is more rapid and simple than previous assays for MPA and MPAG in biological fluids from patients.

Tobramycin pharmacokinetics in patients with cystic fibrosis preceding and following lung transplantation.

The pharmacokinetics of tobramycin in patients with cystic fibrosis before and after lung transplantation were evaluated. Twenty-nine lung transplant recipients with cystic fibrosis who received at least one course of tobramycin pre- and posttransplantation were included in this study. Pharmacokinetic parameters (clearance, volume of distribution, elimination rate and half-life) were calculated using a one-compartment Bayesian method. Comparisons were made both between and within pre- and posttransplant periods for patients receiving multiple courses. Significant differences were noted. Clearance was decreased 40%, volume of distribution increased 20%, elimination rate increased 52%, and half-life increased 141%, respectively, posttransplant as compared to pretransplant. There were no differences within each time period between each tobramycin course. The results indicate that tobramycin pharmacokinetics are significantly altered in patients with cystic fibrosis after lung transplantation. Patients with cystic fibrosis require early and close monitoring of tobramycin after lung transplantation.

Risk stratification after myocardial infarction using signal-averaged electrocardiographic criteria adjusted for sex, age, and myocardial infarction location.

BACKGROUND: The objectives were to investigate the factors influencing signal-averaged ECGs (SAECGs) recorded in patients after myocardial infarction (MI) and to develop criteria for predicting arrhythmic events (AEs) that account for these factors. METHODS AND RESULTS: SAECGs were recorded 5 to 15 days after MI in 2461 patients without bundle-branch block. The duration (QRSd), terminal potential (VRMS), and terminal duration (LAS) of the filtered QRS were measured. During follow-up (17 +/- 8 months), AEs (arrhythmic death; ventricular tachycardia, VT; ventricular fibrillation, VF) occurred in 80 patients (3.3%). Receiver operating characteristic curves showed that QRSd discriminated patients with all types of AEs, but VRMS and LAS discriminated only VT patients; QRSd minus LAS also discriminated AE patients. Sex, age, and MI location significantly affected the SAECG; survivors without VT or VF were divided into subgroups (2 sex x 4 age x 2 MI), and QRSd values exceeding the 70th percentile in each subgroup predicted AEs with a sensitivity of 65.4%. An unadjusted QRSd criterion showed the same overall sensitivity and specificity but with less uniform values for each subgroup. A Cox model was constructed by use of multiple prognostic indicators, and in rank order, QRSd, previous MI, and Killip class were predictive of AEs. CONCLUSIONS: SAECG adjustments for sex, age, and MI location did not improve sensitivity and specificity but produced a more uniform predictive performance. The proposed criteria are based only on QRSd, because late potentials (VRMS and LAS) did not discriminate patients with sudden death. Duration of high-level activity during QRS (QRSd-LAS) can predict AEs, suggesting that the arrhythmogenic substate involves a large mass of myocardium.

Vancomycin serum concentrations in patients with renal dysfunction: a comparison of fluorescence polarization immunoassay and the enzyme-multiplied immunoassay technique.

A study was conducted to determine whether assay-specific quantitative differences exist in the determination of vancomycin serum concentrations obtained from patients with renal dysfunction. Vancomycin serum concentrations were obtained during the first week of therapy for each of three time intervals: 48-96 h, 96-144 h, and 144-192 h after administration of the first dose of vancomycin. Vancomycin serum concentrations were measured using the enzyme-multiplied immunoassay technique (EMIT) and fluorescence polarization immunoassay (FPIA). Twenty patients with an estimated creatinine clearance < 40 ml/min who were receiving intravenous vancomycin were evaluated. Hemodialysis was required in 16 of 20 patients. Fifty samples were included in the data analysis. The mean (+/-SD) serum concentrations obtained with EMIT and FPIA were 10.9 mg/L (+/-5.3) and 12.6 mg/L (+/-5.7), respectively (p = 0.13), and were not statistically different. A linear relationship was observed between EMIT and FPIA (EMIT = 0.89 x FPIA - 0.24; r2 = 0.93). No statistically significant differences were observed in the calculated pharmacokinetic parameters between methods. FPIA and EMIT are comparable methods in determining vancomycin serum concentrations within the first week of vancomycin therapy in patients with moderate to severe renal dysfunction.

Methotrexate elimination in a patient with an orthotopic neobladder with and without a urethral catheter.

Placement of a urethral catheter has been recommended to ensure adequate methotrexate elimination in patients with a neobladder; however, the need for this and its impact on methotrexate elimination have not been determined. A 53-year-old man with a cecal continent urinary diversion received intravenous methotrexate 30 mg/m2 on two occasions, with and without urethral catheter drainage of the neobladder. Serum methotrexate concentrations declined at a rate that resulted in 24- and 48-hour values falling below the accepted toxic concentration threshold of 5-50 mumol/L, and 0.05 mumol/L, respectively. In this man, who received low-dose methotrexate, catheterization of the neobladder did not alter methotrexate elimination sufficiently to justify its cost, risk, and inconvenience.

Platelet membrane receptor glycoprotein IIb/IIIa antagonism in unstable angina. The Canadian Lamifiban Study.

BACKGROUND: Ligand binding to the platelet membrane receptor glycoprotein (GP) IIb/IIIa, the final and obligatory step to platelet aggregation, can now be inhibited by pharmacological agents. This study was designed to evaluate the potential of lamifiban, a novel nonpeptide antagonist of GP IIb/IIIa, for the management of unstable angina. METHODS AND RESULTS: In a prospective, dose-ranging, double-blind study, 365 patients with unstable angina were randomized to an infusion of 1, 2, 4, or 5 micrograms/min of lamifiban or of placebo. Treatment was administered for 72 to 120 hours. Outcome events were measured during the infusion period and after 1 month. Concomitant aspirin was administered to all patients and heparin to 28% of patients. Lamifiban, all doses combined, reduced the risk of death, nonfatal myocardial infarction, or the need for an urgent revascularization during the infusion period from 8.1% to 3.3% (P = .04). The rates were 2.5%, 4.9%, 3.3%, and 2.4% with increasing doses. At 1 month, death or nonfatal infarction occurred in 8.1% of patients with placebo and in 2.5% of patients with the two high doses (P = .03). The highest dose of lamifiban additionally prevented the need for an urgent intervention. Lamifiban dose-dependently inhibited platelet aggregation. Bleeding times were significantly prolonged with platelet inhibition of > 80%. Major (but neither life-threatening nor intracranial) bleedings occurred in 0.8% of patients with placebo and 2.9% with lamifiban. CONCLUSIONS: The nonpeptide GP IIb/IIIa antagonist lamifiban protected patients with unstable angina from severe ischemic events during a 3- to 5-day infusion and reduced the incidence of death and infarction at 1 month, suggesting considerable promise for this new therapeutic approach.

Myocardial infarction patients in the 1990s--their risk factors, stratification and survival in Canada: the Canadian Assessment of Myocardial Infarction (CAMI) Study.

OBJECTIVES: This study sought to evaluate the in-hospital and postdischarge mortality of patients with an acute myocardial infarction in the 1990s. BACKGROUND: The widespread implementation of therapeutic interventions that modify the natural history of coronary artery disease has led to changes in the profile and survival of patients with an acute myocardial infarction. Although data exist for selected subsets of patients with an acute myocardial infarction, at this time there is little recent prospective information on all patients presenting with an acute myocardial infarction, particularly for survival after hospital discharge. METHODS: All patients < or = 75 years old presenting with an acute myocardial infarction between July 1, 1990 and June 30, 1992 at nine Canadian hospitals were prospectively evaluated and followed up for 1 year. From November 1991, patients of all ages were included. In two centers, recruitment continued until December 31, 1992. A total of 3,178 patients were recruited. RESULTS: The in-hospital mortality rate of patients < or = 75 years old was 8.4%, and that at 1 year after hospital discharge was 5.3%. For patients of all ages recruited after November 1, 1991, the in-hospital mortality rate was 9.9% and 7.1% for 1 year after hospital discharge. For patients < or = 75 years old, age carried an independent in-hospital but no post discharge risk. Female patients had a twofold greater risk of dying in hospital. After hospital discharge, only 1.7% of patients < or = 75 years old and 1.9% of patients of all ages died of a presumed arrhythmic death. Premature ventricular contractions had no independent prognostic value. The relatively low in-hospital (5.3%) and postdischarge (6.1%) reinfarction rate may have contributed to improved survival. A greater reinfarction rate in patients >75 years old (17.4% vs. 9.6%, p < 0.001) may have contributed to their poorer outcome. CONCLUSIONS: One-year mortality after acute myocardial infarction continues to decrease, and changes in the prognostic value of traditional methods of risk stratification have occurred.

Multiple delayed peak lithium concentrations following acute intoxication with an extended-release product.

OBJECTIVE: To describe delayed peak lithium concentrations after an overdose of extended-release lithium tablets. CASE SUMMARY: A patient with borderline personality disorder and depression ingested extended-release lithium approximately 20.25 g along with other agents. At presentation, the lithium concentration was 1.4 mEq/L. Significant enteral intake was initiated 27 hours after presentation and the lithium concentration 5 hours later increased to 3.2 mEq/L. A second lithium peak concentration of 5.0 mEq/L was noted 40 hours after presentation. Two hemodialysis sessions lasting 4 hours each were performed along with administration of sodium polystyrene sulfonate in sorbitol 20% to enhance lithium elimination and decrease absorption. Eighty-eight hours after presentation, the lithium concentration had decreased to 1.5 mEq/L. DISCUSSION: Delayed and secondary peak lithium concentrations have been reported following an overdose with an extended-release product. Extended-release lithium may form an aggregate in the gastrointestinal tract and/or have delayed absorption secondary to coingested drugs. Toxicity may result if the patient begins enteral intake of drugs, fluids, or nutrition. CONCLUSIONS: Continued monitoring of lithium concentrations after an acute ingestion with an extended-release product are recommended until lithium concentrations are less than 1.5 mEq/L and there are no signs of toxicity, particularly once the patient begins significant enteral intake.

Approaches to the treatment of hyperlipidemia in the solid organ transplant recipient.

OBJECTIVE: To review the literature investigating increased lipid concentrations in transplant recipients and the use of lipid-lowering agents in this population. DATA SOURCES: Relevant articles were identified from a MEDLINE search using the terms transplantation, hyperlipidemia, immunosuppression, and therapy including diet, gemfibrozil, bile acid sequestrants, nicotinic acid, probucol, and hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors. Selected literature, including controlled studies, was used in this review. STUDY SELECTION: Articles published since 1970 pertaining to hyperlipidemia in solid organ transplant recipients. Emphasis was placed on clinical trials that investigated approaches to the treatment of hyperlipidemia in transplant recipients. DATA EXTRACTION: Original articles and reviews were obtained to select material pertinent to the objectives. DATA SYNTHESIS: Descriptions of lipid concentrations in the transplant patient and treatment approaches used, including potential complications, were reviewed. CONCLUSIONS: Hyperlipidemia is an important risk factor for coronary heart disease in the solid organ transplant patient. Treatment alternatives include diet modification and, in most cases, pharmacologic intervention that should be based on the type of hyperlipidemia. The HMG-CoA reductase inhibitors are effective agents in the treatment of hyperlipidemia in the transplant recipient and generally are used as single therapy in low dosages to minimize the risk of myositis or rhabdomyolysis.

Appropriate use of heparin. Empiric vs nomogram-based dosing.

BACKGROUND: A study involving two groups of patients with cardiovascular disease was conducted to compare empiric (clinician-directed) heparin therapy with therapy based on a nomogram-determined dosage. The comparison was based on (1) the average weight-referenced infusion rate yielding a therapeutic activated partial thromboplastin time (APTT) and (2) the time required to reach a therapeutic APTT (55 to 95 seconds) after empiric or nomogram-based heparin therapy was initiated. METHODS: Data were collected for patients admitted to the cardiology service at a university health science center in two phases: phase 1 (April 1 through June 30, 1992), involving 95 patients receiving heparin therapy, with 88 patients included in the data analysis, and phase 2 (March 11 through June 11, 1993), involving 156 patients receiving heparin therapy, with 45 patients receiving nomogram-guided therapy included in the data analysis. RESULTS: In phase 1, 66 patients (75.0%) achieved a therapeutic APTT some time during their heparin therapy, with an average time to therapeutic APTT of 20.7 + 19.1 hours. Regression analysis demonstrated a statistically significant relationship between the heparin infusion rate at the time of the patient's first therapeutic APTT and the patient's total body weight (r2 = .3043). An initial infusion rate based on total body weight (13 U/kg per hour) was therefore used as the basis for the nomogram in phase 2. In phase 2, 41 patients (91.1%) achieved a therapeutic APTT at some time during their heparin therapy, with an average time to therapeutic APTT of 13.1 + 11.9 hours, statistically significantly shorter than that in phase 1. A greater proportion of patients in phase 2 compared with patients in phase 1 reached the therapeutic range within 12 hours (62.2% vs 34.1%) and within 24 hours (77.8% vs 54.5%). CONCLUSIONS: Use of a weight-based nomogram to determine the initial and maintenance heparin infusion rates was associated with a higher percentage of patients admitted to the cardiology service reaching the targeted therapeutic APTT range at a time earlier in the course of therapy compared with empiric dosing.

Thigmotaxis as an index of anxiety in mice. Influence of dopaminergic transmissions.

When mice are introduced into an open-field, they are inclined to explore mainly the peripheral zone of this open-field. This tendency to remain close the walls, called thigmotaxis, decreases gradually during the first minutes of exploration. We have considered the degree of thigmotaxis during this period of decrease as an index of anxiety in mice. This hypothesis has been validated with several reference anxiogenic drugs (dexamphetamine, pentylenetetrazole, yohimbine, idazoxan) which increased thigmotaxis; and with anxiolytic drugs (buspirone, phenobarbital), which reduced it. On this test the selective or non-selective indirect dopamine agonists GBR 12783, dexamphetamine and cocaine induced an increase of thigmotaxis. Finally, the simultaneous involvement of D1 and D2 dopamine receptors has been evidenced in the anxiogenic-like effect associated with an increase of dopaminergic transmissions.

Salivary theophylline monitoring: reassessment and clinical considerations.

To assess the reliability of salivary theophylline concentrations for patient monitoring, concentrations of theophylline in sera and saliva of 50 patients (ages 6-81 years) receiving oral or parenteral theophylline were determined by two methods: a rapid dry-phase apoenzyme reactivation system (ARIS) and fluorescence polarization immunoassay (FPIA). Saliva production was stimulated by both citric acid (CA) and parafilm (PF). With both analytical methods, there were excellent correlations between salivary theophylline concentration, CS, and unbound serum theophylline concentration CU (r2 > 0.95), and between CS and total serum theophylline concentration, CT (r2 > 0.85). CA- and PF-stimulated CS by FPIA resulted in concentrations within 2.0 micrograms/ml of the actual CU for 100% of the samples measured (n = 47). By ARIS, 100% of the PF-stimulated CS and 93.6% of the CA-stimulated CS determinations were within 2.0 micrograms/ml of the CU (n = 47). To evaluate the predictive capabilities of PF- and CA-stimulated saliva, one-half (n = 24) of the patients were randomly selected and their data used to predict the CT for the remaining patients. FPIA PF-CS predicted 83.3% (20/24) of CT within +/- 2 micrograms/ml, while ARIS CA-CS predicted 75.0% within +/- 2 micrograms/ml. There was no difference between FPIA CS and ARIS CS results by multivariate analysis of variance (MANOVA), but there was a difference between PF-CS and CA-CS (p < 0.05). However, when CU was used as a covariant, there was no significant difference. Using appropriate saliva collection procedures and the FPIA system, we conclude that CS provides adequate reliability for therapeutic drug monitoring of theophylline.