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.

Characterization of a 280-kD protein restricted to the coated pits of the renal brush border and the epithelial cells of the yolk sac. Teratogenic effect of the specific monoclonal antibodies.

Intermicrovillar areas and apical vesicles characterized by an extensive clathrin coat can be identified in some epithelial cell types. We describe a 280-kD protein, characteristic of these areas in the proximal tubule brush border and epithelial cells of the visceral yolk sac. When injected to 9-d pregnant rats, mAbs to the 280-kD protein regularly induced fetal resorption and/or malformations. Antibodies to a 330-kD protein that is also coated-pit-restricted had no effect. Our observations point to a key function for p280 and suggest that immunity to specific constituents of the receptor-mediated endocytotic system may be involved in the induction of fetal abnormalities.

Metalorganic Chemical Vapor Deposition of III-V Semiconductors.

Metalorganic chemical vapor deposition (MOCVD) is a process in which two or more metalorganic chemicals (for instance, trimethylgallium) or one or more metalorganic sources and one or more hydride sources (for instance, arsine, AsH(3)) are used to form the corresponding intermetallic crystalline solid solution. MOCVD materials technology is a vapor-phase growth process that is becoming widely used to study the basic physics of novel materials and to grow complex semiconductor device structures for new optoelectronic and photonic systems. The MOCVD process is described and some of the device applications and results that have been realized with it are reviewed, with particular emphasis on the III-V compound semiconductors.

LSD: no teratogenic action in rats, mice, and hamsters.

Lysergic acid diethylamide tartrate was given to 98 pregnant rats, 67 mice, and 22 hamsters as a single dose of 5 to 500 micrograms per kilogram of body weight per day either at the beginning of gestation or during the period of organogenesis. Examination of the 1003 rat fetuses, 521 mouse fetuses, and 189 hamster fetuses obtained failed to prove any abortifacient, teratogenic, or growth-depressing effects.

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.

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.

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.

Association of microwaves and ionizing radiation: potentiation of teratogenic effects in the rat.

Pregnant Wistar rats were exposed to either microwave-induced hyperthermia or gamma radiation or a combination of both. In microwave-induced hyperthermia, a core temperature of 42 degrees C was slightly teratogenic and a core temperature greater than or equal to 43 degrees C was highly teratogenic. Gamma radiation at 40 cGy was subteratogenic, while a dose of 75 cGy was highly teratogenic. A combination of microwave-induced hyperthermia up to 42 degrees C with 40 cGy of gamma radiation was highly teratogenic, indicating a mutual potentiation of the embryotoxic action of these two teratogens.

Acute valproic acid overdose. Clinical course and pharmacokinetic disposition of valproic acid and metabolites.

Acute toxicity in the setting of valproic acid (valproate sodium) overdose is in most cases benign and readily reversible. However, serious toxicity has been reported. We present a case of accidental acute valproic acid overdose in a 26-month-old female, in whom serious neurological, metabolic, haematological and respiratory sequelae occurred. The major toxicity observed was delayed cerebral oedema. We also present data not previously reported, which describes the pharmacokinetic disposition of valproic acid and several of its metabolites during the course of this acute overdose. A comparison of an enzyme immunoassay and gas liquid chromatographic methodologies for measuring valproic acid in this setting is also presented. It appears that the 2-EN-valproic acid metabolite plays a role in the neurological toxicity.

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.

Preoperative flurbiprofen in oral surgery: a method of choice in controlling postoperative pain.

The analgesic efficacy of a single 50-mg preoperative dose of flurbiprofen was compared with ACC-30 (aspirin 375 mg, codeine 30 mg, caffeine 30 mg) and a placebo. Forty patients scheduled for the surgical removal of impacted maxillary third molars were enrolled in a double-blind, randomized study. Using a within-subject design we compared the analgesic efficacy of (1) preoperative flurbiprofen 50 mg with placebo in 20 patients, and (2) preoperative ACC-30 with placebo in 20 other patients. Using a between-group design, we then compared the analgesic efficacy of (3) each drug given preoperatively and postoperatively, and (4) each drug given postoperatively only. Patients rated 2 pain dimensions, intensity and unpleasantness, hourly for 8 hours after the presurgical dose. The results of this study indicate that better analgesia was obtained when flurbiprofen was given preoperatively compared to only after surgery. Conversely, preoperative administration of ACC-30 did not demonstrate any significant influence on postsurgical analgesia. When comparing the 2 drugs, flurbiprofen proved to be superior in providing pain relief only when it was given prior to surgery. There was no difference between them when given only after surgery. Side effects were moderate and not significantly different between patients receiving flurbiprofen and those receiving ACC-30.

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.

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.

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.

Teratogenic action and embryo lethality of AY 9944R. Prevention by a hypercholesterolemia-provoking diet.

Embryomortality and teratogenesis provoked by inhibitors of cholesterol synthesis are well demonstrated. Teratogenic action is particularly reflected by holoprosencephalies, but also by uro-genital abnormalities. A hypercholesterolemia-provoking diet has been shown to be completely effective for preventing holoprosencephaly, but only partially so for preventing the uro-genital malformations and fetal mortality. It is thus possible that the two types of abnormalities are governed by different mechanisms. In addition, the diet itself, whose hypercholesterolemic effect is considerable, has certain disadvantages. It seems to have a certain effect on fetal mortality and could be responsible for several uro-genital malformations. This deserves further study.