Pharmacokinetics of mycophenolate mofetil in stable pediatric liver transplant recipients receiving mycophenolate mofetil and cyclosporine.

There are few pharmacokinetic data for mycophenolate mofetil (MMF) when used in combination with cyclosporine (CsA) in pediatric liver transplant recipients. The aim of this study was to assess the pharmacokinetics of MMF in stable pediatric liver transplant patients and estimate the dose of MMF required to provide a mycophenolic acid (MPA) exposure similar to that observed in adult liver transplant recipients receiving the recommended dose of MMF (target area under the plasma concentration-time curve from 0 to 12 hours [AUC(0-12)] for MPA of 29 mug.hour/mL in the immediate posttransplantation period and 58 microg x hour/mL after 6 months). A 12-hour pharmacokinetic profile was collected for 8 pediatric patients (mean age 20.9 months) on stable doses of MMF and CsA who had received a liver transplant > or = 6 months prior to entry and who had started on MMF within 2 weeks of transplantation. Mean MMF dosage was 285 mg/m(2) (range, 200-424 mg/m(2)). Of 8 patients, 7 had a MPA AUC(0-12) (range, 11.0-37.2 microg x hour/mL) well below the target. One patient had an AUC(0-12) > or = 58 microg x hour/mL but was considered an outlier and was excluded from analyses. Mean MPA AUC(0-12) and maximum plasma concentration values were 22.7 +/- 10.5 microg x hour/mL and 7.23 +/- 3.27 microg/mL, respectively; values normalized to 600 mg/m(2) (the approved pediatric dose in renal transplantation) were 47.0 +/- 21.8 microg x hour/mL and 14.5 +/- 4.21 microg/mL. In conclusion, assuming that MPA exhibits linear pharmacokinetics, when used in combination with CsA, a MMF dose of 740 mg/m(2) twice daily would be recommended in pediatric liver transplant recipients to achieve MPA exposures similar to those observed in adult liver transplant recipients. This finding should be confirmed by a prospective trial.     

Prospective randomized trial of direct endomyocardial implantation of bone marrow cells for treatment of severe coronary artery diseases (PROTECT-CAD trial).

AIMS: Experimental studies have demonstrated that bone marrow (BM) cells can induce angiogenesis in ischaemic myocardium. Recently, several non-randomized pilot studies have also suggested that direct BM cells implantation appears to be feasible and safe in patients with severe coronary artery diseases (CAD). METHODS AND RESULTS: We performed a randomized, blinded, and placebo-controlled trial in 28 CAD patients. After BM harvesting, we assigned patients to receive low dose (1 x 10(6) cells/0.1 mL, n = 9), high dose (2 x 10(6) cells/0.1 mL, n = 10) autologous BM cells or control (0.1 mL autologous plasma/injection, n = 9) catheter-based direct endomyocardial injection as guided by electromechanical mapping. Our primary endpoint was the increase in exercise treadmill time and our secondary endpoints were changes in Canadian Cardiovascular Society (CCS) and New York Heart Association (NYHA) class, and myocardial perfusion and left ventricular ejection fraction (LVEF) assessed by single-photon emission computed tomography and magnetic resonance imaging, respectively. A total 422 injections (mean 14.6 +/- 0.7 per patient) were successfully performed at 41 targeted ischaemic regions without any acute complication. Baseline exercise treadmill time was 439 +/- 182 s in controls and 393 +/- 136 s in BM-treated patients, and changed after 6 months to 383 +/- 223s and 464 +/- 196 s [BM treatment effect +0.43 log seconds (+53%), 95% CI 0.11-0.74, P = 0.014]. Compared with placebo injection, BM implantation was associated with a significant increase in LVEF (BM treatment effect +5.4%, 95% CI 0.4-10.3, P = 0.044) and a lower NYHA class (odds ratio for treatment effect 0.12, 95% CI 0.02-0.73, P = 0.021) after 6 months, but CCS reduced similarly in both groups. We observed no acute or long-term complications, including ventricular arrhythmia, myocardial damage, or development of intramyocardial tumour or calcification associated with BM implantation. CONCLUSION: Direct endomyocardial implantation of autologous BM cells significantly improved exercise time, LVEF, and NYHA functional class in patients with severe CAD who failed conventional therapy.     

Guidelines for Cardiac Management in Noncardiac Surgery Are Poorly Implemented in Clinical Practice: Results from a Peripheral Vascular Survey in The Netherlands

Background: The American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for Perioperative Cardiovascular Evaluation for Noncardiac Surgery recommend an algorithm for a stepwise approach to preoperative cardiac assessment in vascular surgery patients. The authors' main objective was to determine adherence to the ACC/AHA guidelines on perioperative care in daily clinical practice.

Methods: Between May and December 2004, data on 711 consecutive peripheral vascular surgery patients were collected from 11 hospitals in The Netherlands. This survey was conducted within the infrastructure of the Euro Heart Survey Programme. The authors retrospectively applied the ACC/AHA guideline algorithm to each patient in their data set and subsequently compared observed clinical practice data with these recommendations.

Results: Although 185 of the total 711 patients (26%) fulfilled the ACC/AHA guideline criteria to recommend preoperative noninvasive cardiac testing, clinicians had performed testing in only 38 of those cases (21%). Conversely, of the 526 patients for whom noninvasive testing was not recommended, guidelines were followed in 467 patients (89%). Overall, patients who had not been tested, irrespective of guideline recommendation, received less cardioprotective medications, whereas patients who underwent noninvasive testing were significantly more often treated with cardiovascular drugs ([beta]-blockers 43% vs. 77%, statins 52% vs. 83%, platelet inhibitors 80% vs. 85%, respectively; all P < 0.05). Moreover, the authors did not observe significant differences in cardiovascular medical therapy between patients with a normal test result and patients with an abnormal test result.     

Satellite cells express distinct patterns of myogenic proteins in immature skeletal muscle.

Satellite cells are the myogenic cells lying between the myofiber sarcolemma and basal lamina. The objective of this study was to determine the expression patterns of MyoD, myogenin, and Pax7 within the satellite cell population in the growing rat soleus and extensor digitorum longus (EDL) muscles. Secondly, the expression of the myogenic markers was also studied within the interstitial cell compartment and myonuclei. It was discovered that the soleus contained a higher number of Pax7, MyoD, or myogenin-positive nuclei compared with the EDL. Similarly, myogenin was expressed at a lower level in the myonuclei of the soleus compared with the EDL, and myogenin was expressed at a higher level in the interstitial compartment of the soleus compared with the EDL. When interstitial nuclei, myonuclei, and double-labeled nuclei were used in the estimate of the satellite cell population, it was discovered that approximately of 13% of the myofibers in a transverse section of the soleus muscle and 4.1% of EDL myofibers exhibit a labeled satellite cell nucleus. Overall, results from this study suggest that expression patterns of these markers vary predictably among muscles with different growth dynamics and phenotypic characteristics.     

Clinical and laboratory characteristics of 75 patients with specific polysaccharide antibody deficiency syndrome.

BACKGROUND: There are limited studies of large cohorts of patients with specific polysaccharide antibody deficiency (SPAD) syndrome. OBJECTIVE: To study the clinical and laboratory characteristics of patients with specific polysaccharide antibody deficiency syndrome. METHODS: We retrospectively studied 75 patients with total IgG levels of at least 500 mg/dL and fewer than 9 of 12 responses to vaccination with pneumococcal vaccine polyvalent. Exclusion criteria included an IgG level less than 500 mg/dL, established immunodeficiency syndrome, and secondary immunodeficiency. RESULTS: The most common clinical presentation was frequent infections (n = 69; 92%), including sinusitis (n = 53; 77%), pneumonia (n = 29; 42%), ear infections (n = 18; 26%), and bronchitis (n = 19; 28%). Other presentations were systemic infections (n = 5; 7%), autoimmune or rheumatic diseases (n = 6; 8%), and chronic diarrhea (n = 4; 5%). The median IgG2 level of patients with no response to pneumococcal vaccine polyvalent tended to be lower than that of patients with at least 1 response (150 vs 193 mg/dL, respectively; P = .06). There was no association between total IgG level (categorized as 500-600 or > or = 600 mg/dL) and frequency of infection (P = .43). Patients with fewer responses to pneumococcal vaccine polyvalent and a higher frequency of infections were more likely to receive intravenous immunoglobulin (IVIG) therapy (P = .01 and .003, respectively). Treatment with IVIG significantly reduced the number of infections (P < .001). CONCLUSION: Patients with no response to pneumococcal vaccine polyvalent tended to have lower IgG2 levels; those with fewer responses were more likely to receive IVIG therapy.     

Investigation of melt agglomeration process with a hydrophobic binder in combination with sucrose stearate

The melt agglomeration process of lactose powder with hydrogenated cottonseed oil (HCO) as the hydrophobic meltable binder was investigated by studying the physicochemical properties of molten HCO modified by sucrose stearates S170, S770 and S1570. The size, size distribution, micromeritic and adhesion properties of agglomerates as well as surface tension, contact angle, viscosity and specific volume of molten HCO, with and without sucrose stearates, were examined. The viscosity, specific volume and surface tension of molten HCO were found to be modified to varying extents by sucrose stearates which are available in different HLB values and melt properties. The growth of melt agglomerates was promoted predominantly by an increase in viscosity, an increase in specific volume or a decrease in surface tension of the molten binding liquid. The agglomerate growth propensity was higher with an increase in inter-particulate binding strength, agglomerate surface wetness and extent of agglomerate consolidation which enhanced the liquid migration from agglomerate core to periphery leading to an increased surface plasticity for coalescence. The inclusion of high concentrations of completely meltable sucrose stearate S170 greatly induced the growth of agglomerates through increased specific volume and viscosity of the molten binding liquid. On the other hand, the inclusion of incompletely meltable sucrose stearates S770 and S1570 promoted the agglomeration mainly via the reduction in surface tension of the molten binding liquid with declining agglomerate growth propensity at high sucrose stearate concentrations. In addition to being an agglomeration modifier, sucrose stearate demonstrated anti-adherent property in melt agglomeration process. The properties of molten HCO and melt agglomerates were dependent on the type and concentration of sucrose stearate added.     

Management of filamentary keratitis associated with aqueous-deficient dry eye.

PURPOSE: To review the incidence, underlying pathophysiology, and clinical features of filamentary keratitis and to identify evidence-based best-practice strategies for managing filamentary keratitis. METHODS: A comprehensive review of published literature was undertaken. Recommendations for best-practice management strategies were based on the available evidence. Three cases are presented to illustrate the clinical findings and management of patients with chronic filamentary keratitis. RESULTS: Although the evidence base is limited by the absence of well-designed studies, current evidence indicates the following: (1) Aqueous-deficient dry eye (keratoconjunctivitis sicca) is the most common ocular condition associated with filamentary keratitis. (2) Current best-practice management of filamentary keratitis involves treating the underlying dry eye and specific treatments for the corneal filaments. Proposed treatments include nonpreserved lubricants, topical steroidal and nonsteroidal anti-inflammatory agents, and punctal plugs for aqueous-deficient dry eye as well as mechanical removal of filaments, hypertonic saline, mucolytic agents, and bandage contact lenses for the filaments. (3) Filamentary keratitis can be induced or exacerbated by contact lens wear and ocular surgical procedures such as cataract surgery and corneal graft surgery. Pre- and postoperative ocular surface management strategies should be considered in the surgical planning of patients with, or who are susceptible to, filamentary keratitis. Filamentary keratitis can also be induced and/or exacerbated by chronic use of ocular and/or systemic medications, and alternate medications or additional measures to manage the tear film and ocular surface may be required in these cases. CONCLUSIONS: Filamentary keratitis can be a chronic, recurrent, and debilitating condition. With a systemic approach to diagnosis and management, the condition can be effectively controlled and the incidence and severity of recurrences minimized.