Early, but not late therapy with a vasopressin V1a-antagonist ameliorates the development of renal damage after 5/6 nephrectomy.

INTRODUCTION: Vasopressin, mainly through the V1a-receptor, is thought to be a major player in the maintenance of hyperfiltration. Its inhibition could therefore lead to a decrease in progression of chronic renal failure. To this end, the effect of the vasopressin V1a-receptor-selective antagonist, YM218, was studied on proteinuria and focal glomerulosclerosis in early and late intervention after 5/6 nephrectomy in rats, and compared with an angiotensin-converting enzyme inhibitor (ACE-I). MATERIALS AND METHODS: After 5/6 nephrectomy, early intervention was performed between week 2 and 10 thereafter with the V1a-receptor-selective antagonist (VRA, 10 mg/kg/day, n=10), enalapril (ACE-I, 10 mg/kg/day, n=9), or vehicle (n=8). Late intervention was performed in another group between week 6 and 12 with VRA (10 mg/kg/day, n=7), lisinopril (ACE-I, 5 mg/kg/day, n=7), or vehicle (n=7). RESULTS: In early intervention, proteinuria and focal glomerulosclerosis were significantly decreased by VRA compared to vehicle (44+7% and 59+8% respectively). ACE-I significantly decreased proteinuria (67+7%) and a trend towards a decrease in focal glomerulosclerosis was observed (30+18%). In late intervention, VRA did not decrease proteinuria and focal glomerulosclerosis compared to vehicle (21+20% and 0%, respectively), ACE-I significantly lowered proteinuria (92+2%) and a focal glomerulosclerosis (69+1%) lowering trend was observed. CONCLUSION: These results indicate that VRA may protect against early progression of renal injury after 5/6 nephrectomy, whereas its effectiveness seems limited in established renal damage.     

Spray coated pellets as carrier system for mucoadhesive drug nanocrystals.

High pressure homogenization can be employed to produce drug nanocrystals with a number of advantages, like improved solubility behaviors, better drug targeting or even increased mucoadhesiveness. To obtain a controlled drug delivery system it is necessary to transform the resulting nanosuspension into a solid dosage form. The present study shows the feasibility to use a mucoadhesive nanosuspension of poorly soluble hydrocortisone acetate produced by high pressure homogenization as layering dispersion in a fluidized bed process, followed by the application of an enteric coating to achieve a controlled drug release. To point out the advantages of drug nanocrystals the new fomulation was compared with a formulation containing micronized drug. Both formulations were characterized with regard to their particle size and crystallinity by using laser diffractometry, photon correlation spectroscopy and X-ray diffraction. The pellet morphology was characterized by using the environmental scanning electron microscopy (ESEM). In the in vitro dissolution tests an accelerated dissolution velocity and an increased drug release could be shown for the pellets containing drug nanocrystals.     

Intensive care research coordinators: who are they and what do they do? Results of a binational survey.

Research coordinators in intensive care are a growing specialty about which little is known. This cross-sectional study surveyed the Australia and New Zealand Intensive Care Research Coordinators' Group (n = 49) regarding demographics, education, employment history, job structure, and role content. Most research coordinators were highly qualified and experienced nurses who undertake pharmaceutical trials, multicenter projects, departmental medical and nursing research, audits and data registries, and their own projects.     

Optimal intensity for respiratory muscle endurance training in patients with spinal cord injury.

OBJECTIVE: Respiratory muscle endurance of able-bodied persons, assessed by normocapnic hyperpnoea at 70% of their maximal voluntary ventilation, usually ranges from 10 to 20 minutes. The aim of this study was to determine the level of ventilation that patients with paraplegia and tetraplegia can sustain for 10-20 minutes to later be used as the guideline for respiratory muscle endurance training. DESIGN: Pilot study; cross-over setting. SUBJECTS: Two groups, 8 patients with paraplegia and 6 with tetraplegia. METHODS: Respiratory muscle endurance tests were performed at 3 different intensities of normocapnic hyperpnoea, i.e. 20%, 40% and 60% maximal voluntary ventilation. Subjects performed partial re-breathing from a bag to assure normocapnia. Respiratory endurance was separately analysed for patients with paraplegia and tetraplegia. RESULTS: Mean respiratory endurance times were 46.0, 18.9 and 4.2 minutes at 20%, 40% and 60% maximal voluntary ventilation in patients with tetraplegia and 51.8, 38.8 and 12.2 minutes in patients with paraplegia. The duration differed significantly at 60% maximal voluntary ventilation between the groups. CONCLUSION: Minute ventilation to perform respiratory muscle endurance training can be set at around 40% of maximal voluntary ventilation for patients with tetraplegia and around 60% of maximal voluntary ventilation for patients with paraplegia, as these levels can be sustained for 10-20 minutes.     

Pediatric valve replacement, 15 years experience in Oman

Background Despite improving surgical techniques, treatment of heart valve disease in children remains controversial. Somatic growth and adequate anticoagulation are of concern when children undergo valve replacement. We conducted this study to evaluate the performance of valves in this age group. Methods 42 children under the age of 13 years who underwent valve replacement were included in this study. Totally, 50 valves were implanted in 42 patients: 48 were mechanical prostheses, two were bioprosthetic both in pulmonary position. 37 (74%) valves were implanted in mitral position, 10 (20%) in aortic position, 1 (2%) in tricuspid position and 2 (4%) in pulmonary position. Preoperatively, 14 (33,3%) patients were in New York Heart Association (NYHA) class IV, while 27 (64.2%) were in NYHA class III. Results There were 2 (4.7%) hospital deaths and 2 (4.7%) late deaths while 2 (4.7%) patients were lost to follow up. The mean follow up period was 9.4 yrs. 35 (83.3%) patients are in NYHA Class I and free of all medications except warfarin. 3 (7.1%) patients have undergone 5 successful pregnancies. The median INR was 2.23. Major thrombo-embolic episode occurred in 1 (2.3%) patient. Conclusions In view of the problems of sizing, anticoagulation and need for re-operation at an early age, there is a reluctance to replace valves in children. This study shows that despite these problems, valve replacement can be undertaken safely and successfully in children, when repair has failed or not technically feasible.     

Relationship between insulin-like growth factor I, dehydroepiandrosterone sulfate and proresorptive cytokines and bone density in cystic fibrosis

Introduction Patients with cystic fibrosis (CF) are known to be at risk for early osteoporosis, and the mechanisms that mediate bone loss are still being delineated. The aim of the present investigation was to investigate if a correlation exists in these patients between skeletal measurements by dual-energy x-ray absorptiometry (DXA) and two anabolic factors, dehydroepiandrosterone (DHEA) and insulin-like growth factor I (IGF-I), and proresorptive factors such as the cytokines interleukin-1β, tumor necrosis factor α, and interleukin-6. Methods We studied 32 outpatients (18 females; mean age: 26.2 ± 7.9 years) at a tertiary care medical center. The subjects had venous samples obtained, underwent anthropometric and bone mineral density (BMD) measurements, and completed a health survey. Serum IGF-I concentrations were below the age-adjusted mean in 78% of the participants, and DHEA sulfate (DHEAS) concentrations were low in 72%. Serum concentrations of all cytokines were on the low side of normal; nonetheless, there was a modest inverse correlation between IL-1β and BMD at all sites. Results In univariate analyses, IGF-I and DHEAS were significant correlates of BMD or bone mineral content. In final multivariate models controlling for anthropometric and other variables of relevance to bone density, only IGF-I was identified as a significant independent skeletal predictor. While alterations in DHEAS, IGF-I, and specific cytokines may contribute to skeletal deficits in patients with CF, of these factors a low IGF-I concentration appears to be most strongly correlated with BMD. Conclusions These findings may have therapeutic implications for enhancing bone density in these patients.     

The role of intraoperative monitoring of oculomotor and trochlear nuclei -safe entry zone to tegmental lesions.

OBJECTIVE: A safe entry zone to tegmental lesions was identified based on intraoperative electrophysiological findings, the compound muscle action potentials (CMAP) from the extraocular muscles, and anatomic considerations. This entry zone is bordered caudally by the intramesencephalic path of the trochlear, laterally by the spinothalamic tract, and rostrally by the caudal margin of the brachium of the superior colliculus. METHODS: Four intrinsic midbrain lesions were operated upon via the safe entry zone using the infratentorial paramedian supracerebellar approach. All lesions involved the tegmentum and included an anaplastic astrocytoma, a metastatic brain tumor, a radiation necrosis, and a cavernous angioma. CMAP were bilaterally monitored from the inferior recti (for oculomotor function) and superior oblique (for trochlear nerve function) muscles. RESULTS: In three of four cases, CMAP related to the oculomotor nerve were obtained upon stimulation at the cavity wall after removal of the tumor. Stimulation at the surface of the quadrigeminal plate, however, did not cause any CMAP response. Using this monitoring as an indicator, the lesions were totally removed. CONCLUSIONS: In the surgery of tegmental lesions, CMAP monitoring from extraocular muscles is particularly helpful to prevent damage to crucial neural structures during removal of intrinsic lesions, but less so to select the site of the medullary incision. The approach via the lateral part of the colliculi is considered to be a safe route to approach the tegmental lesions.     

Predictive value and limitations of animal models for human transplantation: do we need more models for facial transplantation?

Animal models have traditionally provided the basis for preliminary investigation of new techniques prior to trials taking place in human subjects. The timing of when to proceed with human trials is difficult, as the accuracy of preclinical models can only be determined with hindsight. This review outlines the progression from transplantation in animal models to man. Now that many transplant procedures are well established, it is possible to assess the predictive value and limitations of animal models. These results are of great importance in the current debate about composite tissue allotransplantation (CTA) and in particular facial transplantation. This progression of CTA from animal models to man is outlined and compared with early renal, cardiac, and liver transplants. There is some evidence to suggest that animal models may have been misleading in CTA and that this has effectively delayed the transition to humans. The role for animal models in facial transplantation, which is currently making the step to clinical trials, is discussed.