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.     

Coronary endarterectomy on beating heart: Our experience

Introduction Coronary artery bypass grafting (CABG) associated with Endarterectomy is a high risk procedure. After the first report of coronary endarterectomy by Bailey et al in 1951, the preference for this surgical procedure was decreased due to increased morbidity and mortality In patients with total or subtotal large coronary artery obstructions in which there is no possibility to receive a conduit as graft for myocardial revascularisation, endarterectomy remains the procedure of choice. This study was designed to study early and midterm results of off pump coronary artery endarterectomy. Methods Of 172 Consecutive Off Pump CABG done at our institution from Jan 2003 to July 2005, 22 patients underwent supplementary coronary endarterectomy. 16 patients had chronic stable angina 4 had unstable angina two required emergency CABG with endarterectomy following perioperative infarction. The mean ejection fraction was 29.2±4.3 and all of the patients were in New York Heart Association (NYHA) III or IV. All patients were planned for complete total arterial revascularisation using Left Internal Mammary Artery (LIMA). Right Internal Mammary Artery (RIMA), Radial composite “Y” graft, Two patients operated for periop infarct received vein graft. In 16 patients closed endarterectomy was done in five patients double endarterectomy in single vessel was done to chase the plaque distally, in one patient open left anterior descending (LAD) endarterectomy with vein patch reconstruction was performed. Results There were no deaths. None of the procedures were converted to on pump operation. All endarterectomies and bypasses were performed on Beating Heart, all patients were completely revascularised. Peri operative cardiac enzymes studied showed no significant rise in the Creatinine Phoshpokinase (CPK)-Creatinine Phosphokinase myocardial Band (CPK-MB). The mean postoperative Ejection Fraction (EF) was 36.7%±7.2% which was significantly higher than the Preoperative one (p<.05). At the end of four months to one and half year 22 patients were in NYHA class I to II and all were angina free in canadian cardiovascular society class.f Conclusions Coronary End Arterectomy without cardiopulmonary bypass can be performed in patients who are expected to benefit from complete revascularisation. It can be performed with closed as well as open method. However to achieve complete endarterectomy by closed technique in some patients it is essential to chase the plaque. Early and mid term results are encouraging.