Pathological structure of the kidney from adult mice with mosaic mutation

Summary: The mosaic (Atp7a ^mo-ms ) is an X-linked, lethal mutation in mice. In mosaic mutant males, many clinical features characteristic of defective copper metabolism have been observed and they die at the age of 15 days, exhibiting strongsimilarities to the brindled and macular mutants. About 4% of the mutant males live to sexual maturity and some of them are fertile. In this paper, alterationsin the structure of the kidney from adult mutants are described. Owing to an inherited defect of efflux, copper is accumulated in the kidney of the mutants up to a toxic level and this leads to severe damage of the renal cortex. Pathological changes in the kidney mostly affected the structure of the renal corpuscle and renaltubules.     

Notification of rheumatic fever in South Africa -- evidence for underreporting by health care professionals and administrators.

OBJECTIVE: To determine whether under-reporting of rheumatic fever occurs at hospital, municipal, provincial and national levels of the South African health system. BACKGROUND: Information on the incidence of rheumatic fever (RF) and the prevalence of rheumatic heart disease (RHD) is required for the prevention of valvular heart disease in developing countries. In South Africa, RF was made a notifiable condition in 1989. It has recently been suggested that the reporting of RF cases may be incomplete, possibly because of underreporting by health care professionals and deficient administration of the disease notification system in South Africa. METHOD AND RESULTS: We assessed whether underreporting of RF cases occurs by comparing the numbers of RF cases reported per year at hospital, municipal, provincial and national levels from 1990 to 2004. There was a fall in the number of RF cases reported per year at national and provincial level over the 15 years of observation. A detailed analysis of the number of RF cases reported at hospital, municipal and provincial level for a 5-year period showed that more cases were diagnosed in one hospital (serving a smaller population) than were captured at municipal and provincial level (serving a larger population), suggesting underreporting by health care professionals. There were discrepancies in the number of cases reported at municipal, provincial and national level, suggesting poor administration of the notification system. CONCLUSION: There appears to be underreporting of RF cases by health care professionals, and poor administration of the RF notification system. Health care professionals need to be educated about the statutory requirement to notify all RF cases in South Africa. An effective national disease notification system is required.     

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.     

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.     

Die Behandlung der Apophysenabrissverletzung des Epicondylus ulnaris im Kindesalter

OBJECTIVE: Surgical reduction and retention of apophyseal avulsion injuries at the medial epicondyle to prevent joint instability, lasting malalignment, or pseudarthrosis. INDICATIONS: Absolute: intraarticular apophyseal dislocation of the medial epicondyle, complete lesion of the ulnar nerve. Relative: dislocation of the apophysis (> 4 mm) in children > 5 years of age; the need for intervention increases in children as the degree of dislocation, age, and athletic activity increase. CONTRAINDICATIONS: Dislocation of the medial epicondyle (< or = 4 mm) in children < 5 years of age, provided the fragment location is not intraarticular. SURGICAL TECHNIQUE: Open reduction of the apophysis through a medial approach. Identification of the ulnar nerve. In young children or with small fragments fixation with Kirschner wire. Screw fixation in older children or for larger fragments. POSTOPERATIVE MANAGEMENT: Long upper-arm plaster cast until wound healing is achieved. Subsequently, upper-arm plaster cast for 3 weeks. Removal of Kirschner wires after 4-6 weeks, screw removal after 8-12 weeks. Physiotherapy only if marked reduction of elbow mobility is found 6 weeks after cast removal. RESULTS: From January 1, 1994 to December 31, 2003, 25 children with an average age of 12 years suffering from medial epicondylar avulsion fractures were operated on using open reduction and Kirschner wire fixation. An average of 3 years after the injury 14 of these children underwent follow-up examination using a procedure that took subjective, clinical and radiologic parameters into account. Two children showed a slight reduction in overall strength of the injured extremity when compared with the contralateral extremity. One child had a flexion deficit of 10 degrees, all other children showed movement limitations of < or = 5 degrees compared to the contralateral extremity. In all the cases available to follow-up, there was a slight increase in valgus alignment of the elbow joint compared with the uninjured side (3 degrees on average). All fractures consolidated within 6 weeks.