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.     

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.     

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.     

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.     

Malignant schwannoma in the posterior tibial nerve

Our group have studied a patient affected by a malignant schwannoma in the posterior tibial nerve. Schwannomas are uncommon neoplasms that originate from the Schwann cells of the peripheral nerves: the most common forms are benign. Malignant transformation is rarer. The therapy is surgical and the operation undertaken, if possible, should be the amputation. Alternatively, where amputation is not possible due to the specific localisation or due to patient refusal, the alternative must be the largest and most radical excision possible.     

Inter- and intraobserver variability in sonographic measurement of the lower uterine segment after a previous Cesarean section.

OBJECTIVE: To evaluate the reproducibility of sonographic measurement of the lower uterine segment in pregnant women at term. METHODS: Two independent observers performed transabdominal sonography on 129 women between 36 and 38 weeks of gestation who had had a previous Cesarean section. Sonography was performed when the patients had a full and a half-full bladder; in 100 patients, the measurements were also performed transvaginally, with the patients having an empty bladder. Agreement was quantified by the intraclass correlation coefficient and, using a cut-off of 3.5 mm, by the kappa coefficient. RESULTS: The intraobserver agreement was generally high (intraclass correlation coefficient > 0.90). The interobserver agreement was higher on transvaginal (intraclass correlation coefficient, 0.94) compared with transabdominal (0.70 and 0.84, with full and half-full bladder, respectively) ultrasound. The kappa coefficient was 0.75 transvaginally, compared with 0.34 and 0.54 using the transabdominal approach, with full and half-full bladder, respectively. CONCLUSION: The agreement between two observers for sonographic transvaginal measurement of the lower uterine segment can be considered good, compared with poor to moderate agreement using the transabdominal approach.     

The effects of KATP channel modulators on counterregulatory responses and cognitive function during acute controlled hypoglycaemia in healthy men: a pilot study.

AIMS: To examine the effects of agents that alter potassium adenosine triphosphate (KATP) channel activity in beta-cells on cognitive function and counterregulatory hormone responses during acute hypoglycaemia, given the physiological similarities between the pancreatic beta-cell and the hypothalamic glucose-sensitive neurones (GSN) and the widespread distribution of sulphonylurea receptors in neuronal cells throughout the brain. METHODS: Ten healthy males were studied on four occasions and in random order underwent three stepped hypoglycaemic (plasma glucose aims: 3.4, 2.8, 2.4 mmol/l) and one euglycaemic (plasma glucose aim: 5 mmol/l) insulin clamps. Prior to each hypoglycaemic study, volunteers received either 10 mg glibenclamide, or 5 mg/kg diazoxide or placebo orally. Cognitive function, symptom scores and counterregulatory hormone responses were measured at each glycaemic level. RESULTS: There was no statistically significant effect of either drug on the symptoms generated or the counterregulatory hormonal response during hypoglycaemia. However, cognitive function was better preserved during hypoglycaemia in the glibenclamide-treated arm, particularly four-choice reaction time which deteriorated at a plasma glucose 2.5 mmol/l compared with 3.0 mmol/l with diazoxide (P = 0.015) and 2.9 mmol/l with placebo (P = 0.114). CONCLUSIONS: Single doses of pharmacological agents which alter membrane KATP channel activity do not affect the counterregulatory response to hypoglycaemia but may modify cognitive function during cerebral glucopenia. The unexpected effects of glibenclamide on cortical function suggest a novel action of sulphonylureas that warrants further investigation.