Spinocerebellar ataxia types 2 and 3 segregating simultaneously in a single family.

Spinocerebellar ataxia (SCA) types 2 and 3 are autosomal-dominant neurodegenerative disorders caused by mutations in two different genes. We identified mutations for SCA2 and SCA3 segregating simultaneously in a single Brazilian family. The index patient had SCA2, whereas her two second-degree cousins had SCA3. Disease was more rapidly progressive in the SCA2 patient, who presented severe brainstem and pancerebellar atrophy, as opposed to the two SCA3 patients, who had only mild cerebellar vermian atrophy. In such situations, molecular confirmation of all patients may avoid misdiagnosis of SCA subtypes and eventual errors in predictive testing of unaffected family members.     

Mechanismen der arteriellen Restenose und Therapieansätze zur Prävention

Both vascular surgery and endovascular interventions traumatise the arterial wall, especially the endothelium. The vessel responds with neointimal hyperplasia and/or constrictive remodelling, and this is still the limiting factor in curative interventions. Stent placement prevents constrictive remodelling but is the main trigger for in-stent restenosis. Hyperproliferation of neointimal tissue is the main response to arterial thrombosis, local inflammation or medio-intimal injury such as occurs, for example, after balloon dilatation in the region of arterial anastomoses or of a thrombectomy (Fogarty-manoeuvre). At present, research on prevention of restenosis is focused on inhibiting neointimal hyperproliferation by using drug-eluting stents, and especially sirolimus- or paclitaxel-eluting stents. In addition, further experimental research work is in progress, with the aim of esablishing new treatment regimens and solving the problem of neointimal formation, thrombosis and constrictive remodelling. These include both local and systemic pharmacological therapy, brachy- and laser therapy, and many genetic treatment options, some of which are currently the subjects of experimental studies and early-stage clinical trials. Gene therapy seems like a promising way of preventing restenosis, but has not yet been tested in clinical trials. In the near future, selective, simultaneous, and perhaps even polyphasic regulation for gene silencing of two or more genes involved in the development of restenosis could improve the long-term patency rate.     

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.     

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.     

Genetic linkage analysis of pulmonary fibrotic response to silica in mice.

Inter-individual variations in the development of silicosis, even within the same environments, have been reported, which suggest the contribution of genetic factors in silicosis aetiology. The aim of the present study was to determine whether there is any significant genetic influence on the development of silicosis. Furthermore, which genetic loci are responsible for the pulmonary response to silica exposure? Eight strains of inbred mice were used to examine the genetic influence on the lung fibrotic response to silica exposure. After intercross-breeding between the most susceptible and most resistant strains, a genome-wide linkage analysis of quantitative trait loci (QTL) was performed. Hydroxyproline was applied as an index, and genotypes of 167 marker genes were analysed by fragment analysis using a capillary-type sequencer. There was significant inter-strain difference in the mean concentration of hydroxyproline contents among the eight strains of mice. Breeding studies were conducted between the most susceptible, C57BL/6J, and the most resistant strain, CBA/J. A genome-wide linkage analysis of silica-exposed intercrossed cohorts identified significant QTL on chromosome 4 and suggestive QTL on chromosomes 3 and 18. The present study demonstrates that genetic factors may play a significant role in fibrotic-lung responses to silica; one significant and two suggestive quantitative trait loci were identified.     

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.