Safety and efficacy of botulinum toxin type A following long-term use

Botulinum toxin serotype A (BoNT-A) has long heritage of use leading to confidence in its safety and efficacy. The application of BoNT-A does not lead to persistent histological changes in the nerve terminal or the target muscle. Clinical trials defined the safety and tolerability profile of BoNT-A across common therapeutic indications and showed an incidence of adverse events of approximately 25% in the BoNT-A-treated group compared with 15% in the control group. Focal weakness was the only adverse event to occur more often following BoNT-A treatment. Long-term BoNT-A administration has been assessed in various treatment settings, with the level and duration of BoNT-A efficacy response being maintained over repeated rounds of injection with no major safety concerns. The treatment of children with cerebral palsy often require long-term, repeated, multimuscle BoNT-A injections that lead to the administration of comparably higher toxin doses. Despite the high total body doses used, their distribution over multiple muscles and injection sites means that systemic side effects are rare. Recent formulation changes have reduced the incidence of antibody development following treatment with BOTOX^®. These findings show long-term BoNT-A treatment to be both safe and efficacious for a wide variety of indications.     

Effect of ankle position on isometric quadriceps strengthening

A prospective study of 20 normal subjects was undertaken to determine the effect of three ankle positions (active dorsiflexion, active plantar flexion, natural or rest position) on comfort and facilitation of quadriceps contraction in isometric strengthening in a supine position with the hip and knee fully extended. Surface EMG activity was found to be greatest for the vastus lateralis followed by the vastus medialis and least for the rectus femoris. Equal facilitation was apparent with either active ankle dorsiflexion or plantar flexion. Both were superior to the natural (rest) position. In situations where isometric quadriceps exercises are required, the authors recommend either active ankle dorsiflexion or plantar flexion to facilitate quadriceps strengthening. The choice between the two positions should be based on patient comfort.     

Assessment of early alveolar particle clearance and macrophage function following an acute inhalation of sulfuric acid mist

Rabbits were exposed to submicrometer sulfuric acid mist at 1 mg/m3 for 1 hr to assess effects on alveolar region clearance of a polystyrene latex tracer aerosol. Bronchopulmonary lavage was performed at selected times after exposure for functional characterization of alveolar macrophages. In vivo, clearance was accelerated in acid exposed animals relative to sham controls. Acid exposure produced no change in the viability or numbers of macrophages recovered. Although an increase in the number of polymorphonuclear leukocytes, primary neutrophils, was observed by 1 hr in both acid and sham groups, compared to nonexposed controls, levels were normal by 12 hr in shams but continued elevated in the acid group through 24 hr. Reduced in vitro macrophage adherence was observed after acid exposure. In vivo uptake of the tracer particles by macrophages was enhanced during the first 3 hr after acid exposure and in vitro phagocytosis by polymorphonuclear leukocytes was increased through 48 hr post-exposure. The results indicate some functional alterations in free cells after in vivo exposure to H2SO4 and the production of a mild inflammatory response. This latter was associated with an acceleration of inert particle clearance from the alveolar region.     

Europäische Forschungsförderung in der Ophthalomologie

Ohne Zusammenfassung     

Parapapillary diameter of retinal vessels. I. Estimating the size of the optic papilla (a papillometric study of over 264 normal eyes)

The diameter of the temporal superior and inferior retinal artery and vein were measured at the optic disk border and 2 mm from the disk center in 264 nonselected normal eyes on the basis of photographs, with correction of magnification. Additionally, the individual ocular magnification factor was determined by Littmann's method. The mean caliber of the artery was 0.113 +/- 0.019 mm at the disk border and 0.118 +/- 0.023 2 mm from the disk center. The corresponding values for the vein were 0.149 +/- 0.026 mm and 0.159 +/- 0.026 mm. The correlations between vessel caliber and disk size were not significant, but the relationship between disk size and the quotient of vessel diameter divided by disk size was highly significant (p less than 0.0001). Vessel diameter can therefore be taken as an independent unit for determining optic disk size in relative and approximately also in absolute units. Thus, mean horizontal disk diameter (1.77 +/- 0.33 mm) corresponded to 16.3 +/- 3.5 artery and 12.3 +/- 2.6 vein diameters (measured at the optic disk border). The mean individual ocular magnification factor was 0.302 +/- 0.017, with a Gauss standard distribution. If the optical characteristics of a photographed eye are not known and the ocular magnification factor is assumed to be 0.302, then 68.3% of all eyes will be covered with an inaccuracy of 5.6% and 95.5% of all eyes with an inaccuracy of 11.2%.     

Down-regulation of inducible nitric oxide synthase (iNOS) in rat with congenital hydronephrosis

BACKGROUND: Most of our knowledge concerning obstructive uropathy has been derived mainly from surgically manipulated animal models, and the pathogenesis of congenital obstructive hydronephrosis is not fully elucidated. Nitric oxide (NO) acts as an important biological modulator with diverse physiological functions, which can be either toxic or protective depending on the situation. NO is synthesized from l-arginine by nitric oxide synthase, and in the kidney iNOS is expressed spontaneously. The aim of our study is to investigate the expression of iNOS protein and its relationship with tubulointerstitial fibrosis and tubular cell apoptosis in congenital hydronephrosis. METHODS: We conducted histological studies on 18 kidneys of six-week-old-rats from an inbred colony of congenital hydronephrosis with reference to the histological grading of the affected kidney, tubulointerstitial fibrosis, renal tubular atrophy, and tubular cell apoptosis. Renal transforming growth factor-beta1 (TGF-beta1) level was determined by a sandwich ELISA assay and the expression of iNOS was analyzed by western blotting. RESULTS: Most of the hydronephrotic kidneys were markedly enlarged with dilatation of the collecting system, parenchymal thinning, tubular atrophy, interstitial infiltration and fibrosis. Renal TGF-beta1 level was higher in hydronephrotic kidneys than normal control kidneys (364.81 +/- 52.60 vs. 221.19 +/- 22.53 pg/mg protein, P < 0.05). Tubular apoptotic score in hydronephrotic kidneys was also significantly higher than in the normal control kidneys (1.97 +/- 0.42 vs. 0.14 +/- 0.02/HPF, P < 0.01). The expression of iNOS protein was lower in the affected kidneys compared with the normal control kidneys (8.79 +/- 0.78 vs. 14.00 +/- 0.83 arbitrary unit, P < 0.01). There was a negative correlation between iNOS expression and histological grading in congenital hydronephrosis. The iNOS expression also correlated negatively with renal interstitial fibrosis, TGF-beta1 level and tubular cell apoptosis. CONCLUSION: Our study confirmed the down-regulation of iNOS expression in affected kidneys from rats with congenital hydronephrosis, in which the cytoprotective effect of NO may be lost or weakened.     

Varix node of the iris with spontaneous regression]

We report the findings in a 76-year-old woman who presented with a varix of the left iris that had manifested with hyphema. Slit lamp examination disclosed a circumscribed prominent round blood-filled lesion of the iris with smooth surface and surrounding hemorrhage. Examination with the laser flare-cell meter disclosed slightly increased flare of the left eye (10.2 photon counts/ms). Iris fluorescein angiography revealed a focal early circular hyperfluorescent area without leakage and a surrounding hypofluorescent area. Additionally, there was bilateral pseudoexfoliation. The iris varix showed complete regression during follow-up of two months. Possible etiological factors, including congenital or acquired changes of the iris vessels and alterations of the iris vessel walls in pseudoexfoliation syndrome, are discussed. Although varices of the iris are rare, they should be included in the differential diagnosis of prominent iris lesions.     

Characteristics of sensory trick-like manoeuvres in jaw-opening dystonia.

We evaluated the effect of different manipulations on the performance of a standardized counting task in 7 patients with idiopathic jaw-opening dystonia. Patients used a small stick as sensory stimulus. Following conditions were examined: stick placed between teeth and cheek (CHEEK), biting on stick (TEETH), voluntary jaw occlusion without stick (OCCLUSION). Articulation was rated by patients and experimenters and surface electromyographic activity (EMG) was recorded. Patient-rating (CHEEK - 36.6%, TEETH - 48.1%) and EMG (-18.1%; -17.3%) were significantly improved for conditions using the stick, whereas experimenter-rating showed a trend for TEETH (-16.2%). Although jaw occlusion during speaking deteriorates articulation in healthy subjects, there was no further deterioration in patients and EMG was even significantly reduced (-18.6%). Comparable results were obtained in 1 patient using a special dental device. We conclude that sensory tricks significantly improve subjective and objective parameters. Besides tactile stimulation, altered proprioceptive feedback and antagonist activation may modulate hyperactive dystonic networks.