Effect of cilobradine in cats with a first episode of congestive heart failure due to primary cardiomyopathy.

INTRODUCTION: Heart rate (HR) is often elevated in cats with cardiomyopathies (CMPs). Pharmacologic modulation of HR may reduce cardiac morbidity and mortality. OBJECTIVES: To investigate the effects of cilobradine vs. placebo, regarding time to cardiac mortality or morbidity in cats with first episode of congestive heart failure (CHF) due to primary CMP. ANIMALS: Three hundred and sixty-seven client-owned cats with primary CMP that had presented with a first episode of CHF at 50 centers in Europe. Per-protocol population comprised 193 cats (n = 89 cilobradine, n = 104 placebo). An interim analysis for futility was planned. METHODS: Prospective, randomized, placebo-controlled, double-blinded, multicenter clinical trial. Primary outcome variable was the time to a composite of cardiac mortality or cardiac morbidity. RESULTS: Median time to primary outcome was 84 days (95% confidence interval [CI]: 63-219 days) in the cilobradine group (CG) and 203 days in the placebo group (95% CI: 145-377 days) with observed hazard ratio of 1.44, indicating a higher hazard for the CG (P = 0.057). Mean HR was 28 beats per minute (bpm) lower at Day 7 (P < 0.0001) and remained 29 bpm lower at Day 360 (P = 0.026) in the CG than that in the placebo group. Although the number of adverse events did not differ, there were more serious adverse events in the CG. CONCLUSIONS: Heart rate reduction by cilobradine in cats with a first episode of CHF due to primary CMP did not reduce cardiac mortality and morbidity.

[Unilateral aplasia of a lateral rectus muscle]. / Einseitige Aplasie eines Musculus rectus lateralis.

BACKGROUND: The congenital absence of an extraocular muscle is rare. The case of an unilateral lateral rectus muscle and a review of the literature are presented. PATIENT AND METHODS: A healthy 7-year old boy with inconspicuous family history was seen in our clinic. The boy had been noted to have a right esotropia from infancy. Clinical orthoptical examinations and magnetic resonance imaging (MRI) were performed. The esotropia was corrected by transposition of the superior and inferior rectus muscle. RESULTS: With correction of the myopic astigmatism the visual acuity of either eye was 0.8. The right eye could not abduct to pass the midline, the left eye passed the midline by 35 degrees. From the primary position the right eye was able to elevate by 20 degrees and the left eye to elevate 15 degrees. The alternate prism and cover test showed in either eye fixation an esotropia of 24 degrees without significant change in elevation or depression. Besides, there was a hypertropia (+VD) of 14 degrees which increased to 21 degrees in left gaze and decreased to 0 degree in right gaze. Indirect ophthalmoscopy showed a bilateral excyclo position of approximately 5-10 degrees. Retraction of either eye was not seen in any gaze direction. The axial length of the right/left eye was 25.2 mm/24.6 mm. Aplasia of the right lateral rectus muscle and hypoplasia of the left lateral rectus muscle could be demonstrated by magnetic resonance imaging. Intraoperatively the right lateral rectus muscle was absent. The vertical eye muscle inserted regularly. Hummelsheim's procedure was performed. Eight months postoperatively, the boy was orthotropic in primary position. The inferior oblique overaction was still present together with a "V" pattern of 8 degrees. The Bagolini test was positive. CONCLUSION: The congenital absence of one or more extraocular muscles is a rare condition, which has to be considered as a differential diagnosis to neurogenic nerve palsy.

Sulfated polysaccharide anticoagulants suppress natural killer cell activity in vitro.

In contrast to the well studied anticoagulant activity of sulfated polysaccharides (SPS), little is known about their influence on immune competent cells. Using two naturally derived SPSs (unfractionated heparin and low molecular weight heparin), one semi-synthetic SPS (pentosanpolysulfate), and one synthetic SPS (lactobionic acid) as well as the polypeptide hirudin we investigated the effect of these drugs on natural killer cell activity in vitro. We demonstrate that all SPSs tested significantly suppress the activity of natural killer cells at clinically relevant dosages. At all concentrations and at all effector:target ratios tested pentosanpolysulfate was the most potent natural killer cell inhibitor. In contrast, hirudin had no effect on natural killer cell function. Furthermore, scanning electron microscopy revealed that reduced natural killer cell activity is paralleled by decreased lymphocyte cell size and altered cell surface structures. Our results indicate that defined therapeutically applied SPSs can interfere with the tumor cell killing process.