Effects of topically applied heterologous serum on reepithelialization rate of superficial chronic corneal epithelial defects in dogs.

OBJECTIVE To assess the effects of topical application of undiluted heterologous serum on time to corneal reepithelialization in dogs with superficial chronic corneal epithelial defects (SCCEDs). DESIGN Multicenter, randomized, double-masked, controlled clinical trial. ANIMALS 41 client-owned dogs. PROCEDURES After collection of baseline clinical and historical data, dogs were randomly assigned to receive topically applied undiluted heterologous serum (n = 22) or isotonic saline (0.9% NaCl) solution (19) along with tobramycin and atropine. Epithelial debridement (at all visits) and grid keratotomy (at visits 2, 3, and 4) of SCCEDs were performed. Ophthalmic examination including fluorescein application was performed once weekly for 4 weeks or until corneal reepithelialization. Clinicians and owners were masked to treatment group. RESULTS No differences in baseline data were detected between treatment groups. No difficulties with medication administration, noncompliance, or adverse reactions were noted. All SCCEDs in both groups healed by 4 weeks after treatment began. Median time to reepithelialization (2 weeks) was not significantly different between serum-treated and placebo-treated eyes. Irrespective of treatment group, median time to reepithelialization was not significantly different for Boxers versus non-Boxer breeds. Direct correlations were detected between time to reepithelialization and vascularization score at study entry, vascularization score at time of reepithelialization, and ulcer area at study entry in both groups. Time to reepithelialization was not correlated with age, sex, or duration of signs in either group. CONCLUSIONS AND CLINICAL RELEVANCE Topical application of undiluted heterologous serum was well tolerated by dogs with SCCEDs but, as an adjunct to standard treatment, did not reduce time to corneal reepithelialization.

Novel mutations of the growth hormone 1 (GH1) gene disclosed by modulation of the clinical selection criteria for individuals with short stature.

Subtle mutations in the growth hormone 1 (GH1) gene have been regarded as a comparatively rare cause of short stature. Such lesions were sought in a group of 41 individuals selected for short stature, reduced height velocity, and bone age delay; a group of 11 individuals with short stature and idiopathic growth hormone deficiency (IGHD); and a group of 154 controls. Heterozygous mutations were identified in all three groups but disproportionately in the individuals with short stature, both with (odds ratio 25.2; 95% CI, 5.1-132.2) and without (odds ratio 3.6; 95% CI, 1.0-12.9) IGHD. Twenty-four novel GH1 gene lesions were found. Thirteen novel missense mutations were characterized by assaying the signal transduction activity of in vitro expressed variants; six (T27I, K41R, N47D, S71F, S108R, and T175A) exhibited a reduced ability to activate the JAK/STAT pathway. Molecular modeling suggested that both K41R and T175A might compromise GH receptor binding. Seven GH variants (R16C, K41R, S71F, E74K, Q91L, S108C, and a functional polymorphism, V110I) manifested reduced secretion in rat pituitary cells after allowance had been made for the level of expression attributable to the associated GH1 proximal promoter haplotype. A further leader peptide variant (L-11P) was not secreted. Eleven novel mutations in the GH1 gene promoter were assessed by reporter gene assay but only two, including a GH2 gene-templated gene conversion, were found to be associated with a significantly reduced level of expression. Finally, a novel intron 2 acceptor splice-site mutation, detected in a family with autosomal dominant type II IGHD, was shown to lead to the skipping of exon 3 from the GH1 transcript. A total of 15 novel GH1 gene mutations were thus considered to be of probable phenotypic significance. Such lesions are more prevalent than previously recognized and although most may be insufficient on their own to account for the observed clinical phenotype, they are nevertheless likely to play a contributory role in the etiology of short stature.

Vecuronium bromide, phenylephrine and atropine combinations as mydriatics in juvenile double-crested cormorants (Phalacrocorax auritus).

Topical vecuronium bromide (Norcuron) and combinations with atropine and phenylephrine, were evaluated as mydriatics in juvenile double-crested cormorants (Phalacrocorax auritus). Nine cormorants were treated with each of four protocols: 1% atropine; 4 mg/mL vecuronium bromide (total 0.16 mg/eye); atropine with vecuronium; and atropine, 2.5% phenylephrine, followed by vecuronium. Drugs were applied topically at 15-min intervals (0.01 mL/drop). Pupil diameter was measured manually every 15 min with a pupil gauge calibrated to the nearest 0.5 mm. No effect was observed with atropine alone. Average +/- SD peak pupil diameter for vecuronium, atropine/vecuronium, and atropine/phenylephrine/vecuronium were 5.4 +/- 1.1 mm, 5.7 +/- 0.8 mm and 6.2 +/- 0.4 mm, respectively; and duration of peak diameters were 38 +/- 28 min, 79 +/- 71 min and 103 +/- 58 min, respectively. The combined atropine, phenylephrine and vecuronium provided the most consistent dilation with larger average pupil size and longer average duration. No side-effects from vecuronium were observed in these birds.