The influence of stimulus size on measured visual field extent in infants.

PURPOSE: To compare measured visual field extent for a 6 degrees stimulus (typical size used in studies of infants) with a 1.5 degrees stimulus (similar to the largest size used in Goldmann perimetry) in young infants. METHODS: A total of 120 infants (60 each at 3.5 months and 7 months of age) and 24 adults were tested monocularly with a kinetic perimetry procedure using a black double-arc perimeter. Each subject was tested with either a 6 degrees or 1.5 degrees white sphere, which was mounted on a black wand and moved smoothly toward the intersection of the perimeter arms at 3.4 degrees /s. Visual field extent along each perimeter arm was defined as the median of 2 to 3 measurements of the position of the leading edge of the stimulus when the subject made an eye movement toward the stimulus. RESULTS: The 6 degrees stimulus produced larger measured visual field extent than the 1.5 degrees stimulus in 3.5-month olds (temporal field only) and in 7-month olds (nasal and temporal field), but not in adults. CONCLUSIONS: Using the testing conditions of the present study, increasing stimulus size beyond the largest used in a Goldmann perimeter (approximately 2 degrees) increases measured visual field extent in young infants, but not in adults. This may relate to differences in peripheral summation areas or to differences in attentional factors between infants and adults.     

Tolerance of ocular iontophoresis in healthy volunteers.

To evaluate ocular tolerance, healthy volunteers were iontophoresed transclerally using novel OcuPhor trade mark hydrogel drug delivery applicators filled with balanced salt solution. In this three-period crossover study in 24 male and female subjects, 16 subjects received 0 mA and two of the following DC currents: 0.1, 0.5., 1.0, 2.0, 3.0, or 4.0 mA for 20 min; 6 subjects received 3 mA for 20 min and 1.5 mA for 40 min (both equivalent to 60 mAmin total charge). Safety and tolerance were determined by subjective VAS and objective ophthalmic assessments. Subjects were evaluated before and up to 22 hr after dosing. The applicators were well-tolerated and no clinically significant changes in symptomology or in ophthalmic assessments were seen following exposure to 0-3.0 mA for 20 min or 1.5 mA for 40 min. At 4.0 mA 2 of 4 subjects reported a burning sensation under the applicator during dosing which resolved by 22 hr post-dose; superficial changes in fluorescein staining were observed at 1 hr, but not at 22 hr. The OcuPhor trade mark system has promise for noninvasive drug delivery to the eye.     

Aortic valve replacement in octogenarians

Background and Aims  

As our population ages and life expectancy increases the number of people aged over 80 and more referred for cardiac surgery is growing. This study sought to identify the outcome of aortic valve replacement (AVR) in octogenarians.     

Development of a new radioimmunoassay for human osteocalcin: evidence for a midmolecule epitope

Osteocalcin is a vitamin K-dependent bone-specific protein that can be found circulating in the serum. The circulating levels of osteocalcin have been shown to be an index of bone turnover. Existing radioimmunoassays for osteocalcin have been shown to be specific for C-terminal epitopes, a region that is identical in the human and bovine osteocalcin. There are, however, five amino acids different in the N-terminal region of the molecule. We describe here an immunoassay for a midmolecule epitope of osteocalcin using osteocalcin purified from human femoral head bone powder. Antibody specificity was determined using tryptic digests and a synthetic fragment of human osteocalcin. This assay has only a partial crossreactivity with bovine osteocalcin. This is the first report of an assay against a midmolecular epitope of osteocalcin involving a region in which the human and bovine osteocalcins differ. Osteocalcin levels determined by this assay have a significant correlation with both the total serum alkaline phosphatase and the serum skeletal alkaline phosphatase levels in normal adult human serum and, to a greater degree, in sera of patients with conditions associated with increased bone turnover (Paget's disease, hyperparathyroidism, and newborn sera). These correlations are greater than those previously reported for C-terminal assays, suggesting the possibility that different regions of the molecule may elicit different information concerning bone turnover.     

Effects of dehydroepiandrosterone treatment in rats with diet-induced obesity

Previous studies showed that administration of dehydroepiandrosterone (DHEA) to lean and genetically obese Zucker rats reduced body weight. In the present experiments, the effect of DHEA treatment in rats with diet-induced obesity was evaluated. In experiment 1, male Sprague-Dawley rats (300 g) were fed a nonpurified diet (reference group) or a condensed milk-corn oil nonpurified diet [diet-induced obese (DIO) rats] for 7 wk. Then, 0.6% DHEA was included in the food of one-half of the DIO rats (DIO + DHEA rats). After 6 wk, DIO rats weighed 23% more and had greater fat pad weights, cell size and cell number than reference and DIO + DHEA rats. Brown fat mitochondrial respiration was similar in all groups. DIO rats had higher serum cholesterol and triacylglycerol concentrations than reference and DIO + DHEA rats. DIO + DHEA rats had lower serum insulin levels than DIO and reference rats. In experiment 2, male Sprague-Dawley rats (460 g) were fed either the nonpurified diet or the condensed milk diet for 8 wk. Condensed milk-fed rats were then divided into DIO and diet-resistant groups. One-half of the rats in each group were fed 0.6% DHEA for 2 wk. Body weights and serum glucose, insulin, triacylglycerol and triiodothyronine levels were lowered by DHEA treatment in all groups. Liver mitochondrial state 3 respiration rates per gram and per liver and peroxisomal beta-oxidation were higher in DHEA-treated than in control rats. In DIO rats, DHEA treatment appears to interfere with hyperplastic adipose tissue growth. In this strain of rats, DHEA appears to have hypolipidemic and hypoinsulinemic effects.     

Results of penetrating keratoplasty in vascularized corneas.

A retrospective longitudinal study of 105 penetrating keratoplasties for vascularized corneal opacities was done. The results of cases with an etiology of healed trachoma or healed corneal ulcers were compared. The vascularization was graded from Grade I to V depending on the quadrant and type of vascularization. Graft clarity of 2+ or more in cases of trachomatous opacity was achieved in 93% of cases and that after postinfectious opacity in 71.8%. Prognosis was poor in cases where deep vascularization was present in more than two quadrants or more than 180 degrees.     

Down-regulation of muscarinic receptors in the striatum of organophosphate-treated swine

Subacute (daily) administration of diisopropylfluorophosphate (DFP) to male swine (Yorkshire white) resulted in a 97% inhibition of cholinesterase and a decrease of [3H]quinuclidinyl benzilate [( 3H]QNB) binding sites in homogenates of striata by approximately 50% after 14 days. The maximal density of receptors (Bmax) decreased from 2.1 +/- 0.3 to 1.0 +/- 0.2 pmole/mg protein. There was no significant change in the dissociation constant (Kd) for [3H]QNB binding (control: 52.6 +/- 10.7 pM; 7-day: 57 +/- 2.8 pM). Carbachol displacement of [3H]QNB binding yielded data best fit by a two-binding site model. The dissociation constants were KiL = 115 +/- 62 microM (55 +/- 3%) and KiH = 1.8 +/- 0.7 microM (45 +/- 3%), respectively, for the low- and high-affinity states. Seven-Day treatment with DFP reduced the percentage of high-affinity receptors to 22 +/- 8.6%, but affected neither the low- nor the high-affinity Kd (100 +/- 20 and 2 +/- 0.6 microM). With the addition of Mg2+, striatal homogenates had low- and high-affinity receptors in the proportion of approximately 1 to 1. In the presence of Gpp(NH)p + Mg2+ the ratio of high- to low-affinity receptors was 3:1 in homogenates of control tissue (to 26 +/- 5%). This treatment had no effect on this ratio in homogenates of tissue from 7-day DFP-treated swine (3:1) since it was already 3:1. Pirenzepine displacement of [3H]QNB binding was best described by a two-binding site model, with Ki values of 38 +/- 14 and 201 +/- 78 nM, which represent 74 and 26% of the binding sites, respectively. The high affinity Kd value was unchanged following 7 days of DFP treatment (24 +/- 5 nM). There appears to be little change in the displacement curves for pirenzepine inhibition of [3H]QNB binding. This suggests that about 75% of the receptors are of the M1 subtype. Thus, subacute administration of DFP causes not only a decrease in the number of receptors, but also a change in the proportion of agonist affinity states which is related to the interaction of the guanine nucleotide binding protein and the muscarinic receptor.     

Mouse chromosome 9 quantitative trait loci for soft tissue regeneration: Congenic analysis and fine mapping

Development of gene therapies for wound healing will depend on the identification of the genes involved in wound healing and tissue regeneration. Previous quantitative trait loci (QTL) studies in mice using the ear punch model have shown that major QTL exist on chromosome (Chr) 9 for soft tissue regeneration. In this study, we have developed a congenic line that contains the Chr 9 QTL chromosomal region from super healer MRL/MpJ in the genomic background of poor-healing SJL/J. The phenotypic effect of this QTL was confirmed in male mice, where the congenic line has shown significant healing improvement over SJL. Fine mapping of the Chr 9 QTL region with 23 markers at an average distance of 4.2 Mb using a total of 1,564 MRL/MpJ x SJL/J F(2) mice revealed the presence of at least three QTL peaks, implying that three separate loci may contribute to the phenotypic effect of this QTL. Based on the 2-LOD intervals, the total QTL region was confined to a combined length of no more than 28.2 Mb. Application of a Bayesian shrinkage estimation indicated that a major locus was located in a region of just 1.3 Mb.