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Fluorescein angiographic findings in 7 carriers and 7 homozygotes of a recessively inherited disease, generalized progressive retinal atrophy of the poodle, are described in detail and comparisons with 24 healthy control poodles are presented. Two angiographic types of the disease could be distinguished. These are: Type 1, a diffuse, widespread choriocapillaris atrophy associated with retinal vascular and depigmentation changes and Type 2, a predominantly retinal involvement combined with focal choroidal atrophic patches lineating major vessels. These findings share similarities with the observations made of the human disease, retinitis pigmentosa. Unaffected carriers of the disease showed characteristic fundus changes in angiography: patchy, hyperfluorescent depigmentation changes and often minor narrowing and irregularities of the arterioles and poorly visible capillary bed.

Cross-linked hyaluronic acid (CLH), a viscoelastic substance with a high viscosity, was injected into the left anterior chamber of 5 rabbits without simultaneous withdrawal of aqueous humour. The right eyes of the same rabbits received an equal amount of sodium hyaluronate (Healon). The intraocular pressure (IOP) of the CLH injected eyes increased four-fold immediately after the injection. One week post injection the IOP had decreased to the pre-injection level where it remained until the euthanatization of the animals 32 days post injection. Biomicroscopically CLH was seen as a slightly opaque curly mass in the anterior chamber in the eyes that otherwise were quiet in four of the rabbits. In one rabbit the injected cross-linked substance reacted immediately with aqueous and turned white. The eye was quiet and showed no inflammatory signs. In all intracamerally injected eyes, slight to moderate aqueous flare was present 4 h post injection. Aqueous flare was still present 1 day post injection in 4 eyes, but was absent 4 days post injection. Histologically no apparent inflammatory reaction was present. Occasional giant cells were seen on the anterior surface of the iris in three animals. Slight accumulation of mononuclear cells was found in the iridocorneal angle of the CLH injected eyes. At histology few mononuclear cells were also found surrounding the subconjunctivally injected CLH still present in 4 additional rabbits when euthanatized 28, 42 and 49 days post injection. The contralateral eye of these 4 animals received an equal amount of sodium hyaluronate subconjunctivally. The substance had been resorbed completely. No reactive or inflammatory signs were present.(ABSTRACT TRUNCATED AT 250 WORDS)

Background and Aims: Ceramic bone graft substitutes have a potential to be used as replacement of allogeneic bone grafting and, under optimal distribution of particle size, they may even provide mechanical support. The current study examined the efficacy of bioactive glass granules as an extender of autogenous bone grafting in a segmental bone replacement model of the canine femur. Material and Method: A 16 mm long segment of the femur shaft was bilaterally replaced with an intercalary titanium implant in eight animals. The implant had cementless grooved proximal and distal stems. In one leg, the peri-implant space was packed with composite graft consisting of a mixture of bioactive glass granules and autogenous bone graft in proportion of 50:50. In the opposite leg, the peri-implant space was treated with autogenous bone graft alone. After surgery, unlimited functional loading was allowed. The outcome was evaluated at three months. Results: Eight out of sixteen autografted implants and seven out of sixteen composite-grafted implants were radiographically incorporated and clinically stable at three months. In the paired comparison, the proximal components of composite-grafted implants showed lower maximum load under torsional testing (p=0.068), less new bone in the longitudinal grooves of the stems (p=0.036) and lower affinity of new bone to implant surface (p=0.046). The distal components of the two sides showed a similar trend for less new bone in the grooves and lower bone affinity of new bone in the distal composite-grafted components. Conclusions: The current study suggests that supplementation of periprosthetic bone graft with bioactive ceramic particles may not help to promote healing of cementless implants under high dynamic loading conditions.

The canine ( Canis familiaris ) retinal rod transducin (G T ) α, β1 and γ1 subunits were sequenced. Cloning of the cDNAs was accomplished by polymerase chain reaction (PCR) using degenerate and wild type retinal cDNA libraries as templates. The deduced amino acid sequences were highly similar to rod transducins from other species: G Tα differed by 5 amino acids from the corresponding human sequence, whereas β1 and γ1 were identical to human sequences. The coding sequence of rod transducin was evaluated as a possible cause for the recessively inherited retinal rod-cone degeneration: there were no nucleotide differences between the wild type and retinal degenerate strains.

Cyclic guanosine 3',5'-monophosphate (cGMP) levels were determined in retinas from a strain of Labrador Retrievers with inherited retinal dystrophy manifesting at early stages of retinal differentiation. The cGMP contents of dystrophic retinas of dogs from 1 to 4 months of age (n = 7) were significantly higher (p = 0.001) than in age-matched controls of the same breed (n = 11). Ultrastructure along the vertical retinal meridian was studied in developing retinas and findings were related to those of age-matched wild-type controls of the same breed. Slow central to peripheral progression of degeneration was observed in affected dogs. No differences were found in total cGMP-phosphodiesterase (PDE) activity, in PDE subunit composition as determined by Western blotting of 2-month-old homozygote affected retinas, or in the amino acid sequence deduced from the nucleotide sequence of the PDE beta-subunit as compared to controls. This model of photoreceptor degeneration thus is the first case of an apparent abnormality of cGMP metabolism that is not associated with a defect in the PDE catalytic subunits, and it is also the first reported model not associated with severe developmental abnormalities and rapid degeneration.

We have tested the efficacy of porous bioactive glass (BG) inlays in enhancement of implant osseointegration. A total of 24 sheep underwent bilateral surgical implantation of three parallel implants on the anteromedial cortical surface of each tibia. The disc-shaped implants made of Ti6Al4V or cobalt chromium (CoCr) alloys had two parallel surface grooves (trapezoidal space with bottom widening) filled with sintered 100% bioactive glass microspheres or a selected mixture of bioactive and biocompatible glass microspheres. The surface of uncoated control implants was smooth, grit-blasted or had unfilled grooves. A subgroup of control smooth CoCr implants was coated with two or three BG layers. Implant incorporation with bone was evaluated using torque testing to failure, scanning electron microscopy and morphometry at 12 and 25 weeks. A total of 144 in vivo implants and 16 ex vivo cemented control implants were analyzed. Control Ti6Al4V implants with unfilled trapezoidal grooves showed highest torsional failure loads with excellent ingrowth of new bone and remodeling of ingrown bone into lamellar bone. Implants with BG inlays and microroughened control Ti6Al4V implants showed significantly lower torsional failure loads than control Ti6Al4V implants with unfilled grooves. In conclusion, BG inlays failed to enhance biological implant fixation. Macrotextured surface was more effective than grit-blasting in promotion of mechanical incorporation.

The aim of the present study was to determine, if bioactive glass (BG) surface inlays improve osseointegration of titanium implants in the proximal femur of adult sheep. In simulation of uncemented primary stems (nine animals), only the proximal part of the implants was grit-blasted and three surface slots of the grit-blasted region were filled with sintered BG microspheres. Primary stems were implanted using press-fit technique. In revision stem simulation (eight animals), grit-blasting was extended over the whole implant and seven perforating holes of the stem were filled by sintered BG granules. Revision stems were implanted with a mixture of autogenous bone graft and BG granules. Comparison with solid partially or fully grit-blasted control stems implanted in the contralateral femurs was performed in the primary and revision stem experiments at 12 and 25 weeks, respectively. Implant incorporation was evaluated by torsional failure testing and histomorphometry. Only one-third of the primary stems anchored mechanically to bone. The revision stems incorporated better and the BG inlays of the revision stems showed ingrowth of new bone. However, there were no significant differences in the torsional failure loads between the stems with BG inlays and the control stems. In conclusion, surface BG inlays gave no measurable advantage in mechanical incorporation of grit-blasted titanium implants. Overall, the proximal sheep femur, characterized by minimal amount of cancellous bone and the presence of adipocytic bone marrow, seemed to present compromised bone healing conditions.

Dark adapted single flash and light adapted 30 Hz photopic flicker ERGs were recorded from a litter of seven Labrador Retrievers bred from parents affected with generalized progressive rod-cone dystrophy. After an initial increase of b-wave amplitudes from 5 weeks to 4 months similar to the controls, the b-wave amplitudes of the litter were significantly decreased (P less than 0.005) at 7 months. At 21 months the b-wave amplitudes were very low, although some response to 30 Hz photopic flicker was still left. The ERG changes indicated a late onset progressive rod-cone dystrophy which developed after maturation of the retina. The development of this photoreceptor dystrophy has not previously been described.

Purpose To further understand a common veterinary anesthetic, propofol (2,6- di-isopropylphenol) and effects of infusion rates on the retinal neurons in Beagle dogs. Methods Standard full-field blue xenon-flash stimulation elicited responses of dark-adapted eyes, which were recorded from dogs before and after a propofol infusion rate increase. Results Electroretinogram b-waves increased significantly after the infusion rate increase and decreased with decline (P

Study design Inflammatory cells were located by immunocytochemistry in areas of experimental intervertebral disc injury in pigs. Objectives To study the occurrence of T lymphocytes and macrophages 1 week, 1 month, and 3 months after partial-thickness transverse scalpel injuries in pig lumbar discs. Summary of background data Inflammatory cells and mediators recently have been observed in disc herniation tissue that was removed at disc prolapse surgery. The prevalence of inflammatory cell infiltrates in such clinical disc tissue material also has been studied. There are no studies, however, that have analyzed, using immunocytochemical methodology, the occurrence of, types of, and time dependence of inflammatory cells in an experimental disc injury model. The role of inflammation in intervertebral disc injury and repair has not been determined. Methods Transverse scalpel injuries 5-mm long and 4-mm deep were cut in the anterolateral anulus of L5-L6 and L4-L5 discs in 16 pigs. The cuts in the center of the anulus did not reach the nucleus pulposus and never produced a disc prolapse. In every pig, two non-adjacent lumbar discs (L1-L2 and L2-L3) were used as controls. Four discs per animal were studied in parallel by two different complementary immunohistochemical staining protocols. T lymphocytes and macrophages were located immunohistochemically using CD3 and CD68 antibodies, respectively. Discs were removed for analysis from four pigs at 1 week, from six pigs at 1 month, and from six pigs at 3 months. Inflammatory cells were categorized by two independent observers as being entirely absent (-), only few scattered cells (+), and at least one larger cellular infiltrate (+2). Results In none of the discs could extensive inflammatory cell infiltration be observed. T lymphocytes were present in significantly more sections cut from injured discs than in sections cut from control discs. The difference was highly significant particularly at 1 week and 1 month after disc removal. Only the 1-month-after-injury sections from injured discs exhibited significantly more macrophages than those from control discs. Conclusions The results suggest the presence of only modest inflammatory cell infiltration in experimental intervertebral disc injury at all follow-up times. The inflammatory response in partial-thickness anterior experimental intervertebral disc injury, in the absence of disc prolapse, seems to be dominated by a T lymphocyte response. The macrophage response is apparently strongest at 1 month after such injury. These findings differ from what has been observed in herniated disc tissue.

The nucleotide (nt) sequence of the cDNA encoding the retinal rod cyclic 3'5'-GMP phosphodiesterase (PDE) alpha and gamma subunits from two strains of dogs-(i) Labrador Retrievers homozygous for autosomally recessively inherited rod-cone degeneration and (ii) the wild-type Beagle-are reported. Cloning of these subunits was accomplished by polymerase chain reaction using retinal cDNA libraries as templates. The nt sequence of alpha PDE predicts a 861-amino-acid polypeptide which is 97.7 per cent and 96.9 per cent identical to the bovine and human counterparts, respectively. PDE gamma encodes an 87-amino-acid polypeptide differing from bovine and murine gamma subunits by only one amino acid. Since no differences were found between these two strains of dogs, the cause of the Labrador Retriever's degeneration remains to be determined.

Purpose To examine the amplification and kinetics of murine rod photoresponses by recording ERG flash responses in vivo and ex vivo from the same retina. We also aimed to evaluate the two available methods for isolating the rod signal from the ERG flash response, that is, pharmacology and paired flash method on the isolated retina. Methods Dark-adapted ERG responses to full-field flashes of green light were recorded from anesthetized (ketamine/xylazine) C57BL/6N mice. ERG flash responses to homogenous light stimuli arriving from the photoreceptor side were then recorded transretinally from the same retinas, isolated and perfused with Ringer's or Ames' solution at 37°C. The responses were analyzed to determine the a-wave kinetics as well as the estimated flash sensitivity and kinetics of the full rod responses derived with the paired flash protocol. The analysis was complemented with pharmacologic blockade of glutamatergic transmission in the isolated retina. Results The a-waves were of comparable size, sensitivity and kinetics in vivo and in the isolated retina, but the onset of the b-wave was delayed in the isolated retina. The Lamb-Pugh activation constants determined for the a-waves were similar in both preparations. The kinetics of the derived photoreceptor responses were similar in both conditions, although the responses were consistently slightly slower ex vivo. This was not explicable as a direct effect of ketamine or xylazine on the photoreceptors or as their indirect effect through hyperglycemia, as tested on the isolated retina. Conclusions Through comparison to the corneal ERG, the transretinal ERG is a valuable tool for assaying the physiologic state of isolated retinal tissue. The rod photoreceptor responses of the intact isolated retina correspond well to those recorded in vivo. The origin of their faster kinetics compared to single cell recordings remains to be determined.

Early ultrastructural findings of a progressive photoreceptor dystrophy and corresponding ERG findings are reported in 3 Labrador Retrievers from a litter of 7 pups bred from 2 dogs clinically and electroretinographically affected with generalized progressive retinal dystrophy. The pups were euthanized at 5, 11 and 15 months post partum. The most prominent ultrastructural finding was photoreceptor dystrophy. At 5 months the outer nuclear layer (ONL) consisted of 8-10 layers and seemed reduced in thickness, pyknotic nuclei were seen in this layer. The receptor outer segments (OS) were short and swollen. Some disorientation of OS discs occurred. In the 11-months specimen 7-8 ONL layers were identified. Overall thinning of the neuro-retina had occurred and fewer receptors compared to the 5-months specimen were present. By 15 months the ONL was further reduced to about 4 layers. Enlarged internuclear spaces were present in the ONL as well as around inner segments (IS). Phagocytic cells were frequent among remains of OS. The pigment epithelium appeared normal. The dark adapted ERG b-wave amplitudes and photopic 30 Hz flicker responses were low in comparison to controls of the same breed, and decreased with age. The condition represents a progressive rod-cone dystrophy which shares similarities with primary receptor dystrophy in man such as retinitis pigmentosa.

Xenon-flash d.c.-electroretinograms were recorded from dark adapted, rod-cone degenerate homozygote affected (n = 6), heterozygote carrier (n = 3) and control retinas (n = 4) at 3 and 4 months of age, starting at 0.6 log units below control PII threshold. One log unit higher stimuli were necessary to evoke PII in heterozygote and affected retinas compared to controls. Unique to the heterozygotes, double peaked PII responses that were evoked by −2 log relative units intensity stimulation were significantly (P = 0.028) lower in amplitude than those of controls. PII amplitudes of homozygotes were significantly (P = 0.005) lower in amplitude than those of controls at both ages examined in response to −2 and 0 log relative intensity stimulation. No differences were found in scotopic threshold response amplitudes or times to peak between the three groups. Homozygote affected PII times to peak were significantly (P = 0.005) shorter in relation to controls at −2 log units. Findings suggest that heterozygotes exhibit an impaired retinal function which can be demonstrated at 3 and 4 months in this mutant. Copyright © 1996 Elsevier Science Ltd