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Biomedical subjects

M Savoldelli

Publications and source records attributed to M Savoldelli.

At least 37 records · Page 2Linked to original sources

Incorporation of a fluorocarbon polymer implanted at the posterior surface of the rabbit cornea.

An implant of porous expanded polytetrafluoroethylene (PTFE) in the corneal stroma allows fast cell colonization and can become translucent. We studied the behavior of the same polymer implanted in the anterior chamber of the rabbit eye and sutured to the posterior surface of the cornea. The expanded tetrafluoroethylene was provided as 200-micron thick sheets in 3 pore diameters (20, 50 and 80 microns). Disks (5 mm) were implanted in the anterior chambers of 20 rabbits and sutured to the posterior surface of the cornea. Histological and ultrastructural studies were performed after 3 and 4 months. Quantimetry was done on TEM images to analyze the fibrillar structure of the intercellular matrix inside and around the implanted polymer. The material was well tolerated. In all cases there was mild central corneal edema, which disappeared after 1 month. Mild neovascularization occurred in five cases, decreasing after 1 month. The polymer became translucent after 8 days. Keratocytes from the corneal stroma colonized the implant via breaks in the Descemet's membrane along the sutures. Quantimetry showed three types of fibrils inside and beside the polymer. Corneal endothelial cells regenerated over the fibroblasts and the polymer. This fluorocarbon polymer implanted in the anterior chamber and sutured to the posterior surface of the cornea was well tolerated, and there was real incorporation, with keratocytes producing collagen fibrils inside the polymer and endothelial cells forming a posterior cell monolayer. This is promising for the development of a keratoprothesis with posterior fixation.

Animals↗

Collagen synthesized in fluorocarbon polymer implant in the rabbit cornea.

The integration of microporous polymer into tissues is of great interest for the production of keratoprosthetic devices. Our previous studies showed functional differentiated cells and collagen synthesis in the pore of an expanded polytetrafluoroethylene implant. This study identifies and quantifies collagen types synthesized in the implant. Expanded polytetrafluoroethylene polymers were implanted in the rabbit corneas. The collagen extracted from the polymer and implanted stroma after 1, 3 and 6 months was quantified by measuring hydroxyproline. The relative proportions of collagen types were determined by densitometric analysis after SDS-PAGE. The collagen-to-protein ratio in the polymer increased from 0.22 to 0.70 between the first and third month after implantation becoming similar to control cornea. So that of the protein and collagen densities in the polymer and implanted stroma were similar to the control from the third month. The collagen synthesized in the polymer was mainly type I (87%) plus a small amount of type III (8%) 1 month after implantation. The collagen distribution from the third month after implantation was similar to that of the controls and remained constant thereafter in the polymer implant and in the implanted stroma. Immunogold labelling techniques confirmed these results. Implantation of this PTFE disc induced no obvious modification of the corneal stroma, confirming that this polymer is a good interface that is compatible with the native corneal stroma. The keratocytes in this polymer rapidly adopted a corneal phenotype, distinct from the dermal or scaring phenotype as shown by the collagen types produced in the implant.

Animals↗

Keratoprosthesis with biocolonizable microporous fluorocarbon haptic. Preliminary results in a 24-patient study.

BACKGROUND: Most complications of a keratoprosthesis occur at the tissue-to-implant interface. The ideal prosthesis would eliminate this interface by having the tissue actually grow into the supporting material. We present a prospective clinical human study of a novel biocolonizable keratoprosthesis in 24 eyes of 24 patients. DESIGN: To promote implant stability, the 9-mm-diameter haptic was fashioned using a custom-made microporous fluorocarbon with a 4-mm-diameter, 2.67-mm-long, central optic made of medical grade polymethylmethacrylate, giving a global visual field of 110 degrees to 130 degrees. Only bilaterally blind patients with untreatable corneal diseases were included in the study. The haptic was inserted into a lamellar pocket delaminated in the stroma, and the optic was positioned through a hole trephined in the central cornea. RESULTS: The average follow-up was 15.7 months (range, 4 to 28 months). The host corneal fibroblasts penetrated and proliferated into the peripheral microporous fluorocarbon and provided anchorage between the cornea and prosthesis. Seventeen patients (70.8%) had visual acuity improvements. Mean corrected final visual acuity was 20/100 (range, 20/30 to 20/400). Five anatomic failures occurred in the first 6 months (three extrusions, one dislocation of the optic, and one endophthalmitis). We had one case (4.1%) of treatable glaucoma. We successfully removed four of five retroprosthetic membranes that had occurred. No retinal detachment occurred. CONCLUSION: The biocompatible inert microporous polymer did not eliminate all mechanical complications associated with a keratoprosthesis.

Adult↗

Paroxysmal dystonia and paroxysmal tremor in a young patient with multiple sclerosis.

A 16-year-old patient with multiple sclerosis (MS) showed paroxysmal movement disorders during a recurrence of the disease. The paroxysms took the form ot brief unilateral dystonic posturings of the right body suggestive of paroxysmal dystonia (PD); they completely receded with acetazolamide. A single episode of a high amplitude, rythmic slow and coarse generalized tremor, present at rest and increasing with movement, particularly involving the head in a no-no movement, occurred soon after recovery from PD and lasted three hours. The present report provides evidence that MS has to be considered in the diagnostic approach to symptomatic childhood PD and underlines the efficacy of acetazolamide in the treatment of PD attacks. It also describes a rare paroxysmal movement disorder, defined as paroxysmal dystonic tremor, that can be considered as falling within the spectrum of PD.

Acetazolamide↗

Miragel versus silastic used as episcleral implants in rabbits. An experimental and histopathologic comparative study.

PURPOSE: Tissue reactions to two different biomaterials implanted on the sclera of rabbit eyes, a silicone implant (Silastic; Dow Corning) and a hydrogel (Miragel; Mira Inc.), were evaluated. METHODS: Both materials were implanted on the scleral surface under the superior rectus to obtain a focal scleral buckling. Histopathologic examination of the 32 eyes was performed with transmission electron microscopy 5 to 8 months after implantation. RESULTS: During the follow-up period, 6 silicone implants were extruded, compared with only one hydrogel implant. Histopathologically, both types of implants were surrounded by a newly formed fibrous capsule. Only the hydrogel implant gave rise to a granulomatous foreign body reaction against its own fragments, however. CONCLUSION: The main difference between the two types of material was a superficial fragmentation of the hydrogel implants. The reason for this fragmentation is unknown. To our knowledge, this is the first reported case of foreign body giant cell granuloma that developed against a hydrogel implant.

Animals↗

Ultraviolet solid-state laser (213-nm) photorefractive keratectomy. In vivo study.

BACKGROUND: The pulsed ultraviolet 213-nm solid-state laser has been demonstrated as an alternative to the gas argon-fluoride 193-nm excimer laser for photorefractive keratectomy (PRK). The authors studied the clinical course and histopathologic changes occurring in rabbit corneas after PRK with a 213-nm solid-state laser. METHODS: The 213-nm output of neodymium:YAG frequency-quintupled laser was used to create 5-mm optical zone ablations in seven pigmented rabbit corneas. The radiant exposure was 250 mJ/cm2 delivered through a computer-controlled scanning delivery system with a spot size of 0.5 mm. The target ablation was 4.0 diopters with an estimated ablation depth of 40 microns. A clinical estimate of corneal epithelial healing and stromal haze was made at intervals over the 3-month study period. Animals were killed immediately after ablation, or at 10 days, 1 month, or 3 months after ablation. Corneal tissue was preserved for light microscopy and transmission electron microscopy at each study interval. RESULTS: All corneas re-epithelialized within 10 days postoperatively. Anterior stromal haze was clinically visible at 3 days, increased until approximately 1 month, and then gradually decreased over the succeeding 2 months. Residual subepithelial haze was visible at 3 months. Results of histopathologic study documented normal epithelium healing over time; the basement membrane retained its regular thickness and hemidesmosomes were abundant at 3 months. The anterior stroma had an increased number of fibroblasts at 10 days, many of which remained until 1 month. A mild, transient, cellular reaction occurred throughout the thickness of the stroma and the endothelium. CONCLUSION: Using the 213-nm ultraviolet solid-state laser with a scanning delivery system, PRK shows a similar clinical course and histopathologic findings to the 193-nm excimer PRK study in rabbits. It is a clinically viable procedure for refractive surgery and requires further human clinical trails to determine its efficacy.

Animals↗

[Mucopolysaccharidosis type I, Hurler-Scheie phenotype with ocular involvement. Clinical and ultrastructural study].

The authors report the case of a 37 year-old male who presented with type I Hurler-Scheie (H-S) mucopolysaccharidosis revealed by ocular complications including bilateral corneal opacification and glaucoma. These complications are identical to those seen in Scheie's mucopolysaccharidosis. The patient underwent a trabeculectomy and a penetrating keratoplasty in both eyes. The corneal storage material was shown on the histological and ultrastructural examination of the buttons. These ocular complications result from excessive tissular storage of acid mucopolysaccharides due to an enzymatic alpha-L-iduronidase deficiency which was proved in our patient. H-S mucopolysaccharidosis is also characterized by dysmorphia and altered intellectual functions like in Hurler's disease in which the prognosis is however. The characteristics of the disease are discussed as well as the different therapeutical strategies which rely on leucocyte injections, skin fibroblast or bone marrow transplantation.

Conjunctiva↗

Corneal wound healing in monkeys after repeated excimer laser photorefractive keratectomy.

Five rhesus monkey eyes underwent repeated argon fluoride (193 nm) excimer laser myopic photorefractive keratectomy 3 months following an initial ablation that had produced mild subepithelial haze. At 3 months all eyes had development of a dense subepithelial opacity and a thickened epithelium (12 cells, 80 microns) with vacuolization of basal cells, fragmented basement membrane, and a layer of subepithelial fibrosis containing activated fibroblasts. By 6 months the opacity was clearing; epithelium was thinner (50 microns); subepithelial fibrosis was more lamellar. By 15 months only mild haze persisted clinically; epithelium was 30 microns thick, with persistent basal vacuolization and focal basement membrane disruption; subepithelial fibrous tissue was more organized. Early repeated excimer laser ablation of the monkey cornea apparently induces vigorous stromal wound healing. Use of shallower ablations, corticosteroids, or a longer delay between ablations may be necessary for repeated laser surgery to be practical clinically.

Animals↗

Recombinant human basic fibroblast growth factor (Rh-bFGF) in three different wound models in rabbits: corneal wound healing effect and pharmacology.

Prior to a clinical trial in humans, we studied the effect and pharmacological distribution of recombinant human basic fibroblast growth-factor (Rh-bFGF) in vivo. Healing experiments on de-epithelialized rabbits corneas (n = 24 animals) compared the efficacy of three bFGF doses to controls and revealed a significantly increased healing rate for both 200 ng and 500 ng per application Rh-bFGF treatment groups compared to the control groups. To assess possible side effects of Rh-bFGF (500 ng topically applied for up to 7 days, twice daily), ten rabbits were involved in a model of an anterior keratectomy wound (performed with Draeger's roto-keratome to a depth of 0.15 mm). Light microscopy of thin sections of treated corneas showed an increased fibrogenesis in the anterior stroma with a more pronounced activation of keratocytes. No evidence for abnormal neovascularization or inflammation was observed when compared to control corneas. Ocular penetration and systemic distribution of topically applied labelled 125I FGF was assessed in three models (iodine vapour epithelial burn, anterior keratectomy and penetrating autokeratoplasty) in 24 rabbits. No intraocular penetration of bFGF occurred as shown by direct gamma counting. Macroautoradiography showed a selective labelling of epithelial basement membrane when denuded and intact, as previously described. Evidence for systemic absorption of breakdown products was confirmed by heparin-sepharose chromatography of blood and urine samples. Under these conditions, we suggest that topical Rh-bFGF promotes corneal wound healing without morphological adverse reaction or intraocular and systemic penetration.

Animals↗

A fish-eye disease-like familial condition with massive corneal clouding and dyslipoproteinemia. Report of clinical, histologic, electron microscopic, and biochemical features.

Fish-eye disease (FED) is a rare familial condition characterized by progressive bilateral corneal clouding and dyslipoproteinemia previously described in one family and an unrelated woman of Swedish descent. Biochemical studies have clearly demonstrated the existence of this entity as a unique dyslipoproteinemia. We present a non-Swedish family of Mediterranean ancestry afflicted with bilateral corneal clouding and lipoprotein analysis consistent with FED-like state. This family's biochemical profile, corneal button histology, and electron microscopy of one member are reviewed. Other dyslipoproteinemias causing corneal changes are considered. Corneal tissue and familial biochemical analyses differed significantly from previous descriptions. On the basis of these findings, explanation of pathologic deposition and disease mechanism is proposed.

Adolescent↗

[The keratocyte or fibroblast of the cornea: morphological and biochemical characteristics in normal stroma and a few cases of corneal dystrophies].

Keratocytes are differentiated mesenchymal fibroblast which are specialized in the production and maintenance of the transparent corneal stroma. These elongated cells with large nuclei and scant cytoplasm produce the collages, proteoglycans, and glycoproteins which make up the stroma, as well as the enzymes involved in post-translation modifications and catabolism of these macromolecules. The characteristic morphological features and specific metabolic activity of keratocytes undergo significant changes during tissue repair and in several corneal diseases. Alterations in keratocyte biosynthetic activity, regardless of their cause, ultimately lead to fibrillar alterations responsible for a loss of corneal transparency.

Collagen↗

Microcomputer software applied to corneal stromal biometry.

Here we report a new method for image analysis of the corneal stroma. To obtain the biometric characteristics of a given area, we perform three different treatments of the same image. These automated predictions closely match each parameter (length, surface area, etc.), as measured manually by a "blind investigator." Furthermore, to obtain quantifiable, average values, we have increased the number of successive image measurements, which has led to the development of a series of programs designed to optimize automated data handling. Finally, the acquired, calculated parameters are summarized in the form of intermediate tables for each series of images, and as a final summary table incorporating t-test values and permitting comparison between two stromas (e.g., normal and pathological). Multivariate analysis and an ascending hierarchical classification demonstrate the main trends in differences of pathological vs. normal stroma.

Algorithms↗

Wound healing after excimer laser keratomileusis (photorefractive keratectomy) in monkeys.

Laser myopic keratomileusis (photorefractive keratectomy) was performed on 29 rhesus monkey corneas with an argon fluoride (193-nm) excimer laser and a computer-controlled, moving slit delivery system. The 4-mm-diameter central ablation zone ranged in depth from 11 microns (-2 diopters effect) to 46 microns (-8 diopters effect). Corneas were studied for the 9 months postoperatively by clinical slit-lamp microscopy, and periodically with light and transmission electron microscopy. By 6 weeks, mild to moderate subepithelial haze was apparent in 93% of the corneas, with considerable variability in density. Progressive clearing occurred so that by 6 to 9 months 12 of 13 surviving corneas (92%) were either completely clear (4 corneas) or trace hazy (8 corneas). The epithelium was thickened at 21 days after ablation and returned to normal thickness by 3 months. At 3 weeks, subepithelial fibroblasts were three times the density of normal keratocytes and returned to nearly normal numbers by 9 months. We concluded that the anterior monkey cornea demonstrated a mild, typical wound healing response after excimer laser keratomileusis.

Animals↗

[Is there a future for the Excimer laser in refractive surgery?].

The refractive surgery concerns all the surgical procedures implicated in the refractive power change of the cornea. Its clinical results are just known, and a new physical procedure is becoming capable to replace surgery: the Excimer laser. Without any instrumental contact with the corneal surface, the laser beam is able to remodel the corneal tissue, and to treat astigmatism, myopia, hypermetropia. Millions of people could be treated by such a laser, and could leave their glasses. Biological effects on rabbit and monkeys are presented. An argon fluoride excimer laser (193 nm) with a moving slit delivery system was used to perform anterior myopic keratomileusis in both eyes of 37 rabbits and 15 monkeys. Histological analysis of the corneas was made after ablation and at intervals up to 20 months. By slit examination at the longer follow up time, 60% of treated rabbits and 40% of treated monkeys keep a clear cornea, but the others had central spotty subepithelial haze. Light and electron microscopy documented corneal healing. In the clear corneas a good reconstitution of the epithelium, its basal lamina was observed, and anterior stromal corneas contained few active fibrocytes with a good preservation of the connective lamellar structure. On the contrary, in the cornea with opacification focal areas of 20 microns thick subepithelial scarring were present and the interface between epithelial cells and anterior stroma remained disturbed by incomplete, disrupted or duplicated basal lamina. Differences between the responses of monkeys, rabbits corneas to the same photoablation procedure remain unclear.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The effect of gentamicin on the corneal endothelium. An experimental study.

Gentamicin sulfate with preservatives was injected into the anterior chamber of a rabbit eye to evaluate its effect on the corneal endothelium. Endothelial toxicity was evaluated by contact specular microscopy and transmission electron microscopy 48 h after injection. The results suggest that doses ranging from 100 to 400 micrograms of gentamicin are not toxic to the corneal endothelium. Endothelial toxicity occurred when 1,000 micrograms of gentamicin was injected.

Animals↗

Corneal stromal wound healing in rabbits after 193-nm excimer laser surface ablation.

An argon fluoride excimer laser (193 nm) with a moving slit delivery system was used to perform anterior myopic keratomileusis in both eyes of 24 New Zealand white rabbits. Rabbits were killed immediately after ablation and at intervals up to 100 days. By slit-lamp microscopy, four rabbits at day 100 exhibited four clear corneas and four corneas had central, spotty, subepithelial haze. Light and electron microscopy documented corneal healing. In the early stages a transient acellular zone in the anterior stroma appeared over a period of three weeks, followed by an increased number of fibrocytes. In the corneas with opacification, focal areas of 20-microns-thick subepithelial scarring were present. An unexpected finding was transient damage to posterior stromal keratocytes and endothelial cells. The endothelium produced a layer of granular material that migrated anteriorly across Descemet's membrane. Immunochemistry at day 6 showed a marked staining for collagen IV, proteoglycans, fibronectin, and laminin.

Animals↗

Terrien's disease: clinical and ultrastructural studies, five case reports.

Terrien's disease occurs in middle-aged patients and is characterised by an insidious thinning of the cornea near the limbus. In most cases, this results in a peripheral ectasia associated with a severe degree of astigmatism. Inflammatory signs are rarely observed in this marginal corneal degeneration which is of unknown aetiology. Electron and light microscopic studies have been performed on five specimens from penetrating keratoplasties. Anatomical and clinical correlations showed the marked marginal degenerations of the corneal stroma to be consistently associated with lipid deposits, but without inflammatory cell infiltrate. These changes are in agreement with previous reported pathological descriptions of Terrien's disease.

Adult↗