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Biomedical subjects

D T Cheung

Publications and source records attributed to D T Cheung.

At least 19 recordsLinked to original sources

Development and validation of a PulseNet standardized pulsed-field gel electrophoresis protocol for subtyping of Vibrio cholerae.

PulseNet is a network that utilizes standardized pulsed-field gel electrophoresis (PFGE) protocols with the purpose of conducting laboratory-based surveillance of foodborne pathogens. PulseNet standardized PFGE protocols are subject to rigorous testing during the developmental phase and careful evaluation during a validation process assessing its robustness and reproducibility in different laboratories. Here we describe the development and validation of a rapid PFGE protocol for subtyping Vibrio cholerae for use in PulseNet International activities. While the protocol was derived from the existing PulseNet protocol for Escherichia coli O157, various aspects of this protocol were optimized for use with V. cholerae, most notably a change of the primary and secondary restriction enzyme to SfiI and NotI, respectively, and the use of a two-block electrophoresis program. External validation of this protocol was undertaken through a collaboration between three PulseNet Asia Pacific laboratories (Public Health Laboratory Centre, Hong Kong, National Institute of Infectious Diseases, Japan, and International Center for Diarrhoeal Diseases Research-Bangladesh) and PulseNet USA. Comparison of PFGE patterns generated by each of the participating laboratories demonstrated that the protocol is robust and reproducible.

Bangladesh↗

Simple and rational approach to the identification of Mycobacterium tuberculosis, Mycobacterium avium complex species, and other commonly isolated mycobacteria.

A novel PCR-restriction fragment length polymorphism analysis of the hsp65 gene was developed. The restriction patterns for Mycobacterium tuberculosis and Mycobacterium avium complex (MAC) species were designed to be highly distinct, and the overall number of restriction patterns was designed to be limited. Four hundred specimens (17 reference strains and 383 clinical isolates) were tested, of which 98 were M. tuberculosis and 132 were MAC species. The assay was virtually 100% sensitive and specific for M. tuberculosis and MAC species. Moreover, it gave highly concordant results for other mycobacterial species other than M. terrae complex species. This assay can be completed in one day and is user-friendly and robust. Therefore, it is highly suitable for large-scale use in a clinical laboratory.

Algorithms↗

A new method for the preservation of aortic valve homografts.

BACKGROUND AND AIM OF THE STUDY: Aortic valve homografts were treated with 50% ethanol and glycerol followed by freeze-drying (D-Hydro). Comparative results of fresh versus D-Hydro-treated aortic roots implanted for up to nine months in the descending aorta of sheep with induced aortic regurgitation (AR) are reported. METHODS: Six fresh and six D-Hydro valves were implanted in 12 sheep for three, six and nine months, and echocardiography and pressures were taken at surgery and sacrifice. Tissue sections were stained with hematoxylin and eosin, von Kossa, Masson's trichrome, Movat's pentachrome, von Willebrand factor, CD3 (a T-cell marker) and smooth muscle alpha-actin. RESULTS: No grafts had increased gradients after implantation, or at sacrifice. At explantation, fresh homografts showed early pannus formation followed by thrombus, annular dilatation and wall calcification. Leaflets were thickened and progressively retracted. All had severe AR. The appearance of D-Hydro-treated homografts was normal, except for mild leaflet retraction in three, resulting in AR (in two animals the induced AR had healed). Histologically, a T-cell-mediated reaction was evident in the fresh homografts, and collagen distortion was noted. Calcification was present in all fresh specimens and was severe at nine months. D-Hydro roots showed only minor calcification in the six-month samples. Normal collagen, and a complete layer of von Willebrand factor-stained cells were present at three months. At nine months, cell rehabitation extended for two-thirds of the leaflets (alpha-actin +). The inflammatory reaction was very mild, with CD3+-stained cells absent in most samples. CONCLUSION: Aortic valve homografts treated with the D-Hydro freeze-drying method performed better than fresh homografts due to the absence of thrombus and annulus dilatation, limited calcification, and rehabitation of the aortic wall and parts of the leaflet by myofibroblasts, as well as the presence of a complete endothelial layer on the aortic wall and leaflet.

Animals↗

Significant increase of aortic root volume and commissural area occurs prior to aortic valve opening.

BACKGROUND AND AIM OF THE STUDY: The increased use of autologous, homologous or heterologous aortic root demands a detailed knowledge of its anatomy and function. The advent of 3-D digital sonomicrometry offered the opportunity to acquire precise information on the root and leaflet movements during the cardiac cycle. METHODS: Under cardiopulmonary bypass, sonomicrometry crystals were implanted in the aortic root and valve of eight sheep. Crystals were sutured at each commissure (n = 3), the top of the sinotubular junction (n = 3), lowest point of the annulus (n = 3), and leaflet tip (n = 3). 3-D coordinates of each crystal were recorded, together with left ventricular and aortic root pressures and ECG. When the animal had returned to a stable hemodynamic condition, the maximum and minimum distances between two crystals, and areas between three crystals, were calculated. Changes in root volume and leaflet position were time-related to the pressure changes. RESULTS: The most significant change between maximum and minimum distance between crystals during the cardiac cycle occurred at the commissural level. Similarly, the triangle defined by the three commissural crystals showed the greatest change in area (47%). The root volume increased by an average of 22%; about 40% of this increase occurred during the isovolumic phase. The aortic leaflets began to open before ejection. CONCLUSION: We postulate that aortic valve opening is initiated by the outward pull of the commissures. These findings should impact on aortic root surgery.

Animals↗

A study of the junction between glutaraldehyde-treated allogeneic aorta and host aorta.

BACKGROUND AND AIM OF THE STUDY: Stentless aortic valve bioprostheses have become popular because of their superior hemodynamics and expected increased durability. However, the stentless bioprosthesis differs from stented valves in that glutaraldehyde (GA)-treated tissue is implanted in direct contact with the native aorta. The effect of GA-treated tissue on host tissue has not been reported. METHODS: In order to analyze the effect of GA in the healing process, sheep descending aortic conduits treated with 0.625% GA were inserted in the descending thoracic aorta of 10 adult sheep. The implants were removed after 4, 5, 10, 12, 15, 25, 30, 32, 60 and 120 days. The upstream and downstream junctions were evaluated macro- and microscopically, and by immunohistology for smooth muscle cell alpha-actin and von Willebrand factor. RESULTS: By day 60 of implantation, the GA-treated conduits were calcified. By days 60 and 120, the calcification had spread to the host aorta, and was seen as foci of calcification in the junctional area. Acellular areas were also seen in the host aorta near the anastomosis. A fibrotic layer spanning the abluminal aspect of the junction between the implant and host aorta was present at day 4 and continued through 120 days. This layer was characterized by a progressive increase in collagenous matrix and cellularity, as well as new blood vessel formation. The luminal aspect of the junction had a neointimal layer of variable thickness containing alpha-actin-expressing cells covered by a monolayer of von Willebrand factor-expressing cells, seen at 15-30 days and present through 120 days. CONCLUSION: In our model, implanting GA-fixed tissue in direct contact with living tissues resulted in cell death and calcification of host tissue within 60 days. The integrity of the junction did not appear to be compromised. This may be of interest in light of the increased popularity of the stentless aortic bioprosthesis.

Actins↗

Relative distribution and crosslinking of collagen distinguish fetal from adult sheep wound repair.

BACKGROUND/PURPOSE: Collagen deposition in midgestation fetal skin wounds occurs rapidly and in a normal reticular pattern unlike adult scar. Although collagen types I, III, and V are present in both fetal and adult skin wounds, their relative distribution and pattern of crosslinking are unknown. We compared the quantity, distribution, and crosslinking of specific collagen types in fetal and adult sheep wounds. METHODS: Nine fetal lambs at 75, 100, and 120 days' gestation (term, 145 days) and their ewes received subcutaneous polyvinylalcohol (PVA) sponge implants. PVA sponges were harvested at 3, 7, or 14 days after implantation, were processed, and then analyzed for collagen content, distribution, and crosslinking by two-dimensional cyanogenbromide (2-D CNBr) peptide mapping. Collagen types were further analyzed in normal skin of fetal sheep at 75, 90, 125, and 140 days' gestation and in their ewes. RESULTS: Between days 3 and 14 after implantation, total collagen deposition within PVA sponges increased 25-fold in fetal lambs but only 10-fold in adult sheep. The type I to III ratios inside 14-day sponges of 75-day gestation fetuses and adult ewes were 6.4 and 1.3, respectively. Thus, by day 14 in both fetal and adult sponges, type I collagen emerged as the major constituent. Although type V comprised less than 2% of normal skin collagen, alpha1(V) chains constituted the greatest collagen fraction in 3-day fetal implants, whereas within 3-day adult sponges only alpha2(V) collagen was detected. The total collagen content of unwounded fetal sheep skin increased twofold from 75 to 90 days' gestation. However, noncrosslinked forms of collagen type I diminished rapidly after 90 days' gestation, corresponding with the transition to scarring of fetal sheep wounds. CONCLUSIONS: Collagen types I, III, and V are deposited rapidly in fetal wounds and display an ontogenic transition in their metabolism from a fetal to an adult phenotype. Crosslinking of type I collagen increases during development and corresponds with the transition to scarring of fetal wounds after midgestation. These observations may help design strategies that induce a more fetallike repair of adult wounds.

Animals↗

Behavior of vital and killed autologous pericardium in the descending aorta of sheep.

OBJECTIVES: Cardiovascular implants of fresh autologous pericardium produced mixed results including fibrosis with retraction or thinning and dilatation. The reasons for these differences are unknown but may involve activation of cells intrinsic to the tissue implant. To better understand the behavior of autologous pericardial implants, we studied the outcomes of vital pericardium (fresh) versus ethanol-killed pericardium. METHODS: Fresh and ethanol-killed autologous pericardium was transplanted as a patch, a conduit, or a rectangular flap bisecting the lumen in the descending aorta of sheep. The implants, recovered at 1, 5, 10, 15, and 30 days, were evaluated macroscopically and microscopically and by immunohistologic studies. RESULTS: Fresh implants showed good preservation with fibrin deposition on day 15. Microscopically, cells positive for alpha-actin and von Willebrand-related antigen appeared in the fibrin by day 10. By day 30 the flap was fibrotic and retracted whereas the patch and conduit retained their original appearance on the luminal aspect. An endothelium-like layer expressing von Willebrand-related antigen was present in the patch and conduit but absent in the flap. In contrast, the ethanol-killed implants were free of fibrin by day 10. By day 30, there were no signs of fibrosis or retraction, and a surface layer of cells expressing von Willebrand-related antigen, characteristic of endothelial cells, was present on all implants. All ethanol-killed implants were repopulated by host cells. CONCLUSION: The transluminal flap is an interesting model for studying the behavior of intraluminal autologous pericardial cardiovascular implants. Killing of the pericardial implants alleviated the fibrosis and tissue retraction observed with fresh flap implants.

Actins↗

Aortic root geometry: pattern of differences between leaflets and sinuses of Valsalva.

BACKGROUND AND AIMS OF THE STUDY: Growing interest in aortic root replacement with the use of stentless auto-, homo- and xenografts, and new developments in aortic valve conservation demand a deeper understanding of the normal aortic root anatomy. METHODS: Ten cryopreserved human aortic roots were pressurized, fixed and measured directly (leaflet free edge and attachment) and using three-dimensional computed tomography imaging software (sinus of Valsalva height and volume). RESULTS: The mean of the measurements of all four parameters yielded a pattern in which the non-coronary sinus (N) structures had the greatest dimensions followed by the right (R) and then the left (L). Non-parametric ANOVA on each of these parameters also showed significant differences among the sinuses yielding a pattern of N > R > L. This pattern determined an angle of tilt between the plane at the base (annulus) and the plane intersecting the sinotubular junction with a mean value of 11 degrees. Linear regression indicated that this angle did not depend on the size of the base (annulus). CONCLUSIONS: The data showed a geometric pattern of the aortic root, with the structures of the non-coronary sinus being the largest followed by the right and then the left. The possible hemodynamic relevance and surgical implications of these findings need to be explored.

Aortic Valve↗

Collagen content is significantly lower in restenotic versus nonrestenotic vessels after balloon angioplasty in the atherosclerotic rabbit model.

BACKGROUND: It is recognized that restenosis is primarily due to alterations in geometric remodeling of the extracellular matrix rather than intimal hyperplasia. Prior studies have shown that angioplasty stimulates an increase in both synthesis and degradation of collagen in the atherosclerotic vessel. However, differences in collagen content and metabolism between restenotic and nonrestenotic vessels have not been examined. METHODS AND RESULTS: Four weeks after angioplasty in an atherosclerotic rabbit model, collagen content in restenotic and nonrestenotic vessels was measured both biochemically by hydroxyproline quantitation and histologically by a digital subtraction method with the use of circularly polarized images of picrosirius red-stained sections. Collagenase and gelatinase activity also were measured in the same restenotic and nonrestenotic vessels by use of a radiosubstrate assay. Collagen content was found to be significantly lower in restenotic vessels than in nonrestenotic vessels both biochemically (127.0 +/- 32.6 versus 212.6 +/- 84.3 micrograms/mg tissue; n = 11 vessels; P < .05) and histologically (67.3 +/- 7.9% versus 76.3 +/- 11.8% area fraction; n = 20 sections from 6 vessels; P = .05). There was a significant inverse correlation between biochemically determined collagen content and gelatinase activity (P = .02) and a significant correlation between histologically determined lumen are and percent collagen content (P = .0071). CONCLUSIONS: Collagen content is significantly decreased in restenotic versus nonrestenotic vessels after angioplasty in the atherosclerotic rabbit model. The increased collagen content in nonrestenotic vessels was associated with preserved lumen area and may play a role in geometric remodeling after angioplasty.

Angioplasty, Balloon↗

Balloon angioplasty significantly increases collagen content but does not alter collagen subtype I/III ratios in the atherosclerotic rabbit iliac model.

Angioplasty has been reported to increase collagen content and to alter vascular collagen alpha 1(I), alpha 2(I), and alpha 1(III) mRNA levels. Collagen synthesis is tightly regulated by complex translational and post-translational mechanisms such that mRNA levels may not necessarily reflect biosynthesis. To test whether collagen subtype I and III protein levels are altered by angioplasty, we quantitatively analysed collagen I/III protein ratios at 4 weeks after balloon angioplasty. Twenty New Zealand White rabbits underwent iliac artery balloon de-endothelialization and then were placed on a 0.5% cholesterol/6% peanut oil diet for 7 weeks at which time angioplasty was performed on arteries with > or = 50% stenosis. Arteries with < 50% stenosis were not dilated and served as controls. Animals were killed 4 weeks later and hydroxyproline (OH-pro) content and subtype I/III ratios were analysed in 5-mm mid-iliac sections. OH-pro was measured by a colorimetric assay. Subtype ratios were determined by a highly quantitative two-dimensional cyanogen bromide peptide mapping method. The degree of stenosis was measured as the minimal vessel lumen diameter and calculated as a percentage stenosis compared to a proximal reference segment. Calculated collagen content (micrograms/mg tissue) was significantly higher 4 weeks following angioplasty compared to the non-dilated group (220.4 +/- 70.8 v 308.2 +/- 26.9, P = 0.04; n = 12), despite similar percentage stenosis in the primary and restenotic lesions. The ratio of collagen I/III subtype protein distribution was not significantly different in the non-dilated and angioplastied groups (4.88 +/- 1.00 v 4.70 +/- 0.82, respectively). These studies are the first to provide data on collagen I/III subtypes following angioplasty and suggest that collagen accumulation may be more important in restenosis than alteration of collagen protein subtypes.

Angioplasty, Balloon↗

Engineering, expression and renaturation of targeted TGF-beta fusion proteins.

This study reports the expression, purification, and renaturation of biologically active Transforming Growth Factor-beta 1 (TGF-beta 1) fusion proteins from Escherichia coli (E. coli). A prokaryotic expression vector was engineered to produce tripartite fusion proteins consisting of (i) a purification tag, (ii) a protease-sensitive linker/collagen binding domain, and (iii) a cDNA sequence encoding the active fragment of human TGF-beta 1. The expressed fusion proteins TGF-B1-F1 and TGF-B1-F2, located in inclusion bodies, were solubilized with 8 M urea and renatured using a glutathione redox-coupled system and protracted dialysis under several experimental conditions. The purification of the recombinant proteins was achieved by binding the His-tag of the fusion proteins on a Ni-NTA metal chelate column. The biological activity of the recombinant growth factor was demonstrated by its ability to inhibit mink lung (Mv1Lu) cell proliferation and/or to stimulate proliferation of NIH-3T3 mouse fibroblasts, where purified human platelet TGF-beta 1 served as a positive control. Purified TGF-B1-F1 and TGF-B1-F2 (collagen-binding) constructs exhibited anti-proliferative activities comparable to purified platelet TGF-beta 1, but at lower specific activities. Binding of the renatured TGF-B1-F2 fusion protein to collagen was demonstrated by stable binding on a collagen-conjugated Sephadex-G15 column. The high affinity binding was also demonstrated by the binding of 3H-collagen to the TGF-B1-F2 protein immobilized on a Ni-NTA column. The TGF-B1-F2 fusion protein bound to collagen coated surfaces with high affinity but exhibited comparatively lower biological activity than the fusion protein in solution, suggesting a potentially latent configuration. Taken together, these results demonstrate that biologically active TGF-beta 1 fusion proteins can be recovered from transformed bacteria by oxidative refolding; thus, providing a means for its high-yield production, purification, and renaturation from microorganisms. Furthermore, these results support the concept that auxiliary domains may be used to modulate and/or target TGF-beta 1 for specific applications.

3T3 Cells↗

Stabilization of pericardial tissue by dye-mediated photooxidation.

Bovine pericardial tissue was stabilized through a dye-mediated photooxidation reaction. Shrink temperature analysis of the stabilized tissue indicated a material with similar properties to untreated pericardial tissue and unlike identical tissue treated with glutaraldehyde. Photooxidized tissue was resistant to extraction when compared with untreated tissue or control tissues treated in the absence of light or dye. Photooxidized tissue was also resistant to enzymatic digestion by pepsin and to chemical digestion by cyanogen bromide (CNBr). In contrast, untreated or control treated tissues were readily digested by these reagents. Reduction of photooxidized tissue with beta-mercaptoethanol prior to CNBr digestion partially restored susceptibility of the tissue to CNBr digestion, indicating the photooxidation of methionine residues. Soluble collagen derived from bovine pericardium was used as a model compound for the photooxidation reaction. Polyacrylamide gel electrophoresis analysis indicated the photooxidative conversion of collagen into higher molecular weight aggregates consistent with intermolecular crosslink formation. Photooxidized tissue was stable to in vivo degradation when compared with control tissue. Results presented here indicate a crosslinked pericardial tissue produced by dye-mediated photooxidation possessing properties of chemical stability, enzymatic stability, in vivo stability, and biomechanical integrity suitable for use as a biomaterial.

Animals↗

Effects of lathyritic drugs and lathyritic demineralized bone matrix on induced and sustained osteogenesis.

Demineralized bone matrix was implanted in normal and lathyritic rats. At 2 weeks, the bone that formed in the lathyritic animals had an elevated alkaline phosphatase activity and a reduced calcium content compared with the controls. Four weeks after implantation, these biochemical parameters were reversed, with a decrease in alkaline phosphatase activity and an increase in calcium content to control levels. The histology of the recovered implants revealed new bone formation. Lathyritic demineralized bone matrix was prepared from bones of rats fed beta-aminopropionitrile for 2 weeks (2-week BAPN-DBM) or 4 weeks (4-week BAPN-DBM), and was implanted in normal rats. Two weeks after implantation, both preparations of lathyritic demineralized bone matrix demonstrated early bone formation, although alkaline phosphatase activity and calcium content were reduced. By 4 weeks after implantation, no biochemical or histological evidence of bone formation remained at the site of the 4-week BAPN-DBM implants; continued but reduced bone formation was observed at the site of the 2-week BAPN-DBM implants. Reconstitution of inactivated normal demineralized bone matrix with the guanidine-soluble extracts restored the osteoinductive capacity. However, reconstitution of inactivated lathyritic demineralized bone matrix (4-week BAPN-DBM) failed to restore the osteoinductive capacity. These results indicate that the degree of crosslinking of the collagen matrix that acts as a carrier for osteoinductive proteins plays a key role in inducing and sustaining osteogenesis.

Aminopropionitrile↗

Comparison of various delivery systems for demineralized bone matrix in a rat cranial defect model.

Demineralized bone matrix (DBM) has been successfully used as a substitute for bone grafting. Autogenous bone grafts may cause site morbidity and undergo significant resorption. DBM may overcome these problems, but it has no mechanical stability until bone formation has occurred. We tested various alloplastic implants (i.e., Surgicel, polydioxanone [PDS], porous polyethylene [Medpor], and Gelfoam) in combination with DBM and compared it with DBM alone in a 9 x 9 mm rat cranial defect model. Histological and biomechanical measurements were performed at postoperative month 2. Among the study groups, Gelfoam/DBM inhibited bone formation to varying degrees and was the only group that displayed an inflammatory response. Mechanical pushout tests using a servohydraulic testing frame were conducted. The Medpor/DBM implant displayed the strongest support at 2 months; maximum load was 95% of intact skull. Surgicel/DBM and DBM alone were comparable; maximum load was 66% of intact skull. Gelfoam/DBM and PDS/DBM displayed the weakest support (48% of intact skull). We conclude that, after 2 months of implantation, alloplastic/DBM composites provide osseous structural integration. Gelfoam/DBM is not an effective delivery system for DBM in our model.

Analysis of Variance↗

Ultrasound debridement of trabeculated bone: effective and atraumatic.

Given the plethora of techniques available for debridement of contaminated bone, no single method can be considered ideal. Ultrasound has been shown to be less traumatic and more effective for debridement of contaminated soft tissue than either abrasive scrubbing or high-pressure jet irrigation. Using the distal femur and condyle of 23 freshly sacrificed adult Sprague-Dawley rats, this study was undertaken to compare ultrasonication to traditional debridement techniques in (1) their effectiveness in decontaminating trabeculated bone, (2) the subsequent effect of each treatment on bone cell function as measured by protein synthesis, and (3) the direct mechanical effects of each technique on the integrity of the bone structure itself. Ultrasonic debridement was found to be as effective as high-pressure jet irrigation or surgical scrubbing in debridement of contaminated trabeculated bone (no significant statistical difference). Overall activated bone cell function 24 hours after each debridement technique also was found to be equivalent (no significant statistical difference). However, electron microscopy reveals radical structural alterations of the bone after high-pressure jet irrigation or abrasive scrubbing that are not seen with ultrasound debridement. Acutely, the devastating effects of abrasive scrubbing and high-pressure jet irrigation leave an exposed bone matrix not only devoid of any cells but also honeycombed with interstices for entrapment of bacteria and other contaminants. All three debridement methods leave the deeper bone cells viable, but only ultrasound maintains the integrity of the directly involved bone trabeculum to reduce contamination, prevent colonization, and decrease possible infection.

Animals↗

Whole organ evaluation of collagen in the developing human larynx and adjoining anatomic structures (hyoid and trachea).

The collagen composition (types I, II, and III) of the normal developing human larynx and trachea was examined by biochemical methods. Autopsy specimens of larynges with attached upper tracheal rings were obtained from 28 humans ranging in age from birth to 44 years. The specimens were randomly collected, but excluded if laryngeal disease existed. The age, sex, and cause of death were documented. Collagen is important in the growth, development, repair, regeneration, and structural and functional integrity of the laryngeal framework. A preliminary report of selected cartilaginous components of the larynx was previously published by the authors, which studied the changes in the phenotypic expression of the collagen genes in children from the newborn period to 5 years 10 months of age. The current study included all of the functioning components of the skeletal larynx and trachea. The results of biochemical examination of these tissues are reported, and the potential clinical significance of the results of the study is discussed.

Adult↗

In situ collagen gel mold as an aid in excimer laser superficial keratectomy.

PURPOSE: The aim of this study is to evaluate the potential use of bovine type I collagen as an adjuvant to excimer laser keratectomy. METHOD: A suspension of collagen with the capability to polymerize into a gel was applied to the anterior corneal surface of freshly enucleated porcine eyes, using 35.0 diopter (D), 45.5 D, or 52.0 D contact lenses as molds. Keratometry, photokeratoscopy, slit-lamp photography, scanning electron microscopy, and light microscopy were performed on the new surfaces. Furthermore, an irregular corneal surface was created and a suspension of collagen was applied to mask protruding irregularities, therefore creating a smooth surface that was subjected to excimer laser keratectomy. Ablation rates for both collagen and cornea were measured. RESULTS: Collagen suspension placed on a cornea and molded with contact lenses created a smooth-surfaced gel that conformed to the shape of the contact lens and adhered to the anterior cornea; it was optically smooth and regular as shown by photokeratoscopy, keratometry, and scanning electron microscopy. The corneal curvature was altered in accordance with the base curvature of the contact lens used. Results of keratometry showed resolution of pre-existing astigmatism without induction of new astigmatism. The ablation rate of the gel was not measurably different than that of cornea; hence, when applied to an irregular corneal surface, a smooth surface was created after excimer laser ablation. CONCLUSION: This study supports the potential value of collagen gel as an adjuvant to excimer laser keratectomy for removal of corneal irregularities as well as for correction of myopia or hyperopia with or without astigmatism.

Animals↗

Effects of non-steroidal anti-inflammatory drugs on demineralized bone-induced bone formation.

The inhibitory effect of some non-steroidal anti-inflammatory drugs (NSAIDs) on bone resorption is well documented. To explore the effect of NSAIDs on bone formation, we investigated the time course and dose/response characteristics of treatment with various non-steroidal anti-inflammatory drugs (NSAIDs) on ectopic bone formation induced by demineralized bone matrix (DBM) in the rat model. Using biochemical assays, both inhibitory and stimulatory effects on bone formation were found in rats treated with NSAIDs prior to DBM implantation depending on the type and amount of drug administered. There appears to be an enhancement of bone formation for acetaminophen (50 mg/kg), acetylsalicylic acid (50 mg/kg), and ibuprofen (50 mg/kg). Indomethacin (4 mg/kg) and piroxicam (4 mg/kg) had inhibitory effects. Flurbiprofen, on the other hand, did not appear to affect bone formation significantly. In contrast, there was no effect of NSAIDs on bone formation in rats treated with the drugs after implantation of the DBM. It appears that the time course of the drug administration is critical, suggesting that early events in bone formation may be modulated by arachidonic acid metabolites.

Acetaminophen↗