Search PubMed⌕ Search

Biomedical subjects

D L Easty

Publications and source records attributed to D L Easty.

At least 19 recordsLinked to original sources
PubMed1999

Reactivation of herpes simplex virus type 1 in the mouse trigeminal ganglion: an in vivo study of virus antigen and cytokines.

Reactivation of herpes simplex virus type 1 (HSV-1) in the trigeminal ganglion (TG) was induced by UV irradiation of the corneas of latently infected mice. Immunocytochemistry was used to monitor the dynamics of cytokine (interleukin-2 [IL-2], IL-4, IL-6, IL-10, gamma interferon [IFN-gamma], and tumor necrosis factor alpha [TNF-alpha]) and viral antigen production in the TG and the adjacent central nervous system on days 1 to 4, 6, 7, and 10 after irradiation. UV irradiation induced increased expression of IL-6 and TNF-alpha from satellite cells in uninfected TG. In latently infected TG, prior to reactivation, all satellite cells were TNF-alpha+ and most were also IL-6(+). Reactivation, evidenced by HSV-1 antigens and/or infiltrating immune cells, occurred in 28 of 45 (62%) TG samples. Viral antigens were present in the TG in neurons, often disintegrating on days 2 to 6 after irradiation. Infected neurons were usually surrounded by satellite cells and the foci of immune cells producing TNF-alpha and/or IL-6. IL-4(+) cells were detected as early as day 3 and were more numerous by day 10 (a very few IL-2(+) and/or IFN-gamma+ cells were seen at this time). No IL-10 was detected at any time. Our observations indicate that UV irradiation of the cornea may modulate cytokine production by satellite cells. We confirm that neurons are the site of reactivation and that they probably do not survive this event. The predominance of TNF-alpha and IL-6 following reactivation parallels primary infection in the TG and suggests a role in viral clearance. The presence of Th2-type cytokines (IL-4 and IL-6) indicates a role for antibody. Thus, several clearance mechanisms may be at work.

Animals↗
PubMed1998

An improved method for examining the corneal endothelium during graft rejection in the rat.

An improved method of removing rat corneal endothelial sheets for study of endothelial pathology is described. The method was validated by examining morphological changes and changes in expression of major histocompatibility complex (MHC) and intercellular adhesion molecule (ICAM)-1 on endothelium undergoing immunological rejection. PVG strain rats received LEW strain corneal transplants or corneal isografts. Just prior to and during graft rejection, animals were killed, together with a group of untreated animals. The corneal stroma was injected with dispase or PBS, the cornea was carefully removed, fixed in acetone and the endothelium was gently peeled off and flattened on to a glass slide. Morphological changes, together with MHC class I, class II and ICAM-1 expression were visualised by immuno-histochemical staining and quantified by image analysis. Near complete endothelial sheets were obtained by this method. Because of the thin cell layer, there was minimal background staining, permitting rejection-associated changes to be clearly seen. MHC class I expression on normal endothelium was low and not significantly increased on endothelial cells of allografts at the time of rejection compared with controls (P = 0.1). MHC class II and ICAM-1 were induced de novo, expression being significantly higher on allografts than on isografts (P = 0.004 for MHC class II and P = 0.01 for ICAM-1). MHC class I and II and ICAM-1 were expressed on many infiltrating cells. Thus, this preparation method permits clear identification of the distribution and morphology of infiltrating cells and other mediators of the immune response in the entire donor endothelium. It confirms that MHC class I expression is low during rejection, while MHC class II and ICAM-I are induced de novo and strongly expressed.

Animals↗
PubMed1998

Combined interrupted and continuous versus single continuous adjustable suturing in penetrating keratoplasty: a prospective, randomized study of induced astigmatism during the first postoperative year.

OBJECTIVE: To compare postoperative astigmatism induced by two different suturing techniques in penetrating keratoplasty (PKP). DESIGN: A monocenter, prospective, randomized clinical trial with a longitudinal 1-year follow-up. PARTICIPANTS: A total of 95 eyes undergoing PKP were randomized into 2 groups. Of these, 51 eyes were allocated to the combined interrupted and continuous suturing group (ICS) and 44 eyes to the single continuous adjustable suturing (SCAS) group. INTERVENTION: In the ICS group, suturing was with a combination of 12 interrupted 10-0 nylon and 1 continuous 11-0 nylon sutures. Eyes in the SCAS group had been sutured with a single running 24-bite 10-0 nylon. Selective suture removal started no earlier than 10 weeks after surgery; suture adjustment could start as soon as possible after surgery. MAIN OUTCOME MEASURES: Astigmatism was measured by topography, keratometry, and refraction at 3-, 6-, 9-, and 12-month postoperative intervals. RESULTS: The difference in mean time of suture manipulation between groups was significant (P = 0.0001), with the SCAS starting earlier. A significant decrease in astigmatism occurred by either interrupted suture removal (6.69 +/- 3.11 diopter [D] before to 4.76 +/- 2.99 D after, P = 0.0002) or suture adjustment (7.18 +/- 3.12 D before to 4.46 +/- 3.24 D after, P = 0.0001). However, the net astigmatic reduction in the SCAS group was not significantly greater (P = 0.250) than in the ICS group. Vector change was 7.40 +/- 4.17 D and 6.28 +/- 4.14 D for SCAS and ICS, respectively (P = 0.13). At no interval (3, 6, 9, or 12 months) was there significant difference in astigmatism between the two groups. Refractive astigmatism (cyl, D) at 1 year was 2.66 +/- 1.70 for the ICS and 3.12 +/- 2.62 for the SCAS, but there was no significant treatment effect (P = 0.945). Furthermore, 66% of the ICS eyes and 58% of the SCAS eyes (P = 0.295) were within the astigmatic target of the study (<3.5 D). CONCLUSIONS: Postkeratoplasty astigmatism can be decreased similarly with either adjustment of a single running suture or selective removal of interrupted sutures. No advantage of the SCAS over ICS in terms of fewer manipulations or less astigmatism was seen as suggested previously.

Adult↗
PubMed1998

Surgical control of late postkeratoplasty astigmatism with or without the use of computerized video keratography: a prospective, randomized study.

OBJECTIVE: To assess the effectiveness of computerized videokeratography (CVK) in refining the surgical design and in improving predictability of surgical correction of postkeratoplasty astigmatism. DESIGN: A prospective, controlled, randomized, clinical trial. PARTICIPANTS: A total of 31 postkeratoplasty eyes, divided into 2 groups (group A, 16 eyes; group B, 15 eyes), with more than 4 diopters (D) of disabling astigmatism were studied. INTERVENTION: All eyes were treated with a combination of arcuate relaxing incisions and compression sutures. The surgical plan in group A was based on topographic information, whereas in the control group B, the surgical plan was based on information obtained by refraction and keratometry alone. MAIN OUTCOME MEASURES: Change in the surgical plan induced by the CVK information, astigmatism, topographic patterns, and factors associated with outcome were measured. RESULTS: In all 16 cases of group A, the use of CVK changed some aspect of the surgical plan. At 12 months after surgery, both groups showed a significant net reduction (P = 0.001) of baseline astigmatism. However, the reduction (47% and 41 % for groups A and B, respectively) did not differ significantly between the two groups. The topographic astigmatism at 12 months measured 4.24 +/- 0.71 D in group A and 5.60 +/- 0.51 D in group B (P = 0.139). Significant differences between the two groups at 12 months were seen only for keratometric astigmatism (3.60 +/- 0.81 D in group A vs. 5.77 +/- 0.52 D in group B, P = 0.035) and refractive astigmatism (2.34 +/- 0.37 D in group A vs. 4.88 +/- 0.52 D in group B, P = 0.000). The mean vector surgical effect was 91 % for group A and 70% for group B. Regular astigmatism patterns had a greater benefit from surgery than irregular patterns (P = 0.008). Previous refractive surgery was associated with less-favorable outcome (P = 0.045). CONCLUSIONS: The current study indicates that the use of CVK provides a benefit compared to keratometry and refraction alone in the planning and outcome of surgical treatment for high postgraft astigmatism.

Adolescent↗
PubMed1998

A murine model of interlamellar corneal transplantation.

AIMS/BACKGROUND: There are more reagents and information available for immunological studies in the mouse compared with other animals. Unfortunately, the mouse penetrating keratoplasty model is associated with high background inflammation which hinders study of the immune response to the graft. To mitigate this drawback, a murine orthotopic corneal interlamellar transplantation model with mild non-specific inflammation was developed. METHODS: A 1.5 mm diameter full thickness donor corneal button was placed in a 2 mm diameter recipient corneal interlamellar pocket without placement of a suture. The clinical course of graft status was studied daily for 60 days in 30 allografts (donor strain CBA 101 (H-2k) to recipient NIH (H-2q) and 30 syngeneic grafts (NIH to NIH) by slit lamp biomicroscopy and scored for neovascularisation, opacity, oedema, and granularity. In another cohort of animals, histological observation was performed after 30 minutes and on days 10, 20, 30, and 40 after transplantation (four allografts and four syngeneic grafts per time point). Histological study was also performed on grafts without donor epithelium and on interlamellar pockets without grafts. RESULTS: There was significantly more neovascularisation (NV), opacity, oedema, and granularity in 24/30 allografts (80%) than in syngeneic grafts. Such grafts were defined as rejected. The median time to rejection was 21 days (range 18 to > 60 days). By histology, some allografts showed moderate to heavy cell infiltration which correlated with clinical scores of NV (4-5), opacity (1-3), oedema (1-3), and granularity (1-3). Such infiltration was absent in other allografts and syngeneic grafts. CONCLUSION: Surgically, corneal interlamellar transplantation could be accomplished in the mouse and rejection could be clearly defined. The model can therefore be useful for in situ study of cell and molecular aspects of corneal graft rejection.

Animals↗
PubMed1998

Purification of an antimicrobial peptide from rabbit aqueous humour.

PURPOSE: To identify an antimicrobial factor previously demonstrated in rabbit aqueous humour. METHODS: Rabbit aqueous humour was fractionated by a multi-stage process involving anion-exchange and size-exclusion liquid chromatography. The antimicrobial effect of aqueous humour fractions upon Staphylococcus aureus were evaluated in an in vitro model. The components of aqueous humour fractions mediating an antimicrobial effect were investigated by SDS-PAGE. RESULTS: A single peptide of molecular weight approximately 8 kDa was identified which mediated an antimicrobial effect upon Staphylococcus aureus. Attempts to identify the peptide have been unsuccessful. CONCLUSIONS: Rabbit aqueous humour contains an unidentified peptide that mediates an antimicrobial effect upon Staphylococcus aureus. If such a peptide is present in human aqueous humour it may contribute to the apparent resistance to bacterial infection manifest in the anterior chamber.

Animals↗
PubMed1997

Immunohistochemical detection of cytokines in paraffin-embedded mouse tissues.

We have successfully developed a method for the immunohistochemical detection of interleukin 2 (IL-2), IL-4, IL-6, IL-10O, IFNgamma and TNFalpha using monoclonal antibodies (MAb), in sections of mouse tissue embedded in paraffin wax. The method involved fixation in periodate-lysine-paraformaldehyde (PLP), rapid dehydration and infiltration under vacuum with paraffin wax at 54 degrees C. Comparative observations demonstrated that the method gives equivalent or better results than formaldehyde fixed, frozen sections. Since reliable controls, both positive and negative, are paramount for interpretation of immunohistochemical staining, such controls were determined. The following tissues were shown to be suitable as positive controls when using paraffin-embedding: spleen for the detection of TNFalpha, small intestine for IL-2, IL-4 and IL-10, and HSV-1 infected eyes for IL-6 and IFNgamma. We conclude that PLP fixation and low temperature paraffin-embedding is a method which provides both preservation of excellent tissue morphology and reliable immunohistochemical identification of cytokines. These attributes will be invaluable in a wide variety of experimental situations.

Animals↗
PubMed1997

Efficacy and safety of 0.3% carbomer gel compared to placebo in patients with moderate-to-severe dry eye syndrome.

PURPOSE: Carbomer gel is a water-soluble polymeric resin that has been reported to maintain the tear film in contact with the eye for an extended period. The efficacy and safety of this new artificial tear were assessed. METHODS: A multicenter, single-masked, randomized, placebo-controlled study was carried out on 123 patients with moderate-to-severe dry eyes. The placebo was a mannitol solution with benzalkonium chloride 0.008% as preservative. Patients were observed over an 8-week period, and subjective and objective changes analyzed, compared to a baseline of no therapy, after 1 to 7 days washout period from previous medication. RESULTS: All primary subjective symptoms decreased significantly in the carbomer gel-treated group compared to the placebo group (i.e., dryness, discomfort, and foreign body sensation). The carbomer gel also significantly improved the rose bengal staining score relative to placebo. When data for the primary subjective efficacy variables were stratified for disease severity, there was a statistically significant improvement from baseline by day 10 for severely affected patients and from day 42 for patients with moderate disease. Secondary subjective symptoms that improved significantly in the tear gel group compared to placebo were photophobia, erythema, tear breakup time, blurry-filmy, dry-sandy sensation, and physician impression. However, no significant improvements in the secondary subjective symptoms of tearing, itching, scaling, conjuctival discharge, palpebral conjunctival redness, bulbar conjuctival redness, conjunctival luster, relief of discomfort, ease of use, and overall acceptability were found in either group over the baseline score. In addition, neither carbomer gel nor placebo improved the baseline fluorescein staining score or the Schirmer test score. Two patients suffered local allergic reactions to the carbomer gel or its preservative, which settled on withdrawal of the medication. CONCLUSIONS: Carbomer gel was more efficacious than was placebo in improving a number of subjective and objective symptoms of moderate-to-severe dry eye syndrome. The results of this study indicate that carbomer gel was a safe as was the placebo.

Acrylic Resins↗
PubMed1997

The Bristol Shared Care Glaucoma Study--validity of measurements and patient satisfaction.

BACKGROUND: The aims of the study were to determine (1) whether community optometrists are able to make valid measurements of visual parameters in patients with established or suspect primary open angle glaucoma and (2) patient satisfaction with follow-up by community optometrists. METHODS: A randomized study was carried out in the former county of Avon in South West England with patients allocated to follow-up by the hospital eye service or by community optometrists. The subjects were 403 patients with established or suspected primary open angle glaucoma attending Bristol Eye Hospital and meeting defined inclusion and exclusion criteria. The main outcome measures were 91) measurements of key visual parameters (intraocular pressure, visual fields and cup/disc ratio) made by hospital eye service and community optometrists, compared with a research clinic reference standard at baseline, and (2) patient satisfaction at baseline and at six months. RESULTS: Community optometrists were able to make measurements of comparable accuracy to those made in the hospital eye service. Patients were significantly more satisfied with a number of aspects of care provided by community optometrists, particularly those relating to waiting times, compared with those from the hospital eye service. CONCLUSIONS: Community optometrists are able to make measurements of key visual parameters in patients with established or suspect primary open angle glaucoma which are of comparable quality to the hospital eye service. Follow-up by community optometrists is acceptable to patients. The costs of each option are reported elsewhere.

Aged↗
PubMed1997

Cytokine production in the nervous system of mice during acute and latent infection with herpes simplex virus type 1.

Immunocytochemistry on serial paraffin sections was used to monitor the production dynamics of cytokines (IL-2, IL-4, IL-6, IL-10, IFN-gamma and TNF-alpha) and viral antigens in the trigeminal ganglion (TG) and the central side of the dorsal root entry zone (DRE) of mice, following infection of the cornea with herpes simplex virus type 1. In normal TG, scattered satellite cells were TNF-alpha+ and in the DRE, TNF-alpha+ and/or low numbers of IL-6+ cells were detected. On day 3 after infection, foci of TG neurons with viral antigens were surrounded by large numbers of TNF-alpha+ and/or IL-6+ cells and low numbers of IFN-gamma+ cells. IL-2+ and/or IL-4+ cells appeared later, when viral antigens had almost cleared. In the TG, the most striking changes occurred with TNF-alpha, with respect to its source (satellite cells, Schwann cells and infiltrating cells) and the extent and long duration of its production. TNF-alpha was the predominant cytokine throughout acute and latent infection and even by day 30, numbers of satellite cells expressing this cytokine were three times higher than those in normal ganglia. Moreover, in the DRE, TNF-alpha was the only cytokine detected during virus clearance and again, its production continued, along with that of IL-6, on days 20 to 30, in both infiltrating cells and astrocytes. Thus, cytokines, particularly TNF-alpha and perhaps IL-6, from infiltrating cells and resident glial cells may have a role both in virus clearance and in normal homeostatic mechanisms in the nervous system such as repair and protection of neurons from damage.

Animals↗
PubMed1997

Conclusions of the corneal transplant follow up study. Collaborating Surgeons.

AIM: On the basis of finalised data from the Corneal Transplant Follow up Study to identify and quantify factors influencing corneal graft outcome in terms of graft survival, rejection, visual acuity, and astigmatism. METHODS: Multifactorial analysis of 2777 grafts registered by the UK Transplant Support Service from July 1987 to June 1991. RESULTS: Several recipient factors influencing graft survival, rejection, and visual acuity were identified, but no donor factors. Of the operative factors amenable to change, mixed suturing was associated with reduced graft survival, and larger grafts with increased risk of rejection but better visual acuity when surviving. There was increased risk of rejection with poor matching at HLA class I antigens, but mismatched HLA-DR grafts suffered less rejection than those with zero HLA-DR mismatches. Recipient age below 10 years was associated with increased risk of both rejection and graft failure. However, whereas increasing age above 10 years was not associated with differential graft survival, it was significantly associated with decreasing risk of rejection. CONCLUSIONS: While confirming possible benefits of HLA-A and B matching, the expense and delay involved in awaiting matched HLA-DR tissue is unlikely to be justified. Other donor factors are unrelated to graft outcome following screening of tissue by eye banks. The highest rates of graft failure and rejection happen in the early postoperative period, and factors influencing visual outcome are also apparent at this stage.

Adolescent↗
PubMed1997

Histopathology and molecular cytogenetics of a corneal opacity associated with the trisomy 8 mosaic syndrome (46,XY/47,XY, +8).

The trisomy 8 mosaic syndrome (Tr8MS), karyotype 46,XY/47,XY, +8, is a rare multisystem disorder that may be associated with corneal opacity. We report the case of a dysmorphic infant with multiple congenital abnormalities referred to our unit with a congenital corneal opacity. Subsequent chromosomal analysis of peripheral leucocytes demonstrated constitutional Tr8MS. At 4 years of age, lamellar keratoplasty was performed. Histological examination confirmed the lesion to be consistent with a corneal choristoma. Cytogenetic studies using in situ hybridisation techniques showed the presence of trisomic cells in cell culture derived from the tissue in higher proportion (92%) than in the blood (44%). Amplification of the c-myc oncogene on chromosome-8 could not be detected in cells cultured from the corneal lesion. Although not proof, these findings lend support to the concept of the corneal lesion representing a focus of viable trisomic cells rather than an inflammatory response to a nidus of effete cells.

Abnormalities, Multiple↗
PubMed1997

Factors influencing the suitability of organ-cultured corneas for transplantation.

PURPOSE: To assess the influence of donor and storage factors on the suitability of organ-cultured corneas for penetrating keratoplasty (PKP) using multifactorial regression analysis. METHODS: Corneas (mean donor age, 57 years; standard deviation, 21 years) were stored by organ culture at 34 degrees C for up to 5 weeks (mean, 22 days; standard deviation, 6 days). The endothelium was assessed by light microscopy, and corneas with < 2200 cells/mm2 were considered unsuitable for PKP. RESULTS: Of the 9250 corneas stored between 1992 and 1994, 59% were issued for PKP, 5% were discarded because of bacterial or fungal contamination, and 30% were unsuitable for PKP owing to endothelial deficiencies. Donor age had the strongest influence on suitability for PKP: > 80% of corneas from donors younger than 40 years of age were issued for PKP compared with only 45% of corneas from donors 80 years of age and older. There was an overall decline in the percentage of corneas suitable for PKP with increasing storage time, but the rate of this decline was inversely related to donor age. Cause of death and post mortem times to enucleation and to storage had only a small influence on suitability for PKP. CONCLUSIONS: Criteria based on endothelial assessment rather than on donor age allow corneas from donors of all ages, stored by organ culture for extended periods, to be used for PKP. Organ culture also allows corneas with bacterial or fungal contamination to be identified and discarded before they are grafted.

Adult↗
PubMed1997

Ganciclovir ophthalmic gel (Virgan; 0.15%) in the treatment of herpes simplex keratitis.

PURPOSE: Ganciclovir is a broad-spectrum virustatic agent. Its efficacy and safety after ocular application have been demonstrated in studies of herpetic keratitis in rabbits. Two strengths of ganciclovir gel (0.05 and 0.15%) were compared with 3% acyclovir ointment in the treatment of superficial herpes simplex keratitis in humans. METHODS: Two multicenter randomized clinical trials were carried out in Africa (Trial 1) and Europe (Trial 2). Sixty-seven patients (Trial 1) and 37 patients (Trial 2) from herpetic ulceration were recruited. RESULTS: The results showed no statistically significant difference between the treatment groups, although the healing rates tended to be better in the group receiving 0.15% ganciclovir gel, with healing rates of 85% (Trial 1) and 83% (Trial 2) as compared with 72% (Trial 1) and 71% (Trial 2) in the group receiving acyclovir ointment. Local tolerance was found to be superior with the gel formulation of ganciclovir with fewer complaints of discomfort (stinging, burning) or blurred vision after application of the drug. Systemic absorption of the drug was low. No hematologic changes were detected. CONCLUSIONS: These findings support the efficacy of ganciclovir gel in the treatment of ulcerative herpes simplex keratitis and demonstrate its superior local tolerance when compared with acyclovir ointment.

Acyclovir↗
PubMed1996

Clinical and surgical factors influencing corneal graft survival, visual acuity, and astigmatism. Corneal Transplant Follow-up Study Collaborators.

PURPOSE: To quantify clinical and operative factors that influence corneal graft outcome. METHODS: A multifactorial analysis was done on 2242 corneal grafts registered by the United Kingdom Transplant Service from July 1987 to June 1991. RESULTS: There was an increased risk of graft failure in patients with preoperative diffuse and other noncentral stromal edema, less-common eye diseases, small trephine size, difference in donor and recipient sizes greater than 0.25 mm, and use of mixed continuous and interrupted sutures. Visual acuity 3 months after surgery was poorer in patients who had glaucoma and low visual acuity preoperatively, small trephine size, and combined vitreous surgery. Use of interrupted sutures resulted in higher astigmatism at 3 months. CONCLUSIONS: After allowing for the effects of recipient factors, surgical factors significantly affected corneal graft outcome. No factors that showed significant benefits for graft survival also adversely affected visual performance. Details of medical history, clinical condition, and surgical method failed to predict more than a small proportion of observed variability in visual performance of functioning grafts.

Astigmatism↗
PubMed1996

Epithelial downgrowth following penetrating keratoplasty with a running adjustable suture.

A 78-year-old female patient who had a third penetrating keratoplasty for aphakic bullous keratopathy and iris fixation of a posterior chamber intraocular lens using a single, 10-0 nylon running suture technique developed a suture track leak postoperatively. Attempts to ease the tension on the suture track reduced the astigmatism and stopped the leak temporarily. Eighteen months after the procedure, epithelial downgrowth was noted on the corneal graft on both sides of the leak site and intraocular pressure was elevated. A fourth penetrating keratoplasty combined with a trabeculectomy was performed. To our knowledge, this is the first report of epithelial downgrowth associated with suture adjustment following the single, continuous suture technique.

Aged↗