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Biomedical subjects

C S Foster

Publications and source records attributed to C S Foster.

At least 199 records · Page 11Linked to original sources

Prevention of recurrence of oesophageal stricture, a comparison of lansoprazole and high-dose ranitidine.

OBJECTIVE: To determine the efficacy of lansoprazole 30 mg given in the morning compared with high-dose ranitidine 300 mg twice daily in the treatment of patients with oesophageal strictures. DESIGN: A multicentre, outpatient, double-blind, parallel group, prospectively randomized clinical trial. PATIENTS: One hundred and fifty-eight patients (lansoprazole 30 mg n = 78, ranitidine 600 mg n = 80) were enrolled from 19 centres in the UK over 23 months. INTERVENTIONS: Patients with an oesophageal stricture were randomized to receive either lansoprazole 30 mg once daily or high-dose ranitidine 300 mg twice daily for 12 months. Dilatation was performed at entry and repeat endoscopies were scheduled at 6 and 12 months and additionally at other times if there was symptomatic relapse. Redilatation was performed as required and according to a predefined scale. The patient's assessment of dysphagia over the previous 7 days was recorded by the investigator at 1, 3, 6, 9 and 12 months. Safety was assessed by laboratory tests, physical examination and all adverse events. MAIN OUTCOME MEASURES: Efficacy was assessed primarily by the time to redilatation, the proportion of patients requiring at least one redilatation, and the number of redilatations over 12 months. The relief of dysphagia and reduction in stricture grade were secondary efficacy measures. RESULTS: The time to redilatation was longer and the probability of no redilatation were higher in the lansoprazole group than in the ranitidine group; for all patients randomized (intention to treat principle), this difference was of borderline significance (life table, P = 0.053). The proportions of patients requiring at least one redilatation during the 12-month treatment period were 30.8% (24/78) with lansoprazole and 43.8% (35/80) with ranitidine (all patients randomized, chi 2 test, P = 0.092). Compared to ranitidine, patients receiving lansoprazole reported significantly lower dysphagia grades at 6 months (stratified Wilcoxon test, P = 0.0086) but not at 12 months (stratified Wilcoxon test, P = 0.074). A greater proportion of patients in the ranitidine group-33.8% (27/80)-withdrew prematurely compared to the lansoprazole group (26.9%, 21/78). The most frequent reasons for premature withdrawal were adverse events and protocol violations. There were no clinically significant differences in incidence or severity of adverse events between the two groups. The mean increase in gastrin levels after 12 months' treatment was significantly greater for patients in the lansoprazole group (124.2 pg/ml, P = 0.0056) than those in the ranitidine group (31.9 pg/ml). No significant changes in gastric mucosal histology were detected for patients in either group. CONCLUSION: It is concluded that lansoprazole 30 mg once daily is superior to ranitidine 300 mg twice daily in relieving dysphagia, and at least as effective in reducing the need for a repeat dilatation.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Herpes zoster peripheral ulcerative keratitis in patients with the acquired immunodeficiency syndrome.

The purpose of this study was to describe the clinical characteristics and course of peripheral ulcerative keratitis (PUK) secondary to herpes varicella-zoster virus in patients with the acquired immunodeficiency syndrome (AIDS). Three AIDS patients with ocular herpes zoster infection (mean age at onset, 33.0 years; range, 30-42) developed PUK. The three patients had skin involvement, and two of them had bilateral keratouveitis. All were treated with high-dose oral acyclovir (4 g/day) with or without topical antiviral therapy. Two of the patients responded well to oral acyclovir, but one of them stopped the treatment, and bilateral progressive outer retinal necrosis and lethal encephalitis developed. The third patient had a recurrent episode of inflammation with PUK, extensive stromal scarring, and deep neovascularization. AIDS patients with herpes varicella-zoster virus infection may have severe and protracted corneal manifestations, including PUK. The correct diagnosis and aggressive early long-term systemic antiviral treatment must be instituted to control inflammation, ulcer progression, and complications.

Acquired Immunodeficiency Syndrome↗

Collagen abnormalities in conjunctiva of patients with cicatricial pemphigoid.

The purpose of this study was to analyze the distribution and types of collagen in the substantia propria of the conjunctiva of patients with ocular cicatricial pemphigoid (OCP). Biopsy specimens were collected from 10 patients with active OCP, five patients with active Behçet's disease, nine patients with atopic keratoconjunctivitis, five patients with chronic rosacea blepharoconjunctivitis, and six normal patients undergoing cataract surgery. Cryostat tissue sections were cut and stained using an indirect immunofluorescence technique, employing a panel of primary antibodies directed against seven collagen types. Differences between OCP, Behçet's, and normal conjunctiva were seen in the staining for collagen types III, IV, and VII. The intensity of staining for type III collagen was increased in the substantia propria of OCP conjunctiva as compared to the other groups. The basement membrane zone (BMZ) of OCP patients was typically disrupted and fragmented in appearance when stained for type IV collagen, a finding not seen in the non-OCP specimens. The BMZ staining pattern for type VII collagen in OCP conjunctiva was even more disrupted than that seen for type IV collagen, particularly on the posterior side, which was thickened and reduplicated with short fibers extending into the superficial stroma. The production of type III collagen by fibroblasts of the substantia propria is a common feature of diseases associated with subepithelial fibrosis. The damage to the epithelial BMZ and the subsequent attempt at repair with aberrant type IV and VII collagen production are unique to conjunctiva affected by OCP.

Collagen↗

Detection of herpes simplex virus type 1 by an in situ polymerase chain reaction technique.

The purpose of our study was to develop a method for detecting herpes simplex virus (HSV) DNA that combined the high sensitivity of the polymerase chain reaction (PCR) with the precise anatomical localization provided by in situ hybridization (ISH). We used in situ PCR (ISPCR), ISH, and standard PCR methods to determine the proportion of Vero cells carrying HSV-1-specific DNA before and after 1, 2, and 4 h of infection with HSV-1 or with HSV-2. Uninfected Vero cells and Vero cells infected with HSV-2 were never found to be positive for HSV-1 DNA by either ISPCR, ISH, or PCR. In contrast, using ISPCR, HSV-1 infected Vero cells showed an increase in the percentage of cells containing HSV-1 DNA from 20% at 1 h to 76% at 4 h after infection. Comparing the ISPCR results with ISH and standard PCR demonstrated that ISPCR was markedly more sensitive than ISH; in fact, the sensitivity of in situ PCR was similar to that seen with standard PCR. These results demonstrate that ISPCR is a highly sensitive method for amplifying genomic DNA sequences within intact single cells. This technique combines the exquisite sensitivity of conventional PCR technology with the precise cellular localization afforded by ISH. In addition, it allows for an accurate quantitative determination of the number of virally infected cells.

Animals↗

Differential expression of voltage-activated Na+ currents in two prostatic tumour cell lines: contribution to invasiveness in vitro.

The voltage-gated ionic currents of two rodent prostatic cancer cell lines were investigated using the whole-cell patch clamp technique. The highly metastatic Mat-Ly-Lu cells expressed a transient, inward Na+ current (blocked by 600 nM tetrodotoxin), which was not found in any of the weakly metastatic AT-2 cells. Although both cell lines expressed a sustained, outward K+ current, this occurred at a significantly higher density in the AT-2 than in the Mat-Ly-Lu cells. Incubation of the Mat-Ly-Lu cell line with 600 nM tetrodotoxin significantly reduced the invasive capacity of the cells in vitro. Under identical conditions, tetrodotoxin had no effect on the invasiveness of the AT-2 cells.

Animals↗

Resistance to herpes stromal keratitis conferred by an IgG2a-derived peptide.

Not all peripheral tissue antigens enter the thymus and it is unclear how the immune system remains tolerant to this class of self antigen. As tolerance to self peptides can generate gaps in the T-cell repertoire for cross-reactive foreign antigens, we investigated whether this mechanism might also diminish autoimmune reactions to similar peptides expressed by peripheral tissues. Herpes stromal keratitis (HSK) is a virally induced autoimmune reaction against corneal tissues mediated by T cells, and is a leading cause of human blindness. Resistance to HSK in mice is associated with allotypic variation in immunoglobulin genes, possibly because circulating immunoglobin-derived peptides can cross-tolerize T cells specific for corneal tissue autoantigens. Here we show that HSK is mediated by T-cell clones specific for corneal self antigens which also recognize an allotype-bearing peptide derived from IgG2a, and that exposure of HSK-susceptible mice to a soluble form of this peptide confers resistance to HSK. Shared expression of peptide subsequences between sequestered tissue proteins and circulating proteins may be important for maintenance of self-tolerance and prevention of autoimmunity.

Animals↗

Recurrence rate of herpetic uveitis in patients on long-term oral acyclovir.

We examined the recurrence rate of herpetic uveitis (HU) in 13 patients (group A) treated prophylactically with long-term systemic acyclovir (600-800 mg/day) and compared it with that of 7 patients with no prophylactic therapy (group B). HU was diagnosed on the basis of a history of dendritic or disciform keratitis accompanied by iridocyclitis and iris atrophy. The study population consisted of 12 men and 8 women with a mean age at onset of uveitis of 52.9 years (range 19-78 years). All patients were followed for at least 8 months. The mean follow-up time of patients on long-term oral acyclovir was 26.0 months. In this group, only one patient experienced a single recurrent episode of uveitis while on 600-800 mg/day of acyclovir therapy; two additional patients had recurrence of HU within 16.2 months after the acyclovir dose was tapered below 600 mg/day. In striking contrast, 16 recurrences occurred in the 7 patients of group B (p < 0.05). Of these, the initial recurrence occurred within an average of 4.3 months following cessation of therapy. There was a significant difference (p < 0.05) in the mean recurrence-free interval between patients in group A (24.6 months) and those in group B (3.4 months). Herpetic uveitis is a serious ocular disease in which recurrence of inflammation results in severe ocular complications. The long-term use of oral acyclovir may be of benefit in the prevention of recurrences, and hence may reduce the blinding complications of this disease. Efforts at completing a randomized, placebo-controlled trial on this matter by the Herpes Epithelial Disease Study Group were unsuccessful due to insufficient patient recruitment.

Acquired Immunodeficiency Syndrome↗

Modulated expression of glycoprotein oligosaccharides identifies phenotypic differentiation in squamous carcinomas of the human cervix.

This study has examined changes in expression of complex oligosaccharides during the development of invasive squamous carcinoma of the human cervix to determine whether particular oligosaccharide structures that might influence the phenotypic behavior of individual human cervical cancers were expressed during neoplasia. An extensive panel of lectins capable of identifying all the core and antennary oligosaccharide structures commonly encountered in human epithelia was chosen to probe a range of 11 benign and 26 malignant cervical tissues, all of the latter being clinically stage I. Lectin histochemistry was performed both before and after tissue desialylation using the enzyme neuraminidase to identify masking of oligosaccharide determinants by sialic acid. Nonneoplastic cervical epithelial cells were found to express only type I antennary structures (Gal beta 1-->3GalNAc-) usually modified by sialic acid linked 2-->6 to terminal Gal- or GalNAc residues. Type II oligosaccharide structures (Gal beta 1-->4GlcNAc-) were not identified in these normal tissues. No other terminal antennary modifications were detected on nonneoplastic cervical squamous epithelia. Conversely, neosynthesis of type II oligosaccharides was detected by Erythrina cristagalli (ECG) binding in 50% of the squamous carcinomas. Five terminal antennary modifications were commonly identified in the carcinomas that were not identified in normal cervical epithelia and comprised the oligosaccharides bound by lectins RCA, SBA, BS-1, LTA, and UEA-1. Synthesis of these oligosaccharides resulted in expression of structures similar to those recognized as ligands for extracellular matrix-binding proteins. We suggest that expression of such novel oligosaccharide structures may be an important promotor of local invasion and further dissemination of human cervical carcinomas through enhanced binding of malignant cells to stromal matrix proteins. This study has demonstrated that identification of expressed oligosaccharide structures is an objective method of identifying individual tumor cell phenotypes and may form the basis of a useful functional classification of human cervical squamous carcinomas.

Carcinoma, Squamous Cell↗

Relapsing acute myeloid leukemia manifesting as hypopyon uveitis.

PURPOSE: Although acute lymphoblastic leukemia may masquerade as hypopyon uveitis, acute myeloid leukemia has only rarely been reported to cause this complication, and ocular relapse generally has been associated with evidence of malignant cells at other sites. We studied a patient with acute myeloid leukemia whose only sign of relapse was bilateral anterior uveitis with pseudohypopyon that was refractory to topical and systemic corticosteroids. METHODS: A 26-year-old woman with acute myeloid leukemia in remission, who had bilateral anterior uveitis and increased intraocular pressure at initial examination, was studied clinically. Blood films, bone marrow smears, and preparations were examined by using immunoperoxidase staining. RESULTS: Although there was no evidence of leukemia in the blood or bone marrow samples, the cells obtained from the anterior chamber showed myeloblastic leukemic cells with morphologic characteristics similar to those present in the original bone marrow biopsy obtained 14 months previously. Irradiation and chemotherapy were used to kill the malignant cells in the eye and central nervous system. The persisting glaucoma resolved after anterior chamber washout of necrotic tumor cells. CONCLUSIONS: Unusual features of uveitis in this patient indicated that she had a masquerade syndrome, despite normal results of bone marrow and blood film tests. Aspiration of intraocular cellular infiltrate for cytopathologic examination was required to obtain the correct diagnosis and enable treatment to commence without delay.

Adult↗

The value of combined serum angiotensin-converting enzyme and gallium scan in diagnosing ocular sarcoidosis.

PURPOSE: To evaluate the role of combined serum angiotensin-converting enzyme (ACE) activity and whole-body gallium (67GA) scanning in diagnosing sarcoidosis in patients with features consistent with ocular sarcoidosis but with normal or equivocal chest radiographs. METHODS: Serum ACE levels and whole-body 67GA scans were obtained as part of the initial workup in 22 patients with active ocular inflammation and ultimately biopsy-proven sarcoidosis (sarcoid uveitis group). A second group consisting of 70 patients with active uveitis in whom sarcoidosis also was considered a diagnostic possibility also was studied. All 70 patients ultimately had a definitive diagnosis other than sarcoidosis (nonsarcoid uveitis). All patients in this group also had a serum ACE and whole-body 67GA scan performed as part of their initial investigations. RESULTS: All patients in the sarcoid uveitis group had either an elevated ACE level or an abnormal scan. In 16 of the 22 patients, results of both tests were abnormal. In no patient in the nonsarcoid uveitis group were results of both tests abnormal. The sensitivity of an elevated ACE in diagnosing sarcoidosis was 73% and the specificity was 83%. Using the combination of a positive 67GA scan and an elevated ACE, the specificity for diagnosis was 100% and the sensitivity was 73%. CONCLUSIONS: The combination of serum ACE level and whole-body 67GA scan increases the diagnostic specificity without affecting sensitivity in patients with clinically suspicious ocular sarcoidosis who have normal or equivocal chest radiographs.

Adolescent↗

Analysis of the acute ophthalmic manifestations of the erythema multiforme/Stevens-Johnson syndrome/toxic epidermal necrolysis disease spectrum.

PURPOSE: To evaluate the epidemiology, possible etiologic factors, complications encountered, and treatment administered to a group of patients with ocular involvement in the erythema multiforme/Stevens-Johnson syndrome/toxic epidermal necrolysis disease spectrum who were seen at two large tertiary referral centers over a 34-year period. METHODS: Hospital records from 1960 to 1994 at the Massachusetts General Hospital and Shriners Hospital for Crippled Children were reviewed for patients with erythema multiforme, Stevens-Johnson syndrome, or toxic epidermal necrolysis. Only patients fulfilling specific clinical diagnostic criteria and those who received a diagnosis by a dermatologist were included in the review. RESULTS: A total of 366 patients with erythema multiforme, Stevens-Johnson syndrome, or toxic epidermal necrolysis were identified. Drugs were the most commonly identified etiologic factor in all three conditions: sulfonamides were the most frequently identified agents. Eighty-nine patients (24%) had ocular manifestations at the time of their acute hospital stay. Ocular involvement was seen in 9% of patients with erythema multiforme, in 69% with Stevens-Johnson syndrome, and in 50% with toxic epidermal necrolysis. The ocular problems were more severe in patients with both Stevens-Johnson syndrome and toxic epidermal necrolysis. There was no significant difference between the number of patients who were treated with systemic steroids and those who were not (P = 0.42). CONCLUSIONS: The erythema multiforme/Stevens-Johnson syndrome/toxic epidermal necrolysis disease spectrum remains an important cause of severe visual loss in a significant number of patients. Systemic steroids used during the acute phase of the disease appear to have no effect on the development of ocular manifestations. Studies on the acute immunopathogenic mechanisms occurring in these disease are warranted if more effective therapies are to be found.

Acute Disease↗

Immunopathologic study of the conjunctiva in patients with behçet disease.

PURPOSE: Even though conjunctiva is not primarily involved in patients with uveitis due to Behçet disease, it may reflect the immunopathologic process when inflammation is induced by biopsy of conjunctiva, a phenomenon similar to the induced inflammation at skin pathergy sites. METHODS: Conjunctival biopsy specimens obtained 48 hours after a 2-mm biopsy of the epibulbar conjunctiva in 26 Turkish patients with inactive ocular Behçet disease and 9 Turkish patients with inactive idiopathic uveitis were studied by immunoperoxidase using a panel of monoclonal antibodies: anti-CD1, -CD3, -CD4, -CD5, -CD14, -CD22, -CD25, and -CD67, HLA-DR, E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1). RESULTS: Immunopathology of the conjunctival specimens obtained at the time of first biopsy was not significantly different between the Behçet disease and the idiopathic uveitis groups. The second-biopsy specimens of the patients with Behçet disease showed significantly greater numbers of T cells (CD3+, CD4+) and granulocytes (CD67+) as well as HLA-DR+ and ICAM-1+ cells in the substantia propria. Vascular endothelium of the conjunctiva in a patient with Behçet disease had significantly more pronounced expression of the adhesion molecules, E-selectin, and ICAM-1. None of the conjunctival specimens in either group showed VCAM-1 positivity. CONCLUSIONS: These results show that a more intense antigen-independent inflammation develops with recruitment of both neutrophils and T lymphocytes of helper/ inducer phenotype in the conjunctiva of patients with Behçet disease in response to surgical trauma. Increased expression of E-selectin and ICAM-1 in the conjunctiva of patients with Behçet disease may suggest a critical role for these adhesion molecules in the initial events of inflammation.

Adolescent↗

Systemic immunosuppressive therapy and the occurrence of malignancy in patients with ocular inflammatory disease.

PURPOSE: To compare the occurrence of malignancy in patients with severe ocular inflammatory disease treated with systemic corticosteroids alone or with systemic immunosuppressive drugs with or without systemic corticosteroids. METHODS: The clinical records of 543 patients with ocular inflammatory disease treated with systemic corticosteroids and/or immunosuppressive chemotherapy were reviewed in a retrospective cohort study. Characteristics of patients treated with corticosteroids alone were compared with characteristics of patients treated with immunosuppressive agents with or without preceding corticosteroid treatment. The rates of malignancy after initiation of drug therapy were compared using an exact test for incidence rate data. RESULTS: Compared with patients treated with corticosteroids alone, patients treated with immunosuppressants with or without corticosteroid treatment were older and had more severe systemic disease. During a total of 1261 person-years of follow-up, a malignancy developed in five patients. The rate of malignancy in the immunosuppressant group (4 malignancies during 968 person-years of follow-up) was not significantly different from the rate in the corticosteroids alone group (1 malignancy during 293 person-years of follow-up) (P > 0.90, exact test for incidence rate data). CONCLUSION: These findings do not support the hypothesis of an increased risk of malignancy in patients with severe ocular inflammatory disease who are treated with systemic immunosuppressive agents compared with patients treated with systemic corticosteroids.

Adult↗

Increasing the diagnostic yield of conjunctival biopsy in patients with suspected ocular cicatricial pemphigoid.

BACKGROUND: Ocular cicatricial pemphigoid is a chronic, progressive, autoimmune disease that scars mucous membranes and may lead to blindness. It is of critical importance to be able to make the diagnosis as early as possible to allow early treatment. Conjunctival biopsy facilitates the early diagnosis of this condition. MATERIALS AND METHODS: Conjunctival biopsy results of 166 consecutive patients seen over a 7-year period, in whom the diagnosis of ocular cicatricial pemphigoid was considered, were reviewed. RESULTS: One hundred twenty-one patients ultimately received a diagnosis of ocular cicatricial pemphigoid. Immunofluorescence studies demonstrated characteristic deposition of immunoreactants at the epithelial basement membrane zone in 63 patients (sensitivity = 52%). When immunofluorescent-negative or inconclusive biopsies were processed further using an immunoperoxidase technique an additional 37 diagnoses were made. This represented an increase in sensitivity from 52% with immunofluorescence only to 83% with the addition of the immunoperoxidase technique. CONCLUSION: The routine use of the immunoperoxidase technique in immunofluorescent-negative biopsies, allied with appropriate harvesting and handling of biopsied conjunctiva, should significantly increase the diagnostic yield in patients with clinically suspect ocular cicatricial pemphigoid.

Adult↗

Scleritis associated with systemic vasculitic diseases.

PURPOSE: Scleritis may occur associated with systemic vasculitic diseases. The detection of systemic vasculitic diseases in patients with scleritis is a sign of poor general prognosis because it indicates potentially lethal systemic complications. This study was undertaken to analyze the ocular prognosis of patients with scleritis and the different systemic vasculitic diseases. METHODS: Patient characteristics, scleritis type, and ocular complications were evaluated in 82 patients with scleritis with systemic vasculitic diseases; comparisons were made between patients with scleritis with a specific systemic vasculitic diseases and patients with scleritis with the other systemic vasculitic diseases. RESULTS: Patients with scleritis with Wegener granulomatosis had more necrotizing scleritis (79%, P = 0.0001), decrease in vision (79%, P = 0.014), and peripheral ulcerative keratitis (50%, P = 0.0139) than patients with scleritis with the other systemic vasculitic diseases. Patients with scleritis with spondyloarthropathies had less decrease in vision (8%, P = 0.001) and peripheral ulcerative keratitis (0%, P = 0.0256) than patients with scleritis with the other systemic vasculitic diseases. Patients with scleritis and systemic lupus erythematosus had less necrotizing scleritis (0%, P = 0.0412) than patients with scleritis with the other systemic vasculitic diseases. CONCLUSIONS: Ocular prognosis of scleritis with systemic vasculitic diseases varies depending on the specific systemic vasculitic diseases: scleritis in spondyloarthropathies or in systemic lupus erythematosus is usually a benign and self-limiting condition, whereas scleritis in Wegener granulomatosis is a severe disease that can lead to permanent blindness; scleritis in rheumatoid arthritis or relapsing polychondritis is a disease of intermediate severity, which should be monitored closely for the development of ocular complications.

Adolescent↗

Penetrating keratoplasty in cicatrizing conjunctival diseases.

PURPOSE: The outcome of successful penetrating keratoplasty (PK) typically is poor in eyes with end-stage chronic cicatrizing conjunctival diseases such as ocular cicatricial pemphigoid (OCP), Stevens-Johnson syndrome, and toxic epidermal necrolysis due to immunologically driven conjunctival inflammation associated with conjunctival cicatrization and lid abnormalities, severe dry eye, and extensive corneal neovascularization. The authors report the results of their experience with PK in 13 patients with OCP, Stevens-Johnson syndrome, and toxic epidermal necrolysis. METHODS: The authors reviewed the records of patients with OCP, Stevens-Johnson syndrome, or toxic epidermal necrolysis seen between 1976 and 1992. Patients who underwent PK were examined for the purpose of this study. Initial and final visual acuity, indications for PK, surgical procedure, postoperative therapy, complications, total number of repeat PKs, length of follow-up, and the final outcome were recorded. RESULTS: Thirty-two PKs were performed in 16 eyes of 13 patients with advanced OCP (6 patients), OCP as a sequela of Stevens-Johnson syndrome (2 patients), Stevens-Johnson syndrome (3 patients), and toxic epidermal necrolysis (2 patients). The indications for the first PK were corneal perforation in six eyes (37.5%) and extensive corneal scarring in ten eyes (62.5%). Preoperative visual acuity was counting fingers in five eyes, hand motions in eight, and light perception in three. Preoperative therapy included systemic chemotherapy (8 patients), mucous membrane grafting (9 eyes), lamellar keratoplasty (2 eyes), superficial keratectomy (1 eye), and corneal dye laser photocoagulation (6 eyes). The mean follow-up period was 4.6 years (3 months-13 years). Eight eyes (50%) had clear grafts, and three eyes (18.7%) had 20/200 or better visual acuity at last visit. The major causes of graft failure were epithelial defect formation/persistence, stromal ulceration, perforation, and graft rejection. CONCLUSIONS: These results indicate that PK may be performed for tectonic reasons, but prospects for restoration of sight in patients with advanced cicatrizing conjunctival diseases, even after extensive preoperative medical and surgical therapy, are limited.

Adolescent↗

Disease relapse in patients with ocular manifestations of Wegener granulomatosis.

PURPOSE: To evaluate possible factors associated with disease relapse in patients with ocular manifestations of Wegener granulomatosis. METHODS: Eight patients with ocular manifestations of Wegener granulomatosis were longitudinally followed for a mean period of 34 months. Serial antineutrophil cytoplasmic antibody (ANCA) levels were determined on all patients. RESULTS: All eight patients had either scleritis alone or scleritis combined with peripheral ulcerative keratitis. Clinical disease remission was achieved in all patients using immunosuppressive chemotherapy. Five patients had subsequent relapse after treatment withdrawal. The serum ANCA level had failed to revert to normal during remission in four of the five patients who had had relapses. The ANCA levels for all three patients who remained in remission without therapy converted to normal. There was no significant difference in the initial serum ANCA level (P = 0.35) or the mean cumulative cyclophosphamide dose (P = 0.13) between those who had a relapse and those who did not. CONCLUSION: Failure of ANCA titers to revert to normal levels may be associated with the potential for relapse in patients with ocular manifestations of Wegener granulomatosis.

Adult↗

Immunisation against HSV-1 keratitis with a synthetic gD peptide.

The authors tested the protective efficacy of, and the immune response to, immunisation with a synthetic peptide of glycoprotein D (gD) of HSV-1 in a murine model of herpes stromal keratitis (HSK). HSV-1 susceptible A/J mice were immunised subcutaneously with a peptide corresponding to the N-terminal epitope gD(5-23) prior to corneal HSV-1 challenge. Divergent immunisation protocols were compared for their protective potency, their ability to prevent the establishment of latency in the trigeminal ganglion, and their effect on the immune system. Low dosages (31 micrograms) of gD(5-23) protected against encephalitis and HSK. Protective efficacy was higher when gD(5-23) was coupled to the carrier protein keyhole limpet haemocyanin (KLH) and was emulsified with adjuvant. Latent infection was found in all control mice but in only 50-75% of immunised mice. The most potent protection was correlated with anti-HSV-1 neutralising antibodies of IgG1 and IgG2a isotypes, but free gD(5-23) protected in the absence of anti-HSV-1 antibodies. Our results suggest that immunisation with gD(5-23) stimulates both humoral and cellular immune mechanisms which protect against HSV-1 keratitis.

Amino Acid Sequence↗