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Biomedical subjects

C S Foster

Publications and source records attributed to C S Foster.

At least 361 records · Page 20Linked to original sources
PubMed1989

Gross factors in treatment of nonhealing corneal ulcers and recurrent erosions.

Epidermal growth factor (EGF) is known to promote corneal epithelial wound healing in experimental scrape and keratectomy models. We studied its efficacy in treating alkali-burned epithelial ulceration. EGF induced hyperplasia and cell proliferation to resurface the denuded and denatured corneal stroma, but it did not prevent recurrent erosions. A combination of EGF with fibronectin (Fn) was noted to enhance epithelial defect closure after alkali burns of the cornea and was seen to prevent recurrent erosions. Histopathologic examination of these corneas revealed marked leukocytic infiltration of the alkali-burned corneal stroma. To find ways to retard this inflammatory response, we studied the role of topical steroids and their efficacy when used with EGF, Fn, and laminin (Ln) in the management of alkali-burned corneas. Use of steroids decreased the incidence of recurrent erosions and corneal perforations. Histologically, steroids markedly decreased the leukocytic infiltration of stromal tissue, thereby retarding the collagenolysis. Topical steroids used with EGF and fibronectin were seen to promote epithelial wound closure and to prevent recurrent erosions in alkali-burned corneas. Combinations of EGF, fibronectin, and steroids may have a place in the treatment of clinical corneal alkali burns.

Adrenal Cortex Hormones↗
PubMed1989

Role of fibronectin and fibrinogen in healing of corneal epithelial scrape wounds.

A provisional fibronectin (Fn)-fibrinogen (Fg) matrix forms de novo on the bare basement membrane (BM) surface of superficial epithelial scrape wounds in rabbit and guinea pig (GP) corneas. We determined whether such a substrate is essential for epithelial cell adhesion and migration, using three different approaches. (1) Polyclonal and monoclonal IgG reactive against GP Fn were topically administered to inhibit Fn formation in a GP epithelial scrape wound model. Immunofluorescence studies showed that deposition of both Fn and Fg was inhibited in antibody-treated corneas. During the first 38 hr after wounding, the healing rates were 0.46 +/- 0.06 mm2/hr in control eyes, 0.43 +/- 0.05 mm2/hr in those treated with rabbit polyclonal IgG anti-GP Fn and 0.45 +/- 0.09 mm2/hr in those treated with murine monoclonal IgG anti-GP Fn (P greater than 0.4). (2) In a rabbit epithelial scrape wound model, ancrod was administered intravenously to induce systemic Fg depletion. Fg deposition was completely inhibited on the wound surface, but Fn deposition was not suppressed. The healing rate was 1.24 +/- 0.41 mm2/hr in ancrod-treated corneal wounds and 1.19 +/- 0.29 mm2/hr in control eyes during the first 48 hr after wounding (P greater than 0.5). These data from the antibody and ancrod inhibition indicate that Fg binds to Fn and that Fn binds to components other than Fg.(ABSTRACT TRUNCATED AT 250 WORDS)

Ancrod↗
PubMed1989

Role of fibronectin in the healing of superficial keratectomies in vitro.

A fibronectin (Fn)-fibrinogen (Fg) surface matrix is not essential for epithelial cell migration in a corneal epithelial scrape wound model, in which the basement membrane is preserved. We have therefore tested whether such a provisional scaffolding becomes more critical in a superficial keratectomy model, when the basement membrane is surgically removed. Exogeneous Fn at 0.3 mg/ml was added to the medium of organ cultures of rabbit superficial keratectomies. At 48 hr after wounding, the healing rate was 1.12 +/- 0.03 mm2/hr in control corneas and 1.11 +/- 0.03 mm2/hr in those cultured with Fn. At 64 hr after wounding, the healing rates were also not significantly different (P greater than 0.5). Immunofluorescence studies showed that Fn was not detectable on the surface of control corneas but could be depicted under the migrating epithelium. In corneas cultured with Fn, it diffused throughout the entire stroma but did not deposit as a surface matrix. We therefore attempted to obtain formation of a provisional Fn-Fg surface matrix before establishment of the in vitro organ culture by leaving the superficial keratectomies in vivo for 8 hr, 24 hr or 64 hr. At 64 hr after wounding, their healing rate was 0.80 +/- 0.04 mm2/hr, 0.86 +/- 0.04 mm2/hr and 0.85 +/- 0.06 mm2/hr, respectively, which were not significantly different from that of contralateral ex vivo-wounded cultured corneas (0.83 +/- 0.04 mm2/hr, P greater than 0.5). Immunofluorescence studies revealed a Fn matrix on the bare surface of in vivo-wounded specimen, which was not detectable on ex vivo-wounded cultured corneas; there was also no diffuse stromal Fn.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Corneal infection in mucosal scarring disorders and Sjögren's syndrome.

We reviewed 69 episodes of microbial keratitis occurring over an 11-year period in 56 patients with a mucosal scarring disorder or Sjögren's syndrome. Gram-positive bacterial isolates were the most common cause of infection, and accounted for almost all cases in patients with Sjögren's syndrome. Trichiasis (cicatricial pemphigoid), topical corticosteroids, bandage contact lenses, and corneal surgery were the main predisposing factors in the development of the corneal infection. In patients with ocular cicatricial pemphigoid, infection was much less common after chemotherapeutic control had been achieved. Recurrent infections were relatively frequent. There was a high rate of major complications, particularly in microbial keratitis complicating Sjögren's syndrome.

Adolescent↗
PubMed1988

Detection of ocular mucus in normal human conjunctiva and conjunctiva from patients with cicatricial pemphigoid using lectin probes and histochemical techniques.

Conjunctival biopsies from patients with cicatricial pemphigoid affecting the conjunctiva and patients undergoing cataract surgery (normal conjunctiva) were snap-frozen, cryostat sectioned and incubated with fluorescein-conjugated lectins; peanut agglutinin (PNA), Helix pomatia agglutinin (HPA), soybean agglutinin (SBA), wheat germ agglutinin (WGA) and succinylated wheat germ agglutinin (S-WGA). Controls consisted of preincubating the lectins with the appropriate blocking sugars before applying the lectins to the sections. PNA and HPA stained the mucus granules contained in the conjunctival goblet cells but did not stain mucus or glycocalyx at the ocular surface distal to the goblet cells. Native WGA and S-WGA had high affinities for conjunctival goblet cells and the apical epithelial cell layers. Native WGA stained mucus and glycocalyx at the ocular surface. This staining of the ocular surface by WGA was confirmed at the transmission electron microscopic level using WGA conjugated to ferritin. Cicatricial pemphigoid patients in this study had reduced numbers of goblet cells; however, those goblet cells which were observed in cicatricial pemphigoid conjunctiva stained positively with HPA, PNA, WGA, and SWGA as did goblet cells in normal conjunctiva.

Conjunctiva↗
PubMed1988

Microbial keratitis complicating penetrating keratoplasty.

A retrospective review of 68 consecutive episodes of microbial keratitis complicating 66 penetrating keratoplasties (PKs) showed major risk associations: suture-related problems (50%), contact lens wear (26%), previous herpes simplex infection (15%), graft failure (15%), and persistent epithelial defects (15%). Topical steroid (85%) and antibiotic (59%) usage were common iatrogenic factors. Half the infections occurred more than 1 year after grafting. Bacterial infections involving gram-positive organisms (59%) predominated, except for patients with extended-wear hydrophilic contact lenses, which usually involved gram-negative bacilli. The incidence of fungal infections (6%) was relatively low. Recommendations to minimize microbial keratitis include prompt attention to exposed, broken, or loose sutures, and preventive and therapeutic management of epithelial defects. The inadequacy of low-dose antibiotics in precluding microbial infection in many cases and the propensity to develop infections with resistant organisms suggest that guidelines for using postoperative and prophylactic topical antibiotics require reevaluation.

Corneal Transplantation↗
PubMed1988

Mitomycin eye drops as treatment for pterygium.

The authors used an antineoplastic-antibiotic agent, mitomycin, in the form of eye drops as adjunctive treatment for primary and recurrent pterygia after surgical excision. Sixteen primary and four recurrent pterygia were treated with 1.0 mg/ml mitomycin eye drops, 14 primary and 10 recurrent pterygia were treated with 0.4 mg/ml mitomycin eye drops, and 18 primary pterygia were treated with placebo eye drops. Postoperative follow-up for the eyes treated with mitomycin eye drops ranged from 3 to 34 weeks (mean, 23 weeks). One of 44 pterygia treated with mitomycin recurred after 5 months (recurrence rate, 2.3%), whereas 16 of 18 primary pterygia treated with placebo eye drops developed postoperative granulomas and recurrent pterygia with a mean postoperative period of 6 weeks (recurrence rate, 88.9%). Topical mitomycin (1.0 mg/ml) caused conjunctival irritation, excessive lacrimation, and mild superficial punctate keratitis. These topical side effects were minimized with the 0.4 mg/ml mitomycin dosage. No systemic toxicity was noted with either dosage. The authors believe that mitomycin eye drops is a safe and effective adjunct to surgical excision in the treatment of primary or recurrent pterygia, or both.

Adolescent↗
PubMed1988

Cataract surgery in ocular cicatricial pemphigoid.

The authors report the results of their experience with cataract surgery in 20 patients (26 eyes) with biopsy-proven cicatricial pemphigoid. All patients were on systemic immunosuppression at the time of surgery (dapsone, azathioprine, cyclophosphamide, or combinations) and were treated with perioperative oral corticosteroids. Patients were evaluated pre- and postoperatively for conjunctival inflammation, conjunctival cicatrization, degree of keratopathy, and disease stage. No patient progressed in disease stage. Vision improved an average of 3.5 Snellen lines (-3 to +8). Worse outcome was associated with chemotherapy intolerance or the presence of any preoperative conjunctival inflammation. Thirteen patients remained on immunosuppressives for the entire study. Corneal ulcers developed postoperatively in three patients in whom continued immunosuppression was not tolerated. Possible mechanisms for inflammatory exacerbation after surgery are discussed. Results indicate that after successful abolition of all conjunctival inflammation through chemotherapy, cataract surgery may be safely performed in patients with cicatricial pemphigoid.

Aged↗
PubMed1988

Episodic conjunctival inflammation after Stevens-Johnson syndrome.

The authors studied the histopathologic, ultrastructural, and immunopathologic characteristics of conjunctiva from patients with Stevens-Johnson syndrome (SJS). A small subset of SJS patients with recurrent conjunctival inflammation unassociated with external factors such as lid margin keratinization, sicca syndrome, trichiasis, or entropion was identified. The ultrastructural and immunopathologic characteristics of the conjunctiva from these patients were distinctly different from those of the conjunctiva from SJS patients without recurrent conjunctivitis, and suggested an active, immunologically mediated inflammation. Vasculitis or perivasculitis, immunoreactant deposition in vessel walls, vascular basement membrane disruption, thickening, and reduplication, and a preponderance of helper T-lymphocytes, macrophages, and Langerhans' cells were the notable distinguishing features in those patients with recurrent conjunctival inflammation. This rare clinical syndrome may represent the ocular counterpart to recurrent dermal or oral mucosal erythema multiforme.

Adolescent↗
PubMed1988

Evaluation of topical cromolyn sodium in the treatment of vernal keratoconjunctivitis.

A randomized, double-masked, placebo-controlled multicenter study was conducted for 6 weeks in 12 centers to evaluate the efficacy and safety of cromolyn sodium 4% ophthalmic solution (Opticrom) for the treatment of active bilateral vernal conjunctivitis. Objective clinical signs were graded weekly by an ophthalmologist while patients kept a daily record of the severity of their symptoms. Sixty-five patients completed the study; 35 received cromolyn sodium and 30 were treated with a matching placebo (the drug vehicle). Statistically significant differences in favor of cromolyn sodium treatment were found for conjunctival injection, limbal injection, limbal edema, tearing, and symptoms summary score. There were few side effects (usually mild stinging and burning which did not require drug stoppage). Only one patient required drug discontinuation for possible drug- or vehicle-related side effects. Cromolyn sodium was found to be significantly more effective than placebo in treating the signs and symptoms of vernal keratoconjunctivitis (VKC). When results were stratified in terms of the atopic status of the patient, it was clear that the allergic patients responded better to cromolyn sodium than did those in whom allergic (IgE-mediated) factors appeared unimportant in the disease process.

Adolescent↗
PubMed1988

Immunomodulation of experimental murine herpes simplex keratitis: I. UV-HSV protection.

A/J mice were immunized subcutaneously with ultraviolet light (UV) inactivated herpes simplex virus type-1, MP strain (HSV-MP). Control A/J mice were immunized subcutaneously either with media (unimmunized controls) or with live HSV-MP (immunized controls). Immunized and control mice were challenged ocularly with either MP or mP strain HSV-1 after corneal scarification and were followed for 3 weeks post corneal challenge. The mice were observed during this time period for signs of herpes simplex keratitis (HSK), lid lesions and encephalitis. At the time of sacrifice, the ipsilateral trigeminal ganglia were removed and assayed for latent HSV-1 using cocultivation on Vero cell monolayers. The results of these studies demonstrated that immunization with UV inactivated HSV (UV-HSV) gave the same protection against keratitis and encephalitis as immunization with live virus. Furthermore, the cocultivation assays indicated that immunization with either live HSV-1 or UV inactivated HSV-1 protected against the establishment of latency.

Animals↗
PubMed1988

Immunomodulation of experimental murine herpes simplex keratitis: II. Glycoprotein D protection.

Subcutaneous immunization with purified HSV-1 glycoprotein D (gD) protects susceptible A/J mice against keratitis and encephalitis following corneal HSV-1 challenge. Mice were immunized with gD, in complete Freund's adjuvant, 3.0 micrograms/mouse followed by two booster doses of 1.5 micrograms/mouse at weeks 2 and 4. Control groups of A/J mice were injected with either complete Freund's adjuvant (unimmunized controls) or live HSV-1 MP strain (immunized controls). All mice were challenged ocularly at week 5 with HSV-1, F strain (6.5 x 10(3) PFU) after corneal scarification. None of the 16 animals immunized with gD developed stromal keratitis; only 3 out of 12 animals immunized with live HSV-1 developed a stromal keratitis; 13 out of 16 CFA primed unimmunized mice developed severe stromal keratitis within 14 days post corneal challenge, and 3 out of 16 control CFA primed animals died within 16 days post corneal challenge. At the time of sacrifice (3 weeks post corneal challenge), the ipsilateral trigeminal ganglia were removed and assayed for latent HSV-1 using cocultivation on Vero cell monolayers. The results of these experiments indicate that immunization with gD produces protection against latent ganglionic infection in 56% of the immunized animals, and provides protection against keratitis and death following HSV corneal challenge.

Animals↗
PubMed1988

Passive transfer of anti-HSV-1 IgG protects against stromal keratitis in mice.

Cellular immune mechanisms are felt to play a primary role in modulating responses to herpes simplex virus (HSV) infections, but the role of anti-HSV antibody is less clear. We first investigated the effects of passive transfer of murine serum containing anti-HSV antibody and then fractionated IgG subclasses on the development of HSV stromal keratitis in mice. Both immune sera and fractionated IgG's from these sera were effective in preventing stromal keratitis in susceptible mice. Non-IgG immunoglobulins and other serum proteins are unnecessary and inadequate in transferring protection; transfer of sera depleted of IgG had no influence on the development of keratitis. These results suggest an important role for anti-HSV antibody in modulating destructive corneal responses to HSV.

Animals↗
PubMed1988

Ganglionic permissivity to HSV-1 replication and acyclovir-induced latency: an in vitro model.

HSV-1 is known to establish latent infections in murine trigeminal ganglia. In order to study the genetic influence of the host on permissivity to HSV-1 replication and latency in mouse trigeminal ganglia, an in vitro culture system was developed. Ganglia from HSV sensitive A/J and resistant C57BL/6J mice were harvested and inoculated in vitro with either MP or KOS strains of HSV-1. Infected ganglia were placed in culture for 7 days with or without 150 micrograms/ml acyclovir. Ganglia were then homogenized and assayed for infectious particles or frozen whole for standard immunostaining. A/J ganglia without acyclovir consistently demonstrated a three-fold higher viral replication compared to C57BL/6J ganglia without acyclovir for both MP and KOS. Indirect immunofluorescent staining of actively infected ganglia using rabbit anti-HSV antiserum showed increased staining in A/J ganglionic axons compared to C57BL/6J ganglionic axons. Ganglia from both murine strains showed total suppression of viral replication with acyclovir treatment. Immunostaining for latent viral protein with mouse monoclonal anti-ICP-4 (VP 175) was positive for both A/J and C57BL/6J strains following acyclovir treatment. Desuppression of acyclovir-treated whole ganglia resulted in 54% spontaneous HSV reactivation. These results suggest that: (1) HSV-1 can establish an active infection in whole murine trigeminal ganglia in vitro; (2) HSV-1 replicates to a greater extent in A/J ganglia compared to C57BL/6 ganglia; and (3) in vitro HSV-1 ganglionic infection in both murine strains is equally suppressed to a latent state by acyclovir treatment.

Acyclovir↗
PubMed1988

Ocular Capnocytophaga infection in an edentulous, immunocompetent host.

Severe microbial keratitis developed in a 74-year-old women receiving long-term corticosteroids. Corneal smears revealed slender, fusiform gram-negative bacilli, but the lesion continued to worsen despite intensive antibiotic treatment. After several days, Capnocytophaga sputigena was identified on culture. Specific antimicrobial therapy was instituted, supplemented with corneal cryotherapy. There was gradual clinical improvement. However, a sterile corneal melt led to the late loss of the eye. Although Capnocytophaga are gingival organisms and usually implicated as opportunists in severely ill, neutropenic patients with oral ulcerations, our patient was edentulous and without systemic immunosuppression. An increased awareness of Capnocytophaga is justified because of their widespread antibiotic resistance, capnophilic cultural requirements, and unusual microscopic and cultural morphology.

Aged↗
PubMed1988

Immunogenetic influence of Igh-1 phenotype on experimental herpes simplex virus type-1 corneal infection.

Patterns of herpes simplex virus type-1 (HSV-1) infection were studied in BALB/c congenic, Igh-1 disparate murine strains to establish the influence of Igh-1 phenotype on the development of keratopathy, trigeminal ganglionic latency and keratocyte permissivity. Eighty-two percent of C.AL-20 (Igh-1d) mice, 40% of BALB/cByJ (Igh-1a) mice and 12% of the C.B-17 (Igh-1b) mice developed herpes simplex keratitis (HSK) following corneal challenge with 2.5 X 10(4) PFU HSV-1 strain KOS. While disease frequency was directly proportional to HSV-1 challenge dose, relative resistance and susceptibility patterns in the congenic mice were constant and highly significant. F1 progeny from C.AL-20 X C.B-17 matings demonstrated the HSK pattern of the C.B-17 parent suggesting that Igh-1 linked resistance to HSK is dominantly inherited. Equivalent trigeminal ganglionic latency was established following ocular HSV-1 inoculation in the three congenic Igh-1 disparate murine strains. Cultured keratocytes from the three Igh-1 disparate murine strains demonstrated equivalent in vitro permissivity to HSV-1 replication. These data illustrate a strong correlation between Igh-1 phenotype and the development of a HSK in congenic mice. The susceptibility/resistance to HSK in these mice is unrelated to trigeminal ganglionic latency or keratocyte permissivity.

Animals↗