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Biomedical subjects

R J Epstein

Publications and source records attributed to R J Epstein.

At least 91 records · Page 5Linked to original sources
PubMed1988

Acanthamoeba keratitis. Potential role for topical clotrimazole in combination chemotherapy.

Clotrimazole is an antifungal agent that has been shown to have excellent in vitro activity against most strains of Acanthamoeba. We encountered four patients who developed Acanthamoeba keratitis while wearing contact lenses that had been stored in homemade saline. Their medical treatment regimens included the use of topical 1% clotrimazole. In two patients in whom conventional therapy failed, clotrimazole was successful in controlling recurrent infection following penetrating keratoplasty. Two other patients were treated with clotrimazole as well as propamidine isethionate and neomycin sulfate-polymyxin B sulfate-gramicidin from the outset, and had an excellent response to medical therapy. In those patients who found the commercially available cream uncomfortable, a 1% clotrimazole suspension formulated in artificial tears was used and found to be well tolerated.

Acanthamoeba↗
PubMed1988

Subpopulation analysis of drug-induced cell-cycle delay in human tumor cells using 90 degrees light scatter.

A mitotic cell subset has been identified with nuclear light scatter. Colcemid-treated T-47D human breast cancer cells were permeabilised, stained with ethidium bromide, and analysed by flow cytometry. Cells with G2M DNA content exhibited a unimodal distribution for DNA fluorescence and forward scatter, but two peaks were discernible with 90 degrees light scatter. A discrete low-scattering cell cluster could be distinguished from the G2 cell subset on two-dimensional contour plots of 90 degrees light scatter vs. DNA fluorescence; this cluster was reproduced by mitotic shake-off experiments and varied quantitatively with mitotic indices determined either by microscopy or by stathmokinetic cell-cycle analysis of DNA fluorescence. Cell sorting confirmed that the low-scattering cell cluster comprised predominantly metaphase and anaphase cells. Identification of mitotic cells with this one-step technique enables rapid analysis of drug-induced cell-cycle delay in cell populations with different rates of cell-cycle traverse. Hence, vincristine-induced cytostasis is shown to arise in part because of premitotic G2 arrest, whereas etoposide is shown to affect cycling cells with equal sensitivity in quiescent and activated cell populations. The use of light scatter to discriminate mitotic cells in this way facilitates analysis of drug-induced cell-cycle delay and supplements the information obtainable by conventional cell-cycle analysis.

Breast Neoplasms↗
PubMed1988

The correction of aphakia in infants with hydrogel extended-wear contact lenses. Corneal studies.

Although hydrogel extended-wear contact lenses (EWCLs) have been used extensively in the correction of aphakia in neonates, little is known about the effects of these lenses on infant corneas. Recent studies have demonstrated that long-term contact lenses can induce endothelial morphometric changes, including an increased coefficient of variation (CV) of mean endothelial cell area. Using wide-field specular microscopy, the authors studied 11 eyes of 10 patients, 1 to 3 years of age who, after lensectomy for congenital cataracts, wore EWCLs for the correction of aphakia. Except for two corneas in which increased pachometric readings and CV developed after repeated episodes of lens loss and inflammation, the EWCL were well tolerated and associated with few complications in this study.

Aphakia, Postcataract↗
PubMed1988

Characterisation of VP-16-induced DNA cleavage in oestrogen-stimulated human breast cancer cells.

Cycling cells are recognised to be more susceptible than quiescent cells to the cytotoxic action of many commonly used cancer chemotherapeutic agents. We have found that oestrogen stimulation of T-47D human breast cancer cells is accompanied by a two-fold increase in VP-16-induced DNA cleavage as measured by alkaline DNA unwinding, and that this increase in DNA cleavage is accompanied by a corresponding enhancement of drug-induced cytostasis. The enhancement of VP-16-induced DNA cleavage seen with oestrogen exposure is antagonised both by antioestrogen treatment and by cycloheximide, an inhibitor of protein synthesis, but not by the DNA synthesis inhibitor aphidicolin. Increased c-myc protein synthesis is detectable within an hour of oestrogen exposure, while increased VP-16-induced DNA cleavage is detectable within 4h and increased DNA synthesis within 16h. Only small changes in cell-cycle distribution occur with oestrogen stimulation. In the absence of VP-16, oestrogen does not reduce DNA double-strandedness, nor does it induce changes in chromatin structure as measured by alterations in DNA superhelicity or chromatin accessibility. These findings suggest that oestrogen enhances VP-16-induced DNA damage in asynchronously growing G1-phase cells and that this enhancement may be dependent at some point upon de novo protein synthesis. Oestrogen pre-treatment of T-47D human breast cancer cells improves the therapeutic index of VP-16 without the need for cell synchronisation or highly precise drug scheduling.

Breast Neoplasms↗
PubMed1987

Penetrating keratoplasty for herpes simplex keratitis and keratoconus. Allograft rejection and survival.

To determine the relationship between corneal allograft rejection and failure, we studied patients who underwent penetrating keratoplasty for herpes simplex keratitis (n = 82) and keratoconus (n = 345), two frequent indications for keratoplasty in young patients, using survival analysis. For first grafts for herpes, the probability of survival was significantly less than it was for keratoconus (P less than 0.0001). For second grafts, this difference was less pronounced, and for three or more grafts, the difference in survival was not significant. The incidence of rejection episodes was similar in first grafts for herpes (16.6%) and keratoconus (18.5%) (P greater than 0.05). However, the incidence of rejection episodes in regrafts for herpes was significantly greater than in keratoconus (23.7 versus 17%, P less than 0.01). The incidence of failure after rejection episodes (first grafts and regrafts combined) was significantly greater in grafts for herpes (52.4 versus 16.2%, P less than 0.001). Because survival after multiple regrafts in both groups is poor, additional measures, such as tissue matching, may be necessary to improve the likelihood of success in these high-risk cases.

Adolescent↗
PubMed1987

Survival of corneal grafts from donors supported by mechanical ventilation.

Eighty-five patients undergoing penetrating keratoplasty with tissue from donors supported by mechanical ventilation (Ventilator group) were compared to a surgeon- and diagnosis-matched group (Control group). Age at surgery, duration of follow-up, and sex of recipient patients were similar in the two groups. The mean donor age in the Ventilator group (26.4 years) was significantly less than in the Control group (45.8 years, P less than 0.0001). Mean time on the ventilator was 99.4 hours (range, 4 hours to 21 days). Overall graft survival rates in the Ventilator and Control groups were similar (P greater than or equal to 0.72). Time on the ventilator did not affect graft survival. Cultures of corneoscleral donor rims were positive more often in the Ventilator group than in Controls (39.7 versus 23.1%), but the difference was not significant (P = 0.09). Prolonged ventilator time was not associated with a higher rate of positive corneoscleral rim cultures, nor did positive cultures affect graft survival. The most common cause of graft failure in both groups was allograft rejection. In no case could postoperative bacterial infection be attributed to contamination of the donor material. One case of primary donor failure occurred in the Ventilator group, but the incidence (1.2%) is similar to that of previously reported studies. The data indicate that corneal tissue from ventilator-supported donors should be considered for use in penetrating keratoplasty.

Adolescent↗
PubMed1987

Corneal neovascularization. Pathogenesis and inhibition.

Corneal neovascularization (CNV) can cause significant visual loss because of the scarring and lipid deposition that frequently accompany it. In addition, penetrating keratoplasty in a vascularized recipient carries a significant risk of failure from allograft rejection. Frequently CNV is induced by nonspecific inflammatory stimuli, mediated primarily by polymorphonuclear neutrophils. Neovascularization can also be associated with specific corneal immune reactions, such as herpes simplex keratitis. Immunologically mediated CNV may be more amenable to treatment than CNV that results from nonspecific inflammation. Photodynamic therapy (PDT) following the intravenous injection of hematoporphyrin derivative or purified dihematoporphyrin ether (DHE) has been shown to suppress tumor growth and blood vessel growth in the eye. We have developed a murine model of CNV induced by the intrastromal injection of stimulated lymphocytes or interleukin-2 (IL-2). We have noted corneal DHE retention following its intravenous injection in mice with IL-2 induced CNV. Preliminary studies indicate that PDT can induce regression of CNV in these mice. Other recent studies that have enhanced our understanding of the pathogenesis and treatment of CNV are reviewed, and directions for future research are discussed.

Animals↗
PubMed1987

HSV-induced blastogenesis in splenic mononuclear cells from inbred mice.

The severity of HSV stromal keratitis varies among inbred mouse strains, with A/J and BALB/c greater than C57BL/6. Since cell-mediated immunity (CMI) is thought to play a role in the pathogenesis of HSV stromal keratitis, we measured the proliferative response of primed splenic mononuclear cells (SMC) from these strains to HSV antigen in vitro. Primed SMC from all three strains showed increased thymidine uptake after incubation with UV-inactivated HSV-1 antigen (UV-HSV) in vitro when compared with control antigen. Uptake by SMC from BALB/c and A/J mice was greater than that by SMC from C57BL/6 mice. The difference between BALB/c and A/J was not significant. Uptake by non-primed SMC cultured with UV-HSV was not significantly greater than uptake induced by control antigen. Thus, among the strains studied, A/J and BALB/c mice, which are relatively susceptible to stromal keratitis, have the greatest proliferative response to UV-HSV antigen. C57BL/6 mice, which are relatively resistant to stromal keratitis, have the least response. These findings suggest that genetically determined differences in CMI may influence the course of HSV keratitis and are consistent with the hypothesis that the host immune response plays a role in the pathogenesis of HSV stromal keratitis.

Animals↗
PubMed1987

Corneal neovascularization induced by stimulated lymphocytes in inbred mice.

The intrastromal implantation of Concanavalin A-stimulated allogeneic lymphocytes induced corneal neovascularization (CNV) in inbred C57BL/6 and BALB/c mice. Control syngeneic stimulated, allogeneic non-stimulated, and allogeneic stimulated irradiated lymphocytes were not angiogenic. CNV induced by allogeneic stimulated lymphocytes in BALB/c recipients was significantly greater than in C57BL/6 recipients. This response reflected host-versus-graft reactivity, since parental recipients responded to F1 hybrid donors, while F1 hybrids did not respond to parental donors. The ability of stimulated lymphocytes to induce CNV may be important in allograft rejection, herpes simplex keratitis, and other corneal immune reactions. The mouse cornea is an excellent model for studying immunologically mediated neovascularization under genetically controlled conditions.

Animals↗
PubMed1987

Acanthamoeba keratitis. A growing problem in soft and hard contact lens wearers.

Eleven contact lens-wearing patients presented with Acanthamoeba keratitis. Eight cases were culture- and/or stain-positive for Acanthamoeba and three were presumed to have Acanthamoeba keratitis based on history and clinical findings. Six wore daily wear soft contact lenses, two wore extended-wear soft contact lenses, one wore a polymethylmethacrylate hard contact lens, one wore a gas-permeable hard contact lens, and one wore a Saturn lens (combined hard and soft lens). Four patients used distilled water and salt tablet saline, three used tap water and salt tablet saline, two used tap water rinse, two used well water rinse or storage, and one used intravenous (IV) saline. It is apparent that all contact lens wearers are at some risk for Acanthamoeba keratitis developing if proper contact lens care is not maintained. Of great concern is the inability of most current chemical sterilization methods to kill the organism if the lens becomes contaminated. Heat disinfection will kill Acanthamoeba trophozoites and cysts but the lens must not be placed into contaminated solutions afterward. Prevention is very important because medical and surgical treatment failures are frequent. Eye care practitioners who fit contact lenses are advised to use heat disinfection for low-water content stock soft contact lenses, and to use hydrogen peroxide without a catalyst for a minimum of 6 hours for all other stock lens fitting sets, to specifically inquire about contact lens care habits used by their patients, and to discourage the use of homemade saline solutions.

Acanthamoeba↗
PubMed1986

Is your initiator really necessary?

There is little hard evidence for the involvement of specific genotoxic initiators in the pathogenesis of the common carcinoma. Recent findings suggest that sporadic carcinogenesis is a dynamic and probabilistic process which requires a critical mass of abnormal cells for its expression, and that this requirement may distinguish the evolution of carcinomas from that of paediatric or haematologic malignancies. The proposal that specific carcinogens are neither necessary nor sufficient for tumourigenesis is consistent with the growing realization that aberrant expression of specific oncogenes is neither necessary nor sufficient for cellular transformation. These new perspectives have major implications for basic research strategy and public health policy.

Carcinogens↗
PubMed1986

Rapid diagnosis of Acanthamoeba keratitis from corneal scrapings using indirect fluorescent antibody staining.

Two soft contact lens wearers using a homemade saline solution developed corneal stromal inflammation and epithelial ulceration and were both treated for months with a presumptive diagnosis of herpes simplex keratitis. Subsequently, corneal scrapings revealed refractile, cystic structures consistent with the appearance of Acanthamoeba. This was rapidly confirmed by indirect fluorescent antibody studies, and Acanthamoeba castellani was later identified by growth in culture in both cases. Acanthamoeba is being reported with increasing frequency as a pathogen responsible for chronic stromal keratitis and ulceration in contact lens wearers. Since specific therapy is required to control this organism, rapid diagnosis is essential. Indirect fluorescent antibody staining of corneal scrapings provides a simple means of accomplishing this goal with a high degree of accuracy.

Adolescent↗
PubMed1986

Extended-wear contact lens correction of aphakia in infant primates. Corneal studies.

Extended-wear contact lenses (EWCL) are being used increasingly for the correction of aphakia in infants, but there is a lack of data documenting their effects on the corneas of young children. Therefore, corneal studies were performed on infant monkeys wearing EWCL for the correction of surgical aphakia. Nine newborn monkeys underwent unilateral lensectomy and anterior vitrectomy. Seven eyes were fitted with aphakic EWCL postoperatively and two wore no lenses. After at least six months, corneas were studied with slit-lamp and specular microscopy, and with light microscopy (LM) and electron microscopy (EM). Small central corneal opacities developed in two aphakic eyes corrected with EWCL after episodes of keratoconjunctivitis. One of these corneas was found to have a mildly increased coefficient of variation (CV) of endothelial cell size (polymegathism). Although EWCL are well tolerated by the corneas of aphakic infant primates, their association with endothelial polymegathism, which may indicate physiologic compromise, mandates careful long-term follow-up.

Animals↗
PubMed1985

Infantile complete heart block associated with maternal Ro(SS-A) ribonucleoprotein autoantibodies: report of two cases.

Two cases of congenital complete heart block arising during pregnancy were observed in association with a circulating maternal autoantibody to the soluble ribonucleoprotein Ro(SS-A). Neither mother had clinical evidence of Sjögren's syndrome or systemic lupus erythematosus usually associated with anti-Ro. However, both had a previous history of first-trimester abortion and laboratory evidence of autoimmunity, and one gave a history of sialadenitis. Maternal anti-Ro antibodies may be predictive of infantile heart block when present in pregnant women with overt or suspected multisystem autoimmune disease.

Adult↗
PubMed1985

Idiopathic myelofibrosis complicated by lymphoma. Report of two cases.

2 cases of diffuse large-cell non-Hodgkin's lymphoma developing in conjunction with idiopathic myelofibrosis are described. In neither case could any predisposition to neoplastic transformation be discerned. The possible pathogenetic implications of this association are discussed, and a brief literature review of the relationship between myeloproliferative and lymphoproliferative disease is presented.

Adult↗