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R R Tamesis

Publications and source records attributed to R R Tamesis.

7 recordsLinked to original sources

Efficacy and adverse effects of medications used in the treatment of glaucoma.

With the advent of several new topically active medications for glaucoma therapy, intraocular pressure (IOP) can be reduced to target levels in more patients before resorting to surgery. Some of these newer agents have a number of advantages over some of the older medications, several of which are seldom used now. The topically active carbonic anhydrase inhibitors are better tolerated than oral formulations, which are infrequently used despite their greater efficacy compared with the topical formulations. The alpha2-adrenergic agonists effectively reduce IOP with few systemic adverse effects. The prostaglandin analogues are even more effective and well tolerated when applied once daily without known systemic adverse effects. The variety of glaucoma medications forces the physician to be selective with various combinations before proceeding with surgery. This article critically reviews the literature pertaining to the newer glaucoma medications, thereby providing guidelines to make rational choices from among the available options.

Adjuvants, Pharmaceutic↗

Systemic drug toxicity trends in immunosuppressive therapy of immune and inflammatory ocular disease.

PURPOSE: To compare the relative toxicities of six systemic immunosuppressive drugs and systemic corticosteroids used to treat patients with severe ocular inflammatory disease and to identify factors influencing their occurrence. METHODS: The authors reviewed the clinical records of 602 patients with ocular inflammatory disease treated with immunosuppressive drug therapy and/or systemic corticosteroids for adverse systemic effects while undergoing therapy. Proportional hazards regression analysis was performed to identify demographic and clinical factors that influence the occurrence of drug toxicity in these patients. RESULTS: Immunosuppressive drug treatment was more likely to result in discontinuation of therapy because of toxic side effects than was corticosteroid treatment. However, unlike many of the side effects of corticosteroid treatment, the side effects of immunosuppressive therapy were reversible with reduction in dosage or discontinuation of the drug. Gastrointestinal symptoms and hematologic abnormalities accounted for the majority of reported side effects of the immunosuppressive medications. Neuro-psychiatric and endocrine side effects were common in patients taking prednisone. In 17 patients treated with prednisone, pathologic fractures developed, which involved the hips and the spine. Female sex and age older than 60 years also were identified as factors associated with intolerance to drug therapy in the authors' study population. Race and type of systemic ocular disease were not significant factors influencing tolerance to drug therapy. CONCLUSION: These findings suggest that when properly administered and monitored for adverse effects, most immunosuppressive agents used in the current study have similar risk profiles with relatively few serious therapeutic mishaps and largely reversible side effects. In contrast, corticosteroids can result in permanent disabilities as a result of long-term treatment.

Adult↗

The role of natural killer cells in the development of herpes simplex virus type 1 induced stromal keratitis in mice.

Natural killer (NK) cells and acquired cell-mediated immunity effector cells (delayed type hypersensitivity (DTH) and cytotoxic T lymphocytes (CTL)) have been reported to play a vital role in the defence of the host against tumour and viral infections in locations other than the eye. A vigorous cellular inflammatory response to viral infections of the cornea, however, with the attendant damage to the corneal clarity, has obvious evolutionary disadvantages, and a substantial body of evidence indicates that in animals (e.g. mice) which are highly susceptible to inflammatory destruction of the cornea following corneal encounter with herpes simplex virus, it is the animal's immunological/inflammatory response which is responsible for the corneal damage. We examined the role of natural killer cells in the development of herpes stromal keratitis (HSK) in NK-deficient (C57BL/6J-bgj (beige)) mice and their NK-competent (C57BL/6J (black) relatives. The beige (NK-deficient) mice were just as resistant to HSK as were the black mice. We also studied the effects of NK cell depletion of BALB/c Igh-1 disparate congenic mice. C.AL-20 (Igh-1d) mice are ordinarily highly susceptible to necrotising HSK. In vivo NK-cell depletion in these mice significantly decreased the incidence and severity of HSK in these animals (p < 0.0005). Corneas from untreated C.AL-20 mice contained T cells, macrophages and NK cells. The corneal infiltrate from NK-depleted C.AL-20 mice consisted of T cells and macrophages but no NK cells. These data indicate that NK cells are participants in the development of HSK in the murine model of this disease.

3T3 Cells↗

Antibody-dependent cellular cytotoxicity against cells infected with herpes simplex virus type 1 in Igh-1 disparate congenic mice.

The mouse Igh-1 locus on chromosome 12 influences herpetic stromal keratitis (HSK) patterns following corneal challenge with herpes simplex virus type 1 (HSV-1). Both cellular and humoral immune mechanisms appear to be important in modulating responses to HSV-1 infections, but the role of antibody-dependent cellular cytotoxicity (ADCC) is unclear. We studied the effector-cell function and antibody in an ADCC assay in Igh-1-disparate mice. Splenocytes from both HSK-susceptible C.AL-20 (Igh-1d) and HSK-resistant C.B-17 (Igh-1b) mice mediated equal amounts of ADCC to HSV-infected cell targets using monoclonal antibodies against HSV-1 glycoprotein D. Natural killer cell activity was significantly greater in C.AL-20 than in C.B-17 splenocytes. IgG2a was less efficient than both IgG1 and IgG2b in mediating ADCC to HSV-1-infected cell targets. The Igh-1 phenotype of the antibody source had no influence on ADCC activity. Our results suggest that the susceptibility of HSK observed in these Igh-1-disparate congenics cannot be explained by qualitative differences in the ADCC activity of effector cells and antibody produced in response to HSV-1 infection.

Animals↗

Depletion of T-lymphocyte subsets in murine herpes-simplex-virus retinitis.

Uniocular injection of herpes-simplex virus type 1 into the anterior chamber of BALB/c mice induced contralateral retinitis with relative preservation of the ipsilateral retina. Overall 95% of T-cell deficient nude mice developed ipsi- and contralateral retinitis, suggesting the importance of T-cells in this model. We then depleted lymphocyte subsets in susceptible BALB/c and resistant CB-17 and C57BL/6J mice using anti-CD4 (helper/inducer cells) or anti-CD8 (suppressor/cytotoxic cells) monoclonal antibody. 85% of CD8-depleted, 58% of CD4-depleted and 50% of untreated BALB/c mice developed contralateral retinitis. All CD4- and CD8-depleted animals developed severe ipsilateral retinitis. These results suggest that CD8 cells (but not CD4 cells) are protective for the contralateral retina in BALB/c mice and that both subsets are important for the ipsilateral protection. In CB-17 and C57BL/6J mice, depletion produced no change in the contralateral retina but resulted in ipsilateral retinitis, suggesting different mechanisms for ipsi- and contralateral protection. The possible role of the anterior-chamber-associated immune deviation is discussed.

Animals↗

Ocular syphilis.

The ability of syphilis to mimic different ocular disorders can lead to misdiagnosis and delay in appropriate antimicrobial therapy. The authors describe their experience over the past 5 years with the ocular manifestations of syphilis in 25 patients who comprised 2.45% of 1020 new patients. Uveitis was the most common ocular manifestation seen. All patients had positive results from FTA-ABS tests, whereas only 68% had reactive serum VDRLs. Two of five patients tested for human immunodeficiency virus (HIV) antibody were reactive. The authors recommend routine FTA-ABS and VDRL screening in patients with uveitis or unexplained ocular inflammation. They also recommend testing for HIV antibody in luetics and aggressive treatment with high-dose aqueous penicillin for syphilis.

Adult↗

Natural killer cellular cytotoxicity against herpes simplex virus-infected cells in Igh-1-disparate mice.

Susceptibility to Herpes simplex virus type 1 (HSV-1) stromal keratitis (HSK) in the mouse has previously been linked to the Igh-1 locus. The role of natural killer cells (NK) in resistance to viral infections is controversial. The authors studied the influence of the Igh-1 locus on in vitro murine NK activity against HSV-1 infected cell lines. The HSV-1 infected targets were lysed better than uninfected cells by murine splenic lymphocytes. Strain had no influence on virus-augmented cell lysis. Spleen cells from naive HSK-susceptible CAL-20 (Igh-1d) and BALB/c (Igh-1a) mice lysed YAC-1 targets better than HSK-resistant C.B-17 (Igh-1b) mice. The reverse was seen 24 hours after in vivo infection intraperitoneally with HSV-1. In contrast, CAL-20 splenocytes lysed PU5-1R targets better than BALB/c and C.B-17 splenocytes 24 hours after intraperitoneal (IP) infection. No significant differences were detected in interferon (IFN) levels after IP challenge with HSV-1 among the Igh-1 congenics. The data show that differences in NK activity were determined by both the Igh-1 genotype and the uninfected target cell. Susceptibility to HSK in these Igh-1-disparate congenics thus cannot be explained simply by differences in NK activity against HSV-1-infected targets.

Animals↗