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R Hemady

Publications and source records attributed to R Hemady.

14 recordsLinked to original sources
PubMed1997

Phase I clinical trial of all-trans-retinoic acid with correlation of its pharmacokinetics and pharmacodynamics.

A phase I trial of all-trans-retinoic acid (ATRA) was conducted to establish the maximum tolerable dose (MTD) of ATRA given once daily to patients with solid tumors. Cancer patients for whom no standard therapy was available were treated with ATRA once daily. Doses were escalated in cohorts of at least three patients. The pharmacokinetics of ATRA were assessed on day 1 for all patients and weekly for 31 patients who received doses of > or = 110 mg/m2 per day. Patients were followed for toxicity and response. Correlations of toxicity frequency and grade with pharmacokinetic parameters were sought. In addition, correlation of changes in ATRA pharmacokinetics with the concentration of ATRA metabolites in plasma were sought. A total of 49 patients received ATRA at doses ranging from 45 to 309 mg/m2 per day. Hypertriglyceridemia was dose-limiting at 269 mg/m2 per day. Other frequent toxicities included mucocutaneous dryness and headache. With chronic dosing, plasma ATRA concentrations fell in 59% of patients. Stable, low, or variable [ATRA] were seen in 16%, 6%, and 16% of patients respectively. Age, gender, smoking, or concurrent medication did not correlate with the pharmacokinetic pattern. Severe toxicities tended to occur with initial peak [ATRA] of > or = 0.5 microgram/ml (1.7 microM), and the toxicity frequency did not change if [ATRA] decreased with continued dosing. No consistent change in 4-oxo-ATRA or retinoid glucuronide concentrations was observed with decreases in plasma [ATRA]. The recommended once-daily ATRA dose is 215 mg/m2, although significant interpatient variability is observed in toxicity and plasma retinoid concentrations. Although not statistically significant, more frequent and severe toxicity tended to occur in patients with higher plasma peak ATRA concentrations. Other factors, such as responses at target tissues, may be at least as important as the plasma ATRA concentration in predicting toxicity and/or response.

Adult↗
PubMed1994

Herpes simplex virus type 2 induced retinal necrosis in BALB/c mice.

We injected herpes simplex virus type 2 of MS- or G-strain into the anterior chamber of BALB/c mice. In the contralateral eye inflammatory cell infiltration began in the ciliary body; focal retinitis, detected by day 8, led to total destruction of the retina by day 10. Contralateral disease was observed in 75% of mice inoculated with 8 x 10(3) pfu herpes simplex virus type 2, but in only 20% of mice receiving 80 pfu herpes simplex virus type 2. Still this low concentration, however, produced a suppressed delayed-type hypersensitivity response. Anti-herpes simplex virus type 2 antibody, first detected on day 8, reached high titers on day 10; by then, most of the mice had died of encephalitis. The G-strain of herpes simplex virus type 2 was more neurotoxic than the MS-strain, but produced the same incidence of contralateral retinitis. Herpes simplex virus type 2 products contralateral necrotizing retinitis comparable to that produced by herpes simplex virus type 1. These findings, like those of other authors, suggest a role for herpes simplex virus type 2 in some cases of acute retinal necrosis in humans.

Animals↗
PubMed1992

Orbital cellulitis caused by Eikenella corrodens.

Eikenella corrodens is a gram-negative, facultative anaerobic bacillus with specific culture and growth requirements and unusual antibacterial susceptibilities. It has only recently been recognized as a human pathogen. Ocular and adnexal infections with this organism are rare especially in children. We treated two children with orbital cellulitis caused by E. corrodens. One was an 8-year-old boy; the other was an 11-year-old girl. Orbital cellulitis in both patients occurred after an upper respiratory tract infection. Sinusitis and a subperiosteal abscess were present in both patients. Eikenella corrodens and Streptococcus viridans were isolated from the boy; E. corrodens was the sole isolate in the girl. Intravenous ampicillin, prolonged hospitalization, and surgical drainage of the orbit were required to control the infection in both patients. Eikenella corrodens must be considered in the differential diagnosis of orbital cellulitis in children, and ophthalmologists must become familiar with the characteristics of this peculiar organism.

Ampicillin↗
PubMed1992

Six cases of scleritis associated with systemic infection.

Isolated scleritis (without keratitis) associated with infections is uncommon, and correct diagnosis and appropriate therapy for it are often delayed. Six patients with infection-associated scleritis were seen at our institution between May 1983 and May 1990 (these patients represented 4.6% of all patients with scleritis [six of 130 patients] in that period). Three of these cases were associated with systemic infections. One was associated with syphilis, one was associated with tuberculosis, and one was associated with toxocariasis. Three cases resulted from local infections. One was associated with infection with Proteus mirabilis, one was associated with infection with herpes zoster virus, and one was associated with infection with Aspergillus. The Aspergillus infection developed after trauma and the P. mirabilis-induced infection developed after strabismus surgical procedures. Four of the six cases were initially misdiagnosed and inappropriately managed. Correct diagnosis was made seven days to four years after onset of symptoms. Review of systems, scleral biopsy, culture, and laboratory investigation were used to make the diagnosis. Differential diagnosis of scleritis must include infective agents.

Aged↗
PubMed1992

Immunohistopathologic findings in herpes simplex virus chorioretinitis in the von Szily model.

After anterior chamber inoculation of herpes simplex virus type 1 (HSV-1), some mice have a characteristic pattern of ocular disease, including ipsilateral anterior uveitis, relative sparing of the ipsilateral retina, and necrotizing contralateral chorioretinitis. It was reported previously that susceptibility to the contralateral chorioretinitis is associated with the Igh-1 locus; congenic mice differing at this locus have different rates of contralateral disease. The immunohistopathologic findings of this model in Igh-1 disparate congenic mice are reported after examining immune cell populations (CD4, CD8, Thy 1.2, Ia, Mac, and immunoglobulin G cells) in both ipsilateral and contralateral eyes and the recruitment kinetics of these cell types in various ocular tissues. In both HSV-susceptible BALB/c and HSV-resistant C.B-17 mice, the ipsilateral eye undergoes early cellular infiltration, and the contralateral retina is devoid of cells until day 10 postinoculation. In BALB/c mice, a late dramatic rise develops in Mac and Ia cells in the ipsilateral and contralateral choroid (P less than 0.005) compared with C.B-17 mice. The C.B-17 mice have an earlier, mild cellular infiltration of the uveal tract in the ipsilateral eye, abrogation of the late Mac and Ia cellular recruitment in the ipsilateral choroid, and an absent contralateral response. These strain-specific immunohistopathologic differences help to explain Igh-1-linked HSV retinitis patterns in this model.

Animals↗
PubMed1991

[Herpes simplex virus retinitis. Role of the immune system in the animal experiment].

Herpes simplex virus (HSV) can induce severe inflammation in the retina. Von Szily described a model in which anterior chamber injection of HSV results in anterior uveitis with relative protection of the retina, but contralateral retinitis. The role of the immune system in the von Szily mouse model was investigated in our experiments. Earlier experiments demonstrated resistance to contralateral retinitis in some mouse strains. Our results suggest that natural killer (NK) cells do not play an important role in this phenomenon. In the next step the role of NK cells and T cells in the retinitis was investigated. After depletion of NK cells with anti-NK antibody, sensitive BALB/c and resistant CB17 mice did not have a higher incidence of retinitis. CB-17 mice developed more encephalitis after depletion, demonstrating an important role of NK cells against generalization of HSV. The role of T cells was investigated using T-cell-deficient nude mice. These mice had bilateral retinitis in about 95% of cases, demonstrating the role of T cells in protection of the retina in this model. Anti-HSV-1 serum transfer provided protection for the contralateral retina.

Animals↗
PubMed1990

Bacillus-induced endophthalmitis: new series of 10 cases and review of the literature.

We reviewed the charts of 10 patients who were admitted to the Massachusetts Eye and Ear Infirmary over a 10-year period with the diagnosis of Bacillus species endophthalmitis. To our knowledge this is the largest single series in the literature and includes the first two reported cases of Bacillus endophthalmitis following glaucoma filtering procedures. Seven cases developed following penetrating ocular trauma. One occurred in an intravenous drug abuser. Five eyes ultimately underwent enucleation; only the two eyes that developed endophthalmitis after elective surgery retained useful vision. Review of the literature indicates that parenteral and intravitreal antibiotic prophylaxis against endophthalmitis after penetrating ocular trauma should include gentamicin, in combination with vancomycin or clindamycin, to provide adequate coverage against infection with Bacillus spp., as prognosis is poor once infection is established. Bacillus spp. cultured from ocular tissues or fluids should not be dismissed as contaminants.

Adult↗
PubMed1990

Viral isolation and systemic immune responses after intracameral inoculation of herpes simplex virus type 1 in Igh-1-disparate congenic murine strains.

Igh-1-disparate congenic murine strains differ in their susceptibility to develop contralateral chorioretinitis after intracameral (AC) inoculation with Herpes simplex virus type 1 (HSV-1): 75% of BALB/cByJ (Igh-1a) and 5% of C.B-17 (Igh-1b) develop necrotizing chorioretinitis. To determine the mechanism of influence of host genetics on development of contralateral chorioretinitis, the authors did viral isolation studies in contralateral eyes, determined in vivo and in vitro T-cell responses, and HSV-antibody levels at various times after AC inoculation of BALB/cByJ and C.B-17 mice with HSV-1. Viral isolation was similar in both mouse strains (P less than 0.2). Similarities in systemic immune responses included suppressed delayed-type hypersensitivity responses 5 days, cytotoxic T-lymphocyte and lymphocyte proliferation responses 8 days, and viral neutralizing antibody titers 5 days postinoculation (PI). Differences in systemic immune responses included: (1) delayed-type hypersensitivity responses were not suppressed in C.B-17 mice (P greater than 0.1) and were hyperactive in BALB/cByJ mice (P less than 0.025) 10 days PI and (2) HSV-neutralizing antibody production was higher in C.B-17 mice 10 days PI. These data suggest that the mere presence of HSV-1 in the uninoculated eye is insufficient for the development of chorioretinitis. Virus-specific delayed-type hypersensitivity reactions might be involved in the pathogenesis of retinitis in BALB/cByJ mice; and virus-neutralizing antibodies and suppressed HSV-specific delayed-type hypersensitivity reactions might be instrumental in the protection enjoyed by C.B-17 mice.

Animals↗
PubMed1990

Keratoconjunctivitis sicca and corneal ulcers.

We reviewed the records of 56 patients (109 eyes) who satisfied our criteria for keratoconjunctivitis sicca (KCS) to determine factors associated with the development of sterile corneal ulcers. The patient's age, sex, and associated local ocular surface and/or systemic disease were studied. We found a statistically significant association between the development of corneal ulceration and the presence of an underlying condition or disease state, especially chronic rheumatoid arthritis. Patient sex and age were not significantly associated with the development of corneal ulceration. We present three case histories that illustrate the complications that arise in managing KCS plus an associated disease and methods of management.

Adult↗
PubMed1989

Chorioretinal disease patterns in congenic mice following intraocular inoculation with HSV-1.

Disease patterns and immunologic parameters were studied employing inbred and Igh-1 disparate congenic mice to determine the role of host genetics and Igh-1-linked gene products in the von Szily model of viral chorioretinitis. Following intracameral inoculation of 1.5 x 10(4) PFU HSV-1 (KOS), 100% of BALB/c (Igh-1a), 62% of A/J (Igh-1e) and none of the C57BL/6J (Igh-1b) inbred mice developed contralateral necrotizing chorioretinitis. Multigenic differences between inbred mice prohibit conclusions about the specific role of Igh-1-linked immune regulation in this model. In order to more exactly define Igh-1-specific restriction of HSV-1-mediated chorioretinitis, Igh-1-disparate, congenic BALB/c mice were studied following both anterior chamber and intravitreal inoculation protocols. Anterior chamber inoculation resulted in contralateral retinal necrosis in 75% of BALB/c (Igh-1a) mice, 30% of C.AL-20 (Igh-1d) and 5% of the C.B-17 (Igh-1b) congenic mice; all strains showed ipsilateral retinal sparing. Following intravitreal inoculation of HSV-1 a similar restricted disease pattern was found in contralateral eyes. Contralateral chorioretinitis developed in 30% of BALB/c, 15% of C.AL-20 and 6% of C.B-17 mice. Ipsilateral disease, however, was found in all murine strains. These disease patterns developed despite equivalent suppression of systemic DTH and equivalent RPE permissivity to viral replication. These data demonstrate that host genetics strongly regulates contralateral HSV-1-mediated chorioretinal disease patterns by a mechanism unrelated to the development of systemic suppression of DTH and specifically support a dominant role for gene products linked to the Igh-1 locus in the immunomodulation of ocular disease.

Animals↗
PubMed1989

Herpes simplex virus type-1 strain influence on chorioretinal disease patterns following intracameral inoculation in Igh-1 disparate mice.

We have previously shown that the Igh-1 locus on chromosome 12 of the mouse influences contralateral disease patterns in the modified von-Szily model. Following intracameral injection with 1.5 X 10(4) PFU of HSV strain KOS (HSV-KOS), 75% of BALB/cByJ (Igh-1a), 30% of C.AL-20 (Igh-1d) and 5% of C.B-17 (Igh-1b) mice develop contralateral chorioretinal necrosis. In contrast, Igh-1 congenic mice do not develop contralateral chorioretinal necrosis following anterior chamber inoculation of the same dose of an HSV-KOS mutant lacking surface glycoprotein-C (HSV-GC-KOS). Similarly, injection of wild type HSV strain mP (HSV-mP) into the anterior chamber of susceptible BALB/cByJ mice induces destructive contralateral chorioretinitis whereas injection of the same dose of the mutant HSV strain MP (HSV-MP) lacking surface glycoprotein-C does not induce a destructive contralateral chorioretinitis. In addition, higher doses of HSV-mP inoculum abrogate the Igh-1-associated contralateral chorioretinal protection seen in C.B-17 mice; protection is restored in C.B-17 mice at lower HSV-mP doses that still cause contralateral chorioretinitis in BALB/cByJ mice. These data demonstrate the influence of the viral isolate on the modified von-Szily model and specifically the requirement for the presence of glycoprotein-C on the surface of HSV for the development of contralateral destructive chorioretinitis.

Animals↗
PubMedDate not supplied

Immunosuppressive drugs in immune and inflammatory ocular disease.

Advances in immunology, particularly ocular immunology, have been accompanied by the emergence of safer, more specific immunosuppressive drugs, notably, cyclophosphamide, chlorambucil, methotrexate, azathioprine, cyclosporine A, bromocriptine, dapsone, and colchicine. These drugs have become an important, and often essential, part of the ophthalmologist's armamentarium against inflammatory and immune-mediated ocular diseases. In order to better acquaint the ophthalmologist with the properties of the most commonly used immunosuppressive drugs, we review the literature and relate our own experience with these agents.

Autoimmune Diseases↗