Biomedical subjects
A Merchant
Publications and source records attributed to A Merchant.
Candidal endophthalmitis after keratoplasty.
PURPOSE: To report a case of explosive fungal endophthalmitis after penetrating keratoplasty and to review additional published and unpublished cases to consider possible strategies for prevention. METHODS: Records of this patient with postkeratoplasty candidal endophthalmitis and previously reported cases of postkeratoplasty candidal endophthalmitis were reviewed. Additional information of 26 unpublished cases was obtained from the Eye Bank Association of America. RESULTS: After standard keratoplasty, the patient developed precipitous endophthalmitis on the second postoperative day. Abundant contamination with Candida was found in the residual donor corneoscleral rim, and Candida albicans was isolated from the aqueous humor of the recipient. Despite therapy with local antimicrobial agents, intraocular amphotericin B, and systemic fluconazole, the patient had a poor outcome with hand-motion visual acuity. Of the 44 collected cases of postkeratoplasty candidal endophthalmitis, 40 (91%) had the same organism cultured from the donor rim or medium. Forty-three donor corneas had been preserved in cold storage medium at 4 degrees C. Of 15 cases in which the outcome was available, 9 (60%) resulted in visual acuity of 20/200 or worse. CONCLUSION: Case reports confirm the occurrence of donor-to-host transmission of postkeratoplasty candidal endophthalmitis. Despite the low reported incidence, the poor prognosis of the affected eye in the ajority of these cases suggests the need for antifungal supplementation of cold preservation media and other preventative strategies.
Effect of Fas and Fas ligand deficiency in resistance of C57BL/6 mice to HSV-1 keratitis and chorioretinitis.
PURPOSE: To investigate the effect of Fas and Fas ligand (FasL) deficiency on the development of herpes stromal keratitis and on the von Szily model of herpes retinitis in C57BL/6 mice, which are ordinarily resistant to development of both of these herpetic diseases. METHODS: Anterior chamber inoculation of the right eye of each mouse with various titers of HSV-1 (KOS strain) was performed. Both eyes of each mouse were enucleated on postinoculation day 15 and processed for histopathologic examination. HSV-1 was inoculated into one cornea of other mice, and the severity of stromal keratitis was scored. RESULTS: Contralateral destructive chorioretinitis developed in susceptible Balb/cByj mice (19/23); ipsilateral chorioretinitis did not occur (0/23). Stromal keratitis developed in susceptible C.AL-20 mice (15/16). None of the C57BL/6 (0/10 for keratitis or 0/20 for retinitis) developed inflammation. Neither did B6.SMN.C3H.gld (FasL deficient; 0/12 or 0/28) or B6.MRL.lpr (Fas deficient; 0/11 or 0/34) mice (keratitis or contralateral chorioretinitis). Minimal scattering of inflammatory cells in the contralateral retina but not destructive chorioretinitis was observed in two C57BL/6, three B6.SMN.C3H.gld, and five B6.MRL.lpr mice. Few inflammatory cells were also found in the ipsilateral vitreous and vitreoretinal interface (but not destructive chorioretinitis) of all C57BL/6, two gld, and three lpr mice. CONCLUSIONS: Immune dysregulation secondary to deficiency in Fas or FasL system does not influence the resistance of the C57BL/6 mice to develop herpes simplex keratitis or destructive herpes simplex chorioretinitis.
Paan without tobacco: an independent risk factor for oral cancer.
Oral cancer is the second most common cancer in women and the third most common in men in Pakistan. Tobacco is smoked and chewed extensively in Pakistan. Paan is a quid of piper betel leaf that contains areca nut, lime, condiment, sweeteners, and sometimes tobacco, which is also used extensively. We did this study to clarify the independent association of paan and oral cancer. Between July 1996 and March 1998, we recruited biopsy-proven, primary cases of oral squamous-cell carcinoma, from 3 tertiary teaching centers in Karachi, Pakistan, and controls pair-matched for age, gender, hospital and time of occurrence, excluding persons with a past or present history of any malignancy. There were 79 cases and 149 controls. Approximately 68% of the cases were men, 49 years old on average, the youngest being 22 years old and the eldest 80. People with oral submucous fibrosis were 19.1 times more likely to develop oral cancer than those without it, after adjusting for other risk factors. People using paan without tobacco were 9.9 times, those using paan with tobacco 8.4 times, more likely to develop oral cancer as compared with non-users, after adjustment for other covariates. This study identifies an independent effect of paan without tobacco in the causation of oral cancer. Its findings may be of significance in South Asian communities where paan is used, and among health-care providers who treat persons from South Asia.
Klebsiella rhinoscleromatis--an innocent or a deadly organism.
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Leukocyte adhesion molecule expression in scleritis.
OBJECTIVE: To analyze the expression and cellular distribution of intercellular adhesion molecule 1, E-selectin (endothelial leukocyte adhesion molecule), vascular cell adhesion molecule 1, very late antigen 4, and lymphocyte function associated antigen 1 (LFA-1) in diseased and normal human sclera. METHODS: Monoclonal antibodies to vascular cell adhesion molecule 1, very late antigen 4, intercellular adhesion molecule 1, LFA-1, and E-selectin were used to perform immunohistochemical staining on frozen sections of 16 cryopreserved human sclera specimens and 5 conjunctival specimens. RESULTS: The normal human sclera did not express any of the adhesion molecules. The expression of LFA-1 was dramatic in all the scleral and conjunctival specimens on the inflammatory cells. Intercellular adhesion molecule 1, the ligand for LFA-1, was expressed in 7 of 12 scleral specimens. Furthermore, the expression of LFA-1 and intercellular adhesion molecule 1 were focally present in areas of inflammatory infiltrate. E-selectin expression was detected on the vascular endothelial cells in 8 of 12 patients. There was variable expression of vascular cell adhesion molecule 1 and very late antigen 4 in the inflamed sclera and conjunctiva. CONCLUSIONS: Our results demonstrate the presence of LFA-1 in the sclera and in the conjunctiva of patients with scleritis. Variable expression of other leukocyte adhesion molecules was noted in the sclera and the conjunctiva of these patients.
Chronic keratoconjunctivitis associated with congenital dyskeratosis and erythrokeratodermia variablis. Two rare genodermatoses.
OBJECTIVE: The purpose of the study was to report the ocular manifestations and immunohistopathologic description of two rare forms of genodermatosis: congenital dyskeratosis (CD) and erythrokeratodermia variabilis (EKV). DESIGN: Case reports. PARTICIPANTS: Two patients with CD and EKV presenting with chronic keratoconjunctivitis were studied. INTERVENTION: Clinical photography to show ocular manifestations and dermatologic findings was performed. Conjunctival biopsy was performed to determine the histopathology and immunohistopathology. RESULTS: In the patient with EKV, the eyelid skin was dry, erythematous, and thickened. The lid margins showed plugging of some of the Meibomian glands, madarosis, and occasional trichiasis. The epibulbar conjunctiva was injected and had a moderate papillary reaction. Both corneas had pronounced vascularization and stromal scarring. Conjunctival biopsy results disclosed a striking number of degranulating mast cells and moderate numbers of plasma cells. Immunohistopathology showed pronounced immunoglobulin G (IgG)-positive cells in the stroma and immunoglobulin A (IgA) positivity in the epithelium. There was scattered immunoglobulin M (IgM) and moderate C3 and C4 positivity in the stroma. In CD, the patient had keratinized lid margins, entropion formation, trichiasis, cicatrizing conjunctivitis, and symblephra formation. The corneal surface was keratinized, with deep and superficial vascularization. Conjunctival biopsy specimens showed pronounced epithelial keratinization and squamous metaplasia. Degranulating mast cells and eosinophils were prominent in the stroma. Immunohistopathology showed C4 and immunoglobulin D positivity on the keratinized epithelial surface with rare foci of immunoglobulin E-positive cells. Basal epithelial cells were positive for IgA and IgG, and a large number of IgA and IgG plasma cells were present in the substantia propria. CONCLUSION: To the authors' knowledge, these case reports represent the first clinical description of the ocular manifestation of EKV and the first immunohistopathologic description of the affected conjunctiva in EKV and CD, both of which should be considered in the differential diagnosis of genodermatosis associated with chronic keratoconjunctivitis.
Pharmacomanipulation of HSV-1 induced chorioretinitis in mice.
In the von Szily mouse model, intracameral inoculation of herpes simplex virus type-1 (HSV-1) results in inflammation of the ipsilateral anterior segment with relative chorioretinal sparing and destructive contralateral chorioretinitis. We studied the effect of the systemic antiviral agent acyclovir (ACV) and anti-HSV-1 antibody therapy in this model. Contralateral chorioretinitis developed in none of the 18 mice receiving ACV from post-inoculation day (pid) 1 (p < 0.0001), in 6 of 10 (60%) mice when treatment was delayed until pid 7 (p = 0.40) and in 14 of 18 (77%) controls. Contralateral disease developed in 8 of 16 (50%) mice that received anti-HSV-1 antibody from pid 1 (p = 0.02), in 13 of 16 (81%) treated from pid 5 (p = 0.64), in 7 of 8 (87.5%) treated from pid 7 (p = 1.0) and in 17 of 20 (85%) controls. We conclude that early treatment with ACV or anti-HSV-1 antibody reduces the incidence of contralateral chorioretinitis in mice.
Primary intraocular lymphoma.
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Ocular rosacea: patient characteristics and follow-up.
PURPOSE: The purpose of this report is to review the presenting symptoms and signs, treatment regimens used, complications encountered, and outcome in a cohort of patients with ocular rosacea. METHODS: The medical records of 131 patients with a diagnosis of ocular rosacea were reviewed retrospectively. Data were entered in a tabulated form, and a descriptive analysis was performed. RESULTS: The age range at presentation was between 23 and 85 years (mean, 56 years). Cutaneous manifestations of rosacea were present in 112 of the patients at their first visit. The most common presenting symptoms were foreign body sensation and burning, and the most common signs were telangiectasia and irregularity of lid margins, and meibomian gland dysfunction. Thirteen patients had decreased visual acuity at the time of presentation due to corneal complications. Six of these patients required penetrating keratoplasty during the course of their disease. Seven patients had severe cicatrizing conjunctivitis at the time of referral. One hundred thirteen patients were treated with oral tetracycline derivatives. Seven patients were left with visual acuity less than 20/400, and one patient underwent enucleation for corneal perforation and endophthalmitis. CONCLUSIONS: Ocular rosacea is a common disease involving the skin and the eyes. It is widely underdiagnosed by many ophthalmologists despite the blinding potential. Successful therapy requires a multidisciplinary approach.
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.
Molecular shape comparison of angiotensin II receptor antagonists.
A new and powerful analytical method for comparing molecular shapes by optimizing the overlap of molecular volumes has been developed. This shape comparison method provides both a quantitative measure of the shape similarity of molecules and a means to align molecules such that shape similarity if maximized. Our MSC method has been enhanced with an option to allow discrimination between groups with different chemical properties. Atoms or groups of atoms may be assigned to different classes based on specific properties such as electrostatic potential, hydrogen bonding ability, or hydrophobicity. This enables matches based on criteria such as alignment of hydrophobic groups or hydrogen bond acceptor groups. In this study, we report shape comparisons of angiotensin II (AII) receptor antagonists from two structural classes, 4-(biphenyl-4-ylmethoxy)-quinoline derivatives such as ICI D8731 and N-(biphenyl-4-ylmethyl)imidazole derivatives, such as DuP753. Starting with a list of low-energy conformations for the two molecules, each conformation of the first molecule is paired with each of the conformations of the second molecule. For each of these conformational pairs, an MSC comparison, which generates multiple MSC maxima, is initiated. Eight high scoring conformational pairings were found with shape matching based on the intersection of the total molecular volume, while nine high-scoring pairs were identified with matching by atom type. MSC identifies conformational pairs with high shape similarity, as measured by the intersection volume, and thus generates and prioritizes several alternative models for the AII antagonist pharmacophore.
Molecular skins: a new concept for quantitative shape matching of a protein with its small molecule mimics.
A novel analytical method for comparing molecular shapes by optimizing the intersection of molecular "SKINS" has been developed. This method provides a quantitative measure of the shape similarity by maximizing the intersection volume of molecular surfaces with a finite thickness; a molecular skin. We report shape matching of a small tripeptide inhibitor (DFKi) of elastase class proteins with the 56 residue turkey ovomucoid inhibitor (TOMI). To match a large elastase inhibitor such as TOMI with a small inhibitor or drug, we found that it is necessary to use a skin match rather than molecular volume. Skin based comparisons of TOMI protein with DFKi successfully found the alignment expected from comparison of their respective crystallographic complexes with elastase (i.e. HLE/TOMI complex and PPE/tripeptide complex). In the skin comparison of the tripeptide with the TOMI protein, blind searching for skin matches involved optimization of the skin intersection from 172 starting positions randomly selected from a set of 500 points on the TOMI van der Waals surface [within 9.5 A of the Leu-18 on the TOMI binding loop (1 point/A2)]. The tripeptide center of mass was placed at these points and its orientation was randomized before optimization was initiated. The best skin intersection, 86.4 A3, was found three times and corresponds to the experimental alignment. The next best skin intersection was 78.1 A3 giving a discrimination factor in this case of 10%. Searches over the entire surface of the TOMI protein did not identify any new matches with skin intersection greater than 78.1 A3. Matching the DFKi with a TOMI structure relaxed from its crystal conformation by molecular dynamics gives similar results.
Systemic (serum) soluble interleukin-2 receptor levels in corneal transplant recipients.
Elevated soluble interleukin-2 receptor levels (sIL-2R), a measure of T cell activation, have been used as a serum marker for early rejection in solid organ transplant patients. In this preliminary study, we measured sequential sIL-2R levels of 53 otherwise immunologically normal corneal transplant recipients. Eleven of these transplants rejected; sIL-2R was significantly elevated during the acute rejection episode, compared to pre-rejection and post-rejection levels (p = 0.01). Five patients' sIL-2R rose one to nine months prior to rejection. These data indicate that sIL-2R levels may correlate with corneal graft rejection and may be predictive of impending rejection. A larger prospective study with many immunologically normal patients and careful monitoring of sIL-2R levels prior to and during the acute rejection episode will be necessary to determine the value of sIL-2R monitoring as a predictive tool for corneal graft rejection.
The epidemiology of psychiatrist-ascertained depression and DSM-III depressive disorders. Results from the Eastern Baltimore Mental Health Survey Clinical Reappraisal.
Psychiatrists used a semi-structured Standardized Psychiatric Examination method to examine 810 adults drawn from a probability sample of eastern Baltimore residents in 1981. Of the population, 5.9% was found to be significantly depressed. DSM-III major depression (MD) had a prevalence of 1.1% and 'non-major depression' (nMD), our collective term for the other depressive disorder categories in DSM-III, had a prevalence of 3.4%. The two types of depression differed by sex ratio, age-specific prevalence, symptom severity, symptom profiles, and family history of suicide. Analyses using a multiple logistic regression model discerned that both types of depression were influenced by adverse life events, and that nMD was influenced strongly by gender, marital status, and lack of employment outside the home. Neither type of depression was influenced by income, education, or race. This study validates the concept of major depression as a clinical entity. Future studies of the aetiology, mechanism, and treatment of depression should distinguish between these two types of depression.
Topical cyclosporine A and corneal wound healing.
The effect of 2% topical cyclosporine A (CsA) ointment on corneal epithelial and stromal wound healing was evaluated in a masked, placebo-controlled study in rabbits. The difference in epithelial would healing rate in the treatment and placebo group was not statistically significant. There was also no difference in the values of bursting strength of 2-mm central penetrating wounds and in the measurement of hydroxyproline content in the central corneal buttons from the wounded area in both the groups. Clinical evaluation of the quality of regenerating epithelium, stromal edema, haze, and iritis did not reveal a difference between the two groups. There was a significantly higher incidence of conjunctival injection in the CsA-treated group. We conclude that topical cyclosporine A 2% does not significantly inhibit epithelial or stromal corneal wound healing.
DSM-III compulsive personality disorder: an epidemiological survey.
A two-stage probability sample of community subjects was developed with a full psychiatric examination employing DSM-III criteria in conjunction with the Epidemiological Catchment Area (ECA) survey conducted in Baltimore, MD. This report details the observation on those subjects diagnosed with compulsive personality disorder and compulsive personality traits. The results indicate that this condition has a prevalence of 1.7% in a general population. Male, white, married and employed individuals receive this diagnosis most often. Our data suggest a dimensional rather than categorical character for this disorder. The disorder imparts a vulnerability for the development of anxiety disorders.
Hemolysis of rabbit erythrocytes in the presence of copper ions. Inhibition by albumin and ceruloplasmin.
The hemolysis of red blood cells (RBC) induced by Cu(II) is modified by ceruloplasmin (Cp) and albumin. The time course of hemolysis for rabbit RBC by Cu(II) consisted of two parts, an induction period followed by a catastrophic lysis period. The induction period decreased and the lysis rate increased with increasing Cu(II) concentration. Cp or albumin, modified Cu(II) induced hemolysis, by increasing the duration of the induction period and decreasing the overall rate of hemolysis of RBC. The catastrophic lysis period coincided with a sharp increase in the formation of metHb within the cell and in a rapid uptake of Cu(II). The presence of Cp led to an increase in the induction period prior to the rapid increase in metHb formation and in Cu(II) uptake. Porcine Cp was prepared with either two or three nonprosthetic copper binding sites (sites where Cu(II) is easily removed by passing over Chelex-100). Cp with three nonprosthetic binding sites gave more protection than Cp with two. Likewise, albumin can be prepared with three and five nonprosthetic copper binding sites. The albumin with five sites gave more protection than the albumin with three sites.