RESUMEN
BACKGROUND: Keratoconus is a noninflammatory disease characterized by thinning and scarring of the central portion of the cornea. The etiology is unclear. In this study, we sought to identify mRNAs that are differentially expressed in the stroma of keratoconus corneas in comparison to those of corneas from normal individuals and patients with other corneal diseases. MATERIALS AND METHODS: Total RNA was isolated from the stromal layer of normal human, keratoconus, and pseudophakic bullous keratopathy corneas. cDNA was synthesized and PCR-select subtractive hybridization experiments were performed. The differentially expressed genes noted were verified by dot blot analysis, cloned, and sequenced. Immunohistochemical staining, in situ hybridization, and/or reverse transcription polymerase chain reaction were used to assess expression of the identified genes at protein and/or mRNA levels in normal, keratoconus, and other diseased corneas. RESULTS: A number of genes were found to be up-regulated in keratoconus specimens. These included heat shock protein 90, decorin, fibronectin, ferritin heavy chain, and keratocan. Among them, keratocan mRNA transcript and protein were demonstrated to be expressed at a higher level specifically in the keratoconus stroma. CONCLUSIONS: Keratocan expression in the stoma was increased in keratoconus corneas. This up-regulation appears to be keratoconus specific. Keratocan is one of the three keratan sulfate proteoglycans in the cornea speculated to be important for structure of the stromal matrix and maintenance of corneal transparency. The overexpressed keratocan may conceivably alter the fibrillogenesis in the stroma, leading to structural defects and contributing to the development of keratoconus.
Asunto(s)
Queratocono/genética , Queratocono/metabolismo , Proteoglicanos/genética , Proteoglicanos/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Expresión Génica , Humanos , Inmunohistoquímica , Hibridación in Situ , Queratocono/patología , Persona de Mediana Edad , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
PURPOSE: Keratoconus is a disease characterized by thinning of the central and paracentral cornea and scarring in advanced cases. This study was performed to examine the expression of type XII collagen, proteins associated with hemidesmosomes, and beta1 integrin in keratoconus corneas. METHODS: Corneal buttons were collected from normal subjects and patients with keratoconus and other corneal diseases. Immunofluorescence staining was performed on frozen sections for type XII collagen, bullous pemphigoid antigen (BP180), and integrin subunits alpha6, beta4, and beta1. RESULTS: To varying degrees, all proteins examined were expressed in normal human corneas. The staining intensity of type XII collagen was diminished in keratoconus corneas in the epithelial basement membrane zone and the stromal matrix. No significant variation was found in either the staining patterns or intensities for BP180, or integrins alpha6, beta4, and beta1. CONCLUSIONS: The level of type XII collagen was reduced in the epithelial basement membrane zone and stromal matrices in keratoconus corneas. These alterations may affect critical interactions of the corneal epithelium with the under-lying basement membrane, and cell-matrix interactions and matrix organization in the stroma.
Asunto(s)
Autoantígenos/metabolismo , Colágeno/metabolismo , Córnea/metabolismo , Hemidesmosomas/metabolismo , Integrinas/metabolismo , Queratocono/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD/metabolismo , Proteínas Portadoras , Córnea/patología , Proteínas del Citoesqueleto , Distonina , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Integrina alfa6 , Integrina beta1/metabolismo , Integrina beta4 , Queratocono/patología , Microscopía Fluorescente , Persona de Mediana Edad , Proteínas del Tejido Nervioso , Colágenos no Fibrilares , Colágeno Tipo XVIIRESUMEN
PURPOSE: Keratoconus is a progressive disease that thins and scars the corneal stroma. In keratoconus corneas, levels of degradative enzymes, including lysosomal acid phosphatase (LAP) and cathepsin B, are elevated, and those of the inhibitors alpha1-proteinase inhibitor (alpha 1-PI) and alpha 2-macroglobulin (alpha 2-M) are reduced, especially in the epithelial layer. An increased expression of the transcription factor Sp1 was also demonstrated. The role of Sp1 in regulation of the genes affected in keratoconus was examined in this study. METHODS: DNA segments, containing 5'-flanking promoter sequences of the alpha 1-PI, LAP, cathepsin B, and alpha 2-M genes were ligated into the secreted alkaline phosphatase (SEAP) reporter gene vector. These constructs, along with the pSV beta-galactosidase control vector, were transfected into cultured human corneal epithelial and stromal cells and skin fibroblasts. Cotransfection with the Sp1 expression vector was performed in parallel. SEAP and beta-galactosidase enzyme activities were assayed. RESULTS: In corneal epithelial cells, as in stromal cells, alpha 1-PI promoter activity was suppressed by cotransfection of pPacSp1. The LAP, cathepsin B, and alpha 2-M promoters were functional in corneal cells, whereas activities of these promoters were much lower in skin fibroblasts. Cotransfection experiments indicated that the up- or downregulation of LAP, cathepsin B, and alpha 2-M observed in keratoconus-affected corneas was not mediated by Sp1. CONCLUSIONS: These results support the theory that the corneal epithelium, along with the stroma, is involved in keratoconus. An upstream role of Sp1 is indicated and the Sp1-mediated downregulation of the alpha 1-PI gene may be a key event in the disease development.
Asunto(s)
Fosfatasa Ácida/genética , Catepsina B/genética , Queratocono/metabolismo , Factor de Transcripción Sp1/fisiología , alfa 1-Antitripsina/genética , alfa-Macroglobulinas/genética , Fosfatasa Ácida/metabolismo , Adulto , Fosfatasa Alcalina/metabolismo , Catepsina B/metabolismo , Niño , Sustancia Propia/metabolismo , Sustancia Propia/patología , Cartilla de ADN/química , Epitelio Corneal/metabolismo , Fibroblastos/metabolismo , Regulación de la Expresión Génica , Vectores Genéticos , Humanos , Regiones Promotoras Genéticas/genética , Piel/metabolismo , Piel/patología , Transfección , alfa 1-Antitripsina/metabolismo , alfa-Macroglobulinas/metabolismo , beta-Galactosidasa/metabolismoRESUMEN
PURPOSE: To report a patient with consecutive Descemet's membrane (DM) detachments after successive phacoemulsification, review other reported patients with bilateral DM detachments, and explore the possibility of anatomic predisposition to DM detachment in some patients. METHODS: Our patient's course was reviewed along with the reported experience with three other patients with bilateral DM detachments. RESULTS: No clear underlying etiology of DM detachment was found in our patient or any of the other three reported patients reviewed. CONCLUSIONS: Some patients may be anatomically predisposed to DM detachment possibly because of an abnormality in the fibrillary stromal attachment to DM. Early postoperative surgical intervention often leads to satisfactory visual results.
Asunto(s)
Enfermedades de la Córnea/etiología , Lámina Limitante Posterior/patología , Facoemulsificación/efectos adversos , Anciano , Enfermedades de la Córnea/diagnóstico , Humanos , Masculino , Agudeza VisualRESUMEN
Sp1, a ubiquitously expressed transcription factor, has been implicated to have a role in cell differentiation and cell proliferation. In keratoconus, a corneal disease characterized by thinning and scarring of the central cornea, Sp1 is found up-regulated. In the present study, we examined the expression of Sp1 in stromal cells cultured from normal human and keratoconus-afflicted corneas and evaluated the influence of varying cell densities. Immunohistochemical staining, Western blotting and electrophoretic mobility shift assays indicated that in both normal human and keratoconus cultures, Sp1 protein levels and binding activities increased with the density of cells. The basal level of Sp1 in keratoconus cultures was higher than that in normals. These results demonstrate a marked density mediated up-regulation of Sp1 in corneal stromal cells, suggesting that the Sp1 expression may be regulated by differentiation states of the cells in the cornea. In addition, cells from keratoconus corneas in vitro appear to carry and retain the Sp1 abnormality as in vivo. The Sp1 defect may be an inborn error in keratoconus.
Asunto(s)
Queratocono/metabolismo , Factor de Transcripción Sp1/metabolismo , Adulto , Western Blotting , Estudios de Casos y Controles , Recuento de Células , Diferenciación Celular , Células Cultivadas , Electroforesis en Gel de Poliacrilamida , Humanos , Queratocono/patología , Mediciones Luminiscentes , Persona de Mediana Edad , Sondas de Oligonucleótidos , Regulación hacia ArribaRESUMEN
OBJECTIVES: To quantify the risk of Creutzfeldt-Jakob disease (CJD) among cornea donors, evaluate supplemental screening strategies, and address concerns about the adequacy of current methods of screening tissue donors in the United States. METHODS: Reported data on deaths due to CJD and from all causes were used to estimate the rate of CJD among cornea donors. The impact of increased screening on risk of CJD and donor supply was evaluated. RESULTS: Only 1.3 of the approximately 45 000 cornea donors in the United States each year might be expected to have CJD. Most of the estimated risk (91%) is due to preclinical (asymptomatic) disease and therefore could not be eliminated by screening for signs or symptoms. If only the highest-risk age group (60 to 69 years) were screened and specificity were 90%, more than 21 000 otherwise acceptable donors would incorrectly be excluded over a period of 17.5 years to correctly exclude a single donor with symptomatic CJD. CONCLUSIONS: Currently, the risk of CJD transmission following cornea transplantation is remarkably low. Screening for symptoms of CJD would have minimal impact on safety, but would reduce donor supply and likely result in many patients not receiving needed treatment.
Asunto(s)
Córnea , Trasplante de Córnea/estadística & datos numéricos , Síndrome de Creutzfeldt-Jakob/diagnóstico , Bancos de Ojos/estadística & datos numéricos , Donantes de Tejidos/estadística & datos numéricos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Síndrome de Creutzfeldt-Jakob/mortalidad , Síndrome de Creutzfeldt-Jakob/transmisión , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Mortalidad/tendencias , Factores de Riesgo , Estados Unidos/epidemiologíaRESUMEN
PURPOSE: To describe a case of Beauveria bassiana keratitis and to discuss the management of this rare condition. METHODS: An 82-year-old woman underwent surgical repair of a graft wound dehiscence. Seven months later, shortly after the removal of sutures, the patient developed a fungal keratitis. B. bassiana was identified as the infecting organism. The patient was treated with topical natamycin and oral fluconazole. RESULTS: Following antifungal therapy, the corneal ulcer was eradicated, but the patient underwent repeat penetrating keratoplasty for decreased vision due to corneal edema. The graft remains clear and visual acuity is substantially improved. CONCLUSION: The medical management of B. bassiana keratitis has previously been unsuccessful. The use of topical natamycin combined with oral fluconazole in the management of this case is discussed.
Asunto(s)
Antifúngicos/uso terapéutico , Úlcera de la Córnea/tratamiento farmacológico , Infecciones Fúngicas del Ojo/tratamiento farmacológico , Fluconazol/uso terapéutico , Hongos Mitospóricos/aislamiento & purificación , Micosis/tratamiento farmacológico , Natamicina/uso terapéutico , Infección de la Herida Quirúrgica/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Úlcera de la Córnea/microbiología , Quimioterapia Combinada , Infecciones Fúngicas del Ojo/microbiología , Femenino , Humanos , Micosis/microbiología , Infección de la Herida Quirúrgica/microbiologíaRESUMEN
PURPOSE: In keratoconus corneas, it has been shown that levels of degradative enzymes and transcription factor Sp1 are elevated and those of inhibitors are reduced, especially in the epithelial layer. This study is to determine whether the biochemical abnormalities identified in corneas also exist in conjunctival tissues. METHODS: Conjunctival tissues were collected from normal subjects and from patients with keratoconus, senile cataract, and other corneal diseases. Immunohistochemical staining for cathepsins B and G, alpha 1-proteinase inhibitor, alpha 2-macro-globulin and Sp1 was performed. RESULTS: The epithelium of all conjunctival specimens showed immunoreactivity toward the antibodies. The staining for cathepsins B and G, and the inhibitors was mostly cytoplasmic, while that for Sp1 was nuclear. The staining intensity in keratoconus specimens was all within normal range. CONCLUSIONS: These results suggest that the abnormalities in cathepsins B and G, protease inhibitors and Sp1 identified in keratoconus corneas are not manifested in the conjunctiva. Keratoconus appears to be a disease localized to the cornea.
Asunto(s)
Catepsinas/biosíntesis , Conjuntiva/metabolismo , Queratocono/metabolismo , Inhibidores de Proteasas/metabolismo , Factor de Transcripción Sp1/biosíntesis , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Catarata/metabolismo , Epitelio/metabolismo , Humanos , Técnicas para Inmunoenzimas , Queratocono/patología , Persona de Mediana EdadRESUMEN
PURPOSE: The use of a temporary keratoprosthesis has allowed earlier surgical intervention in eyes with coexisting vitreoretinal and corneal disease. We analyzed our experience with this type of surgery. METHODS: We retrospectively reviewed charts of patients in whom a temporary keratoprosthesis was used between 1987 and 1998. Analysis was focused on ocular history, indications for surgery, visual acuity (VA), intraocular pressure, anatomic results, and complications. RESULTS: A temporary keratoprosthesis was used in 31 eyes, 22 (71.0%) of which were for trauma-related indications. In 6 (19.4%) of the operated eyes, the fellow eye also had severely reduced VA. Retinal detachments were present in 30 (96.8%) eyes; most had evident proliferative vitreoretinopathy. Twelve (38.7%) eyes had vitreous hemorrhage, and 20 (64.5%) had corneal scars. Improvement in VA was seen initially in 45.1% of patients, and 51.6% maintained equal or better VA at their final visit as compared with before surgery. The common documented reasons for poor final VA were recurrent retinal detachments deemed inoperable (32.3%), phthisis (22.6%), and optic atrophy or macular scar (16.1%). Corneal grafts remained clear in 41.9%. Nine patients had further surgery. The most significant complication was one case of sympathetic ophthalmia. CONCLUSIONS: Combined vitreoretinal and corneal surgery using temporary keratoprostheses has been used in our institution to treat eyes with extreme abnormalities. Outcomes were less favorable than some reported in the literature, probably because of the severity of disease for which temporary keratoprostheses were reserved. Although results are probably better than the natural course of the disease, patients should be informed of realistic expectations for improvement and potential complications when offered this option.
Asunto(s)
Enfermedades de la Córnea/cirugía , Queratoplastia Penetrante , Implantación de Prótesis/métodos , Enfermedades de la Retina/cirugía , Vitrectomía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Enfermedades de la Córnea/etiología , Lesiones Oculares/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades de la Retina/etiología , Estudios Retrospectivos , Aceites de Silicona/administración & dosificación , Resultado del TratamientoRESUMEN
PURPOSE: We present two pairs of monozygotic twins discordant for keratoconus. METHODS: Two pairs of twins, each with one twin with keratoconus, and available family members were examined clinically and with computer-assisted videokeratography. Polymerase chain reaction-based zygosity assays using between nine and 11 unique, anonymous DNA markers were performed on blood obtained from the twins and surviving parents to assess the probability of genetic monozygosity. RESULTS: DNA probes showed a >99% probability that each of the two sets of twins was monozygotic. One twin from each pair had clinically diagnosed keratoconus. The remaining twins were normal by clinical examination and corneal topography. Clinical results for all family members examined were normal except that five of 13 from one family and one of six from the other family demonstrated "suspicious" corneal topography. CONCLUSION: Recent advances in knowledge and understanding of the twinning process suggest that monozygotic twins discordant for keratoconus does not preclude the possibility of a significant genetic component.
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Enfermedades en Gemelos/genética , Queratocono/genética , Gemelos Monocigóticos , Adulto , Córnea/patología , Topografía de la Córnea , ADN/análisis , Sondas de ADN/química , Femenino , Estudios de Seguimiento , Humanos , Queratocono/patología , Masculino , Linaje , Reacción en Cadena de la Polimerasa , Polimorfismo Genético , Refracción OcularRESUMEN
PURPOSE: Levels of alpha1-proteinase inhibitor and alpha2-macroglobulin in the tear film of patients with keratoconus were measured to elucidate their possible roles in the pathogenesis of keratoconus. METHODS: Tear samples were collected from 15 keratoconus patients and 14 age-similar human control subjects. Levels of alpha1-proteinase inhibitor and alpha2-macroglobulin in each tear sample were quantified and compared between the two groups. RESULTS: Mean values for alpha1-proteinase inhibitor were 101.0+/-35.5 and 106.1+/-41.7 ng/microg protein for the keratoconus and control groups, respectively. The corresponding mean values for alpha2-macroglobulin were 13.5+/-6.8 and 14.8+/-7.5 ng/microg protein. Neither inhibitor showed a statistically significant difference between the keratoconus and control specimens. Subset analysis to evaluate the effects of contact lens wear and the presence of a graft in the fellow eye did not reveal a statistically significant difference. CONCLUSION: The tear film of patients with keratoconus contains normal levels of protease inhibitors. Therefore, the tear film may not be a source of the reduced inhibitor levels shown in the corneas of patients with keratoconus.
Asunto(s)
Proteínas del Ojo/metabolismo , Queratocono/metabolismo , Lágrimas/metabolismo , alfa 1-Antitripsina/metabolismo , alfa-Macroglobulinas/metabolismo , Adolescente , Adulto , Lentes de Contacto , Femenino , Humanos , Queratocono/terapia , Masculino , Persona de Mediana EdadRESUMEN
PURPOSE: Keratoconus is characterized by thinning and scarring of the central region of the cornea. Previous research showed that, in corneas obtained from patients with keratoconus, lysosomal enzyme activities are elevated, whereas levels of protease inhibitors such as alpha1-proteinase inhibitor are reduced. This study was undertaken to examine further the expression of a spectrum of proteolytic enzymes and protease inhibitors. METHODS: Corneal buttons were collected from patients with keratoconus, healthy subjects, and patients with other corneal diseases. Immunohistochemical staining was performed on paraffin sections. Enzymatic assays and western blot analysis were carried out for cathepsins B and G. In addition, an in situ zymography procedure was used to examine the gelatin- and casein-digesting activities in corneas with keratoconus. RESULTS: An enhanced staining was found with antibodies to cathepsins B and G. Enzymatic assays and western blotting confirmed that the levels of these two enzymes were elevated in corneas with keratoconus. No alteration was noted with any of the matrix metalloproteinase (MMP) family members and other enzymes and inhibitors examined, although in situ zymography did indicate an increase in net gelatin- and casein-digesting activities in corneas with keratoconus. These activities were mostly abolished by inhibitors for serine and cysteine proteinases, but not by those for MMPs and aspartic proteinases. CONCLUSIONS: Levels of cathepsins B and G are increased in corneas with keratoconus. These enzymes may contribute to the heightened in situ gelatin- and casein-digesting activities, leading to abnormalities in keratoconus.
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Córnea/enzimología , Endopeptidasas/metabolismo , Queratocono/enzimología , Inhibidores de Proteasas/metabolismo , Activador de Tejido Plasminógeno/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Western Blotting , Niño , Preescolar , Córnea/patología , Enfermedades de la Córnea/enzimología , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Técnicas para Inmunoenzimas , Queratocono/patología , Persona de Mediana EdadRESUMEN
The transcripts of the alpha1-proteinase inhibitor in the cornea are different from those in hepatocytes and monocytes, suggesting that alpha1-proteinase inhibitor gene transcription may respond to different cell-specific regulatory mechanisms. Although information on alpha1-proteinase inhibitor gene structure has been obtained, little is known regarding the cis- and trans-acting factors that regulate its expression. In this study, we cloned and sequenced a 2. 7-kilobase 5'-flanking region upstream from the corneal transcription initiation site of the gene, demonstrated functional promoter activity, and identified the regulatory elements. Sequencing revealed that the 5'-flanking element was highly G/C-rich in regions proximal to the corneal transcription start site. DNase I footprinting located 10 potential Sp1-binding sites between nucleotides -1519 and +44. The putative promoter was functional in human corneal stromal cells, but not in human skin, scleral, and conjunctival fibroblasts, suggesting that the promoter may be corneal cell-specific. The promoter activity in the corneal cells was repressed when Sp1 was coexpressed. In the cornea-thinning disease keratoconus, down-regulation of the alpha1-proteinase inhibitor gene and increased Sp1 expression have both been demonstrated. The current results suggest that down-regulation of the inhibitor in keratoconus corneas may be related directly to overexpression of the Sp1 gene. This information may help elucidate the molecular pathways leading to the altered alpha1-proteinase inhibitor expression in keratoconus.
Asunto(s)
Córnea/metabolismo , Regiones Promotoras Genéticas , Factor de Transcripción Sp1/metabolismo , alfa 1-Antitripsina/biosíntesis , alfa 1-Antitripsina/genética , Secuencia de Bases , Células Cultivadas , Clonación Molecular , Córnea/citología , Huella de ADN , Desoxirribonucleasa I , Exones , Regulación de la Expresión Génica , Humanos , Hígado/metabolismo , Datos de Secuencia Molecular , Piel/metabolismo , Células del Estroma/metabolismo , Transcripción GenéticaAsunto(s)
Acreditación/normas , Córnea , Educación Médica Continua/normas , Oftalmopatías , Becas/normas , Oftalmología/educación , HumanosRESUMEN
OBJECTIVE: To examine the 3-dimensional collagen fibril organization in the Bowman layer of keratoconus corneas. METHODS: Eight keratoconus corneas, 8 corneas with other diseases, and 5 normal human corneas were studied. A cell maceration method in combination with scanning electron microscopy was used to examine the collagen network in the Bowman layer. RESULTS: In normal corneas, the surface of the Bowman layer was smooth and collagen fibrils were regularly arranged. By contrast, sharply edged defects in the Bowman layer were found in keratoconus corneas. Lattice-like configurations of the ruptured Bowman layer and collagenous scar tissue were observed, to varying degrees, in all keratoconus corneas examined. None of the other diseased corneas exhibited the ruptures. CONCLUSIONS: Scanning electron microscopy demonstrated alterations in the Bowman layer specific to keratoconus. Fragmentation of the Bowman layer may be an early change leading to keratoconus conditions.
Asunto(s)
Córnea/ultraestructura , Queratocono/patología , Microscopía Electrónica de Rastreo , Adolescente , Adulto , Anciano , Membrana Basal/ultraestructura , División Celular , Preescolar , Colágeno/ultraestructura , Enfermedades de la Córnea/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Rotura EspontáneaRESUMEN
PURPOSE: To determine whether propranolol can decrease surgical tremor and anxiety in residents performing ocular microsurgery without impairing patient or physician safety. METHODS: In this randomized, double-masked, crossover study, 5 third-year ophthalmology residents ingested a capsule containing either propranolol, 40 mg, or placebo 1 hour prior to performing ophthalmic microsurgery. All residents were healthy men under age 30 years. Prior to commencement of the study, all participants had successfully been administered a test dose of propranolol without side effects. The study took place over a 10-week period. At the conclusion of each case, both the resident and attending surgeon observer independently completed a form grading, on a sliding scale: (1) amount of overall tremor; (2) amount of tremor during placement of the first 3 sutures after lens or nucleus extraction; (3) anticipated difficulty of the case; (4) actual difficulty with the case; and (5) anxiety (surgeon only). In addition, the type of procedure performed, complications encountered, and surgeon side effects were recorded. The data were analyzed with a 2-way analysis of variance for unbalanced data. RESULTS: A total of 73 surgical cases were performed; the surgeons were administered propranolol for 40 cases and placebo for 33. As judged by the resident surgeon, there was a highly significant effect of propranolol in decreasing anxiety (P = .0058), reducing surgical tremor overall (P < .0001), and reducing tremor while placing the first 3 sutures following lens extraction (P < .0001). There was no treatment-by-surgeon interaction for any of the measures. Complications and difficulty of the case, as judged by both the resident and attending surgeons, were not significantly different in the propranolol versus placebo groups (P > .05). There were no side effects reported or observed in any of the surgeons. CONCLUSIONS: Propranolol, 40 mg, administered 1 hour prior to surgery, significantly decreases tremor and anxiety in the surgeon without untoward effects to the surgeon and the patient. However, it is unknown whether decreased tremor and anxiety improved surgical outcome.
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Antagonistas Adrenérgicos beta/uso terapéutico , Ansiolíticos/uso terapéutico , Ansiedad/tratamiento farmacológico , Internado y Residencia , Procedimientos Quirúrgicos Oftalmológicos , Propranolol/uso terapéutico , Temblor/tratamiento farmacológico , Adulto , Estudios Cruzados , Método Doble Ciego , Humanos , Masculino , Placebos/uso terapéutico , Calidad de la Atención de Salud , Resultado del TratamientoRESUMEN
PURPOSE: Because corneal tissue with familial subepithelial corneal amyloidosis (FSCA; gelatinous drop-like dystrophy of the cornea) contains lactoferrin the possibility that the FSCA gene was the human lactoferrin (hLF) gene was investigated. Due to contradictory published information we also mapped the hLF gene. METHODS: We mapped the hLF gene using a genomic clone of the entire hLF gene as a probe by fluorescence in situ hybridization (FISH). Utilizing PCR primers that are specific to the hLF gene, we also mapped the hLF via radiation somatic cell hybrid analysis. Linkage of the FSCA gene to the hLF gene was evaluated by genetic linkage analysis using polymorphic markers within and in the vicinity of the hLF gene. RESULTS: The hLF gene mapped to the short arm of chromosome 3 at 3p21. Linkage analysis using polymorphic markers for hLF and haplotype analysis of the 3p21 loci indicates that the FSCA gene is not linked to the 3p21 locus. CONCLUSIONS: The gene for FSCA is not the hLF gene in these families.