RESUMO
PURPOSE: To describe corneal and crystalline lens dimensions before, during, and after myopia onset compared with age-matched emmetropic values. METHODS: Subjects were 732 children aged 6 to 14 years who became myopic and 596 emmetropic children participating between 1989 and 2007 in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error Study. Refractive error was measured using cycloplegic autorefraction, corneal power using a hand-held autokeratometer, crystalline lens parameters using video-based phakometry, and vitreous chamber depth (VCD) using A-scan ultrasonography. Corneal and crystalline lens parameters in children who became myopic were compared with age-, gender-, and ethnicity-matched model estimates of emmetrope values annually from 5 years before through 5 years after the onset of myopia. The comparison was made without and then with statistical adjustment of emmetrope component values to compensate for the effects of longer VCDs in children who became myopic. RESULTS: Before myopia onset, the crystalline lens thinned, flattened, and lost power at similar rates for emmetropes and children who became myopic. The crystalline lens stopped thinning, flattening, and losing power within ±1 year of onset in children who became myopic compared with emmetropes statistically adjusted to match the longer VCDs of children who became myopic. In contrast, the cornea was only slightly steeper in children who became myopic compared with emmetropes (<0.25 D) and underwent little change across visits. CONCLUSIONS: Myopia onset is characterized by an abrupt loss of compensatory changes in the crystalline lens that continue in emmetropes throughout childhood axial elongation. The mechanism responsible for this decoupling remains speculative but might include restricted equatorial growth from internal mechanical factors.
Assuntos
Córnea/patologia , Cristalino/patologia , Miopia/diagnóstico , Refração Ocular/fisiologia , Adolescente , Criança , Topografia da Córnea , Progressão da Doença , Seguimentos , Humanos , Miopia/fisiopatologia , Oftalmoscopia , Estudos RetrospectivosRESUMO
Porphyromonas gingivalis is a Gram-negative obligate anaerobe that has been implicated in the etiology of adult periodontitis. We recently introduced a Drosophila melanogaster killing model for examination of P. gingivalis-host interactions. In the current study, the Drosophila killing model was used to characterize the host response to P. gingivalis infection by identifying host components that play a role during infection. Drosophila immune response gene mutants were screened for altered susceptibility to killing by P. gingivalis. The Imd signaling pathway was shown to be important for the survival of Drosophila infected by nonencapsulated P. gingivalis strains but was dispensable for the survival of Drosophila infected by encapsulated P. gingivalis strains. The P. gingivalis capsule was shown to mediate resistance to killing by Drosophila antimicrobial peptides (Imd pathway-regulated cecropinA and drosocin) and human beta-defensin 3. Drosophila thiol-ester protein II (Tep II) and Tep IV and the tumor necrosis factor (TNF) homolog Eiger were also involved in the immune response against P. gingivalis infection, while the scavenger receptors Eater and Croquemort played no roles in the response to P. gingivalis infection. This study demonstrates that the Drosophila killing model is a useful high-throughput model for characterizing the host response to P. gingivalis infection and uncovering novel interactions between the bacterium and the host.
Assuntos
Drosophila melanogaster/microbiologia , Porphyromonas gingivalis/fisiologia , Animais , Cápsulas Bacterianas , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Deleção de Genes , Regulação da Expressão Gênica/fisiologia , Interações Hospedeiro-Patógeno , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Transdução de SinaisRESUMO
Porphyromonas gingivalis has been implicated in the etiology of adult periodontitis. In this study, we examined the viability of Drosophila melanogaster as a new model for examining P. gingivalis-host interactions. P. gingivalis (W83) infection of Drosophila resulted in a systemic infection that killed in a dose-dependent manner. Differences in the virulence of several clinically prevalent P. gingivalis strains were observed in the Drosophila killing model, and the results correlated well with studies in mammalian infection models and human epidemiologic studies. P. gingivalis pathobiology in Drosophila did not result from uncontrolled growth of the bacterium in the Drosophila hemolymph (blood) or overt damage to Drosophila tissues. P. gingivalis killing of Drosophila was multifactorial, involving several bacterial factors that are also involved in virulence in mammals. The results from this study suggest that many aspects of P. gingivalis pathogenesis in mammals are conserved in Drosophila, and thus the Drosophila killing model should be useful for characterizing P. gingivalis-host interactions and, potentially, polymicrobe-host interactions.
Assuntos
Drosophila melanogaster/microbiologia , Porphyromonas gingivalis/fisiologia , Porphyromonas gingivalis/patogenicidade , Animais , Modelos Animais de Doenças , Feminino , Fatores de Tempo , VirulênciaRESUMO
The purpose of the present study was to evaluate the effectiveness of a 3-carboranyl thymidine analogue (3CTA), 3-[5-{2-(2,3-dihydroxyprop-1-yl)-o-carboran-1-yl}pentan-1-yl] thymidine, designated N5-2OH, for boron neutron capture therapy (BNCT) of brain tumors using the RG2 rat glioma model. Target validation was established using the thymidine kinase (TK) 1(+) wild-type, murine L929 cell line and its TK1(-) mutant counterpart, which were implanted s.c. (s.c.) into nude mice. Two intratumoral (i.t.) injections of (10)B-enriched N5-2OH were administered to tumor-bearing mice at 2-hour intervals, after which BNCT was carried out at the Massachusetts Institute of Technology (MIT) Research Reactor. Thirty days after BNCT, mice bearing TK1(+) L929 tumors had a 15x reduction in tumor volume compared with TK1(-) controls. Based on these favorable results, BNCT studies were then initiated in rats bearing intracerebral (i.c.) RG2 gliomas, after i.c. administration of N5-2OH by Alzet osmotic pumps, either alone or in combination with i.v. (i.v.) boronophenylalanine (BPA), a drug that has been used clinically. The mean survival times (MSTs) of RG2 glioma bearing rats were 45.6 +/- 7.2 days, 35.0 +/- 3.3 days, and 52.9 +/- 8.9 days, respectively, for animals that received N5-2OH, BPA, or both. The differences between the survival plots of rats that received N5-2OH and BPA alone were highly significant (P = 0.0003). These data provide proof-of-principle that a 3CTA can function as a boron delivery agent for NCT. Further studies are planned to design and synthesize 3CTAs with enhanced chemical and biological properties, and increased therapeutic efficacy.
Assuntos
Compostos de Boro/uso terapêutico , Terapia por Captura de Nêutron de Boro/métodos , Neoplasias Encefálicas/radioterapia , Timidina Quinase/metabolismo , Timidina/análogos & derivados , Animais , Compostos de Boro/administração & dosagem , Compostos de Boro/química , Compostos de Boro/metabolismo , Linhagem Celular Tumoral , Camundongos , Camundongos Nus , Estrutura Molecular , Ratos , Timidina/administração & dosagem , Timidina/química , Timidina/metabolismo , Timidina/uso terapêuticoRESUMO
PURPOSE: The purpose of the present study was to evaluate the anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb), cetuximab, (IMC-C225) and the anti-EGFRvIII mAb, L8A4, used in combination as delivery agents for boron neutron capture therapy (BNCT) of a rat glioma composed of a mixture of cells expressing either wild-type (F98(EGFR)) or mutant receptors(F98(npEGFRvIII)). EXPERIMENTAL DESIGN: A heavily boronated polyamidoamine dendrimer (BD) was linked by heterobifunctional reagents to produce the boronated mAbs, BD-C225 and BD-L8A4. For in vivo biodistribution and therapy studies, a mixture of tumor cells were implanted intracerebrally into Fischer rats. Biodistribution studies were carried out by administering (125)I-labeled bioconjugates via convection-enhanced delivery (CED), and for therapy studies, nonradiolabeled bioconjugates were used for BNCT. This was carried out 14 days after tumor implantation and 24 h after CED at the Massachusetts Institute of Technology nuclear reactor. RESULTS: Following CED of a mixture of (125)I-BD-C225 and (125)I-BD-L8A4 to rats bearing composite tumors, 61.4% of the injected dose per gram (ID/g) was localized in the tumor compared with 30.8% ID/g for (125)I-BD-L8A4 and 34.7% ID/g for (125)I-BD-C225 alone. The corresponding calculated tumor boron values were 24.4 mug/g for rats that received both mAbs, and 12.3 and 13.8 mug/g, respectively, for BD-L8A4 or BD-C225 alone. The mean survival time of animals bearing composite tumors, which received both mAbs, was 55 days (P < 0.0001) compared with 36 days for BD-L8A4 and 38 days for BD-C225 alone, which were not significantly different from irradiated controls. CONCLUSIONS: Both EGFRvIII and wild-type EGFR tumor cell populations must be targeted using a combination of BD-cetuximab and BD-L8A4. Although in vitro C225 recognized both receptors, in vivo it was incapable of delivering the requisite amount of (10)B for BNCT of EGFRvIII-expressing gliomas.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Boro/análise , Neoplasias Encefálicas/radioterapia , Receptores ErbB/análise , Glioma/radioterapia , Animais , Sítios de Ligação de Anticorpos , Boro/imunologia , Modelos Animais de DoençasRESUMO
PURPOSE: To evaluate the relationship between accommodation, visual acuity, and emmetropization in human infancy. METHODS: Defocus at distance and near (57 cm) was assessed using Mohindra and dynamic retinoscopy, respectively, in 262 normal birthweight infants at 3, 9, and 18 months of age. Preferential looking provided acuity data at the same ages. The spherical equivalent refractive error was measured by cycloplegic retinoscopy (cyclopentolate 1%). RESULTS: Univariate linear regression analyses showed no associations between the change in refractive error and defocus at distance or near. Change in refractive error was linearly related to the accommodative response at distance (R = 0.17, p < 0.0001) and near (R = 0.13, p < 0.0001). The ten subjects with the poorest emmetropization relative to the change predicted by the linear effects of their refractive error had higher average levels of hyperopic defocus at distance and near (p < 0.043). Logistic regression showed a decrease in the odds of reaching +2.00 diopter or less hyperopia by 18 months with increasing levels of hyperopia at 3 months, or if Mohindra retinoscopy was myopic combined with acuity better than the median level of 1.25 logMAR [area under the receiver operating characteristic curve = 0.78 (95% CI = 0.68 to 0.88)]. CONCLUSIONS: The level of cycloplegic refractive error was the best single factor for predicting emmetropization by 18 months of age, with smaller contributions from visual acuity and Mohindra retinoscopy. The lack of correlation between defocus and change in refractive error does not support a simple model of emmetropization in response to the level of hyperopic defocus. Infants were capable of maintaining accurate average levels of accommodation across a range of moderate hyperopic refractive errors at 3 months of age. The association between the change in refractive error and accommodative response suggests that accommodation is a plausible visual signal for emmetropization.
Assuntos
Acomodação Ocular , Desenvolvimento Infantil , Recuperação de Função Fisiológica , Erros de Refração/fisiopatologia , Acuidade Visual , Feminino , Humanos , Hiperopia/fisiopatologia , Lactente , Masculino , Valor Preditivo dos Testes , Erros de Refração/patologia , RetinoscopiaRESUMO
PURPOSE: To identify whether parental history of myopia and/or parent-reported children's visual activity levels can predict juvenile-onset myopia. METHODS: Survey-based data from Orinda Longitudinal Study of Myopia subjects from 1989 to 2001 were used to predict future myopia. Univariate and multiple logistic regression analyses were performed, and receiver operator characteristic (ROC) curves were generated. Differences among the areas under the ROC curves were compared using the method of multiple comparison with the best. RESULTS: Of the 514 children eligible for this analysis, 111 (21.6%) became myopic. Differences in the third grade between eventual myopes and nonmyopes were seen for the number of myopic parents (P < 0.001) and for the number of sports and outdoor activity hours per week (11.65 +/- 6.97 hours for nonmyopes vs. 7.98 +/- 6.54 hours for future myopes, P < 0.001). Analysis of the areas under the ROC curves showed three variables with a predictive value better than chance: the number of myopic parents, the number of sports and outdoor activity hours per week, and the number of reading hours per week. After controlling for sports and outdoor hours per week and parental myopia history, reading hours per week was no longer a statistically significant factor. The area under the curve for the parental myopia history and sports and outdoor activities model was 0.73. A significant interaction in the logistic model showed a differential effect of sport and outdoor activity hours per week based on a child's number of myopic parents. CONCLUSIONS: Parental history of myopia was an important predictor in univariate and multivariate models, with a differential effect of sports and outdoor activity hours per week based on the number of myopic parents. Lower amounts of sports and outdoor activity increased the odds of becoming myopic in those children with two myopic parents more than in those children with either zero or one myopic parent. The chance of becoming myopic for children with no myopic parents appears lowest in the children with the highest amount of sports and outdoor activity, compared with those with two myopic parents.
Assuntos
Atividades de Lazer , Atividade Motora , Miopia/epidemiologia , Miopia/genética , Esportes/estatística & dados numéricos , Adulto , Criança , Saúde da Família , Humanos , Modelos Logísticos , Estudos Longitudinais , Pais , Valor Preditivo dos Testes , Curva ROCRESUMO
PURPOSE: To evaluate refractive error, axial length, and relative peripheral refractive error before, during the year of, and after the onset of myopia in children who became myopic compared with emmetropes. METHODS: Subjects were 605 children 6 to 14 years of age who became myopic (at least -0.75 D in each meridian) and 374 emmetropic (between -0.25 D and +1.00 D in each meridian at all visits) children participating between 1995 and 2003 in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study. Axial length was measured annually by A-scan ultrasonography. Relative peripheral refractive error (the difference between the spherical equivalent cycloplegic autorefraction 30 degrees in the nasal visual field and in primary gaze) was measured using either of two autorefractors (R-1; Canon, Lake Success, NY [no longer manufactured] or WR 5100-K; Grand Seiko, Hiroshima, Japan). Refractive error was measured with the same autorefractor with the subjects under cycloplegia. Each variable in children who became myopic was compared to age-, gender-, and ethnicity-matched model estimates of emmetrope values for each annual visit from 5 years before through 5 years after the onset of myopia. RESULTS: In the sample as a whole, children who became myopic had less hyperopia and longer axial lengths than did emmetropes before and after the onset of myopia (4 years before through 5 years after for refractive error and 3 years before through 5 years after for axial length; P < 0.0001 for each year). Children who became myopic had more hyperopic relative peripheral refractive errors than did emmetropes from 2 years before onset through 5 years after onset of myopia (P < 0.002 for each year). The fastest rate of change in refractive error, axial length, and relative peripheral refractive error occurred during the year before onset rather than in any year after onset. Relative peripheral refractive error remained at a consistent level of hyperopia each year after onset, whereas axial length and myopic refractive error continued to elongate and to progress, respectively, although at slower rates compared with the rate at onset. CONCLUSIONS: A more negative refractive error, longer axial length, and more hyperopic relative peripheral refractive error in addition to faster rates of change in these variables may be useful for predicting the onset of myopia, but only within a span of 2 to 4 years before onset. Becoming myopic does not appear to be characterized by a consistent rate of increase in refractive error and expansion of the globe. Acceleration in myopia progression, axial elongation, and peripheral hyperopia in the year prior to onset followed by relatively slower, more stable rates of change after onset suggests that more than one factor may influence ocular expansion during myopia onset and progression.
Assuntos
Olho/patologia , Miopia/fisiopatologia , Refração Ocular/fisiologia , Adolescente , Idade de Início , Criança , Olho/diagnóstico por imagem , Feminino , Humanos , Hiperopia/etnologia , Hiperopia/fisiopatologia , Masculino , Modelos Biológicos , Miopia/etnologia , UltrassonografiaRESUMO
PURPOSE: The purpose of the present study was to evaluate a boronated EGFRvIII-specific monoclonal antibody, L8A4, for boron neutron capture therapy (BNCT) of the receptor-positive rat glioma, F98(npEGFRvIII). EXPERIMENTAL DESIGN: A heavily boronated polyamido amine (PAMAM) dendrimer (BD) was chemically linked to L8A4 by two heterobifunctional reagents, N-succinimidyl 3-(2-pyridyldithio)propionate and N-(k-maleimidoundecanoic acid)hydrazide. For in vivo studies, F98 wild-type receptor-negative or EGFRvIII human gene-transfected receptor-positive F98(npEGFRvIII) glioma cells were implanted i.c. into the brains of Fischer rats. Biodistribution studies were initiated 14 days later. Animals received [(125)I]BD-L8A4 by either convection enhanced delivery (CED) or direct i.t. injection and were euthanized 6, 12, 24, or 48 hours later. RESULTS: At 6 hours, equivalent amounts of the bioconjugate were detected in receptor-positive and receptor-negative tumors, but by 24 hours the amounts retained by receptor-positive gliomas were 60.1% following CED and 43.7% following i.t. injection compared with 14.6% ID/g by receptor-negative tumors. Boron concentrations in normal brain, blood, liver, kidneys, and spleen all were at nondetectable levels (<0.5 microg/g) at the corresponding times. Based on these favorable biodistribution data, BNCT studies were initiated at the Massachusetts Institute of Technology Research Reactor-II. Rats received BD-L8A4 ( approximately 40 microg (10)B/ approximately 750 mug protein) by CED either alone or in combination with i.v. boronophenylalanine (BPA; 500 mg/kg). BNCT was carried out 24 hours after administration of the bioconjugate and 2.5 hours after i.v. injection of BPA for those animals that received both agents. Rats that received BD-L8A4 by CED in combination with i.v. BPA had a mean +/- SE survival time of 85.5 +/- 15.5 days with 20% long-term survivors (>6 months) and those that received BD-L8A4 alone had a mean +/- SE survival time of 70.4 +/- 11.1 days with 10% long-term survivors compared with 40.1 +/- 2.2 days for i.v. BPA and 30.3 +/- 1.6 and 26.3 +/- 1.1 days for irradiated and untreated controls, respectively. CONCLUSIONS: These data convincingly show the therapeutic efficacy of molecular targeting of EGFRvIII using either boronated monoclonal antibody L8A4 alone or in combination with BPA and should provide a platform for the future development of combinations of high and low molecular weight delivery agents for BNCT of brain tumors.
Assuntos
Receptores ErbB/análise , Glioma/radioterapia , Animais , Anticorpos Monoclonais/uso terapêutico , Compostos de Boro/uso terapêutico , Terapia por Captura de Nêutron de Boro , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/radioterapia , Receptores ErbB/genética , Receptores ErbB/metabolismo , Glioma/patologia , Humanos , Injeções , Radioisótopos do Iodo/farmacocinética , Radioisótopos do Iodo/uso terapêutico , Ratos , Proteínas Recombinantes/metabolismo , TransfecçãoRESUMO
PURPOSE: To evaluate accommodative lag before, during the year of, and after the onset of myopia in children who became myopic, compared with emmetropes. METHODS: The subjects were 568 children who became myopic (at least -0.75 D in each meridian) and 539 children who were emmetropic (between -0.25 D and +1.00 D in each meridian at all visits) participating between 1995 and 2003 in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study. Accommodative lag was measured annually with either a Canon R-1 (Canon USA., Lake Success, NY; no longer manufactured) or a Grand Seiko WR 5100-K (Grand Seiko Co., Hiroshima, Japan) autorefractor. Subjects wore their habitual refractive corrections while viewing a letter target accommodative stimulus of 4 D (either in a Badal system or at 25 cm from the subject, designated Badal and near, respectively) or of 2 D (Badal only). Refractive error was measured with the same autorefractor in subjects under cycloplegia. Accommodative lag in children who became myopic was compared to age-, gender-, and ethnicity-matched model estimates of emmetropic values for each annual visit from 5 years before, through 5 years after, the onset of myopia. RESULTS: In the sample as a whole, accommodative lag was not significantly different in children who became myopic compared with model estimates in emmetropes in any year before onset of myopia for either the 4-D or 2-D Badal stimulus. For the 4-D near target, there was only a greater amount of accommodative lag in children who became myopic compared with emmetropes 4 years before onset (difference, 0.22 D; P = 0.0002). Accommodative lag was not significantly elevated during the year of onset of myopia in any of the three measurement conditions (P < 0.82 for all three). A consistently higher lag was seen in children after the onset of their myopia (range, 0.13-0.56 D; P < 0.004 for all comparisons). These patterns were generally followed by each ethnic group, with Asian children typically showing the most, African-American and white children showing the least, and Hispanic children having intermediate accommodative lag. CONCLUSIONS: Substantive and consistent elevations in accommodative lag relative to model estimates of lag in emmetropes did not occur in children who became myopic before the onset of myopia or during the year of onset. Increased accommodative lag occurred in children after the onset of myopia. Elevated accommodative lag is unlikely to be a useful predictive factor for the onset of myopia. Increased hyperopic defocus from accommodative lag may be a consequence rather than a cause of myopia.
Assuntos
Acomodação Ocular/fisiologia , Miopia/fisiopatologia , Adolescente , Criança , Etnicidade , Feminino , Humanos , Masculino , Miopia/etnologiaRESUMO
Primary central nervous system lymphoma (PCNSL) that arises in immune-deficient patients is an aggressive B-cell neoplasm that is universally associated with the EBV. Patients with EBV(+) PCNSL face a particularly poor prognosis with median survival times of 2-12 months despite aggressive management with radiation therapy. We have developed a preclinical model of EBV(+) PCNSL to explore strategies that specifically target EBV-infected B lymphoblasts in vivo. Stereotactic implantation of EBV-transformed human lymphoblastoid B-cell lines into the caudate nucleus of the nude rat resulted in lethal CNS tumor burden manifested by the onset of focal neurological symptoms within 21 days. Histological evaluation at autopsy revealed a multifocal, perivascular human EBV(+) lymphoblastic B-cell infiltrate that displayed a latency type III EBV gene expression profile similar to PCNSL that develops in some immune-deficient patients. Radiation (1600 cGy) of lymphoblastoid B-cell lines resulted in up-regulation of the EBV thymidine kinase (EBV-TK) transcript and sensitization of these cells to drug-induced apoptosis using nucleoside analogs. Enhanced expression of EBV-TK mRNA in EBV(+) PCNSL tumors by radiation therapy occurred in a dose-dependent fashion. In vivo trials using the nude rat PCNSL model demonstrated significantly improved mean survival time (MST) with single fraction whole-brain radiotherapy (WBRT) and antiviral therapy consisting of zidovudine (AZT) and ganciclovir (GCV; MST 41.3 +/- 3.3 days; P = 0.05), compared with either antiviral therapy (MST 32.1 +/- 1.1 days) or WBRT alone (MST 22 +/- 0.8 days). We found constitutive and abundant EBV-TK mRNA expression in a stereotactic core biopsy specimen from a solid organ transplant patient with EBV(+) PCNSL. Withdrawal of immunosuppression did not result in disease regression. This patient achieved a complete response after therapy with high-dose AZT and GCV in the absence of WBRT, and remains in remission on oral maintenance AZT/GCV therapy 3 years after diagnosis. These results suggest that antiviral therapies can be effectively explored in vivo using a preclinical animal model of human EBV(+) PCNSL with subsequent translation to patients with EBV(+) PCNSL.
Assuntos
Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/virologia , Infecções por Vírus Epstein-Barr/terapia , Herpesvirus Humano 4 , Linfoma de Células B/terapia , Linfoma de Células B/virologia , Animais , Antivirais/farmacocinética , Antivirais/farmacologia , Neoplasias Encefálicas/metabolismo , Terapia Combinada , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/genética , Infecções por Vírus Epstein-Barr/metabolismo , Ganciclovir/farmacocinética , Ganciclovir/farmacologia , Herpesvirus Humano 4/enzimologia , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/efeitos da radiação , Humanos , Transplante de Rim/efeitos adversos , Linfoma de Células B/metabolismo , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Ratos , Timidina Quinase/biossíntese , Timidina Quinase/genética , Regulação para Cima/efeitos da radiação , Ensaios Antitumorais Modelo de Xenoenxerto , Zidovudina/farmacocinética , Zidovudina/farmacologiaRESUMO
PURPOSE: To compare ocular component growth curves among four refractive error groups in children. methods Cycloplegic refractive error was categorized into four groups: persistent emmetropia between -0.25 and +1.00 D (exclusive) in both the vertical and horizontal meridians on all study visits (n = 194); myopia of at least -0.75 D in both meridians on at least one visit (n = 247); persistent hyperopia of at least +1.00 D in both meridians on all visits (n = 43); and emmetropizing hyperopia of at least +1.00 D in both meridians on at least the first but not at all visits (n = 253). Subjects were seen for three visits or more between the ages of 6 and 14 years. Growth curves were modeled for the persistent emmetropes to describe the relation between age and the ocular components and were applied to the other three refractive error groups to determine significant differences. results At baseline, eyes of myopes and persistent emmetropes differed in vitreous chamber depth, anterior chamber depth, axial length, and corneal power and produced growth curves that showed differences in the same ocular components. Persistent hyperopes were significantly different from persistent emmetropes in most components at baseline, whereas growth curve shapes were not significantly different, with the exception of anterior chamber depth (slower growth in persistent hyperopes compared with emmetropes) and axial length (lesser annual growth per year in persistent hyperopes compared with emmetropes). The growth curve shape for corneal power was different between the emmetropizing hyperopes and persistent emmetropes (increasing corneal power compared with decreasing power in emmetropes). conclusions Comparisons of growth curves between persistent emmetropes and three other refractive error groups showed that there are many similarities in the growth patterns for both the emmetropizing and persistent hyperopes, whereas the differences in growth lie mainly between the emmetropes and myopes.
Assuntos
Olho/crescimento & desenvolvimento , Hiperopia/fisiopatologia , Miopia/fisiopatologia , Adolescente , Câmara Anterior/crescimento & desenvolvimento , Criança , Humanos , Corpo Vítreo/crescimento & desenvolvimentoRESUMO
PURPOSE: To evaluate the contribution made by the ocular components to the emmetropization of spherical equivalent refractive error in human infants between 3 and 9 months of age. METHODS: Keratophakometry in two meridians was performed on 222 normal-birthweight infant subjects at 3 and 9 months of age. The spherical equivalent refractive error was measured by cycloplegic retinoscopy (cyclopentolate 1%). Anterior chamber depth, lens thickness, and vitreous chamber depth were measured by A-scan ultrasonography over the closed eyelid. RESULTS: Both the mean and SD for spherical equivalent refractive error decreased between 3 and 9 months of age (+2.16 +/- 1.30 D at 3 months; +1.36 +/- 1.06 D at 9 months; P < 0.0001, for the change in both mean and SD). Average ocular component change was characterized by increases in axial length, thinning, and flattening of the crystalline lens, increases in lens equivalent refractive index, and decreases in lens and corneal power. Initial refractive error was associated in a nonlinear manner with the change in refractive error (R(2) = 0.41; P < 0.0001) and with axial growth (R(2) = 0.082; P = 0.0005). Reduction in hyperopia correlated significantly with increases in axial length (R(2) = 0.16; P < 0.0001), but not with changes in corneal and lenticular power. Decreases in lenticular and corneal power were associated with axial elongation (R(2) = 0.40, R(2) = 0.12, respectively; both P < 0.0001). CONCLUSIONS: Modulation in the amount of axial growth in relation to initial refractive error appeared to be the most influential factor in emmetropization of spherical equivalent refractive error. The associations between initial refractive error, subsequent axial growth, and change in refractive error were consistent with a visual basis for emmetropization. The cornea and crystalline lens lost substantial amounts of dioptric power in this phase of growth, but neither appeared to play a significant role in emmetropization.
Assuntos
Córnea/fisiologia , Olho/crescimento & desenvolvimento , Cristalino/fisiologia , Refração Ocular/fisiologia , Retinoscopia , Visão Ocular/fisiologia , Acomodação Ocular/fisiologia , Feminino , Humanos , Lactente , Masculino , Fenômenos Fisiológicos Oculares , Erros de Refração/fisiopatologiaRESUMO
Complaints of excessive numbers of flies were reported by citizens living in a rural area surrounding a large (>2 million laying hens) egg-layer facility in northwestern Ohio. Sticky cylinder traps and hanging fly strips were used at outdoor and indoor locations, respectively, at known distances from the layer farm and from control sites to determine the most likely source of the flies and to determine the severity of the problem compared with fly populations in nearby rural settings. House flies, Musca domestica (L.), were the predominant flies captured on fly traps located within 6.4 km of the poultry operations. There was a significantly greater number of M. domestica trapped in the study area surrounding the layer facility than in the control areas. The quantity of house flies captured decreased with increased distance from the layer farm. Two years into the study, a second egg-layer facility opened in an area that was originally a control site. With regard to this second farm, after 4 yr of study, there was a significant difference shown between the population of house flies during the 2-yr control phase and the 2-yr period when the egg-layer facility was operational. This study documented that large egg layer facilities can significantly increase the house fly population in the surrounding community up to 6.4 km from the source of the flies and may result in a severe nuisance up to 3.2 km away.
Assuntos
Demografia , Moscas Domésticas/fisiologia , Movimento/fisiologia , Criação de Animais Domésticos , Animais , Ohio , Dinâmica Populacional , Aves Domésticas , Manejo de Espécimes/métodos , Estatísticas não ParamétricasRESUMO
PURPOSE: Boron neutron capture therapy (BNCT) has been used clinically as a single modality treatment for high-grade gliomas and melanomas metastatic to the brain. The purpose of the present study was to determine whether its efficacy could be enhanced by an X-ray boost administered after BNCT. Two brain tumor models were used, the F98 glioma as a model for primary brain tumors and the MRA 27 human melanoma as a model for metastatic brain tumors. METHODS AND MATERIALS: For biodistribution studies, either 10(5) F98 glioma cells were implanted stereotactically into the brains of syngeneic Fischer rats or 10(6) MRA 27 melanoma cells were implanted intracerebrally into National Institutes of Health (NIH)-rnu nude rats. Biodistribution studies were performed 11-13 days after implantation of the F98 glioma and 20-24 days after implantation of the MRA 27 melanoma. Animals bearing the F98 glioma received a combination of two boron-containing drugs, sodium borocaptate at a dose of 30 mg/kg and boron phenylalanine (BPA) at a dose of 250 mg/kg. MRA 27 melanoma-bearing rats received BPA (500 mg/kg) containing an equivalent amount of 10B (27 mg B/kg). The drugs were administered by either intracarotid or i.v. injection. RESULTS: The tumor boron concentration after intracarotid injection was approximately 50% greater in the F98 glioma and MRA 27 melanoma after intracarotid injection (20.8 and 36.8 microg/g, respectively) compared with i.v. injection (11.2 and 19.5 microg/g, respectively). BNCT was carried out at the Brookhaven National Laboratory Medical Research Reactor approximately 14 days after tumor implantation of either the F98 glioma or the MRA 27 melanoma. Approximately 7-10 days after BNCT, subsets of animals were irradiated with 6-MV photons, produced by a linear accelerator at a total dose of 15 Gy, delivered in 5-Gy daily fractions. F98 glioma-bearing rats that received intracarotid or i.v. sodium borocaptate plus BPA, followed 2.5 h later by BNCT and 7-10 days later by X-rays, had similar mean survival times (61 days and 53 days, respectively, p = 0.25), and the non X-irradiated, BNCT-treated animals had a mean survival time of 52 and 40 days, respectively, for intracarotid vs. i.v. injection; the latter was equivalent to that of the irradiated animals. The corresponding survival time for MRA 27 melanoma-bearing rats that received intracarotid or i.v. BPA, followed by BNCT and then X-irradiation, was 75 and 82 days, respectively (p = 0.5), 54 days without X-irradiation (p = 0.0002), 37 days for X-irradiation alone, and 24 days for untreated controls. In contrast to the data obtained with the F98 glioma, MRA 27 melanoma-bearing rats that received i.v. BPA, followed by BNCT, had a highly significant difference in mean survival time compared with the irradiated controls (54 vs. 37 days, p = 0.008). CONCLUSION: Our data are the first to suggest that a significant therapeutic gain may be obtained when BNCT is combined with an X-ray boost. Additional experimental studies are required to determine the optimal combination of X-radiation and neutron doses and whether it is more advantageous to administer the photon boost before or after BNCT.
Assuntos
Compostos de Boro/uso terapêutico , Terapia por Captura de Nêutron de Boro , Neoplasias Encefálicas/radioterapia , Glioma/radioterapia , Melanoma/radioterapia , Animais , Boroidretos/uso terapêutico , Neoplasias Encefálicas/secundário , Linhagem Celular Tumoral , Humanos , Melanoma/secundário , Dosagem Radioterapêutica , Ratos , Ratos Endogâmicos F344 , Ratos Nus , Compostos de Sulfidrila/uso terapêuticoRESUMO
PURPOSE: Multicentric cerebral metastases of melanoma represent an important clinical problem for which there currently is no satisfactory treatment. We previously developed a model for melanoma metastatic to the brain employing nude rats bearing intracerebral implants of the human MRA27 melanoma. The purpose of the present study was to determine if the efficacy of boron neutron capture therapy (BNCT) could be improved by either Cereport (RMP-7) mediated modulation of blood-brain barrier (BBB) permeability or hyperosmotic mannitol-induced BBB disruption using boronophenylalanine (BPA) as the capture agent. METHODS AND MATERIALS: Biodistribution studies were carried out at 0.5, 2.5, and 4 h after intracarotid administration of Cereport (1.5 microg/kg) and intracarotid or i.v. administration of BPA (500 mg/kg). Peak tumor boron concentrations (65.4 microg/g) and the best composite tumor:brain (6.1:1) and tumor:blood (6.3:1) ratios were observed at 2.5 h after intracarotid administration. BNCT was initiated at the Brookhaven Medical Research Reactor 13-14 days after intracerebral implantation of 10(6) MRA27 cells. RESULTS: Untreated control rats had a median survival time (MeST) of 22 days and for irradiated controls, it was 30 days. Rats that received i.v. or intracarotid BPA without Cereport followed by BNCT 2.5 h later had MeSTs of 41 days and 57 days, respectively, with 20% long-term survivors (>180 days) in the latter group. Rats that received intracarotid BPA with Cereport had an MeST of 86 days with 36% long-term survivors, which was very close to that of rats that had hyperosmotic mannitol-induced disruption of the BBB (85 days with 25% long-term survivors). When these two groups were combined, and survival times were compared, using the Wilcoxon rank sum test, to those of rats that received intracarotid BPA without blood-brain barrier disruption, these differences were significant at the level p = 0.01. CONCLUSIONS: Our data show that optimizing the delivery of BPA by means of intracarotid injection combined with opening the BBB by infusing Cereport or a hyperosmotic solution of mannitol significantly enhanced survival times and produced long-term cures of MRA27 melanoma-bearing rats. These observations are relevant to future clinical studies using BNCT for the treatment of intracerebral melanoma.
Assuntos
Barreira Hematoencefálica/efeitos dos fármacos , Compostos de Boro/uso terapêutico , Terapia por Captura de Nêutron de Boro , Bradicinina/análogos & derivados , Bradicinina/uso terapêutico , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Manitol/uso terapêutico , Melanoma/radioterapia , Melanoma/secundário , Fenilalanina/uso terapêutico , Radiossensibilizantes/uso terapêutico , Animais , Compostos de Boro/farmacocinética , Bradicinina/farmacocinética , Neoplasias Encefálicas/mortalidade , Humanos , Manitol/química , Melanoma/mortalidade , Osmose , Fenilalanina/análogos & derivados , Fenilalanina/farmacocinética , Radiossensibilizantes/farmacocinética , Ratos , Ratos NusRESUMO
PURPOSE: To study retrospectively the frequency of myopia progression and risk factors for progression in a sample of adult contact lens wearers. METHODS: From a database of 815 soft contact lens wearers, patients were identified whose age was between 20 and 40 years, who had at least -0.50 D spherical equivalent of myopia in both eyes, three or more refractions, and > or =5 years of follow-up. Only data from the right eye were used. Progression was defined as an increase of at least -1.00 D over 5 years. Subjects were also asked to complete a questionnaire regarding their ocular history, demographics, family history, and the amount of time spent performing different tasks at home and at work. RESULTS: Two hundred ninety-one subjects met the eligibility criteria with a mean baseline refractive error of -3.29 +/- 1.92 D and a mean age of 28.5 +/- 5.0 years. Of these, 21.3% progressed by at least -1.00 D over the 5-year period. The 5-year rate of progression decreased with increasing age (chi(2) = 12.44, P = 0.006). One hundred ninety-seven subjects (67.6%) completed and returned questionnaires. "Progressors" (N = 41) did not differ from "nonprogressors" (N = 156) in terms of hours per day spent reading and writing, computer use, education level, family history of myopia, age of onset of myopia, and contact lens wear. CONCLUSIONS: In this database of soft contact lens wearers, myopia progression was common for subjects in their twenties and less common for those in their thirties.
Assuntos
Lentes de Contato Hidrofílicas/efeitos adversos , Miopia/etiologia , Adulto , Envelhecimento/fisiologia , Progressão da Doença , Feminino , Humanos , Masculino , Miopia/fisiopatologia , Miopia/terapia , Refração Ocular , Estudos Retrospectivos , Fatores de RiscoRESUMO
PURPOSE: To quantify the degree of association between juvenile myopia and parental myopia, near work, and school achievement. METHODS: Refractive error, parental refractive status, current level of near activities (assumed working distance-weighted hours per week spent studying, reading for pleasure, watching television, playing video games or working on the computer), hours per week spent playing sports, and level of school achievement (scores on the Iowa Tests of Basic Skills [ITBS]) were assessed in 366 eighth grade children who participated in the Orinda Longitudinal Study of Myopia in 1991 to 1996. RESULTS: Children with myopia were more likely to have parents with myopia; to spend significantly more time studying, more time reading, and less time playing sports; and to score higher on the ITBS Reading and Total Language subtests than emmetropic children (chi(2) and Wilcoxon rank-sum tests; P < 0.024). Multivariate logistic regression models showed no substantial confounding effects between parental myopia, near work, sports activity, and school achievement, suggesting that each factor has an independent association with myopia. The multivariate odds ratio (95% confidence interval) for two compared with no parents with myopia was 6.40 (2.17-18.87) and was 1.020 (1.008-1.032) for each diopter-hour per week of near work. Interactions between parental myopia and near work were not significant (P = 0.67), indicating no increase in the risk associated with near work with an increasing number of parents with myopia. CONCLUSIONS: Heredity was the most important factor associated with juvenile myopia, with smaller independent contributions from more near work, higher school achievement, and less time in sports activity. There was no evidence that children inherit a myopigenic environment or a susceptibility to the effects of near work from their parents.
Assuntos
Escolaridade , Hereditariedade/genética , Miopia/epidemiologia , Miopia/genética , Pais , Trabalho/estatística & dados numéricos , Adolescente , Adulto , Estudos Transversais , Avaliação Educacional , Saúde da Família , Feminino , Humanos , Masculino , Miopia/etiologia , Razão de Chances , Ohio/epidemiologia , Prevalência , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
Systolic and diastolic time intervals were measured in 11 patients with heart failure before and 1 and 3 months after the placement of atrial biventricular pacemakers for cardiac resynchronization therapy (CRT). CRT shortened the preejection period, principally by reducing left ventricular (LV) electromechanical delay with lesser reduction of isovolumic contraction time, and shortened the duration of LV systole, with a consequent trend of lengthening diastolic time.
Assuntos
Insuficiência Cardíaca/terapia , Marca-Passo Artificial , Idoso , Bloqueio de Ramo/etiologia , Estimulação Cardíaca Artificial , Eletrocardiografia , Feminino , Seguimentos , Sistema de Condução Cardíaco/fisiopatologia , Sistema de Condução Cardíaco/cirurgia , Insuficiência Cardíaca/fisiopatologia , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Contração Miocárdica/fisiologia , Complicações Pós-Operatórias/etiologia , Volume Sistólico/fisiologia , Fatores de Tempo , Resultado do Tratamento , Disfunção Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Esquerda/terapiaRESUMO
OBJECTIVES: Several oral pathologists have described oral leukoplakia of the maxillary vestibule in patients with no traditional risk factors for the condition. On questioning these patients, it was determined that Viadent mouthrinse or Viadent toothpaste was commonly used by them. A hypothesis was developed that Viadent or a component of Viadent caused the lesions. This paper evaluates the association between oral leukoplakia and use of Viadent products. METHODS: A matched case-control study was designed to test the hypothesis that use of Viadent products increases an individual's risk of oral leukoplakia. Cases included 58 patients diagnosed with oral leukoplakia identified through the biopsy service at the Ohio State University, College of Dentistry, Oral Pathology Section. The matched control was a friend or relative of the patient. Cases and controls were administered a questionnaire about their use of Viadent, and other known risk factors for leukoplakia such as tobacco and excessive alcohol use. RESULTS: An age difference was seen between cases and controls, the cases being older (P < .001). After controlling for confounding factors, results of exact conditional logistic regression analyses showed that use of Viadent products was a risk indicator for oral leukoplakia (odds ratio = 10.0; 95% confidence interval = 2.0, 89.2). CONCLUSIONS: Viadent use is a risk indicator for oral leukoplakia, confirming our previous findings.