Corneal and crystalline lens dimensions before and after myopia onset.

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.

Relative peripheral refractive error and the risk of onset and progression of myopia in children.

PURPOSE: To investigate whether relative peripheral hyperopia is a risk factor for either the onset of myopia in children or the rate of myopic progression. METHODS: The risk of myopia onset was assessed in 2043 nonmyopic third-grade children (mean age ± SD = 8.8 ± 0.52 years) participating in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study between 1995 and 2007, 324 of whom became myopic by the eighth grade. Progression analyses used data from 774 myopic children in grades 1 to 8. Foveal and relative peripheral refractive error 30° in the nasal visual field was measured annually by using cycloplegic autorefraction. Axial length was measured by A-scan ultrasonography. RESULTS: The association between more hyperopic relative peripheral refractive error in the third grade and the risk of the onset of myopia by the eighth grade varied by ethnic group (Asian children odds ratio [OR] = 1.56, 95% confidence interval [CI] = 1.06-2.30; African-American children OR = 0.75, 95% CI = 0.58-0.96; Hispanics, Native Americans, and whites showed no significant association). Myopia progression was greater per diopter of more hyperopic relative peripheral refractive error, but only by a small amount (-0.024 D per year; P = 0.02). Axial elongation was unrelated to the average relative peripheral refractive error (P = 0.77), regardless of ethnicity. CONCLUSIONS: Relative peripheral hyperopia appears to exert little consistent influence on the risk of the onset of myopic refractive error, on the rate of myopia progression, or on axial elongation.

Porphyromonas gingivalis-host interactions in a Drosophila melanogaster model.

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.

Porphyromonas gingivalis virulence in a Drosophila melanogaster model.

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.

Accommodation, acuity, and their relationship to emmetropization in infants.

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.

Efficacy of intracerebral delivery of Carboplatin in combination with photon irradiation for treatment of F98 glioma-bearing rats.

PURPOSE: To evaluate the efficacy of prolonged intracerebral (i.c.) administration of carboplatin by means of ALZET osmotic pumps, in combination with radiotherapy for the treatment of intracranial F98 glioma in rats. METHODS AND MATERIALS: Seven days after stereotactic implantation of F98 glioma cells into the brains of Fischer rats, carboplatin was administrated i.c. by means of ALZET pumps over 6 days. Rats were treated at the European Synchrotron Radiation Facility with a single 15-Gy X-ray dose, either given alone or 24 h after administration of carboplatin. RESULTS: Untreated rats had a mean survival time (MST) +/- SE of 23 +/- 1 days, compared with 44 +/- 3 days for X-irradiated animals and 69 +/- 20 days for rats that received carboplatin alone, with 3 of 13 of these surviving >195 days. Rats that received carboplatin followed by X-irradiation had a MST of >142 +/- 21 days and a median survival time of >195 days, with 6 of 11 rats (55%) still alive at the end of the study. The corresponding percentage increases in lifespan, based on median survival times, were 25%, 85%, and 713%, respectively, for carboplatin alone, radiotherapy alone, or the combination. CONCLUSIONS: Our data demonstrate that i.c. infusion of carboplatin by means of ALZET pumps in combination with X-irradiation is highly effective for the treatment of the F98 glioma. They provide strong support for the approach of concomitantly administering chemo- and radiotherapy for the treatment of brain tumors.

Thymidine kinase 1 as a molecular target for boron neutron capture therapy of brain tumors.

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.

Parental history of myopia, sports and outdoor activities, and future myopia.

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.

Refractive error, axial length, and relative peripheral refractive error before and after the onset of myopia.

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.

Changes in periodontal health status are associated with bacterial community shifts as assessed by quantitative 16S cloning and sequencing.

The gingival sulcus contains a complex ecosystem that includes many uncultivated bacteria. Understanding the dynamics of this ecosystem in transitions between health and disease is important in advancing our understanding of the bacterial etiology of periodontitis. The objective of this longitudinal study was to examine the stability of bacterial colonization in the gingival crevice and to explore the relationship between shifts in microbial composition and changes in periodontal health status using a comprehensive, quantitative, culture-independent approach. Subgingival plaque samples and periodontal data were collected from 24 subjects over 2 years. Baseline and 2-year plaque samples were analyzed using quantitative ribosomal 16S cloning and sequencing. Ten subjects remained periodontally healthy over 2 years, the periodontal health of seven subjects worsened, and seven subjects showed clinical improvement. Bacterial stability was greatest among healthy, clinically stable subjects and lowest for subjects whose periodontal status worsened (P = 0.01). Higher numbers of species lost or gained were also observed for subjects whose clinical status changed (P = 0.009). This provides evidence that a change in periodontal status is accompanied by shifts within the bacterial community. Based on these data, measures of microbial stability may be useful in clinical diagnosis and prognosis. Regarding individual species, increases in levels of the uncultivated phylotype Veillonella sp. oral clone X042, a gram-negative bacterium and the most common member of the subgingival bacterial community, were associated with periodontal health (P = 0.04), suggesting that this is an important beneficial species. Filifactor alocis, a gram-positive anaerobe, was found at higher levels in subjects with disease (P = 0.01).

Molecular targeting and treatment of EGFRvIII-positive gliomas using boronated monoclonal antibody L8A4.

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.

Accommodative lag before and after the onset of myopia.

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.

Effect of platelet antigen polymorphism on platelet inhibition by aspirin, clopidogrel, or their combination.

OBJECTIVES: We studied the modifier effect of platelet antigen polymorphism (PlA2) on platelet inhibition by acetylsalicylic acid (ASA, i.e., aspirin), clopidogrel, or their combination in patients with coronary heart disease. BACKGROUND: Clopidogrel, when administered with ASA, was shown to significantly improve the outcome of patients with acute coronary syndromes compared with patients receiving only ASA. We have shown previously that the effect of ASA on platelets is modified by the glycoprotein IIIa single nucleotide polymorphism PlA2. Hence, an important pharmacogenetic question remains whether the antiplatelet effect of clopidogrel is uniform for all patients or, like acetylsalicylic acid, more selective. METHODS: Thirty PlA1/A1 and 30 PlA1/A2 patients were assigned randomly to ASA 325 mg/day, clopidogrel 75 mg/day, or both. After 10 days, platelet function was studied. RESULTS: Clopidogrel provided stronger platelet inhibition than ASA with adenosine diphosphate as the agonist, and combination therapy resulted in greater inhibition than either inhibitor used alone (p < 0.0001). The use of ASA resulted in greater inhibition compared with clopidogrel with epinephrine (p < 0.0001) and collagen as agonists (p < 0.0001). With collagen as the agonist, platelets from PlA1/A2 donors were markedly and significantly less inhibited by ASA (p = 0.005). In contrast, with clopidogrel, no significant difference could be detected between inhibition of Pl(A1/A1) and Pl(A1/A2) platelets. CONCLUSIONS: The combination of ASA and clopidogrel appears superior to either agent alone in inhibiting platelet function. Pl(A2) functions as an important modifier for platelet responsiveness to ASA but not to clopidogrel. These findings could have significant impact on the future design of pharmacogenetic antithrombotic strategies for patients with coronary heart disease.

Spread of Musca domestica (Diptera: muscidae), from two caged layer facilities to neighboring residences in rural Ohio.

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.

Identification of candidate periodontal pathogens and beneficial species by quantitative 16S clonal analysis.

Most studies of the bacterial etiology of periodontitis have used either culture-based or targeted DNA approaches, and so it is likely that pathogens remain undiscovered. The purpose of this study was to use culture-independent, quantitative analysis of biofilms associated with chronic periodontitis and periodontal health to identify pathogens and beneficial species. Samples from subjects with periodontitis and controls were analyzed using ribosomal 16S cloning and sequencing. Several genera, many of them uncultivated, were associated with periodontitis, the most numerous of which were gram positive, including Peptostreptococcus and Filifactor. The genera Megasphaera and Desulfobulbus were elevated in periodontitis, and the levels of several species or phylotypes of Campylobacter, Selenomonas, Deferribacteres, Dialister, Catonella, Tannerella, Streptococcus, Atopobium, Eubacterium, and Treponema were elevated in disease. Streptococcus and Veillonella spp. were found in high numbers in all samples and accounted for a significantly greater fraction of the microbial community in healthy subjects than in those with periodontitis. The microbial profile of periodontal health also included the less-abundant genera Campylobacter, Abiotrophia, Gemella, Capnocytophaga, and Neisseria. These newly identified candidates outnumbered Porphyromonas gingivalis and other species previously implicated as periodontopathogens, and it is not clear if newly identified and more numerous species may play a more important role in pathogenesis. Finally, more differences were found in the bacterial profile between subjects with periodontitis and healthy subjects than between deep and shallow sites within the same subject. This suggests that chronic periodontitis is the result of a global perturbation of the oral bacterial ecology rather than a disease-site specific microbial shift.

Axial growth and changes in lenticular and corneal power during emmetropization in infants.

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.

Comparison of ocular component growth curves among refractive error groups in children.

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.

Refractive astigmatism and the toricity of ocular components in human infants.

PURPOSE: Many studies have characterized astigmatism in infancy, but few have been longitudinal or contained ocular component data. This study characterized the frequency, orientation, and longitudinal change with age of infant astigmatism. Additional factors investigated were the influence of early astigmatism on emmetropization and its relation to corneal and lenticular toricity. METHODS: Three hundred two infants were enrolled in the study. Of these, 298 provided data for at least one visit at 3 +/- 1 months, 9 +/- 1 months, 18 +/- 2 months, and 36 +/- 3 months. Testing included cycloplegic retinoscopy (cyclopentolate 1%), video-based keratophakometry, and ultrasonography over the closed eyelid. RESULTS: Astigmatism > or =1.00 DC was common at 3 months of age (41.6%) but decreased in prevalence to 4.1% by 36 months (p < 0.0001). The most common orientation was with-the-rule at 3 months (37.0% compared with 2.7% for against-the-rule) but against-the-rule at 36 months (3.2% compared with 0.9% for with-the-rule). Most of the change in the average value of the horizontal/vertical component of astigmatism (J0) occurred between 3 and 9 months (-0.26 +/- 0.36 D; p < 0.0001) with no significant change between 9 and 36 months (-0.05 +/- 0.36 D; p=0.09). Spherical equivalent refractive error was not correlated with J0 at 3 and 9 months (R=0.002, p=0.48 and R=0.001, p=0.56, respectively). The two were only weakly correlated at 18 and 36 months (R=0.06 for each age, p <0.0001, p=0.0002, respectively). Changes in spherical equivalent between 3 and 9 months were unrelated to either the initial value of J0 (partial R for J0=0.0001; p=0.85) or the change in J0 (partial R for change in J0=0.0031; p=0.31). Across all the ages, corneal toricity was with-the-rule, and lenticular toricity was against-the-rule (produced by the toricity of the posterior lens surface). The cornea and anterior lens surface became more spherical with age, contributing to the shift away from with-the-rule refractive astigmatism. Toricity of all the refractive surfaces became less variable with age. CONCLUSIONS: Consistent with many reports, astigmatism was common in early infancy but decreased in prevalence with age, particularly when with-the-rule in orientation. The reduction in percentage of infants with astigmatism appeared to be caused by decreases in the toricity of the cornea and the anterior lens combined with decreases in the variability of corneal and lenticular surfaces. Astigmatism in infancy appeared to be unrelated to emmetropization of spherical equivalent refractive error.

Time intervals of cardiac resynchronization therapy in heart failure.

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.

Normal eye growth in emmetropic schoolchildren.

PURPOSE: The purpose of this report is to describe the normal growth pattern of the optical components of the eye in a cohort of emmetropic, school-aged children. METHODS: Emmetropia was defined as refractive error (measured by cycloplegic autorefraction) in the vertical and horizontal meridians of the right eye between +1.00 D and -0.25 D at all the visits. This definition resulted in a sample of 194 children enrolled in the Orinda Longitudinal Study of Myopia (OLSM) between ages 6 and 14 years with at least 2 years of follow-up evaluation (across three annual visits) between 1989 and 2000. The optical components measured included corneal power, anterior chamber depth, crystalline lens thickness, Gullstrand lens power, calculated lens power, crystalline lens index, vitreous chamber depth, and axial length. RESULTS: Corneal power and anterior chamber depth were best modeled as quadratic functions of ln (age). The model involving the square of the inverse of age best described calculated lens power and crystalline lens index. The relationship between age and crystalline lens thickness was best described using a linear function of age with a point of inflection. A linear function of ln (age) with a point of inflection best described the relationship between age and axial length, Gullstrand lens power, and vitreous chamber depth. For five of the eight components (crystalline lens thickness, Gullstrand lens power, calculated lens power, corneal power, and crystalline lens index), the line modeling the data was negative in overall direction, indicating that the component value decreased with age. The upward trend of the line modeling axial length, anterior chamber depth, and vitreous chamber depth reflected the continued growth of the eye from age 6 years to age 15 years. CONCLUSIONS: A picture of normal eye growth in emmetropes from ages 6 to 15 years is provided based on a combination of cross-sectional and longitudinal data. Axial elongation, crystalline lens flattening and thinning, and decrease in lens power are its hallmarks.