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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 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 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.

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.

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.

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.

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.

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Recent investigations of the human subgingival oral flora based on ribosomal 16S cloning and sequencing have shown many of the bacterial species present to be novel species or phylotypes. The purpose of the present investigation was to identify potential periodontal pathogens among these newly identified species and phylotypes. Species-specific ribosomal 16S primers for PCR amplification were developed for detection of new species. Associations with chronic periodontitis were observed for several new species or phylotypes, including uncultivated clones D084 and BH017 from the Deferribacteres phylum, AU126 from the Bacteroidetes phylum, Megasphaera clone BB166, clone X112 from the OP11 phylum, and clone I025 from the TM7 phylum, and the named species Eubacterium saphenum, Porphyromonas endodontalis, Prevotella denticola, and Cryptobacterium curtum. Species or phylotypes more prevalent in periodontal health included two uncultivated phylotypes, clone W090 from the Deferribacteres phylum and clone BU063 from the Bacteroidetes, and named species Atopobium rimae and Atopobium parvulum.

Purpose: To describe the refractive error and ocular components of a large group of school-aged children as a function of age and gender., Methods: In this report, we describe the refractive error and ocular components of 2583 school-aged children (49.3% girls, overall mean [+/-SD] age 10.0 +/- 2.3). Measurement methods included cycloplegic autorefraction, autokeratometry, videophakometry, and A-scan ultrasonography. For statistical comparisons across gender and age, a critical point of alpha = 0.005 was used to assess significance because of the large sample size and the large number of comparisons made., Results: Of these 2583 children, 10.1% were myopic (-0.75 D or more myopia in both meridians), and 8.6% were hyperopic (+1.25 D or more hyperopia in both meridians). As would be expected, there was a significant effect of age on refractive error (spherical equivalent, p < 0.0001), toward less hyperopia/more myopia. There was no significant difference in the average refractive error between girls and boys (p = 0.0192). Girls had steeper corneas than boys (0.74 D steeper in the vertical meridian and 0.63 D steeper in the horizontal meridian, p < 0.0001). There were no significant differences in corneal power with age (p = 0.16). Both older age and male gender were significantly associated with deeper anterior chambers (p < 0.0001 for both). The crystalline lens showed significant thinning with age (p < 0.0001), however, there was no significant difference in the lens thickness between girls and boys (p = 0.66). Both Gullstrand lens power and calculated lens power showed significant effects of age and gender (p < 0.0001 for both). Girls, on average, had Gullstrand lens powers that were 0.28 D steeper and calculated lens powers that were 0.80 D more powerful than boys. Axial length also showed significant effects of age and gender (p < 0.0001 for both). Girls' eyes were, on average, 0.32 mm shorter than those of boys., Conclusions: These cross-sectional data show a general pattern of ocular growth, no change in corneal power, and crystalline lens thinning and flattening between the ages of 6 and 14 years. Girls tended to have steeper corneas, stronger crystalline lenses, and shorter eyes compared with boys.

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.

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.

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.

Although substantial epidemiologic evidence links Streptococcus mutans to caries, the pathobiology of caries may involve more complex communities of bacterial species. Molecular methods for bacterial identification and enumeration now make it possible to more precisely study the microbiota associated with dental caries. The purpose of this study was to compare the bacteria found in early childhood caries (ECC) to those found in caries-free children by using molecular identification methods. Cloning and sequencing of bacterial 16S ribosomal DNAs from a healthy subject and a subject with ECC were used for identification of novel species or uncultivated phylotypes and species not previously associated with dental caries. Ten novel phylotypes were identified. A number of species or phylotypes that may play a role in health or disease were identified and warrant further investigation. In addition, quantitative measurements for 23 previously known bacterial species or species groups were obtained by a reverse capture checkerboard assay for 30 subjects with caries and 30 healthy controls. Significant differences were observed for nine species: S. sanguinis was associated with health and, in order of decreasing cell numbers, Actinomyces gerencseriae, Bifidobacterium, S. mutans, Veillonella, S. salivarius, S. constellatus, S. parasanguinis, and Lactobacillus fermentum were associated with caries. These data suggest that A. gerencseriae and other Actinomyces species may play an important role in caries initiation and that a novel Bifidobacterium may be a major pathogen in deep caries. Further investigation could lead to the identification of targets for biological interventions in the caries process and thereby contribute to improved prevention of and treatment for this significant public health problem.

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.

Chronic periodontitis is a common infectious disease in the adult population. The etiology is clearly bacterial, and a small number of bacterial species have been consistently associated with periodontitis, including Bacteroides forsythus and Porphyromonas gingivalis. Comparatively little attention has been paid to the identification of health-associated and potentially beneficial bacterial species that may reside in the gingival sulcus. The purpose of the present study was to examine the relationship of the presence of B. forsythus and a newly identified Bacteroides phylotype, oral clone BU063, to periodontal health status. The study was accomplished with a set of samples that were collected from subjects with periodontitis and healthy controls. These samples had previously been analyzed for the presence of P. gingivalis. An oral sampling strategy that included every tooth and a PCR-based detection method were used to maximize detection sensitivity. The presence of B. forsythus in the oral cavity was strongly associated with periodontitis, and its nearest genetic neighbor, oral clone BU063, was associated with oral health (P < 0.0001 for both). Colonization with P. gingivalis was independent of the presence of either Bacteroides species, but the two Bacteroides species were found together less often than would be expected by chance (P < 0.0001). This suggests the presence of a specific exclusionary mechanism between the two Bacteroides species. Comparisons between these two organisms may prove useful for studies that determine how B. forsythus functions in the disease process. In addition, oral clone BU063 deserves further study as a possible preventive or therapeutic intervention for periodontitis.

Objectives: The objective of this paper is to report on data on the perceptions regarding smoking and environmental tobacco smoke as well as the health communication patterns of a representative sample of 715 adult Chinese families with children under age 18 who had not banned smoking in the home., Methods: We selected a representative sample of Chinese American families residing in New York's five boroughs: Brooklyn, Bronx, Manhattan, Queens, and Staten Island based on Chinese family surnames and interviewed them by telephone between December 2000-March 2001. All except 4% of the interviews were conducted in English; most respondents chose to speak Cantonese and lesser numbers chose Mandarin., Findings: For the most part, respondents believed in the hazards of smoking, especially as it harms children living at home. To address smoking, respondents believed the physicians is the most trustworthy source of health information and the sources of health information consulted would be overwhelmingly the Chinese language newspaper, followed by Chinese language radio and television., Conclusions: This study represents the first systematic assessment of Chinese Americans in New York with regard to selected tobacco control issues. The findings provide the empirical base for developing potential messages using the source considered most trustworthy (the physician) and the vehicle most consulted (Chinese language media).

Objective: The purpose of this study was to obtain tumor and normal brain tissue biodistribution data and pharmacokinetic profiles for sodium borocaptate (Na2B12H11SH) (BSH), a drug that has been used clinically in Europe and Japan for boron neutron capture therapy of brain tumors. The study was performed with a group of 25 patients who had preoperative diagnoses of either glioblastoma multiforme (GBM) or anaplastic astrocytoma (AA) and were candidates for debulking surgery. Nineteen of these patients were subsequently shown to have histopathologically confirmed diagnoses of GBM or AA, and they constituted the study population., Methods: BSH (non-10B-enriched) was infused intravenously, in a 1-hour period, at doses of 15, 25, and 50 mg boron/kg body weight (corresponding to 26.5, 44.1, and 88.2 mg BSH/kg body weight, respectively) to groups of 3, 3, and 13 patients, respectively. Multiple samples of tumor tissue, brain tissue around the tumors, and normal brain tissue were obtained at either 3 to 7 or 13 to 15 hours after infusion. Blood samples for pharmacokinetic studies were obtained at times up to 120 hours after termination of the infusion. Sixteen of the patients underwent surgery at the Beijing Neurosurgical Institute and three at The Ohio State University, where all tissue samples were subsequently analyzed for boron content by direct current plasma-atomic emission spectroscopy., Results: Blood boron values peaked at the end of the infusion and then decreased triexponentially during the 120-hour sampling period. At 6 hours after termination of the infusion, these values had decreased to 20.8, 29.1, and 62.6 microg/ml for boron doses of 15, 25, and 50 mg/kg body weight, respectively. For a boron dose of 50 mg/kg body weight, the maximum (mean +/- standard deviation) solid tumor boron values at 3 to 7 hours after infusion were 17.1+/-5.8 and 17.3+/-10.1 microg/g for GBMs and AAs, respectively, and the mean tumor value averaged across all samples was 11.9 microg/g for both GBMs and AAs. In contrast, the mean normal brain tissue values, averaged across all samples, were 4.6+/-5.1 and 5.5+/-3.9 microg/g and the tumor/normal brain tissue ratios were3.8 and 3.2 for patients with GBMs and AAs, respectively. The large standard deviations indicated significant heterogeneity in uptake in both tumor and normal brain tissue. Regions histopathologically classified either as a mixture of tumor and normal brain tissue or as infiltrating tumor exhibited slightly lower boron concentrations than those designated as solid tumor. After a dose of 50 mg/kg body weight, boron concentrations in blood decreased from 104 microg/ml at 2 hours to 63 microg/ml at 6 hours and concentrations in skin and muscle were 43.1 and 39.2 microg/g, respectively, during the 3- to 7-hour sampling period., Conclusion: When tumor, blood, and normal tissue boron concentrations were taken into account, the most favorable tumor uptake data were obtained with a boron dose of 25 mg/kg body weight, 3 to 7 hours after termination of the infusion. Although blood boron levels were high, normal brain tissue boron levels were almost always lower than tumor levels. However, tumor boron concentrations were less than those necessary for boron neutron capture therapy, and there was significant intratumoral and interpatient variability in the uptake of BSH, which would make estimation of the radiation dose delivered to the tumor very difficult. It is unlikely that intravenous administration of a single dose of BSH would result in therapeutically useful levels of boron. However, combining BSH with boronophenylalanine, the other compound that has been used clinically, and optimizing their delivery could increase tumor boron uptake and potentially improve the efficacy of boron neutron capture therapy.

Purpose: To examine how the response AC/A ratio (the amount of accommodative convergence per unit of accommodative response) varies as a function of refractive error and age, to determine whether it is a risk factor for the onset of myopia, and to examine the relation between ocular structural features and the AC/A ratio., Methods: Accommodation was stimulated by a letter target presented in a Badal system at 0.00, 2.25, and 4.37 D to 828 children aged 6 through 14 years in 1996. Of these, 726 had no myopia in 1996 and were available for examination the following year. Accommodative response and cycloplegic refractive error were measured by autorefraction and convergence by monitoring the relative movement of Purkinje images I and IV. Lens radii of curvature were measured by video phakometry, corneal radius of curvature by topography, and ocular axial dimensions by A-scan ultrasonography., Results: Adjusted for age, the response AC/A ratio was highest in myopes (6.39 delta/D), intermediate in emmetropes (3.94 delta/D), and lowest in hyperopes (3.40 delta/D; P < 0.0001; two-way analysis of variance [ANOVA]). The stimulus AC/A ratio did not vary with refractive error. Adjusted for refractive error, the response AC/A ratio did not change as a function of age. In non-myopic children, having a response AC/A ratio of 5.84 delta/D or more elevated the risk of development of myopia within 1 year by 22.5 times (95% CI = 7.12-71.1). In a subsample of children without myopia who had refractive errors less than +0.75 D, having a response AC/A ratio of 5.84 delta/D or more elevated the risk of development of myopia within 1 year by 3.21 times (95% CI = 1.14-9.07). The AC/A ratio was associated with all measured ocular features except lens spherical volume. Only the negative correlations with refractive error and the shape of the crystalline lens (Gullstrand lens power) were significant in a multiple regression model (adjusted R2 = 0.16)., Conclusions: An elevated response AC/A ratio was associated with myopia and was an important risk factor for its rapid onset. The association between higher AC/A ratios and flatter crystalline lens shapes, as well as other reported features of accommodation in myopia, may be explained by "pseudocycloplegia," which the authors define as tension on the crystalline lens that increases the level of effort needed to accommodate. Accommodative deficits in myopia may be the functional consequences of the underlying anatomy of the enlarged eye.

Objectives: We hypothesized that plasma factors important for the development of atherosclerosis play a major role in the occurrence of cardiac allograft vasculopathy (CAV)., Background: Cardiac allograft vasculopathy is a major cause of death among heart transplant recipients, has a poorly understood pathogenesis and has similarities to atherosclerotic coronary disease., Methods: The study population consisted of 93 postcardiac transplant recipients. Thirty-one patients with congestive heart failure (CHF) and 18 healthy individuals served as control subjects. Posttransplant coronary anatomy was evaluated by angiography and intravascular ultrasound. Laboratory analyses of lipids, homocysteine, vitamin B12 and folate, fibrinogen, von Willebrand factor antigen (vWFAg) and renin were obtained on all participants., Results: Posttransplant patients were found to have elevated serum triglycerides, total cholesterol/ high-density lipoprotein cholesterol ratio, lipoprotein (a), homocysteine, vWFAg, fibrinogen and renin and lower high-density lipoprotein cholesterol. Most of these laboratory atherogenic factors were also elevated to a similar degree in the CHF control population. Although most atherogenic markers were elevated, there was little correlation with CAV severity. Cardiac allograft vasculopathy severity varied with time after transplantation, 3-hydroxy-methyl-glutaryl-coenzyme A reductase inhibitor use and prior cytomegalovirus infection. Even within the normal range, lower RBC folate levels were associated with increased severity of CAV., Conclusions: The posttransplant course is associated with increased clinical and laboratory atherogenic factors, some of which likely contribute to the severity of coronary vasculopathy. Compared with normal control subjects, many of these markers are already increased in pretransplant CHF patients with or without occlusive coronary artery disease.

Objective: Cereport (Alkermes, Inc., Cambridge, MA), or, as it has been previously called, RMP-7 (receptor-mediated permeabilizer-7), is a bradykinin analog that has been shown to produce a transient, pharmacologically mediated opening of the blood-brain barrier. The purpose of the present study was to determine whether the efficacy of boron neutron capture therapy (BNCT) could be enhanced by means of intracarotid (i.c.) infusion of Cereport, in combination with intravenous (i.v.) injection or i.c. infusion of boronophenylalanine (BPA) in the F98 rat glioma model., Methods: For biodistribution studies, Fischer rats bearing intracerebral implants of the F98 glioma received i.v. or i.c. injections of 300 or 500 mg/kg body weight (b.w.) of BPA with or without i.c. infusion of 1.5 microg/kg b.w. of Cereport. For therapy studies, BNCT was initiated 14 days after intracerebral implantation of 10(3) F98 cells. The i.v. or i.c. injection of BPA (500 mg/kg b.w.) was given with or without Cereport, and the animals were irradiated 2.5 hours later at the Brookhaven Medical Research Reactor with a collimated beam of thermal neutrons delivered to the head., Results: At a BPA dose of 500 mg/kg b.w., tumor boron concentrations (mean +/- standard deviation) were 55.7 +/- 9.6 microg/g with Cereport versus 33.6 +/- 3.9 microg/g without Cereport at 2.5 hours after i.c. infusion of BPA, and concentrations were 29.4 +/- 9.9 microg/g with Cereport versus 15.4 +/- 3.5 microg/g without Cereport (P < 0.05) after i.v. injection of BPA. After i.c. administration of BPA and Cereport, the tumor-to-blood ratio was 5.4 +/- 0.6, and the tumor-to-brain ratio was 5.2 +/- 2.4. After BNCT with BPA at a dose of 500 mg/kg, the survival time was 50 +/- 16 days for i.c. administration of BPA with Cereport versus 40 +/- 6 days without Cereport (P = 0.05), 38 +/- 4 days for i.v. administration of BPA with Cereport versus 34 +/- 3 days without Cereport (P = 0.02), 28 +/- 5 days for irradiated controls, and 23 +/- 3 days for untreated controls. Compared with untreated controls, there was a 117% increase in lifespan in rats that received an i.c. infusion of Cereport and then BPA, and an 86% increase in lifespan in rats that received i.c. administration of BPA without Cereport., Conclusion: These studies have established that i.c. administration of Cereport can not only increase tumor uptake of BPA, but also enhance the efficacy of BNCT.

Background: Depression predicts morbidity and mortality among individuals who have coronary heart disease (CHD), and there is increasing evidence that depression may also act as an antecedent to CHD. The studies that have reported a relationship between depression and CHD incidence or mortality either were restricted to men only or analyzed women and men together. The present investigation was conducted to evaluate the differential effect depression may have on CHD incidence and mortality in women and men., Research Methods: We analyzed data from 5007 women and 2886 men enrolled in the first National Health and Nutrition Examination Survey (NHANES I) who were free of CHD at the 1982-1984 interview and who had completed the Center for Epidemiologic Studies Depression Scale (CES-D). Participants were evaluated from the 1982 interview date either until the end of the study (1992 interview date) or until the occurrence of a CHD event. Using CHD incidence and CHD mortality (International Classification of Disease, Ninth Revision, codes 410-414) as the outcome variables, Cox proportional hazards regression models were developed to evaluate the relative risk (RR) of CHD incidence and mortality in the depressed women and men separately, controlling for standard CHD risk factors., Results: The women experienced 187 nonfatal and 137 fatal events, compared with 187 nonfatal and 129 fatal events among the men. The adjusted RR of CHD incidence among depressed women was 1.73 (95% confidence internal [CI], 1.11-2.68) compared with nondepressed women. Depression had no effect on CHD mortality in the women (RR, 0.74; 95% CI, 0.40-1.48). The adjusted RR of CHD incidence among depressed men was 1.71 (95% CI, 1.14-2.56) compared with nondepressed men. Depressed men also had an increased risk of CHD mortality compared with their nondepressed counterparts, with an adjusted RR of 2.34 (95% CI, 1.54-3.56)., Conclusions: In this sample, while controlling for possible confounding factors, depression was associated with an increased risk of CHD incidence in both men and women, as well as CHD mortality in men. Depression had no effect on CHD mortality in women.

We discuss a sample size calculation for a pair-matched case-control study to test for interaction between a specific exposure and a second risk factor. The second risk factor could be either binary or continuous. An algorithm for the calculation of sample size is suggested which is based on a logistic regression model that relates the logarithm of the disease-exposure odds ratio to the second risk factor. This problem is motivated by a study comparing the prevalence of GP-IIIa Pl(A2) polymorphism (the exposure) in individuals with and without myocardial infarction (case-control). One of the hypotheses in this study is whether or not there is an interaction between the prevalence of GP-IIIa Pl(A2) polymorphism and a second risk factor such as smoking status and homocysteine level. We introduce the algorithm in detail with several numerical examples., (Copyright 2000 John Wiley & Sons, Ltd.)

Purpose: Boronophenylalanine (BPA) and sodium borocaptate (Na(2)B(12)H(11)SH or BSH) have been used clinically for boron neutron capture therapy (BNCT) of high-grade gliomas. These drugs appear to concentrate in tumors by different mechanisms and may target different subpopulations of glioma cells. The purpose of the present study was to determine if the efficacy of BNCT could be further improved in F98-glioma-bearing rats by administering both boron compounds together and by improving their delivery by means of intracarotid (i.c.) injection with or without blood-brain barrier disruption (BBB-D)., Methods and Materials: For biodistribution studies, 10(5) F98 glioma cells were implanted stereotactically into the brains of syngeneic Fischer rats. Eleven to 13 days later animals were injected intravenously (i.v.) with BPA at doses of either 250 or 500 mg/kg body weight (b.w.) in combination with BSH at doses of either 30 or 60 mg/kg b.w. or i.c. with or without BBB-D, which was accomplished by i.c. infusion of a hyperosmotic (25%) solution of mannitol. For BNCT studies, 10(3) F98 glioma cells were implanted intracerebrally, and 14 days later animals were transported to the Brookhaven National Laboratory (BNL). They received BPA (250 mg/kg b.w.) in combination with BSH (30 mg/kg b.w. ) by i.v. or i.c. injection with or without BBB-D, and 2.5 hours later they were irradiated with a collimated beam of thermal neutrons at the BNL Medical Research Reactor., Results: The mean tumor boron concentration +/- standard deviation (SD) at 2.5 hours after i. c. injection of BPA (250 mg/kg b.w.) and BSH (30 mg/kg b.w.) was 56. 3 +/- 37.8 microgram/g with BBB-D compared to 20.8 +/- 3.9 microgram/g without BBB-D and 11.2 +/- 1.8 microgram/g after i.v. injection. Doubling the dose of BPA and BSH produced a twofold increase in tumor boron concentrations, but also concomitant increases in normal brain and blood levels, which could have adverse effects. For this reason, the lower boron dose was selected for BNCT studies. The median survival time was 25 days for untreated control rats, 29 days for irradiated controls, 42 days for rats that received BPA and BSH i.v., 53 days following i.c. injection, and 72 days following i.c. injection + BBB-D with subsets of long-term survivors and/or cured animals in the latter two groups. No histopathologic evidence of residual tumor was seen in the brains of cured animals., Conclusions: The combination of BPA and BSH, administered i.c. with BBB-D, yielded a 25% cure rate for the heretofore incurable F98 rat glioma with minimal late radiation-induced brain damage. These results demonstrate that using a combination of boron agents and optimizing their delivery can dramatically improve the efficacy of BNCT in glioma-bearing rats.

Understanding the contribution of race to factors associated with cigarette smoking and nicotine metabolism is essential for the characterization of patterns of tobacco use, nicotine dependence and incidence of tobacco-related diseases. This paper reports an investigation of cotinine levels among Southeast Asian smokers in two separate studies. Study 1 included 327 male and female smokers who participated in community-based interviews where smoking history information was obtained and a saliva continine sample was collected. Results indicated that subjects smoked an average of 11.2 cigarettes/day, with men reporting significantly higher consumption rates as compared to women (p < 0.0001). Subjects' mean cotinine level was 65 ng/ml with an average cotinine/cigarette ratio of 8.2. In Study 2, plasma and saliva cotinine in six Southeast Asian adult smokers were measured during 2 days of smoking followed by 6 days of abstinence. On day 1, mean plasma and saliva continine levels were 268 and 235 ng/ml, respectively. After 6 days of abstinence, mean levels had dropped to 12 ng/ml for plasma and 8 ng/ml in saliva. On average, it required at least 4.7 days for saliva continine levels to reach < 14 ng/ml. Mean cotinine concentrations during smoking differed in these two separate studies. Implications of these findings are discussed and future research recommendations are presented.

To determine if there is variability in virulence among strains of Porphyromonas gingivalis in human periodontitis, their distribution in a group of subjects with clear indicators of periodontitis and in a healthy, age-matched control group was examined. The presence of heteroduplex types of P. gingivalis in the two groups was determined with a PCR-based assay. This assay relied on detection of polymorphisms in the ribosomal internal spacer region (ISR). ISR fragments generated by PCR with P. gingivalis-specific primers were hybridized to fragments from reference strains, and the formation of heteroduplexes from the hybridization of nonidentical sequences was observed by polyacrylamide gel electrophoresis. Characteristic fingerprints from comparison with a panel of reference strains allowed the identification of heteroduplex types in clinical samples. One hundred thirty adults with periodontitis and 181 controls were sampled. With this approach, 11 heteroduplex types of P. gingivalis were detected in the population. Sufficient numbers were available for statistical analysis of six of these types. Heteroduplex type hW83 was found to be very strongly associated with periodontitis (P = 0.0000), and two additional types, h49417 and hHG1691, were also significantly associated with disease. The remaining types, h23A4, h381, and hA7A1, were detected more frequently in subjects with periodontitis than in healthy subjects, but the difference was not significant. These data indicate that virulence in human periodontitis varies among strains of P. gingivalis, and they identify an apparently highly virulent subgroup.

Purpose: The purpose of this study was to identify reliable predictors of the onset of juvenile myopia., Methods: The data from 554 children enrolled in the Orinda Longitudinal Study of Myopia (OLSM) as nonmyopes with baseline data from the third grade were evaluated to develop a predictive profile for later onset of juvenile myopia. Myopia was defined as at least -0.75 D of myopia in the vertical and horizontal meridians of the right eye as measured by cycloplegic autorefraction (n = 45 children). Chosen predictors were refractive error and the ocular components: corneal power, Gullstrand crystalline lens power, and axial length. Sensitivity and specificity were calculated. Receiver operating characteristic (ROC) curves were generated to evaluate and compare these predictors singly and combined., Results: Refractive error, axial length, Gullstrand lens and pod corneal power were all significant predictive factors for the onset of juvenile myopia. The best single predictor of future myopia onset in the right eye was the right eye's cycloplegic autorefraction spherical refractive error value (mean sphere across 10 readings) at baseline. For a cut point of less than +0.75 D hyperopia in the third grade, sensitivity was 86.7% and specificity was 73.3%. The area under the ROC curve for this mean sphere was 0.880. Producing a logistic model combining mean sphere, corneal power, Gullstrand lens power, and axial length results in a slight improvement in predictive ability (area under the ROC curve = 0.893)., Conclusions: Onset of juvenile myopia can be predicted with moderate accuracy using the mean cycloplegic, spherical refractive error in the third grade. Measurement of other ocular components at this age improves predictive ability, albeit incrementally. Further improvements in the prediction of myopia onset will require the use of longitudinal data in addition to one-time measurement of refractive error and the ocular components.

Purpose: An association between tonic accommodation, the resting accommodative position of the eye in the absence of a visually compelling stimulus, and refractive error has been reported in adults and children. In general, myopes have the lowest (or least myopic) levels of tonic accommodation. The purpose in assessing tonic accommodation was to evaluate it as a predictor of onset of myopia., Methods: Tonic accommodation was measured in children enrolled in the Orinda Longitudinal Study of Myopia using an infrared autorefractor (model R-1; Canon, Lake Success, NY) while children viewed an empty lit field or a dark field with a fixation spot projected in Maxwellian view. Children aged 6 to 15 years were measured from 1991 through 1994 (n = 714, 766, 771, and 790 during the 4 years, successively). Autorefraction provided refractive error and tonic accommodation data, and videophakometry measured crystalline lens curvatures., Results: Comparison of the two methods for measuring tonic accommodation shows a significant effect of age across all years of testing, with the lit empty-field test condition yielding higher levels of tonic accommodation compared with the dark-field test condition in children aged 6 through 11 years. For data collected in 1994, mean (+/-SD) tonic accommodation values for the lit empty-field condition were significantly lower in myopes, intermediate in emmetropes, and highest in hyperopes (1.02 +/- 1.18 D, 1.92 +/- 1.59 D, and 2.25 +/- 1.78 D, respectively; Kruskal-Wallis test, P < 0.001; between-group testing shows each group is different from the other two). Age, refractive error, and Gullstrand lens power were significant terms in a multiple regression model of tonic accommodation (R2 = 0.18 for 1994 data). Lower levels of tonic accommodation for children entering the study in the first or third grades were not associated with an increased risk of the onset of myopia, whether measured in the lit empty-field test condition (relative risk = 0.90; 95% confidence interval = 0.75, 1.08), or the dark-field test condition (relative risk = 0.83; 95% confidence interval = 0.60, 1.14)., Conclusions: This is the first study to document an association between age and tonic accommodation. The known association between tonic accommodation and refractive error was confirmed and it was shown that an ocular component, Gullstrand lens power, also contributed to the tonic accommodation level. There does not seem to be an increased risk of onset of juvenile myopia associated with tonic accommodation.

Objective: Using the well-characterized F98 rat glioma model, the purpose of the present study was to determine whether the delivery of boronophenylalanine (BPA) could be enhanced by prior administration of the bradykinin analog Cereport (Alkermes, Inc., Cambridge, MA) (previously known as Receptor-Mediated Permeabilizer-7), which produces a transient, pharmacologically mediated opening of the blood-brain barrier., Methods: Two series of experiments were performed in F98 glioma-bearing rats that had received either intracarotid (i.c.) or intravenous infusions of Cereport (at doses ranging from 1.5 to 7.5 microg/kg of body weight), followed by i.c. (or intravenous) injection of BPA (300 mg/kg of body weight). Animals were killed 0.5, 2.5, or 4 hours later, samples of blood, skin, muscle, and eye were obtained, brains were removed, and tumors were excised for boron determination by direct current plasma-atomic emission spectroscopy., Results: Averaged over all time points, i.c. infusion of Cereport significantly enhanced tumor boron uptake (P = 0.0001), compared with the excipient (saline) control values. Tumor boron values were equivalent at 0.5 (36.0 microg/g) and 2.5 hours (38.5 microg/g) after i.c. administration of Cereport and BPA and then decreased by 33% (to 25.7 microg/g) at 4 hours. These tumor boron uptake values were significantly different (alpha = 0.05), compared with values measured at the corresponding times after i.c. administration of BPA without Cereport (22.6, 21.8, and 15.3 microg/g, respectively). Although no time-related effects were observed, i.c. administration of Cereport followed by intravenous administration of BPA also significantly enhanced (alpha = 0.05) tumor boron uptake at 0.5, 2.5, and 4 hours (27.4, 30.3, and 28.0 microg/g, respectively), compared with values obtained without Cereport (11.3, 13.4, and 15.2 microg/g, respectively). Boron levels in normal brain tissue from tumor-bearing and non-tumor-bearing cerebral hemispheres and in blood were not significantly different from those measured in saline-treated control animals., Conclusion: This study established that i.c. infusion of Cereport significantly increased delivery of BPA to F98 rat gliomas, and this could enhance the efficacy of boron neutron capture therapy of this tumor.

Thirteen high-yielding Holstein herds in Ohio were ranked according to the prevalence and severity of lesions associated with subclinical laminitis (pododermatitis aseptica diffusa). One hundred and seventy-three first lactation cows, most of them in their first 100 days of lactation, and 30 pregnant heifers were assessed. The lesions evaluated were yellow waxy discoloration of the sole, haemorrhage of the sole, separation of the white line, and erosion of the heel. Each herd consisted of more than 100 lactating cows and all the herds were producing over 8500 kg of milk per cow on a rolling herd average basis. The lactating cows were housed in cubicles and maintained in concrete yards. The lesions associated with subclinical laminitis were prevalent among the 13 herds, but when each category of lesion was considered independently, significant differences in prevalence and severity were detected among the herds. These differences suggest that it may be possible to make changes in herd management which may influence the prevalence of lesions.

The agricultural industry has consistently been ranked among the most hazardous in the U.S. To date, few analytic studies of occupational injury among farm operators and workers have been conducted. A case control study was undertaken to investigate risk factors for agricultural work-related injury among Ohio farm operators. Cases were selected from among 1,793 respondents to a questionnaire administered during the first phase of the NIOSH-sponsored Ohio Farm Family Health and Hazard Study (OFFHHS). Analysis consisted of description of the injury experience of the sample as a whole, followed by logistic estimation of prevalence odds ratios (pORs) measuring the effect of potential risk factors on injury risk. The case series consisted of 90 white male principal operators (POs) injured doing farm work in the 12 months prior to questionnaire completion. Controls consisted of 1,475 white male POs who reported no injuries. The overall rate of injury was 5 per 100 person-years. The most notable result is the relationship between self-reported neurotoxic symptoms and injury, suggesting those with more reported symptoms were at greater risk of injury. The crude OR, when compared to the reference score of < or = 27, increased from 1.74 (95% CI = 0.60-5.09) in the 28-30 category, to 1.89 (95% CI = 0.71-5.03) in the 31-35 category, to 2.96 (95% CI = 1.10-7.96) in the highest category of test score. The P value for trend was 0.0218. These associations largely persisted after controlling for potential confounders with multiple logistic regression. Risk was inversely related to age. The results show marked increases in risk of injury associated with farmers younger than 30 and increased severity of self-reported neurological symptoms, controlling for potential confounding.

Periodontitis is a common, progressive disease that eventually affects the majority of the population. The local destruction of periodontitis is believed to result from a bacterial infection of the gingival sulcus, and several clinical studies have provided evidence to implicate Porphyromonas gingivalis. If P. gingivalis is a periodontal pathogen, it would be expected to be present in most subjects with disease and rarely detected in subjects with good periodontal health. However, in most previous studies, P. gingivalis has not been detected in the majority of subjects with disease, and age-matched, periodontally healthy controls were not included for comparison. The purpose of the study reported here was to compare the prevalence of P. gingivalis in a group with periodontitis to that of a group that is periodontally healthy. A comprehensive sampling strategy and a sensitive PCR assay were used to maximize the likelihood of detection. The target sequence for P. gingivalis-specific amplification was the transcribed spacer region within the ribosomal operon. P. gingivalis was detected in only 25% (46 of 181) of the healthy subjects but was detected in 79% (103 of 130) of the periodontitis group (P < 0.0001). The odds ratio for being infected with P. gingivalis was 11.2 times greater in the periodontitis group than in the healthy group (95% confidence interval, 6.5 to 19.2). These data implicate P. gingivalis in the pathogenesis of periodontitis and suggest that P. gingivalis may not be a normal inhabitant of a periodontally healthy dentition.

Objective: To evaluate, in primiparous cows, the effect of dietary biotin supplementation on severity of lesions of aseptic subclinical laminitis., Animals: 100 primiparous cows in a 800-cow commercial dairy herd., Procedure: Cows were assigned after calving to a biotin-supplemented (20 mg/head/d) or control group on an alternating basis. Digits 3 and 4 of the left forelimb and right hind limb were examined at a mean of 25, 108, and 293 days after parturition. Toe length, hoof angle, and heel depth were measured, and hooves were examined for solear hemorrhage, yellow solear discoloration, separation of the white line, and heel erosion. Serum and milk biotin concentrations were also measured., Results: Serum biotin concentrations were significantly higher for supplemented than for control cows. During the second examination, prevalence of separation of the white line of digits 3 and 4 of the hind limb and digit 4 of the forelimb was lower for supplemented than for control cows. Mean decrease in heel depth between the first and third examinations was approximately twice as great for digit 4 of the forelimb and 4 times as great for digit 3 of the forelimb in supplemented, versus control, cows. Other differences were not found., Conclusions and Clinical Relevance: Results suggest that supplemental dietary biotin may have a beneficial effect on hoof health in intensively managed primiparous dairy cows.

Boronophenylalanine (BPA) has been used for boron neutron capture therapy (BNCT) of brain tumors in both experimental animals and humans. The purpose of the present study was to determine if the efficacy of BNCT could be enhanced by means of intracarotid (i.c.) injection of BPA with or without blood-brain barrier disruption (BBB-D) and neutron irradiation using a rat brain tumor model. For biodistribution studies, F98 glioma cells were implanted stereotactically into the brains of Fischer rats, and 12 days later BBB-D was carried out by i.c. infusion of 25% mannitol (1.373 mOsmol/ml), followed immediately by i.c. administration of 300, 500 or 800 mg of BPA/kg body weight (b.w.). At the 500 mg dose a fourfold increase in tumor boron concentration (94.5 micrograms/g) was seen at 2.5 hours after BBB-D. compared to 20.8 micrograms/g in i.v. injected animals. The best composite tumor to normal tissue ratios were observed at 2.5 hours after BBB-D, at which time the tumor: blood (T: Bl) ratio was 10.9, and the tumor: brain (T:Br) ratio was 7.5, compared to 3.2 and 5.0 respectively for i.v. injected rats. In contrast, animals that had received i.c. BPA without BBB-D had T : Bl and T:Br ratios of 8.5 and 5.9, respectively, and the tumor boron concentration was 42.7 micrograms/g. For therapy experiments, initiated 14 days after intracerebral implantation of F98 glioma cells, 500 mg/kg b.w. of BPA were administered i.v. or i.c. with or without BBB-D, and the animals were irradiated 2.5 hours later at the Brook-haven Medical Research Reactor with a collimated beam of thermal neutrons delivered to the head. The mean survival time for untreated control rats was 24 +/- 3 days, 30 +/- 2 days for irradiate controls, 37 +/- 3 days for those receiving i.v. BPA, 52 +/- 15 days for rats receiving i.c. BPA without BBB-D, and 95 +/- 95 days for BBB-D followed by i.c. BPA and BNCT. The latter group had a 246% increase in life span (ILS) compared to untreated controls and a 124% ILS compared to that of i.v. injected animals. These survival data are the best ever obtained with the F98 glioma model and suggest that i.c. administration of BPA with or without BBB-D may be useful as a means to increase the efficacy of BNCT.