New bacterial species associated with chronic periodontitis.

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.

Preparing the "Ground War" against tobacco among Chinese Americans in New York City: baseline data.

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).

Cotinine levels in Southeast Asian smokers.

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.

Boron neutron capture therapy of brain tumors: biodistribution, pharmacokinetics, and radiation dosimetry sodium borocaptate in patients with gliomas.

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.

Plasma atherogenic markers in congestive heart failure and posttransplant (heart) patients.

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.

AC/A ratio, age, and refractive error in children.

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.

Improved survival after boron neutron capture therapy of brain tumors by Cereport-mediated blood-brain barrier modulation to enhance delivery of boronophenylalanine.

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.

Depression as an antecedent to heart disease among women and men in the NHANES I study. National Health and Nutrition Examination Survey.

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.

Boron neutron capture therapy of brain tumors: enhanced survival and cure following blood-brain barrier disruption and intracarotid injection of sodium borocaptate and boronophenylalanine.

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.

Sample size to test for interaction between a specific exposure and a second risk factor in a pair-matched case-control study.

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.

Porphyromonas gingivalis strain variability and periodontitis.

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.

Ocular predictors of the onset of juvenile myopia.

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.

Tonic accommodation, age, and refractive error in children.

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.

Enhanced delivery of boronophenylalanine for neutron capture therapy of brain tumors using the bradykinin analog Cereport (Receptor-Mediated Permeabilizer-7).

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.

Subclinical laminitis in dairy cows: use of severity of hoof lesions to rank and evaluate herds.

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.

A cross-sectional case control study of work-related injuries among Ohio farmers.

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.

Prevalence of Porphyromonas gingivalis and periodontal health status.

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.

Supplemental dietary biotin for prevention of lesions associated with aseptic subclinical laminitis (pododermatitis aseptica diffusa) in primiparous cows.

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.

Enhanced survival of glioma bearing rats following boron neutron capture therapy with blood-brain barrier disruption and intracarotid injection of boronophenylalanine.

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.

Boron neutron capture therapy of brain tumors: enhanced survival following intracarotid injection of either sodium borocaptate or boronophenylalanine with or without blood-brain barrier disruption.

The purpose of the present study was to determine whether the efficacy of boron neutron capture therapy could be enhanced by means of intracarotid (i.c.) injection of sodium borocaptate (BSH) or boronophenylalanine (BPA) with or without blood-brain barrier disruption (BBB-D). For biodistribution studies, F98 glioma-bearing rats were injected i.v. or i.c. with either BSH (30 mg of boron/kg of body weight) or BPA (24 mg of boron/kg of body weight) with or without mannitol-induced, hyperosmotic BBB-D and killed 2.5 h later. The highest tumor boron concentrations for BSH and BPA were attained following i.c. injection with BBB-D (48.6 and 94.0 microg/g, respectively) compared to i.c. (30.8 and 42.7 microg/g) and i.v. injection (12.9 and 20.8 microg). Using the same doses of BSH and BPA, therapy experiments were initiated 14 days after intracerebral implantation of F98 glioma cells. Animals were irradiated 2.5 h after i.v. or i.c. administration of the capture agent with or without BBB-D using a collimated beam of thermal neutrons at the Brookhaven Medical Research Reactor. The median survival times of rats given BSH or BPA i.c. were 52 and 69 days, respectively, for rats with BBB-D; 39 and 48 days for rats without BBB-D; 33 and 37 days for i.v. injected rats; 29 days for irradiated controls; and 24 days for untreated controls. i.c. injection of either BSH or BPA resulted in highly significant enhancement (P = 0.01 and P = 0.0002, respectively) of survival times compared to i.v. injection, and this was further augmented by BBB-D (P = 0.02 and P = 0.04, respectively) compared to i.c. injection. Normal brain tissue tolerance studies were carried out with non-tumor-bearing rats, which were treated in the same way as tumor-bearing animals. One year after irradiation, the brains of these animals showed only minimal radiation-induced changes in the choroid plexus, but no differences were discernible between irradiated controls and those that had BBB-D followed by i.c. injection of either BSH or BPA. Our data clearly show that the route of administration, as well as BBB-D, can enhance the uptake of BSH and BPA, and, subsequently, the efficacy of boron neutron capture therapy.