John Paul Jones: An Overlooked Autopsy Finding that May Explain His Terminal Illness.

A finding in the autopsy of John Paul Jones, the American Revolutionary War naval hero, may explain his terminal illness. During his last 2 years, he had a persistent productive cough and dyspnea. Ten days before death, he developed rapidly progressive dependent edema and ascites. He died in France in 1792. His body, preserved in alcohol in a lead coffin, was, in 1905, removed to the United States. Glomerulonephritis was noted on an autopsy, performed in France, but there was no comment then or since about ventricular wall thickness being the same in both ventricles at 5-6 mm. Hypertrophy and dilatation with biventricular failure followed by tissue shrinkage during 113 years in alcohol could have resulted in these ventricular wall findings. Systemic hypertension and left ventricular failure are consistent with his respiratory symptoms complicated perhaps by pulmonary emboli, right ventricular failure with tricuspid regurgitation, peripheral congestion, and jaundice.

Robotic microsurgery: corneal transplantation.

BACKGROUND: Robotic ocular microsurgery including corneal suturing has been proven to be feasible in porcine eyes. AIM: To determine whether or not bimanual teleoperated robotic penetrating keratoplasty (PK) can be performed in porcine and human eyes. METHODS: Three arms of the da Vinci surgical robot were loaded with a dual-channel video and two, 360 degrees -rotating, 8 mm, wrested-end effector instruments and placed over porcine eyes or over a human cadaver head. The surgeon remotely performed mechanical trephination, cardinal sutures, continuous 10.0 nylon sutures and suture adjustments on both eyes. The procedures were documented with still and video photography. RESULTS: Using the da Vinci robot, penetrating keratoplasty procedures were successfully performed on both porcine eyes and human eyes in natural anatomical conditions. The precise placement of continuous sutures was facilitated by the wrested-end forceps. Orbital rims and nose did not limit surgical motions. CONCLUSION: Teleoperated robotic penetrating keratoplasty is technically feasible in humans. Further studies are pending to implement the procedure with femtosecond laser and other automated steps.

Flock differences in the impact of maternal dietary restriction on offspring growth and glucose tolerance in female offspring.

Variable impacts of in-utero programming stimuli on postnatal offspring development suggest that genotype may play a role in this response. In this study, ewes from two flocks of similar breeding but adapted for 6-8 generations to one of two markedly different production environments were utilized (Baggs ewes--nomadic lifestyle and limited nutrition; UW ewes--sedentary lifestyle and adequate nutrition). Ewes from each flock were fed 50% (nutrient restricted) or 100% (control) National Research Council (NRC) requirements between day 28 and 78 of gestation; some ewes in each dietary group were then necropsied. Remaining ewes were fed 100% NRC requirements from day 79 to term. Weights of singleton female fetuses were reduced (P < 0.05) in nutrient restricted UW ewes compared to control UW ewes on day 78. Two month old ewe lambs from nutrient restricted UW ewes had greater (P < 0.05) baseline glucose concentrations, and exhibited greater (P < 0.05) glucose and insulin concentrations to an intravenous glucose bolus than lambs from control UW ewes. From 4 to 12 months of age, ewe lambs from nutrient restricted UW ewes were heavier (P < 0.05) than lambs from control UW ewes. In contrast, no differences in fetal weight, baseline glucose, glucose and insulin concentration to an intravenous glucose bolus, or body weight were observed for nutrient restricted and control Baggs ewes. These data suggest that a multigenerational adaptation of ewes to different production systems impacts their ability to protect their fetus against a bout of early to mid-gestational nutrient restriction.

Lead exposure and periodontitis in US adults.

BACKGROUND AND OBJECTIVE: Lead is known to have significant effects on bone metabolism and the immune system. This study tested the hypothesis that lead exposure affects periodontitis in adults. MATERIAL AND METHODS: This study used the data from the Third National Health and Nutrition Examination Survey (NHANES III, 1988-94). It analyzed data from 2500 men and 2399 women, 20-56 yr old, who received complete periodontal examination. Periodontitis was defined as the presence of > 20% of mesial sites with >or= 4 mm of attachment loss. Lead exposure was grouped into three categories: < 3; 3-7; and > 7 microg/dL. Covariates were cotinine levels, poverty ratio, race/ethnicity, education, bone mineral density, diabetes, calcium intake, dental visit, and menopause (for women). All analyses were performed separately for men and women and considering the effect design. Univariate, bivariate, and stratified analysis was followed by multivariable analysis by estimating prevalence ratios through poisson regression. RESULTS: After adjustment for confounders, the prevalence ratios, comparing those with a lead blood level of > 7 microg/dL to those with a lead blood level of < 3 microg/dL was 1.70 (95% confidence interval (CI): 1.02, 2.85) for men and 3.80 (95% CI: 1.66, 8.73) for women. CONCLUSION: The lead blood level was positively and statistically associated with periodontitis for both men and women. Considering the public health importance of periodontitis and lead exposure, further studies are necessary to confirm this association.

Carbonated soft drinks and dental caries in the primary dentition.

We analyzed fluid intake data among children aged 2-10 years from a 24-hour dietary recall interview in the NHANES III (1988-94) to investigate the effect of high consumption of carbonated soft drinks on caries in the primary dentition. We used cluster analysis to determine fluid consumption patterns. Four distinct fluid consumption patterns were identified: high carbonated soft drinks, high juice, high milk, and high water. About 13% of children had a high carbonated soft drink consumption pattern; they also had a significantly higher dental caries experience in the primary dentition than did children with other fluid consumption patterns. A fluid intake pattern comprised mainly of milk, water, or juice was less likely to be associated with dental caries. Findings of this study suggest that high consumption of carbonated soft drinks by young children is a risk indicator for dental caries in the primary dentition and should be discouraged.

Prevalence and trends in periodontitis in the USA: the [corrected] NHANES, 1988 to 2000.

Trends in periodontal diseases in the USA have been documented for years. However, the results have been mixed, mostly due to different periodontal assessment protocols. This study examined change in the prevalence of periodontitis between the NHANES III and the NHANES 1999-2000, and differences in the prevalence of periodontitis among racial/ethnic groups in the USA. Analysis was limited to non-Hispanic black, non-Hispanic white, and Mexican-American adults aged 18+ yrs in the NHANES III (n=12,088) or the NHANES 1999-2000 (n=3214). The prevalences of periodontitis for the NHANES III and the NHANES 1999-2000 were 7.3% and 4.2%, respectively. In multivariable analyses, blacks were 1.88 times (95%CI: 1.42, 2.50) more likely to have periodontitis than whites surveyed in the NHANES III. However, the odds of periodontitis for blacks and Mexican-Americans did not differ from those for whites surveyed in the NHANES 1999-2000. Our findings indicate that the prevalence of periodontitis has decreased between the NHANES III and the NHANES 1999-2000 for all racial/ethnic groups in the USA.

Fluorosis development in seven age cohorts after an 11-month break in water fluoridation.

This study used an 11-month break in water fluoridation to identify the time when developing incisors are most sensitive to fluorosis development. The study was based in Durham, NC, where an interruption to water fluoridation occurred between September, 1990, and August, 1991. A total of 1896 children was dentally examined. Fluorosis was measured by the TF index, and parents or guardians completed a questionnaire on demographics and fluoride history. Age cohorts ranged from those born 5 years before the break, to those born 1 year after the resumption of fluoridation. Fluorosis prevalence for seven age cohorts whose birth years ranged from 1985-86 to 1991-92 was 57.1, 62.3, 33.0, 32.3, 39.8, 30.2, and 36.8%, respectively. Children aged from birth to 3 years at the break, and those born 1 year after it, had less fluorosis than those aged 4-5 years at the break.

Definitions of risk.

Risk-related terms such as risk factor, modifiable risk factor, demographic risk factor, risk indicator, determinant, and risk marker are often not well defined in the literature. This short report supports the use of a 1996 definition of risk factor, as probably the most commonly used term related to risk, for the Consensus Development Conference on Diagnosis and Management of Dental Caries Throughout Life, March 26-28, 2001.

Sugar consumption and caries risk: a systematic review.

This systematic review addresses the question: In the modern age of extensive fluoride exposure, do individuals with a high level of sugar intake experience greater caries severity relative to those with a lower level of intake? The MEDLINE and EMBASE databases were searched for English-language papers published between 1980 and 2000 using a search expression developed in conjunction with an experienced librarian. There were 809 papers located in the initial search. A review of titles and abstracts to identify clearly irrelevant papers reduced this number to 134. Two readers each read one half of these papers, and application of predetermined inclusion/exclusion criteria reduced this number of papers to sixty-nine. Criteria were established for scoring the quality of each of these papers on evidence tables. The maximum score for each paper was 100; the sixty-nine papers rated scored between 12 and 79. Final judgment of results was limited to those thirty-six papers that scored 55 or higher on the evidence tables and that reported studies carried out in countries where there is moderate-to-extensive fluoride exposure. Results showed that only two papers found a strong relationship between sugar consumption and caries development, sixteen found a moderate relationship, and eighteen found weak-to-no relationship. It was concluded that the relationship between sugar consumption and caries is much weaker in the modern age of fluoride exposure than it used to be. Controlling the consumption of sugar remains a justifiable part of caries prevention, however, if not always the most important aspect.

Does low birthweight increase the risk of caries? A systematic review.

Low birthweight is a major public health and social problem in the United States. While a long list of mortality and morbidity conditions have been associated with low birthweight, dental conditions have not received much attention. This systematic review addresses this question: Do low-birthweight children (birthweight <2500 grams) subsequently develop more caries than do children with normal-to-high birthweight? The MEDLINE and EMBASE databases were searched for English-language papers published between January 1966 and July 2000 using a search expression developed in conjunction with an experienced librarian. There were 198 papers located in the initial search; a title and abstract review to identify clearly irrelevant papers reduced this number to 37. Two readers each read these papers, and application of predetermined inclusion/exclusion criteria reduced this number to only four papers. Quality criteria were established for scoring each of these papers on evidence tables. The maximum score for each paper was 100; the four papers rated scored between 31 and 61. Results showed that no relationship between low birthweight and subsequent development of caries was reported in any of the four papers. However, conclusions must be cautious because of the scarcity of studies on the subject and the limited scope of the four papers judged. The relationship of low birthweight to subsequent development of caries, especially in the permanent dentition, needs further exploration.

Sugared soda consumption and dental caries in the United States.

Because of the complexity of the caries process, the potential cariogenicity of specific food items is difficult to assess. The purpose of this study was to investigate the associations between sugared soda consumption and caries. Dietary and dental examination data from the 1988-94 Third National Health and Nutrition Examination Survey (NHANES III) were used. From the food frequency questionnaire and 24-hour recall data, significant associations between DMFS and soda consumption were generally seen in persons over age 25. No differences in DMFS, relative to soda consumption, were seen in persons under age 25, or in analyses of dfs for children under age 12. The observed associations could be due to the cumulative effects of the long-term consumption of sugared soda. The absence of apparent effects of sugared soda consumption in younger people may also be related to the increased use of fluorides since the 1960s.

Using positron emission tomography with [(18)F]FDG to predict tumor behavior in experimental colorectal cancer.

This study investigates the relationship between FDG uptake as determined by positron emission tomography (PET) imaging and rates of tumor growth, cellular GLUT1 transporter density, and the activities of hexokinase and glucose-6-phosphatase in a solid tumor implant model. Five different human colorectal xenografts of different growth properties were implanted in athymic rats and evaluated by dynamic (18)F-FDG-PET. The phosphorylating and dephosphorylating activities of the key glycolytic enzymes, hexokinase and glucose-6-phosphatase, were measured in these tumor types by spectrophotometric assays and the expression of GLUT1 glucose transporter protein was determined by immunohistochemistry. Correlations among FDG accumulation, hexokinase activity, and tumor doubling time are reported in these colon xenografts. The results indicate that the activity of tumor hexokinase may be a marker of tumor growth rate that can be determined by (18)F-FDG-PET imaging. PET scanning may not only be a useful tool for staging patients for extent of disease, but may provide important prognostic information concerning the proliferative rates of malignancies.

Functional interaction between fluorodeoxyuridine-induced cellular alterations and replication of a ribonucleotide reductase-negative herpes simplex virus.

G207 is an oncolytic herpes simplex virus (HSV) which is attenuated by inactivation of viral ribonucleotide reductase (RR) and deletion of both gamma(1)34.5 genes. The cellular counterparts that can functionally substitute for viral RR and the carboxyl-terminal domain of ICP34.5 are cellular RR and the corresponding homologous domain of the growth arrest and DNA damage protein 34 (GADD34), respectively. Because the thymidylate synthetase (TS) inhibitor fluorodeoxyuridine (FUdR) can alter expression of cellular RR and GADD34, we examined the effect of FUdR on G207 bioactivity with the hypothesis that FUdR-induced cellular changes will alter viral proliferation and cytotoxicity. Replication of wild-type HSV-1 was impaired in the presence of 10 nM FUdR, whereas G207 demonstrated increased replication under the same conditions. Combined use of FUdR and G207 resulted in synergistic cytotoxicity. FUdR exposure caused elevation of RR activity at 10 and 100 nM, whereas GADD34 was induced only at 100 nM. The effect of enhanced viral replication by FUdR was suppressed by hydroxyurea, a known inhibitor of RR. These results demonstrate that the growth advantage of G207 in FUdR-treated cells is primarily based on an RR-dependent mechanism. Although our findings show that TS inhibition impairs viral replication, the FUdR-induced RR elevation may overcome this disadvantage, resulting in enhanced replication of G207. These data provide the cellular basis for the combined use of RR-negative HSV mutants and TS inhibitors in the treatment of cancer.

Fluid consumption related to climate among children in the United States.

OBJECTIVE: Recommended fluoride concentrations in US public water systems are between 0.7-1.2 ppm, depending on the mean daily maximum temperature. This range assumes that water intake is higher in warmer than in cooler climates, based on research from the 1950s. The aim of this analysis is to relate fluid consumption among American children aged 1-10 years to the local climate under modern conditions. METHODS: The quantities of daily total fluid intake per body weight (ml/kg) and plain water intake per body weight (ml/kg) of children were calculated from the 24-hour recall diet survey in the third National Health and Nutrition Examination Survey (NHANES III, 1988-94). The mean daily maximum temperature from 1961 to 1990, averaged for the month during which the NHANES III exam was conducted, was obtained for each survey location from the US Local Climate Historical Database. Multiple regression analysis was conducted using SAS and SUDAAN. RESULTS: Fluid intake was significantly associated with age, sex, socioeconomic status (SES), and race and ethnicity. No significant association could be found between the amount of either total fluid or plain water intake and mean daily maximum temperature, either before and after controlling for sex, age, SES, and race or ethnicity. CONCLUSIONS: Results indicate that there is no evidence that fluid consumption among children is significantly related to mean temperature in modern conditions. This suggests that the national temperature-related guidelines for fluoride concentration in drinking water may be due for reevaluation.

Water consumption and nursing characteristics of infants by race and ethnicity.

OBJECTIVES: The purpose of this project was to determine racial/ethnic differences in water consumption levels and nursing habits of children younger than 2 years old. METHODS: Data from the 1994-96 Continuing Survey of Food intakes by individuals (CSFII) were used for these analyses. Water consumption and breast-feeding data on 946 children younger than 2 years old were used. RESULTS: For black non-Hispanic children younger than 2 years old (n = 121), 5.3 percent of the children were currently being breast fed. This percentage was less than that seen in other racial/ethnic groups. For white non-Hispanic children (n = 620), this percentage was 10.8 percent; for Hispanic children (n = 146), 12.2 percent; for "other" children, 18.5 percent (n = 59). Black non-Hispanic children had the highest total water consumption (128.6 ml/kg/day) among all groups, white non-Hispanic had the lowest (113.2 ml/kg/day). These differences were not statistically significant in multivariate regression modeling. Black non-Hispanic children also drank more tap water (21.3 ml/kg/day) than white non-Hispanic children (12.7 ml/kg/day) and Hispanic children (14.9 ml/kg/day). The difference was statistically significant in multivariate regression modeling. CONCLUSIONS: The differences in breast feeding and water consumption observed among black children younger than 2 years of age could be a factor in the observed higher levels of fluorosis in black children compared to other children.

Effects of preexisting immunity on the response to herpes simplex-based oncolytic viral therapy.

Herpes simplex viruses (HSV) type 1 are the basis of a number of anticancer strategies that have proven efficacious in animal models. They are natural human pathogens and the majority of adults have anti-HSV immunity. The current study examined the effect of preexisting immunity on the response to herpes-based oncolytic viral treatment of hepatic metastatic cancer in a murine model designed to simulate a clinical approach likely to be utilized for nonneurological tumors. Specifically, the anticancer effects of NV1020 or G207, two multimutated HSV-1 oncolytic viruses, were tested in immunocompetent mice previously immunized with a wild-type herpes simplex type 1 virus. Mice were documented to have humoral as well as cell-mediated immunity to HSV-1. Tumor response to oncolytic therapy was not measurably abrogated by immunity to HSV at the doses tested. The influence of route of viral administration was also tested in models of regional hepatic arterial and intravenous therapy. Route of viral administration influenced efficacy, as virus delivered intravenously produced some detectable attenuation while hepatic arterial therapy remained unaffected. These results demonstrate that when given at appropriate doses and in reasonable proximity to tumor targets, HSV-based oncolytic therapy can still be expected to be effective treatment for patients with hepatic malignancies.

The effects of a break in water fluoridation on the development of dental caries and fluorosis.

Durham, NC, fluoridated since 1962, had an 11-month cessation of fluoridation between September, 1990, and August, 1991. The purpose of this study was to assess the effects of this break on the development of caries and fluorosis in children. Study participants were continuously-resident children in Kindergarten through Grade 5 in Durham's elementary schools. There were 1696 children, 81.4% of those eligible, for whom a questionnaire was completed and clinical data recorded. Age cohorts were defined by a child's age at the time that fluoridation ceased. Caries was recorded in children in the Birth Cohort through Cohort 3, and fluorosis for children in Cohorts 1 through 5. Caries was assessed in the primary first and second molars according to the decayed-filled index; fluorosis on the labial surfaces of the upper permanent central and lateral incisors was assessed by the Thylstrup-Fejerskov (TF) index. Mother's education was associated with caries; higher education of the mother had an odds ratio of 0.53 (95% CI 0.40, 0.76) for caries in the child. No cohort effects could be discerned for caries. Overall prevalence of fluorosis was 44%. Prevalence in Cohorts 1, 2, 3, 4, and 5 was 39.8%, 32.3%, 33.0%, 62.3%, and 57.1%, respectively. These cohort differences remained statistically significant in regression analysis. It was concluded that while the break had little effect on caries, dental fluorosis is sensitive to even small changes in fluoride exposure from drinking water, and this sensitivity is greater at 1 to 3 years of age than at 4 or 5 years.

Oral Chlamydia trachomatis in patients with established periodontitis.

Periodontitis is considered a consequence of a pathogenic microbial infection at the periodontal site and host susceptibility factors. Periodontal research supports the association of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, and Bacteroides forsythus, and periodontitis; however, causality has not been demonstrated. In pursuit of the etiology of periodontitis, we hypothesized that the intracellular bacteria Chlamydia trachomatis may play a role. As a first step, a cross-sectional study of dental school clinic patients with established periodontitis were assessed for the presence of C. trachomatis in the oral cavity, and in particular from the lining epithelium of periodontal sites. C. trachomatis was detected using a direct fluorescent monoclonal antibody (DFA) in oral specimens from 7% (6/87) of the patients. Four patients tested positive in specimens from the lining epithelium of diseased periodontal sites, one patient tested positive in healthy periodontal sites, and one patient tested positive in the general mucosal specimen. In conclusion, this study provides preliminary evidence of C. trachomatis in the periodontal sites. Planned studies include the use of a more precise periodontal epithelial cell collection device, the newer nucleic acid amplification techniques to detect C. trachomatis, and additional populations to determine the association of C. trachomatis and periodontitis.

Water consumption in the United States in 1994-96 and implications for water fluoridation policy.

OBJECTIVES: The purpose of this project was to describe current water consumption patterns and to compare them to findings from earlier studies. Current water consumption data also were used to reevaluate the association between water consumption and climate. These findings are of importance in estimating fluoride intake from fluoridated water. METHODS: Findings from the 1994-96 Continuing Survey of Food Intakes by Individuals (CSFII) were compared to those from two earlier dietary studies, the 1977-78 Nationwide Food Consumption Survey (NFCS) and the pioneering research of Galagan and colleagues in the 1950s. Food consumption data were analyzed for 14,619 persons with food and beverage intake data for two 24-hour periods in the CSFII. RESULTS: Increased consumption of infant formulas and decreased consumption of tap water and cow's milk were seen in the CSFII for infants compared to the NFCS. Older children and adults showed increased consumption of carbonated beverages and juices. While Galagan and colleagues found about a 60 percent increase in water consumption between the coldest (55 degrees F) and warmest (85 degrees F) conditions, only a 20 percent difference was seen between the winter and summer months in certain regions in the CSFII. CONCLUSIONS: No obvious strong or consistent association between water intake and month or season was apparent in these recent data. These findings are preliminary, and suggest that water fluoridation policy requires further research regarding water consumption and climate.