Periodontal disease and gene-expression levels of metalloendopeptidases in human buccal mucosal epithelium.

BACKGROUND AND OBJECTIVE: Endopeptidases, such as neutral endopeptidase (NEP), endothelin-converting enzyme-1 (ECE-1) and a disintegrin and metalloprotease 17 (ADAM17), are believed to have various important roles in oral mucosal and epidermal tissue for the regulation of defensive biological responses in the oral cavity, and their expression and activity are influenced by various factors, including oral diseases. However, knowledge concerning these endopeptidases in the oral cavity has been minimal until now. This study focused on three metalloendopeptidases - NEP, ECE-1 and ADAM17 - in the oral buccal mucosal epithelium of patients with periodontal diseases and investigated the relationship between their gene-expression levels and periodontal disease. MATERIAL AND METHODS: The levels of expression of NEP, ECE-1 and ADAM17 mRNAs in tissue samples collected from the oral buccal mucosal epithelium of 61 patients were investigated by relative quantification using real-time RT-PCR analysis. information on oral and systemic health was obtained from the clinical record of each patient. RESULTS: Among the three groups, classified based on the diagnosis of periodontal diseases (healthy/gingivitis, early periodontitis and moderate/advanced periodontitis), the relative expression level of NEP mRNA was significantly increased in the early periodontitis group and in the moderate/advanced periodontitis group compared with that in the healthy/gingivitis group. Moreover, the relative expression levels of ECE1 and ADAM17 mRNAs were significantly increased in the moderate/advanced periodontitis group compared with those in the healthy/gingivitis group. The correlation coefficients between the mean relative expression levels of NEP and ECE1 mRNAs, NEP and ADAM17 mRNAs, and ECE1 and ADAM17 mRNAs were r = 0.758, r = 0.707 and r = 0.934, respectively (p < 0.001). Furthermore, among the oral-related factors, there was a significant correlation between the number of sites with probing pocket depths of more than 4 mm and of more than 6 mm and the relative expression levels of NEP, ECE1 and ADAM17 mRNAs. In stepwise logistic regression models, high relative expression levels of ECE1 and ADAM17 mRNAs were significantly associated with moderate/advanced periodontitis. CONCLUSION: The present study suggests that the severity of periodontal disease may be associated with the expression of metalloendopeptidase genes, including NEP, ECE1 and ADAM17, in the buccal mucosal epithelium.

Estimating the lifetime economic burden of Parkinson's disease in Singapore.

BACKGROUND AND PURPOSE: We aimed to estimate the lifetime cost of Parkinson's disease (PD) from the societal perspective. METHODS: A convenience sample of English or Chinese-speaking patients with PD was recruited from a PD and Movement Disorders Centre in Singapore to complete a financial burden questionnaire. Sociodemographic and clinical data were retrieved from hospital databases. Markov cohort model analysis was performed (cycle length, 1-year; duration, death or reached 100 years old). Patients were assumed to progress from one Markov state to the next state or death without skipping states or regressing. All model parameters were based on published local data. RESULTS: In 195 patients with PD (median age: 68.9, male: 51.8%), the simulated lifetime cost of PD was Singapore Dollar (SGD) 60,487 (EUR purchasing power parity 56,253) per patient. Direct medical, non-medical and indirect cost accounted for 18.8%, 12.8% and 68.4% of total lifetime cost, respectively. The top three components of total lifetime cost were productivity losses (67.6%), pharmacotherapy (11.4%) and home care (8.7%). One-way sensitivity analysis and probabilistic sensitivity analyses revealed that estimates were sensitive to cost at H&Y stage 1, 2 and 2.5 and productivity losses. CONCLUSIONS: The lifetime cost of PD is evaluated for the first time. This cost is substantial and comparable to the lifetime cost of intracerebral haemorrhage in at least one study. Our study identified several priority areas for research and policy formulation: reducing productivity losses, reducing cost of pharmacotherapy, avoiding hospitalization and reducing home care cost.

Applicability of both dentist and patient perceptions of dentists' explanations to the evaluation of dentist-patient communication.

OBJECTIVES: Very little is known about dentist-patient communicative behaviours in actual practice. This study evaluated dentist and patient perceptions of dentist-patient communication and patient outcome. PARTICIPANTS: The subjects were 171 dentist-patient pairs in Kitakyushu, Japan. RESEARCH DESIGN: Dentists and patients answered the same questionnaire items using the same response categories to evaluate dentist-patient communication. Based on the scores of patient and dentist perceptions with respect to dentist-patient communication, patient-dentist pairs were categorised into one of 3 groups. Data analyses used one-way ANOVA, multiple linear regression analysis, and multiple logistic regression analysis. RESULTS: We found that, with respect to dentist-patient communication, patients in the 'patient better' group (i.e., the patient's evaluation was more positive than the dentist's evaluation) were more likely to have a positive outcome (e.g., 'improvement of health and fear,' 'satisfaction with care') than those in the other two groups. Patients in the 'doctor better' group (i.e., the dentist's evaluation was the more positive) were more likely to have a negative outcome than those in the other two groups. CONCLUSIONS: A positive patient outcome is more likely when the patient's evaluation is better than a dentist's evaluation with respect to dentist-patient communicative behaviours. The method based on patient and dentist perceptions with respect to dentist-patient communication might be effective in evaluating dentist-patient communication.

Cognitive function and number of teeth in a community-dwelling elderly population without dementia.

Although the number of sound or decayed teeth has been reported to be associated with cognitive function in elderly populations with dementia, little is known about this association in elderly populations without dementia. We evaluated this relationship, with adjustment for confounding factors, in Japanese populations of 60-year-old (n = 270; 120 males and 150 females) and 65-year-old (n = 123; 57 males and 66 females) individuals residing in Fukuoka Prefecture of Japan. Dental examinations were performed in all subjects, along with the Mini-mental state examination (MMSE) for assessing cognitive function. Among the total of 393 subjects, the mean MMSE score was 27.9 +/- 1.9, and 391 subjects scored 24 or higher. The mean numbers of sound and decayed teeth were 12.0 +/- 6.3 and 0.5 +/- 1.2, respectively. Associations were found between the numbers of sound and decayed teeth and MMSE in total subjects and males, but not in females, by multiple regression analysis adjusted for gender, age, level of education, marital status, smoking, alcohol drinking, working status, systolic blood pressure and blood glucose. An association was also found between MMSE and the number of sound teeth in a logistic regression analysis. In conclusion, associations were found between normal-range cognitive function and the numbers of sound and decayed teeth, after adjustment for various confounding factors, in an elderly Japanese population.

Physical fitness and cognitive function in an 85-year-old community-dwelling population.

BACKGROUND: Little is known about the association between physical fitness and cognitive function in very elderly people (over 80 years of age). OBJECTIVES: To evaluate that relationship in 85-year-old community-dwelling individuals. METHODS: Out of 207 participants (90 males, 117 females) who were 85 years old and community-dwelling, 205 completed the Mini-Mental State Examination (MMSE) for evaluating cognitive function. The numbers of subjects who completed physical fitness measurements such as hand-grip strength, isometric leg extensor strength, one-leg standing time, stepping rate, and walking speed were 198, 159, 169, 168, and 151, respectively. RESULTS: There were significant associations in MMSE with hand-grip strength (right or left hand), isometric leg extensor strength, stepping rate, and walking speed by simple regression analysis. MMSE was still significantly associated with hand-grip strength (beta = 0.305, p = 0.005 for right side; beta = 0.309, p = 0.004 for left side), stepping rate (beta = 0.183, p = 0.046), and walking speed (beta = -0.222, p = 0.014) by multiple regression analysis after adjustments for the amount of education, gender, smoking, drinking, complication of stroke, body weight, body height, regular medical care, serum albumin, blood HbA1c, and marital status. By logistic regression analysis, the prevalence of a normal MMSE score (MMSE >or=24) was increased by 9% with each 1-kg increase in hand-grip strength of the left hand (OR 1.087, 95% CI 1.003-1.179, p = 0.042), and was increased by 6% with each step per 10 s in stepping rate (OR 1.060, 95% CI 1.000-1.122, p = 0.048). CONCLUSION: In a very elderly population of 85-year-olds, cognitive function was associated with some physical fitness measurements, independent of confounding factors.

Oral health and mortality risk from pneumonia in the elderly.

Although poor oral health influences the occurrence of pulmonary infection in elderly people, it is unclear how the degree of oral health is linked to mortality from pulmonary infection. Therefore, we evaluated the relationship between oral health and four-year mortality from pneumonia in an elderly Japanese population. The study population consisted of 697 (277 males, 420 females) of the 1282 individuals who were 80 years old in 1997. Data on oral and systemic health were obtained by means of questionnaires, physical examinations, and laboratory blood tests. One hundred eight of the study persons died between 1998 and 2002. Of these, 22 deaths were due to pneumonia. The adjusted mortality due to pneumonia was 3.9 times higher in persons with 10 or more teeth with a probing depth exceeding 4 mm (periodontal pocket) than in those without periodontal pockets. Therefore, the increase in teeth with periodontal pockets in the elderly may be associated with increased mortality from pneumonia.

Number of teeth and serum lipid peroxide in 85-year-olds.

OBJECTIVES: To investigate influence of dental status on systemic oxidative stress, we evaluated the association between number of teeth and serum lipid peroxide, an oxidative stress index, in 85-years old residents of Japan. METHODS: In October 2003, 207 subjects 85-years old agreed to participate in the present follow-up study after five years from the 8020 Data Bank Survey of Fukuoka prefecture in 1998. Dental health condition including number of teeth was examined by dentists. Data from 204 subjects (88 male, 116 female) who completed nonfasting venous blood examination including lipid peroxide and blood chemistry were analyzed. The examination included a medical questionnaire regarding smoking history, physical activity, alcohol consumption, educational duration, and regular dental care, anthropometric and manometric measurements. RESULTS: Albumin, lipids, and lipid peroxide in serum all were within the normal range. Number of teeth correlated positively with height and white blood cell count, and correlated negatively with lipid peroxide. In a multiple regression analysis to adjust for confounding factors, tooth number retained this correlation with lipid peroxide. By analysis of variance with a Bonferroni-Dunn correction, edentulous subjects showed significantly higher lipid peroxide than those retaining 20 teeth or more. CONCLUSION: The negative association between number of teeth and lipid peroxide links more teeth remaining with less oxidative stress in an 85-year-old population; this may decrease risk of atherosclerotic complications.

Relationship between chewing ability and 4-year mortality in a cohort of 80-year-old Japanese people.

OBJECTIVE: Poor oral health has been reported to be a risk indicator of mortality, however, few data are available regarding the relationship between chewing ability and mortality. We examined the relationship between self-assessed chewing ability and mortality in elderly subjects. DESIGN: Prospective study. SUBJECTS AND METHODS: Participating in the study were 697 people (277 males, 420 females) from 1282 individuals (80 years old) residing in Fukuoka Prefecture, Japan. Data on oral and systemic health status through questionnaires, accompanied by physical and laboratory blood examinations were obtained. Chewing ability was assessed based on the number of types of food each subject reported as able to chew by questionnaire. RESULTS: A total of 108 subjects died between 1998 and 2002. Those with the lowest number of chewable foods were associated with higher risk of mortality than those with the ability to chew all of the 15 types of food surveyed [hazard ratio (HR) = 2.38, 95% confidence interval (95% CI) = 1.07-5.29], though other parameters including current smoking, low serum albumin, and poor physical health status were more significant. Further, reduced chewing ability of soft foods increased the risk (HR = 2.65, 95% CI = 1.20-5.87). CONCLUSION: Chewing ability was associated with mortality in a population of 80-year-old community residents, and may be a predictor for survival rate.

Relationship of number of remaining teeth to health-related quality of life in community-dwelling elderly.

OBJECTIVE: The aim of this study was to evaluate the relationship between number of remaining teeth and health-related quality of life in community-dwelling elderly. SUBJECTS: A total of 207 participants who were community-dwelling, 85 years of age. Data were from a population-based study of age-related general and oral health in Fukuoka Prefecture, Japan. MEASUREMENTS: The Japanese version of the Short Form 36 Health Survey (SF-36). RESULTS: The mental component score for the participants, from the SF-36, was higher than the Japanese national norm for those aged > or = 70 years. There were no significant differences in the mean of any scores on the SF-36 by having spouse, living with family, or education level. The mean of the SF-36 scores of physical functioning (PF) and of the physical component scores were significantly higher in the 85-year-old participants with > or = 20 teeth than in those with < or = 19 teeth (p < 0.05 and p < 0.01 respectively). In addition, a significant difference (p < 0.05) was observed between the mean of participants with > or = 20 teeth and those with < or = 19 teeth after adjustment for region where the participant lived, activities of daily living (ADL), and sex. The PF (p < 0.001), role-physical (p < 0.005), bodily pain (p < 0.001), vitality (p < 0.001), social functioning (p < 0.05), and physical component (p < 0.001) scores were significantly higher in participants with a good activities of daily living (ADL) assessment. However, ADL was not associated with the number of teeth. CONCLUSIONS: The findings of the present study indicated that 85-year-old participants with > or = 20 teeth had better subjective physical health than those with < or = 19 teeth.

Relationship between dental care and oral health in institutionalized elderly people in Japan.

This study examined the relationship between dental care and dental health status in institutionalized elderly people in Japan through a 6-year prospective cohort study. All the 719 subjects received both baseline and follow-up surveys. The uptake of dental care was examined at the follow-up survey. We examined the relationship between baseline variables and the provision of dental care, and the relationship between dental care and change of oral health status. About 47% of the subjects and about 60% of the baseline dentate subjects received some dental treatment during the 6-year follow-up period. The subjects who were in better systemic and dental health at baseline used dental services frequently. The number of teeth needing extraction decreased in the subjects who received dental treatment, and increased in the untreated subjects. Denture status was better in the treated subjects than in the untreated subjects. Dental care appears to be an important factor in maintaining a healthy oral status for the institutionalized elderly.

The assessment of methyl mercaptan, an important clinical marker for the diagnosis of oral malodor.

OBJECTIVE: This study aimed to determine the clinical assessment of volatile sulfur compound (VSCs) for the evaluation of noticeable oral malodor using gas chromatography (GC). METHODS: The oral malodor of 127 adult patients was investigated using the organoleptic test and GC, and the relation between the organoleptic evaluation and VSCs were analyzed. RESULTS: The optimum cut-off values of CH3SH, H2S and total VSC (CH3SH + H2S) to discriminate between the patients with and without noticeable oral malodor were obtained from ROC curves, and determined to be 0.44, 1.10 and 2.20 ng/10 ml, respectively. The logistic regression was analyzed for estimation of the association between an organoleptic evaluation greater than a slight level and the groups with CH3SH, H2S or total VSC with concentrations above the optimum cut-off value. Only CH3SH showed an independent association with noticeable oral malodor. CONCLUSIONS: It was evident that CH3SH was a more useful marker for the evaluation of oral malodor than H2S. Moreover, it appears CH3SH is the predominant causative factor of noticeable oral malodor.

The Internet as a source of health information among Singaporeans: prevalence, patterns of health surfing and impact on health behaviour.

OBJECTIVE: The Internet is an increasingly popular source of healthcare information. This study describes the prevalence of health surfers in Singapore and their health-surfing patterns. It also assesses their confidence in online health information and the impact the Internet has on health-seeking behaviour. MATERIALS AND METHODS: A cross-sectional survey using a standardised questionnaire was carried out among residents aged 13 to 55 years in 1852 units in Bishan North. These units were selected by single-stage simple random cluster sampling method. RESULTS: The household response rate was 51% (n = 950) and the individual response rate was 69% (n = 1646). Responding and non-responding households were similar in terms of ethnicity and housing type. Of the responders, 62.9% surfed the Internet and 37.7% have surfed for health information. Health surfers tended to be younger (20 to 39 years) and have higher education status. Indians were also more likely than other ethnic groups to surf for health. Professional health-related sites comprised the majority (68%) of sites visited, and the most common search keywords concern chronic degenerative diseases, e.g. hypertension. The top preferred sources of health information were doctors (25.9%), the Internet (25.3%) and the traditional mass media (20.5%). Almost half (45.1%) considered online health information trustworthy if it was from a professional source or if the website displayed the source, while 10.6% trusted the information if it concurred with the doctors' advice. The vast majority (91.7%) had taken some action in response to the information. CONCLUSION: The Internet is being used as an accessible source of health information by a substantial proportion of the lay public. While this can facilitate greater partnership in healthcare, it underlines the need for doctors to be pro-active in the practice of evidence-based medicine, and for guidelines to enable patients to use this tool in a discerning manner.

Influence of dentition status on physical disability, mental impairment, and mortality in institutionalized elderly people.

The loss of teeth is known to influence the mastication of foods and nutritional status. Therefore, we hypothesize that poor dentition status can impair the systemic health of the aged. To clarify the influence of dentition status on deterioration in physical ability, mental impairment, and mortality, we conducted a six-year prospective cohort study of the institutionalized elderly living in 29 of the 30 institutions for the elderly in Kitakyushu, Japan. Bivariate analysis revealed that worse dentition status at baseline led to significantly worse physical and mental impairment, and higher mortality. In a multiple logistic regression analysis, the physical ability of edentulous subjects without dentures significantly deteriorated compared with that of dentate subjects with 20 or more teeth. The six-year mortality rate of the edentulous subjects without dentures was significantly higher than that of the subjects with 20 or more teeth. Poorer dentition status, especially edentulousness without dentures, may therefore be related to deterioration in the systemic health of the aged.

Antigenic characterization in ampiroxicam-induced photosensitivity using an in vivo model of contact hypersensitivity.

Ampiroxicam (APX), a prodrug of piroxicam (PXM), has been reported to induce photosensitivity. Antigenic characterization of these photosensitivities, however, is still insufficient. The purpose of the present study was to elucidate further mechanism of photosenstivity induced by APX and PXM using an in vivo model of contact hypersensitivity in guinea pigs. Animals sensitized with ultraviolet-A (UVA)-irradiated 1% APX showed positive reaction in the patch testing to UVA-irradiated 1% APX and 1% thiosalicylate (TOS), while they were negative in challenge with UVA-irradiated 1% PXM, non-irradiated APX and PXM, whereas none of UVA-irradiated or non-irradiated APX and PXM showed positive patch test reaction in animals sensitized with UVA-irradiated 1% PXM or control vehicles. Animals sensitized with 1% TOS were successfully challenged by 1% TOS and cross-reacted with UVA-irradiated 1% APX; however, they failed to react with UVA-irradiated PXM, non-irradiated APX and PXM. Indeed, the in vitro study revealed that the concentration of APX was easily reduced by the increase of UVA irradiation dose, as compared with that of PXM. Interestingly, absorption spectrum of UVA-irradiated APX was similar to that of TOS, which is thought to be an active hapten of PXM. In the present study, we succeeded in the development of a novel animal model reflecting the clinical observations. Furthermore, these results suggested that contact hypersensitivity induced by UVA-irradiated APX is developed by photoproducts of APX itself, but not by the biotransformation of APX to PXM.

[Two regimens of combined 5'-deoxy-5-fluorouridine and cisplatin showing different dose intensities--investigation based on relative performances].

Patients with inoperable gastric cancer were given either of two regimens of combined 5'-deoxy-5-fluorouridine and cisplatin with different dose intensities. The results were compared based on ratios of the actual and the scheduled total doses of the regimens [relative performance (RP)]. The overall response rates and survival curves between the regimens showed no differences, but the incidences of severe adverse drug reactions was higher with regimen A, which had a higher dose intensity. Furthermore, survivals with regimen A were no different between the responding and non-responding patients, whereas the survivals of responding patients under regimen B were significantly longer than those of non-responding patients. Average RP were 0.87 with regimen A and 0.93 with regimen B. The mean RP of responding and non-responding patients were 0.94 and 0.84, respectively, with regimen A, and 0.99 and 0.89 with regimen B. Regarding survivals in both the RP = 1.0 and the RP < 1.0 groups, no difference was observed with regimen A. However, with regimen B, the RP = 1.0 group exhibited significantly better survival curves. Furthermore, survivals of the RP = 1.0 group under regimen B were much more favorable than in the RP = 1.0 group under regimen A. The above findings show that a regimen with an appropriate dose intensity has a favorable survival effect on patients.

Differential property of antigenic characterization between piroxicam and ampiroxicam in contact hypersensitivity.

Piroxicam (PXM; a non-steroidal anti-inflammatory drug) has been reported to induce photosensitivity. In our previous report, however, ultraviolet-A (UVA)-irradiated or non-irradiated PXM did not induce any reactions in the in vivo model of contact hypersensitivity, while positive patch testing was shown by ampiroxicam (APX; a prodrug of PXM). The purpose of the present study was to clarify the influence of protein on the antigenicity of PXM using this model. Animals sensitized by UVA-irradiated 1% APX showed positive patch testing (open application) in UVA-irradiated 1% APX, while they were negative in challenge by UVA-irradiated PXM with or without 5% human serum albumin (HSA). Although animals sensitized by 1% thiosalicylate (TOS), which is thought to be an active hapten of PXM, were cross-reacted with UVA-irradiated 1% APX, they failed to react with UVA-irradiated 1% PXM with or without HSA. On the other hand, intra-dermal testing (intra-dermal application) in UVA-irradiated 0.1% PXM with 5% HSA was positive in animals sensitized by UVA-irradiated 1% APX, while 5% HSA alone, 0.1% PXM with 5% HSA and UVA-irradiated 0.1% PXM did not induce any reactions under this condition. Furthermore, concentration of PXM in the presence of HSA was reduced by UVA-irradiation in a time dependent manner, while the degradation of PXM was not observed in the absence of HSA. Finally, PXM almost disappeared at 120 min after the initiation of UVA-irradiation. The degradation of PXM irradiated by UVA was dependent on the concentration of HSA at the range of 0 to 4%. Hence, these results suggest that the presence of protein is necessary for the induction of the antigenic activity of PXM and the antigenic characterization of PXM is different from that of APX in contact hypersensitivity.

[Differential diagnosis of post-transfusion graft-versus-host disease (GVHD) by rapid immunopathologic examination of the skin].

The diagnosis of post-transfusion graft-versus-host disease (GVHD) in early period is critical for the prognosis of the patients. Exanthema and fever are the earliest symptom of the post-transfusion GVHD and usually precede the disturbance of the liver and bone marrow. Snap-frozen, cryostat-sectioned specimens from the lesional and perilesional skin were labeled by monoclonal antibodies against HLA-ABC, HLA- DR, ICAM-1, CD1a and CD8. The reaction was visualized by indirect immunofluorescence. Graft-versus-host reaction (GVHR) was immunopathologically characterized by extensive expression of HLA-DR and ICAM-1 in the epidermal keratinocytes, exocytosis of CD8 positive cytotoxic T-cell and the reduction or disappearance of CD1a expression by epidermal dendritic cells. The other GVHRs such as erythema exudativum multiforme (EEM), fixed drug eruption, toxic epidermal necrolysis (TEN) and lichen planus could not be separated. Our protocol of the immunopathologic examination could be done quickly (within 3 hours) and provides more detailed and useful information for the diagnosis of GVHD in early period compared with conventional histopathology.