Effects of occupational environmental controls and work management on chromosomal damage in dental technicians in Japan.

Dental technicians use various materials, particularly metal alloys and monomers and polymers based on methylmethacrylate. Environmental hygiene issues surrounding the work of dental technicians have been recognized. Despite the need for observance of occupational environmental controls and work management, compliance among dental laboratories appears to be low. We evaluated the relationship between genotoxic effects in dental technicians and occupational environmental controls and work management. We used cytokinesis-blocked micronuclei (CB-MN) frequencies in peripheral lymphocytes and metal levels in scalp hair. We also assessed nutritional factors related to anti-genotoxic effects using a self-administered brief diet history questionnaire. Study subjects were 54 male dental technicians and 38 male clerical workers. The parameters on the micronuclei (MN) frequency in dental technicians and clerical workers were analyzed by forward stepwise multiple regression analyses. Age (P < 0.01, ß = 0.561), occupation as a dental technician (P < 0.01, ß = 0.636) and aluminum levels in scalp hair (P < 0.05, ß = 0.213) were risk factors that significantly increased MN frequency. The significant parameters on the MN frequency in dental technicians were observance of hand-washing as work management (P < 0.01, ß = -0.304), work period (P < 0.01, ß = 0.509), germanium levels in scalp hair (P < 0.01, ß = -0.314) and workplace (P < 0.05, ß = 0.235). To avoid genotoxic effects, observance of occupational environmental controls and work management is necessary for dental technicians.

Developing a new appliance to dissipate mechanical load on teeth and improve limitation of vertical mouth.

OBJECTIVES: The principle of leverage to superpose the convex surfaces of two shells was applied to develop a device for treating limitation of mouth opening and called it the "shell-shaped mouth opener" and analyzed pressure on the teeth with the TheraBite(®) appliance and the shell-shaped mouth opening appliance. MATERIAL AND METHODS: To compare the TheraBite(®) appliance and the shell-shaped mouth opening appliance, pressure on the teeth in the dentition model with both devices was analyzed using the Inastomer(®) flexible conductive sensor. RESULTS: The load was better dispersed to each tooth in the shell-shaped mouth opening appliance in the all quadrants compared to the TheraBite(®) appliance. CONCLUSIONS: The present study revealed that the shell-shaped mouth opening appliance which was originally invented in our lab, dissipated the mechanical load on teeth more evenly than the TheraBite(®) appliance.

Surgery for gastric cancer increases plasma levels of vascular endothelial growth factor and von Willebrand factor.

BACKGROUND: Angiogenesis and hemostatic activation are important factors in tumor progression and metastasis. Because surgical intervention induces tissue hypoxia and hemostatic activation, we analyzed the effect of gastric surgery on the plasma concentrations of vascular endothelial growth factor (VEGF), soluble P-selectin (sP-selectin), and von Willebrand factor (vWf). METHODS: Plasma VEGF, sP-selectin, and vWf concentrations were measured in 14 patients with gastric cancer before operation and on postoperative day 1 (POD 1). Correlations between disease stage and the effect of surgical intervention were analyzed. RESULTS: The plasma concentrations of these three factors did not correlate with the disease stage. Plasma levels of sP-selectin did not change after operation (before surgery, 87.6 +/- 34.1 ng/ml; on POD 1, 101.1 +/- 48.1 ng/ml; P = 0.123). Plasma VEGF and vWf concentrations were significantly elevated on POD 1 (VEGF, 33.3 +/- 20.5 pg/ml before surgery and 61.9 +/- 35.6 pg/ml on POD 1; P = 0.0013; vWf, 164 +/- 31.1% before surgery and 211.1 +/- 66.1% on POD 1; P = 0.027). CONCLUSION: Because VEGF and vWf are involved in angiogenesis, tumor-platelet adhesion, and tumor-endothelial cell adhesion, surgical intervention could influence tumor growth and metastasis.

The novel germline mutation of hMSH2 gene in a case of a colon cancer patient without family history.

Hereditary non-polyposis colorectal cancer (HNPCC) is generally found from the patient's family history. The functional disorder of mismatch repair genes has been reported to be responsible for HNPCC. The proband was a 28-year-old Japanese female who was admitted to our hospital with a diagnosis of descending colon cancer. Although there was no previous or family history of malignant disorders within the first- and second-degree relatives, the early onset of colon cancer prompted genetic analysis with suspicion of HNPCC. PCR analysis of the primary tumor showed DNA replication errors at the six microsatellite regions. PCR/direct sequential analysis of the peripheral lymphocytes revealed a germline frameshift mutation due to deletion of TTCAA at nt. position from 650 to 654 in exon 4 of the hMSH2 gene. According to the Human Mutation Database and International Collaborative Group on HNPCC Database, this type of the frameshift mutation is the first report in the hMSH2 gene.

Pharmacokinetic study of S-1, a novel oral fluorouracil antitumor agent in animal model and in patients with impaired renal function.

PURPOSE: S-1 is a novel oral fluorouracil antitumor drug that combines tegafur (FT), 5-chloro-2,4-dihydroxypyridine (CDHP), which inhibits dihydropyrimidine dehydrogenase (DPD), and potassium oxonate (Oxo). As 50% of CDHP is excreted in the urine, renal dysfunction may directly affect the DPD inhibitory effect and lead to increased 5-fluorouracil (5-FU) concentrations. We sought to determine the influence of impaired renal function on the pharmacokinetics of S-1 in an animal model and in patients with gastric cancer. METHODS: An experimental renal failure model induced by cisplatin was developed in rabbits, and plasma concentrations of FT, 5-FU, CDHP and Oxo were determined after S-1 injection. Four patients with various degrees of renal impairment with unresectable gastric cancer were recruited to the study, and the pharmacokinetics in these four patients were analyzed following single and consecutive S-1 administrations. RESULTS: In experimental renal failure, plasma clearance of CDHP and 5-FU was retarded corresponding to the degree of renal impairment and there was a close correlation between creatinine clearance (CLcr) and plasma CDHP and 5-FU clearance. In the single administration study, half standard dose was used in three patients (CLcr > or = 50 ml/min) and one-third in the other (CLcr <50 ml/min). In patients with CLcr more than 75 ml/min, C(max), T(max), AUC((0-infinity)), and T(1/2) of 5-FU and CDHP were not different between single and consecutive administrations. In contrast, in patients with mild and moderate renal dysfunction (CLcr 55 and 36 ml/min, respectively), the T(1/2) values of CDHP with consecutive administrations (7.6 and 15.3 h, respectively) were longer than the values with single administration (4.6 and 8.2 h, respectively). The T(1/2) of 5-FU was 5.7 h with single administration and 8.5 h with consecutive administration in patients with moderate renal impairment. The AUC((0-infinity)) of 5-FU with consecutive administrations (3089.7 ng.h/ml) was far greater than with single administration (430.4 ng.h/ml). There was also a strong correlation between CLcr and plasma CDHP clearance. Based on the pharmacokinetics following multiple consecutive administrations, S-1 administration resulted in no severe adverse reactions in any of the four patients. CONCLUSIONS: CDHP clearance was prolonged in the presence of renal impairment, leading to a delayed T(1/2), and high AUC of 5-FU. These findings demonstrate that administration of S-1 to patients with impaired renal function may need individualized dosing and pharmacokinetic monitoring.

Poor prognosis associated with thrombocytosis in patients with gastric cancer.

BACKGROUND: Thrombocytosis is commonly associated with malignant disease and has recently been suggested to be a poor prognostic indicator in patients with lung cancer and gynecological cancers. The prevalence of thrombocytosis in patients with gastric cancer was reviewed, and its association with poor prognosis was investigated. METHODS: Platelet count (PLT) and hemoglobin concentrations (Hb) were reviewed in 369 consecutive patients with histologically verified gastric cancer from 1994 to 2000. Differences between categories were analyzed with analysis of variance, and survival was compared by using the log-rank test on the Kaplan-Meier life table. Multivariate Cox regression analysis was used to evaluate whether thrombocytosis is an independent prognostic marker. RESULTS: Thrombocytosis was found in 42 patients, and anemia was found in 200 patients. PLT was negatively correlated with Hb. Mean PLT was significantly increased in patients with noncurative operations. There was a positive correlation between the depth of tumor invasion and PLT. One- and 3-year survival expectancies in patients with or without thrombocytosis were 52.4% and 23.4% and 85.7% and 72.9%, respectively. PLT was identified as an independent prognostic factor after lymph node metastasis and depth of tumor invasion. CONCLUSIONS: Thrombocytosis is an independent prognostic indicator of survival in patients with gastric cancer.