Hypophosphatasia: Evaluation of Size and Mineral Density of Exfoliated Teeth.

OBJECTIVE: Most cases of hypophosphatasia (HPP) exhibit early loss of primary teeth. Results of micro-computed tomography (micro-CT) analysis of teeth with HPP have not yet been reported. The purpose of the present study was to describe the size and mineral density distribution and mapping of exfoliated teeth with HPP using micro CT. STUDY DESIGN: Seven exfoliated teeth were obtained from a patient with HPP. Exfoliated teeth sizes were measured on micro CT images and mineral densities of the mandibular primary central incisors were determined. RESULTS: Partial dentures were fabricated for the patient to replace the eight primary teeth which had exfoliated. Most primary teeth sizes were within the normal range. The mean values of enamel and dentin mineral densities in teeth with HPP were 1.35 and 0.88 g/cm3, respectively, in the mandibular primary central incisors. CONCLUSION: Mineral density distribution and mapping revealed that the values in teeth with HPP were lower than the homonymous teeth controls in all regions from the crown to apex. Furthermore, it was demonstrated that the differences between HPP and controls were larger on the crown side and the differences tended to converge on the apex side. These results suggested that the present patient showed mild hypomineralization in the primary dentition.

Self-Esteem and Oral Condition of Institutionalized Abused Children in Japan.

OBJECTIVE: Abused children have been reported to have low self-esteem. The aim of this study was to investigate the effects of dental intervention on self-esteem, oral condition, and concern for oral health in abused children admitted to a child protection service facility. STUDY DESIGN: We examined the oral condition of 65 children (34 boys, 31 girls; aged 2-15 years), instructed them in tooth-brushing. Self-esteem was examined using Pope's five-scale test for children. Before discharge, the children completed questionnaires on concern about their oral health. RESULTS: The findings revealed the reasons for admission were child abuse and neglect (n=45), domestic violence against the mother (n= 20), special needs (n=11), delinquency (n=7), school refusal (n=2), and other reasons (n=3). Thirty-five of the 65 residents (54%) needed treatment for caries. Of these, 24 (69%) were abused children and 11 (31%) were admitted due to other reasons. Mean self-esteem score differed significantly between the resident children (n=43) and an outpatient control group (n=102) (59.16±14.54 vs 73.92±16.81, respectively; p<0.01). CONCLUSION: Although the abused children had low self-esteem, after dental intervention, positive answers regarding oral health were obtained. The findings suggest that dental interventions might be effective for helping to improve the self-esteem of abused children.

Effect of the antineoplastic agent busulfan on rat molar root development.

OBJECTIVE: The antineoplastic bifunctional-alkylating agent busulfan (Bu) induces developmental anomalies. We examined histopathological changes in the molar roots of rats that received Bu at different stages of root formation. DESIGN: At different developmental stages, i.e., on postnatal days (P) 13, 15, and 19, rats were administered 7.5 mg/kg of Bu dissolved in dimethyl sulfoxide (DMSO) and then killed on P 30. After micro-computed tomography analysis, the maxillary first molars underwent immunohistochemical analysis for cytokeratin 14 (CK14), nestin, and dentin sialoprotein (Dsp). This was followed by histomorphometric analysis. RESULTS: The rats receiving Bu at an early stage (i.e., P 13 and P 15) showed osteodentin formation and complete destruction of the Hertwig's epithelial root sheath (HERS). Cells around osteodentin showed nestin and Dsp immunoreactivity. The root lengths in rats treated with Bu at P 13 (1228.44 ± 62.17 µm) and P 15 (1536.08 ± 109.71 µm) were lower than that in the control rats (1674.10 ± 40 µm). A narrowed apical foramen and an increased amount of osteodentin were also present, depending on the rat's age at the time of treatment (P < 0.05). CONCLUSION: Busulfan treatment in juvenile rats resulted in abnormal root development, depending on the stage at which Bu was administered. This abnormal development may result from the destruction of the HERS. The administration of Bu caused a shortage of HERS cells, which are required for normal root development. This disturbs root formation, resulting in osteodentin formation and a narrowed apex foramen.

Tooth development included in the multifocal jaw lesions of Langerhans cell histiocytosis.

Many cases demonstrating the oral manifestations of Langerhans cell histiocytosis (LCH) have been reported; however, tooth development in jaw lesions has rarely been mentioned. This paper reports the case of a 3-year-old Japanese girl with LCH suffering from multiple osteolytic lesions of the skull and jaw bones. She was referred to our paediatric clinic because of swelling of the mucogingival folds in the upper and lower primary molar regions. The patient responded well to steroid therapy and the osteolytic lesions resolved. There was an accompanying development of permanent tooth germs included in the lesions. Langerhans cell histiocytosis in children usually has a long-term clinical course and paediatric dentists should be involved with oral health care for affected patients.

[Combination chemotherapy of doxifluridine plus mitomycin C for colorectal lung metastasis--phase II study].

PURPOSE: We conducted a multi-center study to investigate the usefulness of a combination drug therapy with doxifluridine (5'-DFUR) and mitomycin C (MMC) in colorectal cancer patients with lung metastasis. PATIENT AND METHODS: Subjects were advanced/recurrent colorectal cancer patients with lung metastasis, who underwent concomitant drug administration with 533 mg/m2/day of 5'-DFUR orally and 4 mg/m2/day of MMC every 2 weeks intravenously. RESULTS: Of 84 patients registered, 54 patients who were evaluable for tumor response showed results such as: complete response, one; partial response, 4; no change, 30; and progressive disease, 19, corresponding to a response rate of 9.3%. The median survival period of 54 patients was long at 473 days. The median administration days of 5'-DFUR was 201.5 days and the median number of MMC administrations was 14, indicating a long administration period of the combined therapy. The incidence of adverse drug reactions (ADRs) was 37.2% which included thrombocytopenia, 16.7%, and leukocytopenia, 11.5%; only a few ADRs were grade 3 or over. CONCLUSIONS: While combined therapy with 5'-DFUR and MMC resulted in a low response rate, the regimen suggested a survival effect in the patients.

Thymidine phosphorylase expression and effect of doxifluridine: a phase II study.

Doxifluridine (5'-DFUR), an active intermediate metabolite of capecitabine, is converted to 5-fluorouracil by thymidine phosphorylase (TP). We used immunohistochemical staining to investigate the relation between TP expression and 5'-DFUR effects in 40 patients with advanced/recurrent lung metastases from colorectal cancer. Cox regression analysis suggested that TP-positive cancer cells (risk ratio 3.72), were independent factors in survival whereas factors in progression-free survival were TP-positive cancer cells (2.93), and TP-positive stromal cells (0.24). It is suggested that TP expression in cancer cells and in stromal cells are opposite prognostic factors in patients treated with 5'-DFUR.

A review of clinical features in 13 cases of impacted primary teeth.

AIM: The aim of this study was to review clinical findings in 14 impacted primary teeth in 13 cases treated at a Paediatric Dental Clinic over a period of 18 years. METHOD: The retrospective study used clinical records, radiographs and oral photographs. Data included age, gender, presenting complaints, location, radiographic findings, aetiological factors, treatment and prognosis of impacted primary teeth and their permanent successors. RESULTS: The patients included five males and eight females aged from one year two months to seven years five months. One case had impacted bilateral, mandibular primary central incisors and the remaining 12 cases each had one impacted tooth. The maxillary second primary molar was the tooth most frequently involved. Permanent successor tooth germs were identified in 12 teeth but not in two. Five cases were impacted because of odontomas, in the case with bilaterally affected mandibular primary central incisors these were malpositioned and were erupting ectopically. In seven cases, aetiology was unknown. Four impacted primary teeth were extracted because eruption was unlikely. In four cases, odontomas were surgically removed and the teeth kept under observation. The remaining six were surgically exposed. Traction was applied in two of the six. Eight of the teeth erupted. In two teeth in which traction was used, one was subsequently extracted, and one erupted. In the cases of seven, permanent successors erupted. These were hypoplastic teeth and were delayed in development and eruption. CONCLUSIONS: Impacted primary teeth may be associated with defects in development and eruption of their permanent successors, long-term observation is therefore necessary until the permanent successors erupt.

Feasibility of a novel weekday-on/weekend-off oral UFT schedule as postoperative adjuvant chemotherapy for colorectal cancer. UFT Compliance Study Group, Kanagawa, Japan.

PURPOSE: When oral anticancer agents are used for adjuvant chemotherapy of colorectal cancer, compliance and feasibility become issues because of the long treatment time. Appropriate studies of these issues are lacking. We investigated compliance and feasibility during a weekday-on/weekend-off schedule of oral UFT (uracil-tegafur) over a period of 1 year administered as adjuvant chemotherapy to patients with colorectal cancer. PATIENTS AND METHODS: A UFT dose of 600 mg/day was prescribed according to a weekday-on/weekend-off schedule to 87 patients after potentially curative resection. Compliance was investigated in three ways: physician interview, patient self-report, and chemical analysis of urine. The results were compared with the dose prescribed. Feasibility was evaluated on the basis of two indices: relative performance (RP), which was the ratio of the actual total dose taken to the total dose planned, and individual dose intensity (IDI), which was the ratio of the actual dose taken to the dose planned during a given period. RESULTS: The compliance assessed by physician interview and by patient self-report conformed well with the prescribed dose, the rate of agreement among the three compliance measures being more than 94%. Chemical analysis of urine in 38 of the patients revealed that they were actually taking the drug. The RP was 0.72, and the IDI was 0.8. CONCLUSION: From these results, the feasibility of the weekday-on/weekend-off schedule was judged to be good. It is suggested that the feasibility would be even better if the dose of UFT was set according to body surface area.

[Optimal dosage of UFT in a weekday-on/weekend-off schedule as a postoperative adjuvant chemotherapy for colorectal cancer].

In evaluations of adjuvant chemotherapy with oral anticancer agents, compliance in taking the drug as prescribed (compliance), adverse reactions, and feasibility are important factors in setting the dose. A weekday-on/weekend-off schedule, in which 600 mg/day of UFT was taken for 5 consecutive days and not taken on the following 2 days, was carried out as a postoperative adjuvant chemotherapy for one year in 87 patients with colorectal cancer who had undergone potentially curative resection. The prescribed dose and the dose of ingestion confirmed by physician interview were both highly consistent with the dose of ingestion according to the patients' self reports, with consistency rates of more than 94% for both. Relative performance (RP) yielded a value of 0.72, and individual dose intensity (IDI) yielded 0.8 on average. Female gender, low body weight, and low body surface area were factors that negatively affected feasibility. None of the adverse reactions was serious. Based on the feasibility and adverse reactions, the dosage of UFT should be set according to the body surface area at 375-425 mg/m2/day. When this schedule is used as one arm of a controlled study, it is suggested that the dose should be decided with 400 mg/m2 as a guideline.

Prognosis of replanted primary incisors after injuries.

Between 1979 and 1997, 58 avulsed primary teeth were treated at the Pedodontic Clinic of Niigata University Dental Hospital. Among these, we replanted six avulsed incisors of four patients and treated two teeth of two patients replanted at other dental clinics. Referring to the clinical records, oral photographs and radiographs, we examined the injury age, cause of injury, condition of tooth storage, length of time until replantation, and also the prognosis after replantation. Three teeth of two cases remained until eruption of their permanent successors, and one tooth of one case remained under observation without extraction. Although the other four teeth of three cases resulted in extraction, no secondary infection was detected due to replantation. The following reasons were suspected for the poor prognosis of the four teeth. One avulsed tooth was not fixed immediately after replantation. One replanted tooth might not have been compatible with the alveolar socket. In the other two teeth, the periodontal vital tissues might have been removed before replantation. It is generally suggested that replantation of primary teeth is not a good option. However, from the present results, it was considered that replantation can be an effectual method when the condition of the avulsed primary tooth is suitable.

Evaluation of the accuracy of preoperative staging in thoracic esophageal cancer.

BACKGROUND: Exact clinical staging before treatment of esophageal cancer has become increasingly important in the evaluation and comparison of the results of different treatment modalities, including surgery, chemotherapy, and radiotherapy. METHODS: The accuracy of preoperative tumor staging by using an esophagography, esophagoscopy, percutaneous and endoscopic ultrasonography, and computed tomography was assessed in 224 patients with resectable esophageal cancer. The results of tumor staging by these tests were compared prospectively with the pathologic stage of the esophagectomy specimens with respect to the T and N categories defined by the International Union Against Cancer TNM classification. RESULTS: For the T category, the overall accuracy was 80%. For the N category, overall accuracy was 72%, with a sensitivity of 78%, a specificity of 60%, and a positive predictive value of 78%. Overall, the accuracy of stage grouping was 56%. CONCLUSIONS: Either the T or N categories can be predicted reliably by clinical staging techniques. However, the preoperative stage grouping might not be valid in resectable, localized esophageal cancer.

Assessment of the proliferative activity of superficial esophageal carcinoma using MIB-1 immunostaining for the Ki-67 antigen.

BACKGROUND AND OBJECTIVES: Lymph node metastasis or vascular invasion may occur in superficial esophageal squamous cell carcinoma when it invades to or into the muscularis mucosae. Therefore, the correlation between histopathological characteristics and the proliferative activity of superficial esophageal carcinoma was investigated. METHODS: Thirty-eight cases of esophageal squamous cell carcinoma, including 14 cases of mucosal carcinoma and 24 cases of submucosal carcinoma, who underwent surgical resection without preoperative treatment, were studied using monoclonal antibody MIB-1 for the Ki-67 antigen immunohistochemically. The labeling index (LI) was calculated with a computed image analyzer. RESULTS: The LI of MIB-1 at the invasive tip of m3 carcinoma was significantly higher than that of m1 or m2 carcinoma (P < 0.01). The LI at the invasive tip was significantly higher than that at the core of sm2 (P < 0.05) and submucosal carcinoma overall (P < 0.01). The LI values at both the invasive tip and core of poorly differentiated carcinoma in submucosal carcinoma were higher than that of well or moderately differentiated carcinoma with a significant difference (P < 0.05). The LI at the invasive tip of submucosal carcinoma with lymph node metastasis or lymphatic invasion was significantly higher than that without them (P < 0.05). CONCLUSION: Proliferative activities of cancer cells in superficial esophageal squamous cell carcinoma, immunostaining with the MIB-1, were related to the depth of invasion, differentiation, lymph node metastasis, and lymphatic invasion with a significant difference.

Gut bacterial translocation during total parenteral nutrition in experimental rats and its countermeasure.

BACKGROUND: The use of total parenteral nutrition (TPN) is commonly associated with mucosal lining of the intestinal tract, causing degenerative changes within the gut-associated lymphoid tissue (GALT). These phenomena are probably caused by the translocation of indigenous intestinal bacteria into other organs and tissues where they induce infections. METHODS: Using TPN model rats, this paper looks at the result of the investigation of the action of PSK (proteoglycan), a biological response modifier, which appears to suppress bacterial translocation and maintain local immunity activity. RESULTS: Culture of mesenteric lymph nodes obtained post-TPN demonstrate a bacterial rate as high as 60%. Immunohistochemical examination indicates a reduction in the number of plasma cells and a decrease in S-IgA production and secretion. A similar reduction in S-IgA within bile and portal venous blood was also confirmed. Continuous oral administration of PSK in a daily dose of 1,000 mg/kg had a protective effect against the degeneration of GALT. A staining in immunocytes of Peyer's patches using immunohistochemical study was performed after administration of PSK and revealed constant levels of MHC-I, MHC-II, T helper cells, and interleukin-2 producing cells, supporting the protective role of PSK against degeneration of GALT with a subsequent reduction in bacterial translocation. CONCLUSIONS: Proteoglycan can restore the impaired local immunity in the intestinal tract to normal levels and suppression of the bacterial translocation to provide an important function for patients receiving TPN treatment.

Twenty-four-hour profile of growth hormone in cyclic nocturnal total parenteral nutrition.

OBJECTIVE: To detect the effect of the loss of alimentation rhythmicity on a circadian rhythm of human growth hormone (HGH) secretion, a 24-hour profile of HGH was studied in a growing child on cyclic nocturnal total parenteral nutrition (TPN). Twenty-four-hour profiles of substrates and metabolic hormones were also studied to evaluate the efficiency of cyclic nocturnal TPN on childhood growth. STUDY DESIGN: Periodic blood samples from a child with megacystis-microcolon-intestinal-hypoperistalsis syndrome were obtained on five occasions, at ages 6, 7, 8, 9, and 11, when she was on cyclic nocturnal TPN. RESULTS: Peak HGH secretion appeared with the onset of deep sleep despite the concomitant hyperglycemia and hyperinsulinemia induced by TPN at night. Smaller peaks of HGH were also observed during the noninfusion period during the day. Twenty-four-hour profiles of substrates and metabolic hormones indicated a switch from glucose use during the infusion phase to an oxidation of lipids during the noninfusion period. CONCLUSION: The fact that the patient's growth curve remains within normal limits suggests that cyclic nocturnal TPN would be an efficient method of nutritional support. During cyclic nocturnal TPN, regular rhythm of HGH secretion occurs, and normal childhood growth is achieved.

[Lymph node dissection for T1 esophageal cancer].

Proper mucosal cancer of esophagus of esophageal has no lymph node metastasis, and lymph node metastasis occurs when the tumor invades to muscularis mucosa. Submucosal cancer of esophagus has lymph node metastasis in the rate of 44.4% (40/90). The incidence and number of metastatic lymph node increase with the depth of invasion. Lymph node metastasis of esophageal cancer spreads widely to cervix, mediastinum and abdomen. It's same in submucosal cancer and first metastasis occurs also appears at everywhere from cervix to abdomen. There are high rate of lymph node metastasis in 101L, 105, 106rR, 106rL, 108, 110, 1, 2, 3, 7 lymph nodes. The cancer in upper thoracic esophagus has high rate of lymph node metastasis in cervix and upper mediastinum and lymph node metastasis of lower thoracic esophageal cancer is liable to appear in lower mediastinum and abdomen. Then the cancer in middle thoracic esophagus should be performed the lymph node dissection in cervix, mediastinum and abdomen, especially 101, 102m, 104, 105, 106r, 106t, 107, 108, 110, 1, 2, 3, 7 lymph nodes. On the other hand, cancers limited to proper mucosal layer should be treated with endoscopic mucosal resection. And its same as in the greater part of cancers invaded to muscularis mucosa and shallow layer of esophageal submucosa. The 5 year survival rate of T1 cancers of esophagus is 85.6%, which were performed surgical treatment.

HLA-A2 antigen status predicts metastasis and response to immunotherapy in gastric cancer.

Our previous studies have shown that HLA-DR4 and -B52 antigens are associated with an increased risk of lymph node metastasis in patients with gastric cancer. We hypothesized that a putative HLA antigen, correlated with a low risk of lymph node metastasis, may also be correlated with the response to anticancer therapy. The microcytotoxicity assay was used to examine 49 HLA antigens of the A, B, C, DR, and DQ loci, and the association between HLA class I and II antigen status and lymph node metastasis in 847 patients with gastric cancer as well as the response to the therapy in 739 patients were analyzed. HLA-A2 antigen was significantly associated with a low risk of lymph node metastasis in patients with T2-T4 advanced cancer [58.8% compared to 37.0% in patients with lymph node metastasis; corrected P, Pc (98), = 0.011], especially in those with moderately differentiated adenocarcinoma [71.0% compared to 26.4% in patients with lymph node metastasis, Pc (294) = 0.00294] and with a better response to post-operative immunotherapy using protein-bound polysaccharide K (PSK), a nonspecific immunomodulator, than to chemotherapy. HLA alleles may be associated with resistance or susceptibility to lymph node metastasis and HLA-A2 antigen may be a useful predictor of the response to PSK. The data suggest that the predictive power of this HLA antigen may prove useful in the selection of anticancer therapy.

[Effect of intraperitoneal therapy in gastric cancer with peritoneal dissemination].

Eighty gastric cancer patients with peritoneal dissemination were analyzed to evaluate the effect of intraperitoneal chemo- and/or immunotherapy on abdominal ascites. Among them, 19 were treated with intraperitoneal chemo- and/or immunotherapy, and 21.1% of them showed decreased ascites and better QOL. Patients treated with intraperitoneal administration with OK-432 showed good survival. Among patients with OK-432 administration, those receiving postoperative chemotherapy showed better survival than those given immunochemotherapy. Conversely, among patients with chemotherapy, those given postoperative immunochemotherapy showed better survival than those on chemotherapy. Patients with HLA-type I and III, and those with preoperative normal immune status showed good response when they received intraperitoneal therapy.

A case of multiple endocrine neoplasia type 2B.

A sporadic case of multiple endocrine neoplasia type 2B in a twenty-six year old man who manifested medullary thyroid carcinoma, multiple mucosal neuromas of the tongue and a marfanoid habitus is reported. At the time of diagnosis, he also had multiple liver and lung metastases. Genetic analysis of his lymphocytes revealed a point mutation in exon 16 of the RET proto-oncogene. Since multiple endocrine neoplasia type 2B has a relatively poor prognosis because of the occasional aggressive behavior of medullary thyroid carcinoma, the necessity of the genetic diagnosis of multiple endocrine neoplasia in the early stage is suggested.

Alterations in glutathione peroxidase activity following reperfusion injury to rat liver.

Prevention of cellular damage after warm ischemia is of major importance in liver transplantation. In this study, we determined the extent to which lipid peroxides contribute to the pathogenesis of hepatic cell damage induced by transient warm ischemia with subsequent reperfusion. In addition, the function and immunohistochemical features of glutathione peroxidase, a potent physiological lipid peroxide scavenger of the liver, was assessed. Reperfusion following 15 or 30 minutes of warm ischemia resulted in a significant elevation in serum and liver lipid peroxidase (LPO) levels. In addition, necrosis of the hepatic periportal area accompanied with remarkable rises in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were observed. In contrast, 30 min of ischemia without reperfusion caused minimal hepatocellular damage. The adverse changes after ischemia/reperfusion were minimized by pretreatment with superoxide dismutase (SOD). These results indicate that increased lipid peroxidation by production of radicals after reperfusion caused the liver cell damage. After ischemia/reperfusion, liver glutathione peroxidase (GSH-PO) activity was significantly decreased and its location altered in the damaged liver. These findings suggest that GSH-PO contributes significantly to the protection against hepatic reperfusion injuries.