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.

Incorporation of alpha-1-antichymotrypsin into carcinoma cell nuclei of human stomach adenocarcinoma transplanted into nude mice.

Human stomach adenocarcinomas containing alpha-1-antichymotrypsin (ACT) in their cell nuclei were transplanted into nude mice. The presence of ACT was monitored using an immunohistochemical technique with horseradish peroxidase-labeled rabbit anti-ACT Fab' as well as single radial immunodiffusion. Two weeks after transplantation, ACT could be found neither in transplanted carcinoma cells nor in the sera of carcinoma-bearing nude mice. However, if human ACT was injected i.v., it could be detected in the transplanted carcinoma cell nuclei 2 h after injection. The ACT was detected immunohistochemically and was confirmed by biochemical fractionation using 125I-labeled ACT. On the other hand, the amount of ACT production was not sufficient to indicate biosynthesis. These results demonstrated that ACT detected in stomach carcinoma cell nuclei was not synthesized in carcinoma cells but was incorporated from the blood circulation.

Mosaicism in the expression of tumor-associated carbohydrate antigens in human colonic and gastric cancers.

Serial sequential sections from a single tumor were examined by immunohistological staining with several monoclonal antibodies directed, respectively, to different tumor-associated carbohydrate epitopes. Staining patterns were compared with those of conventional staining with hematoxylin-eosin or periodate/Schiff's reagent. Each tumor showed different areas of staining with different antibodies, and the combined staining map shows a clear mosaicism of antigen expression within the same tumor. For example, some areas of a given tumor were stained by FH4 (defining dimeric Le(x)), while other complementary areas were strongly stained, in a mutually exclusive manner, by SH1 (defining Le(x)), AH6 (defining Le(y)), FH6 (defining sialosyl dimeric (Le(x)), or TKH2 (defining sialosyl-Tn). Some areas were stained by two or three of these antibodies. Comparisons of the mosaic-staining patterns with cytohistological properties of tumor cells within specific areas suggested that the pattern of antigen expression is correlated with degree of differentiation; e.g., poorly-differentiated cells with severe dysplasia did not express high levels of Le(x) or Le(y) but did express sialyl-Le(x) or dimeric Le(x); on the other hand, moderately or well-differentiated tumor cells in some areas expressed high levels of Le(x) or Le(y) but lower levels of sialyl-Le(x). Areas showing strong expression of sialyl-Tn in their secretions were consistently correlated with presence of well-differentiated tumor cells, whereas secretions from normal mucosae were consistently characterized by lack of sialyl-Tn expression. It is postulated that the original in situ tumors (which had homogeneous glycosylation patterns) evolved into several spatially discrete cell populations displaying different degrees of glycosylation, reflecting stages of tumor cell differentiation and progression.

HLA antigens are candidate markers for prediction of lymph node metastasis in gastric cancer.

We investigated the association between human leucocyte antigen (HLA) antigens and lymph node metastasis in 724 gastric cancer patients. Among patients who had poorly differentiated adenocarcinoma with or without HLA-DR4 antigen, lymph node metastasis was detected in 80.8 and 54.9%, respectively (relative risk (RR) = 3.5, P = 0.0005, corrected P = 0.0285). It was more common in patients with a family history of cancer death (RR = 7.7). Among signet ring cell carcinoma patients with or without HLA-B52 antigen, lymph node metastasis was detected in 57.7 and 19.7%, respectively (RR = 5.6, P = 0.0001, corrected P = 0.0086). It was more common in patients who were smokers (RR= 8.3). Our findings suggest that HLA-DR4 and HLA-B52 antigens are associated with lymph node metastasis in gastric cancer.

Polypoid carcinoma of the esophagus. A unifying term for "carcinosarcoma" and "pseudosarcoma".

Polypoid carcinomas with spindle-cell sarcomatous features have been designated either as carcinosarcoma or pseudosarcoma. The distinction between these two tumors has depended on the presence of "intermingling" of the carcinomatous and sarcomatous components in so-called carcinosarcoma. But unlike the carcinosarcoma, the sarcomatous component in pseudosarcoma has been considered benign. A polypoid tumor of the esophagus in a 57-year-old male was predominantly composed of spindle cell, sarcomatous cells. The presence of adjacent intraepithelial epidermoid carcinoma with transitional and ultrastructural features confirmed the epithelial origin of this tumor. Because of the absence of "intermingling," the primary tumor was considered to be a pseudosarcoma. However, our postmortem examination showed metastases composed of both carcinomatous and sarcomatous features. A review of the literature on carcinosarcomas and pseudosarcomas shows that only one case of pseudosarcoma reported by Hughes and Cruickshank showed a similar situation and indicates that the sarcomatous component in pseudosarcomas has the same metastatic potentiality as has been reported in carcinosarcomas. We conclude from these studies a basic similarity of the carcinosarcoma and pseudosarcoma. The term polypoid carcinoma is proposed for both these lesions.

Natural cytotoxic T cells responsible for anti-CD3-induced cytotoxicity in mice.

T cells obtained from normal mouse spleen cells showed significant cytotoxic activity against Fc receptor positive tumor cells in the presence of anti-CD3 monoclonal antibody (mAb). This activity was designated as natural cytotoxic T cell (NCT) activity and compared with natural killer (NK) activity. Considerable levels of NCT activity were detected in mouse strains with both high and low NK activity. NCT cells were distributed in both lower and higher density fractions of Percoll discontinuous density gradients, while NK cells were enriched in the lower density fraction of Percoll gradients. Moreover, NCT activity was resistant to in vivo anti-asialo GM1 treatment, in contrast to NK cells. These results indicate that NCT cells, which have different characteristics from NK cells, are present in normal, nonimmunized mouse spleen cells. Unexpectedly, CD4+ T cells sorted from normal mouse spleen T cells revealed significant NCT activity, as did CD8+ T cells. It was also demonstrated that NCT cells require the LFA-1 molecule to lyse tumor cells in the presence of anti-CD3 mAb.

Quantification of serum-soluble HLA class I antigens in patients with gastric cancer.

The amount of sHLA-I in serum was examined in 74 patients with gastric cancer and 15 normal healthy controls. For mAbs, W6/32 specific for HLA-A, -B, -C, and biotin IOT2 specific for HLA class I associated with beta 2 microglobulin, were used to determine the values of sHLA-I using an ELISA. The patients in stage-IV gastric cancer showed lower values of sHLA-I (445.4 +/- 247.1 ng/ml) than those in stage I (725.9 +/- 575.8 ng/ml), stage II (752.8 +/- 255.0 ng/ml), and normal controls (868.9 +/- 715.0 ng/ml) (P < 0.05). In analysis of the patients with HLA-A24, the allele that has been reported to secrete more sHLA-I than other alleles, the results were nearly the same. These results suggest that the secretion of sHLA-I is low in patients with very advanced cancer. However, there was no correlation between the sHLA-I level and the metastasis or prognosis in longitudinal studies in 11 patients.

Tracheoesophageal anastomosis for intractable aspiration pneumonia.

Permanent tracheostomy and tracheoesophageal anastomosis were performed as a means of surgical intervention for the treatment of intractable aspiration pneumonia. Conventional methods of tracheoesophageal anastomosis have entailed various problems. The improved method devised by us uses the special histological features and enables safe and reliable anastomosis. By this method, the tracheal perichondrium is retained and the strength of the anastomosed portion of the trachea is maintained, the failure of sutures due to tension on the anastomotic site being prevented. Also, reanastomosis can be performed after the cure of primary disease.

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.

High-dose chemotherapy with autologous hematopoietic stem-cell transplantation in breast cancer.

Since 1981 we have conducted four studies of the treatment of metastatic and postoperative high-risk breast cancer with high-dose chemotherapy supported by autologous hematopoietic stem-cell transplantation (AHSCT). Study I, involving 56 metastatic cancer patients, proved that induction chemotherapy produces a lasting complete response (CR) in only a few cases despite the achievement of a CR rate higher than that expected from standard chemotherapy. Study II was designed to examine consolidation chemotherapy in metastatic cancer patients responding to induction chemotherapy. At a median follow-up of 26 months (range 2-66), consolidation therapy produced a 5-year progression-free survival rate of 27.1% in 30 patients showing a CR or a partial response to induction therapy and 58.6% in 13 patients showing a CR to consolidation therapy. No treatment-related death occurred during study II. The same regimen used in study I was employed for 58 postoperative high-risk patients in study III. The 10-year disease-free survival rate recorded for patients with > or = 10 positive axillary lymph nodes was significantly higher (P < 0.05) in the AHSCT-supported chemotherapy group than in the conventional chemotherapy group. A double high-dose regimen was adopted for 21 postoperative high-risk patients in study IV. The 3-year disease-free survival rate recorded for 9 patients with > or = 10 positive axillary lymph nodes was 71.4% at a median follow-up of 25 (range 8-45) months. No treatment-related death occurred during study IV. Peripheral blood stem-cell transplantation shortened the duration of bone marrow suppression more effectively than did bone marrow transplantation, thereby optimizing high-dose chemotherapy.

Effects of oral lentinan on T-cell subsets in peripheral venous blood.

The effect of oral lentinan, a biological response modifier, on the control of systemic immune function was studied in six-week-old male Wistar-Imamichi specific-pathogen free rats. In the lentinan-treated group, 1 mg of lentinan dissolved in 1 ml of physiological saline was administered forcibly into the stomach twice weekly for four or eight weeks. Physiological saline alone was administered in a similar fashion to the control group. Leukocyte and lymphocyte counts were made and lymphocyte subsets measured using monoclonal antibodies W3/13, W3/25, and OX8, and a laser flow cytometry system. The T-cell level, the helper/inducer T-cell level, and the suppressor/cytotoxic T-cell level were measured. The peripheral leukocyte and lymphocyte counts did not change significantly in either group during treatment. After four weeks of treatment, however, the lentinan group had a significantly higher T-cell level, helper-cell level, and helper-suppressor ratio, and a significantly lower suppressor-cell level than did the control group. No significant between-group differences in the lymphocyte subsets or the helper-suppressor ratio were noted after eight weeks of treatment. Oral administration of lentinan appears to modulate the systemic immune function through stimulation of T cells, especially helper cells. Continued administration produced less effect, possibly due to a tolerance to the effect of lentinan.

Postoperative intravenous administration of lysine acetylsalicylate: effect on pain relief and platelet function.

The effects of lysine acetylsalicylate, a new injectable salicylate, on postoperative pain relief and platelet function were studied in ten men who had surgery for peptic ulcer. Four of five patients receiving lysine acetylsalicylate had satisfactory pain relief. One patient required an additional injection of 15 mg of pentazocine. Of the five patients in the control group, an average (+/- SD) dose of 90 +/- 23.7 mg of pentazocine was required to achieve adequate postoperative pain relief. Lysine acetylsalicylate decreased platelet aggregability but without resulting in hemorrhage. We concluded that this new salicylate administered intravenously to patients in the postoperative period provided adequate analgesia while allowing effective hemostasis despite its inhibitory effect on platelet aggregation.

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.

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.

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.

Successful nutrition management of megacystis-microcolon-intestinal hypoperistalsis syndrome--a case report.

Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS), a visceral myopathy causing intestinal obstruction in the newborn, is a generally fatal condition, with death being secondary either to sepsis or to malnutrition if long-term intravenous feeding is not provided. A patient with MMIHS is described who has been raised by total parenteral nutrition (TPN) for seven years since her birth. Severe hepatic dysfunction was encountered in early infancy, which gradually cleared after the initiation of milk feeding by mouth, although the milk could not be absorbed because of the high-output jejunostomy. The patient also experienced a bone disease similar to scurvy but caused by copper deficiency at the age of 9 months. The central venous catheter now in situ is the 25th one for the patient. When these catheters were evaluated, the Broviac proved more efficacious than the traditional Silastic for use in long-term TPN. The patient does not yet have normal bowel function and still requires TPN.

Use of total parenteral nutrition in pediatric bone marrow transplantation.

To evaluate the extent of the nutritional stress of pediatric bone marrow transplantation (BMT) and to evaluate the use of total parenteral nutrition (TPN), 35 consecutive pediatric patients who received BMT were studied retrospectively. Voluntary cessation of oral nutrition in almost all patients was observed, and significant decreases of serum albumin levels were seen after BMT. In 85% of these patients, TPN was necessary in response to severe wasting and fasting. No deaths were related to indwelling central venous catheters during the period of 2968 catheter-use days in these severely myelosuppressed patients. The mean of the total daily energy intake was 104% of basal energy expenditure (BEE), and 70% of patients lost their weight. Predicted energy requirement to maintain body weight after BMT would be 128% of BEE from a simple linear regression step in this study. Significant correlations were found between the marrow recovery time and the initial nutritional state, expressed as the percentage of ideal weight height ratio, as well as benign nature of the disease. The use of TPN did not show any beneficial effects on the time course of marrow recovery, although it showed favorable effects on the maintenance of body weight.

Clinical and biochemical aspects of thiamine treatment for metabolic acidosis during total parenteral nutrition.

We encountered six cases of total parenteral nutrition (TPN)-associated lactic acidosis during the 6-y period of 1988-1993. The patients were characterized by severe disease of the digestive organs, minimal food intake before surgery, and postoperative TPN with no food intake and with no vitamin supplements. Within 4 wk of TPN, they developed hypotension (< or = 80/60 mmHg), Kussmaul's respiration, and clouding of consciousness, as well as abdominal pain not directly related to the underlying disease. Routine laboratory examinations revealed no acute aggravation in hepatic, renal, or pancreatic functions. Arterial blood gas analysis showed pH < or = 7.134 and base excess < or = -17.5 mmol/L. Additional laboratory examinations revealed serum lactate > or = 10.9 mmol/L, serum pyruvate > or = 159 mumol/L, and lactate/pyruvate ratio > or = 0.029. None of the patients responded to sodium bicarbonate or other conventional emergency treatments for shock and lactic acidosis. After the first case, we suspected that thiamine deficiency might be responsible for this pathologic condition, Serum thiamine was proved to be < or = 196 nmol/L in 5 patients. Thiamine replenishment at intravenous doses of 100 mg every 12 h resolved lactic acidosis and improved the clinical condition in 3 patients. This article includes a review of 11 relevant reports published from 1982-1992 and a discussion of the biochemical mechanism of onset of thiamine deficiency-associated lactic acidosis. We emphasize the needs (1) to supplement TPN with thiamine-containing vitamins for the patients whose food intake does not meet nutritional requirements; (2) to monitor the patients routinely measuring serum thiamine concentration and erythrocyte transketolase activity during TPN; and (3) to intravenously replenish using high-dose thiamine simultaneously with the manifestation of signs and symptoms of lactic acidosis.

Copper deficiency in an infant on prolonged total parenteral nutrition.

An infant with the megacystis microcolon intestinal hypoperistalsis syndrome, required total parenteral nutrition due to ineffective gastrointestinal function, and developed copper deficiency after a prolonged course in total parenteral nutrition in conjunction with a chronic draining jejunostomy. She responded promptly to copper supplementation.