Effects of fluoride tablets on caries and fluorosis occurrence among 6- to 9-year olds using fluoridated salt.

OBJECTIVE: The aim of this retrospective cohort study was to investigate the association between the use of fluoride tablets among users of fluoridated salt and the occurrence of caries and fluorosis. MATERIALS AND METHODS: We examined 583 school children aged 6-9 years in Berlin, Germany for caries-status (modified defs > or = 1; d(3)-level) and fluorosis occurrence on central incisors (TSIF > or = 1). Parents completed questionnaires about several sociodemographic and oral health related factors of the previous years. To adjust for confounding, we used log-risk regression and estimated relative risks (RR) and 95% confidence intervals. RESULTS: The mean modified defs was 3.2 (SD = 5.9) and 58% children were caries-free. Twenty-two per cent of the children revealed mild fluorosis (TSIF 1 and 2). Length of fluoride tablet use was inversely associated (adjusted for age and SES) with caries-status: 2-4 years: RR = 0.8, 95%CI: 0.7-1.0, > or =5 years: RR = 0.5, 95%CI 0.3-0.7 (reference: 0-1 year use). This inverse association could mainly be observed in children who consumed fluoridated salt as well. Relative risks for mild fluorosis were 1.8 (95%CI: 1.1-2.9) and 2.7 (95%CI: 1.6-4.5) for fluoride tablet use of 2-4 years and > or =5 years, respectively compared with 0-1 year use. CONCLUSIONS: Fluoride tablets seem to be effective in reducing the occurrence of caries in children with low caries levels in particular among those using fluoridated salt as well. However, fluoride tablets increase the occurrence of mild fluorosis in permanent incisors.

New aspects of cell biology in osteosarcoma.

Among the solid tumors of childhood and adolescence, osteosarcoma (OS) represents the most prominent example of efficient aggressive chemotherapy with secondary surgical therapy. A specific subclassification of the tumor is indispensable and must include recent results of cell biology. The co-distribution of different collagen types I-VI reflects the diverse differentiation of osteosarcoma cells, supporting the concept of a pluripotent mesenchymal cell to be the stem cell of the tumor. In contrast, osteonectin (SPARC) may not be considered as a reliable marker for osteosarcoma. The experience of special proteins being secreted by osteosarcoma cells is rather limited. Detailed molecular biological studies are still lacking. A loss of alleles on chromosome 17, particularly in the defined region 17p 13, can be observed in more than 75% of all OS, suggesting the contribution of a tumor suppressor gene, p53, located in that region. It is a 53 kd nucleophosphoprotein binding the major transforming protein, the large T antigen of Simian Virus 40. Immunohistological results showed positive staining with the antibody Pab 240 in 13 of 18 cases. In one osteoblastic OS, a novel splice mutation resulting in a fusing of exon 5 directly to exon 7 was detected. RB1 gene is also of major importance for the tumorigenesis of OS. The multidrug resistance (mdr) is associated with a membrane-bound channel-forming transport protein, the P-glycoprotein. It is a conserved plasma membrane component of about 170 kd. Both the human isoforms mdr 1 and mdr 3 are localised in the long arm of chromosome 7.(ABSTRACT TRUNCATED AT 250 WORDS)

Current aspects of the pathology of osteosarcoma.

Since the introduction of standardized chemotherapy protocols of osteosarcoma a lot of new aspects in prognosis and curability of these have best developed. Current subclassification which divided osteosarcoma into a conventional type and eleven important recognizable varieties is one of the reason for this success. Cytological grading also serves as a good indicator for the prognosis and is an important criterion for application of adjuvant chemotherapy. Several structure proteins of the extracellular matrix have gained importance in making the diagnosis of an osteosarcoma. Immunohistochemically and biochemically evaluations could show that different collagenous-proteins can be useful for the differential diagnosis of bone tumors. The integration of molecular pathologic methods into the structural morphologic findings will be helpfull in the identification of mutated structure proteins. Oncogenes and tumor suppressor genes are of major importance for the tumorigenesis of osteosarcoma. The prognostic significance of the inactivation of p53 and RBI gene remains to be elucidated. Resistance to chemotherapy is the major mechanism responsible for the failure of osteosarcoma treatment. The main cause for this failure is multidrug resistance, which is often related to a plasma membrane protein, the P-glycoprotein. Immunohistologic investigations of P-glycoprotein are not sufficient to demonstrate the possible association between overexpression of this protein and tumor progression.

Autopsy as clinical quality control: a study of 15,143 autopsy cases.

The results of autopsy records at the Institute of Pathology of Münster University documented between 1961-70, 1978-87 and 1988-92 were compared with the documented clinical diagnoses of these cases. In the decade 1961-70, 23% of clinical diagnoses were found incorrect (with therapeutic relevance). In the decade 1978-87, the error rate was 18% and in 1988-92, 12%. The difference between the three groups was statistically significant (p < 0.01). Specific data were assembled for the main malignant tumor types. With respect to infectious diseases, the agreement between clinical and autopsy diagnosis is even poorer. Lues (syphilis) is now rarely recognized in clinical diagnosis, even if it is fatal. Merely 50% of all patients with active tuberculosis as primary disease and cause of death, had been diagnosed clinically. Endocarditis in all its forms was underdiagnosed clinically in 75% of the cases. In view of the widely ranging discussion about the value of autopsy today, and in view of the fact that in epidemiological studies the correctness of in vivo diagnosis is tacitly presumed, it has to be stated that autopsy is the best quality control for progress in clinical medicine.

[Immunomodulator action of living, nonpathogenic Enterococcus faecalis bacteria from humans]. / Immunmodulatorische Wirkung lebender nicht-pathogener Enterococcus faecalis-Bakterien des Menschen.

Immunomodulating Effect of Living Nonpathogenic Enterococcus faecalis Originated from Humans Symbioflor 1 is a pharmaceutical preparation, consisting of a suspension of living nonpathogenic Enterococcus faecalis (E. faecalis). The effect on the liberation of cytokines of E. faecalis was investigated in in-vitro experiments with human peripheral mononuclear blood cells revealing the following results: 1. E. faecalis stimulates the liberation of interleukin 1 (IL-1 beta) and interleukin-6 (IL-6) in a dose-dependent manner; the E. faecalis induced liberation of IL-1 beta and IL-6 is inhibited by dexamethasone (Dm) but not by cyclosporin A (CsA). 2. E. faecalis stimulates the liberation of gamma-interferon (IFN-gamma) in a dose-dependent manner, which is inhibited by both Dm and CsA. 3. Phytohemagglutinin (PHA)-induced liberation of gamma-IFN and interleukin-2 (IL-2) is inhibited by E. faecalis in a dose-dependent manner. The relevancy to clinical trials of the in vitro results is discussed.

Adenocarcinomas of esophagus and cardia in comparison with gastric carcinoma.

Since the carcinomas of the cardia and the adenocarcinomas of the esophagus show many similarities in their histological and morphological descriptions, a detailed comparative study was attempted on the basis of 66 esophageal carcinomas in adenoid differentiation, 359 carcinomas of the cardia, 1288 gastric carcinomas in infracardial localisation, and 492 squamous carcinomas of the esophagus. The evaluation yielded no significant differences between the adenocarcinomas of the esophagus and the cardia neither in age and sex distribution nor with regard to the classifications of Borrmann, WHO, Ming, and Laurén, but a significant discrimination was possible between esophageal and cardial adenocarcinoma together, on the one hand, and infracardial gastric carcinoma on the other. Furthermore, esophageal adenocarcinomas were localized preferentially in the lower third, unlike squamous carcinomas of the same organ. These results suggest that esophageal adenocarcinoma and carcinoma of the cardia must be considered as one separate entity, probably originating from a common stem cell. They further suggest that the cardia belongs to the esophagus rather than to the stomach.

Cancer morbidity and mortality in USA Mormons and Seventh-day Adventists.

Comparison of cancer morbidity and mortality rates between Mormons and Seventh-day-Adventists and the corresponding rates in the Federal Republic of Germany and the United States, reveals that mortality from malignant neoplasms in general is much lower in Mormons and Seventh-day Adventists than in the Federal Republic of Germany. The difference concerns in particular the tobacco-dependent tumors: compared to the rate of affected males in the Federal Republic of Germany, only some 25% of Mormon males are getting lung cancer. Similar patterns are found in laryngeal carcinoma. Tumors that are related to both alcohol and tobacco, such as carcinomas of tongue, pharynx and esophagus, are also significantly less frequent in Mormons. Malignant neoplasms of the female genital tract show distinct analogies: cervical carcinoma has a morbidity rate of only 26.7% of affected women in Germany. Accordingly, mortality rates of Mormons and Seventh-day Adventists show a significant lower level when compared with cancer data of lung, colon and rectum, and prostate from the best German cancer registry (Saarland). Some tumor rates are higher in Mormons, e.g. malignant melanoma, also all types of malignant lymphoma and myeloma. The life expectancy is generally elevated by 2-4 years in Mormons and Seventh-day Adventists. The association with the particular life style of both religious groups, especially the strict reduction of tobacco consumption, and factors of dietary and other habits is discussed.

Metastasizing eccrine porocarcinoma. Report of two cases with fatal outcome.

The clinical, histopathological and ultrastructural features of a metastasizing eccrine porocarcinoma are described in a 75-year-old woman and a 82-year-old woman. The previously not recognized tumors were identified by its distinct pattern of metastasis. Metastatic spreading was restricted for years to a circumscribed region of the skin. Histology and electron microscopy disclosed pronounced epidermotropism of the PAS-positive tumor cells. The characteristic pattern of dissemination obviously represents a homing phenomenon of the tumor cells derived from the intraepidermal sweat gland duct.

Autopsy diagnosis versus clinical diagnosis, particularly in malignant disease. Comparison of two periods: 1961-70 and 1978-87.

We present a comparison of autopsy records in the Institute of Pathology of Münster University during 1961-70 with those from 1978-87. The study was based on 11,716 autopsy cases in which reliable documentation of clinical diagnosis could be adequately correlated and compared with the respective autopsy diagnoses. In the decade 1961-70, 34% of the clinical diagnoses were correct, 15% were nearly correct and 23%, incorrect (24% had to be supplemented without relevance to therapy or prognosis, 4% side diagnoses). In the decade 1978-87, 50% of the clinical diagnoses were correct, 15% nearly correct and 18% incorrect (17% supplemented). With respect to malignant tumours, in 1961-70 clinical diagnoses were correct in 37% of cases and incorrect for 26%; in 1978-87, 47% were correct and 15% incorrect. This comparison covered all major tumour locations. The difference in incorrect clinical diagnoses between the two periods is statistically significant. With respect to infectious diseases, the concordance between clinical and autopsy diagnoses is even poorer. Lues (syphilis) is now rarely recognized in clinical diagnoses, even though it may be fatal; 50% of tuberculosis patients die from miliary tuberculosis without a correct diagnosis. Endocarditis in all its forms was underdiagnosed clinically in 75% of cases. These data provide substantial arguments in favour of autopsy control of clinical diagnosis, also including histological findings in biopsy specimens.

Flow cytometric DNA analysis of bone tumors.

Flow cytometric DNA analysis was performed in a total of 203 bone tumors, benign and malignant. In more than 80% of cases the material studied was paraffin-embedded tumor tissue, mainly from the archives of the Bone Tumor Registry of Westphalia in Münster. Compared with ethanol-fixed fresh tumor samples, the variation coefficient in DNA histograms of the stored material was increased by a factor of 1.2-1.5, which means that resolution was decreased and that, in many cases, accurate cell cycle analysis was not feasible. However, the results of cell cycle analysis in bone tumors, even if performed on optimally fixed specimens, have to be evaluated with caution and full reference to the corresponding histological slides, since these histograms are apt to show various superpositions from the inflammatory infiltrate. The assessment of DNA ploidy is unimpaired if, in agreement with most researchers today, deviations smaller than +/- 10% from the diploid standard are still defined as DNA diploid, peridiploid, or pseudodiploid. The coefficient of variation should be kept as low as possible. If it is between 10% and 15%, the near-diploid stemlines with DNA indices of 0.9 or 1.1 may be hard to delineate. On account of the particularly marked regressive changes, the resolution of DNA histograms was most strongly impaired in chondromatous tumors, whereas it was mostly excellent in highly cellular viable tumor tissue, such as that from Ewing's sarcoma or osteoblastoma. On the whole, there was a distinct correlation between DNA ploidy and the biological behavior of bone tumors (Table 8). The highest rates of DNA aneuploidy were found in highly malignant OSs (18/21) and FSs (14/16), thus reflecting their poor prognosis. Of six juxtacortical OSs, three well-differentiated parosteal OSs and two periosteal OSs were DNA diploid, whereas one highly malignant surface OS and five highly malignant extraskeletal OSs, all DNA aneuploid, corresponded fully to the medullary OSs. Judging by preliminary results, adjuvant preoperative chemotherapy (COSS 80/82: Bösing et al. 1987) may reduce the rate of DNA aneuploidy and, consequently, of stem cell heterogeneity in general. A selective destruction of those stemlines that respond particularly to chemotherapy appears probable. In contrast to their high malignancy, Ewing's sarcomas showed an unexpectedly low proportion of DNA aneuploid stemlines (14/24). The comparatively favorable prognosis of MFH of bone is reflected in a lower rate of aneuploidies (2/10), which is also rather low (probably too low) when compared to our own data from soft tissue MFH (9/19).(ABSTRACT TRUNCATED AT 400 WORDS)