[Dental and oral symptoms of diabetes mellitus].
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Biomedical subjects
Publications and source records attributed to M Albrecht.
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Cell lines established from advanced mammary and ovarian carcinomas were assayed for the inhibition of in vitro proliferation by various antineoplastic drugs. The assays were performed with multiple experimental cultures derived from stock cultures of the tumor cell lines in early passages of the cultivation. As determined by comparison of the 50% inhibition of in vitro growth, differential sensitivity of the individual cell lines was observed. Based on the 2-h plasma level of the drugs as discriminatory threshold between resistance and sensitivity, the in vitro effectiveness of each drug on the individual cell lines was compared with the clinical results of chemotherapy applied to the corresponding patients. In total, positive in vitro/in vivo correlations were observed in 39 of 42 cases. The 17 cell lines evaluated retrospectively were resistant to those drugs which had been tried unsuccessfully during chemotherapy. Among the 25 cases tried prospectively 11 cases showed sensitivity in vitro and in vivo, and furthermore 11 prospective cases were resistant in vitro and in vivo.
Procedures for the in vitro determination of the drug-induced inhibition of mammary and ovarian carcinoma cell growth were established. In monolayer cultures derived from advanced tumors, separation of epithelial carcinoma cells from concomitant cells of fibroblast-like or mesothelial appearance was achieved by differential trypsinization. The carcinoma cell character of the stock cultures was verified by chromosome analyses showing a high degree of aneuploidy for the epitheloid cell lines and euploidy for cells of apparently mesenchymal origin. When cultured carcinoma cells were injected in nu/nu mice, the tissue and cell cultures obtained from the heterotransplantation tumors closely resembled the original tumors and cell cultures in morphology, karyotype, and expression of tumor markers. The action of carcinostatic drugs in the logarithmic phase of the carcinoma cell proliferation was tested by kinetics experiments in multiple experimental cultures. In cell proliferation assays based on cell counts the 50% inhibition dose (ID50) of the drug effects was determined from the dose-response curves. Comparison of the ID50s revealed highly differential effectiveness of the drugs examined. The inhibitory effects were reproducible, rendering the procedures used suitable for testing the chemosensitivity of newly explanted gynecological carcinoma cells by proliferation assays.
25 patients with stage III and IV ovarian carcinoma were treated with radical surgery and postoperative chemotherapy. Analysis of the disease-free intervals and the survival rates indicated significant differences related to the stage of the disease. Furthermore patients with minimal residual disease (tumor mass less than 2 cm in diameter) had a far better prognosis than patients with extensive residual disease (greater than 3 cm). No correlation could be demonstrated between histological grading, in vitro proliferation rates, hormone receptor status, type of postoperative chemotherapy and survival rates.
In 58 out of 515 patients with a primary carcinoma of the breast there was local-regional recurrence. Treatment consisted in generous excision and local radiation (50-60 Gy). After a mean observation period of 65.4 +/- 22.2 months, distant metastasization was found to have occurred in 22 patients (37.9%). Of the other 36 patients 23 (39.7%) had suffered no further recurrence at the end of this time, while 13 patients (22.4%) had a new local-regional recurrence. In a retrospective study a variety of parameters of prognosis were investigated in order to determine to their predictive value. It was found that there were significant differences in overall survival rates with tumors of histological differentiation stage I as compared to tumors of differentiation stages II and III (p = 0.003). There were no differences in the recurrence-free interval (p = 0.34). The presence or respectively lack of steroid receptors in the primary tumor made no significant differences to the recurrence-free interval and the survival rates. Those of the patients on whom this study was based whose axillary nodal status was N+ had received (adjuvant) treatment with cytostatics. This resulted in no differences in the recurrence-free interval (p = 0.28) or the overall survival rates (p = 0.3) when the N+ and N- patients were compared. The therapeutic conclusion drawn from these results is that breast carcinoma patients with an exclusively local-regional recurrence should initially receive local treatment only; systemic therapy should be reserved for the generalization stage.
The aim of the study was 1) to compare the caries prevalence of preschoolchildren in Baja with data from 1975 and 2) to evaluate the effect of 0.2% sodium-fluoride mouthrinsings practiced during the last 4 yr. In 20 kindergartens of Baja 1462 children between 3 and 6 yr of age were investigated. All the children were participants in an oral hygiene motivation program and fluoride rinsings, performed generally monthly, but at least 10 times in a year. The dental investigations of the primary teeth were carried out by the same team as in 1975. The frequency of caries-free children increased from 18.8% in 1975 to 24.8% in 1982. The dmft mean values decreased only in the 5- and 6-yr-old children.
A recombinant plasmid harboring both genomic termini of tupaia herpesvirus (THV) DNA was characterized by restriction enzyme analysis and by determination of the nucleotide sequence. A unique NotI cleavage site was found that is located approximately 19 base pairs upstream of the THV terminal junction. THV DNA fragments from virion DNA were analyzed by using the same restriction enzymes as for the recombinant plasmid. The comparative fine mapping of virion THV DNA revealed heterogeneous molecules of variable lengths with the NotI cleavage site conserved. A number of short direct and inverted repeats and palindromes were found surrounding the THV terminal joint. The THV repetitive sequences were compared with the repeats reported for the DNA termini of herpes simplex virus, varicella-zoster virus, and Epstein-Barr virus and are discussed in respect to signals for a site-specific endonuclease required for packaging.
Buprenorphin, 0,3 mg i.v., was used in 20 patients in the age of 51 to 75 years for analgesia after surgery for aortic aneurysm. Haemodynamic parameters of peripheral and pulmonary circulation, cardiac output, as well as blood gases were determined during routine postoperative controlled ventilation. The main results were an initial vasodilation and a decrease in heart rate, both of which reduce myocardial oxygen consumption. This effect is beneficial in the presence of sufficient volume substitution and optimal oxygenation in high-risk patients.
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During early cultivation steps of the newly derived and karyotyped human mammary carcinoma line EFM-19, the cells developed faster growth rates and became increasingly less responsive to the presence of serum in the culture medium. No drastic alterations of the morphology and of the karyotype were observed, and carcinoembryogenic antigen remained expressed during the course of the cultivation. In experimental incubations at various time intervals after the explantation, the cell proliferation was analyzed for dose-dependent effects of estradiol, cortisol, progesterone, and testosterone. After 16 wk of cultivation of the stock culture in the presence of estradiol, the cells had acquired a distinct sensitivity to estradiol resulting in permanent growth enhancement. The withdrawal of cortisol from the medium of the stock culture subsequently provoked the loss of the initially noted stimulation of the proliferation by cortisol. The stimulatory effect of progesterone on the proliferation was reversed to inhibition when the stock culture was deprived of cortisol in the growth medium. The results indicate that the choice of steroid hormones in the stock culture medium was determining the quality of the cellular growth responses.
Enhanced NADPH-dependent LPO in rat liver postmitochondrial supernatants in vitro due to depletion of GSH by treatment with phorone (diisopropylidene acetone) in vivo was inhibited by Fe2+-chelating agents (desferrioxamine, DETAPAC), but not by scavengers of .O2-, H2O2, singlet oxygen or .OH-radicals, indicating that a perferryl ion (Fe2+ . O2) is needed as an initiating factor. In vivo, rats treated with phorone (250 mg/kg i.p.) exhaled 1.4 times as much ethane within 4 h as compared to controls. Pretreatment with FeSO4 resulted in a 6.9-fold enhancement of LPO as compared to Fe2+-pretreated controls. Our results indicate that GSH-depletion results in a strong enhancement of NADPH-dependent LPO also in vivo, provided that an initiating factor is present.
In a combined study of the Free University, Amsterdam and the Semmelweis Medical University, Budapest, the presence of epithelial dysplasia was studied in 100 cases of oral lichen planus. The criteria of epithelial dysplasia which were used in this study correspond with those reported by the WHO Collaborating Centre for Oral Precancerous Lesions in 1978. In approximately 25% of all cases, moderate or at least mild dysplasia was observed. The number of dysplastic changes per section did not show any significant correlation with the clinical type, nor with age or sex. There were no marked differences between the Amsterdam and Budapest material. Long-term data on the follow-up were not available yet. No comment can therefore be given about the meaning of the finding of epithelial dysplasia in lichen planus being a sign of premalignancy or not.
In 515 patients with primary carcinoma of the breast T1a-3aN1a-bM0, the authors conducted simple mastectomy with radical lymphonodectomy of the axilla from 1976 onwards to the time of reporting. In 190 patients with affected lymph nodes, assisting chemotherapy was effected with a combination of three drugs, namely, trofosfamide, methotrexate and 5-fluoro-uracil for a period of 12 months postoperatively. Patients whose lymph nodes remained free were not subjected to follow-up treatment. For both groups of patients, the rates of relapses and survival times were established for an average follow-up time of 41 months (15-75). No significant differences in the rates of relapses and localisation were seen on comparing both groups (P = 0.27). In the patients with affected lymph nodes, local relapses were somewhat more frequent than with patients whose lymph nodes were not affected (11.1% vs. 9.8%); the same also applied to the occurrence of metastases distant from the primary tumour (12.1% vs. 7.4%). Significant differences in survival rates in patients with affected lymph nodes were seen only in the tumour stages T1/T2 (P = 0.001) and for the stages T2/T3 (P = 0.009). The menopausal status of the patients did not show any significant differences in respect of probability of survival for both groups (N-:P = 0.75; N+:P = 0.79).
Individually different growth responses of 10 cell lines newly derived from metastasizing mammary carcinomas were determined by cell counts in experimental incubations with the steroid hormones 17 beta-estradiol, progesterone, testosterone, hydrocortisone (cortisol), the antiestrogenic compound tamoxifen, or prolactin. Of 7 cell lines derived from ductal carcinomas, 5 were stimulated by prolactin. The growth of 4 of 7 cell lines established from the tumors of postmenopausal or ovariectomized patients was enhanced by doses of testosterone, which are in the range of the physiologic serum level. The proliferation of 5 cell lines was promoted by hydrocortisone in the physiologic concentration of 100 nM, supporting the notion that concentrations of testosterone or hydrocortisone normally present in body fluids may facilitate the in vivo growth of breast cancer. The in vitro growth of cells derived from tumors after relapse under treatment with medroxyprogesterone acetate or tamoxifen was markedly enhanced by progesterone or tamoxifen (CAS: 10540-29-1) in concentrations corresponding to therapeutical serum levels and in accordance with in vivo resistance to the endocrine therapy applied before cell sampling. The results of this suggest the occurrence of positive endocrine selection mechanisms operating in vivo on human mammary tumor cell populations.
The keratinization process has been investigated by ultrastructural methods in different clinical types of oral leukoplakia in 12 biopsy specimens from the buccal mucosa. Simple and verrucous clinical types of oral leukoplakia showed the presence of well-defined keratohyaline granules and the formation of tonofibrils. Erosive leukoplakias showed a lack of keratohyaline granules and a decreased aggregation of tonofilaments; in the upper cell layers dark and clear cells were found. The formation of a granular layer occurred in connection with orthokeratosis, mainly in simple and verrucous leukoplakias; erosive leukoplakias showed no corneal layer.
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Incubation of premitochondrial liver homogenate supernatants of phenobarbital-induced rats with sodium vanadate led to a time- and concentration-dependent formation of malondialdehyde and a parallel release of beta-glucuronidase from lysosomes. Both were inhibited in the presence of glutathione, (+)-catechin or dithiocarb, and took place after a lag phase of 30 min. In contrast, the glutathione content dropped immediately after addition of vanadate. Scavengers of reactive oxygen species had no effect on vanadate-induced lipid peroxidation. In liver homogenates of non-induced rats vanadate-promoted lipid peroxidation was 7.3 times lower than in those of phenobarbital-induced animals, suggesting the involvement of the microsomal mixed-function oxidase system. Thus, vanadate seems to act as a pro-oxidant of the enzymatically-promoted lipid peroxidation.