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250 patients in long-term treatment (about 12, 4 years) were examined concerning their oral symptoms (DMF/T, CPITN, GPM, Plaque-index, Sulcus-bleeding-index of Mühlemann and Son), number of teeth, number of extracted teeth and teeth with endodontic treatment during the treatment period. These patients were compared with 250 patients, who were not under regularly treatment. There are clear differences between both groups. It can be concluded that long-term treatment with exact fillung therapy, endodontic and periodontic treatment is able to maintain teeth until a high age of life.

Preventive measures, continuously realized in children of dentists cause significantly lower values of Plaque index, Sulcus-bleeding-index, CPITN and caries in all groups of age in comparison to other groups.

The slight therapeutic breadth involved means that manic depressive lithium prophylaxis may call for life-long routine management. The lithium/serum-level checks required hitherto are here compared with a non-invasive method, that of determining the lithium level from a mixture of the patient's saliva, a method involving no danger that will eventually assume considerable importance.

Caffeine is mainly metabolized by 3-methyl-cholanthrene-inducible cytochrome P-450, whereas metamizol (Analgin) is probably mainly metabolized by phenobarbital inducible cytochromes P-450. Therefore the elimination of caffeine from serum and the amount of the main metabolites of metamizol excreted into urine reflect the activity of these two cytochrome P-450 families. Sex hormones can influence the activity of cytochrome P-450. Dienogest is a new gestagen, used for temporary contraception. We investigated the effect of this new sexual hormone alone and in combination with ethynylestradiol on the elimination of both testdrugs. In 10 healthy volunteers dienogest 2 mg daily for 14 days have no effect on the metabolism of model drugs whereas the combination with 0.05 mg ethynylestradiol has an influence on the elimination of caffeine and metamizol.

A radioimmunoassay for ethinylestradiol (EE2) which was developed in the pharmacological department of VEB Jenapharm has been modified and fully validated. It was the purpose of the present study to extend the still limited data concerning EE2-serum levels after a single and repeated ingestion of combination pills with different doses of EE2. 10 volunteers aged 17-25 years with normal body weight and length received a single tablet of either Gravistat (0.05 mg ethinylestradiol + 0.125 mg levonorgestrel) or Minisiston (0.03 mg ethinylestradiol + 0.125 mg levonorgestrel). 11 other women were involved into the study after ingestion of the 21st tablet of a contraceptive cycle. Peak serum levels which were significantly higher in the Gravistat- than in the Minisiston-group were observed 90 to 120 minutes after the oral administration. Detectable EE2 levels were determined in all volunteers after 24 hours. Pharmacokinetic data showed pronounced interindividual variations. Whereas the mean 24 hours levels of EE2 increased progressively during the treatment cycles, kinetic values obtained at the end of the cycle exhibited a significantly higher level than those after ingestion of a single dose. Area under curve (AUC) was calculated by the trapezoidal rule with the aid of a compartment free model.

The effects of two sequential oral contraceptive preparations, Sequostat (6 days ethinylestradiol 0.05 mg, 15 days ethinylestradiol 0.05 mg + norethisterone acetate 1.0 mg) and Sequence-Ovosiston (9 days mestranol 0.1 mg, 12 days mestranol 0.08 mg + chlormadinone acetate 2.0 mg) on triglycerides, total cholesterol, HDL- and LDL-Cholesterol, glucose tolerance, total plasma proteins, plasma protein fractions, plasma transaminases, gamma-glutamyl-transferase, alkaline phosphatase and antithrombin III were studied in two groups of 46 and 29 young women respectively. Investigations were performed prior to the hormonal intake and after treatment for 3, 6 and 12 months. In nearly all parameters studied significant but minimal changes could be demonstrated which in most cases showed a minor degree in the Sequostat-group, while Sequence-Ovosiston exerted a less effect on glucose tolerance. A significant increase of HDL-cholesterol and a reduction of LDL/HDL-cholesterol relation could be demonstrated at least in the first six months, resulting from the estrogen dominance of the contraceptives.

The influence of drug stimulated biotransformation on the biological effectiveness of two different contraceptives (Deposition and Gravistat) was observed.--Phenobarbital, a potent enzyme inducer, is known to increase the metabolism of steroid hormones, including estrogens and progrestogens. -- The clinical symptoms of drug mediated enzyme induction of hormonal steroid contraceptives are dysfunctional bleedings. This phenomenon is discussed.

The behaviour of butanol-extractable iodine in serum was tested, during and on completion of administration of Non-Ovlon, Ovosiston, Gravistat, and Deposiston, the latter being a longacting contraceptive. Action of synthetic sexual steroids led to an increase in butanol-extractable iodine. However, this change proved to be easily reversible, soon after the end of medication, even after long-time application. Yet, complete normalisation should not be expected to occur before the second cycle without contraceptives, which applies, in particular, to women who had been on long-acting contraceptives.

Intravenous administration of gonadotropin-releasing hormone (GnRH) induces not only a rapid release of pituitary LH and FSH stored, but also stimulates biosynthesis of these hormones by a long acting process. Repeated injection of GnRH after an interval of 90 to 120 minutes evokes an increased response compared with the first period of stimulation. This pattern of reaction is principally maintained on therapy with steroidal contraceptives. The twofold stimulation provides additional information on hypothalamic-pituitary reactivity exceeding the results yielded by the simple GnRH stimulation test. On the contrary examination of prolactin response to twofold TRH-administration gives no increased diagnostic aid.

Female sex hormones have an influence not only on the reproductive process, but on nearly all organs and functional systems. This explains their broad spectre of side-effects, which by their degree of subjective annoyance may impair the acceptability of hormonal contraception or--through a suggested risk to the patient--even enforce discontinuation of medication. The significance of quite a number of alterations in biochemical and metabolic parameters cannot yet be fully elucidated. The author offers a summary of the principal side-effects of present-day hormonal contraceptives.

The possible connection between long continued oestrogen intake and dilatation of the upper urinary tract was examined urographically in nine female rabbits. The degree of dilatation was judged on eleven parameters. The results of the study indicate that oestrogens without simultaneous mechanical influence on the urinary tract does not lead to dilatation of the pelvis or ureter. The results are illustrated graphically and are compared with the findings in the literature.

Submandibular saliva from 111 persons was collected and the secretion rate was determined before and after stimulation with Ascorvit. Analyses from Na, K, Ca, Mg and Zn were carried out by atomic absorptions spectroscopy respectively by flame emission analysis.

Use of the antiandrogen cyproterone acetate in the treatment of hirsutism.--25 women with hirsutism or hypertrichosis faciei were subject to a "reverse sequential therapy" with cyproterone acetate (Hammerstein's regimen) for 1 to 3 years. In 8 patients, a limited, in 14 patients a satisfactory and in one woman a good result could be recorded. Cycle irregularities and subjective side effects were within a tolerable range. Studies of the hair pattern in 15 patients revealed a higher telogen rate as well as increased diameters of the hair stalks, compared with controls, in the temporal region of the head. These alterations disappeared in the course of the treatment. In the parietal region of the head no significant differences of the hair pattern were found in comparison with the controls and during application of the steroids.

Sera of 21 clinically intact women, who had been on Non-ovlon, Gravistat or Deposiston, were tested for their haptoglobin levels, during two control cycles and in the first three cycles on contraceptives. Serum-haptoglobin concentrations were reduced. A primary role is played, in that context, by oestrogens.

The term, 'proliferation dosage' of an estrogen is defined differently in the gynecologic literature. In this article the authors were concerned critically with the methods of its determination. They came to the conclusion that under standardized conditions sufficiently sure and reproducible results can be received in postmenopausal women. 7 short acting and 3 long acting estrogens, some of which are clinically unknown substances, were examined using the following definition of proliferation dosage: 'Proliferation dosage is the amount of an estrogen which induces the signs of the late proliferation phase after being administered daily in the course of 10 to 14 days to postmenopausal women with atrophic endometrium.' In order to investigate the proliferating properties of 3 depot estrogens a modified test procedure was performed, derived from animal experiments' results and the planned clinical mode of application.

The renal function of a total of 137 women without renal diseases taking contraceptive steroids continuously but for different periods of time (up to a maximum of 8 years) was investigated by isotope nephrography. Checking is done by using the semiquantitative evaluation prameters according to Zum Winkel. The results show that the application of hormonal contraceptives does not induce significant changes of renal function in the isotope nephrogram.

Karyopycnotic and keratinisation indices were determined in buccal smears which had been taken from newborns. An assessment was made of 239 smears which had been obtained from newborns in their first eight weeks of age, with the probands being subdivided into two groups, depending on breast feeding and feeding on powdered milk (Ki-Na).--Both indices were extremely high on the first day after birth, but they declined up to the eighth or 14th days of age which was attributed to postnatal reduction of high foetal oestrogen levels. Both indices then went up, with some difference being recordable between the two groups, depending on the modes of feeding. The keratinisation index of the breast-feeding group was much higher than that of the Ki-Na group, on account of very high oestrogen levels in breast milk, between the fourth and seventh days from delivery, with consequences on mucous membrane proliferation. The keratinisation index declined gradually along with oestrogen drop of breast milk and turned to be equal to that of the Ki-Na group, eight weeks after delivery.--Proliferation of buccal mucous membrane and its importance to efficient defence against infection during the first four weeks of age are discussed.

The ability of the sexual steroids to induce extragenital organ-effects is set in connection to the preovulatory decrease of x-chromatin frequency during the regular menstrual cycle as found by Schmidt and coll. [11]. Under modified techniques of investigation and exact criteria of selection, reproducibility of the results and the behaviour of the x-chromatin-frequency in the artificially controlled anovulatory cycle are checked. The absence of preovulatory decrease shows that a hormonal influence may be assumed.

A method utilizing the reflex contraction of the retractor muscle of the hamster cheek pouch was developed to evaluate onset and duration of blockade produced by a local anesthetic agent infiltrated into or absorbed through the pouch epithelium. It provides a quantitative measure of reflex tension developed by the muscle as a function of afferent nerve conductivity in the pouch. The method is based upon the fact that when the pouch is everted activation of the retractor muscle results in the pouch being pulled toward the oral cavity. The method was validated by comparing the results with those obtained with other animal models and clinical trials. Ketocaine, an experimental drug, was evaluated for its efficacy as a local anesthetic when administered topically. In its present formulation the long latency of onset of blockade renders it impractical for clinical use.

In order to check the long-term effects of oral contraceptives used in the GDR on certain serum-lipid-fractions, triglycerides, phospholipids, total and free cholesterol, and beta-lipoproteins were determined in four groups of 15 women each, taking the contraceptive preparations Ovosiston, Nonovlon, Gravistat, and Deposiston. Determinations were carried out before and following 3, 6, 12, and 18 month of drug administration. Statistically significant increases of triglycerides occurred under the combined preparations, of phospholipids under Ovosiston and Deposiston and of the beta-lipoproteins under Ovosiston and Gravistat. Total cholesterol showed a slight decrease under all preparations tested. At present the prognostic significance of these slight alterations of serum-lipid-concentrations cannot be estimated completely.

Following the real pathogenesis-concepts of periodontal diseases proposals are given for stomatological care, gradual and postgradual education and research work. This material is the short summary of a large one which was discussed at the 3d working session of the Society of Periodontology of GDR.

The elimination of caffeine from serum and that of the main metabolites of metamizol in serum were investigated in 9 healthy women on days 1, 8, 14 and 21 of the menstrual cycle. In the luteal phase, when the progesterone level is highest and the estradiol concentration is high as well, the elimination of caffeine is about 25% longer than in the follicular phase. In contrast to caffeine, the metabolism of metamizol is slightly accelerated if the endogenous hormone level is high. The present results suggest that endogenous hormones have different effects on biotransformation activities. These results are without practical consequences yet.

The results obtained from the cytological examination of gingival smears taken during one cycle demonstrate that the effect of the depot contraceptive Deposiston on the gingivae is measurable.

The toxicity of 17 alpha-cyanomethyl-17 beta-hydroxy-estra-4, 9-dien-3-one (STS 557) was studied by its oral administration of 0.1, 1.0 or 10.0 mg/kg/day to Wistar rats for six months, and of 0.01, 0.1 or 1.0 mg/kg/day to beagle dogs for six months, respectively. Levonorgestrel at a dose of 1.0 mg/kg/day was used as the standard in the dog study. With respect to the progestational activity of the compound the main target organs were the hypophysis, the reproductive organs and the adrenals. Mammary hyperplasia was observed in dogs treated with STS 557 or levonorgestrel at the dose of 1.0 mg/kg/day, but in no case mammary nodules could be detected. At the dose of 1.0 mg/kg/day STS 557 and levonorgestrel were found to increase the plasma insulin response to i.v. glucose in bitches, but neither the mean blood glucose levels nor the glucose utilization were affected. Moreover, during administration of both steroids to dogs temporary changes in serum concentrations of triglycerides and total cholesterol were noted. The results obtained in rats and dogs from functional and morphological investigations did not reveal any toxic side effects of STS 557 on the liver, the kidneys, the bone marrow or on blood coagulation. The effects on the reproductive organs observed following STS 557 especially in dogs are related to both the hormonal effects of the compound and the specific response of the dog to potent progestagens.

Studies were conducted into 40 women who were afflicted with first-degree and second-degree urinary incontenence. The results are broken down by diagnostic methods used. The same methods were applied for control to 14 women without any incontinence complaints. - The contributions actually made by each of the methods to the definite presurgical diagnosis in its totality are described by graphic presentation of the results. - The findings reported in this paper suggest that complex consideration has to be given to all results to introduce adequate therapy in given any case. While the methods reported proved to differ by informative value, none of them should be abandoned in routine examination.

The changes in cytohormonal patterns we have studied on 34 patients using various combinations of exogenous estrogenes and progestagens. Comparative analysis of data with the progestagen compounds Non-Ovlon or Gravistat showed a same effect on vaginal smear.

The duration of pregnancy as assessed by the rule of Naegele was significant different between patients who became pregnant following termination of oral contraception and patients, who had not taken oral contraceptives. The intervall between stopping the pill and pregnancy was two month. We found a relatively high pregnancy rate in the first three month. The clinical significance is discussed.

The behaviour of the C-reactive protein--an acute phase reactant=-in sera from pregnant women and women with different applications of hormonal contraceptives was analysed. A significant increase of the CRP as a consequence of the effect of the sexualsteroids in 627 single measurements could be shown.

Placentas of different gestational age from women with oral contraception in the early phase of gravidity were studied morphometrically. An elevated risk for a placental insufficiency could not be found.

Progesterone as the main representative of gestagen-effective sexual steroide does not cause allone a statistically significant dilation of the lumina of the ureters compared with the adequate values of the control urogrammes. The fact that in pregnant rabbits no dilation of the ureters and of the renal pelvis was to be found allows the suspicion that during the pregnancy of the animal species used there are other mechanical conditions than during the human gravidity.

Reversibility of changes induced by sexual steroids was studied in 19 different serum protein fractions of 20 women. The following preparations were available for testing: Gravistat (ethinyl-oestradiol/norgestrel), Non-Ovlon (ethinyloestradiol/norethisterone-acetate), Ovosiston (mestranol/chlormadinone-acetate), and Deposiston (ethinyloestradiol-sulphonate/norethisterone-acetate). The tests were made towards the end of the 24th cycle on the pill and in the first cycle thereafter.--The proteins tested were found to be affected in a differentiated way and, throughout, depending on oestrogen levels. Reversal was rapid, but the phase of restitution usually was longer than the period of testing and follow-up. The long-lasting action of Deposiston was visualised also in its "reversal effect".

The influence of non-active ingredients in the manufacture of pellets on in-vitro dissolution rate and on bioavailability of hydrochlorothiazide has been studied. Pellets were formulated using either microcrystalline cellulose or microcrystalline cellulose-carboxymethylcellulose sodium blends as matrix, and hydrochlorothiazide as the active ingredient. In-vitro drug release from the different pellet formulations was retarded in comparison to a conventional tablet formulation and was dependent on the nature of the non-active ingredient and, for the microcrystalline cellulose-carboxymethylcellulose sodium blend, of the dissolution medium. In-vivo bioavailability of both pellet formulations was low compared with that of the conventional tablet and the plasma concentration-time profiles did not suggest slow release.

The authors have been using with success calcium peroxide as a root-canal filling material for many years. Its bactericidal and bacteriostatic effects are tested. Germ carrier tests illustrate the suitability of its pasty preparation for root-canal disinfection.

In studies for the chronic toxicity of estrogens and gestagens, lysozyme and hemolytic complement (CH50U) in sera of beagle dogs and minipigs were measured. Various doses of the sexsteroids were given: 0.01 mg, 0.1 mg and 1.0 mg/kg respectively. The influence of the steroids on the tested parameters after an application for 6 months was not significant, only in a single series with unphysiologically, high dosages of the preparations were some values changed significantly.

The problem of ethinylestradiol sulphonate excretion in human milk was qualitatively and quantitatively studied. In two women 0.0012 or 0.03000 per cent of total radioactivity were detected within the first nine days from application. Parallel thin-layer chromatography revealed the occurrence of ethinyloestradiol sulphonate in both its depot form and as ethinylestradiol.

Endometrium was investigated histologically in 55 fertile women and by electron-microscope in 6 women under the influence of Deposiston (Jenapharm), a sequential contraceptive containing a long acting oestrogen--ethinyloestradiolsulfonate. The drug was administered orally in 1 mg doses on the 5., 12. and 19. day of each cycle. To achieve proper withdrawal bleeding a single oral dose of 10 mg norethisteronacetate was given on the 26. day of the cycle. Whereas Sequenz- Ovosiston (Jenapharm), a "classical" sequential preparation causes only insignificant variations from the physiological endometrium of fertile women, Deposiston developes irregularly proliferated patterns in more than 50% of the patients, due to differences of the elimination rate of ethinyloestradiolsulfonate. The degree of proliferation covers a wide range from a slightly proliferated endometrium to changes similar to hyperplasia of the endometrium with cystically enlarged glands. The secretory transformation takes place 2 or 3 days following the progestogen application. In 2 of the cases a secretory pattern could be found several days before the intake of the progestogen. This indicates break-through-ovulations.

The effect of hormonal contraceptives administered for 24 months on the hydroxyproline content in urine was investigated. -- The results suggest an increase of hydroxyproline by application of sexual steroids. The reversibility is discussed.