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Biomedical subjects

A Teichmann

Publications and source records attributed to A Teichmann.

At least 19 recordsLinked to original sources
PubMed2006

Phase II trial of docetaxel and carboplatin in recurrent platinum-sensitive ovarian, peritoneal and tubal cancer.

OBJECTIVE: Docetaxel and carboplatin are active in relapsed ovarian, peritoneal and tubal cancer. Recently, two prospective-randomized trials showed an advantage of carboplatin combination regimen with paclitaxel or gemcitabine over carboplatinum alone in platinum-sensitive cases. The question on the most effective combination with the best tolerable side effects still needs to be answered. METHODS: Eligible patients had recurrent ovarian, peritoneal or tubal cancer (platinum-free interval >6 months), performance status 0-2 and normal bone marrow, renal and hepatic function. 25 patients (age 18-75 years) were enrolled into this phase II trial. Patients with debulking operation of recurrence were excluded from this study. Docetaxel 75 mg/m(2) via 30-min infusion was given on day 1 followed by carboplatin (area under curve [AUC] 5) on day 1. The administration was repeated every 3 weeks over 6 courses. Primary endpoint of this trial was the response rate; secondary endpoints were progression-free survival, overall survival and toxicity. RESULTS: In the intent-to-treat population, there were 16 (64.0%) complete and 2 (8.0%) partial responses resulting in an overall response rate of 72.0%. Three patients (12.0%) showed a stable disease and other 2 patients (8.0%) a progression of cancer. Two patients (8.0%) were not evaluable for response. Neutropenia was the most frequent G3/G4 hematologic toxicity in 15/25 patients (60.0%); but no neutropenic fever occurred in this trial. Diarrhea G3 was the most frequent G3/G4 non-hematologic toxicity in only 3/25 patients (12.0%). Dose-limiting toxicities were hypersensitivity reaction in one and depressive mood alteration requiring therapy in another case. CONCLUSION: Carboplatin in combination with docetaxel is highly active and well tolerated in patients with recurrent platinum-sensitive ovarian, peritoneal and tubal cancer. Prospective-randomized trials comparing this with other carboplatin therapeutic doublets in patients with recurrent ovarian cancer are a possible option for the future to answer the question on the best combination regimen.

Adult↗
PubMed2006

Semiquantitative determination of the penetration of a fluorescent hydrogel formulation into the hair follicle with and without follicular closure by microparticles by means of differential stripping.

Recently, hair follicles were shown to be of great importance concerning the penetration and reservoir behavior of topically applied substances. Especially microparticles are known to be efficient drug carriers into the hair follicles. It has been shown in various investigations that, depending on their size, microparticles can be utilized to enhance the penetration of substances into the hair follicles. In the present study, it was investigated whether they could also be used to block the hair follicles to stop penetration. For this purpose, the follicular penetration of a sodium fluorescein-containing hydrogel and follicular reservoir depletion were investigated by means of differential stripping in vivo. In a second study design, the skin areas were pretreated with microparticles 5 microm in diameter. Subsequently, the follicular penetration of sodium fluorescein-containing hydrogel was likewise investigated by differential stripping. The results showed that the hair follicle infundibula contained a significant fluorescent signal when sodium fluorescein in hydrogel was applied. In contrast, in the case of pretreatment with microparticles, only a very low fluorescence signal was measurable in the hair follicle infundibula. The microparticles clearly blocked the follicular orifices so that a penetration of sodium fluorescein was almost completely inhibited. This was confirmed by histological investigations. Thus, depending on their size, microparticles act as efficient drug carriers or can be utilized as follicle blockers to stop the penetration of topically applied substances. This could be very useful in skin protection to prevent the storage of harmful topically applied substances in the hair follicles, known to represent long-term reservoirs.

Adult↗
PubMed2006

Hair follicles - a long-term reservoir for drug delivery.

Nanoparticles represent an important drug carrier system. Recently, we have reported on the penetration and storage behavior of particular and non-particular substances revealing the superiority of particular substances in the range of 300-400 nm. In this regard, it was assumed that the rigid hair shaft acts as a geared pump, moving the particles deeper into the hair follicle. In the present investigation, the storage reservoir capacity of the stratum corneum and the hair follicle infundibulum and canal are compared. Interestingly, we could demonstrate a 10 times longer storage within the hair follicles. These results underscore the importance of the hair follicle for drug delivery purposes, mainly highlighting new possibilities for the future concerning retarded delivery, application frequency, and galenic design.

Administration, Topical↗
PubMed2006

[Functional food and bioavailability in the target organ skin].

Reactive free radicals can be produced in the skin by the action of environmental factors, such as sun radiation and toxins. These radicals can damage the DNA, proteins and lipids of the living cells. The consequences can be skin aging, immune suppression and even skin cancer. Humans have developed a protective mechanism against the action of free radicals in the form of antioxidant substances. Several of these antioxidants cannot be produced by humans and have to be acquired via food, such as carotenoids. Optical, non-invasive methods, like resonance Raman spectroscopy, allow a qualitative and quantitative online detection of the kinetics of antioxidants such as carotenoids in the skin. By employing this method it has been shown that the uptake of carotenoids in food can lead to an accumulation in the skin. On the other hand, stress, illness and UV-radiation can reduce the concentration of antioxidant substances in the skin. A high concentration of antioxidant substances is protective and associated with a reduction in skin wrinkling.

Antioxidants↗
PubMed2004

[Penetration of microparticles into human skin].

The efficacy of the penetration of microparticles into the human skin depends on the size and the type of the formulation with which they are topically applied. Microparticles with a diameter of >1 microm barely penetrate into the human skin. They are located on the skin surface and form a film which, for instance, can be used for camouflage or protection against UV radiation in sunscreens. While the penetration of the microparticles in the lipid layers of the stratum corneum is limited, they penetrate efficiently into the hair follicles up to a depth >2 mm, providing their diameter is <1.5 microm. Thus, microparticles can be used for drug delivery into the hair follicles.

Drug Carriers↗
PubMed2004

The role of combined oral contraceptives in the management of acne and seborrhea.

Acne and seborrhea (or facial oiliness) are related androgenic skin disorders which affect a high proportion of women after menarche. They can have a negative effect on psychological well-being and social life. Androgens play an important role in the pathogenesis of acne through the stimulation of sebum secretion, increasing sebaceous gland size and possibly through follicular hyperkeratinization. Conversely, estrogens decrease sebum production by suppressing gonadotropin release and androgen production and increasing sex hormone binding globulin production. One of the treatment options for these conditions is hormonal therapy, especially for women who require contraception. The effect of combined oral contraceptives in androgenic skin disorders depends on their estrogen:progestogen balance and on the antiestrogenic activity of the progestogen component. Improved understanding of what women value about oral contraceptives suggests that the choice of product should be tailored as much as possible to the individual. Several combined oral contraceptives containing new-generation progestogens (e.g. desogestrel, gestodene) or progestational antiandrogens (e.g. cyproterone acetate, chlormadinone acetate) have demonstrated efficacy in the treatment of women with acne, although comparisons between trials are difficult because of differing endpoints. Seborrhea has been less well studied, but the few studies that are available show an improvement in women with this condition using combined oral contraceptives.

Acne Vulgaris↗
PubMed2003

Pharmacology of estradiol valerate/dienogest.

The particular features of the pharmacology of a new continuous regimen for hormone replacement therapy containing 2 mg estradiol valerate (E2V) and 2 mg dienogest (DNG) (Climodien, Schering AG, Berlin, Germany) depend largely on its progestogenic component. Dienogest has the essential properties of an effective progestogen, so that it protects against endometrial proliferation and remarkably does not counteract the effects of estrogens. It is a derivative of 19-nortestosterone, but, instead of having an alkyl group at position C17, it has a cyanomethyl group, which endows it with a unique pharmaceutical profile. Its pharmacokinetics make it suitable for oral administration, without accumulation following repeat dosing. The strength of its effect on the endometrium is reflected by the fact that its progestogenic potency (ovulation dose/transformation dose) is about four times greater than that of any other progestogen. It does not bind to sex hormone binding globulin (SHBG), a feature that helps to keep free serum levels of dienogest high and free testosterone levels low. The low antiestrogenicity of dienogest has been well demonstrated in studies of estrogen-related parameters, such as SHBG levels and vasodilatation markers (cyclic guanosine monophosphate, 5-hydroxylindole acetic acid). Receptor binding studies show similar antiandrogenic effects for dienogest and cyproterone acetate, although the Hershberger test of clinical androgenicity suggests that dienogest is not as strongly antiandrogenic as cyproterone acetate, but is more antiandrogenic than chlormadinone acetate or drospirenone. In summary, E2V/DNG is well suited as an effective hormone replacement therapy, with the potential for good bleeding patterns and low androgenicity, owing to its formulation with a progestogenic component that is highly endometriotropic, has low antiestrogenicity and exhibits considerable antiandrogenicity.

Drug Administration Schedule↗
PubMed2001

Comparison of six different commercial IgG-ELISA kits for the detection of TBEV-antibodies.

BACKGROUND: Tick-borne encephalitis virus (TBEV) is a pathogenic human flavivirus endemic in some parts of Europe and Asia. Commercial enzyme immunoassays (EIA) for the detection of IgG antibodies are often used in TBEV-seroprevalence studies, as well as for the confirmation of a successful vaccination against TBEV. However, the detection of TBEV-specific antibodies can be biased by the cross-reactivity between different flavivirus genera. OBJECTIVES: To compare different EIA test systems for the detection of TBEV-IgG antibodies. STUDY DESIGN: Six commercial EIA kits for the detection of TBEV-specific antibodies are compared, using serum panels (n=139) of subjects with a documented clinical history (109 sera from TBEV infected patients, 30 sera from people vaccinated against TBEV). For the analysis of possible cross-reactivities, 24 sera from yellow fever vaccinated people and 13 sera positive for Dengue virus-specific antibodies were also included. RESULTS: The sensitivity of the different TBEV test systems ranges from 73 to 99%. However, when testing the yellow fever and Dengue virus positive specimens, problems with the flavivirus cross- reactivity become obvious, resulting in specificities between 14 and 81%. CONCLUSIONS: This study shows the necessity of further improvement of the existing TBEV test systems regarding both sensitivity and specificity.

Antibodies, Viral↗
PubMed1996

The effects of a new low-dose combined oral contraceptive containing levonorgestrel on ovarian activity.

OBJECTIVE: The study was designed to evaluate the effects of a new low-dose monophasic combined oral contraceptive (100 micrograms levonorgestrel/20 micrograms ethinylestradiol) on ovarian activity. METHOD: This was an open-label study in 15 healthy female volunteers. After an ovulatory pretreatment cycle, subjects were treated for three consecutive cycles. RESULTS: Out of 15 healthy females with an ovulatory pretreatment cycle, 13 completed the study and two dropped out. In ten females, various degrees of ovarian activity were characterized, mainly in the second and third treatment cycle. In eight cases follicle-like structures either persisted or developed throughout the pill-free interval, growing up to luteinized unruptured follicles or cyst-like structures that reduced their size or disappeared in the following treatment cycle. CONCLUSION: Ovarian follicular activity was significantly suppressed during treatment with levonorgestrel 100 micrograms/ethinylestradiol 20 micrograms. Similarly, endogenous ovarian steroid production was almost uniformly decreased. A 'dissociation' of ovarian and endometrial development was also seen during this therapy.

Adolescent↗
PubMed1995

Laboratory scale production of monoclonal antibodies in a tumbling chamber.

A simple device for laboratory scale production of monoclonal antibodies has been developed. Hybridomas were cultured in four individual dialysis tubes containing 40-50 ml medium with 10% foetal calf serum, surrounded by 1.5-2 litres supply medium without any serum supplement. Once placed on a roller the special design of the apparatus leads to an eccentric rotation, thus keeping the cells in a stable homogeneous suspension. The system is automatically gassed, and this makes long term cultivation possible. Several hybridomas were tested over a culture period of at least 3 weeks, with supply medium changes every 3-4 days. Cell densities of up to 2.5 x 10(7)/ml and antibody concentrations of 0.3-1.9 mg/ml after purification were obtained. Results with this in vitro system allow a complete renunciation of the established in vivo method. The so called 'tumbling chamber' apparatus is easy to handle and to sterilize, is economic and universally adaptable in any research laboratory.

Antibodies, Monoclonal↗
PubMed1995

Metabolic profile of six oral contraceptives containing norgestimate, gestodene, and desogestrel.

The alterations in lipid metabolism that occur with the use of oral contraceptives (OCs) have aroused considerable concern that OCs might increase the risk of premature atherosclerosis. However, most studies examining the role of OCs in atherogenesis were performed using earlier-generation preparations employing larger doses of sex hormones than present formulation. Therefore, we undertook a comparative and standardized determination of the effects on lipid metabolism of six modern, low-dose OCs. This open, randomized, comparative study included patients recruited at 21 study centers throughout Europe. Four hundred sixty-six women, aged 18-38 years, participated. They were randomly assigned to the following OC formulations:(1) norgestimate 250 micrograms + ethinyl estradiol (EE) 35 micrograms (Cilest); (2) norgestimate 180/215/250 micrograms + EE 35 micrograms (Tricilest); (3) desogestrel 150 micrograms + EE 20 micrograms = (Marvelon); (4) desogestrel 150 micrograms + EE 30 micrograms (Mercilon); (5) gestodene 75 micrograms + EE 30 micrograms (Femovan); and (6) gestodene 50/70/100 micrograms + EE 30/40/30 micrograms (Trifemovan). There were three parallel studies with six parallel patient groups. Fasting blood samples were drawn at baseline (between days 24 and 28) and on days 18-22 of cycle 6, and cycle 12. Sample were analyzed for total cholesterol,high-density lipoprotein (HDL) cholesterol, HDL2 cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, apolipoprotein (apo)A1, and apoB at one central laboratory. Two hundred eighty-two women completed all 12 cycles and were included in the final evaluation. As expected, triglyceride and total cholesterol concentrations increased in all study groups but to lesser levels with the formulations containing gestodene. All OCs, except the monophasic gestodene preparation, slightly but significantly increased HDL. The HDL2 subfraction did ot change significantly except in the group using the monophasic gestodene preparation; in this group, the HDL2 subfraction slightly but significantly decreased. The LDL concentration increased slightly with the monophasic and triphasic norgestimate preparations and with desogestrel + 20 micrograms EE. The LDL/HDL ratio did not change significantly except with the use of the triphasic norgestimate preparation, in which case it decreased slightly. ApoA1 and apoB levels increased only slightly with all formulations. Importantly, while all of the OCs tested altered lipid levels to some extent, after 12 cycles there were no statistically significant differences in lipid effects among OC preparations. Modern, combined OCs that contain norgestimate, desogestrel, or gestodene all have some impact on lipid levels. However, it would appear likely that they do not contribute to atherogenesis in healthy women.

Adolescent↗
PubMed1992

Paracrine actions of oxytocin, prostaglandin F2 alpha, and estradiol within the human corpus luteum.

Human luteal cells are known to interact in an auto- and paracrine fashion using a variety of substances, including prostaglandins (PGs), steroids, and peptides. In cultures of dispersed luteal cells obtained from several animal species prostaglandin F2 alpha (PGF2 alpha) and oxytocin (OXT) inhibit progesterone (P) secretion, indicating a luteolytic effect of these substances. The disadvantage of luteal cell cultures is that the different luteal cell types do not communicate with each other, i.e. auto- and paracrine effects cannot be studied. Therefore, we used a microdialysis tubing, which is implanted in human corpora lutea (CL) kept under short term organ culture conditions. Ringer's solution is pumped through the dialysis tubing, and substances secreted by the luteal tissue can be determined in the effluent fractions. This system also allows topical application of substances with putative intraluteal effects. In the present report we used PGF2 alpha, OXT, and estradiol (E2) to examine the effects of these substances on the respective other hormones and on P release from young human CL. Intraluteal application of PGF2 alpha stimulated OXT, E2, and P release. OXT was stimulatory to E2 and P secretion, an effect that can be blocked by a specific OXT antagonist and by tamoxifen. Elevation of intraluteal E2 concentrations also had marked stimulatory effects on P secretion. From luteal cell culture experiments it is known that PGF2 alpha and OXT have direct inhibitory effects on P production, but both substances stimulate E2 release. It was also shown that E2 counteracts the inhibitory effects on P release. Therefore, the PGF2 alpha- and OXT-induced E2 release may be responsible for the increased P release. This assumption is further substantiated by the observation that intraluteally applied E2 stimulates P secretion, and preexposure of human CL to tamoxifen prevents the OXT-induced stimulation of P, but not E2, secretion. We conclude that in young human CL, PGF2 alpha and OXT have dual effects: direct inhibitory effects on P release and E2-mediated stimulatory effects, which in young CL result in a net stimulation of P secretion.

Chorionic Gonadotropin↗
PubMed1991

Occurrence of antibodies to L1, L2, E4 and E7 gene products of human papillomavirus types 6b, 16 and 18 among cervical cancer patients and controls.

Sera from 118 women of 33 to over 90 years of age, with or without a history of cervical squamous-cell carcinoma, were examined for the presence of antibodies to HPV-6b, HPV-16 and HPV-18, L1, L2, E4, and E7 gene products by the use of bacterially derived beta-Gal fusion proteins and Western-blot analysis. Among the cervical cancer patients, 29/46 (63.0%) were positive for antibodies to E4 and/or E7 of HPV-16 and/or E7 of HPV-18. In contrast, only 2 of 31 (6.5%) non-genital cancer patients and 4 of 41 (9.8%) healthy individuals were antibody-positive for HPV-16 E4 or E7, while antibodies to the homologous proteins of HPV-18 could not be detected. Prevalence rates of antibodies to the HPV-16/18 late proteins were 25/46 (54.3%) in the cervical carcinoma group, 13/31 (41.9%) among women with non-genital cancer types, and 18/41 (43.9%) among normal, healthy individuals. Antibodies to HPV-6b late gene products ranged between 6.5% and 12.2% in the different patient groups. Antibodies to HPV-6b E4 and E7 were detected only once. By studying an additional control group of 207 women with a different age distribution, age-dependence of antibodies to HPV gene products could be ruled out. Whereas antibodies to late proteins may indicate that, regardless of clinical stage, HPV infections are wide-spread among the female population, the striking difference between the prevalence rates of antibodies to early proteins of HPV-16 and HPV-18 among cervical cancer patients and controls (p less than 0.001) supports the idea of the involvement of these virus types in carcinogenesis of the cervix.

Adult↗
PubMed1991

Antibodies to human papillomavirus type-16 in human sera as revealed by the use of prokaryotically expressed viral gene products.

Open reading frames of human papillomaviruses were expressed in Escherichia coli as beta-galactosidase fusion proteins. These bacterially derived papillomaviral gene products were used to examine sera from 67 women (63 healthy subjects, 4 patients with genital carcinoma) for antibodies to papillomavirus type-16 antigens (E1, E2, E4, E5, E6, E7, L1, L2) and the L2 proteins of HPV-6b and HPV-18 by Western-blot analysis. The serologic data were compared with cytological findings classified according to Papanicolaou and with nucleic acid hybridization data from cervical smears of the same individuals. Twenty-three of the normal individuals showed antibodies exclusively directed against L2 gene products; whereas in the sera from the four genital cancer patients, antibodies to the early gene products E4 and/or E7 could be detected. In one case these antibodies were found to be combined with antibodies to L2 of HPV-16 and -18 and in another case with those to E1 and E2 of HPV-16. In none of the sera examined could antibodies to L1, E5 or E6 be identified. Three of the antibody positive normal women were found to be also positive for HPV-16/18 DNA, while all of the 40 seronegative women were HPV-16/18 DNA negative. These data indicate that serology may be a valuable means to study the epidemiology of genital human papillomavirus infection.

Adult↗
PubMed1991

Definitive radiation therapy in the treatment of carcinoma of the uterine cervix. Treatment results and prognostic factors.

219 patients suffering from cervix carcinoma received definitive radiation therapy using moderate doses of external beam therapy and high dose-rate afterloading brachytherapy from 1979 to 1986. At five years, the actuarial survival (AS) for stage Ib patients was 81%, for stage IIa 53%, for stage IIb 56%, for stage IIIa 25%, for stage IIIb 33% and for stages IVa and IVb 0%. Significant prognostic factors for actuarial survival were FIGO stage, histological type, grading and, marginally, age of the patient at the time of diagnosis. The survival data censored for death caused by intercurrent disease (tumor related survival, TUS) at five years were: 90% (Ib), 66% (IIa), 63% (IIb), 50% (IIIa), 41% (IIIb) and 0% (IVa and IVb). The prognostic factors were stage and grading. Age and histology failed to be a significant prognostic factor. The disease-free survival (DFS) according to FIGO stage at five years were: Ib 84%, IIa 64%, IIb 59%, IIIa 50%, IIIb 38%, IVa and IVb 0%. Prognostic factors for disease-free survival were limited to FIGO stage and grading. The five-year local control results (LC) according to stage were 90% (Ib), 64% (IIa), 67% (IIb), 43% (IIIb) and 0% (IVa and IVb) with stage as prognostic factor. High dose-rate afterloading therapy for cervix carcinoma yields good results for local control and survival with a low ratio of severe side effects (6%). Radiation therapy eliminates the prognostic influence of histological type and grading of the tumor on local control. External beam and afterloading doses, however, are relevant factors for prognosis, if the patients are stratified by FIGO stage.

Adenocarcinoma↗
PubMed1990

Occurrence of human papillomavirus DNA types 16 and 18 (HPV-16/18) in cervical smears as compared to cytological findings.

Cervical smears from 2336 women were examined for the presence of HPV-16/18 by dot-blot hybridization using 32P-labeled HPV-16/18 DNA under high stringency conditions. The hybridization data were compared with cytological findings classified according to Papanicolaou. The ages of the patients ranged from under 20 to over 70 years. Ninety-eight (4.4%) of the 2237 cytologically normal cervical samples (Pap I and II) were HPV-16/18 positive. Thirteen out of 32 (40.6%) samples showing signs of mild and moderate dysplasia (Pap IIID) were found to be HPV-16/18 positive. In 5 out of 7 (71.4%) samples from women with severe dysplasia or carcinoma in situ (Pap IV) and in 9 out of 25 (32.1%) samples from patients with invasive cervical carcinoma (Pap V) HPV-16/18 DNA was detected. Thirty-two smears were from women with severe unspecific cervical inflammation (Pap III). Two (6.2%) out of them were HPV-16/18 positive. Normal smears showed an apparent age-dependent pattern of HPV-16/18 positivity with a peak prevalence of 10.6% among women younger than 20 years old. The majority of premalignant lesions was detected among women younger than 40 years old; whereas all invasive lesions were from women older than 39 years. Compared to the HPV-16/18 prevalence rate in normal smears, abnormal smears harbored HPV-16/18 DNA approximately 9 times more frequently. This finding supports the hypothesis that HPV-16/18 may be involved in the development of cervical cancer.

Adult↗
PubMed1990

[Clinical management of cystic ovarian tumors].

In a prospective study at the University of Göttingen 206 cystic ovarian tumours were examined vaginosonographically. Basing on a graduated schedule, the individual therapy of each ovarian tumour was determined. By use of this clinical management, all blastomas could be detected correctly and in 6.8% of all cases a follicle or corpus luteum cyst was operated per laparotomiam. Basing on the created data, the authors suggest a simple and effective clinical management of cystic ovarian tumours.

Adolescent↗