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Biomedical subjects

S Arrenbrecht

Publications and source records attributed to S Arrenbrecht.

At least 19 recordsLinked to original sources
PubMed2002

Effects of transdermal estradiol delivered by a matrix patch on bone density in hysterectomized, postmenopausal women: a 2-year placebo-controlled trial.

This 2-year, double-masked, randomized, placebo-controlled trial was designed to evaluate the safety and efficacy in preventing bone loss in postmenopausal women of two doses of transdermal 17betaestradiol (estradiol) delivered by a matrix patch, compared with placebo. One hundred and sixty healthy, hysterectomized postmenopausal volunteers aged 40-60 years with serum estradiol levels < 20 pg/ml were started on treatment at four centers in The Netherlands. Every 6 months, bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA) at the lumbar spine, non-dominant wrist and left hip, and markers of bone turnover were assessed in urine and serum. The treatment arms were: estradiol, 100 microg/day (E-100, n = 53), oestradiol, 50 microg/day (E-50, n = 54), placebo (P-100, placebo to E-100, n = 27 or P-50, placebo to E-50, n = 26). Treatment was continued for up to 2 years. After 24 months, BMD of the lumbar spine in the E-100 group differed by 7.7% [5.8-9.5%] (mean [95% confidence interval]) from the placebo group and showed a mean (s.e.m.) increase in BMD from baseline of 5.9% (0.69%). For the E-50 group the difference compared with placebo was 6.2% [4.4-8.0%] and the absolute increase was 4.5% (0.62%); in the placebo group, the absolute change was -2.3% (0.48%). In the total wrist, the changes were: E-100: difference compared with placebo 2.5% [1.5 3.6%], absolute increase 0.6% (0.3%); E-50: difference compared with placebo 2.9% [1.8-3.9%], absolute increase 0.7% (0.25%); and absolute change on placebo: -2.5% (0.35%). In the total hip, the changes were: E-100: difference compared with placebo 3.7% [2.2-5.2%], absolute increase 2.8% (0.5%); E-50: difference compared with placebo: 3.2% [1,8-4.7%], absolute change 2.4% (0.36%); and absolute change on placebo -1.4% (0.66%). Three markers of bone turnover--serum bone-specific alkaline phosphatase, serum osteocalcin and urinary CTX--fell significantly during the trial. Breast pain was reported by 8% of women on placebo, by 6% of women on E-50 and by 17% of women on E-100. Estradiol delivered by the E-50 matrix patch effectively reversed bone loss in hysterectomized postmenopausal women with few side-effects. The marginal additional gain in BMD with the higher dose may be offset by a more important side effect profile.

Administration, Cutaneous↗
PubMed1997

Comparison of continuous and sequential transdermal progestogen with sequential oral progestogen in postmenopausal women using continuous transdermal estrogen: vasomotor symptoms, bleeding patterns, and serum lipids.

OBJECTIVE: The efficacy, bleeding patterns, and safety of continuous transdermal and sequential transdermal progestogen therapy were compared with those of oral progestogen therapy in postmenopausal women receiving transdermal estrogen. METHODS: In an open-label, 1-year (13 treatment periods, 28 days each), randomized study, 774 postmenopausal women were assigned to receive 50 micrograms/day of continuous trans dermal estradiol with either continuous or sequential transdermal norethisterone acetate (NETA) in daily doses of 170 or 350 micrograms in a single transdermal patch or sequential oral progestogen (1 mg norethisterone [NET] or 20 mg dydrogesterone/day). RESULTS: The average number of hot flushes/day decreased from prestudy by over 90% (P < .001), and this reduction was unaffected by different progestogen regimens. With sequential progestogen, bleeding incidence and the number of bleeding days did not change over the course of the study but were lower in the low-dose transdermal progestogen group. With continuous progestogen, the incidence of bleeding decreased in both the low- and high-dose groups, from 35% and 45% in treatment period 1 to 25% and 15%, respectively, at the end of treatment. Adverse event incidence was similar in all groups, with 23% to 36% of subjects reporting events possibly or probably related to HRT (excluding vaginal bleeding). Two cases of simple hyperplasia were reported (one in each low-dose progestogen group). Beneficial effects on coronary heart disease risk factors, such as reductions in total cholesterol and low-density lipoprotein cholesterol and increases in high-density lipoprotein-2 cholesterol levels, were measured in all treatment groups. Lipoprotein (a) was reduced in all but the oral progestogen group. CONCLUSIONS: Continuous and sequential transdermal estrogen/progestogen treatments with estradiol/NETA appear to be effective and safe alternatives to continuous transdermal estrogen and oral sequential progestogen for the treatment of menopausal symptoms. Continuous transdermal therapy with estradiol/NETA may be more acceptable for a majority of patients, i.e., those who wish to avoid monthly bleeds, whereas the sequential regimen may be preferable when the clinician and/or patient believes monthly bleeding to be appropriate.

Administration, Cutaneous↗
PubMed1997

Transdermal sequential and continuous hormone replacement regimens with estradiol and norethisterone acetate in postmenopausal women: effects on the endometrium.

OBJECTIVE: To evaluate, in postmenopausal women, the endometrial safety and histologic effects of two doses of transdermal norethisterone acetate (NETA) administered in sequential and continuous treatment regimens added to continuous transdermal estradiol, against a reference regimen consisting of sequential oral progestogen and continuous transdermal estradiol. METHODS: A total of 774 postmenopausal women were enrolled in the open-label study of 13 treatment cycles of 28 days each and randomly assigned evenly to regimens consisting of transdermal estradiol, 50 micrograms/day and NETA, given sequentially (last 14 days of each treatment cycle) or continuously at two doses (170 and 350 micrograms/day). Estradiol and NETA were delivered from a transdermal system containing both hormones. The reference group received estradiol, 50 micrograms/day transdermally and either 1 mg/day NET or 20 mg/day dydrogesterone orally during the last 14 days of each treatment cycle. Endometrial biopsies were taken pre-study and at the end of the treatment, if treatment had lasted at least 3 months. Safety was to be assessed in terms of the incidence of hyperplasia. Endometrial biopsies were assigned to one of the following histological classes: proliferative (predominant estrogen effect), suppressed proliferation (slightly, moderately, strongly progestogenic effect), progestational atrophy (predominant progestogenic effect), hyperplastic, cancerous, or other. RESULTS: No case of hyperplasia was recorded in any of the treatment groups, each with > 150 subjects enrolled, after one year of treatment. One case of serous carcinoma was found in the LP-C group. Progestational atrophy was seen frequently in women receiving continuous transdermal HRT (84%, high-dose NETA, 66%, low-dose NETA); it was much rarer with the sequential regimens (i.e., between 32% and 38%). The proportion of estrogen-dominated endometria was low, 0.9% and 2.6% with the high- and low-dose NETA continuous regimens, respectively, 6.2% and 12.5% with the high- and low-dose NETA sequential regimens, respectively; and, 4.5% in the oral progestogen group. CONCLUSION: Transdermal administration of either dose of NETA, whether given sequentially or continuously, prevents the emergence of hyperplasia expected with unopposed estradiol. Since differences in outcomes of endometrial histology between the two NETA doses were minor for both continuous and sequential regimens, use of the lower NETA dose is considered sufficient for a safe transdermal combination hormone replacement therapy.

Administration, Cutaneous↗
PubMed1986

[Estrogen and progesterone receptors in human liver: does their study contribute to a better understanding of benign contraceptive-associated liver tumors?].

The estrogen and progesterone receptor content of liver cytosol was measured in female patients with focal nodular hyperplasia associated with oral contraceptive use and compared with the receptor content of non-tumorous liver and of primary hepatocellular carcinomas. Receptors were found in very low concentrations or were not measurable at all. In one case of focal nodular hyperplasia the estrogen receptor content of the tumor was higher than that in the adjacent normal liver. Malignant liver tumors and the male liver were characterized by a low or non-measurable receptor content. The study of nuclear receptors combined with the use of monoclonal antibodies may be more helpful in elucidating the complex relationship between oral contraceptive use, benign liver tumors and hepatic steroid receptors.

Adult↗
PubMed1986

A human testicular germ cell tumor with borderline histology between seminoma and embryonal carcinoma secreted beta-human chorionic gonadotropin and alpha-fetoprotein only as a xenograft.

Two macroscopically distinguishable components (designated soft and firm) of a human testicular germ cell tumor with borderline histology between seminoma, embryonal carcinoma and yolk sac tumor, were maintained as xenografts in nude mice for over 20 passages. Levels of beta-human chorionic gonadotropin (beta-HCG) and of alpha-fetoprotein (AFP) were normal in the patient's serum and were undetectable by immunohistochemical studies of the surgical specimen. The xenografted soft part, however, with morphologic characteristics of an embryonal carcinoma, secreted beta-HCG and AFP during early passages. The firm variant, histologically resembling a seminoma, did not produce these markers. Chromosomal and flow cytophotometric analyses showed genetic differences between the clonally stable variants. A common origin, however, is indicated by two similar marker chromosomes present in both variants.

Animals↗
PubMed1986

Interactions of cytotoxic and other drugs: rapid cell culture assay.

In order to investigate the interactions of cytotoxic and other drugs, a cell culture assay was devised where changes in the ability of cytotoxic drugs to induce cytopathogenic effects can easily be visualized. A human mammary carcinoma cell line (BT 20) and a human hypernephroma cell line were used. Seventeen commonly used cytotoxic drugs were titrated in this assay. As an example of drug interactions the neutralization of nitrogen mustard, cis-dichlorodiammine-platinumII, and 4-hydroperoxycyclophosphamide by thiol-containing drugs shows that this assay is well suited to detect interactions of cytotoxic and other drugs.

Antineoplastic Agents↗
PubMed1985

Hairy cell leukemia: kinetics and intercellular relationships of cells in leukemic colonies grown in a semisolid medium.

We examined cellular relationships and cytokinetics of hairy cells in colonies formed in an in vitro cloning system. Cells in small colonies and at the periphery of larger ones were separated by wide, irregular intercellular spaces. Cells in the core of large colonies were elaborately intertwined by their cytoplasmic processes and so densely packed that their intercellularity was greatly reduced. Cell labeling with 3H-thymidine revealed indices ranging from less than 1% to 35%. The combination of autoradiography with a stain for tartrate-resistant acid phosphatase showed that the enzyme was not expressed by cells in S-phase. The cellular relationships of hairy cells in colonies grown in this system closely mimic those of their in vivo counterparts in the spleen and bone marrow.

Acid Phosphatase↗
PubMed1985

Hairy cell leukemia. Ultrastructural and cytochemical evaluation of leukemic colonies grown in a semi-solid medium.

We examined the fine structure and enzymatic activity of cells composing colonies grown from blood and/or spleen of eight patients with hairy cell leukemia. Mononuclear cells (MNC) were plated over an agar layer in a medium containing methylcellulose and leukocyte-conditioned medium. After 7-10 days incubation colonies were harvested for cytologic study. Colony cells possessed a euchromatic nucleus with an occasional nucleolus. Their cytoplasm contained a prominent Golgi region, numerous mitochondria and small vesicles, many short strands of rough endoplasmic reticulum (RER) and an infrequent phagosome. Well-developed ribosome-lamella complexes and what may have been their intermediate forms appeared in colony cells from three patients. Strong activity for tartrate-resistant acid phosphatase, localized in the RER, nuclear envelope and some Golgi vesicles, was evident in 50-95% of all colony cells. Our results indicate that a high proportion of MNC forming colonies in this culture system maintain the characteristic morphology and cytochemical activity of hairy cells.

Acid Phosphatase↗
PubMed1985

Evaluation of microtitre plates for the routine assay of oestrogen and progesterone receptors in tissue extracts.

A time- and material-saving assay of oestrogen and progesterone receptors in tissue extracts using enzyme-linked immunosorbent assay quality microtitre plates and microtitre-compatible equipment is described. The results from simultaneous determinations in microtitre plates and in conventional tubes show the former to yield higher receptor values. Furthermore, the results of a large series of measurements in microtitre plates compare favourably with previously obtained results from assays in tubes.

Breast Neoplasms↗
PubMed1983

[Spontaneous radial segmentation of cell nuclei: morphologic marker of T-cell neoplasms?].

Radial segmentation (RS) of leukocyte nuclei has been observed, for example, in leukemias (Rieder cells). In 6 of 8 patients with T-ALL, RS of neoplastic cells was found in the peripheral blood, whereas in 14 patients with non-T-ALL no RS cells were present. RS may be a morphologic marker for certain T-cell neoplasms, and with regard to ultrastructure it seems to be identical to heat-induced RS of non-neoplastic cells.

Cell Nucleus↗
PubMed1983

[Semisynthetic penicillins and cephalosporins inhibit in vitro myelopoiesis in a dose-dependent manner].

Penicillin-G degradation products have been shown to inhibit in vitro myelopoiesis in a dose-dependent manner. Similar inhibition was seen with 6 semisynthetic penicillins and 2 cephalosporins. 50% inhibitory doses in vitro well matched total and daily doses given in vivo before neutropenia developed. These findings suggest a toxic rather than an immune-mediated pathogenesis for betalactam-induced neutropenia.

Bone Marrow Cells↗
PubMed1983

Penicillin-G degradation products inhibit in vitro granulopoiesis.

38% of penicillin-G in solution decays at 20 degrees C within 24 h, 50% at 37 degrees C and 66% within 3 h at 56 degrees C. These degraded penicillin-G solutions strongly inhibit growth and maturation of granulocytic stem cells in vitro. Inhibitory concentrations are in the range obtainable with high dose penicillin therapy in vivo. No cytotoxicity of degraded penicillin solutions on bone marrow cells was seen over 24 h. It is suggested that penicillin-G degradation products are responsible for severe granulocytopenia observed after high dose penicillin-G therapy.

Bone Marrow↗
PubMed1983

Radial segmentation of nuclei (Rieder cells): a morphological marker of T-cell neoplasms?

Pretreatment blood smears of adult patients with acute lymphoblastic leukemia were examined for neoplastic cells showing nuclear radial segmentation (RS). RS was present in 6 of 7 patients with immunologically proven T-cell leukemia, but not in 11 patients whose leukemic cells lacked T-cell markers. Electron microscopic studies of neoplastic cells showed multiple nuclear indentations and abundant cytoplasmic microfilaments and microtubuli in connection with pericentriolar dense material. RS formation was decreased in 1 patient after chemotherapy with a vincristine-containing regimen, while the white cell count remained unchanged. Radial segmentation (RS) of leukocyte nuclei is a well-known phenomenon, which is observed ex vivo (Rieder cells), and can be induced in vitro. Convoluted or multilobulated nuclei in lymphoid neoplasms are similar to RS nuclei both with regard to their structure and their sensitivity to spindle-blocking drugs. We propose that the nuclear alterations observed in a variety of different T-cell neoplasms are identical with RS, and suggest that RS might be a morphological marker for subsets of lymphoproliferative disorders of T-cell origin.

Adult↗
PubMed1983

[Idiopathic chronic oral candidiasis in T-helper cell defect and heterozygote (MZ) alpha-1-antitrypsin deficiency].

The case of a 14-year-old girl is reported, suffering from a chronic oral candidiasis for the past 2 years. An immunologic T-cell defect was discovered: anergy in skin tests with recall antigens, negative lymphocyte stimulation tests with antigens and marked T-helper-cell depression in lymphocyte subpopulations. Thymopoietin-pentapeptide normalized the T-helper-cell number without clinical improvement. Complete remission was achieved after oral ketoconazole therapy.

Adolescent↗
PubMed1983

Early antiviral antibody response after immunization with viral oncolysate: a powerful prognostic marker for acute myelogenous leukemia remission patients.

Twenty-four acute myelogenous leukemia (AML) patients in first clinical remission received, as a part of their maintenance therapy, repeated injections of viral oncolysate (i.e., avian influenza virus-infected, formalin-inactivated, allogeneic leukemia cells). The anti-oncolysate-virus antibody responses after a single injection, tested by a radioimmunoassay, were in inverse correlation to the remission duration (p less than or equal to 0.01). The 25% of patients with the lowest responses had a median remission duration of more than 36 mo, with no relapses within the first 18 mo. In contrast, the 75% of patients with higher responses had a median remission time of less than 5 mo, and more than 80% relapsed within 18 mo. Despite the small number of patients, these differences are highly significant (p less than or equal to 0.001). Immunization of remission AML patients with viral oncolysate provides a powerful prognostic test. Most early relapses can be predicted, with a modest rate of false-positive and false-negative predictions.

Antibodies, Viral↗
PubMed1982

A quality control study to assess the inter-laboratory variability of routine estrogen and progesterone receptor assays.

The steroid hormone receptor laboratories of Bern, Basel, Zürich, Locarno, Lausanne and Geneva have participated in a quality control study to assess potential inter-laboratory variability in results of tests for determination of steroid hormone receptor status in human breast tumor biopsies. Homogeneous breast tumor powders containing low, medium and high concentrations of estrogen receptors (ER) and progesterone receptors (PR) were prepared in Bern and dispatched on solid CO2 to each laboratory within 1 day of preparation. Each laboratory was requested to assay each powder for ER and PR by their usual procedures. The results revealed that the quantitative discrepancies in ER and PR binding values among the participants could be attributed in part to variations in the methods used for measuring cytosol protein content and also to the differences in hormone receptor assay methods. Nevertheless, all of the laboratories were able to identify the samples containing low, medium and high concentrations of ER and PR.

Breast Neoplasms↗