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51.
Lisa Marlene Krassuski Sibylle Kautz-Freimuth Vera Vennedey Kerstin Rhiem Rita K. Schmutzler Stephanie Stock 《Geburtshilfe und Frauenheilkunde》2021,81(6):679
Introduction Women with a pathogenic BRCA1/2 mutation have a markedly increased lifetime risk of developing breast and/or ovarian cancer. The current preventive treatment alternatives that are offered are an intensified breast cancer screening programme and risk-reducing operations. Before deciding on one option, medical and personal factors such as life situation and individual preferences must be weighed carefully. Decision aids are used internationally to support BRCA1/2 mutation carriers during their decision-making process. In this study these are analysed structurally for the first time and their applicability to the German context is examined. Material and Methods A systematic literature search in five electronic databases and a manual search were performed. The identified decision aids were evaluated with regard to formal criteria, medical content and quality. The qualitative assessment used the criteria of the International Patient Decision Aid Standards Collaboration (IPDASi v4.0), which examined various dimensions (e.g., information, probabilities, values). Results Twenty decision aids, which were published between 2003 and 2019 in Australia (n = 4), the United Kingdom (n = 3), Canada (n = 2), the Netherlands (n = 2) and the USA (n = 9), were included. Nine focus on BRCA1/2 mutation carriers and eleven include other risk groups. Eighteen include risk-reducing operations as decision options, 14 list screening methods for breast and/or ovarian cancer, and 13 describe the possibility of pharmacological prevention by means of selective oestrogen receptor modulators or aromatase inhibitors. Nine of the 20 decision aids meet fundamental quality criteria (IPDASi v4.0 qualification criteria). Conclusion International decision aids can serve formally as a basis for a German decision aid for BRCA1/2 mutation carriers. Some of them differ markedly in content from the recommendations of German guidelines. Only a few achieve a high quality. Key words: BRCA1, BRCA2, decision aid, familial breast cancer, familial ovarian cancer 相似文献
52.
Summary The steady-state kinetics of chlorophenoxyisobutyric acid (CPIB) and of bezafibrate were investigated in a strictly controlled, randomised cross-over study in 10 female volunteers, after the conventional oral doses of clofibrate 0.5 g and bezafibrate 0.2 g at 8-h intervals. The mean steady-state concentration of CPIB in serum was 34 times higher than that of bezafibrate, which was due to the considerable cumulation of CPIB, whereas no cumulation of bezafibrate was observed. This is supported by comparison of the AUCs, and of the maximum and mean concentrations of bezafibrate after the first and last doses. (0.44 and 0.49 h–1) and the half-lives (1.6 and 1.4 h) were almost identical after the first and last doses of bezafibrate. The median total clearances of CPIB and bezafibrate amounted to 10.5 and 142.5 ml/min, respectively, if complete absorption of both drugs is assumed. Since the apparent volumes of distribution were in the same range for both drugs, the amount of drug present in the organism in steady-state also differed by a factor of approximately 30 under the usual dosage regimen. 相似文献
53.
The aim of the present study was to investigate whether amperozide, an antipsychotic drug which possesses anti-aggressive and anxiolytic-like properties, stimulates the secretion of oxytocin and if so, by which receptor mechanism. For this purpose, female or male Sprague Dawley rats were given amperozide (0.5, 2.5 and 5.0 mg/kg IP), ritanserin (5.0 mg/kg), raclopride (2.0 mg/kg) and prazosin (1.0 mg/kg) and were subsequently decapitated for collection of blood (30 and 120 min) after injection. Oxytocin levels were measured with radioimmunoassay. Amperozide 2.5 and 5 mg/kg increased plasma levels of oxytocin significantly (P<0.05 and <0.001). The effect appeared maximal about 30 min after injection of the drug and oxytocin levels were almost back to basal within 120 min. Similar effects were obtained in female and male rats as well as in animals that were freely fed or food deprived for 24 h. CSF levels of oxytocin were also increased. Ritanserin, a 5-HT2-receptor antagonist but not the D2 receptor antagonist raclopride or the 1-adrenoceptor antagonist prazosin stimulated oxytocin release. In addition, clozapine, a neuroleptic with potent HT2-antagonistic properties, was a potent releaser of oxytocin, whereas haloperidol was without effect. A possible role for oxytocin in the behavioural effects of amperozide and clozapine remains to be explored. 相似文献
54.
U. Abshagen H. Rennekamp G. Luszpinski 《Naunyn-Schmiedeberg's archives of pharmacology》1976,296(1):37-45
Summary Five healthy male volunteers received 500 mg Aldactone® orally together with 100 Ci 3H-20-21-spironolactone; one elderly patient received 1 mCi 3H-spironolactone without additional cold drug. For 6 days the disposition kinetics of the drug were studied in plasma, urine and feces. The tritium concentrations in plasma reached a peak between 25–40 min after administration amounting to 2–3% of the dose/1. Up to the 12th h, they fell rapidly and showed a monoexponential decline (t
1/2
: 2.57±0.27 days) between the 36th and 96th h. Later, a striking increase in the speed of elimination of radioactivity from plasma (t
1/2
: 1.66±0.21 days) was observed. The biological half-life of labeled material in plasma was longer than that of fluorigenic compounds. 47–57% of the dose were excreted in urine and the remaining amount culd be detected in feces (total recovery 90%). The half-life of the urinary excretion rate was distinctly shorter (t
1/2
: 0.9±0.11 days) than that of total radioactivity in plasma. This, together with an observed increase of the polar fraction in urine from 35 up to 85%, which was accompanied by a decrease in plasma from 55 to 35%, suggests either tubular reabsorption or enterohepatic recirculation of lipophilic compounds. TLC-separation of the lipophilic fraction in urine revealed two previously unknown compounds of which the main congener was identified as 3-(3-oxo-7-methylsulfonyl-6, 17-dihydroxy-4-androsten-17-yl) propionic acid -lactone, as well as canrenone and the metabolites which have already been described (Karim and Brown, 1972; Karim et al., 1975). This metabolite represents the main lipophilic degradation product in urine within the first hours, whereas the 6-OH-7-methylsulfinylspirolactone leveled off and seemed to be an endexcretion product. For further characterisation, the polar fraction was subjected to acidic hydrolysis. The known metabolic pathways of spironolactone degradation are discussed.The paper includes parts of the thesis of G. Luszpinski 相似文献
55.
Athanassios Argiris Bruce E Brockstein Daniel J Haraf Kerstin M Stenson Bharat B Mittal Merrill S Kies Fred R Rosen Borko Jovanovic Everett E Vokes 《Clinical cancer research》2004,10(6):1956-1962
PURPOSE: The purpose of this retrospective analysis was to evaluate the emergence of second primary malignancies and the contribution of different causes of death to the outcome of patients with locoregionally advanced head and cancer receiving primary chemoradiotherapy. EXPERIMENTAL DESIGN: We studied 324 patients with stage IV squamous cell head and neck cancer who were enrolled on five consecutive multicenter Phase II studies of concurrent chemoradiotherapy. All of the regimens included concurrent 5-fluorouracil and hydroxyurea on an alternate week schedule with radiotherapy, either alone (FHX) or with cisplatin (C-FHX) or paclitaxel (T-FHX). The cumulative incidence of second primary tumors or death from any cause was estimated using methods of competing risk analysis. RESULTS: Median follow-up of surviving patients was 5.2 years (2-10.6 years). The 5-year overall survival and progression-free survival of the cohort were 46% and 65%, respectively. Causes of death and median time of occurrence were as follows: disease (n = 88; 1.5 years), treatment-associated acute or late complications (n = 30; 4 months), second primary tumors (n = 18; 3.5 years), comorbidities (n = 41; 1.9 years), and unknown (n = 20; 5.1 years). Predominant causes of death from comorbidities were cardiac and respiratory illnesses. Twenty-six patients (8%) developed a second primary tumor at a median time of 2.8 years (4 months to 10 years). The cumulative incidence of second primary tumors was 5%, 7%, and 13% at 3, 5, and 10 years, respectively. The most frequent site of second primaries was the lung (n = 13), followed by the esophagus (n = 3) and head and neck (n = 2) CONCLUSIONS: Patients with locoregionally advanced head and neck cancer treated with concurrent chemoradiotherapy are potentially curable but face significant risks of mortality from causes other than disease progression. Ameliorating toxicity, and implementing secondary screening and chemoprevention strategies are major goals in the management of head and neck cancer. 相似文献
56.
Phase II trial of ZD1839 in recurrent or metastatic squamous cell carcinoma of the head and neck. 总被引:11,自引:0,他引:11
Ezra E W Cohen Fred Rosen Walter M Stadler Wendy Recant Kerstin Stenson Dezheng Huo Everett E Vokes 《Journal of clinical oncology》2003,21(10):1980-1987
PURPOSE: The epidermal growth factor receptor (EGFR) is a mediator of squamous cell carcinoma of the head and neck (SCCHN) development. ZD1839 is an orally active, selective EGFR tyrosine kinase inhibitor. This phase II study sought to explore the activity, toxicity, and pharmacodynamics of ZD1839 in SCCHN. PATIENTS AND METHODS: Patients with recurrent or metastatic SCCHN were enrolled through the University of Chicago Phase II Consortium. Patients were allowed no more than one prior therapy for recurrent or metastatic disease and were treated with single-agent ZD1839 500 mg/d. Patient tumor biopsies were obtained and stained immunohistochemically for EGFR, extracellular signal-regulated kinase 1 (ERK1), and phosphorylated ERK1 (p-ERK). Study end points included response rate, time to progression, median survival, and inhibition of p-ERK. RESULTS: Fifty-two patients were enrolled (40 male and 12 female) with a median age of 59 years (range, 34 to 84 years). Fourteen patients received ZD1839 through a feeding tube. Half the cohort received ZD1839 as second-line therapy. Forty-seven patients were assessable for response, with an observed response rate of 10.6% and a disease control rate of 53%. Median time to progression and survival were 3.4 and 8.1 months, respectively. The only grade 3 toxicity encountered was diarrhea in three patients. Performance status and development of skin toxicity were found to be strong predictors of response, progression, and survival. Ten biopsy samples were assessable and revealed no significant change in EGFR or p-ERK expression with ZD1839 therapy. CONCLUSION: ZD1839 has single-agent activity and is well tolerated in refractory SCCHN. In contrast to other reports, development of skin toxicity was a statistically significant predictor of response and improved outcome. 相似文献
57.
Everett E Vokes Kerstin Stenson Fred R Rosen Merrill S Kies Alfred W Rademaker Mary Ellyn Witt Bruce E Brockstein Marcy A List Bing Bing Fung Louis Portugal Bharat B Mittal Harold Pelzer Ralph R Weichselbaum Daniel J Haraf 《Journal of clinical oncology》2003,21(2):320-326
PURPOSE: The paclitaxel, fluorouracil, and hydroxyurea regimen of paclitaxel, infusional fluorouracil, hydroxyurea, and twice-daily radiation therapy (TFHX) administered every other week has resulted in 3-year survival rates of 60% of stage IV patients. Locoregional and distant failure rates were 13% and 23%, respectively. To reduce distant failure rates, we added a brief course of induction chemotherapy to TFHX. PATIENTS AND METHODS: Sixty-nine patients received six weekly doses of carboplatin (AUC2) and paclitaxel (135 mg/m2) followed by five cycles of TFHX. RESULTS: Ninety-six percent had stage IV disease. Response to induction chemotherapy was partial response 52% and complete response (CR) 35%. Symptomatically, there was a significant reduction in mouth and throat pain. The most common grade 3 or 4 toxicity was neutropenia (36%). Best response following completion of TFHX was CR in 83%. Toxicities of TFHX consisted of grade 3 or 4 mucositis (74% and 2%) and dermatitis (47% and 14%). At a median follow-up of 28 months, locoregional or systemic disease progression were each noted in five patients. The overall 3-year progression-free survival was 80% (95% confidence interval [CI], 71% to 90%), and the 2- and 3-year overall survival rates were 77% (95% CI, 66% to 87%) and 70% (95% CI, 59% to 82%), respectively. At 12 months, five patients were completely feeding-tube dependent. CONCLUSION: Administration of carboplatin and paclitaxel before TFHX chemoradiotherapy results in high response activity and may decrease distant failure rates. Overall survival, progression, and organ preservation/functional outcome data support definitive evaluation of this approach. 相似文献
58.
59.
Athanasia Apsemidou Kerstin Rauwolf Athanasios Tragiannidis Angela Brentrup Manfred Schiborr Karsten Becker Martina Ahlmann Andreas H. Groll 《Pediatric blood & cancer》2019,66(4)
Bartonella henselae, the causative agent of cat‐scratch disease, has been recognized to be responsible for a broad range of clinical syndromes. We report the case of a patient with disseminated B. henselae infection mimicking Langerhans cell histiocytosis at presentation and its successful management with neurosurgery, prolonged antibacterial therapy, and observation. 相似文献
60.
Rita K. Schmutzler Bjrn Schmitz-Luhn Bettina Borisch Peter Devilee Diana Eccles Per Hall Judith Balmaa Stefania Boccia Peter Dabrock Günter Emons Wolfgang Gaissmaier Jacek Gronwald Stefanie Houwaart Stefan Huster Karin Kast Alexander Katalinic Sabine C. Linn Sowmiya Moorthie Paul Pharoah Kerstin Rhiem Tade Spranger Dominique Stoppa-Lyonnet Johannes Jozef Marten van Delden Marc van den Bulcke Christiane Woopen 《Breast care (Basel, Switzerland)》2022,17(2):208
BackgroundRisk-adjusted cancer screening and prevention is a promising and continuously emerging option for improving cancer prevention. It is driven by increasing knowledge of risk factors and the ability to determine them for individual risk prediction. However, there is a knowledge gap between evidence of increased risk and evidence of the effectiveness and efficiency of clinical preventive interventions based on increased risk. This gap is, in particular, aggravated by the extensive availability of genetic risk factor diagnostics, since the question of appropriate preventive measures immediately arises when an increased risk is identified. However, collecting proof of effective preventive measures, ideally by prospective randomized preventive studies, typically requires very long periods of time, while the knowledge about an increased risk immediately creates a high demand for action.SummaryTherefore, we propose a risk-adjusted prevention concept that is based on the best current evidence making needed and appropriate preventive measures available, and which is constantly evaluated through outcome evaluation, and continuously improved based on these results. We further discuss the structural and procedural requirements as well as legal and socioeconomical aspects relevant for the implementation of this concept. 相似文献