Biomedical subjects

E Quebe-Fehling

Publications and source records attributed to E Quebe-Fehling.

12 recordsLinked to original sources

PubMed2005

Hormone replacement therapy and breast density changes.

OBJECTIVES: To compare the incidence of increased breast density and tenderness in postmenopausal women associated with transdermal (Estalis/Combipatch), Novartis, Basel, Switzerland) and oral (Kliogest), Schering AG, Berlin, Germany) hormone replacement therapy (HRT). METHODS: A total of 202 postmenopausal women were randomized to transdermal or oral HRT. Mammograms obtained at study entry and after 1 year of treatment were assessed for percent breast density by means of the digital segmentation and thresholding technique. Breast tenderness was assessed at each study visit. RESULTS: The mean breast density by ANCOVA after adjusting for screening value at study end was significantly lower for women using Estalis (38.4%, standard error 0.9%) compared with Kliogest (46.9%, standard error 1.5%) (p<0.0001). Significantly fewer women using transdermal HRT had an increase in mammographic breast density or breast tenderness compared to oral HRT. Of the women using transdermal HRT, 39.1% had no change in breast density compared to 15.7% for women using oral HRT. Only 4% of women using transdermal HRT had a marked increase in density (>25%) compared to 15.7% of women using oral HRT. Overall, 36.0% of patients in the transdermal group reported breast tenderness at some point during the 1-year study, compared with 57.6% in the oral HRT group (p=0.0002). CONCLUSION: Transdermal HRT use is associated with a significantly lower incidence of increased mammographic breast density and breast tenderness compared with oral HRT.

Administration, Cutaneous↗

PubMed2003

Comparative bioequivalence studies with Estradot and Menorest transdermal systems.

OBJECTIVES: To compare the relative bioavailability of Estradot, a small size, new generation estradiol transdermal system (ETS) to Menorest, in healthy postmenopausal women. METHODS: In two open-label, single center, randomized, crossover, bioequivalence studies, healthy postmenopausal women aged 40-65 years received treatment with all the test regimens. In Study 1 (single-dose study), patients wore 5 cm(2) (50 microg/day), 10 cm(2) (100 microg/day) Estradot and 29 cm(2) (100 microg/day) Menorest for 84 h. In Study 2 (multiple-dose study), patients wore a regimen of four consecutive treatments with a 5 cm(2) (50 microg/day) new generation patch, Estradot and a 14.5 cm(2) (50 microg/day) patch, Menorest. Blood samples were drawn at various time-points in both studies. Estradiol and estrone serum levels were determined by gas chromatography/mass spectrometry or radioimmunoassay methods. Skin irritation (erythema and edema), patch adherence and local skin reaction were assessed following patch removal. RESULTS: In Study 1, baseline-uncorrected C(max) for estradiol for Estradot 50 and 100 microg/day and Menorest 100 microg/day was 54.8, 106.2 and 101.6 pg/ml, respectively, and C(max) for estrone was 75.6, 97.0 and 98.3 pg/ml, respectively. In Study 2, the baseline-uncorrected mean maximum serum concentration (C(max)) for estradiol for Estradot 50 microg/day and Menorest 50 microg/day patches was 56.7 and 52.7 pg/ml, respectively, and C(max) for estrone was 41.7 and 41.3 pg/ml, respectively. No significant skin irritation was observed in either study, but Estradot caused less skin irritation than Menorest. CONCLUSIONS: Estradot produced comparable serum concentrations of estradiol and estrone and caused less skin irritation than Menorest.

Administration, Cutaneous↗

PubMed2002

Comparative study to evaluate skin irritation and adhesion of Estradot and Climara in healthy postmenopausal women.

OBJECTIVES: To compare the local tolerability, adhesion and estradiol delivery of a 5-cm(2) transdermal patch (Estradot), Novartis Pharmaceuticals, Basel, Switzerland) and a 12.5-cm(2) patch (Climara, Berlex Laboratories, Wayne, NJ, USA). METHODS: This was an open-label, randomized, intrapatient, comparative study. One hundred healthy postmenopausal women applied the 50 micro g/day 5-cm(2) patch and the 12.5-cm(2) patch concurrently for 7 days; safety and tolerability were assessed. Twelve women continued to apply the 5-cm(2) and 12.5-cm(2) patches separately for 7 days in a two-way cross-over study, to investigate the reproducibility of estradiol delivery. RESULTS: The proportion of subjects with a clinically significant erythema score was higher with the 12.5-cm(2) patch. The 5-cm(2) patch had a significantly lower incidence of very slight erythema than the larger patch (21.4% vs. 32.3%; p = 0.0028). Overall erythema scores were 0.22 and 0.41, respectively. More 5-cm(2) patches had > 90% adherence than the 12.5-cm(2) patches (87.5% vs. 82.0%, not significant) and fewer became detached (0.5% vs. 3.0%). Both the patches showed reproducible delivery of estradiol. CONCLUSION: The 5-cm(2) patch was associated with less skin irritation and better adherence than the 12.5-cm(2) patch, although the majority of the differences were not significant. The 5-cm(2) patch was well tolerated and showed reproducible estradiol delivery, as did the 12.5-cm(2) patch.

Adhesiveness↗

PubMed2001

Letrozole is more effective neoadjuvant endocrine therapy than tamoxifen for ErbB-1- and/or ErbB-2-positive, estrogen receptor-positive primary breast cancer: evidence from a phase III randomized trial.

PURPOSE: Expression of ErbB-1 and ErbB-2 (epidermal growth factor receptor and HER2/neu) in breast cancer may cause tamoxifen resistance, but not all studies concur. Additionally, the relationship between ErbB-1 and ErbB-2 expression and response to selective aromatase inhibitors is unknown. A neoadjuvant study for primary breast cancer that randomized treatment between letrozole and tamoxifen provided a context within which these issues could be addressed prospectively. PATIENTS AND METHODS: Postmenopausal patients with estrogen- and/or progesterone receptor-positive (ER+ and/or PgR+) primary breast cancer ineligible for breast-conserving surgery were randomly assigned to 4 months of neoadjuvant letrozole 2.5 mg daily or tamoxifen 20 mg daily in a double-blinded study. Immunohistochemistry (IHC) for ER and PgR was conducted on pretreatment biopsies and assessed by the Allred score. ErbB-1 and ErbB-2 IHC were assessed by intensity and completeness of membranous staining according to published criteria. RESULTS: For study biopsy-confirmed ER+ and/or PgR+ cases that received letrozole, 60% responded and 48% underwent successful breast-conserving surgery. The response to tamoxifen was inferior (41%, P =.004), and fewer patients underwent breast conservation (36%, P =.036). Differences in response rates between letrozole and tamoxifen were most marked for tumors that were positive for ErbB-1 and/or ErbB-2 and ER (88% v 21%, P =.0004). CONCLUSION: ER+, ErbB-1+, and/or ErbB-2+ primary breast cancer responded well to letrozole, but responses to tamoxifen were infrequent. This suggests that ErbB-1 and ErbB-2 signaling through ER is ligand-dependent and that the growth-promoting effects of these receptor tyrosine kinases on ER+ breast cancer can be inhibited by potent estrogen deprivation therapy.

Antineoplastic Agents↗

PubMed2001

Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: a pooled analysis of two randomized, controlled clinical trials.

PURPOSE: Two identical, concurrent, parallel, multicenter, randomized, double-blind, double-dummy trials were conducted to compare the efficacy and safety of zoledronic acid and pamidronate for treating hypercalcemia of malignancy (HCM). PATIENTS AND METHODS: Patients with moderate to severe HCM (corrected serum calcium [CSC] > or = 3.00 mmol/L [12.0 mg/dL]) were treated with a single dose of zoledronic acid (4 or 8 mg) via 5-minute infusion or pamidronate (90 mg) via 2-hour infusion. A protocol-specified pooled analysis of the two parallel trials was performed. Clinical end points included rate of complete response by day 10, response duration, and time to relapse. RESULTS: Two hundred eighty-seven patients were randomized and evaluated for safety; 275 were evaluated for efficacy. Both doses of zoledronic acid were superior to pamidronate in the treatment of HCM. The complete response rates by day 10 were 88.4% (P = .002), 86.7% (P = .015), and 69.7% for zoledronic acid 4 mg and 8 mg and pamidronate 90 mg, respectively. Normalization of CSC occurred by day 4 in approximately 50% of patients treated with zoledronic acid and in only 33.3% of the pamidronate-treated patients. The median duration of complete response favored zoledronic acid 4 and 8 mg over pamidronate 90 mg with response durations of 32, 43, and 18 days, respectively. CONCLUSION: Zoledronic acid is superior to pamidronate; 4 mg is the dose recommended for initial treatment of HCM and 8 mg for relapsed or refractory hypercalcemia.

Adult↗

PubMed1998

Efficacy and tolerability of formoterol in elderly patients with reversible obstructive airways disease.

This study has compared the efficacy and tolerability of formoterol (FORADIL) dry powder and salbutamol in elderly patients with reversible obstructive airways disease (ROAD). A total of 262 elderly outpatients with clinically stable ROAD participated in a multicentre, double-blind, parallel study. Patients were randomized in equal numbers to receive formoterol 12 micrograms b.i.d. formoterol 24 micrograms b.i.d. or salbutamol 400 micrograms q.i.d. for a 3 month period. All study drugs were inhaled through an Aeroliser device. Daily morning and evening peak expiratory flow (PEF) values, symptom scores and additional bronchodilator use were recorded by the patients throughout the study. Clinic assessment which included spirometry and PEF measurements was made at 4, 8 and 12 weeks. Morning and evening PEF values were significantly higher with both doses of formoterol compared with salbutamol. This difference was statistically significant both for the overall study period and during the week preceding each of the clinic visits (4, 8 and 12 weeks). There was no significant difference for the two doses of formoterol with respect to PEF values. The FEV1 and FVC values between the three treatment groups were similar. The daily use of rescue medication was significantly lower for the formoterol 24 micrograms group compared with the salbutamol group. The percentage of patients rating the therapeutic effect as 'very good' was significantly higher for formoterol: 41% on 12 micrograms; 34% on 24 micrograms; 19% on salbutamol. All treatments were well tolerated. This study demonstrates that formoterol 12 micrograms and 24 micrograms b.i.d. by dry powder inhalation are equally effective and are both significantly superior to salbutamol 400 micrograms q.i.d. in the treatment of ROAD in the elderly.

Administration, Inhalation↗

PubMed1998

A 6-month comparison between formoterol and salmeterol in patients with reversible obstructive airways disease.

The aim of this randomized, open, parallel group study was to compare the clinical efficacy of formoterol dry powder capsule 12 micrograms b.i.d. and salmeterol dry powder 50 micrograms b.i.d. in the treatment of patients with reversible obstructive airways disease. The 6-month treatment was preceded by a 2 week run-in period. Morning pre-dose peak expiratory flow (PEF) during the last 7 days of treatment was the primary variable. Throughout the study, patients recorded morning and evening pre-dose PEF, use of rescue medication, respiratory symptoms and adverse events. Clinic visits were scheduled at monthly intervals. Of the 482 patients randomized (equal numbers in the two treatment groups), 428 completed the study. Four hundred and twenty-five patients were included in the efficacy analysis for the primary variable. For mean morning pre-dose PEF during the last 7 days of treatment, the 95% confidence interval (CI) for the treatment contrast formoterol minus salmeterol was included entirely in the pre-defined range of equivalence (CI limits = -8.69, +9.841 min-1). This was also the case for the morning PEF during the last week before each clinic visit. For mean evening pre-dose PEF, the estimated treatment contrasts showed a trend towards superiority of formoterol over salmeterol, which became statistically significant at 2, 3 and 4 months (P < 0.05; estimated contrasts 7.27, 10.45 and 10.511 min-1, respectively). No treatment group differences were found in use of rescue medication and respiratory symptom scores. The incidence of adverse events was similar in the two groups. These findings demonstrate that formoterol 12 micrograms b.i.d. and salmeterol 50 micrograms b.i.d., both formulated as dry powders, have similar long-term efficacy and safety profiles in patients with reversible obstructive airways disease.

Administration, Inhalation↗

PubMed1996

The duration of action of inhaled formoterol dry powder.

The duration of action of formoterol inhaled as a dry powder formulation is compared with placebo and a reference treatment of salbutamol dry powder in patients with bronchial asthma. This single-centre, double-blind, cross-over study recruited 23 outpatients with clinically stable asthma. These patients were treated with 12 micrograms formoterol, 400 micrograms salbutamol or placebo in a randomly allocated sequence, with at least 2 days between treatments. Forced expiratory volume in 1s of expiration (FEV1) was measured at specified time points from 15 min to 15 hours post-treatment. Formoterol produced significantly higher values of FEV1 at the primary endpoint of 12 hours compared with placebo and salbutamol. No differences between FEV1 values were seen for the active treatments of formoterol and salbutamol for the first 5 hours post-inhalation. Formoterol was significantly superior to placebo at all time points, whereas salbutamol was significantly superior to placebo for the first 5 hours. This study demonstrates that formoterol, when given as a dry powder inhalation, has a significantly longer duration of acute bronchodilator action than 400micrograms salbutamol inhaled as a dry powder. The duration of action of formoterol of at least 12 hours seen in this study is at least as long as that reported following administration from a metered dose inhaler (MDI) at the same dose level. The study also demonstrates that 12micrograms formoterol dry powder is well tolerated by patients.

Administration, Inhalation↗

PubMed1994

[Prospective study of the incidence and prevalence of ulcerative colitis in a large urban population in Germany (western Ruhr area)].

A prospective epidemiological study of the incidence and prevalence of ulcerative colitis was conducted from 1980 to the end of 1984. The population at risk comprised 1.6 million inhabitants in the four industrial cities Essen, Duisburg, Mülheim and Oberhausen of the western Ruhr-area. All 35 hospitals of the area with 79 departments of internal medicine, surgery and pediatrics with in- and outpatients took part in the study. 225 patients with substantial ulcerative colitis (excluded proctitis) were newly diagnosed during the study period (129 men, 96 women); patients suffering only from ulcerative proctitis were not included. The mean incidence was 2.9 new cases per 100,000 inhabitants and year ranging from 2.3 to 3.7 without significant difference between these 5 years. Incidence figures were somewhat higher for men (3.5) than for women (2.4) and this difference was significant (p < 0.05). The age- and sex-adjusted incidence was found to have a broad range for both sexes between 20 and 65 years of age without a high incidence-peak in young adults or a second peak later in life. Additionally all formerly diagnosed cases of ulcerative colitis were registered during this time period and the hospital archives were looked backward for prevalent cases til 1975 retrospectively. From all these cases the prevalence of ulcerative colitis at December 31, 1984 was calculated for 27.3 patients per 100,000 inhabitants (n = 417) similarly with a significant preponderance of men against women (31.1 vs. 22.1 per 100,000 inhabitants, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

[Postprandial serum bile acid level and 75SeHCAT retention in diagnosis of bile acid malabsorption syndrome. A comparative study].

Postprandial serum bile acids (expressed as integrated bile acid response [IR]) after a standardized test meal were compared with 75SeHCAT retention, measured in a whole body counter, in healthy controls (n = 20), in 44 patients with ileal disease or resection and in 23 patients with colitis without ileal involvement. In the controls the IR after 180 min was 736 +/- 186 mumol x min x 1(-1) (mean +/- standard deviation), the 75SeHCAT retention 31 +/- 9%. 80% of the patients with ileal disease or resection had a decreased 75SeHCAT retention, indicating bile acid malabsorption, but only 59% had a diminished IR. One of the 23 patients with colitis and radiologically normal ileum had a decreased 75SeHCAT retention but a normal IR, reflecting a dysfunction of the morphologically normal ileum. The characteristics of the two tests are: 75SeHCAT retention test: sensitivity 80%, specificity 98%, accuracy 89%; postprandial serum bile acids: sensitivity 64%, specificity 74%, accuracy 69%. With respect to chronic inflammatory bowel disease the positive predictive value of the 75SeHCAT retention test is 1.0%, for postprandial serum bile acids 0.1%, whereas the negative predictive values amount to 99% for both tests. Thus 75SeHCAT retention is more reliable in detecting bile acid malabsorption than the determination of postprandial serum bile acids, although both tests are not usefull for screening the population for ileal disease.

Adolescent↗

PubMed1989

Clinical relapse of Crohn's disease under standardized conservative treatment and after excisional surgery.

The course of 205 patients with Crohn's disease at one gastroenterological center was studied in patients with conservative drug treatment or with operative management of their disease. The decision for one or the other treatment regimen was made by an interdisciplinary team of gastroenterologists and surgeons. Using life-table analysis the 205 patients showed a clinical relapse rate of 27% after two years and 38% after four years. Clinical relapse was defined by a Crohn's disease activity index (CDAI) over 150. We used a standardized drug regimen of salazosulfapyridin and prednisone; the indication for excisional surgery was limited strictly to life-threatening situations, absolute nonresponse to drug treatment, and severe intervisceral fistulae. The operated patients (N = 93) had a lower relapse rate than the patients treated conservatively (N = 112), 20% and 51%, respectively, after four years. There were considerably fewer relapses in Crohn's colitis patients who were operated upon than in conservatively treated patients (18% versus 67% after four years); the same was found for ileocolitis (20% vs 49% after four years), but there was no difference between the treatment groups in ileitis (25-30% relapses for both after four years). In addition the patients with Crohn's disease of the colon had a more favorable course after resection with respect to symptoms, clinical and laboratory findings, and CDAI in remission. This paper gives data only for surgery in severe clinical situations and does not give a rationale for earlier surgery. This problem should now be studied in a randomized trial.

Adult↗

PubMed1985

[Function tests of the lower small intestine with 75selenium-labeled homotaurocholic acid in Crohn disease and resections of the small intestine].

UNLABELLED: Faecal excretion of bile acids was investigated using 75Se-homotaurocholic acid (75SeHCAT) in a total of 75 patients: 9 with irritable colon, 58 with Crohn's disease and 8 with small-bowel resection due to various indications but without Crohn's disease. Bile acid malabsorption, taken as a pathological bile acid retention of less than 19%, was found present in 43 patients with diseased terminal ileum or with more than 20 cm resection of this organ, except in one case (12 cm). On the other hand a normal bile acid retention (21 to 27%) was found in 29 of 72 patients (including 9 patients with irritable colon) who showed either no radiologically detectable lesion of the ileum (n = 21) or changes involving an extension of up to 30 cm (inflammation or resection) in the terminal ileum (n = 8), with the exception of one case (50 cm). Three patients had a raised bile acid excretion contrary to clinical expectation: they had colitis Crohn without radiologically detectable involvement of the small intestine. Thus using the 75SeHCAT-retention test it seems possible to recognize functional disorders in diseased segments of the bowel before the appearance of radiologically detectable changes. CONCLUSION: 75SeHCAT is a suitable substance for investigations on the function of the lower small intestine.

Adolescent↗