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O Camara

Publications and source records attributed to O Camara.

12 recordsLinked to original sources

Phase II study of weekly docetaxel in patients with recurrent or metastatic endometrial cancer: AGO Uterus-4.

OBJECTIVE: The aim of this phase II multicenter study was to evaluate the safety, toxicity and efficacy of docetaxel administered weekly as first line chemotherapy in patients with recurrent or metastatic endometrial cancer. PATIENTS AND METHODS: Thirty five patients with recurrent or metastatic endometrial cancer without previous chemotherapy were enrolled to receive three 6-week cycles of docetaxel 35 mg/m(2)/week with 2-week breaks between the cycles. Therapy response was evaluated after every 6-week cycle, and therapy was continued in case of at least stable disease. Final therapy response was evaluated after three 6-week cycles of docetaxel. RESULTS: Thirty five patients with a median age of 65 years (range, 37-80 years) were evaluable for toxicity assessment, one patient presented with severe anaphylactic reaction during the second application of docetaxel and therapy was discontinued. Subsequently, this patient received doxorubicin-cisplatin combination chemotherapy. Another patient was initially documented with uterine papillary serous cancer but secondarily confirmed as uterine carcinosarcoma. Thus, 33 patients were assessable for response. Overall response rate was 21% (3 PR and 4 CR). Three patients showed stable disease. Median TTP and OAS were 12 weeks and 43 weeks, respectively. Therapy with weekly docetaxel was well tolerated; in particular, no grade 3 or 4 hematological toxicities occurred. CONCLUSION: Docetaxel weekly has a favorable toxicity profile, is well tolerated and shows encouraging activity in patients with advanced endometrial cancer.

Adult↗

Cardiac function estimation from MRI using a heart model and data assimilation: advances and difficulties.

In this paper, we present a framework to estimate local ventricular myocardium contractility using clinical MRI, a heart model and data assimilation. First, we build a generic anatomical model of the ventricles including muscle fibre orientations and anatomical subdivisions. Then, this model is deformed to fit a clinical MRI, using a semi-automatic fuzzy segmentation, an affine registration method and a local deformable biomechanical model. An electromechanical model of the heart is then presented and simulated. Finally, a data assimilation procedure is described, and applied to this model. Data assimilation makes it possible to estimate local contractility from given displacements. Presented results on fitting to patient-specific anatomy and assimilation with simulated data are very promising. Current work on model calibration and estimation of patient parameters opens up possibilities to apply this framework in a clinical environment.

Adult↗

Biweekly pegylated liposomal doxorubicin in patients with relapsed ovarian cancer: results of a multicenter phase-II trial.

BACKGROUND: The obvious benefit of pegylated liposomal doxorubicin (PLD) for tumour control in recurrent ovarian cancer is frequently offset by severe palmar-plantar erythrodysesthesia (PPE). There is evidence that dose reduction from 50 to 40 mg/m(2) reduces the incidence of PPE without compromising cytotoxic activity. We set out to investigate whether biweekly application further improves the therapeutic index of PLD. PATIENTS AND METHODS: Patients with recurrent ovarian cancer after surgery and adjuvant chemotherapy with platinum and taxane compounds were eligible to participate in this multi-institutional phase II study. PLD was administered at a dose of 20 mg/m(2) every two weeks. Eligible patients had ECOG performance status of < or =2, and sufficient organ function. We employed an optimized two-stage design to test the hypothesis that biweekly application of PLD reduces the frequency of grade III and IV PPE from 25% to 10%. Response and survival were addressed descriptively. RESULTS: Between October 2001 and February 2004, 64 patients with median age of 59 (range 38-81) years were recruited onto this trial. We evaluated 553 (median 7, range 1-25) courses of PLD treatment. Most patients were in their third or fourth line of chemotherapy. PPE was noted in 30 patients (47.6%), but only three participants progressed to grade 3 severity (4.7%, 95% confidence interval 1.0-13.1%). Partial response, stable disease, and tumour progression were observed in 5, 13, and 24 patients, respectively. Median overall and progression-free survival were 18.2 (range, 1.4-34.0) and 4.3 (range 0.5-22.3) months. CONCLUSIONS: Biweekly PLD may reduce the incidence of PPE while retaining efficacy in relapsed ovarian cancer. Our data support the need for a randomized trial to strengthen these assumptions.

Adult↗

Aberrant methylation of the Wnt antagonist SFRP1 in breast cancer is associated with unfavourable prognosis.

The canonical Wnt signalling pathway plays a key role during embryogenesis and defects in this pathway have been implicated in the pathogenesis of various types of tumours, including breast cancer. The gene for secreted frizzled-related protein 1 (SFRP1) encodes a soluble Wnt antagonist and is located in a chromosomal region (8p22-p12) that is often deleted in breast cancer. In colon, lung, bladder and ovarian cancer SFRP1 expression is frequently inactivated by promoter methylation. We have previously shown that loss of SFRP1 protein expression is a common event in breast tumours that is associated with poor overall survival in patients with early breast cancer. To investigate the cause of SFRP1 loss in breast cancer, we performed mutation, methylation and expression analysis in human primary breast tumours and breast cell lines. No SFRP1 gene mutations were detected. However, promoter methylation of SFRP1 was frequently observed in both primary breast cancer (61%, n=130) and cell lines analysed by methylation-specific polymerase chain reaction (MSP). We found a tight correlation (P<0.001) between methylation and loss of SFRP1 expression in primary breast cancer tissue. SFRP1 expression was restored after treatment of tumour cell lines with the demethylating agent 5-aza-2'-deoxycytidine. Most interestingly, SFRP1 promoter methylation was an independent factor for adverse patient survival in Kaplan-Meier analysis. Our results indicate that promoter hypermethylation is the predominant mechanism of SFRP1 gene silencing in human breast cancer and that SFRP1 gene inactivation in breast cancer is associated with unfavourable prognosis.

Adult↗

Simulation of cardiac pathologies using an electromechanical biventricular model and XMR interventional imaging.

Simulating cardiac electromechanical activity is of great interest for a better understanding of pathologies and for therapy planning. Design and validation of such models is difficult due to the lack of clinical data. XMR systems are a new type of interventional facility in which patients can be rapidly transferred between X-ray and MR systems. Our goal is to design and validate an electromechanical model of the myocardium using XMR imaging. The proposed model is computationally fast and uses clinically observable parameters. We present the integration of anatomy, electrophysiology, and motion from patient data. Pathologies are introduced in the model and simulations are compared to measured data. Initial qualitative comparison on the two clinical cases presented is encouraging. Once fully validated, these models will make it possible to simulate different interventional strategies.

Algorithms↗

A phase II study of topotecan plus gemcitabine in the treatment of patients with relapsed ovarian cancer after failure of first-line chemotherapy.

BACKGROUND: Second-line chemotherapy for patients with ovarian cancer who failed platinum and paclitaxel treatment remains a therapeutic challenge. We investigated the toxicity profile and therapeutic efficacy of a novel combination regimen, topotecan plus gemcitabine, in a clinical phase II study. PATIENTS AND METHODS: Women with relapsed epithelial ovarian cancer after platinum and paclitaxel treatment were eligible to participate in this trial. Topotecan was given at an initial dose of 0.5 mg/m(2) daily (days 1-5), combined with gemcitabine 800 mg/m(2) and 600 mg/m(2) on days 1 and 8, respectively. Precluding good tolerability, this protocol facilitated subsequent dose increases of topotecan up to 1.0 mg/m(2). The primary objective was to determine the dose-limiting toxicity, whereas secondary objectives comprised measurable and CA-125 response rates, disease-free and overall survival. RESULTS: The twenty-one patients (median age 57 years, range 37-70 years) who were allocated to this trial received a total of 94 courses of chemotherapy. Median follow-up was 20.5 months. Topotecan dosage could be escalated to 0.75 mg/m(2) in nine patients and 1 mg/m(2) in another two patients. Dose reduction was not necessary in any case. There were no episodes of neutropenic fever, sepsis or chemotherapy-related fatalities. Only one patient developed CTC grade 4 leukopenia after the first treatment cycle, whereas three patients showed grade 3/4 anaemia. Five patients experienced thrombocytopenia grade 4 without clinical sequelae. Non-hematological toxicities were mild and rare. Eleven patients could be evaluated for clinical tumour response, with three complete, and four partial remissions. Two patients each had stable and progressive diseases. The median progression-free survival rate was 8.8 months [95% confidence interval (CI) 6.3-13.4 months]. The median overall survival rate was 21.1 months (95% CI 14.8-22.1 months). CONCLUSIONS: Topotecan combined with gemcitabine has a favourable toxicity profile and encouraging efficacy in patients with recurrent ovarian cancer.

Adult↗

Local cost sharing in Bamako Initiative systems in Benin and Guinea: assuring the financial viability of primary health care.

The fourth in a series of five, this article presents and analyses data on cost recovery and community cost-sharing, two key aspects of the Bamako Initiative which have been implemented in Benin and Guinea since 1986. The data come from approximately 400 health centres and result from the six-monthly monitoring sessions conducted from 1989 to 1993. Community involvement in the financing of local operating costs in the two national scale programmes is also described. In Benin and Guinea, a user fee system generates the community financed revenue with the aim of covering local operating costs including drugs. Health worker salaries remain the responsibility of the government and donor funding covers vaccine and investment costs. Village health committees manage and control resources and revenue. The community is also involved in decision making, strategy definition and quality control. In Benin in 1993, community financing revenue amounted to about US$0.6 per capita per year and generally covered all local recurrent non salary costs except vaccines and left a surplus. Although total costs and revenues were slightly lower in Guinea for the same period, over-all user fee revenue (around US$0.3 per capita per year) covered local recurrent costs (not including salaries or vaccines). A comparison of costs and revenue between regions and individual health centres revealed important differences in cost recovery ratios. In Benin, some centres recovered more than twice the local costs targeted for community financing. Twenty-five per cent of centres in Guinea did not manage to cover their designated local recurrent costs. The longitudinal analysis showed that the level of cost recovery remained stable over time even as preventive care (and especially EPI) coverage rose significantly. To better understand the most important characteristics affecting cost recovery levels, best performing health centres in terms of cost-recovery levels in 1993 were compared to worst performing centres. This analysis showed that the size of the target population of the health centre is a key determinant of cost-recovery in both countries. In addition, in Guinea the utilization of curative care linked to geographical access and in Benin the average revenue per case linked to the number of deliveries proved to be additional factors of importance. In best performing centres, financial viability improved over time in both countries between 1990 and 1993. Finally, the implications of these conclusions for the planning of health centre revitalization in West Africa are discussed.

Benin↗

Affordability, cost-effectiveness and efficiency of primary health care: the Bamako Initiative experience in Benin and Guinea.

Since 1986 two West African countries, Benin and Guinea, have been actively reorganizing their peripheral health systems according to strategies subsequently called the "Bamako Initiative". Two preceding articles described the strategies implemented and the increased effectiveness of primary health care (PHC) witnessed over a period of six years. This article presents an analysis of cost and coverage data from biannual monitoring sessions between 1988 and 1993 in approximately 200 health centres in Benin and 214 in Guinea. In order to assess affordability, the total and per capita recurrent costs for operational health centres are analysed and then compared. The cost analysis reveals a mean total cost per health centre per year of slightly over US+11,000 in Benin and nearly US+9,000 in Guinea. The median cost per capita per year is approximately US+1.0 in Benin and between US+0.60 and US+0.80 in Guinea. Comparisons of these costs between regions, health centres and over time (as coverage levels evolved) show very little variation in either country. Cost-effectiveness is estimated by allocating these costs to immunization, antenatal and curative care and comparing them to the coverage achieved with these interventions. First, the cost-effectiveness of the Bamako Initiative (BI) system as a whole is analysed. The cost per fully vaccinated child is calculated at US+10.9 in Benin and US+8.8 in Guinea. The cost per woman receiving at least three antenatal visits is US+7 in Benin and US+4.7 in Guinea. For curative care, cost per full treatment is US+1.6 in Benin and half this amount in Guinea. Cost-effectiveness is variable between regions, health centres reveals that these differences in cost-effectiveness are mainly caused by the coverage levels achieved, since total costs are relatively stable. Finally the efficiency of drug management and prescriptions as well as of outreach for the expanded programme of immunizations (EPI) is estimated by relating specific drug and outreach activities costs to the number of beneficiaries. The average cost of drugs per treatment is around US+0.5 in Benin and around US+0.3 in Guinea. Cost analysis of outreach activities undertaken for EPI in Guinea revealed a similar average cost per child completely vaccinated for health centres with different intensities of outreach (approximately US+10) and an additional cost per child vaccinated attributable to outreach of US+1-2.

Benin↗

[Possibilities and limits of mammography with special reference to breast carcinoma--a comparison of clinical, mammography and histologic diagnoses].

This paper informs about the diagnostical accuracy of clinical examination and mammography at the women's Hospital of the Städtische Klinikum Zwickau from 1989 to 1992 when pathological changes of breasts are diagnosed. A total of 508 diagnostical biopsies was performed during this study period. The histological examination resulted in 276 benign breast lesions and in 232 breast cancers. In 432 cases there was a lump palpable in the breast that was noticed at first by more than 60% of women themselves. 288 (56.7%) correct and 220 (43.3%) false diagnoses were established following the clinical examination. This resulted in a sensitivity of 100% with a specificity of 20.3% and an overall accuracy of 56.7%. However, with the help of mammography 386 (76.6%) pathological changes of breasts were found to be correct. 118 mammograms proved to be false. Out of these 90 (17.8%) had a false-positive diagnosis and 28 (5.6%) a false-negative one. The overall accuracy of mammography was 76.6% (sensitivity 87.9%, specificity 67%).

Biopsy↗

Pelviscopic Survey in Eastern Germany

In 1994 a survey conducted in eastern Germany reported 27,595 pelviscopies from 101 clinics and 3307 hysteroscopies from 53 clinics. Clinics reported 129 serious complications by pelviscopy that required laparotomy or second-look laparoscopy. The complication rate was 4.6/1000 procedures. One death occurred during pelviscopy and none during hysteroscopy. The trend to perform endoscopy was 71.7% for pelviscopy and 80.5% for hysteroscopy, which is continuously increasing.

Journal Article↗