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Biomedical subjects

A Casado

Publications and source records attributed to A Casado.

At least 19 recordsLinked to original sources
PubMed2006

Phase I/II trial of doxorubicin and fixed dose-rate infusion gemcitabine in advanced soft tissue sarcomas: a GEIS study.

The aim of the study was to determine the dose-limiting toxicity and maximum tolerated dose of a first-line combination of doxorubicin and gemcitabine in adult patients with advanced soft tissue sarcomas and to explore its activity and toxicity, and the presence of possible interactions between these agents. Patients with measurable disease were initially treated with doxorubicin 60 mg m(-2) by i.v. bolus on day 1 followed by gemcitabine at 800 mg m(-2) over 80 min on days 1 and 8, every 21 days. Concentrations of gemcitabine and 2',2'-difluorodeoxyuridine in plasma, and gemcitabine triphosphate levels in peripheral blood mononuclear cells were determined during 8 h after the start of gemcitabine infusion. Myelosuppression and stomatitis were limiting toxicities, and the initial dose level was applied for the Phase II trial, where grade 3-4 granulocytopenia occurred in 70% of patients, grade 3 stomatitis in 46% and febrile neutropenia in 20%. Objective activity in 36 patients was 22% (95% CI: 9-35%), and a 50% remission rate was noted in leiomyosarcomas. Administration of doxorubicin preceding gemcitabine significantly reduced the synthesis of gemcitabine triphosphate. Clinical activity, similar to that of single-agent doxorubicin, and the toxicity encountered do not justify further studies with this schedule of administration.

Adult↗
PubMed2005

Randomized phase II trial of carboplatin versus paclitaxel and carboplatin in platinum-sensitive recurrent advanced ovarian carcinoma: a GEICO (Grupo Espanol de Investigacion en Cancer de Ovario) study.

BACKGROUND: The aim of this study was to determine whether the response rate for the paclitaxel-carboplatin combination is superior to carboplatin alone in the treatment of patients with platinum-sensitive recurrent ovarian carcinoma. PATIENTS AND METHODS: Patients with recurrent ovarian carcinoma, 6 months after treatment with a platinum-based regimen and with no more than two previous chemotherapy lines, were randomized to receive carboplatin area under the curve (AUC) 5 (arm A) or paclitaxel 175 mg/m(2) + carboplatin AUC 5 (arm B). The primary end point was objective response, following a 'pick up the winner' design. Secondary end points included time to progression (TTP), overall survival, tolerability and quality of life (QoL). RESULTS: Eighty-one patients were randomized and included in the intention-to-treat analysis. The response rate in arm B was 75.6% [26.8% complete response (CR) + 48.8% partial response (PR)] [95% confidence interval (CI) 59.7% to 87.6%] and 50% in arm A (20% CR + 30% PR) (95% CI 33.8% to 66.2%). No significant differences were observed in grade 3-4 hematological toxicity. Conversely, mucositis, myalgia/arthralgia and peripheral neurophaty were more frequent in arm B. Median TTP was 49.1 weeks in arm B (95% CI 36.9-61.3) and 33.7 weeks in arm A (95% CI 25.8-41.5). No significant differences were found in the QoL analysis. CONCLUSIONS: Paclitaxel-carboplatin combination is a tolerable regimen with a higher response rate than carboplatin monotherapy in platinum-sensitive recurrent ovarian carcinoma.

Adult↗
PubMed2004

Allele-frequency determination of BsmI and FokI polymorphisms of the VDR gene by quantitative real-time PCR (QRT-PCR) in pooled genomic DNA samples.

The vdr gene is a candidate for osteoporosis susceptibility, with conflicting results in association studies. We have designed and optimized an individual allele-specific and DNA pooling PCR-based methodology to quantitate BsmI and FokI polymorphisms of the vdr gene and studied single-nucleotide polymorphisms (SNPs) from pooled DNA samples. The allele frequency in DNA pooling experiments has been analyzed by kinetic PCR: quantitative real-time PCR (QRT-PCR). A Spanish cohort of 225 healthy postmenopausal women was studied. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DEXA) and quantitative ultrasound calcaneous densitometry. Allele-specific PCR amplification of BsmI and FokI genes showed full concordance with the PCR-RFLP approach. The prevalence of the three BsmI VDR genotypes was 19.1, 44.9 and 36.0% for BB, Bb and bb, respectively. In the case of the FokI locus, the prevalence of genotypes was 40.4, 48.0 and 11.6% for FF, Ff and ff, respectively. No positive correlation was found between polymorphism and BMD. The DNA pooling procedure was validated. No differences were found in allele frequencies and T-score data obtained using the high throughput DNA pooling approach, as compared to known individual frequencies. In our hands, this is a very useful approach to study quantitative (thus polygenic) traits like osteoporosis susceptibility.

Absorptiometry, Photon↗
PubMed2004

Psychometric validation of a generic health-related quality of life measure (EQ-5D) in a sample of schizophrenic patients.

OBJECTIVE: The aim of this study was to evaluate the construct validity of a generic health related quality of life (HRQOL) instrument - the EQ-5D - in a sample of schizophrenic patients receiving antipsychotic treatment. RESEARCH DESIGN AND METHODS: A total of 2128 schizophrenic patients treated with olanzapine, 417 treated with risperidone, and 112 with haloperidol responded to the EQ-5D. The study also assessed the effect of patient age, gender, and co-morbidity variables on patient's HRQOL Main outcomes measures: EQ-5D scores at the start of treatment and after 3 and 6 months of therapy were compared with results from the Clinical Global Impression (CGI) severity of illness scale and the (GAF) scale. The effect of antipsychotics and sociodemographic variables on patient's HRQOL over time was tested through a three-factor doubly multivariate repeated measures MANCOVA. RESULTS: High scores in the GAF scale and low scores in the CGI were linked with high scores on the EQ-5D scale. The correlational effects observed between the EQ-5D and the clinical indices ranged from 0.33 to 0.54. A significant effect of 'visit time' as well as an interaction of 'visit time' x drug, 'visit time' x gender, and 'visit time' x co-morbidity was observed. CONCLUSIONS: Results suggest the EQ-5D is a valid instrument capable of detecting HRQOL differences between schizophrenic patients with different degrees of severity of illness.

Antipsychotic Agents↗
PubMed2003

Cost-minimisation analysis of pegylated liposomal doxorubicin hydrochloride versus topotecan in the treatment of patients with recurrent epithelial ovarian cancer in Spain.

The study consisted of a cost-minimisation analysis since the findings from a multicentre randomised phase III trial showed that pegylated liposomal doxorubicin hydrochloride was at least as efficacious as topotecan. An economic model from the Spanish hospitals perspective was constructed to compare the costs derived from the treatment using both drugs in patients with recurrent epithelial ovarian cancer who failed a first-line platinum-containing regimen. The cost evaluation included direct medical costs: drug, drug administration and costs of managing adverse events. Estimation of resources used in managing adverse events was made retrospectively through an expert panel. Results obtained per patient were: cost of drug and administration, 8647.70 euros for pegylated liposomal doxorubicin hydrochloride and 8519.94 euros for topotecan, while cost of managing adverse events was 967.02 euros in the pegylated liposomal doxorubicin hydrochloride arm and 3304.75 euros for topotecan. The total cost per patient was therefore estimated to be 9614.72 euros for pegylated liposomal doxorubicin hydrochloride and 11 824.69 euros for topotecan, showing that pegylated liposomal doxorubicin hydrochloride produces a cost saving of 2209.97 euros per patient in comparison to topotecan. Sensitivity analyses verified the robustness of the results. These findings suggest that pegylated liposomal doxorubicin hydrochloride is an efficient therapy and can be used as a cost-saving option for treatment of patients with recurrent epithelial ovarian cancer who have failed a first-line platinum-containing regimen.

Antineoplastic Agents↗
PubMed2003

Validation of the Spanish version of the Liver Disease Quality of Life questionnaire in transplant patients.

OBJECTIVE: Our aim was to validate Spanish and Catalan versions of the Liver Disease Quality of Life questionnaire (LDQOL) for use in liver transplant patients. METHODS: The LDQOL consists of the SF-36 generic measure of health-related quality of life (HRQOL) and 12 disease-specific dimensions for liver disease patients. The Spanish and Catalan versions of the questionnaire were administered to 138 patients with a liver transplant. Cronbach's alpha coefficients (CAC) were used to test the internal consistency of disease-specific scales. Test-retest reliability was calculated using the Intraclass Correlation Coefficient (ICC) in a sub-group of 41 patients who completed the questionnaire on two occasions 1 to 2 weeks apart. Validity was analysed by determining the instrument's capacity to discriminate between patient groups classified according to years since transplant, disease etiology, and symptom severity. Ceiling and floor effects were also calculated. RESULTS: Internal consistency in the disease-specific dimensions was acceptable or good (CACs 0.60-0.97), as was test-retest reliability in all dimensions (statistically significant CCIs of 0.62-0.89), except the symptoms dimension (CCI=0.46, P<.05). Few differences were found in disease-specific dimension scores between patients classified according to number of years since transplant or etiology, but differences were found in some dimensions according to symptom severity. Moderate to severe ceiling effects were found in several disease-specific dimensions. CONCLUSIONS: The Spanish and Catalan versions of the LDQOL may be useful for measuring HRQOL in this population, though it will be important to investigate further the instrument's sensitivity to change.

Activities of Daily Living↗
PubMed2003

Sibutramine decreases body weight gain and increases energy expenditure in obese Zucker rats without changes in NPY and orexins.

The aim of the present work was to describe the effects of sibutramine on body weight and adiposity and to establish the potential involvement of neuropeptide Y (NPY) and orexins in the anorectic action of this drug. Male obese Zucker rats were daily administered with sibutramine (10 mg/kg, intraperitoneal) for two weeks. Carcass composition was assessed using the official methods of the Association of Official Analytical Chemists. Total body oxygen consumption was measured daily for 60 min before sibutramine or saline injection and for 30 min (from 60 to 90 min) after drug or saline injection. Hypothalamic arcuate and paraventricular nuclei, and the lateral hypothalamic area were immunostained for NPY, orexin A and orexin B. Commercial kits were used for serum determinations. Reductions in body weight and adipose tissue weights were observed after sibutramine treatment in obese Zucker rats. No changes in NPY immunostaining in the arcuate and paraventricular nuclei were found. Orexin A and orexin B immunostaining was not modified in the lateral hypothalamic area in treated rats. The reduction in body weight and adiposity induced by sibutramine was achieved by both a reduction in food intake and an increase in energy expenditure. NPY and orexins do not seem to be involved in the anorectic effect of sibutramine.

Adipose Tissue↗
PubMed2003

Doxorubicin in combination with fluorouracil and cyclophosphamide (i.v. FAC regimen, day 1, 21) versus methotrexate in combination with fluorouracil and cyclophosphamide (i.v. CMF regimen, day 1, 21) as adjuvant chemotherapy for operable breast cancer: a study by the GEICAM group.

BACKGROUND: The purpose of this study was to determine the relative efficacy of doxorubicin versus methotrexate in combination with intravenous cyclophosphamide and 5-fluorouracil (FAC versus CMF) as adjuvant chemotherapy for operable breast cancer. PATIENTS AND METHODS: Over a 4-year period, 985 women undergoing curative surgery for breast cancer (T1-3 N0-2 M0, stage I-IIIA, UICC) from nine hospitals were stratified with respect to axillary node involvement (node positive versus node negative) and randomized to receive either FAC (500/50/500/m(2)) every 3 weeks for six cycles or CMF (600/60/600/m(2)) every 3 weeks for six cycles. RESULTS: The relative dose intensities of FAC and CMF were 87% and 85% of planned doses, respectively. Unadjusted data indicated a non-significant trend towards better results with FAC. In the prospectively formed subset of node-negative patients, disease-free survival and overall survival were statistically superior in the FAC treatment arm (P = 0.041 and 0.034, respectively), but this advantage was not seen in the subset of node-positive patients, probably because of a difference in the percentage of patients with four or more positive nodes. Adjusting data for size of treatment effect and potential interactions (number of positive nodes, tumor size, treatment center), the overall relative risk (RR) of disease recurrence and death were significantly lower with FAC treatment (RR 1.2, P = 0.03, and RR 1.3, P = 0.05, respectively). This result was mainly due to the difference observed in the node-negative patient population. Toxicity was mild: FAC induced more alopecia, emesis, mucositis and cardiotoxicity; this last was of clinical concern, but was infrequent and manageable. CMF induced more conjunctivitis and weight gain. There were no toxic deaths. CONCLUSIONS: Doxorubicin in combination with day 1 i.v. cyclophosphamide and 5-fluorouracil is superior to methotrexate in combination with day 1 i.v. cyclophosphamide and 5-fluorouracil as adjuvant chemotherapy for operable breast cancer. A treatment effect is particularly evident in the node-negative patients. Although the clinical toxicity of FAC is greater than that of CMF, the levels were manageable and clinically acceptable.

Adolescent↗
PubMed2003

Phase II study of pemetrexed in breast cancer patients pretreated with anthracyclines.

BACKGROUND: To assess antitumor activity and toxicity of pemetrexed in metastatic breast cancer (MBC) patients previously treated with anthracyclines. PATIENTS AND METHODS: Seventy-seven MBC patients from 12 European institutions were entered into the study. Seventy-two patients were considered evaluable for response and toxicity. Forty-two patients were classified as anthracycline-failure (relapse >30 days after completion of a prior anthracycline regimen) and 30 as anthracycline-refractory (progression within 30 days after anthracycline therapy). Pemetrexed 600 mg/m(2) was administered intravenously every 3 weeks until progressive disease or unacceptable toxicity. RESULTS: There were three complete and 12 partial responders [response rate 21% (95% confidence interval 12%)]. Response rates in the anthracycline-failure and anthracycline-refractory groups were 24% and 17%, respectively. A subset of 31 patients pretreated with anthracyclines and taxanes had a response rate of 26%. Median duration of response and median survival were 5.5 and 10.7 months, respectively (13 months in the failure group and 5.7 months for refractory). Grade 3/4 toxicities included neutropenia and thrombocytopenia in 56% and 19% of patients, respectively. Nine patients (12%) experienced neutropenic fever. Grade 3/4 non-hematological toxicities included skin rash (10%), nausea (12%), fatigue (10%) and stomatitis (5%). CONCLUSION: Our trial demonstrates pemetrexed to be active in breast cancer, with manageable toxicity. Activity of pemetrexed did not appear to be adversely affected by prior taxane, 5-fluorouracil or endocrine treatments.

Adult↗
PubMed2002

Nefazodone alters NPY immunostaining in rat arcuate-paraventricular projection without changes in food intake and body weight.

Nefazodone is an antidepressant drug that inhibits serotonin and noradrenaline reuptake. The aim of the present work was to study the effects of nefazodone on food intake, body weight, adiposity and hypothalamic NPY immunostaining in rats. For this purpose, male Sprague-Dawley rats (3-month-old) were administered with nefazodone (20 mg/kg; i.p) daily for two weeks. The control group was given 0.9% NaCl solution. Hypothalamic arcuate, paraventricular, periventricular, supraoptic and suprachiasmatic nuclei and the lateral hypothalamic area were immunostained for NPY. Chronic nefazodone administration in rats did not modify food intake, body weight and adipose depot size (subcutaneous, perirenal and epididymal white adipose tissues, and interscapular brown adipose tissue). However, a significant decrease in paraventricular NPY immunostaining was found in the nefazodone group compared with the control group. No changes in other hypothalamic regions such as arcuate, periventricular, supraoptic and suprachiasmatic nuclei, and lateral and medial preoptic areas were observed. Because nefazodone is an alpha1-adrenoceptor antagonist, it can be proposed that the expected decrease in food intake after nefazodone administration, due to its effects on NPY arcuate-paraventricular projection, could be masked by the opposite orexigenic effect of alpha1-adrenoceptor blockade.

Adipose Tissue↗
PubMed2002

Immediate vs. delayed imipenem treatment in cancer patients with profound neutropenia induced by high-dose chemotherapy: results of a randomized study.

A study was carried out to compare the use of prophylactic imipenem administered at the onset of profound neutropenia (immediate) with therapeutic imipenem administered at the onset of neutropenic fever (delayed) in cancer patients treated with high-dose chemotherapy. A total of 65 patients who were scheduled to receive two cycles of high-dose cyclophosphamide, etoposide, cisplatin (CEP) chemotherapy were randomized to receive imipenem either at presentation of neutropenia (immediate imipenem arm, prophylactic arm) or at commencement of neutropenic fever (delayed imipenem arm, therapeutic arm). Treatment was crossed over when the second CEP chemotherapy cycle was received. Of the 65 patients, 41 received the two planned cycles and 24 received only the first. Compared with the delayed imipenem arm, the immediate imipenem arm was associated with lower fever incidence (86.3% vs. 100%, p=0.0142) and Gram-negative bacteria infection [4/51 (7.8%) vs. 14/55 (25.5%), OR=0.24, p =0.031]. There were fewer episodes of pneumonia (2% vs. 12.7%), septic shock (0% vs. 3.6%) and deaths from infection (0% vs. 3.6%), but these differences did not reach statistical significance. With regard to delayed imipenem, for every seven patients with immediate imipenem, one episode of febrile neutropenia was avoided; for every six patients administered immediate imipenem, one case of Gram-negative infection was avoided; and for every nine patients administered immediate imipenem, one episode of pneumonia was avoided. There were no differences in the incidence of Gram-positive infections nor in the length of hospitalization between the two treatment arms. In conclusion, compared to its conventional delayed use, immediate imipenem significantly reduces the frequency of febrile neutropenia and Gram-negative infections in patients with high-dose chemotherapy.

Adolescent↗
PubMed2001

Prognostic value of DNA quantification in early epithelial ovarian carcinoma.

OBJECTIVE: To evaluate the prognostic value of flow cytometric DNA quantification and immunohistochemical expression of c-erbB-2 and p53, and traditional clinicopathologic variables in stages I-II invasive epithelial ovarian cancer. METHODS: We retrospectively reviewed 77 cases of stages I-II ovarian cancer after comprehensive surgical staging. We recorded anthropometric data (age, menopausal status, weight loss, Karnofsky index) and pathologic variables (tumor size, bilaterality, capsular status, ascites, peritoneal cytology, histologic type, and grade). In 72 cases representative paraffin-embedded samples were available for DNA quantification and immunohistochemical evaluation of c-erbB-2 and p53 overexpression. Most women (87%) had received cisplatin-based adjuvant chemotherapy. RESULTS: The median follow-up was 90 months (range 50-148 months). The 6-year overall disease-free survival rate was 70% (95% confidence interval [CI] 60%, 81%), and overall global survival was 77% (95% CI 67%, 87%). Multivariable analysis using Cox stepwise regression identified DNA content (odds ratio [OR] 12.3; P <.001) and stage (OR 1.4, P =.09) as independent poor prognosis factors for relapse, and DNA content (OR 9.8, P <.001) as the main independent factor for survival. In stepwise discriminant analysis the combination of DNA content and stage provided a correct prediction of relapse in 78% of women. CONCLUSION: Flow cytometric DNA quantification was the main independent prognostic factor of relapse and survival in these women with stages I-II epithelial ovarian cancer.

Adult↗
PubMed2000

Doxorubicin and paclitaxel in advanced breast carcinoma: importance of prior adjuvant anthracycline therapy.

BACKGROUND: The authors undertook a Phase II multicenter trial to assess the efficacy and toxicity of doxorubicin and paclitaxel in combination in the treatment of patients with metastatic breast carcinoma. METHODS: Doxorubicin (50 mg/m2, bolus) followed by paclitaxel (175 mg/m2 over 3 hours) was administered every 21 days (for a maximum of 10 cycles) as first-line chemotherapy in 77 patients, 41 of whom had received prior adjuvant chemotherapy. Monitoring of cardiac function (left ventricular ejection fraction[LVEF]) and total doxorubicin cumulative dose were included in the study protocol. RESULTS: Grade 4 hematologic toxicities were neutropenia (58%) and thrombocytopenia (4%). Neutropenic fever occurred in 9% of patients. Nonhematologic Grade 4 toxicity was limited to mucositis (3%). Grade 3 toxicities were neutropenia (35%), anemia (3%), alopecia (93%), peripheral neuropathy (18%), arthralgia/myalgia (8%), and mucositis (9%). No clinical cardiotoxicity (Grades 3 or 4) occurred. Treatment was discontinued in 5 patients who showed a decrease of LVEF of greater than 15% during therapy. Of 73 patients assessable for response, 15 were complete response, 42 partial response, 15 stable disease, and 1 disease progression; overall response rate being 78% (95% confidence interval [CI], 67-87). Median follow-up was 22 months. Median time to progression (TP) was 10 months (95% CI, 7-12). Time to progression was poorer in cases with adjuvant anthracycline therapy than those without adjuvant chemotherapy (7 vs. 12.3 months; P = 0.022), but TP in patients with adjuvant chemotherapy not containing anthracyclines was not different from the cases without adjuvant chemotherapy (8.6 months). Estimated 2-year survival was 51% (standard error, 7%). CONCLUSIONS: Our results confirm that the combination of paclitaxel and doxorubicin is effective in the treatment of metastatic breast carcinoma, and that it is well tolerated. No clinical cardiotoxicity was observed on close cardiac monitoring, and prior adjuvant anthracycline treatment compromised its efficacy.

Adult↗
PubMed2000

Evaluating changes in health status in HIV-infected patients: Medical Outcomes Study-HIV and Multidimensional Quality of Life-HIV quality of life questionnaires. Spanish MOS-HIV and MQOL-HIV Validation Group.

OBJECTIVE: To compare the sensitivity to change of two HIV-health-related quality of life (HRQoL) questionnaires--the Medical Outcomes Study (MOS-HIV) and Multidimensional Quality of Life (MQOL-HIV) for use in clinical research. METHODS: A sample of 296 HIV-infected patients starting or switching antiretroviral treatment were randomly assigned either the MOS-HIV or MQOL-HIV questionnaires at baseline and after 3 months of treatment. Ceiling and floor effects were evaluated. Sensitivity to change was assessed by comparing the percentage of dimensions with statistically significant pre-post-treatment changes and the effect sizes in those groups of patients who reported improvement and no change in self-report questions (overall, physical, mental and social health status) and clinical characteristics (number of opportunistic infections, number of symptoms, viral load level and CD4+ count). RESULTS: Ceiling effects were found in HRQoL scores at baseline and after 3 months of treatment in Pain (42.3-41.6%), Role Function (73.1-77.6%) and Social Function (60.9-63%) on MOS-HIV subscales, and in Social Support (38.2-37.6%) and Partner Intimacy (38.2-33.7%) on MQOL-HIV. For patients who improved in self-reported and objective clinical indicators of health status, mean percentage of dimensions with statistically significant pre-post-treatment changes was 86.4% on MOS-HIV and 50% on MQOL-HIV, where mean standardized effect size was 0.45 on MOS-HIV and 0.33 on MQOL-HIV for the total of dimensions. CONCLUSIONS: Based on sensitivity to change the results suggest that for 3 months both questionnaires can be used, but the MOS-HIV is more sensitive than the MQOL-HIV for use in clinical research.

Adolescent↗
PubMed2000

Enamel pearls and cervical enamel projections on 2 maxillary molars with localized periodontal disease: case report and histologic study.

Presented here is an unusual case of teeth with aberrant enamel. One small and 3 large enamel pearls were identified in 2 maxillary third molars of a patient. One long enamel projection was connected to one of the large enamel pearls, along with 2 short cervical enamel projections. The ectopic enamel was associated with advanced localized periodontal destruction. After extraction, the molars were investigated radiographically and under the scanning electron microscope. The 3 large pearls contained distinct dentinal cones. The enamel of the pearls and the long cervical projection exhibited most of the structural attributes of crown enamel but were somewhat irregular, with variable shape and course of the prisms. Morphologic considerations suggest that these enamel pearls were aberrations and should not be regarded as attempts at new cusp or new tooth formation.

Dental Enamel↗