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Biomedical subjects

A Abad

Publications and source records attributed to A Abad.

At least 19 recordsLinked to original sources
PubMed2006

Guides for adjuvant treatment of colon cancer. TTD Group (Spanish Cooperative Group for Gastrointestinal Tumor Therapy).

The choice of the most suitable chemotherapy schedule for the adjuvant treatment of colon cancer has been reviewed by the TTD group, as well as the principles of risk assessment for patients with stage II disease. In the light of data now available, oxaliplatin- based schedules (FOLFOX4 or FLOX) are recommended. Alternatives in special situations are monotherapy with capecitabine, UFT/LV, or 5- FU/LV in infusion. In patients with stage II disease, the indication of chemotherapy must be individualized and based on the patient's risk of recurrence (perforation, obstruction, peritumoral lymphovascular involvement, poorly differentiated histology, number of lymph nodes examined < or = 11, pre-surgical CEA), and comorbidities that can compromise the safety of treatment or survival of the patient.

Adenocarcinoma↗
PubMed2006

Recent developments in clinimetric instruments.

Assessment of impairment and function is essential in order to monitor joint status and evaluate therapeutic interventions in patients with haemophilia. The improvements in the treatment of haemophilia have required the development of more sensitive tools to detect the more minor dysfunctions that may now be apparent. This paper outlines some of the recent developments in this field. The Haemophilia Joint Health Score (HJHS) provides a systematic and robust measure of joint impairment. The MRI Scoring System has been designed to provide a comprehensive scoring system combining both progressive and additive scales. The Functional Independence Score for Haemophilia (FISH) has been developed to assess performance of functional activities and can be used in conjunction with the Haemophilia Activities List (HAL) which provides a self report measure of function. It is recommended that both measures are evaluated as these tools measure different constructs. Further refinement and testing of the psychometric properties of all of these tools is in progress. More widespread use of these tools will enable the sharing of data across the world so promoting best practice and ultimately enhancing patient care.

Activities of Daily Living↗
PubMed2006

Expression analysis of genes involved in oxaliplatin response and development of oxaliplatin-resistant HT29 colon cancer cells.

The interrelationship between platinum resistance and clinical response is not well established. The purpose of this study is to evaluate the expression of 14 genes involved in platinum resistance in a colon cancer cell line (HT29) and its oxaliplatin (OXA)-resistant sublines. Resistant cells exhibited lower expression of many of these genes suggesting that several pathways may be implicated in OXA resistance. Particularly, OXA resistance is accompanied by defects in drug uptake (downregulation of the hCTR1 transporter) and enhanced DNA repair (upregulation of the XPD gene). Our data also confirmed that copper transporters and chaperones are involved in OXA resistance in colorectal cancer cells as evidenced by the overexpression of ATP7A and CCS in response to OXA exposure. Moreover, increased CCS expression suggests a role for SOD1 in OXA detoxification. Whereas exposure to OXA in HT29 induced significant changes in expression of many of the genes analyzed, only ATP7A, XPD and SRPK1 gene expression was increased in OXA-treated HTOXAR3 resistant cells. To our knowledge, this is the first report of implicating SRPK1 in OXA resistance. This study provides the basis for further evaluation of these putative markers of OXA response and resistance in colorectal cancer patients who are candidates for treatment with OXA.

Adenosine Triphosphatases↗
PubMed2005

Clinical and immunological characteristics of type 1 diabetes mellitus in a northwestern Colombian population.

We underwent a project aimed to define the clinical and immunological characteristics of type 1 diabetes (T1D) in a Colombian population. This was a multicenter and cross-sectional study. Patients were systematically interviewed and their medical records reviewed, using a questionnaire that sought information about demographic, clinical and immunological characteristics. Glutamic acid decarboxylase antibodies (GADA), tyrosine phosphatase antibodies (IA-2A) and insulin antibodies (IAA) were examined by radioimmunoassay. There were 107 patients with T1D. Male:female ratio was 1:1. Half of the patients developed diabetes ketoacidosis at onset. GADA, IA-2A, and IAA were detected in 45%, 40%, and 69% of the cases, respectively. GADA positive patients were older and had a less duration of disease than patients without these autoantibodies (p<0.01). Association between breast feeding with the presence of antibodies or clinical characteristics was not observed. The results highlight some differences of T1D expression according to geographic location and ethnicity. Differences in age at onset and clinical variables may point to an environmental factor or deficient access to health care system. Genetic studies underway will provide important information in this population. These results might help to define public health policies in our population to improve T1D diagnosis, patients' quality of life and their outcome.

Adult↗
PubMed2005

Determination of carbaryl in natural water samples by a surface plasmon resonance flow-through immunosensor.

The analysis of carbaryl in natural water samples was accomplished using a portable immunosensor based on surface plasmon resonance (SPR) technology. The assay was based on a binding inhibition immunoassay format with the analyte derivative covalently immobilized on the sensor surface. An alkanethiol self-assembled monolayer (SAM) was formed onto the gold-coated sensor surface to allow the reusability of the same sensing surface during 220 regeneration cycles. Reproducibility was evaluated by performing three independent assays in triplicate on 3 different days. The batch-assay variability was also calculated using three different gold-coated sensor surfaces. The intra- and inter-day relative standard deviation were 8.6 and 15.3%, respectively, whilst a variation of 7.4% in assay sensitivity was obtained by employing different sensor chips. The lowest detection limit, calculated as the concentration providing a 10% decrease of the blank signal, was of 1.38 microg L(-1). Matrix effects were also evaluated in different water types, showing I50 values (carbaryl concentrations that produced a 50% decrease of the blank signal) within the range of carbaryl standard curves in distilled water (2.78-3.55 microg L(-1)). The carbaryl immunoassay performance was validated with respect to conventional high-performance liquid chromatography-mass spectrometry (HPLC-MS). The correlation between methods was in good agreement (r2 = 0.998, 0.999 and 0.999) for the three types of natural water samples tested. A complete assay cycle, including regeneration, is accomplished in 20 min. All measurements were carried out with the SPR sensor system (beta-SPR) commercialised by the company SENSIA, SL (Spain). The small size and low-time of response of the beta-SPR platform would allow its utilization in real contaminated locations.

Biosensing Techniques↗
PubMed2004

Synthesis and cytotoxicity of hydrophobic esters of podophyllotoxins.

Diverse norbornenecarboxylate esters of podophyllotoxin and its epimers and diastereoisomers have been prepared through Diels-Alder cycloaddition by treating the dienophilic acrylates of cyclolignans with cyclopentadiene. Their cytotoxicities against several cancer cell lines have been evaluated and the results compared with those found for other lignan esters. Podophyllotoxin adducts showed a one-fold increase in activity when compared to the natural product. The preparation of more hydrophobic esters, which showed less cytotoxicity, demonstrated that this activity is not primarily due to the lipophilic factor, but mainly to the spatial arrangement of the bulky moiety, which could contribute to increase the binding to the target site.

Animals↗
PubMed2004

Phase I/II trial of irinotecan plus high-dose 5-fluorouracil (TTD regimen) as first-line chemotherapy in advanced colorectal cancer.

BACKGROUND: We conducted a phase I/II study of weekly irinotecan [30 min intravenous (i.v.) infusion] combined with 5-fluorouracil (5-FU 3 g/m(2) weekly 48 h i.v. infusion, TTD regimen) as first-line chemotherapy for patients with advanced colorectal cancer (CRC). PATIENTS AND METHODS: The maximum tolerated dose (MTD) and the dose-limiting toxicity (DLT) in the treatment of gastrointestinal solid tumors (in phase I), and the antitumor activity and toxicity of the recommended phase I dose (in phase II) were determined. RESULTS: Diarrhea was the DLT, and irinotecan 80 mg/m(2) plus 5-FU 3 g/m(2) was the recommended phase I dose. In phase II, the confirmed response rate was 44% [95% confidence interval (CI) 29% to 59%] and the median overall survival was 23.8 months. However, grade 3/4 diarrhea affected 59% of patients and led to withdrawal of three patients. A second cohort of patients studied using the same schedule but with a reduced 5-FU starting dose of 2.25 g/m(2) showed improved tolerance (the incidence of grade 4 diarrhea decreased from 28% to 11% and overall grade 3/4 diarrhea to 56%, with no patient withdrawals) but the confirmed response rate was 28% (95% CI 14% to 45%) and median overall survival was 17.2 months. CONCLUSIONS: We found weekly irinotecan 80 mg/m(2) plus TTD regimen (5-FU 2.25 g/m(2) given as 48-h i.v. infusion) to be a feasible and active combined chemotherapy for the first-line treatment of advanced colorectal cancer.

Adult↗
PubMed2003

A phase II study of cisplatin, etoposide and gemcitabine in an unfavourable group of patients with carcinoma of unknown primary site.

BACKGROUND: The aim of this phase II study was to determine toxicity, response rate, time to progression, and overall survival of cisplatin, etoposide and gemcitabine in patients with carcinoma of unknown primary tumour site. PATIENTS AND METHODS: Thirty patients with no previous chemotherapy and not belonging to a treatable group were treated with cisplatin 70 mg/m(2) on day 1, etoposide 70 mg/m(2) on days 1 and 2, and gemcitabine 700 mg m(2) on days 1 and 8, administered every 3 weeks. Stable or responding patients received a maximum of eight cycles. Twenty patients (67%) had more than three affected sites, and 25 patients (84%) had adenocarcinomas. RESULTS: Overall response rate was 36.6% (11 patients), including four complete responses (13.3%) and seven partial responses (23.3%), with a 95% confidence interval of 19.9-56. Median survival was 7.21 months and eight patients remained alive for >1 year. Myelosuppression was the most important toxicity, with grade 3-4 neutropenia in 18 patients (60%) in 32% of the cycles: eight patients had neutropenic fever and 10 patients had thrombopenia in 11% of cycles. No non-haematological grade 4 toxicity occurred. CONCLUSIONS: Cisplatin, etoposide and gemcitabine is an active combination, inducing objective responses in a subset of heavily advanced disease patients with carcinoma of unknown primary site. The role of adding gemcitabine to cisplatin and etoposide remains to be resolved as to the best schedule to diminish toxicity for the three-drug combination.

Adult↗
PubMed2003

Irinotecan (CPT-11) in metastatic colorectal cancer patients resistant to 5-fluorouracil (5-FU): a phase II study.

The efficacy and toxicity of irinotecan (CPT-11) 350 mg/m(2) i.v. once every 3 weeks was assessed in 60 patients with advanced colorectal cancer (CRC) showing failure to 5-fluorouracil (5-FU) treatment. The overall objective response rate was 13.6% (1 complete response and 4 partial responses) and 25 patients (42.4%) showed stable disease; the median time to disease progression was 4.4 months and the median survival was 10.5 months. The main non-hematological toxicities were alopecia (80.3% of patients), diarrhea (75.0%), and nausea/vomiting (71.7%); neutropenia was the main hematological toxicity. Grade 3 or 4 diarrhea appeared in 21 of 131 cycles (16.1%), whereas grade 3 or 4 neutropenia appeared in 78 cycles (25.0%). In conclusion, the present phase II study confirms that CPT-11 350 mg/m(2) every 3 weeks is active and well tolerated as second-line chemotherapy for CRC in 5-FU resistant patients.

Adenocarcinoma↗
PubMed2003

Chromosomal imbalance maps of human 5FU-resistant colorectal cancer cell lines: implications in the analysis of 5FU-acquired resistance mechanisms.

Thymidylate synthase (TS), a critical enzyme in the de novo synthesis of thymidylate, is an important target for fluoropyrimidines and folate-based TS inhibitors. Overexpression of TS has been correlated to 5-fluorouracil (5FU)-resistance. Because 5FU still remains a basic component of the treatment of colorectal cancer, circumvention of resistance is of vital importance. A panel of sensitive (HT29 and LoVo) and 5FU-resistant colorectal cancer cell lines (HT29-5FUR and LoVo-5FUR) were subjected to comparative genomic hybridization (CGH) analysis to identify possible amplified/deleted regions associated with 5FU-resistance in colon tumours. We have identified chromosomal gains at 5p, 6, 7p, 7q and 8q and one loss at 3q in 5FU-resistant cells as compared to corresponding sensitive cell lines. Neither chromosomal gains at 18p nor gene amplification of TS were observed in our resistant cell lines although an overexpression of TS gene exists (at mRNA level) in these cell lines as compared with corresponding parental cells. Most of the chromosomal gains identified in this study occur frequently in sporadic colorectal tumours and has been associated to a poor prognosis and a greater progression of the tumour and could be related to a worse chemotherapy response. The chromosomal imbalance profile detected in 5FU-resistant cell lines should provide a basis for interpreting mechanisms of 5FU-resistance in colorectal cancer and also possibly in other tumours treated with this agent. This study also identified new genes potentially implicated in 5FU-resistance and suggests new targets that could be useful for the chemotherapy treatment of colorectal cancer.

Antimetabolites, Antineoplastic↗
PubMed2003

Improving nitrogen removal in predenitrification-nitrification biofilters.

The effect on NH4-N removal rates in nitrification biofilters of filtered biodegradable COD and particulate COD leaving predenitrification biofilters was studied in a lab scale plant configured with the separated system of biofilters for secondary nitrogen removal from urban wastewaters. Applying a typical COD load of 11 kg/m3 x day to the predenitrification biofilter and maximizing its COD removal by adding nitrates or by operating an improved control of the internal recycle, only 60% removal of filtered biodegradable COD was found. This value corresponds to the complete removal of the readily biodegradable substrate (30% of influent filtered COD) and 36% of filtered slowly biodegradable substrate (50% of influent COD). The remaining 64% of the latter entered the nitrification biofilter, causing competition between heterotrophs and nitrifiers for dissolved oxygen in the inner layers of the biofilm. Consequently the nitrification rate had relatively low values (0.5 kgN/m3 x d) at 14 degrees C despite using dissolved oxygen levels of 6 mg/l. This behaviour may explain the lower nitrification rates obtained in some cases of nitrification biofilters compared to those in tertiary nitrification after activated sludge processes. The particulate COD entering the nitrification biofilter is associated with the suspended solids leaving the denitrification biofilter which are adsorbed by the external layers of the biofilm, increasing its thickness. The activity of the nitrifiers was affected because of a lack of oxygen when the thickness was left to grow considerably. Therefore no significant particulate COD effect is expected to occur as long as backwashing is carried out with the appropriate frequency.

Adsorption↗
PubMed2002

Phase I study of weekly CPT-11 (irinotecan)/docetaxel in patients with advanced solid tumors.

Based on the synergistic cytotoxicity demonstrated in vitro by topoisomerase I inhibitors followed by docetaxel and the feasibility of giving both drugs on a weekly schedule avoiding overlapping toxicities, we designed a phase I trial of weekly CPT-11 (irinotecan)/docetaxel to determine the dose-limiting toxicities (DLT) and the maximum-tolerated dose (MTD) of this combination. Eighteen patients with advanced solid tumors treated with at least one prior chemotherapy regimen were included in this trial. CPT-11 was administered as a 90-min (intravenous) IV infusion followed immediately by docetaxel as a 30-min IV infusion. Both drugs were given on days 1, 8 and 15 in 4-week cycles. Four escalating dose levels of CPT-11/docetaxel (level I: 60/20 mg/m(2), level II: 60/25 mg/m(2), level III: 70/25 mg/m(2), and level IV: 70/30 mg/m(2)) were studied. Forty-seven cycles were administered (range, 1-5 courses) with a median number of 2.6 cycles per patient. Grade 4 leukopenia was the DLT reached at dose-level IV (CPT-11/docetaxel 70/30 mg/m(2)). Four patients had grade 3 anemia at dose levels III (two patients) and IV (two patients), while grade 3/4 thrombocytopenia was not seen. Grade 3/4 non-hematologic toxicities included grade 3 diarrhea in two patients (dose levels II and IV), grade 3 asthenia in one patient (dose level II) and grade 3 stomatitis in one patient (dose level I). The recommended dose of this weekly schedule is CPT-11 70 mg/m(2) and docetaxel 25 mg/m(2). DLT of this regimen is leukopenia, although toxicity is manageable at the recommended dose level. The activity of this regimen is being evaluated in a phase II study in previously treated patients with advanced non-small cell lung cancer.

Adult↗
PubMed2001

Prognostic value of K-ras mutations and allelic imbalance on chromosome 18q in patients with resected colorectal cancer.

PURPOSE: We designed this study to assess the frequency of K-ras mutations in patients with resected colorectal tumors and their association with survival. A second objective was to analyze the prognostic value of different K-ras genotypes. In a subgroup of patients we also investigated the presence of allelic imbalance on chromosome 18q and its relationship to clinical outcome. METHODS: One hundred fourteen colorectal tumors resected between 1983 and 1986 were analyzed to detect K-ras point mutations at codons 12, 13, and 61 by polymerase chain reaction followed by allele specific oligonucleotide hybridization. A subgroup of 77 tumors was further screened to detect loss of heterozygosity on chromosome 18q using three polymorphic microsatellite markers (D18S67, D18S474 and D18S58). RESULTS: K-ras mutations were detected in 29 percent (33/114) of patients. K-ras mutations correlated with age and preoperative carcinoembryonic antigen levels, and there was some indication that they may be linked to poor survival, especially in Stage II tumors, where a subgroup of patients with aspartic and serine mutations showed significantly reduced survival (P = 0.03) compared with K-ras-negative patients. 18q loss of heterozygosity was present in 39 percent (25/63) of tumors. A multivariate analysis of Stage II tumors showed that 18q loss of heterozygosity was significantly associated with a worse prognosis (P = 0.006). A significant decrease in survival was identified in ten patients harboring both genetic alterations (K-i mutations and 18q loss of heterozygosity; P = 0.02). CONCLUSIONS: In colorectal tumors, K-ras mutations and 18q loss of heterozygosity are two genetic markers which may identify patients with more aggressive behavior, mainly in Stage II tumors. These findings warrant further research, because they can be useful in customizing adjuvant chemotherapy.

Allelic Imbalance↗
PubMed2001

Production of monoclonal antibodies to the N-methylcarbamate pesticide propoxur.

Monoclonal antibodies (MAbs) to the pesticide propoxur were produced from haptens with carboxylic spacer arms of different lengths introduced at the carbamate group of the analyte structure. MAbs were subsequently characterized in the conjugate-coated format using these immunizing haptens and newly synthesized compounds as homologous and heterologous assay conjugates, respectively. Appropriate combinations of immunoreagents resulted in competitive enzyme immunoassays (ELISA) with I(50) values in the low nanomolar range (6.5-17.9 nM). A modification of the conjugate-coated format consisting of the simultaneous incubation of the MAb and the peroxidase-labeled secondary antibody in the presence of the analyte resulted in an assay with an I(50) value of 4.4 nM. This one-step conjugate-coated ELISA format is as simple and fast as the antibody-coated format but without the need of synthesizing enzyme-hapten conjugates. Major N-methylcarbamate pesticides were not recognized by the MAb. This immunoassay should reasonably allow the rapid, low-cost, and sensitive determination of propoxur in food, soils, and the environment at levels of regulatory and practical importance.

Animals↗
PubMed2001

Validation of a monoclonal enzyme immunoassay for the determination of carbofuran in fruits and vegetables.

The N-methylcarbamate pesticide carbofuran is a very important insecticide used worldwide. In the present work, the validation of a monoclonal antibody-based enzyme immunoassay (ELISA) to determine this compound in fruits and vegetables is described. The immunoassay is a competitive heterologous ELISA in the antibody-coated format, with an I(50) value for standards in buffer of 740 ng/L and with a dynamic range between 200 and 3100 ng/L. For recovery studies, peppers, cucumbers, strawberries, tomatoes, potatoes, oranges, and apples were spiked with carbofuran at 10, 50, and 200 ppb. After liquid extraction, analyses were performed by ELISA on extracts purified on solid-phase extraction (SPE) columns and crude, nonpurified extracts. Depending on the crop, mean recoveries in the 43.9--90.7% range were obtained for purified samples and in the 90.1--121.6% range for crude extracts. The carbofuran immunoassay performance was further validated with respect to high-performance liquid chromatography (HPLC) with postcolumn derivatization and fluorescence detection (EPA Method 531.1). Samples were spiked with carbofuran at several concentrations and analyzed as blind samples by ELISA and HPLC after SPE cleanup. The correlation between methods was very good (y = 0.90x + 2.66, r(2)() = 0.958, n = 25), with HPLC being more precise than ELISA (mean coefficients of variation of 4.1 and 11.5%, respectively). The immunoassay was then applied to the analysis of nonpurified extracts of the same samples. Results also compared very well with those obtained by HPLC on purified samples (y = 1.02x + 10.44, r(2)() = 0.933, n = 29). Therefore, the developed immunoassay is a suitable method for the quantitative and reliable determination of carbofuran in fruits and vegetables even without sample cleanup, which saves time and money and considerably increases the sample throughput.

Antibodies, Monoclonal↗
PubMed2001

Monoclonal enzyme immunoassay for the analysis of carbaryl in fruits and vegetables without sample cleanup.

The N-methylcarbamate pesticide carbaryl is one of the most important insecticides used worldwide. In the present work, the validation of a monoclonal antibody-based enzyme immunoassay (ELISA) for the determination of this compound in fruits and vegetables is described. The immunoassay is a competitive heterologous ELISA in the antibody-coated format, with an I(50) value for standards in buffer of 101.0 +/- 26.9 ng/L and with a dynamic range between 31.6 and 364.0 ng/L. For recovery studies, peppers, cucumbers, strawberries, tomatoes, potatoes, oranges, and apples were spiked with carbaryl at 10, 50, and 200 ppb. After liquid extraction, analyses were performed by ELISA on both extracts purified on solid-phase extraction (SPE) columns and crude, nonpurified extracts. Depending on the crop and the fortification level, recoveries in the 59.0--120.0% range were obtained for purified samples and in the 70.0--137.7% range for crude extracts. The carbaryl immunoassay performance was further validated with respect to high-performance liquid chromatography (HPLC) with postcolumn derivatization and fluorescence detection (EPA Method 531.1). Samples were spiked with carbaryl at several concentrations and analyzed as blind samples by ELISA and HPLC after SPE cleanup. The correlation between methods was excellent (y = 1.04x + 0.71, r(2) = 0.992, n = 33), with HPLC being more precise than ELISA (mean coefficients of variation of 5.2 and 12.0%, respectively). The immunoassay was then applied to the analysis of nonpurified extracts of the same samples. Results also compared very well with those obtained by HPLC on purified samples (y = 1.28x - 0.59, r(2) = 0.987, n = 33) while maintaining similar precision. Therefore, the developed immunoassay is a suitable method for the quantitative and reliable determination of carbaryl in fruits and vegetables even without sample cleanup, which saves time and money and considerably increases sample throughput.

Antibodies, Monoclonal↗