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Biomedical subjects

E Espinosa

Publications and source records attributed to E Espinosa.

At least 19 recordsLinked to original sources

Bioabsorbable staple-line reinforcement to reduce staple-line bleeding in the transection of mesenteric vessels during laparoscopic colorectal resection: a pilot study.

BACKGROUND: Staple line hemorrhage and leak are the 2 most dreaded complications of laparoscopyassisted resection of colorectal cancer (LARCC). Recently, anastomotic staple lines have been reinforced with a range of absorbable and non-absorbable bioprosthetic reinforcement materials. This pilot prospective study used the bioabsorbable Seamguard (BSG; WL Gore & Associates, Flagstaff, AZ) for routine reinforcement of the mesenteric vascular staple transection to prevent mesenteric hemorrhage and to assess its safety and feasibility in a consecutive series of laparoscopic colonic resections. METHODS: Twenty-five patients consecutively scheduled to undergo LARCC were enrolled in the study. All operations were performed with a standard LARCC technique which included loading of the BSG sleeves onto the jaws of the cutter/stapler. RESULTS: There were 23 wholly LARCC cases and 2 open conversions. BSG was used in all 25 patients. No patient experienced staple-line bleeding or other complications during the surgical procedure. The mean number of staple-line reinforcement sleeves used was 2.6 (range, 2-4). The mean operative time was 118 minutes (range, 65-184 minutes). Additional measures to achieve hemostasis were not required in any case. The mean cost was US 475.20 dollars for the procedure. CONCLUSIONS: This small pilot study has shown the routine use of BSG mesenteric staple line reinforcement to be safe, quick and effective during LARCC.

Absorbable Implants↗

A CXCL2 tandem repeat promoter polymorphism is associated with susceptibility to severe sepsis in the Spanish population.

Sepsis describes a complex clinical syndrome resulting from a systemic inflammatory response to bacteria. Functional studies in animal models of sepsis have catalogued CXCL2 as a candidate gene for the development of the disease. We hypothesized that CXCL2 polymorphisms may confer susceptibility to sepsis and performed an association study using 178 severe sepsis patients and 357 population-based controls. We selected two polymorphisms from the promoter of the gene (-437A/G and -665(AC)n), and analyzed whether haplotypes or single loci were associated with disease susceptibility. An overall test of differentiation showed that haplotype distribution was not different between cases and controls (P=0.407). Likewise, -437A/G was not associated with disease susceptibility (heterozygote odds ratio (OR) 0.68 (0.47-1.03), and homozygote OR 0.86 (0.56-1.32); P=0.706). However, for the -665(AC)n, we found that the 24+/-1 repeat alleles were associated with susceptibility (heterozygote OR 2.82 (1.10-7.24), and homozygote OR 3.65 (1.41-9.43); P=0.0006). This association remained significant when using a multiple logistic regression analysis (OR 2.23; 95% confidence intervals (95% CI) 1.22-4.03; P=0.008) and after a genomic control adjustment (P=0.017). Although replicate studies and functional assays are needed, these results suggest that CXCL2 gene variants may contribute to the development of severe sepsis.

Aged↗

Breast cancer prognosis determined by gene expression profiling: a quantitative reverse transcriptase polymerase chain reaction study.

PURPOSE: We sought to reproduce with quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) the results obtained with a 70-gene expression profile that has been described previously in breast cancer. PATIENTS AND METHODS: Frozen breast cancer samples from patients who were operated on were used to isolate tumor RNA. Ninety-six patients with stage I to II disease were included. Median age was 57 years (range, 27 to 80 years). Forty-eight patients had lymph node-negative and 48 lymph node-positive disease. qRT-PCR amplifications were performed and the results were correlated with clinical data. RESULTS: After a minimum follow-up of 5 years, 25 patients had a relapse. The gene profile divided patients into two groups with poor and good prognosis. Significant differences with regard to grade of differentiation, size and hormone receptors were seen between the two groups. The gene profile was significantly associated with relapse-free survival and overall survival in the whole group of 96 patients. Multivariate analysis showed that only lymph node status and gene profile were significantly correlated to overall survival. CONCLUSION: qRT-PCR reproduced the results obtained with microarrays for a prognostic gene profile in women with early-stage breast cancer.

Adult↗

Localisation of COX-2 protein is different in breast ductal carcinoma and adjacent non-tumour ductal epithelium.

INTRODUCTION: A number of findings suggest that cyclooxygenase-2 (COX-2) is overexpressed in breast tumours. However, there is a lack of consensus in the literature regarding the pattern of expression of this protein in invasive breast ductal carcinoma and in the adjacent non-tumour ductal epithelium. This study compares the expression of COX-2 mRNA and protein in breast ductal carcinoma relative to non-tumour breast tissue. MATERIAL AND METHODS: We analysed the expression of COX-2 mRNA by quantitative PCR, and COX-2 protein by immunohistochemistry in invasive ductal carcinoma as well as in non-tumour adjacent ductal epithelium from 34 breast biopsies diagnosed as being invasive ductal carcinoma. As control, we analysed expression of COX-2 protein by immunohistochemistry in surgically-resected benign breast lesions. RESULTS: Our results show that COX-2 mRNA and protein are overexpressed in non-tumour ductal epithelium compared with invasive ductal carcinoma. However, the pattern of the protein expression is different in tumour and non-tumour tissue: COX-2 protein is expressed predominantly in the membrane of the non-tumour ductal epithelium (including in benign breast lesions) while, in invasive ductal carcinoma cells, it is localised in the cytoplasm. CONCLUSIONS: The non-tumour ductal epithelium adjacent to invasive ductal carcinoma shows a higher COX-2 expression than does the invasive ductal carcinoma. However, the different localisation of the immunohistochemically-detected protein suggests a possible post-translational regulation of the protein.

Adult↗

Effect of the in vitro maturation medium on equine oocytes: comparison of follicular fluid and oestrous mare serum.

The present study evaluated the effect of supplementing the medium used to mature equine oocytes in vitro with oestrous mare serum (EMS) or horse follicular fluid (HFF). To this end, 144 ovaries were obtained from mares aged 16-21 months and transported to the laboratory in Dulbecco's phosphate buffered saline (D-PBS) at 30 degrees C. Oocytes were harvested from the ovaries by slicing, and then selected for in vitro maturation (IVM) according to the number of cumulus cell layers and the characteristics of the cytoplasm. The selected oocytes were washed three times in TCM199 medium plus HEPES (TCM-199H) or in the same medium plus glutamine (TCM-199G), then matured in vitro in six study groups established according to the in vitro maturation (IVM) treatment to see possible interactions between HEPES and glutamine on other supplements: Ten percent EMS was added to two of these media (TCM-199H+EMS and TCM-199G+EMS) and 10% HFF was added to the media in two other groups (TCM-199H+HFF and TCM-199G+HFF). IVM was performed at 38.5 degrees C for 40 h in a controlled atmosphere (5% CO2, 95% relative humidity). The findings indicate that the presence of EMS or HFF in the TCM-199H medium gives rise to the best results in terms of the proportions of oocytes reaching maturity (37.7% and 36.8%, respectively). The values obtained with EMS and HFF were statistically similar to each other but differed from the other treatments. The media containing glutamine led to the highest proportions of degenerated oocytes.

Animals↗

Docetaxel and high-dose epirubicin as neoadjuvant chemotherapy in locally advanced breast cancer.

PURPOSE: Epirubicin and docetaxel are two of the most active drugs against breast carcinoma. As the achievement of a pathological complete response (pCR) is important for survival of patients with locally advanced disease, we used both drugs as neoadjuvant chemotherapy. PATIENTS AND METHODS: Women with locally advanced or inflammatory breast cancer received epirubicin 120 mg/m2 followed by docetaxel 75 mg/m2, both on day 1, every 21 days for four cycles. Lenograstim was administered for 10 days in all cycles. RESULTS: Of 51 patients included, 50 received a total of 188 cycles, with a median of 4 per patient. The median age was 47 years, tumour stage was IIIA in 14 patients and IIIB in 36. Oestrogen receptors were positive in 65% of tumours. There were 10 clinical complete responses (20%) and 29 partial responses (58%). Surgery consisted of mastectomy in 40 patients and tumorectomy in 6. After surgery, 9 pCR were recorded (18%). One patient progressed and died soon after the end of chemotherapy. After a median follow-up of 22 months, the median disease-free survival was 33.7 months. Grade 3/4 neutropenia was observed in 32% of patients, anaemia in 6%, and thrombocytopenia in 4%. Five patients had febrile neutropenia. There were no toxic deaths or grade 4 nonhaematological toxicities. CONCLUSIONS: Docetaxel plus high-dose epirubicin showed promising activity in patients with locally advanced and inflammatory breast cancer, at the cost of moderate toxicity.

Adult↗

Neoadjuvant therapy of rectal carcinoma with UFT-leucovorin plus radiotherapy.

BACKGROUND: The object of this phase II study was to assess the impact of preoperative external radiation therapy combined with UFT and leucovorin on tumor response, sphincter preservation and tumor control in patients with rectal carcinoma. PATIENTS AND METHODS: Forty-one patients with resectable extraperitoneal rectal adenocarcinoma received radiation therapy and two courses of chemotherapy. Chemotherapy consisted of a 2-h infusion of 6S-steroisomer of leucovorin (6SLV) 250 mg/m2 on day 1, oral 6SLV 7.5 mg every 12 h on days 2-14, and UFT either 350 or 300 mg/m2 on days 1 to 14 every 28 days. Six additional courses of chemotherapy were given after surgery. RESULTS: Seven of 16 patients (43%) who received 350 mg/m2/day of UFT had grade 3-4 diarrhea and two other patients (12%) had grade 3-4 dermatitis. The next 25 patients received 300 mg/m2/day of UFT and only 14% of them had grade 3-4 diarrhea. Surgery consisted of low-anterior resection in 26 patients (63%) and abdominal-perineal amputation in 15 (37%). There were six histological complete responses (15%). Downstaging occurred in 25 patients (63%). The overall survival at 3 years was 90% and the pelvic disease-free survival 92%. CONCLUSIONS: Preoperative therapy with radiotherapy and UFT-6SLV downstaged 63% of tumors and allowed a sphincter-preserving procedure in some patients. Toxicity was moderate. This scheme is convenient because of the oral administration of chemotherapy.

Adenocarcinoma↗

Phase II study of a fixed dose-rate infusion of gemcitabine associated with uracil/tegafur in advanced carcinoma of the pancreas.

BACKGROUND: The objectives of this study were to evaluate the efficacy and toxicity of a fixed dose-rate infusion of gemcitabine associated with uracil/tegafur (UFT) in patients with advanced adenocarcinoma of the pancreas. PATIENTS AND METHODS: Forty-three chemotherapy-naïve patients with adenocarcinoma of the pancreas were included in this phase II study. All of whom had a Karnofsky performance status >or=50 and bi-dimensionally measurable disease (either advanced non-resectable or metastatic); median age 59 years (range 39-77); male:female ratio 29:14. Eight patients (19%) had locally advanced disease and 35 (81%) distant metastases. Treatment consisted of gemcitabine 1200 mg/m(2) given as a 120-min infusion weekly for 3 consecutive weeks, plus oral UFT 400 mg/m(2)/day (in 2-3 doses per day) on days 1-21, cycles were given every 28 days. Measurements of efficacy included response rate, clinical benefit response, time to disease progression and overall survival. RESULTS: A total of 192 cycles of chemotherapy were delivered with a median of four per patient. There were two complete responses (5%) and 12 partial responses (28%), producing an overall response rate of 33% [95% confidence interval (CI) 16% to 49%]. Thirteen patients (30%) had stable disease, whereas 16 (37%) had a progression. The median time to progression was 6 months and the median overall survival was 11 months. Twenty-five patients (64%, 95% CI 47% to 78%) experienced a clinical benefit response. Grade 3-4 WHO toxicities were: neutropenia in nine patients (21%); thrombocytopenia in four (9%); anaemia in five (12%); diarrhoea in four (9%); and asthenia in one (2%). CONCLUSIONS: A fixed dose-rate infusion of gemcitabine associated with UFT was well tolerated and showed promising activity in patients with locally advanced or metastatic carcinoma of the pancreas. This is an appropriate palliative treatment in this setting.

Adenocarcinoma↗

Unprecedented oxidation of a phenylglycinol-derived 2-pyridone: enantioselective synthesis of polyhydroxypiperidines.

[reaction: see text]. The phenylglycinol-derived 2-pyridone 1 undergoes m-CPBA oxidation steroselectively leading to the chiral nonracemic unsaturated bicyclic hydroxylactam 2, from which the enantioselective synthesis of (3R,5R)-3,4,5-trihydroxypiperidine (16) and the formal synthesis of the azasugar epiisofagomine are described. The enantioselective synthesis of (S)-N-Boc-3-hydroxypiperidine and (3R,4S)-3,4-dihydroxypiperidine is also reported.

Enzyme Inhibitors↗

Dichloro(d-methionine-n,s)platinum(ii) at 130 k.

The asymmetric unit of the title compound, [PtCl2(C5H11NO2S)], a D-methionine derivative, contains two molecules with opposite chirality at the S atoms. The amino acid acts as a bidentate ligand and coordinates simultaneously through the N (amino) and S (thioether) atoms. The molecules are packed in pairs which are connected through two hydrogen bonds between the protonated carboxyl groups, with O.O distances of 2.633 (10) and 2.663 (12) A.

Crystallography, X-Ray↗

Chemical synthesis and biological activity of bromohydrin pyrophosphate, a potent stimulator of human gamma delta T cells.

Small phosphorylated metabolites from mycobacteria stimulate human gammadelta T lymphocytes. Although such phosphoantigens could prove useful in the composition of vaccines involving gammadelta T cell-mediated immunity, their very low abundance in natural sources limits such applications. Here, we describe the chemical production, purification, and bioactivity of a phosphorylated bromohydrin (BrHPP) analogue that mimics the biological properties of natural phosphoantigens. This compound can be obtained in gram amounts, is easy to detect, and is of high stability in aqueous solutions. Whereas unspecific binding of BrHPP to a wide panel of cell surface receptors is not detected even at micromolar concentrations, nanomolar concentrations specifically trigger effector responses of human gammadelta T lymphocytes. Thus, BrHPP is a novel molecule enabling potent immunostimulation of human gammadelta T lymphocytes.

Alcohols↗

Differential activation of human gammadelta cells by nonpeptide phosphoantigens.

Human T cells expressing Vgamma9Ndelta2-encoded TCR recognize several nonpeptide phosphoantigens in the absence of major histocompatibility complex restriction. As these cells respond differentially to increasing concentrations of structurally related phosphoantigens, such ligands constitute agonists of different strengths. By analyzing early cellular events and late effector responses of gammadelta T cells, we compared their patterns of stimulation by weak, medium and strong phosphoantigen agonists. We found that, although the early metabolic activation as assessed by cytosensor microphysiometry directly reflects the intensity of subsequent effector response by gammadelta cells, TCR down-modulation is dissociated from the latter. Weak and mid-range phosphoantigen agonists induce a time- and dose-dependent down-modulation of the gammadelta TCR, whereas strong phosphoantigen agonists induce little or no TCR down-regulation. This indicates that gammadelta TCR down-modulation does not match the extent of TCR signaling as assessed by microphysiometry or conventional effector responses (TNF-alpha production and cytotoxicity). This differential pattern of gammadelta cell activation by phosphoantigens could explain the stronger potencies of some of these agonists.

Acids↗

Interactions of d(10) metal ions with hippuric acid and cytosine. X-ray structure of the first cadmium (II)-amino acid derivative-nucleobase ternary compound.

The interactions of Zn(II), Cd(II) and Hg(II) with hippuric acid (hipH) were studied and several novel compounds were synthesized and studied by NMR. Some new metal-hippuric-cytosine ternary compounds were formed and the structure of the [Cd(hip)(2)(cyt)(H(2)O)](2) ternary complex resolved. Each cadmium (II) atom has a distorted trigonal bipyramid coordination which is linked to a water molecule, a cytosine via N(3), a carboxylic oxygen atom of a hippurate moiety and two bridging dicoordinated hippurates bound through the carboxylic oxygen atoms. To these five main bonds, two longer ancillary interactions can be observed: the second oxygen of the monocoordinated hippurate group and the carboxylic oxygen of the cytosine ligand. The compound is stabilized by an intramolecular stacking between the benzene and cytosine rings and by the hydrogen bonds between the coordinated water molecules and the ligands. This is, to our knowledge, the first structure of a cadmium-amino acid derivative-natural nucleobase compound described so far.

Cadmium↗

Sequential therapy in advanced non-small-cell lung cancer with weekly paclitaxel followed by cisplatin-gemcitabine-vinorelbine. A phase II study.

OBJECTIVES: New effective therapies are needed to improve the outcome of patients with advanced non-small-cell lung cancer (NSCLC). The aim of this study was to assess the response rate and survival obtained with a sequential regimen of chemotherapy. PATIENTS AND METHODS: Patients with newly diagnosed stage IIIb-IV NSCLC were included. They all had measurable disease and a good performance status (0-2 in the Eastern Cooperative Oncology Group scale). Chemotherapy consisted of weekly paclitaxel 150 mg/m2 x 6, followed two weeks later by cisplatin 100 mg/m2 on day 1, gemcitabine 1,000 mg/m2 on days 1 and 14, and vinorelbine 25 mg/m2 on days 1 and 14 (CGV). CGV was administered every 28 days for a maximum of six courses. RESULTS: Fifty-two patients were included, 19 (37%) with stage IIIb and 33 (63%) with stage IV disease. After therapy with weekly paclitaxel. 29 partial responses were obtained (56%, 95% confidence interval (95% CI): 38%-67%), whereas 15 patients had stable disease (29%) and eight had a progression (15%). After CGV, there were four complete remissions (8%) and 24 partial responses (46%), for an overall response rate of 54% (95% CI: 37%-65%). Eight patients had stable disease (15%) and 16 had a progression (31%). No patient progressing after paclitaxel responded to CGV, whereas 5 out of 15 patients with stable disease reached a partial response with CGV (33%). On the contrary, 5 out of 29 patients with a partial response to paclitaxel progressed after CGV (17%). Median survival has not been reached after a median follow-up of 14 months. Median time to progression was nine months. Fifty-six percent of patients remain alive at one year. Two hundred eighty-nine courses of paclitaxel and 170 of CGV were given, with a median of 5.5 and 3.4 per patient, respectively (ranges 2-6 and 0-6. respectively). WHO grade 3-4 toxicities for paclitaxel were: neutropenia in two patients (4/) and peripheral neuropathy in five (10%). Two patients had allergic reactions requiring paclitaxel withdrawal, whereas four (8%) had hyperglycemia >250 mg/ml. Grade 3-4 toxicities for CGV were: neutropenia in ten patients (20%), peripheral neuropathy in six (12%), anemia in four (8%), nausea/vomiting in five (10%). thrombocytopenia in two (4%), and fatigue in four (8%). CONCLUSION: Our results suggest that sequential chemotherapy with weekly paclitaxel followed by CGV is highly active in patients with advanced NSCLC and has an acceptable toxicity. This schedule deserves further evaluation in a phase III study.

Adult↗

Evaluation of the chemotherapy patient monitor: an interactive tool for facilitating communication between patients and oncologists during the cancer consultation.

Effective communication between oncologists and patients with cancer is of paramount importance. The Chemotherapy Patient Monitor (CPM) is a novel tool designed to assist doctor-patient communication regarding patient concerns and side-effects. Initially, the CPM was assessed in a primary evaluation study of its use during consultations with 26 patients with advanced colorectal cancer (one consultation without, followed by two with, the CPM per patient). This led to a further dissemination/audit of 34 patients attending oncology centres in the UK, who had completed the survey prior to three consultations. The CPM contains a checklist of common side-effects of chemotherapy regimens used in advanced colorectal cancer, and other common concerns of patients with advanced colorectal cancer. The CPM records the presence of side-effects/concerns, the distress caused, whether patients wish to discuss them further, and actions taken as a result. Questionnaires explored the views of patients and oncologists in the UK and Spain regarding the effectiveness of consultations during a baseline visit conducted without the CPM, and then with the CPM in subsequent visits. These data were then complemented by the dissemination/audit study of the CPM across nine centres in the UK. All patients understood the CPM. The CPM was rated as useful by oncologists in 83% of consultations, and did not lengthen 82% of visits. Patients felt it had improved the visit in 95% of cases. Responses from patients (100%) and oncologists (84%) indicated willingness to use the CPM for at least some consultations in the future. The results of the dissemination/audit study supported these conclusions. We conclude that the CPM appears to be a useful new tool for improving patient-doctor communication during cancer consultations.

Antineoplastic Agents↗

Renal tolerance to cisplatin in patients 70 years and older.

The purpose of this study was to evaluate cisplatin nephrotoxicity in patients 70 years and older and to identify factors influencing nephrotoxicity occurrence. Forty-nine (N = 49) patients older than 70 years were studied retrospectively. All patients received treatment with cisplatin. Variables under study were as follows: prechemotherapy serum creatinine levels (Crb), maximum serum creatinine level during treatment (Crmax), steady serum creatinine level 3 months after treatment completion (Crstb), as well as their corresponding creatinine clearance values (CrbC, CrmaxC, CrstbC) as calculated by the Cockroft and Gault formula. Maximum creatinine increment (Imax = Crmax - Crb), stable creatinine increment (Istb = Crstb - Crb) and the corresponding clearance decrements (Dmax and Dstb) were calculated as well. The potential relationship of the above variables to cisplatin dose intensity and accumulated dose as well as to different prognostic factors were also considered. Assessment of associated conditions was carried out by means of Charlson comorbidity index. The patients' mean age was 73 years (range: 70-79 years). There were 43 men (88%) and 6 women (12%). Mean cisplatin dose intensity was 27 mg/m2/wk. A total of 157 chemotherapy courses were administered with a mean of 3.2 per patient. Mean Crb was 1.02 mg/dl (95% CI = 1.02-1.12), mean Crmax was 1.45 (95% CI = 1.34-1.46), and mean Crstb was 1.24 (95% CI = 1.16-1.32). Imax was equal to 0 in 13 patients (26%) and more than 0.4 mg/dl in 21 patients (43%). Istb was equal to 0 or negative in 22 (45%) and more than 0.4 in only 9 patients (18.3%). No significant relationship of serum creatinine levels, creatinine clearance levels, or of their increments or decrements to cisplatin dose intensity or accumulated dose were found. These levels also did not correlate with age, sex, comorbidity or Eastern Cooperative Oncology Group score. In 85% of patients, Crmax was reached between chemotherapy initiation and the third chemotherapy course, and thereafter renal function began to recover despite continued administration of cisplatin. Cisplatin is well tolerated by patients 70 years and older and dose intensity does not seem to influence renal function deterioration. Therefore, we failed to find reasons to encourage modification or limitation of cisplatin treatment in the elderly population.

Aged↗