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Biomedical subjects

R Molina

Publications and source records attributed to R Molina.

At least 37 records · Page 2Linked to original sources

A note on the effects of calf stimuli on the response of Zebu cows to Synchro-mate-B.

The effect of Synchro-mate-B (SMB) was measured on the estrous response and the establishment of cyclicity using different calf stimuli. Multiparous Zebu cows, were divided in three groups. In the first, 32 animals were treated with SMB leaving the calves present (SMB+CP). In the second, 33 cows were treated with SMB and calves partially removed (fence-line contact) for 48h (SMB+CPR). In the third group (n=33), cows received SMB and calves were removed for 48h (SMB+CCR) with no visual or olfactory contact. A control group (CG, n=33) involved neither SMB or calf separation. Blood samples for progesterone assessment were obtained at 11 and 4d prior to SMB treatment and on days 7 and 11 after the average return to estrous for each group. All animals were observed continuously for mounting activity during 72h after SMB implant removal. A significant difference (P<0.05) in estrous response was found between SMB-treated and non-treated animals, regardless of calf management (56 versus 8%, respectively). Cows with SMB+CCR and SMB+CPR came into estrous sooner (P<0.05) (26.5+/-2.6 and 18.1+/-4.94h, respectively), than those that remained with their calf present (40.4+/-12.8h). Cows with SMB+CCR displayed longer (P<0.05) periods of mounting behavior (13.0+/-4.4h) in comparison with SMB+CPR and SMB+CP (7.4+/-1.8 and 8.1+/-4.0h), respectively. Furthermore, 84% (P<0.05) of the cows in the SMB+CCR had high concentrations of progesterone after mounting behavior was displayed, in comparison with 68 and 54% in the other two groups, respectively. No difference was found (P>0.05) in the number of mounts per hour in estrous. It was concluded that: (1) SMB increases the number of cows that display estrous; (2) temporary weaning shortens the period from SMB implant withdrawal to mounting activity, and (3) SMB+CCR, increases the length of sexual receptivity and the number of cows that continue to cycle.

Journal Article↗

CA27.29: a valuable marker for breast cancer management. A confirmatory multicentric study on 603 cases.

Recently, a fully automated method has become commercially available to measure the MUC-1-associated antigen CA27.29. The present investigation was performed in order to compare CA27.29 and CA15.3 in a wide series of patients affected with breast cancer. Overall, 603 cases with breast cancer and 194 healthy controls were investigated. Patients were enrolled in 4 institutions, while assays were performed in one laboratory. CA27.29 was measured by the ACS:180 BR assay (Bayer Diagnostics) and CA15.3 by the AxSYM (Abbott Laboratories). An excellent correlation was found between the results obtained by the two methods. The two markers showed comparable results in healthy controls, with higher levels in post-menopausal than in pre-menopausal subjects. The markers were significantly higher in primary breast cancer than in controls. The areas under the receiver operating characteristics (ROC) curves of the two tests were comparable, but CA27.29 showed better sensitivity in cases with low antigen concentrations (below the cut-off point). Accordingly, when comparing each test in different stage categories, significance levels of the differences were higher for CA27.29 than for CA15.3 for all T categories versus healthy controls, for pT1 versus pT2, for all N categories versus healthy controls and for node-negative versus N1-3 patients. From the results of the present study, that has been performed on samples taken at diagnosis and prior to any treatment from the widest series of patients with primary breast cancer reported so far, we can draw the following conclusions: CA27.29 provides comparable results to CA15.3; CA27.29 seems more sensitive than CA15.3 to limited variations of tumour extension; however, it cannot help clinicians in distinguishing stage I patients from stage II patients. However, from the point of view of clinical decision making, CA27.29 provides comparable results to CA15.3. CA27.29 is therefore suitable for routine use in the management of patients with breast cancer.

Adolescent↗

Graft failure in a patient with systemic lupus erythematosus (SLE) treated with high-dose immunosuppression and autologous stem cell rescue.

A 32-year-old female with WHO grade IV, dialysis dependent, lupus nephritis was treated with high-dose immunosuppression and autologous stem cell rescue. Stem cells were mobilized with cyclophosphamide (CY) and G-CSF, and 4.07 x 10(6) CD34+ cells/kg were obtained after CD34+ cell selection using the CellPro column. The preparative regimen consisted of CY, and antithymocyte globulin (ATG), with methylprednisolone. After apparent primary engraftment of neutrophils on day 9, the patient developed recurrent neutropenia on day 19. She showed no evidence of engraftment by day 35, and back-up unmanipulated stem cells were given without effect. Subsequently, she received unmanipulated peripheral stem cells (2 x 10(6) CD34+ cells/kg) from an HLA-identical sibling. The patient remained pancytopenic and expired on day 62 from disseminated fungal infection. An autopsy revealed no evidence of hematopoietic recovery. Progenitor cell assays were performed with the patient's stem cells, which were collected prior to transplantation, and serum collected day 27. Morphologic examination of the patient's cell colonies grown in the presence of her serum revealed abnormal shapes and non-adherent cells. There were significantly fewer BFU-e colonies and a trend toward fewer CFU-GM colonies with the patient's cells and serum compared to normal donor cells. We concluded that a substance present in her serum mediated graft failure and prevented engraftment after additional stem cell infusions.

Adult↗

Prognostic value of HER-2/neu and p53 expression in node-positive breast cancer. HER-2/neu effect on adjuvant tamoxifen treatment.

HER-2/neu and p53 expression, conventional clinical and pathologic prognostic factors, were evaluated in a retrospective series of 283 node-positive breast cancer patients. Overexpression was determined by immunohistochemistry in formalin-fixed paraffin-embedded tissue blocks. Twenty one percent were HER-2/neu positive and 40% p53 positive. HER-2/neu expression was related to axillary lymph node metastasis (P=0.014), inflammatory infiltrates (P=0.004), and the absence of oestrogen (ER) (P=0.0026) and progesterone (P=0.01) receptors (PR). p53 expression was related to lymph node involvement (P=0.03), necrosis (P=0.036), absence of ER (P=0.028) and PR (P=0.065). p53 was not associated with outcome. HER-2/neu was an unfavourable prognostic factor for disease-free (DFS) (P=0.05) and overall survival (OS) (P=0.02) in univariate analysis. Multivariate analysis showed that the number of involved axillary nodes (P<0.00001), age (P=0.004), grade (P=0.04), and PR (P=0.04) were independent predictors for OS. ER-positive patients treated with adjuvant tamoxifen had shorter DFS and OS when they were HER-2/neu positive.

Journal Article↗

Binding specificity of mannose-specific carbohydrate-binding protein from the cell surface of Trypanosoma cruzi.

The sugar binding specificity of the recently described mannose-specific carbohydrate-binding proteins (CBP) isolated to homogeneity from both the epimastigote and trypomastigote stages of the pathogenic protozoa Trypanosoma cruzi has been studied by quantitative hapten inhibition of the biotinylated CBPs to immobilized thyroglobulin using model oligosaccharides. The results clearly show a differential specificity toward high-mannose glycans between the CBPs from the two developmental stages. Thus, the isolated CBP from epimastigotes exhibited stronger affinity for higher mannose oligomers containing the Manalpha1-2Manalpha1-6Manalpha1-6 structure. Its affinity decreased, as did the number of mannose residues on the oligomer or removal of the terminal Manalpha1-2-linked mannose. By contrast the CBP isolated from the trypomastigote stage showed about 400-fold lower avidity than the epimastigote form, and contrary to it, it was slightly more specific toward Man5GlcNAc than Man9GlcNAc. Analysis of the interaction of epimastigote-Man-CBP with its ligands by UV difference spectroscopy indicates the existence of an extended binding site in that protein with a large enthalpic contribution to the binding. The thermodynamic parameters of binding were obtained by isothermal titration calorimetry and been found that the DeltaH values to be in good agreement with the van't Hoff values. The binding reactions are mainly enthalpically driven and exhibit enthalpy-enthropy compensation. In addition, analysis of the high-mannose glycans from different parts of the digestive tract of the reduviid insect vector of T. cruzi suggest a role of the CBP in the retention of the epimastigote stage in the anterior portion of the gut.

Animals↗

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↗

Glucose-induced activation of rubidium transport and water flux in sunflower root systems.

Excised 20-d-old sunflower roots (Helianthus annuus L. cv. Sun-Gro 393) were used to study the effect of different sugars on rubidium and water fluxes. The roots sensed and absorbed glucose from the external medium inducing the activation of rubidium accumulated in the root (Rb(+) root), the flux of exuded rubidium (J(Rb)) and, to a lesser degree, the exudation rate (J(v)). These effects were also triggered by fructose, but not by 6-deoxyglucose (6-dG), a glucose analogue which is not a substrate for hexokinase (HXK). The effect of 2-deoxyglucose (2-dG), an analogue that is phosphorylated but not further metabolized, was complex, suggesting an inhibitory effect on solute transport to the xylem. The amounts of glucose required to activate rubidium and water fluxes were similar to those previously reported to regulate different processes in other plants (0.5--10 mM). When sorbitol was used instead of glucose, neither rubidium uptake (Rb(+) root plus J(Rb)) nor J(v) was activated. It is proposed that glucose present in the root plays an important signalling role in the regulation of Rb(+) (K(+)) and water transport in plant roots.

Carbon Radioisotopes↗

Sexual behaviour of Zebu bulls in the humid tropics of Costa Rica: single versus multiple-sire groups.

This study compares the courtship and mounting behaviour of Bos indicus bulls in single- and multiple-sire groups in Costa Rica (latitude 10 degrees 25'N, longitude 84 degrees 32'W, annual precipitation of 3096mm, temperature of 24 degrees C and humidity of 85.3%). Four, 3-4 year-old Brahman bulls with previous sexual experience were used to sire a group of 120 multiparous cows (average of 128 days post-partum and a body condition score of 2.5) allocated to two groups of 60 each: (1) single-sire mating group (SSM) and (2) multiple-sire mating group of three bulls (MSM). Bulls were rotated among groups every 7 days for 28 days. The frequency, type and duration of sexual activities (mounting and mounting attempts) and courtship activities (smelling and licking genital area, butting, supporting the head over a female and the sign of Flehmen) were calculated for each mating group. Descriptive and non-parametric statistics (Wilcoxon, Mann-Withney tests) were used to calculate differences between mating programmes. Sexual activities tended to be more frequent in the SSM group than the MSM group (267 versus 124, P>0.05). Differences in the ratios of sexual to courtship activities between both groups were significant (1:3 in SSM and 1:6 in MSM, P>0.05). Pregnancy rate averages were 28 and 37%, respectively, (P>0.05). It is concluded that under these conditions multiple-sire mating and single-sire mating achieved similar pregnancy rates.

Animals↗

Experimental infection of Phlebotomus perniciosus and determination of the natural infection rates of Leishmania infantum in dogs.

Direct xenodiagnosis has been used to determine the infection rates in sand flies of 12 dogs parasitized by Leishmania infantum and classified in function of clinical signs. The dogs were divided into three clinical groups and no statistically significant differences in the infection rates of female sand flies were observed among them. This result indicates the epidemiological importance of asymptomatic and oligosymptomatic dogs. Indirect xenodiagnosis uses sand flies fed on the blood of dogs ex vivo. This technique was not found to be useful as an alternative to the direct method for the detection of dogs parasitized by L. infantum. The clinical worsening of the disease was not reflected in the increasing number of parasites detected in the animals' blood by the indirect technique, thereby rejecting its utility as an indicator of the prognosis of the disease.

Animals↗

Analysis of type T1 and T2 cytokines in patients with prostate cancer.

BACKGROUND: It has been proposed that a dysregulation in the balance between type T1 (IL-2, IFN-gamma) and type T2 (IL-4, IL-10) cytokines may be implicated in the development of cancer. METHODS: We determined the expression of IL-2, IL-4, IL-10, and IFN-gamma in CD4 and CD8 lymphocytes by flow cytometry in 12 patients with prostate cancer and in 7 healthy subjects. In addition to the basal expression of these cytokines, their expression was also determined, following stimulation of lymphocytes with PMA (phorbol 12-mystirate 13 acetate) and ionomycin. RESULTS: The basal expression of cytokines was scarce, while following stimulation this increased markedly. On the other hand, there was a dysregulation in the balance between T1 and T2 lymphocytes in patients with prostate cancer. To this effect, in relation to healthy subjects, we observed an increase in IL-10 expression and a decrease in IL-2 expression. CONCLUSIONS: The disequilibrium observed in the balance between type T1 and type T2 cytokines may be implicated in the evolution of neoplastic disease.

CD4-Positive T-Lymphocytes↗

Measurement of complexed PSA in the differential diagnosis between prostate cancer and benign prostate hyperplasia .

BACKGROUND: To enhance the specificity of PSA in diagnosis of cancer, several approaches have been evaluated, having in common the study of fractions of PSA. The aim of this study was to evaluate the usefulness of complexed PSA in the differential diagnosis between benign prostate hyperplasia (BPH) and prostate cancer. METHODS: We determined the concentrations of complexed PSA (Bayer, Tarrytown, NY) and total PSA (Tandem-R Assay, Hybritech Incorporated, San Diego, CA) in 196 patients with BPH and in 55 patients with prostate cancer. Likewise, the percentage of free PSA (Wallac, Turku, Finland) was determined for 124 of these patients. RESULTS: The specificity of complexed PSA was found to be greater than that of total PSA for the cutoff values corresponding to sensitivities of 80%, 85%, and 90%. Similarly, the area under the curve obtained by receiver-operating curve analysis was greater for complexed PSA than for total PSA, although significant differences were not observed. The diagnostic usefulness of complexed PSA in the differential diagnosis between BPH and prostate cancer was found to be lower than the percentage of free PSA. CONCLUSIONS: We believe that differential diagnosis with complexed PSA between BPH and prostate cancer is of little use, due to low efficacy when PSA results are extreme.

Diagnosis, Differential↗

Prognostic significance of CA 125 and TPS levels after 3 chemotherapy courses in ovarian cancer patients.

OBJECTIVE: To evaluate the prognostic significance of and predictive value for survival of CA 125 and TPS levels after three chemotherapy courses in ovarian cancer patients. METHODS: We analyzed in a prospective multicenter study the 1- and 2-year overall survival (OS) in ovarian carcinoma patients. The prognostic significance of CA 125 and TPS levels above the discrimination value (25 kU/L and 100 U/L, respectively) was examined by univariate and multivariate analyses. RESULTS: Of the 213 cases included, 64 patients were staged as FIGO I + II and 149 patients were staged as FIGO III + IV. Tumor marker levels in stage I + II were not correlated with survival. However, stage III and IV patients with elevated levels of CA 125 or TPS after three chemotherapy courses had a worse 2-year OS (69% vs 26%, P < 0.0001 and 57% vs 20%, P < 0.0001, respectively) than patients with normal levels of the markers. In univariate analysis the result of operation (staging laparatomy and partial debulking) and advanced FIGO stage (IV) were also adverse prognostic factors. Independent factors predictive of low 2-year OS by multivariate analysis were staging laparotomy, TPS elevated, and CA 125 elevated. The only factors predictive of low 1-year OS were TPS elevated and staging laparotomy. CONCLUSIONS: Ovarian cancer patients with elevated CA 125 levels after three chemotherapy courses have a poor prognosis. However, the prognostic accuracy can be significantly increased by the parallel determination of serum TPS.

Antineoplastic Combined Chemotherapy Protocols↗

NAD(P)H:quinone oxidoreductase-dependent risk for colorectal cancer and its association with the presence of K-ras mutations in tumors.

NAD(P)H:quinone oxidoreductase (NQO1) is a polymorphic enzyme involved in the detoxification of potentially mutagenic and carcinogenic quinones. The homozygous C609T NQO1 genotype resulting in loss of reductase activity is found in 2-20% of individuals. In the present study, the NQO1-dependent risk for sporadic colorectal cancer (CRC) was studied in 247 incident CRC cases and 296 hospital-based controls recruited during 1996-1997. Four subgroups of cases were studied: (i) all CRCs; (ii) a molecular CRC subgroup (n = 117, cases with molecular tumor analyses); (iii) within the molecular subgroup those tumors with K-ras mutations in codon 12 (CRC K12); (iv) within the molecular subgroup those tumors with K-ras mutations in codon 13 (CRC K13). The C609T NQO1 genotype was found to be twice as prevalent in all CRC patients (6.8%) compared with controls (3%) and six times more common in the subset CRC K12 (20%). Multivariant analyses in the overall population of 247 cases and 296 controls showed a significant age and gender adjusted risk for CRC associated with the C609T NQO1 genotype (OR 2.9, 95% CI 1.19-6.97; P = 0.01) or with any variant genotype (the low activity allele frequency, i.e. heterozygotes plus homozygotes) (OR 1.41, 95% CI 1.02-1.92; P = 0.03). Within cases of the molecular subgroup (n = 117) the C609T NQO1 genotype was associated with the presence of K-ras codon 12 mutation (OR 6.5 95%, CI 1.39-34.9; P = 0.003). Logistic regression showed an age and gender adjusted risk for K-ras codon 12 mutant CRC associated with the C609T NQO1 genotype (OR 10.5, 95% CI 2.99-36.7; P: = 0.0002) or with any variant NQO1 genotype (OR 2.23, 95% CI 1.23-4.00; P = 0.007) compared with the control group. Genetically determined variations in NQO1 may modify the risk for CRC and these risks may be greatest for tumors containing K-ras codon 12 mutations. CRC with K-ras codon 12 mutations may represent a distinct and etiologically more homogeneous subtype of the disease, which may be associated with toxicants that are metabolized via a NQO1-dependent pathway.

Age Factors↗

External evaluation of LIAISON tumour marker assays on the fully automated chemiluminescent LIAISON immunoassay analyser.

The LIAISON immunoassay analyser was tested in a multicentre evaluation performed by 8 laboratories. The analytes evaluated were CA 15-3, CA 19-9, CA 125II, AFP, CEA, NSE and PSA. Excellent results were obtained for within-run and between-run precision with most assays showing within-run CVs < 5% and between-run CVs between 4 and 8%. The linearity of all assays was acceptable, however, for PSA, NSE and CA 19-9 a recovery > 110% was obtained for some of the samples tested. None of the assays revealed a high-dose hook effect. Method comparisons were performed by using the routine method of the respective study centre. Results generally showed an acceptable agreement between the LIAISON system and the different methods of comparison. The reference ranges for all assays were found to be in accordance with data known from the literature. All assays showed similar results for serum, heparinised plasma and EDTA plasma. Additionally, two experiments were performed with only one of the analytes tested: the sample-to-sample carry-over, using the CA 19-9 assay (3.3 x 10(-6)-2.3 x 10(-5)) and the functional sensitivity for the PSA assay (0.2 ng/ml).

Biomarkers, Tumor↗

Prevalence of haematozoa in birds of prey in Catalonia, north-east Spain.

Blood samples from birds of prey, 95 Strigiformes and 190 Falconiformes, were examined for the presence of haematozoan parasites. The birds had been admitted to a raptor recovery centre in Catalonia, north-east Spain. Parasites were counted in positive smears. A second blood sample was obtained from 99 birds at least seven days after their arrival at the centre. Haematozoa were detected in all seven species of Strigiformes and in nine of 19 species of Falconiformes. The overall prevalences in the two groups were significantly different, 30.5 per cent and 46.3 per cent in the nocturnal and diurnal raptors, respectively. Eleven species of haematozoan parasites were identified. The genus most commonly detected in members of the nocturnal Strigiformes was Leucocytozoon, followed by Haemoproteus, Plasmodium and Trypanosoma. In the diurnal Falconiformes only Leucocytozoon and Haemoproteus were detected. The highest infection rates were found in Accipiter nisus (sparrow hawks), Accipiter gentilis (goshawks) and Athene noctua (little owls). Relapses were detected in 9 per cent of the birds sampled twice. The highest intensity of infection (6.2 per cent) was observed in a Buteo buteo (buzzard) infected with Haemoproteus.

Animals↗

Factor VIII/von Willebrand factor complex in methylene blue-treated fresh plasma.

BACKGROUND: The effect of virus inactivation of fresh plasma with methylene blue has been studied on the factor VIII/von Willebrand factor molecular complex (FVIII/vWF), factor XIII, and fibrinogen. STUDY DESIGN AND METHODS: FVIII function or activity, vWF activity, vWF antigen, vWF:Ag, vWF multimeric structure, fibrinogen, and factor XIII were analyzed in paired samples of control fresh plasma (untreated) and the same fresh plasma treated with methylene blue. Treated plasma was filtered (0.8-1.2 microm), mixed with a methylene blue solution (300 microg/L), and illuminated at 50,000 lux for 30 minutes on both sides. RESULTS: Average loss of biologic activity of coagulation factors studied was 25 percent (FVIII function, 29%; fibrinogen, 39%; factor XIII, 16%; and vWF activity, 18%). Reduction in vWF activity was significantly lower than that in FVIII function (p<0.05), and the vWF multimeric structure did not show alterations. CONCLUSION: Methylene blue-treated plasma and the cryoprecipitates obtained from it may be effective for replacement therapy in cases of von Willebrand disease and deficiencies of factor XIII and fibrinogen, but the clinical studies are needed to verify that possibility.

Dimerization↗