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Biomedical subjects

F Casanova

Publications and source records attributed to F Casanova.

At least 19 recordsLinked to original sources

Bronchodilating effect of oxitropium bromide in heart disease patients with exacerbations of COPD: double-blind, randomized, controlled study.

Anti-cholinergic agents are considered the bronchodilator therapy of first-choice in the treatment of patients with stable chronic obstructive pulmonary disease (COPD) associated with heart disease since they may be as effective or more effective than inhaled beta2-agonists and, moreover, they do not interact with cardiac beta-adrenoceptors. The aim of our study was to evaluate the bronchodilator activity of oxitropium bromide in outpatients suffering from exacerbations of COPD associated with heart diseases (ischaemic heart disease and/or arrhythmias). We recruited 50 consecutive outpatients (33 males and 17 females, mean age 68.6 years, 15 current smokers and 35 ex-smokers). Each patient performed body plethismography in basal condition and 30 min after inhalation of 200 microg metered dose inhaler (MDI) oxitropium bromide administered by a device (Fluspacer). FEV1, FVC, MMEF25-75, sRaw and tRaw were evaluated. Thirty minutes after 200 microg oxitropium bromide administration, we observed a significant improvement in FEV1 11.6% +/- 1 (mean +/- SEM) (P<0.01); FVC, MMEF25-75 sRaw variation was respectively: 9.2% +/- 0.6, 31.4 +/- 2.9, -19.9 +/- 1.1. Placebo did not significantly change pulmonary function. Our data suggest that oxitropium bromide bronchodilator activity is effective in exacerbations of COPD.

Acute Disease↗

Solid state proton imaging detected by quadrupole resonance.

A double resonance method for imaging of solid materials containing quadrupole nuclei via the coupled protons is reported. The technique uses a static field gradient to encode the position on the protons and the method of double resonance spin-echo to detect the occurrence of proton resonances by affecting the zero-field echo signal from the quadrupole system. The double resonance imaging method offers the advantages of higher spatial resolution and straightforward image reconstruction for powder samples compared with rotating-frame and Zeeman-perturbated nuclear quadrupole resonance encoding techniques.

Journal Article↗

Improving resolution in fast rotating-frame experiments.

The rapid rotating-frame technique allows significant reduction in data-acquisition time compared with the two-dimensional method by stroboscopic observation of the nuclear magnetization during its evolution in the rotating frame. A onefold reduction in the dimensionality of the original rotating-frame experiment is achieved by using a train of strong radiofrequency pulses separated by short acquisition windows. The penalty for shortening experimental time is a reduction in spectral resolution compared with the two-dimensional method due to relaxation of transverse magnetization components during the observation windows. A variant of the rapid-rotating frame technique for improving spectral resolution based on undersampling and self-phase encoding is presented. An M-fold resolution improvement requires M experiments, thus, making possible a tradeoff between spectral resolution and experimental time. The technique was applied for spatial localization of quadrupole nuclei in powder solids, and resolution improvement is demonstrated on one- and two-dimensional NQR images.

Journal Article↗

Oral vaccination with autologous platelets in chronic autoimmune thrombocytopenic purpura.

Idiopathic thrombocytopenic purpura (ITP) is a common disease of autoimmune mechanism in which nearly 40% of patients need a third-line treatment after steroids and splenectomy failure. Due to the variable results of the multiple therapeutic modalities in refractory patients it is necessary to develop a more effective treatment. Following previous assays of immunotolerance with the administration of "oral vaccines", we propose a therapeutic protocol in chronic ITP patients with autologous cryopreserved or liophilized platelets administered in enteric capsules. The procedure is theoretically feasible and technically easy and does not need the isolation of the specific antigen target of the autoantibodies in each particular case.

Administration, Oral↗

Early and delayed consolidation chemotherapy significantly improves the outcome of children with intermediate risk acute lymphoblastic leukemia. Final results of the prospective randomized PETHEMA ALL-89 TRIAL.

BACKGROUND AND OBJECTIVES: To evaluate the impact of early and delayed consolidation chemotherapy on the outcome of children with acute lymphoblastic leukemia (ALL) stratified according to risk groups. DESIGN AND METHODS: From 1989 to 1994, 195 children (< or = 15 years old) diagnosed as having ALL (ALL-L3 excluded) in 15 Spanish hospitals entered the prospective, randomized PETHEMA ALL-89 trial. Patients were stratified into low-risk (LR), intermediate-risk (IR) and high-risk (HR) groups according to their initial features and the rate of response to induction therapy. LR-ALL patients were randomized to receive or not early consolidation chemotherapy (C-1). After receiving C-1, IR patients were randomized to receive or not delayed consolidation chemotherapy (C-2). HR patients received C-1 and C-2 chemotherapy. Standard maintenance chemotherapy was administered to all patients for 2 years. High doses of intravenous methotrexate and 12 triple intrathecal doses were given as prophylaxis against central nervous system (CNS) disease. RESULTS: The mean (and standard deviation) age was 6 (4) years and 120 patients were males. Fourteen patients had early pre-B-ALL, 149 common or pre-B-ALL, and 32 T-ALL. Complete remission (CR) was attained in 189 patients (97%), 11 of whom (6%) had a slow response. Risk group stratification after CR was: LR 89, IR 50 and HR 56 patients (including a subset of 26 patients at very high risk). Ten-year event-free survival (EFS) and overall survival (OS) probabilities for the whole series were 58% (95% CI: 52-64%) and 69% (61-77), respectively, with a median follow-up of 8.7 years. Dividing the patients according to risk group, the 10-year EFS and OS probabilities in the LR group were 71% (63-79) and 86% (80-92), respectively; in the IR group 69% (57-81) and 76% (64-88), respectively, and in the HR group 30% (18-42) and 44% (32-57), respectively. For LR patients receiving C-1, EFS and OS were 79% (57-92) and 90% (82-98), respectively, versus 62% (48-76) and 66% (51-81) in patients not receiving C-1 (p= 0.06). For IR patients, EFS and OS were significantly improved in those receiving early and delayed consolidation (EFS 87% (74-88) vs. 52% (41-70), and OS 92% (87-97) vs. 61% (51-71)(p=0.036). Prognostic factors for EFS identified in multivariable analyses were: age >10 years in the LR group (OR 3.5, 95% CI 1.3-9.5, p=0.01), and treatment with C-2 in IR patients (OR 5.0, 95% CI 1.4-17.8, p=0.01). The CNS relapse rate was 4% for all the series (including the HR subset). Tolerance to treatment was good. INTERPRETATION AND CONCLUSIONS: In this study, early consolidation seemed to improve the prognosis of children with LR-ALL, but differences in EFS were not significant. Delayed consolidation had a favorable influence on the outcome of IR-ALL. CNS preventive treatment without cranial irradiation was effective in all the groups of ALL patients.

Antineoplastic Combined Chemotherapy Protocols↗

Psychological issues in the treatment of asthmatic patients.

Recently published research contends that anxiety and depression are more common in asthmatic patients than in the general population. Particular psychological profiles could even be a risk factor contributing to deaths caused by asthma. The purpose of our research was to evaluate the anxiety and depression level in a population of 80 asthmatic patients who were treated in our department, and to judge whether data collected on psychological profiles of these asthmatic patients can be of any significance when dealing with their pathology. The study consisted of 40 patients suffering from chronic viral hepatitis B or C, and 40 healthy subjects who served as a control group. Both sets of patients were homogeneous with regard to sex, age and education. All subjects were tested for anxiety and depression levels with the S.T.A.I. and Zung questionnaires. A structured questionnaire was employed to assess the daily approach to living with the disease only in asthmatic patients. The anxiety and depression levels were noticeably higher in asthmatic patients than in patients with chronic liver disease and healthy subjects. In particular, 34 asthmatic patients scored higher than the S.T.A.I. cut-off (40/80) and 27 attained the same results in the Zung questionnaire. Results from the asthmatic population and healthy subjects illustrated that women had a higher incidence of anxiety and depression compared to men, although no statistically significant relationship between sex and questionnaire results was apparent in patients with liver disease. In the year before assessment, hospitalization and emergency treatment due to asthmatic exacerbation was correlated in females with a high incidence of anxiety. Additionally, the asthmatic population's level of education is significantly related to the incidence of anxiety and depression. With higher education, incidence of depression and anxiety decreased. This result was not apparent in control groups. The results of our study were: (1) we confirmed that asthmatic pathology is associated with an increase in incidence of anxiety and depression, whose presence and seriousness should be taken into consideration in therapeutic programmes when dealing with a patient; (2) we indicated that a specific approach towards therapy is crucial when dealing with an asthmatic patient; (3) we suggested how important it is to identify categories of patients that require more care because of their psychological profile. These findings should provide for the optimal use of informational resources with important applications for educational programmes and the future treatment of the asthmatic population.

Adult↗

Evaluation of the effects of zafirlukast 40 mg b.i.d. in addition to preexisting therapy of high-dose inhaled steroids on symptomatic patients with reversible respiratory obstruction: preliminary data.

Clinical evidence of the efficacy of zafirlukast is available for mild-to-moderate asthma, but further evidence is needed on its use in the more severe forms, uncontrolled by traditional therapy. The aim of this study was to evaluate the efficacy of zafirlukast 40 mg b.i.d. as an add-on to high dose inhaled corticosteroids (HDICs). A secondary aim was to assess the drug's safety and the patients' evaluation of oral therapy and compliance. Twenty-two asthmatic patients (13 females, aged 12-70 years) taking short-acting beta 2-agonists as needed and HDICs as maintenance therapy, entered a 2-week screening phase. At the end, 18 patients with baseline forced expiratory volume (FEV)1 = 50-80% of predicted, a reversibility of > or = 15% and a > or = 10 weekly total of daytime symptom score, were given zafirlukast 40 mg b.i.d. and were reevaluated every 4 weeks for 12 weeks. Adverse events, withdrawals and changes in hematology were recorded. A diary and a questionnaire were used for subjective patient assessment. Sixteen patients (nine females, mean age 40) completed the study. Mean FEV1, (absolute value and percentage vs. predicted) was significantly higher (p < 0.05) vs. baseline after zafirlukast, with a mean improvement of 0.2 l/sec (2.4 vs. 2.2) or 6% (76% vs. 70%) of predicted. Similarly, a significant (p < 0.001) increase in peak expiratory flow was observed (6 vs. 5.5 l/sec). There was no statistically significant variation in forced expiratory flow 25-75. Analysis of the diaries showed a statistically significant reduction (p < 0.05) of morning symptoms (0.73 vs. 4.6) and of daytime symptoms score (2.3 vs. 5.3). There was no evidence of improvement in night time symptoms and use of beta 2-agonists. Three patients experienced adverse events and four suffered a single exacerbation not requiring hospital admission. Subjective evaluation was positive: 75% reported an improvement, 25% found no change and 40% particularly appreciated the oral therapy. In conclusion, treatment with zafirlukast (40 mg b.i.d.) showed a significant improvement in function parameters and symptoms. Zafirlukast was well tolerated and accepted by patients. Further research is needed, as the small number of patients does not allow definitive conclusions to be drawn.

Administration, Inhalation↗

Phase-modulated rotating-frame NQR techniques for spatial encoding

The rotating-frame method of localization for spatially resolved spectroscopy and imaging in the pure quadrupole regime relies on a gradient B(1) field in which spins experience a flip angle dependent on their position in the B(1) field strength. So far, the techniques have been implemented as amplitude-modulated methods, i.e., the spatial nuclear quadrupole distribution is encoded in the amplitude of the free-induction decay signals. In this work, we describe the implementation of phase-modulated variants of both two-dimensional and rapid rotating-frame imaging techniques. The experiments are discussed for both single crystalline and powder samples. The phase-modulated experiment offers some advantages over the amplitude-encoding technique: It enables one to distinguish the sign of the spatial coordinate and the signal-to-noise ratio is higher than for the simplest amplitude-encoding method. Copyright 1999 Academic Press.

Journal Article↗

[Radioimmunoscintigraphy of colorectal cancer using the anti-CEA monoclonal antibody BW 431/26. Final results].

The anti-carcinoembryonic antigen (CEA) antibody, BW 431/26 (Scintimun CEA, Behringwerke, Marburg, Germany ) labeled with technetium pertechnectate (99mTc), is an intact immunoglobulin G1, monoclonal antibody that has been used to image colorectal cancer. Planar and SPECT images of chest, abdomen and pelvis were performed at 10 minutes, 4-6 and 18-24 hours after the intravenous antibody injection. 44 patients were studied and the pathological antibody concentration localization by radioimmunoimaging (RI) were correlated with surgical, clinical and other imaging modality findings to validate the RI. The RI was positive in 29 patients and negative in the other 15 patients. The CEA and CA 19.9 were elevated in the serum of some patients with primary tumors or recurrence. The HAMA were determined in all the patients before and after the RI.

Adult↗

Mapping molecular orientation in solids by rotating-frame NQR techniques

A multi-dimensional NQR technique to image both the spatial distribution of quadrupolar nuclei and the local orientation of the electric field gradient tensor at the quadrupole sites in solids is reported. The encoding procedure is based on the irradiation of the sample by a pulse sequence composed of spatially homogeneous and inhomogeneous radiofrequency fields. A method that encodes the spatial and orientation information in the amplitudes of the free-induction decay signals and a proper three-dimensional reconstruction procedure that yields the space-orientation-dependent NQR spectra are described. A two-dimensional variant allows rapid measurement of the spatially dependent orientation distribution of molecules, disregarding the spectroscopic information. Copyright 1998 Academic Press.

Journal Article↗

Analysis of natural killer-associated antigens in peripheral blood and bone marrow of multiple myeloma patients and prognostic implications.

The aim of this study was to analyse the expression of NK-associated antigens in both peripheral blood and bone marrow lymphocytes from a large series of newly diagnosed multiple myeloma patients. 112 patients with untreated multiple myeloma (MM) were included in the study. 36 sex- and age-matched healthy volunteers were used as controls for peripheral blood (PB) studies and 14 for the bone marrow (BM) studies. Simultaneous stainings with the CD3/CD56, CD2/CD16 and CD8/CD57 monoclonal antibodies were systematically performed in PB and CD3/CD56 and CD2/CD16 in BM in order to analyse their relationship with the clinical and biological characteristics of the disease and survival. The expression of NK-associated antigens (CD56, CD16 and CD57) assessed within the lymphoid gate, was significantly increased (P < 0.001) in the PB of MM patients both in relative and absolute numbers. In the BM a significant increase in the percentage of CD56+ lymphocytes (P < 0.001) was also observed; in contrast, the proportion of CD16+ cells did not differ significantly from that of normal BM samples. The number of CD56+CD3- lymphocytes increased significantly within high-risk patients (869 +/- 671) as compared to intermediate (388 +/- 212) and low-risk patients (274 +/- 199) (P = 0.04). Moreover, patients with high values of CD56+CD3- lymphocytes showed a statistically significant association with several adverse prognostic factors including anaemia, hypoalbuminaemia, renal failure, high beta 2M, DNA diploidy and high S-phase plasma cells. In addition, patients with higher absolute numbers of PB CD56+CD3-lymphocytes displayed a poorer prognosis, whereas patients with higher values of CD57+CD8- cells had a better outcome.

Adult↗

A new staging system for multiple myeloma based on the number of S-phase plasma cells.

In the present study, we analyzed the cell cycle distribution of bone marrow (BM) cells in 120 untreated multiple myeloma patients using a DNA/CD38 double-staining technique at flow cytometry in which plasma cells (PCs) can be clearly discriminated from residual BM cells based on their CD38 expression. This approach allows us to determine the proliferative activity of both PCs and residual normal BM cells. The percentage of S-phase cells in the myelomatous population was found to be significantly lower than that of the residual normal BM cells (P < .001). Regarding the proliferative activity of myelomatous cells, patients with a high number of S-phase PCs (> 3%) showed a significantly (P < .05) increased incidence of anemia and hypercalcemia; higher values of beta 2-microglobulin (beta 2M), urea, and creatinine; and higher numbers of peripheral blood natural killer cells, as well as a poor prognosis as assessed both by response duration and overall survival. With respect to the residual BM normal fraction, a low proliferative activity was significantly (P < .05) associated with the presence of anemia and neutropenia together with increased numbers of BM PCs, a higher incidence of Bence Jones myelomas, and DNA diploidy. Multivariate analysis showed that the number of S-phase PCs was the most important independent prognostic factor, allowing us to discriminate two subgroups of patients with different prognoses, even within the same clinical stage. Moreover, the S-phase PCs, together with beta 2M, age, and performance status, represent the best combination of disease characteristics for stratifying patients according to prognosis and allow the establishment of a simple and powerful staging system for multiple myeloma patients. In addition, this classification can be used for planning treatment in patients who are candidates for transplantation.

ADP-ribosyl Cyclase↗

Prognostic implications of DNA aneuploidy in 156 untreated multiple myeloma patients. Castelano-Leonés (Spain) Cooperative Group for the Study of Monoclonal Gammopathies.

In this study the incidence of DNA aneuploidy in a large series of untreated multiple myeloma (MM) patients was assessed in order to determine its clinical and prognostic significance. A total of 156 MM patients were included in the study. DNA measurements were performed in all cases at diagnosis using two different flow cytometry methods: (1) propidium iodide (PI) staining on isolated nuclei, and (2) CD38/PI double staining on whole cells. The DNA ploidy status was correlated with the most relevant clinical and haematological disease characteristics. From the 156 cases analysed, 91 (58%) were aneuploid (56% hyperdiploid and 2% hypodiploid). The correlation between the two techniques on the detection of DNA aneuploidy was excellent, although CD38/PI double staining would be preferable in cases with < 5% of DNA aneuploid plasma cells (PC). Upon comparing the clinical and haematological disease characteristics of hyperdiploid versus diploid cases, the former group was characterized by a lower age, reduced incidence of anaemia, lower beta 2M levels, higher proliferative activity within the residual normal haemopoietic cells, increased expression of CD56 antigen in PC, and higher proportion of PB CD4+ T cells. In contrast, diploid cases had a higher expression of the CD10, CD20 and CD15 antigens and greater numbers of PB CD56+CD3- NK cells (P < 0.05). Circulating PC were identified in six cases, all being diploid. Overall survival was significantly longer in hyperdiploid compared to diploid MM (P = 0.02). These results show that over 50% of MM patients are aneuploid, almost all of them being hyperdiploid. This characteristic is associated with better prognosis.

Adult↗

Topical flurbiprofen in extracapsular cataract surgery: effect on pupillary diameter and iris fluorescein leakage.

Recent clinical studies indicate that flurbiprofen, a cyclooxygenase inhibitor, prevents miosis and breakdown of the blood-aqueous barrier during cataract surgery. Yet based on clinical and experimental data, some researchers do not agree that flurbiprofen prevents miosis. We conducted a double-blind clinical study of the effects of topical 0.03% flurbiprofen sodium on intraoperative pupillary diameter and iris fluorescein leakage after extracapsular cataract surgery. In the first phase of the study, 120 patients who had extracapsular cataract extraction with posterior chamber intraocular lens implantation were randomly assigned to receive preoperative topical flurbiprofen or a placebo, with or without intraoperative epinephrine, in addition to the standard regimen. In the second phase, 60 of the 120 patients continued the topical flurbiprofen or placebo for one month postoperatively. Iris fluorescein angiography was performed at the end of the first and the fourth weeks. The results indicate that flurbiprofen was significantly more effective (P < .0001) in maintaining mydriasis during surgery than the placebo. This action was enhanced by intraoperative epinephrine. Flurbiprofen also significantly reduced (P < .001) postoperative iris fluorescein leakage.

Administration, Topical↗

Increased expression of natural-killer-associated and activation antigens in multiple myeloma.

The expression of both natural-killer (NK)-associated and activation antigens was studied by flow cytometry in the peripheral blood of 47 untreated multiple myeloma (MM) patients. A significant increase in both absolute and relative numbers of CD57 positive cells as well as in the proportion of CD16 and CD11b cells was observed in patients with MM, specially in those in early stages of the disease (clinical stages I and II), suggesting a possible surveillance mechanism in response to an emerging malignant clone. Additional double stainings showed that strong CD16+ NK cells coexpress the CD56, CD11b, and CD2 antigens, while they lacked CD3, CD5, and WT31 antigens. Moreover, the previously reported increase in CD8 cells present in MM would be mainly due to a subset of CD8 cells that coexpress the CD57 Ags. The expression of activation antigens, especially CD38, was increased in peripheral blood lymphocytes of MM patients, the differences reaching statistical significance both in absolute and relative numbers in those cases with high numbers of CD16 NK cells and thus suggesting that these cells are functionally activated. These results reveal the existence of an increase in NK and activated cells in the peripheral blood of myeloma patients that may reflect a host's immunological mechanism in an attempt to modulate tumor cell growth.

ADP-ribosyl Cyclase↗

Lymphoid subsets and prognostic factors in multiple myeloma. Cooperative Group for the Study of Monoclonal Gammopathies.

In a uniform series of 170 untreated myeloma patients (MM) we investigated the distribution of T cell subsets in peripheral blood (PB) and their relationship with the most relevant disease characteristics, including survival. CD4 cells were significantly decreased both in percentage and absolute numbers (P less than 0.0001). On the other hand, the CD8 cells only showed a slight increase in relative numbers. Upon correlating the abnormalities in the distribution of T cells with other clinical and biological disease characteristics the most remarkable correlation was with survival. A low number of CD4 cells (less than 700 x 10(6)/l) was associated with both an advanced clinical stage and a shorter survival (20 v. 43 months, P = 0.01). Moreover, a significant correlation also exists between the decrease in CD4 cells and both high beta 2-microglobulin (beta 2M) levels and anaemia. On the other hand, no relationship was found with the type of M-component nor with the plasma cell phenotype. Finally multivariate analysis showed that the number of CD4 cells add independent prognostic information to other well-established tests for the assessment of disease outcome in patients with multiple myeloma.

Age Factors↗

[Utility of the examination of plasma-cell morphology in the study of multiple myeloma].

PURPOSE: To assess the classification of Greipp et al in a group of multiple myeloma (MM) patients, in an attempt to correlate the morphological patterns with the clinico-biological features of the disease. MATERIAL AND METHODS: Bone marrow aspirates from 135 patients with multiple myeloma were examined by two different observers. RESULTS: Full accordance existed in 122 cases (90%). The four morphological MM subgroup distribution was: mature, 38%; intermediate, 30%; immature, 18%, and plasmoblastic, 14%. The analysis of the M component types with regard to morphology showed increased IgA cases within the intermediate (40%) and immature (48%) MM (p = 0.01), and Bence-Jones cases within the plasmoblastic MM (32%). On the contrary, no differences were found with regard to the clinical stage, although none of the plasmoblastic MM was in stage I. The incidence of renal insufficiency and of high bone-marrow infiltration progressively increased from mature to plasmoblastic MM, the difference between the extreme morphological groups being significant. The incidence of hypercalcaemia and lower paraprotein rates was higher in plasmoblastic myeloma, with significant difference with respect to mature myeloma (p = 0.05). The median survival was longer in intermediate (27.8 months) and mature (22.5 months) myelomas than in plasmoblastic (17.9 months) and immature (13.6 months) myelomas. After grouping the mature forms (intermediate plus mature) and the immature ones (plasmoblastic plus immature) the survival differences approached statistical significance (p = 0.07). CONCLUSIONS: This study suggests that the morphological examination of plasma cells should be included in the prognostic criteria of multiple myeloma.

Aged↗

Intraocular dapiprazole for the reversal of mydriasis after extracapsular cataract extraction with intraocular lens implantation. Part I: Dose-response correlation.

Dapiprazole, an alpha-blocking miotic drug, was used intracamerally at the end of extracapsular cataract extraction with posterior chamber intraocular lens (IOL) implantation. The double-blind study included 120 patients divided into four groups of 30 eyes; the groups received balanced salt solution, 0.125%, 0.25%, or 0.5% intraocular dapiprazole after IOL implantation and before suturing. Pupillary diameter recordings were performed immediately before and a few minutes after drug injection and two, four, and eight hours after surgery. The results showed a significant reversal of mydriasis by intraocular dapiprazole, especially with the 0.25% and 0.5% concentrations which did not differ significantly in effectiveness and safety.

Adrenergic alpha-Antagonists↗