[Cardiovascular pharmacology (II). The current validity of old drugs: nitrates].
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Biomedical subjects
Publications and source records attributed to J García.
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We began our program in September 1992, using the Nucleus 22 Channel Cochlear Implant. To date, we have operated on four patients, one child with congenital hearing loss, two prelinguistically deaf adults and one perilingually deaf adult. Our results have shown a significant increase in auditory and speech reception and perception skills in the child. The perilingually deaf adult is able to understand speech in open set speech discrimination testing and, although we do not expect open set speech discrimination in the prelinguistically deaf adults, to date their results have been satisfactory. The two prelingually deaf adults are in an audiological rehabilitation program. Their response in prosodic aspects of speech and lipreading ability with sound have improved significantly. The only surgical complication was an infection of the flap in the child, but it was treated satisfactorily with i.v. penicillin.
The epitopes of 10 monoclonal antibodies (MAbs) directed against the phosphoprotein (P) of human respiratory syncytial (RS) virus (Long strain) were mapped onto the protein primary structure by testing their reactivity with both protein fragments and synthetic peptides. Seven epitopes were clustered in the N-terminal end, two others were located in the central region, and one epitope was mapped in the C-terminal end of the P molecule. The location of epitopes in the P protein sequence correlated with other properties, such as antigen binding competition and immunofluorescence staining of RS virus-infected cells. The antibodies that recognized epitopes of the N-terminal end revealed the presence of cytoplasmic inclusions while others gave mainly a diffuse cytoplasmic staining. Thus, accessibility of certain P protein epitopes seems influenced by the incorporation of this molecule to the inclusions of RS virus-infected cells.
Immunofluorescence staining and immunoelectron microscopy of respiratory syncytial (RS) virus-infected cells revealed the presence of cytoplasmic inclusions that were specifically labeled with monoclonal antibodies directed against the nucleoprotein (NP), the phosphoprotein (P), or the 22K protein. Transient expression of these three proteins with the vaccinia-T7 system, either individually or in different combinations, demonstrated that coexpression of NP and P was sufficient to induce the formation of cytoplasmic inclusions similar to those found in RS virus-infected cells. In addition, the 22K protein was also incorporated to the inclusions when coexpressed with both NP and P proteins. Immunobinding assays revealed the presence of NP-P and NP-22K complexes in extracts of RS virus-infected cells. These complexes were also detected in extracts of transfected cells that coexpressed the corresponding proteins. The implications of these results for the RS virus replicative cycle are discussed.
The use of lymphokine-activated killer (LAK) cell therapy in delayed treatment requires the use of cryopreserved effector cells. The purpose of this study was to determine the optimal cryopreservation protocol for the maintenance of cytotoxic activity in mononuclear cells (MNCs). MNCs were cryopreserved with dimethyl sulfoxide or 1,2-propanediol before and after 3 days of culture with recombinant interleukin 2. The effects of cryopreservation on cell recovery, LAK cell and natural killer (NK) cell cytotoxic activities, and surface antigen markers were studied. Recovery of nonactivated MNCs was higher with 1,2-propanediol than with dimethyl sulfoxide (p < 0.05). Cytotoxic activities, measured with a 51Cr release assay, significantly decreased after thawing, on both activated cells (76.3%; range, 35.8-92.2%) and fresh cells (54.6%; range, 17.5-75.4%). A 6-day kinetic test was used to compare the cytotoxic activity of cryopreserved and fresh cells. The results showed different patterns for NK cells (cryopreserved cells had lower levels of activity than fresh cells) and LAK cells (cryopreserved cells had higher levels of activity than fresh cells). Phenotype changes of effector cells in culture, with and without cryopreservation, were monitored by flow cytometry using monoclonal antibodies. These results were compared with changes in the cytotoxicity of cells with and without cryopreservation. After thawing, there was a decrease in MNCs expressing CD14 and CD56. Recovery of the CD56 marker correlates with increased cytotoxic activity. Despite some loss of NK cell activity, it is concluded that MNCs may be successfully cryopreserved before their use in immunotherapeutic treatment.
Using a combination of polymerase chain reaction and single-strand conformation polymorphism techniques (PCR-SSCP) we have analyzed 78 brain tumor samples (70 primary and 8 metastatic) for the presence of mutations in the conserved regions of the Tp53 (tumor p53) gene. We have found that only two groups, gliomas (exclusively in astrocytomas) and metastases, displayed Tp53 mutations. Three of eight (37.5%) metastases showed a mutant Tp53 allele accompanied by loss of the normal one. In contrast, the frequency of Tp53 mutations in the primary brain tumors examined was lower (5.7%). Although we have examined different types of primary brain tumors, Tp53 mutations were exclusively observed in both, low and high-grade astrocytomas (four of 24). The Tp53 mutations detected in astrocytic tumors appear to be correlated with the malignancy grade. The low-grade astrocytomas were heterozygous for the mutation, whereas the high-grade astrocytomas had affected the two Tp53 alleles, suggesting a two-steps model for inactivation of the p53 gene in astrocytomas. Thus, single p53 mutation seems to occur in initial stages of astrocytoma tumorigenesis; the later lost of the remaining wild-type allele appears associated with the progression towards a more malignant stage.
The results of autologous bone marrow transplantation (ABMT) in acute leukemia (AL) and the prognostic factors for outcome were analyzed in a series of 90 consecutive patients treated at a single institution (mean +/- SD age: 25 +/- 11 years). Diagnosis was: AML (n = 43), ALL (n = 44), acute undifferentiated leukemia (n = 2) and acute bilineage (n = 1). Disease stage at ABMT was: first complete remission (CR1) 46 cases, CR2 33, other stages 11. Conditioning consisted of cyclophosphamide and total body irradiation in 88 patients. The 3 year probability of disease-free survival (DFS) was influenced by disease stage at ABMT: CR1 48%, CR2 28%, CR3 plus CR4 15%. The characteristics associated with a high probability of relapse were: in AML a FAB subtype other than M1 or M3 (p = 0.01) and in ALL an interval between CR1 and ABMT of < 3 months (p = 0.002). A WBC > 15 x 10(9)/l at diagnosis (p = 0.01), splenomegaly at diagnosis (p = 0.002) and time to CR1 > 4 weeks (p = 0.06) increased the risk of relapse in the entire group in CR1. In multivariate analysis, WBC at diagnosis (p = 0.006) and disease stage at ABMT (p = 0.03) independently influenced DFS. This study confirms the encouraging results of ABMT in CR1 but further antileukemia measures are necessary in patients with adverse prognostic features.
UNLABELLED: BACKGROUND. The increasing age of the population, makes necessary to have "normal values" in order to make diagnosis and treatment in this population group. The purpose of this study is to determine the morphological and functional changes in a group of healthy aged above 70 years. METHODS: We studied 125 subjects older than 70 years, mean of 74.9 and 50 healthy aged 9-45, with a mean of 25.8, who served as control group. Twenty-five were excluded by history, chest X-Ray, ECG and Echocardiogram because cardiac disease. An echocardiographic M and 2D and pulsed Doppler study, was done to obtained several morphological and systolic and diastolic function parameters. A good quality echo to measure morphologic and systolic function was obtained in 69 study group patients. In all study and control group, was obtained a good quality mitral flow signal to measure diastolic function.
A 46-year-old female, who underwent an orthotopic heart transplantation 5 years ago, presented an occlusive coronary artery disease with severe stenosis of the left anterior descending artery and a large septal perforator. An isonitrile scintigraphy showed a decreased uptake involving the anterior and inferior segments of the left ventricle. Percutaneous transluminal coronary angioplasty was successfully performed in both lesions. Three months after dilatation, improvement of the uptake in both myocardial segments was detected. The results of the percutaneous transluminal coronary angioplasty published in the literature are reviewed.
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BACKGROUND: Fracture of the hip constitutes a serious social/health care problem with very little information concerning incidence in Spain being available. METHODS: The diagnosis of hospital admissions and the diagnosis of release from the traumatology units of health care centers for acute patients in Cantabria were reviewed. The study was carried out from the 1st of January to the 31st of December 1988 and only included patients over 49 years of age. Patients who did not habitually reside in the region were excluded. The following data were collected in each case: age, sex, place of residence (urban or rural), time of the year, side fractured, type of injury, previous contralateral fracture and perioperative mortality. RESULTS: The rate of fracture referred to the population of more than 49 years of age was 277/100,000 in the case of females and 100/100,000 for males. The mean age of women was 80.4 +/- 8.5 years and of men was 76.9 +/- 10.9 years (p > 0.02), respectively. No differences were observed with regard to the place of residence or the time of year. The fracture was left sided in 61% of the females and 58% of the males. The injury was almost always due to a fall. Six percent of the patients had a previous contralateral fracture. Perioperative mortality was 6%. CONCLUSIONS: The incidence of hip fracture in Cantabria is similar to that of other regions in Spain and lower to that of parts of central and northern Europe and the United States.
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BACKGROUND: To observe whether patients with breast cancer of an epithelial strain consult physician with a less advanced disease, the patients attended by the Valencian Interhospital Group were studied between January 1981 and December 1990. METHODS: The same diagnosis of disease spread (anamnesis, physical examination, blood analysis and imaging techniques of the thorax, bones and liver) was carried out in all cases. Surgical techniques and histopathologic criteria were homogenous throughout the study. The classification used was that of the International Union Against Cancer of 1987. Histopathologic correlations were studied. RESULTS: Seven hundred seventy-nine patients with a mean age of 57.3 years (range: 24-85) were studied. A statistically significant (S) progressive reduction in the size of the tumor was observed (p less than 0.003) with the percentage of stage II progressively increasing and stage IIIa (more advanced disease than stage II) parallelly diminishing (p less than 0.0019) (S). In patients over the age of 55 this diminution was not observed. To the contrary, more advanced stages (stage IIIb--locally advanced, and stage IV--metastatic disease) were presented than in younger women (p = 0.000) (S). There is a direct correlation between the size of the tumor, the degree of tumoral differentiation and lymphatic metastases. CONCLUSIONS: Patients under the age of 55 spontaneously and progressively consult the physician with a less advanced breast cancer. This is expected to have beneficial effects on survival. It is suggested that primary medicine may play a fundamental role in making women more aware of breast cancer, particularly those over 55 years of age regardless of early detection campaigns.
BACKGROUND: To describe the clinical features and prognosis of the patients with cardiac tamponade admitted in the coronary care unit. METHODS: Analysis the clinical data, etiology, treatment, and short term outcome of fifty three patients presenting with cardiac tamponade that required pericardiocentesis. RESULTS: Neoplasm (21 cases) and idiopathic pericarditis (10 cases) were the most frequent causes of cardiac tamponade. In forty four patients an haemorrhagic fluid was obtained. Neoplastic pericardial fluid showed a higher haematocrit than the rest (18 +/- 8% vs 7 +/- 5%, p less than 0.01). Recurrence of tamponade occurred in all but one neoplastic patients, and was early (less than 48 h) in 18 patients. Twenty seven patients underwent pericardiectomy, and recurrence was the most frequent indication (18 cases). Overall in-hospital mortality was 26%. Ten out of 14 deaths occurred in neoplastic patients and 2 deaths after myocardial perforation related to temporary pacemaker. No patient with idiopathic or post-pericardiotomy cardiac tamponade died. CONCLUSIONS: Short term outcome and prognosis in patients with cardiac tamponade mainly depends on the etiology. A high rate of early recurrence and death characterize the malignant cardiac tamponades.
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OBJECTIVE: To determine the cellular source of the angiogenic activity displayed by follicular fluid (FF). DESIGN: Human granulosa cells were harvested from 27 follicular aspirates obtained 34 to 36 hours after eight patients, previously treated with human menopausal gonadotropin (hMG), follicle-stimulating hormone plus hMG, or clomiphene citrate and hMG received human chorionic gonadotropin (10,000 IU intramuscularly). Granulosa cells from individual follicles were plated at 50,000 cells/cm2 in Medium 199 (Sigma, St. Louis, MO) supplemented with either 5% calf serum or 0.1% bovine serum albumin; media collected 24 hours later was assayed in vitro measuring endothelial cell migration. Fractions depleted of steroids by reversed phase C1 chromatography were assayed as well. RESULTS: Granulosa cell-conditioned media from 18 of 27 follicles significantly stimulated endothelial cell migration (P less than 0.05). Chemoattractant activity did not appear to be related to steroid accumulation in the media and was not diminished in steroid depleted fractions. CONCLUSIONS: These findings suggest that human granulosa cells are a source of (nonsteroidal) endotheliotropic-angiogenic activity in FF.
1. The Vaseline-gap technique was used to record calcium currents (ICa) and charge movement in single cut fibres from normal human muscle. Experiments were carried out in 2 or 10 mM-extracellular Ca2+ concentration ([Ca2+]o) and at 17 or 27 degrees C. 2. The passive electrical properties of the fibres with this technique were: membrane resistance for unit length rm = 59.4 k omega cm; longitudinal resistance per unit length ri = 4.9 M omega/cm; longitudinal resistance per unit length under the Vaseline seals re = 438 M omega/cm; specific membrane resistance Rm = 1.176 k omega cm2; input capacitance = 5.53 nF; specific membrane capacitance = 8.9 microF/cm2. 3. The maximum amplitude of ICa at 17 degrees C was: in 2 mM [Ca2+]o, -0.42 microA/microF and in 10 mM [Ca2+]o, -1.44 microA/microF. At 27 degrees C and in 10 mM [Ca2+]o, it increased to -3.04 microA/microF. The calculated temperature coefficient (Q10) for the increase in amplitude from 17 to 27 degrees C was 2.1. 4. Ca2+ permeability (PCa) was calculated using the Goldman-Katz relation; in 2 mM [Ca2+]o at 17 degrees C, PCa = 1.26 x 10(-6) cm/s; in 10 mM [Ca2+]o at 17 degrees C, PCa = 2.23 x 10(-6) cm/s; in 10 mM [Ca2+]o at 27 degrees C, PCa = 4.03 x 10(-6) cm/s. 5. The activation curve calculated from the PCa was shifted by 10 mV to positive potentials when raising [Ca2+]o from 2 to 10 mM. Increasing the temperature did not change the curve. The mid-point potentials (Va 1/2) and steepness (k) of the activation curves were: at 17 degrees C, in 2 mM [Ca2+]o, Va 1/2 = -1.53 mV and k = 6.7 mV; in 10 mM [Ca2+]o, Va 1/2 = 9.96 mV and k = 6.8 mV; at 27 degrees C and 10 mM [Ca2+]o, Va 1/2 = 11.3 mV and k = 7.7 mV. The activation time constant in 10 mM [Ca2+]o reached a plateau at potentials positive to 10 mV, with a value of 93.8 ms at 17 degrees C and 17.4 ms at 27 degrees C. The calculated Q10 was 4.5. 6. The deactivation of the current was studied from tail currents at different membrane potentials in 10 mM [Ca2+]o.(ABSTRACT TRUNCATED AT 400 WORDS)