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Biomedical subjects

C Tejero

Publications and source records attributed to C Tejero.

At least 19 recordsLinked to original sources

Lamotrigine and epilepsy in the elderly: observational study of low-dose monotherapy.

A one-year prospective, observational study was conducted in 222 elderly patients (>65 years old) with epilepsy. Patients received 25 mg/day lamotrigine for the first 15 days. The dose was then increased to 50 mg/day; further increases were allowed if necessary. Vascular epilepsy was the most frequent diagnosis (56% of patients), and concomitant medication was required by 75% of patients. The mean dose was 72.17 mg/day in the 132 patients who completed the study; the initial dose of 50 mg/day was maintained in 52% of these patients. There was a marked reduction in the number of seizures with 89% of the patients who completed the study continuing to be seizure-free after 1 year. Tolerability was generally good with 15 adverse events in nine patients. Only two patients developed a rash. In conclusion, low-dose lamotrigine is an effective and well tolerated therapy for the control of epilepsy in elderly patients.

Aged↗

Canine long-term bone marrow culture neutrophil production and functionality.

This in vitro study has been conducted to determine the optimal experimental conditions under which to produce canine neutrophils in long-term bone marrow cultures (LTBMC), establish functional parameters of neutrophils obtained from LTBMC and peripheral blood and to ascertain whether these cells display physiological similarities. Our aim is to provide an experimental model, enabling a correlation between hemopoietic injury and neutrophil functionality. The authors demonstrate for the first time that canine neutrophils grown in cultures are able to produce oxyradicals capable of killing bacterial products. Moreover, culture-grown neutrophils contain gelatinase granules, a marker of terminal neutrophil differentiation, and express a specific surface antigen. The results described in this article illustrate the development of a dynamic system that mimics physiological hemopoiesis.

Adenosine Triphosphate↗

Delayed neutrophil apoptosis after total body irradiation in mice. The role of granulocyte-macrophage colony-stimulating factor in neutrophil function.

We performed an in vitro study of the long-term effects of a sublethal dose (5 Gy) of x-irradiation on the survival and function of neutrophils in adult mice. For this purpose, we incubated control neutrophils harvested from long-term bone marrow cultures (LTBMCs) with supernatant withdrawn from cultures obtained in adult mice 6 or 9 months postirradiation. We noted a significant increase in superoxide anion production, NADPH, and protein levels in these cells after 3, 6, and 15 hours of incubation compared with the same cells incubated with supernatant from control LTBMCs. We also observed a delay in apoptosis that was correlated with maintenance of adenosine triphosphate levels and survival. Similar differences were found when control LTBMC neutrophils were incubated with granulocyte-macrophage colony-stimulating factor (GM-CSF) (1.3 nM). Indeed, enzyme-linked immunosorbent assay revealed a significant overproduction of this cytokine, together with higher interleukin (IL)-6 and IL-3 levels, in the supernatant from cultures of irradiated mice. Our results suggest that GM-CSF is one of the cytokines responsible for promoting the survival and activation of neutrophil function after total body irradiation.

Animals↗

[The referral of hospitalized patients with cerebrovascular pathology. Where, when and why. A cross-sectional multicenter study of the referral of patients with ischemia and predisposing factors].

OBJECTIVES: Referral of patients with ictus on discharge from hospital is a daily problem for neurologists, both because of the suitability of one place or another for maximum recovery of the patient and because of the effect on average stay, complications and use of resources. The aim of this study was to determine where and when patients with ictus were referred and what factors affect whether a patient goes to one place or another. PATIENTS AND METHODS: A transversal multicentric study (3 months) using a questionnaire was sent to all Insalud hospitals in Aragon, recording data of 128 patients from four hospitals. There were questions on medical, functional, demographic and socio-economic factors which might affect referral. RESULTS: On discharge 20% of the patients did not return to their own homes. In 50% of the cases where patients went to a supporting hospital (SH) socio-economic factors were decisive and in 20% were the only cause. Referral to SH was related to functional state and type of ictus, need for nursing care or rehabilitation, age, sex, marital status and place of residence. CONCLUSIONS: Apart from clinical criteria, many socio-economic factors determine the need for referral of patients to one place or another.

Adult↗

Methodological contributions for the morphometric study of the lung: approximation to the ideal sample size and quantification of collagen fiber.

BACKGROUND: A morphometric study of the rat lung was done to determine the importance, within the precision of a morphometric study, of the sample size in relation to the quality of the image and to propose a method for the quantification of lung collagen fiber. METHODS: Sixty Wistar rats, divided into two age groups consisting of adult and old rats, were used. The left lungs were studied and processed for light microscopy. Methylene blue, resorcin-fuchsin, and Sirius red stainings were performed. The variables were quantified automatically. In the sections stained with methylene blue, the variables alveolar chord, wall thickness, mean linear intercept index, tissue density, and internal alveolar perimeter were quantified, in two series, one with x40 magnification (panoramic image) and the other with x100 magnification. In the sections stained with resorcin-fuchsin, elastic fiber was quantified and the result related with that obtained for the variable tissue density. The results were compared statistically, and those obtained with different magnifications for single variables were related by using the correlation test; the misclassification indices were also calculated. In the sections stained with Sirius red, the surface that was birefringent to polarized light was quantified and related to the collagen fiber; the results were compared statistically. RESULTS: Concerning results obtained for single variables with different magnifications good, correlation indices were obtained (r > or = 0.62) for all but the wall thickness (r = 0.3). The results obtained for the panoramic images were the highest. The misclassification index was lower for the panoramic images. Significant differences (P < 0.5) were not found when comparing the mean birefringent surface in the two groups of animals. CONCLUSIONS: The results obtained lead us to consider that, despite the fact that the quality of the panoramic images is poorer, the results for these images are more accurate, possibly because a greater number of structures was analyzed. The measurement of the birefringent surfaces of the sections stained with Sirius red may be used in the study of lung collagen fiber.

Animals↗

Architecture, elastic fiber, and collagen in the distal air portion of the lung of the 18-month-old rat.

BACKGROUND: The increase in the distal air spaces which takes place with age is the only sufficiently documented datum for differentiation between the senile and the adult lung. There are other pulmonary components which may be modified as the lung enters the phase of old age, but they have not as yet been sufficiently studied. The purpose of this study is to make a morphometric comparison between the wall thickness of the distal air spaces, elastic fiber, and collagen in lungs of rats of between 5 and 18 months of age. METHODS: The left lung of each rat was histologically processed for light microscopy. The sections were contrasted using methylene blue, resorcinfuchsin and Sirius red. Systematic randomized sampling was used for the selection of the histological fields studied. Morphometric variables were studied, and were systematized into three groups, namely: variables related with the alveolar architecture, variables which quantify elastic fiber, and those which quantify collagen. RESULTS: The old animals exhibited significant differences (p < 0.05) in the following variables: 1. In relation with the alveolar architecture, mean linear intercept, alveolar chord and wall thickness increased, whereas internal alveolar perimeter and tissue density decreased. 2. The relation elastic fiber density/lung tissue density increased. None of the variables which quantify collagen displayed significant differences. CONCLUSION: Our data lead us to consider that the lungs of the old animals displayed, not only an enlargement of the distal air spaces, but also a thickening of the alveolar wall and an increase in elastic fiber in relation to the rest of the lung tissue.

Aging↗

Glucose metabolism in bone marrow cells and granulocytes of adult mice after X-ray (5 Gy) irradiation: relationship to cell functionality.

Our experiments focused on the metabolic implications of the residual haemopoietic damage in adult mice given 5 Gy X-rays. Bone marrow cells from irradiated mice exhibited an increase in protein synthesis and a decrease in ATP levels, which could be related to the enhancement of the proliferative activity of haemopoietic precursor cells. However, the kinetic parameters (Vmax and Km) of glucose uptake, the glycolytic flux and the hexose monophosphate (HMP) shunt activity were similar to those found in the control group. On the other hand, a reduction of glucose uptake (Vmax) was found in both resting and stimulated granulocytes from irradiated mice. This reduction was accompanied by a decrease in the glycolytic rate and ATP levels. However, HMP shunt activity was similar in resting granulocytes in both the control and the irradiated mice. The stimulation by PMA produced a significantly higher increase in the activity of the pathway in granulocytes from the irradiated mice and was in accordance with the enhancement of superoxide anion production that has been previously described in these cells.

Adenosine Diphosphate↗

Long-term haemopoietic injury in mouse by 1 Gy X-rays at different postconceptional stages.

Haemopoietic effects in mice produced by a single acute dose of 1 Gy X-rays given on the 4th (4R) and 13th (13R) day postconception were evaluated throughout the 9-month post-irradiation. The quality of the stroma was measured in long-term bone marrow cultures (LTBMC). LTBMC granulocyte production was always markedly lower among the irradiated offspring than among controls. IL-6 supernatant levels were significantly higher in both experimental models with respect to controls. However, supernatants from 13R mice had a greater colony-stimulating activity than 4R mice and controls. Granulocytes, from culture or peripheral blood, did not show changes in their functional activity after either treatment. With regard to the content of the femoral granulocyte-macrophage colony forming cells (GM-CFC), there was an enhancement of the GM-colony number as determined from the marrow of 13R mice. In these mice, an alteration in colony size and number due to different combinations of colony-stimulating factors was observed. In summary, our results obtained with irradiation during the foetal period suggest that this 1 Gy X-rays is sufficient to produce measurable, effects on developing murine haemopoiesis.

Animals↗

Changes occurring with increasing age in the rat lung: morphometrical study.

BACKGROUND: It was hypothesized that the evolution towards the senile lung is progressive, being initiated in the adult stage; and for this reason changes similar to those described in the senile lung can be detected in the lungs of middle-aged rats. To test the hypothesis, the following design was used. The lungs of two groups of rats, adult (mean age of 16 weeks) and middle-aged (mean age of 56 weeks) were morphometrically compared. METHODS: Thirty-one Wistar rats were used for the study; their lungs were processed histologically. The microscopic fields were analysed in a computer, and 20 variables were quantified. These were grouped into a) variables which describe the shape and size of the distal airspace, b) variables which describe the distal lung tissue, and c) variables which describe elastic fibers. The results were statistically compared: correlation tests were carried out, and the specificity, sensitivity, and misclassification indices were calculated. RESULTS: All the results of the variables which define the size of the airspaces were found to be significantly higher (P < 0.0001) in the middle-aged animals; the results obtained when the lung tissue was quantified directly from the histological section suggested a loss of tissue in the middle-aged animals. However, when these data were converted into absolute values, no loss was indicated in the total lung tissue. The values of the variables which describe the elastic fiber were found to have increased significantly (P < 0.0001) in the middle-aged animals. The misclassification index was found to be lower than 10% in six variables and between 10% and 20% in four. CONCLUSION: The low misclassification indices found lead us to consider that our morphometric method is ideal for distinguishing the lungs of the two groups of animals used. The results of the quantification of the variables show that the middle-aged animals exhibit simple enlargement of the distal airspaces, without tissue loss, which coincides with the current definition of the senile lung.

Aging↗

Pharmacokinetics of aztreonam in healthy elderly and young adult volunteers.

Aztreonam is a monobactam exhibiting an antibacterial spectrum similar to that of the aminoglycosides, with activity against aerobic gram-negative bacilli, and is the only related drug that may be given to patients hypersensitive to beta-lactams. The pharmacokinetics of aztreonam were compared in two groups of healthy volunteers. The young group comprised 10 adults between the ages of 18 and 30 years, and the elderly group included 10 adults older than 65 years of age. The two groups each received two doses (1 and 2 g) aztreonam, separated by 1 week. Although the mean peak serum concentrations of aztreonam for the two groups were similar, there were differences in other pharmacokinetic parameters. For example, for the 2-g dose the mean half-life (1.8 +/- .51 versus 3.1 +/- .9 hour), and area under the curve (AUC) (294.42 +/- 64.08 versus 469.01 +/- 144.02 micrograms x hour/mL per 1.73 m2) were less for the younger group compared with the elderly group. The mean total body clearance of aztreonam was greater for the younger than the elderly group. The results were similar to the pharmacokinetic parameters derived from the 1-g dose. These results mirror the lower creatinine clearances and higher serum creatinine levels found in the elderly group. The data suggest that lower doses of aztreonam given at less frequent intervals may be appropriate in the elderly population.

Adolescent↗

Residual haematopoietic damage in adult and 8 day-old mice exposed to 7 Gy of X-rays.

Our experiments have focused on the analysis of residual haematopoietic damage in 8-day-old and 12-week-old mice X-irradiated with a single dose of 7 Gy. In the case of the adult mice, analysis of the femoral and splenic CFU-S, CFU-GM and BFU-E showed a persistent depletion of these haematopoietic progenitor cells after irradiation. In contrast, in 1-week-old irradiated mice, a progressive recovery of the femoral haematopoietic progenitors was observed, achieving essentially normal values 1 year after irradiation. The spleens of these mice, however, contained significantly less haematopoietic progenitors than the control group, mainly as a consequence of the size reduction of this organ. In the peripheral blood, normal cellularity values were observed in most cases, although in the adult group a decline in numbers or circulating cells was noted after the first year following irradiation. Long-term bone marrow cultures (LTBMCs) established 1 year after the irradiation of adult mice generated poor adherent layers, while confluent stromas were observed in flasks corresponding to 8-day-old irradiated mice. Analyses of the functional activity of granulocytes obtained from either the peripheral blood or LTBMCs revealed that both young and adult irradiated mice produced granulocytes generating high levels of superoxide anion, in relation to age-matched controls. This finding was correlated with a long-term microenvironmental activation which resulted in an overproduction of granulocyte-macrophage colony-stimulating factor.

Age Factors↗

A relationship between residual stromal damage in hematopoietic tissue and the functional activity of granulocytes.

This paper analyzes the function of mouse granulocytes in the long term, after external irradiation with x- and gamma-rays and 239Pu contamination at different gestational ages and in a variety of culture conditions. These treatments can produce persistent defects in the stroma, which regulates hematopoiesis. Superoxide-anion production has been measured in granulocytes from peripheral blood and from long-term bone marrow cultures (LTBMC). A significant enhancement of O2- is produced using single or fractionated doses of x-rays; however, little or no increase is observed with gamma-rays. With 239Pu, enhancement of O2- depends on gestational age at contamination. The absence of hydrocortisone (HC) in LTBMC and the irradiation of the adherent layer with 15 Gy stimulate O2- production. The increased production of O2- appears to be correlated with an excess of colony-stimulating factors (CSFs) released to the supernatant by stromal cells. Neutralization with anti-granulocyte-macrophage CSF (anti-GM-CSF) monoclonal antibody shows that GM-CSF is the main factor produced. In summary, conditions that lead to residual stromal damage also result in the generation of granulocytes that are functionally primed for excess superoxide-anion production.

Animals↗

Mechanisms towards compensation of long-term haemopoietic injury in mice after 5 Gy irradiation: in vivo and in vitro enhancement of superoxide anion production by granulocytes.

This paper analyzes the long-term (6 and 12 months) function of mouse granulocytes after total body irradiation with a single dose (5 Gy) of X-rays. Superoxide anion production has been investigated in granulocytes from peripheral blood, and also in those harvested from long term bone marrow cultures, with the aim of correlating the environmental damage induced by radiation with the functional properties of granulocytes. An in vivo and in vitro enhancement of superoxide anion production and protein levels in granulocytes from irradiated mice is described. The presence of some colony stimulating factor in the supernatant of cultures from irradiated mice could play an important role in the priming of granulocytes.

Animals↗

Transferrin binding of bone marrow cells and metabolic activity of erythrocytes after 5 Gy irradiation.

The effect of total body irradiation (5 Gy) on functional mouse erythroid lineage has been studied. The transferrin binding capacity by bone marrow cells and the activity of glycolytic regulatory enzymes and intracellular levels of 2,3 bisphosphoglycerate in peripheral blood erythrocytes have been determined. Results obtained along one year post-irradiation period suggest a complete recovery in the erythroid cell lineage with respect to the biological endpoints investigated.

2,3-Diphosphoglycerate↗

Kinetic studies of pyruvate kinase during in vitro differentiation of GM-CFC haemopoietic precursor and bone marrow cells in mice.

Pyruvate kinase studies in the granulocyte-macrophage lineage during in vitro differentiation have been performed using culture techniques on GM-CFC cells and a study has also been done in bone marrow cells. The enzyme exhibits biphasic behaviour with respect to both of its substrates in cells derived from in vitro cultures at 5 and 7 days of incubation period. However in bone marrow cells these kinetics are only observed for ADP. The different kinetic behaviour of pyruvate kinase toward Fru-1,6-P2, Ala, Phe and ATP in the three cellular populations allows us to conclude that the expression of pyruvate kinase is associated with the differentiation of these cells.

Adenosine Diphosphate↗

Role of phosphofructokinase during trout haemopoiesis: physiological regulation of glycolysis.

1. The regulatory properties of phosphofructokinase (PFK) has been investigated in two cellular population representatives of trout haemopoiesis; haemopoietic cells (capable of replication and differentiation) and erythrocytes (highly specialized cells). 2. The intracellular levels of substrates and effectors have been quantified and their effect on PFK activity determined. 3. Fructose 1,6-bisphosphate anc cyclic AMP show a higher activation of the PFK from haemopoietic cells than the enzyme from erythrocytes. 4. AMP and phosphoenolpyruvate act as activators of the haemopoietic cell PFK while for erythrocytes PFK, AMP is an inhibitor and phosphoenolpyruvate does not display any effect. 5. Citrate inhibits PFK activity from haemopoietic cells but was not assayed in erythrocytes since it was not detected in these cells. 6. The differences in PFK regulation in both cellular populations may be attributed to the intracellular levels of the effectors and/or different isoenzymatic patterns. 7. The different regulation of PFK together with the higher enzymatic activity of PFK and pyruvate kinase from haemopoietic cells are related to the higher glycolytic flux that exhibits the haemopoietic cells. 8. The results shown in this investigation allow us to conclude that PFK has a specific role depending on the energetic requirements of the cellular population in which the enzyme is present. 9. The requirements are related to the physiological function of each type of cell.

Animals↗