FK 506-based immunosuppression in clinical pancreas transplantation.
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Biomedical subjects
Publications and source records attributed to R Perez.
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Traumatic aneurysms constitute a very small percentage of all intracranial aneurysms. A high mortality results of a catastrophic rupture and they run an unpredictable course. Traumatic aneurysms usually involve the large basal arteries or the middle meningeal arteries. We report a case of an association of a traumatic aneurysm with a congenital aneurysm located on the same middle cerebral artery. At our knowledge, it is the first described case of the literature.
Cardiovascular variables of both mother and fetus and total bile acid levels were monitored in amniotic fluid and in maternal and fetal plasma after the administration of a single intravenous high dose (29 mg) of cholic acid to a pregnant ewe. We observed the diffusion of significant quantities of cholic acids from the mother to the fetus and amniotic fluid. Nevertheless, cardiovascular parameters (heart rate, blood pressure, PO2, PCO2 and pH) were not affected, neither did intra-amniotic pressure show significant changes compared with the initial experimental conditions. It is concluded that an acute increase in maternal plasma levels of bile acids does not produce important adverse effects in either the mother animal or the fetus and consequently, if bile acids should be deemed responsible for any deleterious effect observed in a preterm fetus in intrahepatic cholestasis, this should be considered as the consequence of a chronic process.
Insulin and nerve growth factor are peptides that share several chemical and functional properties. While the total or relative deficiency of insulin causes diabetes, the possible disorders due to deficiency of nerve growth factor have not been clearly defined. However, the intense biological actions of nerve growth factor in the maintenance and growth of several neural cells make feasible its participation in the physiopathology of some diseases of the peripheral nervous system. We measured the contents of nerve growth factor in serum, submaxillary gland and sciatic nerve of mice with streptozotocin-induced diabetes. Nerve growth factor in diabetic mice was diminished in serum and submaxillary gland when compared with matched controls (P < 0.01). This finding further supports a similar observation in diabetic patients and suggests a possible etiological involvement of neural growth factor in the development of diabetic neuropathy.
Plasma concentrations of beta-carotene and retinol after supplementation of children with beta-carotene in supplements and in foods were compared in Guatemalan children. The children received 6 mg/d beta-carotene [1000 retinol equivalents (RE)] as purified supplements or as carrots for 20 d and the effects on plasma beta-carotene and retinol concentrations were assessed. Plasma concentrations of beta-carotene were increased by 0.59 +/- 0.65 and 0.60 +/- 0.67 mumol/L after supplementation with beta-carotene capsules for 10 and 20 d, respectively. Addition of cooked carrots to the diet resulted in no significant change in plasma beta-carotene. Fasting plasma retinol concentrations were 1.23 +/- 0.35 mumol/L and were not significantly changed in response to supplementation with either of the carotene treatments with retinyl palmitate (1000 RE/d) for 20 d. Possible explanations for the differences in effects of plasma concentrations between the two methods of supplementation are discussed.
Xylazine has been characterized as a selective alpha 2-adrenoceptor agonist, which has explained its central nervous system depressant and other pharmacological effects. In order to characterize the effect of xylazine on uterine motility during the oestrus cycle in goats, intrauterine pressure changes were recorded in cycling goats using balloon-tipped catheters placed in the uterine horns and connected to pressure transducers and a recorder. The effect of xylazine on myometrial activity was studied by giving increasing doses of the drug (1.0, 10.0, 100.0 or 500.0 micrograms/kg) intravenously (i.v.) to animals either in the follicular or the luteal phase of the cycle. To establish the subtype of alpha adrenergic receptor mediating the action of xylazine, goats were pretreated with either prazosin (1.0 mg/kg, i.v.) or yohimbine (1.0 micrograms/kg, i.v.). To establish whether the effect of xylazine was pre- or post-synaptic, xylazine (100 mg/kg, i.v.) was administered to goats pretreated with reserpine (0.8 mg/kg, i.p.) to deplete presynaptic catecholamine stores. Xylazine induced a significant and dose-dependent increase on uterine motility in cycling goats, apparently mediated by post-synaptic alpha 2-adrenoceptors.
The specific influence of malnutrition on the pathophysiological changes induced by chronic alcoholism is controversial; most studies are inconclusive because they have been made in chronic alcoholics that develop malnutrition as a complication of alcoholism. However, in vast human groups, alcoholism evolves in individuals that belong to a chronically undernourished population. In an attempt to simulate real-life conditions of malnutrition-alcoholism in humans, we studied in rats: (1) the effects of chronic malnutrition with tortilla, a corn bread that constitutes the main diet of large human groups; (2) the effects of chronic alcoholism with commercial brandy; and (3) the effects of chronic alcoholism and malnutrition combined. The damage induced either by alcoholism or that induced by malnutrition alone were of similar degree, whereas the combination of malnutrition and alcoholism led to a worsening of some parameters studied: body weight, leucocyte count and, more remarkably, in the tissue damage of several areas of the central nervous system.
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Small cell lung cancer, an aggressive malignancy characterized by early dissemination, is highly responsive to radiotherapy and cytotoxic chemotherapy. Since the introduction of combined-modality regimens that incorporate both radiotherapy and chemotherapy, the median survival time for patients with localized disease has increased to 12 to 15 months, but median length of survival of patients with extensive disease has remained at a plateau of only 6 to 8 months. New cytotoxic agents, such as ifosfamide, etoposide, and carboplatin, have contributed to a reduced toxicity profile and an increase in complete response rates to combination regimens of 40% to 50%, but they have not contributed to any major increase in long-term survival. Potential strategies for improving efficacy and reducing toxicity of the chemotherapy of small cell lung cancer are reviewed.
Because of the horizontal separation of both ocular globes, the projection angles are slightly different. These differences are commonly termed retinal disparities. Vertical and horizontal retinal disparities occur constantly in normal life. We have investigated the responses of single cells in cortical areas V1 and V2 of behaving Macaca mulatta monkeys to retinal disparities by using dynamic random dot stereograms. Our findings show that cortical visual cells are sensitive to both vertical and horizontal disparities. To calculate the distance between two objects in a three-dimensional space from horizontal disparities, it is necessary to know the fixation distance. It has been suggested that the horizontal gradient of vertical disparity contains information to estimate the fixation distance and therefore to scale horizontal disparities. We suggest that these cells sensitive to horizontal and vertical disparities represent a neural mechanism that provides information to the visual system in order to achieve a correct eye alignment and depth perception.
This paper presents results obtained from experiments performed on two behaving monkeys (Macaca mulatta) viewing correlated and uncorrelated dynamic random dot stereograms. Extracellular single unit activity was recorded from areas V1 and V2. We found that cells sensitive to correlated stereograms (38%) were also sensitive to uncorrelated stereograms. Regarding their response to both situations, these cells were grouped into two types. The first type (57%), termed "correlation-sensitive cells", responded with statistically significant difference to correlated and uncorrelated stereograms. The second type responded equally to both stereograms (43%), and therefore they were termed "correlation-insensitive cells". Our data suggest that these two types may form two populations with different functions subserving depth perception.
Experimental autoimmune orchitis (EAO) was induced in adult Wistar rats by active immunization with a testicular homogenate (TH) and adjuvants. Fifty per cent of the immunized rats developed EAO. Testicular damage became evident at 50 days after the primary immunization and increased in severity at 80 days. Phenotypic characterization of T-cell subsets (CD4+ and CD8+) and Ia+ cells was performed on cryostat sections of testis obtained from normal rats, rats immunized with adjuvant (control group) and rats immunized with TH and adjuvants (experimental group) at 50 and 80 days. Labelled cells were only detected in the interstitial area; no labelled cells were observed inside the seminiferous tubules with any of the monoclonal antibodies used (W3/25, OX-8, OX-6). A significant increase in the numbers of CD4+ and CD8+, as well as of Ia+ cells, were observed in the testis of rats with severe EAO at 80 days after the first immunization. Rats of the same experimental group without testicular damage showed no major differences compared to rats from the control group, with the exception of a lower number of CD8+ cells. Variations in the lymphocyte subsets in lymph nodes draining the site of immunization showed the opposite pattern to that observed in the testis. In conclusion, these data suggest the traffic of specifically sensitized lymphocytes from lymph nodes to the testis and an active role of CD4+, CD8+ and Ia+ cells in the pathogenesis of EAO in the rat.
The aim of this study was to evaluate the role of clomiphene citrate (CC) therapy in the hypothalamus-pituitary-gonadal axis of male uremic subjects. Thirty-four patients on hemodialysis (HD) and 8 successful kidney transplant subjects (RT) were evaluated. Nine healthy males were used as controls (C). At baseline, zinc, testosterone (TEST), prolactin (PRL), FSH, LH and estradiol plasma concentrations were measured. All subjects were treated with CC (100 mg/day) for a week. The aforementioned parameters were determined again on the seventh day of CC therapy, and 3 days after drug withdrawal. Following CC, there was a rise in FSH, LH and TEST levels in all subjects (p < 0.05); it is interesting to stress that TEST became normal in HD. In addition, we observed a decrease of PRL after CC only in HD patients (p < 0.01). In summary, CC was able to partially correct most of the hormonal disturbances of the gonadal axis in uremic patients.
Patients who undergo organ transplantation receive immunosuppressive drugs in the posttrans-plant period. All of these drugs influence host metabolic response or alter nutrient intake. One of the most prominent aspects of the posttransplant period is the occurrence of hyperlipidemia, which may require dietary or pharmacologic control. Dietary recommendations for this patient population include limiting carbohydrate intake, restricting caloric intake to maintain ideal body weight, and maintaining a low cholesterol/saturated fat diet.
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The prognostic significance of the epidermal growth factor receptor status (EGF-R-status) for certain human tumors requires the development of antibodies useful for clinical application. We used purified receptor preparations to generate monoclonal antibodies immunoreactive with the EGF-R purified from placenta membranes and A431 tumors. Four of the hybridomas contained antibodies (R2, R3, R5, and R9) which recognized both antigens. Antibody R3 was shown to display the following properties: it binds with a KD value of about 10(-9)-10(-10) M to the receptor, a half maximal inhibition of EGF-binding is achieved at 5 x 10(-8) M, and in Western blots of cell membranes R3 specifically detects the EGF-R at 0.1 micrograms/ml. R3 inhibits EGF-dependent clonogenic growth of NRK cells and completely blocks EGF stimulated autophosphorylation of the receptor. Moreover, R3 also detects EGF-R in paraffin-embedded tissue sections taken from human salivary gland, term placenta, and adult skin and mammary carcinomas. Thus, R3 can be used in retrospective diagnostic clinical studies and might help to develop new immunotherapeutic intervention.
A study was undertaken in five draught horses of 648 +/- 33 kg body weight to find the effects of continuously pulling loads on their cardiovascular, respiratory and metabolic responses. A cart equipped with an odometer, for measuring distance, and a hydraulic dynamometer, for measuring draught force, was used. Heart and respiration rates and rectal temperatures were recorded. Blood samples for measuring arterial and venous pH and blood gases, haemoglobin, glucose and lactic acid concentrations and the serum activity of the enzymes creatine phosphokinase (CK), lactate dehydrogenase, aspartate aminotransferase and alkaline phosphatase were taken before exercise and immediately after each journey (morning and afternoon) of the daily work. Draught exercise, with loads which generated forces of between 0.57 and 0.59 kN, at speeds of 1.60 to 2.11 m/s, for 8 h daily for five consecutive days, with resting intervals of 10 min each hour, was well tolerated. Exercise tolerance was evaluated from the recovery from the changes observed in the biochemical and physiological parameters induced by the work. The analysis of these showed that, when the horses were subjected to prolonged periods of resting, their loss of fitness for work was shown by significant increases in the serum activity of muscle-derived enzymes and in blood lactate concentrations during the first day of work. However, over the following days the horses adapted to the work, so that the decreases in serum enzyme activities and blood lactate concentrations were reduced. Since similar observations have been described for racehorses, the determination of blood lactate concentrations and the serum activities of muscle-derived enzymes, specifically CK, seem to be good indicators of fitness in draught horses.