Erythropoietin therapy for uremic pruritus.
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Biomedical subjects
Publications and source records attributed to J Pascual.
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We assessed, by quantitative autoradiography, the density of high-affinity alpha 2-adrenoceptors in hippocampus and frontal cortex sections from 18 patients dying with Alzheimer's disease (AD) in comparison with a control group of 13 matched cases. The full agonist [3H]bromoxidine (UK-14304) was used as a ligand. In AD brains, the specific binding of [3H]bromoxidine was markedly decreased both in frontal cortex, the reduction ranging from 55% on layer I (P less than 0.0005) to 40% loss on layers IV-VI (P less than 0.01), and in the hippocampus where the mean of alpha 2-receptor loss was 53% both for the CA1 (P less than 0.0005) and the dentate gyrus (P less than 0.005). This dramatic decrease in the density of functional, high-affinity alpha 2-adrenoceptors very probably reflects the neuronal loss described in locus coeruleus of AD brains. The important implications of these findings for the pharmacological treatment of AD are discussed.
In the present work the anatomical distribution of alpha 2-adrenoceptors in the human central nervous system was studied in detail by quantitative autoradiography using the selective alpha 2 agonist [3H]bromoxidine ([3H]UK-14304) as a ligand. Only postmortem tissues from subjects free of neurological disorders were used in this study. Very high or high densities of alpha 2-adrenoceptors were found along layers I and III in non-visual neocortex, layers III and IVc of the visual cortex, CA1 field--stratum lacunosum-moleculare--and dentate gyrus--stratum granularis--at the hippocampal formation, nucleus arcuatus at the hypothalamus, locus ceruleus, nucleus dorsalis of vagus and at the stratum granularis of the cerebellar cortex. Relevant densities of alpha 2-adrenoceptors were also observed along the remaining layers of neocortex, nuclei centralis, medialis and corticalis at the amygdala, anterior thalamic group and rotundocellularis nuclei, paraventricular and ventromedial hypothalamic nuclei, substantia innominata, superior colliculus--stratum zonale--and lateral periaqueductal area at the midbrain, nucleus tractus solitarii and dorsal horn--substantia gelatinosa--of the spinal cord. [3H]Bromoxidine specific binding was very low or negligible in the remaining brain areas. Although a general parallelism between the distribution of these receptors could be observed for the rat and human brain, dramatic species differences in the level of alpha 2-receptors were found in several brain areas, such as thalamus, amygdala or cerebellar cortex. In general, the distribution of alpha 2-adrenoceptors in the human brain found here was parallel to that described for the noradrenergic presynaptic terminals in the mammalian central nervous system, lending some weight to the proposed predominant presynaptic localization of these receptors. The relevance of the anatomical distribution of alpha 2-adrenoceptors in the human brain for a better knowledge of the neurochemistry of neuropsychiatric disorders is discussed.
AIMS: To find out the validity, reliability and quality of the epidemiological information which comes from the System of Statutory Declarations. The example used is the incidence of Meningitis. DESIGN: Descriptive study of the coverage of the Declaration, with the help of the EDO (Illnesses requiring a Statutory Declaration) index, of the pediatric (up to 14 years old) cases of meningitis attended in our Area between 1984 and 1989. We analysed how the Declaration had been filled in and the agreement between the information gathered through the notification system and clinical records. SITE. The whole network of epidemiological vigilance: hospitals, provincial epidemiological services and primary care services. PATIENTS: All the cases of child meningitis (120 cases) seen in the Mother and Child Hospital in our area between 1984 and 1989. MAIN MEASUREMENTS AND RESULTS: The meningitis declaration covered 47.5% of the total number of cases seen. In the cases declared, the diagnosis of meningococcal meningitis on the EDO index was 89.5%, whereas the rate in the clinical reports was only 20%. Thus agreement in the diagnosis does not exceed what could be produced by chance (Kappa = 2.5%; p = NS), as agreement for all diagnoses is 7.1%. CONCLUSIONS: Our results demonstrate a low level of declaration, poor standard of compliance and scant agreement between the Statement of Declaration and the clinical report. The validity and reliability of this information is extremely low and suggests a need to re-consider the usefulness of this vigilance system for health-service practice, especially in Primary Health Care.
Dopamine D1 and D2 receptors were studied in brain tissue sections from a typical patient with progressive supranuclear palsy and in 7 age-matched brains. The density of D1 receptors in the caudate-putamen and frontal cortex of the patient was within control limits. By contrast, the density of nigral D1 receptors and striatal D2 receptors was dramatically reduced in the patient as compared to the control brains. This work shows again that the loss of striatal D2 receptors is the most plausible explanation for the poor response to dopaminergic drugs in patients with progressive supranuclear palsy. While the loss of nigral D1 receptors can be explained by the loss of nigral neurons, it seems that neurons bearing striatal D1 receptors are spared in progressive supranuclear palsy. The clinical effects of selective D1 agonists are worth testing in this devastating disorder.
The epidemiology of head injury was studied in Cantabria, Spain, using a methodological design consisting of a cross-selectional analysis of one year of duration and an additional one year follow-up of all the patients included in the initial sample. The 477 cases identified represent a rate of 91/100,000, with males showing a head injury rate 2.7 times higher that than for females. Sixty per cent of all cases involved traffic accidents, falls accounted for 24% and industrial accidents were the cause in 8%. The annual age-adjusted mortality rate was 19.7/100,000. Over 92% of all deaths occurred prior to hospital admission. The presence of alcohol intoxication was evaluated in 211 cases by determining the osmolar gap. It was found that 51% of all the cases examined presented clear evidence of acute alcohol intoxication.
The effect of relapse to opiate use on blood pressure and heart rate has been studied in heroin-withdrawn addicts treated with clonidine in an outpatient detoxification procedure. The daily dose of clonidine was established according to body weight and amount of heroin usually consumed at the onset of treatment. Patients who returned to heroin use were detected by increased urinary levels of opiates. Clonidine elicited significant reductions of blood pressure and heart rate reaching a plateau in the second day of treatment. Heroin consumption was found to provoke a further decrease of both systolic and diastolic pressure when the time interval between the relapse and the cardiovascular determinations was about 3 h as estimated by the patients. At longer intervals (16 h) this effect was reversed and both the hypotensive and the bradycardiac actions of clonidine seemed to be impaired. The possible impact of endogenous opioids and alpha-2 receptor sensitivity on these biphasic alterations is discussed.
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Lidocaine (lignocaine) was given in 42 episodes of status epilepticus (SE) in 36 patients either because of limited pulmonary reserve (22 patients) or because of lack of response to diazepam (14 patients). Lidocaine (1.5-2 mg/kg) was given intravenously in two minutes. A further identical bolus was infused if no response had occurred or if seizures recurred. With the first bolus 11 episodes of SE did not stop, but 31 responded, always in less than one minute. In 19 episodes, however, this response lasted less than 30 minutes. Twelve episodes did not recur, but 30 needed a second bolus because of recurrence. Of these, 19 episodes responded at once but SE reappeared in seven. In these seven episodes the mean control time with the second dose was 102 minutes. Five of these subsequently responded to a continuous infusion of lidocaine. Eleven patients, who had not responded to the first bolus, had no response to the second. Lidocaine is a drug that may be epileptogenic at high doses. At the doses used here, however, lidocaine seems to be a rapid acting anticonvulsant, useful in the short term management of SE and may be indicated in patients in whom respiratory or consciousness depression is undesirable and in those with no response to diazepam. The absence of response to lidocaine indicates SE resistant to treatment and poor prognosis. These data show that prompt lidocaine administration may be worthwhile when management of respiratory depression is not possible.
A case of non-secretory multiple myeloma presenting as primary plasma cell leukaemia in a 65 year old woman is presented. Bone pain was the initial clinical manifestation. Laboratory analysis showed 20% of circulating immature plasma cells. Despite the presence of osteolytic lesions, no M-component could be demonstrated in serum protein electrophoresis, and serum and urine immunoelectrophoresis. Bone marrow aspirate demonstrated an 83% infiltration of plasma cells showing various degrees of immaturity. Immunofluorescence with monoclonal antisera demonstrated intracytoplasmic kappa light chains in a high percentage of plasma cells. Immature plasma cells without cellular capacity to synthesize and excrete complete immunoglobulins could be more aggressive, leading to an initial leukaemic process. Previous work regarding possible pathogenetic mechanisms, clinical and laboratory features, and response to treatment of this extremely rare association are reviewed.
The objective of this study was to investigate quantitative and qualitative intrathecal IgG synthesis in 51 patients with clinically definite multiple sclerosis, taking previous immunosuppressive treatment into account. Four formulae were used to assess quantitative synthesis. Oligoclonal bands (OB) were investigated using isoelectric focusing (IEF) and silver staining. Abnormal quantitative values were detected in 42 (82%) patients, whereas OB occurred in 38 (74.5%) patients. Steroid therapy lowered quantitative synthesis in 6 out of 9 patients when given within 3 months before lumbar puncture (LP). Untreated patients with OB systematically had abnormal formulae. Patients treated with corticosteroids 10 or more months prior to LP had abnormal formulae. This fact suggests a transient depressor effect of steroids on quantitative synthesis. OB were present in patients recently treated with corticosteroids. Quantitative synthesis was higher in patients with OB than in those without OB. Azathioprine treatment did not significantly lower quantitative synthesis. We conclude that for routine purposes evaluation of intrathecal immunoglobulin synthesis could begin by performing quantitative tests. IEF seems to be mandatory for patients with normal formulae who have recently been treated with steroids.
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