[The basic treatment of arterial hypertension (II). Pharmacological treatment].
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Biomedical subjects
Publications and source records attributed to J Pascual.
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[3H]Hemicholinium-3 ([3H]HC-3) binding, as a marker of the presynaptic high-affinity choline uptake carrier (HACU), and cholinergic muscarinic receptors were measured by autoradiography in several brain regions of levodopa-responsive parkinsonism and matched cases. A significant increase in the density of [3H]HC-3 binding sites was found in the striatum of parkinsonian brains, while there was a slight decrease in the parkinsonian hippocampus. Total, M1 and non-M1 muscarinic receptors remained unchanged in frontal cortex and striatum of parkinsonian brains as compared to controls. Total and non-M1 muscarinic receptors were significantly reduced in the parkinsonian hippocampus, whereas hippocampal M1 receptors were preserved. These data demonstrate a hyperactivity of the HACU, and thus of the acetylcholine synthesis, in parkinsonian brains probably compensatory of the loss of both dopaminergic terminals in the striatum and of basal forebrain neurons in the hippocampus. Our results emphasize the value of [3H]HC-3 binding in the study of the functional status of the cholinergic synapse in neurodegenerative disorders.
The appearance and distribution of 5-HT1A receptors in the human cerebellum during the ontogenetic development was studied in samples from a group of fetal, neonatal and adult cases, by means of quantitative autoradiography and membrane binding. [3H]8-OH-DPAT was used as a ligand. High densities of 5-HT1A receptors were found during the fetal and neonatal stages over the whole cerebellar cortex, with a slight predominance in the external part, in a band which included the molecular layer. In contrast, the adult cerebellum was nearly devoid of such sites. This finding supports a role for 5-HT1A receptors in the regulation of development in the human cerebellum.
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The state of different aminergic receptors was assessed, by quantitative autoradiography in tissue sections, in several representative brain regions from a typical progressive supranuclear palsy (PSP) patient and from 9 matched brains. The densities of muscarinic receptors were within control limits in most of the brain areas of this PSP brain. Serotonin1 receptors were clearly reduced only in areas with very relevant neuropathological damage, such as locus niger and globus pallidus. The density of D1 dopamine receptors in the caudate-putamen and frontal cortex of the patient was within control limits. By contrast, nigral D1 and striatal D2 dopamine receptors were dramatically reduced in the patient as compared to controls. Finally, alpha 2-adrenoceptors were clearly reduced in all the examined areas of this PSP patient as compared to control group. Both the potential role of these receptor changes in the pathophysiology of the clinical features of PSP and their correlation with the neuropathological findings of this PSP patient are discussed.
We report a primary leptomeningeal lymphoma (PLML) presenting as a cerebellopontine angle lesion. CT showed slight enlargement of the ventricular system, obliteration of the basal cisterns and a dense lesion in the left cerebellopontine angle which enhanced with contrast medium. Cerebrospinal fluid abnormalities included sterile lymphocytic pleocytosis without malignant cells, low sugar and high adenosine deaminase levels. An erroneous diagnosis of tuberculous meningitis was made, but autopsy revealed a leptomeningeal B-cell lymphoma with infiltration of the middle cerebellar peduncle giving the appearance of a cerebellopontine angle lesion. Seven cases of cerebellopontine angle lymphoma have previously been described, only one of which could be classified as PLML.
Using autoradiographic techniques we studied the changes that in adrenergic receptors occurred in the cerebellum of two olivopontocerebellar atrophy (OPCA) patients as compared with a control group. In OPCA cerebellum the densities of total beta-adrenoceptors were reduced along the cortex but increased in the white matter. Although mainly the beta 1 subtype was decreased along the cerebellar cortex, the increase of beta-receptors over the white matter was due to a selective raise in the beta 2 subtype. These findings suggest a postsynaptic neuronal location for the beta 1 subtype and a glial location for the beta 2-adrenoceptor. On the other hand, alpha 2-adrenoceptors were clearly reduced all along the cerebellar cortex of these OPCA brains, this probably being secondary to the loss of presynaptic adrenergic terminals arising from the locus coeruleus. These results help clarify both the subcellular location of adrenoceptors in human cerebellum and the neurochemical pathophysiology of OPCA.
3H-hemicholinium-3 (3H-HC-3) binding, a marker of the presynaptic high-affinity choline uptake carrier (HACU), was measured by autoradiography in several brain regions of 17 Alzheimer's disease (AD) patients and of 11 matched controls. A significant decrease in the density of 3H-HC-3 binding sites was found in entorhinal cortex, hippocampus and layers I-III of the frontal cortex. By contrast, in the caudate-putamen the number of 3H-HC-3 binding sites in AD cases was comparable to that of control striata. These data concur with previous results using classical presynaptic markers and reflect the loss in the activity of HACU, and, hence, in the synthesis of acetylcholine, that selectively occurs in cortical areas of AD brains due to the degeneration of presynaptic cholinergic terminals arising from the basal forebrain. However, the relatively low mean reduction in HACU in cortical areas (-40%), together with the apparent indemnity of this marker in certain severely demented AD cases, suggest that AD dementia cannot be explained simply by the loss of presynaptic terminals originating in the basal forebrain. These data seem to be a good explanation for the poor response to cholinergic replacement in AD.
Renal involvement by some types of thrombotic microangiopathy has been associated with the presence of antiphospholipid antibodies in both patients with systemic lupus erythematosus (SLE) and in those with other types of connective tissue disorders. To assess the prevalence and clinical significance of these antibodies in renal disease we prospectively studied anticardiolipin antibodies and lupus anticoagulant activity in 138 patients. These patients were classified into four groups: chronic glomerulonephritis (n = 57), acute and non-SLE systemic nephropathies (n = 13), non-immune-related nephropathies (n = 39), and SLE nephropathies (n = 29). The prevalence of antiphospholipid antibodies in patients with chronic primary glomerulonephritis (9%) was lower than in the SLE group (34%) and higher, but not significantly, than in patients with non-immunologically mediated renal diseases (2.6%). Positive patients in this group correspond to atypical "lupus-like" SLE forms or sporadic cases. In the group of patients with acute nephropathy and non-SLE systemic disorders, lupus anticoagulant was present in sic and anticardiolipin was present in four. In most cases the finding was transient and probably related to concomitant infection or active immune response. We conclude that there is a low prevalence of antiphospholipid antibodies in primary chronic glomerulonephritides, similar to that found in non-immunologically based nephropathies. The presence of these antibodies associated with chronic glomerulonephritis should raise the suspicion of SLE. On the other hand, positivity of these antibodies is a frequent finding in acute and systemic nephropathies. Therefore, the clinical and prognostic significance of their presence in these disorders should be further studied in a larger series of patients.
We prospectively studied over two years the incidence of headache as the initial and isolated clinical manifestation of adult patients suffering from intracranial tumors (n = 183). Fifteen patients (8%) exhibited headache as their first and isolated clinical manifestation. Age, sex, neoplasm localization, or pathological diagnosis did not correlate with the presence of headache. Posterior fossa location and hydrocephalus, though not reaching statistical significance, were more frequent in patients who presented with headache as the first symptom. At the moment of diagnosis, 59 (31%) of the patients admitted to headache, though only 1 out of the 15 patients starting as headache still had this symptom as the only manifestation. From our experience in adults, isolated headache for longer than 10 weeks will only exceptionally be secondary to an intracranial neoplasm.
To examine directly in the brain the status of alpha 2-adrenoceptors in major depression, the specific binding of the agonist [3H]UK 14304 was measured by quantitative receptor autoradiography in the hippocampus and frontal cortex of suicide victims (n = 17) with a retrospective diagnosis of depression (n = 7) or other psychiatric disorders (n = 10) as well as of matched control subjects (n = 9). In suicide victims, a significant increase in the number of alpha 2-adrenoceptors was found in the CA1 field (40%) and dentate gyrus (20%) of the hippocampus and in the external layers I (33%) and II (31%) of the frontal cortex, compared with that in matched controls. In depressed suicide victims, the increase in alpha 2-adrenoceptors in the CA1 field (57%) was significantly greater (24%, p < 0.05) than that observed in the group of suicide victims with other diagnoses (26%). In the same depressed suicide victims, the increase in cortical alpha 2-adrenoceptors was restricted to layer I (34%) and it was equivalent to that found in layer I (33%) of suicide victims with other diagnoses. The results indicate that suicide is associated with increases in the high-affinity state of brain alpha 2-adrenoceptors adrenoceptors and that there is a pronounced localized increase of this inhibitory receptor in the hippocampus of depressed suicide victims.
The diagnoses of the 193 patients aged 65 and over who attended the service of neurology in the past 15 years with de novo headache as their initial and main symptom were specifically analysed. Headaches beginning in elderly people represented only 5.4% of headaches in all ages, whereas 12.1% of the population in this health area was 65 or over. Head pain appeared more often in women (63%), although post-traumatic, cluster, and benign cough headaches were almost restricted to men. Tension type headache (83 patients, 43% of the aged patients) and idiopathic trigeminal neuralgia (36, 19%) were the most frequent diagnoses. Fifteen per cent of the elderly patients v 1.6% of patients under 65 presented headache secondary to serious conditions, such as stroke, temporal arteritis, or intracranial neoplasm. Only one patient over 65 met migraine criteria. It is concluded that whereas the incidence of patients with headache attending a general hospital decreases with age, the risk of headaches due to serious conditions increases 10-fold after 65.
Limited attention has been paid to the composition of the small amounts of urine that are frequently produced by patients with acute renal failure (ARF) of vascular origin. We have investigated the value of basic urinary parameters in the early diagnosis of total or partial acute renal artery occlusion (ARAO). We have reviewed the records of 30 patients with ARF: group 1 (n = 10) had total ARAO; group 2 (n = 10) had unilateral ARAO with a contralateral functioning kidney, and group 3 (n = 10) had hemodynamically mediated ARF subsequent to a major vascular abdominal surgical procedure, without arterial thrombosis. Serum sodium, potassium, urea, creatinine and osmolality, as well as urinary sodium, potassium, urea, creatinine and osmolality, were determined by standard techniques, and the fractional excretion of sodium (FENa) was calculated. Serum parameters were similar in all groups. Urinary sodium and FENa were higher in group 1 than in the other groups (p < 0.01), while urinary potassium was lower (p < 0.05). Urinary urea (p < 0.01) and osmolality (p < 0.05) were higher in group 2 than in the other groups, revealing a prerenal pattern in some cases. Serum and urinary concentrations of sodium, urea and creatinine and osmolality were similar in group 1, while respective serum and urinary concentrations and osmolality were different from each other in the other groups. Analysis of urine provides a useful diagnostic tool in ARF of vascular origin. When urinary concentrations of sodium, urea and creatinine are similar to those in serum and FENa approaches 100%, the strong likelihood of total ARAO should be acknowledged, and renal arteriography is mandatory.
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We report a case of cervical spinal subdural haematoma as the presenting manifestation of a small intradural schwannoma. In patients without a bleeding diathesis and an apparently spontaneous spinal subdural haematoma, the possibility of an underlying tumour should always be considered.
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