Myasthenia gravis unmasked by cocaine abuse.
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Biomedical subjects
Publications and source records attributed to J Pascual.
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We examined the density and the state of affinity of [3H]hemicholinium-3 ([3H]HC-3) binding sites, a marker of the presynaptic high-affinity choline uptake (HACU) carrier, in 4 representative regions of 13 postmortem Alzheimer's disease (AD) brains, as well as in 12 matched control brains. Significant reductions in the densities of [3H]HC-3 binding sites were found both in frontal cortex (-44.7%) and hippocampus (-36.5%) of AD brains in comparison to controls. On the other hand the densities of [3H]HC-3 binding sites in AD brains in caudate-putamen and cerebellar cortex showed no significant differences when compared to controls. No significant change in the state of affinity of these sites could be observed in the saturation assays carried out in hippocampus and frontal cortex. Our findings concur with the reported data by using other presynaptic cholinergic markers in AD and confirm that some degree of cholinergic degeneration, highly specific for the basal forebrain neurons, occurs in AD. However, these results, obtained in a group of AD brains belonging to severely demented patients, do not show a dramatic loss of the HACU in many AD brains. Although this fact could be due to the existence of a compensatory mechanism, our results probably suggest that dementia in AD cannot be explained only by the loss of neocortical cholinergic presynaptic terminals arising from the basal forebrain and also may clarify as to why the acetylcholine precursors or the muscarinic agonists are not effective in AD dementia.
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The substrate for olivopontocerebellar atrophy parkinsonism is obscure due to the lack of clinical and pathological reports and the absence of studies on dopamine receptors in this entity. We describe a patient with olivopontocerebellar atrophy whose clinical presentation was levodopa-responsive parkinsonism in whom pathological examination disclosed pronounced nigral cell loss with no striatal damage. Autoradiographic labeling with 3H-spiperone showed normal densities of D2 dopamine striatal receptors. These data show that indistinguishable nigral, presynaptic parkinsonism occurs in patients with idiopathic Parkinson's disease and in patients with olivopontocerebellar atrophy, and also how a favorable response to levodopa is neither synonymous with idiopathic Parkinson's disease, nor does it exclude multiple-system, atrophy-related parkinsonism.
Hemicholinium-3 (HC-3) is a potent inhibitor of the high-affinity choline uptake system (HACU). Here we report on the biochemical characterization and autoradiographic distribution of [3H]hemicholinium-3 binding sites in rat brain, confirming and expanding results from previous studies. The binding of [3H]HC-3 to striatal membranes was specific, to a single site, sodium-dependent, saturable, and of high-affinity, Kd values being about 3 nM for striatum, 5 nM for the hippocampus and 12 nM for neocortex. [3H]HC-3 specific binding exhibited a pharmacological profile suggestive of physiologically relevant interactions and fully comparable to that reported for HACU. The uneven distribution of [3H]HC-3 binding sites exhibited a high degree of correspondence with the reported distribution of HACU and other enzymatic presynpatic cholinergic markers. The punctual differences between our study and previous works on [3H]HC-3 binding are analysed. We conclude that [3H]HC-3 labelling may be used as a selective and quantifiable marker of the cholinergic presynaptic terminals in close relationship with HACU.
Because of evidence that supports an important role for the 5-HT1A receptor subtype in migraine, buspirone--the novel 5-HT1A receptor agonist with anxiolytic properties--was given to 33 patients suffering from severe migraine exacerbations. Patients took 15-20 mg/daily for 10 weeks; six (18%) patients did not improve. Although buspirone was well tolerated, two additional patients (6%) did not finish the trial, due to undesirable side effects. On the other hand, 25 (76%) patients improved; 17 (52%) exhibited an excellent response; and 8 (24%), a moderate response. Potential reasons for the observed antimigraine effect of buspirone and its possible consequences in migraine pathophysiology are discussed. Our results, at first, seem to support the role of a 5-HT1A hypersensitivity in migraine pathogenesis, and warrant further trials to confirm whether buspirone represents an alternative in preventive treatment of migraine exacerbations.
Several approaches have been attempted to manage renal allograft dysfunction in cyclosporine-prednisone (CsA-Pred)-treated patients. Conversion to conventional therapy and perioperative triple drug have been associated with high rates of acute rejection episodes, infections, or neoplasms. We report our experience in delayed addition of azathioprine (1-2 mg/kg/day) to CsA/Pred protocol in three groups of patients. Group I (n = 9) had chronic renal function deterioration due to chronic rejection; group II (n = 10) had repeated or severe acute rejection episodes despite adequate CsA levels; and group III (n = 8) had CsA toxicity despite drug tapering. In group I, serum creatinine (SCr) had risen from 2.2 +/- 0.9 to 2.9 +/- 0.7 mg/dl over the 6 months prior to Aza addition (P less than 0.05), renal function declining at a rate of -0.14 +/- 0.12 Cr-1/year. In the 6-month post-Aza, renal function improved at a rate of 0.06 +/- 0.06 Cr-1/year and during the entire follow-up at a rate of 0.04 +/- 0.12 Cr-1/year (P less than 0.05) with stable CsA levels (288 +/- 167 vs. 251 +/- 172 ng/dl, NS). In group II response was worse, though the rate of declining renal function prior to Aza (-0.10 +/- 0.10 Cr-1/year) was almost stopped after Aza. In group III there was very good response to Aza addition, as 7 out of 8 patients improved graft function (baseline SCr 2.5 +/- 0.7 mg/dl vs. 1.9 +/- 0.6 mg/dl at last follow-up, P less than 0.05), with significantly decreased CsA levels (480 +/- 97 vs. 268 +/- 120, P less than 0.05). One patient from group II died from pneumonia, and 6 patients (1 from group I and 5 from group II) lost their grafts. Fifteen patients improved graft function, and 9 worsened after addition of Aza. The bad-responders had significantly higher SCr at baseline compared with the good-responders (3.8 +/- 1.8 vs. 2.7 +/- 0.6 mg/dl, P less than 0.01). Amelioration of chronic graft dysfunction can be achieved by delayed addition of Aza to CsA-Pred in patients with chronic rejection or CsA toxicity. This is accompanied by low rate of acute rejection, good patient and graft survival, and low rate of infections. A worse outcome can be seen in patients with high-baseline SCr levels, suggesting the need for addition of Aza in the initial chronic graft dysfunction.
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A year long multicentre prospective study was carried out in the Valencia region of Spain, to determine the cause of community acquired pneumonia. The study was based on 510 of 833 patients with pneumonia. Of these, 462 were admitted to hospital, where 31 patients died. A cause was established in only 281 cases--208 of bacterial, 60 of viral, and 13 of mixed infection. The most common microorganisms were Streptococcus pneumoniae (14.5%), Legionella sp (14%), Influenza virus (8%), and Mycoplasma pneumoniae (4%). There was a higher incidence of Legionella sp than in other studies.
In order to ascertain whether there are abnormalities of nonenzymatic glycosylation in uremia, the levels of nonenzymatically glycosylated hemoglobin (GHb), and total plasmatic glycosylated proteins (PGP) were studied using the thiobarbituric acid (TBA) method, a procedure not interfered with by carbamylation. Total hemoglobin A1 (HbA1) and the A1c fraction were also determined by ion exchange chromatographic methods. Sixty-six end-stage renal disease patients (29 nondiabetic and 8 diabetic uremic patients on conservative treatment, 29 nondiabetic hemodialysis patients) and 56 controls (32 nonuremic diabetic patients and 24 healthy controls) were studied. High levels of GHb and total PGP were found in the nondiabetic uremic group on conservative treatment with all the methods used, but the persistence of high chromatographically determined HbA1 levels in hemodialysis patients contrasts with the results obtained with the other techniques, which showed lower values on hemodialysis. Nondiabetic uremic patients with abnormal oral glucose tolerance curves had significantly higher levels of TBA-determined GHb and PGP. Uremic diabetic patients had the highest glycosylation levels of all the studied groups. We conclude that there is an abnormal nonenzymatic glycosylation of proteins in uremia, independent of carbamylation reactions and partially corrected by hemodialysis.
Evolution of cardiac index in 12 patients with severe renal anemia on regular hemodialysis (hematocrit 19.9 +/- 2.8%) was studied during the first 4 months of treatment with recombinant human erythropoietin (rhEPO). At the end of the study period, hematocrit rose to 31.1 +/- 3.5% (p less than 0.001) and cardiac index significantly decreased (5.34 +/- 1.25 vs. 3.81 +/- 0.84 liters/min/m2, p less than 0.001). Cardiac index fell mainly because of reduction of stroke volume (108 +/- 27 vs. 81 +/- 25 ml, p less than 0.001), while heart rate did not change during the study period. Before starting rhEPO cardiac index was elevated in 11 out of the 12 patients, whereas after 4 months of treatment this was only maintained in 4 of them. We conclude that substitution with rhEPO in hemodialysis patients significantly decreases cardiac index, confirming anemia as the main factor for hyperdynamic circulatory state in these patients. Whether this reduction in cardiac index will ameliorate cardiac morbidity or not and hematocrit levels for achieving the major benefits require further studies.
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Two patients on maintenance hemodialysis after terminal renal failure due to mesangial glomerulonephritis with IgA deposits and the nephrotic syndrome, received cadaver renal allografts. After several years of functioning transplants, both patients developed slowly progressive proteinuria and finally the nephrotic syndrome, 1 of them with renal function deterioration. Renal biopsies revealed findings indicating recurrence of the original disease.
A 47-year-old woman with overlap scleroderma-polymyositis syndrome and positive circulating lupus anticoagulant developed scleroderma nephropathy, characterized by rapidly progressive renal failure caused by thrombotic microangiopathy with widespread thrombi in small arteries and glomeruli. The possible relationship between lupus anticoagulant and the development of thrombosis at the small renal vessels level with the triggering of the scleroderma crisis is discussed.
BACKGROUND: This is to describe a restricted sensory syndrome of unique distribution due to thalamic infarct. CASE DESCRIPTION: We report a case of pure sensory disturbance involving the left intraoral and perioral regions and the tips of the thumb and forefinger of the left hand. Magnetic resonance imaging revealed a small infarct in the contralateral thalamus, presumably affecting the nucleus ventralis posterior. CONCLUSIONS: This patient provides an excellent correlation between clinical findings and thalamic representation of body surface as established during stereotactic procedures.
Myocardial effects of recombinant human erythropoietin (rhEPO) treatment were prospectively investigated in 15 hemodialysis (HD) patients with severe anemia (hematocrit [Ht] 19.7 +/- 2.5%). Echocardiographic studies were performed after a midweek HD session just before and after a year of rhEPO. At the end of the study period, Ht had improved to 32.2 +/- 3.5% and cardiac index significantly decreased (5.48 +/- 1.54 vs 3.97 +/- 0.94 l/min/m2, p less than 0.001). Left ventricular mass index (LVMi) decreased with rhEPO (210.7 +/- 48.3 vs 139 +/- 50 g/m2, p less than 0.05). This decrease was concomitant with a decrease of LV end-diastolic diameter (4.89 +/- 0.44 vs 4.57 +/- 0.64 cm, p less than 0.05), interventricular septum thickness (IVST, 1.42 +/- 0.33 vs 1.07 +/- 0.13 cm, p less than 0.01) and LV posterior wall thickness (LVPWT, 1.28 +/- 0.21 vs 1.01 +/- 0.11 cm, p less than 0.01). Eight patients were hypertensive well controlled with hypotensive drugs (group I) and 7 normotensive (group II). LVMi was higher in group I than in group II before rhEPO (235.2 +/- 40 vs 182.7 +/- 43.1 g/m2, p less than 0.05) and significantly decreased after rhEPO in both groups (28.5% and 41.4% respectively). LVMi remained higher in group I than in group II at the end of the study (168.5 +/- 0.9 vs 106.7 +/- 24 g/m2, p less than 0.025). A moderately elevated IVST/LVPWT was reduced with a year of rhEPO (1.14 +/- 0.40 vs 1.05 +/- 0.15, p less than 0.05), disclosing correction of asymmetric septal hypertrophy. We conclude that left ventricular hypertrophy (LVH) regression is obtained after partial correction of anemia with rhEPO. Previous hypertension with current need of antihypertensive treatment has also a significant effect in the development of LVH. Whether this regression would improve outcome in HD patients remains to be established.