[The inefficacy of zidovudine (AZT) in progressive multifocal leukoencephalopathy (PML) associated with the acquired immunodeficiency syndrome (AIDS)]. / Ineficacia de la zidovudina (AZT) en la leucoencefalopatía multifocal progresiva (LMP) asociada al síndrome de inmunodeficiencia adquirida (SIDA).

The clinical case of a patient suffering AIDS who presented a progressive multifocal leukoencephalopathy (PML), diagnosed by CT scan, magnetic resonance imaging (MRI) and cerebral biopsy, is here described. A therapeutic trial was carried out with zidovudine (200 mg/4 hours p.o.) during 75 days. Although this treatment diminished the number of infections, a progression of PML was clinically observed, as well as the appearance of new lesions in the cerebral white matter in the MRI. The inefficacy of zidovudine in PML associated to AIDS is discussed.

Carbohydrate metabolism and plasma levels of insulin and glucagon in patients with atherosclerotic vascular disease.

In non-obese, non-diabetic patients suffering acute myocardial infarction, angina pectoris, previous myocardial infarction and peripheral vascular disease, the plasma levels of glucose, insulin, C-peptide and glucagon were determined in basal condition and during an intravenous glucose tolerance test. In the four groups there was a high frequency of glucose intolerance. Basal hyperinsulinism was present in all groups; in groups; in those which maintained normal glucose tolerance there was a high B-cell response to the sugar. Basal hyperglucagonemia was found in the early stage of acute ischemic heart disease, in patients with previous myocardial infarction and in those with peripheral vascular disease. The elevated plasma glucagon levels may play a role in the complex disturbance of carbohydrate metabolism present in patients with atherosclerotic vascular disease.

Anomeric specificity of glucose-induced insulin release in normal and diabetic subjects.

The alpha- and beta-anomer of D-glucose (3.5 or 5.0 g) were injected intravenously in 15 normal subjects and 13 non-insulin-dependent diabetic patients with mild fasting hyperglycaemia. In the normal subjects, alpha-D-glucose increased more than beta-D-glucose the plasma insulin concentration. Thus, 2 min after injection of D-glucose, the concentration of insulin relative to paired basal value was 61% higher in response to alpha- than beta-D-glucose (p less than 0.05). In 8 diabetic subjects, the secretory response to D-glucose was insufficient to allow characterization of its anomeric specificity. In the remaining 5 diabetic patients, a preferential response to alpha-D-glucose was observed in 3 cases, but not so in the other 2 cases. These results indicate that glucose-stimulated insulin release is alpha-stereospecific in normal subjects. A possible perturbation of such a stereospecificity in certain diabetic subjects warrants more extensive investigation on its precise incidence and etiopathogenic significance.

Renal catabolism of 125I-glicentin.

The renal catabolism of 125I-glicentin has been studied in vivo by the disappearance of this peptide from the plasma of bilaterally nephrectomized, ureteral-ligated, or normal rats and by using tubular microinfusion techniques. In addition the catabolism of glicentin by the isolated, perfused kidney has been studied. Results from in vivo studies demonstrated that half-disappearance time was lower in control (59.5 +/- 1.8 min) than in bilaterally nephrectomized rats (97.2 +/- 2.6 min), and this value was significantly higher than that of ureteral-ligated animals (83.2 +/- 1.1 min, P less than 0.005). Microinfusion experiments revealed that when 125I-glicentin was injected into the proximal tubule, no trichloroacetic-precipitable radioactivity was recovered in the urine, whereas most of inulin injected was recovered. By contrast most of the 125I-glicentin injected into the distal tubule was recovered in the urine. In isolated kidney experiments, organ clearance rate of 125I-glicentin averaged 0.88 +/- 0.10 ml/min, a value significantly higher than that of glomerular filtration rate (0.72 +/- 0.06 ml/min, P less than 0.005, paired data), and both parameters showed a close linear relationship (r = 0.90). Urinary clearance of glicentin was negligible. These results demonstrate that the kidney plays a major role in the catabolism of glicentin, mainly by glomerular filtration and tubular catabolism. The site of tubular catabolism appears to be the proximal tubule. Peritubular uptake was minimal.

Plasma glucagon and glucagon-like immunoreactive components in Type 1 (insulin-dependent) diabetic patients and normal subjects before and after an oral glucose load.

Biogel P-30 filtration of plasma from Type 1 (insulin-dependent) diabetic patients and normal subjects in basal state and after an oral glucose load was assayed with a C-terminal (30 K) and a glucagon-like immunoreactivity-cross-reacting antiserum (R8). Up to four immunoreactive peaks of approximate molecular sizes of greater than 20,000 (fraction I), 9000 (fraction II), 3500 (fraction III) and 2000 (fraction IV) were detected with the two antisera in both groups. In the basal state, the only significant difference observed between both groups was a higher R8-reactivity in fraction II in the group of diabetic patients, although the R8 minus 30 K values for this fraction did not show a significant difference between both groups. After glucose the only significant differences were an increase of R8-reactivity in fraction II in both groups (p less than 0.01) and a decrease of 30 K-reactivity in fraction III (IRG3500) in normal subjects (p less than 0.05). In seven out of 12 diabetic patients, 30 K-reactivity in fraction II (IRG9000) and III (IRG3500) increased above their basal values. The gut-glucagon-like immunoreactivity response to oral glucose (delta R8-delta 30 K values in fraction II) was similar in both the diabetic and normal subjects. These results indicate that the paradoxical rise in plasma immunoreactive glucagon after oral glucose in diabetic patients may be due to an increase of both IRG3500 and/or IRG9000, the gut-glucagon-like immunoreactivity released during glucose absorption has a molecular weight of approximately 9000, and no differences in plasma gut-glucagon-like immunoreactivity were observed in Type 1 diabetic patients when compared with normal subjects, either in the basal state or after glucose ingestion.

Immunoreactive pancreatic polypeptide components in plasma from normal subjects and patients with chronic renal failure in basal and postprandial conditions.

Gel filtration of plasma from normal subjects and patients with chronic renal failure (CRF) yielded four immunoreactive human pancreatic polypeptide (IRhPP) peaks of approximately greater than 20,000, 10,000, 4200, and 2000 daltons. In normal subjects, the basal plasma distribution was 36 +/- 2%, 16 +/- 3%, 25 +/- 1% and 23 +/- 2%, respectively. In the CRF patients, the total plasma IRhPP was close to ten times higher than in the normal group. This difference was due to an increase in IRhPP10000 and IRhPP4200 plasma levels. After a standard breakfast, plasma IRhPP10000 and IRhPP4200 levels increased in the normal subjects and in the CRF patients, while the levels of the other two plasma components were not affected by the meal. In a patient with multiple endocrine adenomatosis type 1, the basal plasma levels of IRhPP10000 and IRhPP4200 were, respectively, 41 and 44 times higher than the mean value in the normal subjects; these fractions appeared to be further increased after breakfast. In trying to characterize the IRhPP10000, it was found that treatment with urea, guanadium hydrochloride, and acetic acid (pH 2.2) did not alter its molecular size, whereas limited trypsin treatment was able to destroy part of the immunoreactivity and to produce greater than 20,000-dalton and 4200-dalton immunoreactive materials. Plasma IRhPP10000 seems to be a co-secretory product of the PP cell, and the kidney plays a role in its catabolism as well as in that of the IRhPP4200 component. The IRhPP10000 component may correspond to a PP precursor.