[Intrauterine growth retardation].
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Biomedical subjects
Publications and source records attributed to R Bianchi.
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The pathophysiology of albumin metabolism in uremia was investigated by turnover measurements in a large series of uremic patients, either on conservative management or on dialysis therapy. A total of 62 turnover studies were performed in patients on dietary treatment, divided into two groups according to the duration of the low protein diet: 35 subjects from 6 to 30 days, 27 subjects from 6 months to 5 years. Albumin catabolism and distribution were measured by the two-tracer technique (131I-albumin and 125I-iodide, simultaneously injected iv), while albumin synthesis was directly determined in 10 patients by the use of 14C-carbonate and 131I-albumin. Sixteen turnover studies were also performed in a group of end-stage uremics on dialysis therapy by a two-tracer procedure especially designed to determine albumin catabolism in the course of a single peritoneal or hemodialytic treatment. The main features of albumin metabolism observed in the patients on dietary management were: normal intravascular albumin mass, marked reduction of the extravascular and total albumin pools, with proportionally reduced catabolism. No significant turnover difference was found between the short-term diet group and the patients on low-protein diet from 6 months to 5 years. As to the uremics on dialysis therapy, catabolic rate of albumin was 3-fold increased in three patients showing clinical features of "hypercatabolism" in the early phase of uremia, or during relapse from it. Albumin turnover rate returned to normal when measured during clinical steady-state conditions. All these findings suggest that a marked body protein depletion exists in chronic uremia, and that dietary treatment per se is not responsible for such a depleted state. Instead, the depletion of protein stores observed in the steady phase of chronic uremia may have been originated by the exaggerated increased catabolism in the early phase of renal failure, not compensated by a proportional increase of the synthetic rate, due to both the state of uremic intoxication and to the reduced dietary protein intake during the early phase.
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Triiodothyronine (T3) kinetics was evaluated using [125I]T3 and the single injection technique; 5 hypothyroid, 6 hyperthyroid patients, and 10 euthyroid control subjects were studied. Plasma-labeled T3 concentration was measured by means of a new method based on extraction of the hormone on Sephadex G-25 columns followed by elution with the specific antiserum. This technique allows a far better separation of the hormonal radioactivity from the labeled iodide produced from T3 catabolism in comparison with the TCA-precipitation-butanol extraction method. The analysis of the experimental data has been performed using non-compartmental treatment (integral approach); results of mono-compartmental analysis of the same data are also reported for comparison. Average metabolic clearance was 15.3 +/- 0.6 (mean + SEM) liters/day/m2 body surface in normal subjects; it was significantly decreased in hypothyroid patients (11.4 +/- 1.1) and significantly increased (33.4 +/- 4.0) in hyperthyroidism. The total plasma equivalent distribution volume was found significantly enlarged in hyperthyroid patients (22.6 +/- 0.9 liters/m2) in respect to that measured in the control group (15.6 +/- 0.4), whereas it was not different from normal value in hypothyroid patients (17 +/- 1.7). Using plasma concentration of native T3, absolute turnover rate and extrathyroidal pool were also estimated; their values were 6.5, 23.7, and 131.7 micrograms/day/m2 and 10.1, 24.2, and 90.6 micrograms/m2, respectively, in hypothyroid, normal, and hyperthyroid groups.
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Albumin loss in the dialysate was evaluated during a total of 5 peritoneal dialyses carried out on 3 uraemic patients. The measurements were made by two different methods, the first based on the evaluation in the dialysate of intravenously injected radioiodinated albumin, the second one based on a radioimmunoassay of the protein in the dialysate. The results obtained showed three main mechanisms of protein loss during peritoneal dialysis: 1) albumin shift from extravascular sites adjacent to the peritoneum, 2) direct passage of albumin from blood stream to peritoneal cavity, and 3) tendency of the inter-dialysis peritoneal fluid to equilibrate with plasma proteins. Furthermore, the observations made on a patient with evident peritonitis proved the importance of the intrinsic biological properties of the peritoneum in determining the amplitude of protein wasting by the dialysate.
A method is described for the determination C3-hydroxylated benzodiazepine glucuronides in biological samples. Oxazepam and lorazepam glucuronides are measured as methyl esters and trimethylsilyl derivates by a gas chromatographic procedure. The applicability of the method has been tested on the urine of rats, guinea pigs, rabbits and man, receiving oxazepam orally. Oxazepam glucuronide was not found in rat urine but it was present in the urine of rabbits (5.7% of the administered dose), guinea pigs (9.5%) and man (13.4-26.9%).
In the spinal ganglia of two species of reptiles (gecko and lizard) the volume of the perikaryal satellite cell sheath was found directly proportional both to the volume and surface area of the related neuronal body. This result agrees with that obtained in a previous research on two species of mammals (cat and rabbit). A quantitative balance between neuronal bodies and their associated glial tissue therefore exists also in the spinal ganglia of zoological species phylogenetically quite distant from mammals. The quantitative relationship between glial and nerve tissue was found to be lower in the gecko and lizard than in the cat and rabbit. This difference could have a phylogenetic significance, and/or it could be explained by the lower metabolic rate in the nervous system of the poikilotherms in respect to mammals.
17-Chloroacetylajmaline and 17-acetylajmaline are reported to have in vivo antiarrhythmic activity and are metabolized by hydrolysis. Since the hydrolysis product, ajmaline, may be the actual antiarrhythmic agent, the hydrolysis of these derivatives by various tissues of the guinea pig, rat, and mouse was determined in vitro by a titrimetric method and compared to hydrolysis by alpha-naphthylacetate. The heart is the most active tissue in the guinea pig for hydrolyzing 17-chloroacetylajmaline. The hydrolyzing activity is greater in the guinea pig than in rat or mouse heart, corresponding with the more significant pharmacological activity in the guinea pig. 17-Chloroacetylajmaline has a significantly lower Km value than 17-acetylajmaline, which is in agreement with the in vivo activity.
131I-labelled Human Serum Albumin and 125I-sodium iodide were used to measure protein loss from the peritoneum and peritoneal clearance of iodide in a group of 8 uraemic patients, each one being studied after a different number of dialyses. Both albumin loss and iodide clearance reached a maximum at about the 10th dialytic treatment and then tended towards the initial levels. Protein loss as determined isotopically was markedly lower than indicated by direct radioimmunoassay measurements performed in three cases. Fitting experimental points by a model which assumes direct passage of protein from plasma to peritoneal cavity suggests the presence of a "delay" pool between plasma and the peritoneal cavity itself (extravascular sites adjacent to peritoneum?). The shorter retention time of the dialysis solution in the abdomen (4-8 minutes) seemed to us to cause lower protein losses than reported by authors using longer retention times.
The effects of long-term low protein diet on albumin metabolism of uremic patients were evaluated. Studies were performed on 62 patients divided into two groups depending on the duration of the diet (35 subjects from 6 to 30 days, 27 subjects from 6 months to 5 years). All patients received a diet containing at least 20 g of high biological value proteins per day. Albumin catabolism and distribution were measured by the two-tracer technique, after simultaneous i.v. injection of 131I-human serum albumin and of free 125I-iodide. Albumin synthesis was directly determined in 10 patients by two tracers, 14C-carbonate and 131I-albumin, according to the xanthydrol technique for specific activities of urea and albumin guanido carbon in plasma. The main features of albumin metabolism observed in both groups studied were: normal intravascular albumin mass, marked reduction of extravascular and total albumin pools, with proportionally reduced catabolism. No significant turnover difference was found between the first group and the patients on diet from 0.5 to 5 years, thus suggesting that dietary treatment per se is not responsible for the albumin depletion observed in chronic uremia.
This report analyzes age-specific glucose (PG) and immunoassayable insulin (IRI) responses during oral glucose tolerance testing (OGTT) and examines test results in children and adolescents with OGTT abnormality using the age-appropriate control data. Controls' (n = 93) and patients' (n = 63) results were compared on the basis of statural age (SA) at the time of testing. Control tests (n = 101) showed significant positive correlation of fasting and four-hour postingestion PG with SA (p less than 0.001), but mean area under the PG curves did not vary between the SA groups (I--18.69 months, II--70-131 months, III--132+ months). The absence of differences of other sampling times permits uniform diagnostic criteria for this age group. IRI was positively correlated with SA at all testing times, and mean levels differed significantly between each SA group at every sampling time; the mean areas under the IRI curve also differed significantly between SA groups as did the mean ratios of IRI area to PG area (group I--0.2639 +/- 0.0175 S.E.M., group II--0.3864 +/- 0.0235, group III--0.6262 +/-0.0491). Patient tests (n = 110) were separated into normal (N), borderline (B), and chemical-diabetic (C) for each SA group. IRI means were above control data for each test type in each SA group at all sampling times; one fourth of these differences were significant. IRI responses also increased within each SA group from N to B to C tests. Mean IRI areas and IRI area to PG are mean ratios were higher than in controls, and this difference was greatest with the most abnormal (C) test type in each SA group. A subgroup of three patients who had low IRI responses from the outset and developed overt diabetes in one to three years was excluded from the analysis. In contrast to apparent relative insulin inefficiency with normal maturation and with chemical diabetes, they had exceptional responsiveness to their low IRI levels. Variable involvement of alpha as well as beta cells in the pathophysiology of diabetes is suggested as one explanation for these paradoxic observations. Changing receptor affinity might also be implicated.
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