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Biomedical subjects

A Pilo

Publications and source records attributed to A Pilo.

At least 55 records · Page 3Linked to original sources
PubMed1985

The disposal of an oral glucose load in healthy subjects. A quantitative study.

Although it is an established concept that the liver is important in the disposition of glucose, the quantitative contribution of the splanchnic and peripheral tissues, respectively, to the disposal of an oral glucose load is still controversial. In the present investigation, we have employed the hepatic venous catheter technique in combination with a double-tracer approach (in which the glucose pool is labeled with 3H-glucose and the oral glucose load is labeled with 14C-glucose) to quantitate the four determinants of oral glucose tolerance: rate of oral glucose appearance, splanchnic glucose uptake, peripheral glucose uptake, and suppression of hepatic glucose production. Studies were carried out in 11 normal volunteers in the overnight-fasted state and for 3.5 h after the ingestion of glucose (1 g/kg body wt; range, 55-93 g). In the postabsorptive state, the rate of endogenous (hepatic) glucose production, evaluated from the 3H-glucose infusion, was 2.34 +/- 0.06 mg/min X kg. Glucose ingestion was accompanied by a prompt reduction of endogenous glucose output, which reached a nadir of 0.62 +/- 0.23 mg/min X kg at 45 min and remained suppressed after 3.5 h (0.85 +/- 0.22 mg/min X kg). The average inhibition of hepatic glucose output during the absorptive period was 53 +/- 5%. The appearance of ingested glucose in arterial blood, as derived from the 14C-glucose measurements after correction for recycling 14-C radioactivity, reached a peak after 15-30 min, and 14C-glucose continued to enter the systemic circulation throughout the observation period. The rate of appearance of ingested glucose was 2.47 +/- 0.45 mg/min X kg at 3.5 h. A total of 73 +/- 4% of the oral load was recovered in the systemic circulation within 3.5 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1984

Comparison of plasma and urinary methods for the direct measurement of the thyroxine to 3,5,3' - triiodothyronine conversion rate in man.

A further development of a new method recently proposed for the direct measurement of the conversion ratio (CR) of T4 to T3 in man is presented. [125I]T4 and [131I]T3 are injected simultaneously, and Sephadex chromatography is performed on urine samples to determine [125I]T3 formed in vivo, while plasma samples are used to measure the injected tracers. CR is calculated with the assumption that urinary [125I]T3 closely reflects [125I]T3 appearing in plasma after the injection of precursor [125I]T4. Four normal subjects and six patients with various thyroid disorders were studied using this method. The experimental data were also analyzed by our previous method based on plasma sampling only and by two recently described methods based on urinary measurements. These comparisons were made in an attempt to ascertain whether there is any systematic difference between the conversion values derived from plasma data and those derived from urinary data. Using plasma data alone, the CR was 28.6 +/- 3.4% (mean +/- SEM) in a group of four normal subjects, 37%, in two untreated hypothyroid patients, 40.2% in one hypothyroid subject receiving T4 treatment, 30.9% in one hyperthyroid patient, 24.9% in one patient with selective hyperthyroxinemia due to amiodarone treatment, and 10.7% in one normal subject after iopanoic acid administration. These values were in excellent agreement with those obtained by the modified procedure described here, in which both urinary and plasma measurements are used. Of the methods using urinary data alone, however, one gave similar results, while the other systematically overestimated the CR, possibly due to delayed excretion of labeled T4 metabolites into the urine. We conclude that 1) the analytical procedure to separate the labeled tracers and metabolites in urine or plasma is critical for the accurate estimation of CR; 2) when an adequate separation procedure is available, plasma and urinary methods for measuring CR yield comparable results; and 3) the plasma method should be used when, in addition to CR, other kinetic (distribution and turnover) parameters of T4 and T3 metabolism are to be estimated.

Adult↗
PubMed1984

Progress report on a national quality-control survey of triiodothyronine and thyroxin assay.

In January 1980, a national external quality-control survey was organized to evaluate assays for triiodothyronine (T3) and thyroxin (T4). Currently, about 150 laboratories are involved. Each participant has received and assayed 100 quality-control samples during four periods of about six months each. The average analytical performance achieved by the participants in each six-month period was estimated by computing the average between-laboratory agreement (CVT), the overall average bias, and the average laboratory imprecision. During the 2.5 years of the survey, analytical performance has improved for both assays (CVT decreased from 17.0 to 15.7% for T3 and from 13.1 to 12.7% for T4). Analysis of survey results according to the method/kit used (mean kit bias and kit imprecision for the nine kits most used by participants) showed that the analytical reliability of the T4 assay is generally better than that observed for T3, mainly because of the larger systematic differences among T3 kits.

Chemistry, Clinical↗
PubMed1982

Impaired insulin degradation in a patient with insulin resistance and acanthosis nigricans.

The kinetics of plasma insulin were studied in a 14 year old girl with the syndrome of insulin resistance and acanthosis nigricans. The clearance of plasma insulin was found to be strikingly reduced (135 ml/min . m2 versus 456 +/- 22 in 17 normal control subjects), whereas the basal systemic insulin delivery rate was increased about 10-fold (25.5 mU/min . m2 versus 2.6 +/- 0.3 in normal subjects). Thus, reduced insulin clearance and excessive posthepatic delivery of the hormone both contributed to the severe fasting hyperinsulinemia (218 microunits/ml) associated with the other clinical features of the syndrome (glucose intolerance, primary amenorrhea, polycystic ovaries, hirsutism). Following ovarian wedge resection, insulin clearance rose to 264 ml/min . m2, and insulin delivery fell to 9.8 microunits/ml min . m2. The resulting abatement of the patient's hyperinsulinism (fasting plasma insulin = 37 microunits/ml) was accompanied by the appearance of menses, normalization of glucose tolerance, and amelioration of the acanthosis. The improvement in menstrual function and acanthosis, however, was not sustained. This case provides evidence for interdependence of insulin action and insulin degradation in humans.

Acanthosis Nigricans↗
PubMed1982

Four methods for glucose assay compared for various glucose concentrations and under different clinical conditions.

Glucose was measured by the ferricyanide, the Beckman glucose oxidase, and the hexokinase procedures in 228 plasma samples taken during standard oral glucose-tolerance tests in 17 normal subjects and in 21 chemical diabetics. The neocuproine method was also used to measure glucose concentration in 156 samples (78 before and 78 after dialysis) collected from six diabetic and uremic patients who were on maintenance hemodialysis. Ferricyanide in all conditions and neocuproine in uremic patients overestimated glucose concentrations over the entire experimental range as compared with either enzymic method. This bias or systematic error of the reducing vs the enzymic procedures, due to nonglucose reducing substances ("saccharoids"), becomes considerably greater when their concentration is increased as in chronic uremia. Also, the inverse relation between glucose concentration and overestimation of glucose by the reducing methods has been detected. With respect to the hexokinase method, a mild but significant underestimate of glucose oxidase readings has been observed for higher glucose concentrations. We find neocuproine to be the most imprecise of these procedures.

Autoanalysis↗
PubMed1980

Labeled metabolites appearing in human serum after 125I-triiodothyronine (T3) administration: a quantitative reappraisal.

The appearance in human serum of labeled iodothyronines arising from 3,5,3'-triiodothyronine (T3) catabolism was measured after bolus administration of 125I-T3. The use of column chromatography made it possible to separate in the plasma samples iodoproteins, iodide, T3 and a fourth peak ("pre-T3") eluting just before T3. The radioactivity associated with this pre-T3 peak was found to be 0.5% of T3 activity 30 min after injection, and reached a plateau value of 5.6% +/- 1.2 (mean +/- SD) from the 10th hr onward. From these data, we calculated that a maximal 5% underestimation in T3 metabolic clearance rate is inherent in those analytical methods that do not completely separate pre-T3 from T3 radioactivity. The MCR of 3,3'-diiodothyronine (T2) was also measured from the plasma disappearance curve after single injection of 125I-3,3'-T2. From these data and the mean disappearance curve of T3, the appearance curve of 3,3'-T2 in plasma was reconstructed by convolution under the assumption of a 100% conversion of T3 to 3,3'-T2. A plateau value of 4.6% of T3 activity was computed, very comparable to the experimentally determined 5.6%. This suggest that, if labeled 3,3'-T2 is the main component of the pre-T3 peak, the conversion into 3,3'-T2 represents a major pathway of T3 metabolism in man.

Chromatography, Gel↗
PubMed1979

The response to intravenous glucose of patients on maintenance hemodialysis: effects of dialysis.

To learn whether a single dialysis can acutely improve the intravenous glucose tolerance (i.v.GTT) of chronically dialyzed patients, a standard i.v.GTT was performed on 10 nonobese uremic subjects on maintenance hemodialysis for 27 +/- 9 (mean +/- SEM) mo, and on a control group of 13 normal subjects. The uremic patients were tested first 0.2-17 (range) hr, and then 65-109 hr, from last dialysis. In the uremic sera, plasma glucose was analyzed by 4 methods; 2 reducing (neocopurine and ferricyanide) and 2 enzymatic (hexokinase and glucose oxidase). The reducing methods markedly overestimated plasma glucose concentration because of the presence of nonglucose reducing substances (notably, creatinine). This inteference was significantly cut down by dialysis. A single dialysis, on the other hand, failed to improve the glucose fractional decay rate (KG) computed from the glucose oxidase data (1.69 +/- 0.2%/min before and 1.35 +/- 0.1 after dialysis, versus 1.47 +/- 0.1 of the normal subjects). The same conclusion was derived from the data measured by the other 3 methods of glucose assay. Fasting plasma insulin concentrations were, on average, above normal (5.5 +/- 0.6 muU/ml) both before (12.3 +/- 2.7, p less than 0.05) and after (17.2 +/- 3.5, p less than 0.01) a single dialysis. Likewise, the area under the glucose-induced plasma insulin curve was significantly greater than normal (1.46 +/- 0.21 mU/ml . min) both before (2.26 +/- 0.34, p less than 0.05), and after (2.86 +/- 0.43, p less than 0.01) dialysis. A single dialysis had little effect on either basal or glucose-stimulated insulin release, and no significant difference in the insulinogenic index (insulin area/glucose area) was found between the control and the uremic group in either test. Insulin response was not correlated with KG, whereas it was significantly associated with higher triglyceride levels. Creatinine, urea or methylguanidine did not appear to have any influence on KG, but lower serum potassium levels were significantly associated with poorer i.v.GTT's. Plasma calcium bore a reciprocal relation to the insulinogenic index. Chronically dialyzed subjects show some degree of tissue insulin resistance, which a single dialysis fails to correct. Electrolyte disturbances may play a role in this metabolic derangement.

Adolescent↗
PubMed1979

Triiodothyronine turnover studies in euthyroid patients with autonomous thyroid nodules.

Triiodothyronine (T3) kinetic studies were carried out using 126I-T3 and the single injection technique in eight clinically euthyroid patients with autonomous thyroid nodules and the metabolic results were compared to those obtained in a group of 12 healthy control subjects. Plasma labeled T3 concentration was measured by a chromatographic method based on the extraction of the hormone on Sephadex G-25 columns, followed by its elution with a specific anti-T3 antiserum. The analysis of the experimental plasma disappearance curves of the labeled hormone was performed using the noncompartmental method. The results obtained showed a significantly increased metabolic clearance rate of T3 in the patients with autonomous thyroid nodules, as compared to the control group. On the average, the T3 production rates were increased more significantly than the corresponding circulating levels of the hormone, therefore, suggesting that the significant TSH inhibition observed in the euthyroid patients with autonomous thyroid nodules could be related with an increased peripheral utilization of triiodothyronine.

Adolescent↗
PubMed1979

Pattern of insulin delivery after intravenous glucose injection in man and its relation to plasma glucose disappearance.

Plasma insulin concentrations after pulse intravenous injection of glucose show an early rise, which declines towards the prestimulation level smoothly. This pattern is the effect of both continuing secretion and hormone disappearance from the plasma. To reconstruct the time-course of the acutal secretory response, we measured insulin disappearance from the plasma of 17 healthy volunteers by means of a bolus intravenous injection of 125I-insulin, and then performed an intravenous glucose tolerance test with frequent blood sampling. The data were analyzed by deconvolution, which made it possible to compute the glucose-induced posthepatic insulin delivery rate minute by minute. Under basal conditions, 2.64 +/- 0.28 (mean +/-SEM) mU/min.m2 reaches the systemic circulation. In the 90 min that follow acute glucose stimulation, 0.86 +/- 0.11 U/m2, a 270% increment over the basal production rate, is made available to the periphery. A wide individual variability was found to exist in both the basal and the glucose-stimulated delivery. They were strongly (P less than 0.001) related to each other in a direct fashion. A first spike of insulin release (107 +/- 12 mU/min) occurred in all the subjects at 2.2 +/- 0.2 min followed, in 16 subjects, by a second spike (38 +/- 6 mU/min), at 11.3 +/- 0.9 min. Two-thirds of the total postglucose insulin output were associated with the initial, oscillatory phase (from 0 to 25 min, on average), and one-third with the "tail" phase (from 25 to 90 min), during which the average delivery rate was 5.0 +/- 0.9 mU/min.m2. The delivery curves were closely (mean squared deviation of 4.5 +/- 0.5 mU/min) reproduced by computer stimulation upon assuming that insulin secretion is a function of both glucose concentration and glucose rate of change. Both the first and the second spike of insulin delivery, but not the total insulin output during the test, showed a significant, positive correlation with the plasma glucose disappearance rate computed between 10 and 60 min. Furthermore, with a time shift of approximately equal to 15 min, a significant relationship between the phases of insulin secretion and the glucose decay rates, computed over corresponding time intervals, was evident throughout the test.

Adolescent↗
PubMed1978

The kinetics of plasma noradrenaline in normal and hypertensive subjects.

1. The kinetics of plasma noradrenaline have been determined in normal and essential hypertensive patients by intravenous injection of tritiated noradrenaline and serial mixed venous sampling. 2. The metabolic clearance rate of plasma noradrenaline in normal subjects was approximately 1 1 min-1 m-2, whereas in essential hypertensive patients it was significantly reduced to approximately 0.6 1 min-1 m-2. 3. Metabolic clearance rate was negatively correlated to mean arterial blood pressure and total peripheral resistances. 4. Particularly low values of metabolic clearance rate were found in two patients with congestive heart failure and one with phaeochromocytoma. 5. We propose that the access of plasma noradrenaline to the main removal mechanisms takes place in competition with the flow of unlabelled endogenous noradrenaline directly released by nerve endings. The slower removal of plasma noradrenaline in essential hypertension could then express a larger release of endogenous noradrenaline in this condition.

Adrenal Gland Neoplasms↗
PubMed1978

Kinetic analysis of plasma insulin disappearance in nonketotic diabetic patients and in normal subjects. A tracer study with 125I-insulin.

The studies so far reported on the metabolic clearance rate of insulin in human diabetes mellitus have given conflicting results, probably because they have been conducted on few patients and have used a variety of experimental techniques and data treatments. We investigated the kinetics of insulin distribution and degradation in 35 normal subjects and in 42 nonketotic, nonobese, overtly diabetic patients, of whom 26 were above 40 yr old and 16 were 40 yr old or less at diagnosis. The design of the study combined (a) the use of a tracer to perturb minimally the steady state and to avoid glucose infusion; (b) the preparation of purified [(125)I]-monoiodoinsulin, which has a metabolic behavior similar to that of native insulin; and (c) noncompartmental analysis of the plasma immunoprecipitable (125)I-insulin disappearance curves, which were recorded for 2 h after pulse i.v. injection of the tracer.Metabolic clearance rate was found to be similar in diabetics (404+/-18 ml/min.m(2), mean+/-SEM) and in normals (420+/-14), although the latter-onset patients had slightly, if not significantly, lower metabolic clearance rate values than the earlier-onset diabetics (385+/-19 and 443+/-36, respectively). The initial distribution volume of the hormone also did not significantly differ in diabetics and normals and was similar to plasma volume. The reentry rate into the initial distribution volume of the hormone and the total, plasma-equivalent distribution volume of insulin were both significantly raised in diabetics (251+/-12 ml/min.m(2) and 10.3+/-0.5 liters/m(2)) in comparison with normals (195+/-8 and 7.5+/-0.3). The posthepatic delivery rate of insulin was found to be slightly raised in later-onset diabetics (194+/-20 mU/h.m(2)), but somewhat reduced in earlier-onset diabetics (133+/-15) in comparison with normals (172+/-14); these differences reflected the different basal plasma insulin concentrations in these three groups. Chronic treatment with oral hypoglycemic drugs, age, duration of the disease, and degree of metabolic control appeared to have only little effect on the kinetics of insulin.On the basis of these results, we conclude that insulin-independent adult diabetics show, already in the fasting state, a combination of insulin resistance and insulin deficiency and a derangement in insulin distribution, the precise significance of which is uncertain.

Adult↗
PubMed1978

Evaluation of triiodothyronine (T3) kinetics in normal subjects, in hypothyroid, and hyperthyroid patients using specific antiserum for the determination of labeled T3 in plasma.

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.

Adolescent↗