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Biomedical subjects

G Leb

Publications and source records attributed to G Leb.

At least 73 records · Page 4Linked to original sources

[Pharmacology and dosage of thyrostatic drugs].

The iodine organification in thyroid gland was inhibited by application of Thyrostatic (Methimazole, Carbimazole) and consequently, thyroid hormone production and excretion were diminished. Carbimazole is converted to Methimazole in vivo and in vitro. Equivalent doses of Carbimazole and Methimazole are 0.6 to 1.0. Methimazole penetrates through the placenta, therefore established therapy with Methimazole (or Carbimazole) and thyroid hormone are contradicted in states of gravidity. In hyperthyroidism, preferred therapy strategy is accepted as Methimazole and/or Carbimazole only and in low doses, respectively (40-60 mg Methimazole as first step, consequently to doses down to 5-10 mg daily); accompaning rates of hematopoetic damage are dose responded.

Antithyroid Agents↗

Effect of pancreatic polypeptide on the motility of the guinea-pig small intestine in vitro.

The effect of porcine pancreatic polypeptide (PP) on the motor activity of the longitudinal and circular muscles of the guinea-pig isolated small intestine was investigated. PP (0.2-20 nM) inhibited cholinergic contractions of the longitudinal muscle in response to electrical field stimulation, the maximal effect being a 30% reduction of the contraction amplitude. Carbachol-induced contractions of the longitudinal muscle were not affected by PP (10 nM). PP (0.3-30 nM) also inhibited reflex contractions of the circular muscle elicited by balloon distension and recorded orally to the site of distension; the maximal effect was a 80% reduction of the reflex contraction. In contrast, carbachol-induced contractions of the circular muscle remained unaltered by PP (10 nM). It was further found that PP (10 and 100 nM) enhanced the threshold intraluminal pressure at which peristaltic waves were triggered. All these effects of PP appeared to be transient. Taken together, these data indicate that PP does not act on intestinal smooth muscle but can modulate the activity of certain enteric neurones which are involved in the regulation of intestinal motility.

Animals↗

[Diagnostic significance of immunoradiometric serum TSH determination].

TSH measurements using sensitive TSH-IRMA method makes differentiation of euthyroidism and hyperthyroidism possible without TSH stimulation after TRH. TSH-basal values less than 0.1 mU/L proof pituitary TSH suppression (clinical overt and latent hyperthyroidism, thyroid hormone therapy etc.). TSH-basal values between 0.4 and 4.0 mU/L are found in euthyroidism. TSH-basal values greater than 4.0 mU/L indicate latent or manifest hypothyroidism. With basal TSH values between 0.1 and 0.4 mU/L (borderline values between euthyroidism and "relative pituitary hormone excess") a TRH-test ist still necessary as it is not possible to predict stimulated TSH values from basal TSH concentrations with adequate accuracy. TSH measurements using sensitive IRMA methods may be recommanded as a screening test of thyroid function.

Humans↗

[Significance of pancreatic polypeptide in gastrointestinal diseases].

Release of pancreatic polypeptide (PP) into blood by pancreatic PP cells is closely correlated with pancreatic exocrine secretion and is thus stimulated by food intake. PP causes inhibition of exocrine pancreatic secretion and bile acid output. In insufficiently treated diabetics elevated basal and postprandial serum levels of PP are found, which return to normal when adequate treatment is administered. In patients with autonomous diabetic neuropathy insulin induced hypoglycemia leads to subnormal increases of serum PP levels. Low PP secretion is found in chronic pancreatitis only when pronounced pancreatic insufficiency is observed. In patients with duodenal ulcus significantly elevated but also normal serum PP concentrations were found. Endocrine active pancreatic tumors may cause highly increased PP levels together with other hormones and elevated serum PP levels may be used as a diagnostic indication in such rare cases. However the determination of PP serum levels is not suited as a routine diagnostic method.

Blood Glucose↗

[Determination of the free thyroxine concentration (FT4) in serum using the FT4 fraction and total thyroxine concentration].

A new equilibrium assay for the determination of serum free thyroxine was evaluated in 514 patients. The assay comprises a two-vial-procedure to measure total thyroxine and free thyroxine fraction by use of monoclonal antibodies. Free thyroxine concentrations are calculated from fT4-fraction and total thyroxine concentration readings. In euthyroidism the average free thyroxine fraction (%fT4) was 0.011%, in hyperthyroidism this fraction was elevated, in hypothyroidism it was below normal. In patients with TBG anomalies, TBG values were inversely correlated with fT4 fraction readings. The "euthyroid reference range" of FT4 (SPAC ET) was between 0.70 to 1.78 ng/dl. This euthyroid range of FT4 was determined from TT4 concentrations measured by T4-RIA (SPAC T4 MONO) which were 30% above TT4 values measured by conventional T4-RIA (SPAC T4 POLY; polyclonal antibodies). However, a different euthyroid range of FT4 between 0.55 to 1.30 ng/dl was observed as well as by other investigators when conventional T4-RIA measurements were used for calculation of FT4 values. Our results indicate that calculated FT4 concentration values are highly dependent on the methods used for determination of total thyroxine concentrations. Precision and reproducibility of this two vial equilibrium assay did not meet the requirements mandatory for the application as a clinical routine diagnostic procedure, and its general use for this purpose can as yet not be recommended.

Adult↗

The evaluation of free thyroid hormones (FT4 and FT3) in the routine diagnosis of thyroid function.

The validity of the free thyroid hormone parameters (FT4 and FT3) was verified in a random sample of 154 ambulatory patients with thyroid conditions. The "euthyroid range" of FT4 was between 15.67 and 30.66 pmol/l; median 21.98 pmol/l. The distribution of the FT4 readings peaked on the left and sloped to the right (log normal). In our laboratory, the "euthyroid reference range" of FT4 is between 10-28 pmol/l. The "euthyroid range" of FT3 extended from 4.6 to 9.7 pmol/l; median 6.63 pmol/l. The distribution of the readings was likewise log normal. The values of FT4 and FT3 are not significantly influenced by TBG concentration anomalies in otherwise healthy thyroid patients. For purposes of discrimination between euthyroidism and hyperthyroidism, FT3 (95%) and FT4 (90%) are better suited than the corresponding quotients for the free hormone fraction or the total hormone concentrations. On the other hand, the free hormone parameters are less suitable for the diagnosis of hypothyroidism. These results were deduced theoretically from mathematical function analyses between the TBG-independent free hormone parameters and the TBG-dependent hormone concentrations.

Adolescent↗

Influence of calcitonin on serum levels of pancreatic polypeptide in man.

In groups of 8 patients each, the increases in pancreatic polypeptide (hPP) serum level were measured after a protein-rich test-meal; one group received an infusion of 200 IU Salmon-calcitonin for a period of 3 hour while the other group did not. Calcitonin causes a significant inhibition of both the basal and the stimulated hPP serum level. Among the patients who did not receive a calcitonin infusion, the stimulated values after 15 to 120 minutes were significantly higher than the initial values, while patients receiving calcitonin did not show a significant increase. With calcitonin, the area under the secretion curve was 43% smaller. yet, on the basis of our results, the known gastrointestinal effects of calcitonin on pancreas secretion cannot be completely explained by the observed inhibition of hPP secretion.

Adult↗

[Hypotheses on the validity of the radioimmunologic measurement of FT4].

In patients undergoing long-term thyroid hormone therapy with constant doses the results of FT4 concentrations measured by radioimmunoassay (FT4-AMERLEX) were compared with calculated FT4 values and related to total thyroxine, serum TBG levels, respectively T4/TBG, to control the validity of radioimmunologic FT4 measurements for clinical routine diagnostic purposes. Based on mathematical analyses on the interdependence of these values the following principles were confirmed: free thyroxine measurements are dependent on total thyroxine with a power of x to the exponent and on T4/TBG-ratio with an exponential function. The percentage of free thyroxine (FT4/TT4 ratio) is inversely and exponentially related to serum TBG concentrations. Indeed, the RIA-FT4 results are largely independent of the concentration of binding globulin within certain limits. In thyroid patients without extrathyroid disorders no grossly false hypo- or hyperthyroid FT4 values are to be expected by deviating thyroxine globulin concentrations.

Goiter↗

[Modification of the FT4-level and the nonspecific peripheral thyroid parameter by heparin].

Heparin produces changes in FT4-levels both in vivo and in vitro as determined by commercial kits. Methods utilising the principle of equilibrium dialysis show significant increases whereas methods using T4-tracer analogue techniques reveal marked decreases in FT4-values. Possible clinical side-effects of heparin administration such as heparin-induced hyperthyroidism and tachyarrhythmias are discussed. The present results confirm the FT4-decreasing effect of in vivo and in vitro administration of heparin with FT4-RIAs based on the tracer analogue technique; however, the unspecific peripheral thyroid parameter of systolic time-intervals did not reveal any tendency towards hyperthyroidism. Also the discrepant results dependent on the method used, indicate that, following heparin administration FT4-levels do not reflect that hormone concentration is relevant to the metabolism of the whole body.

Adult↗

[Clinical application of alkaline phosphatase bone-isoenzyme determination with acetate foil].

Clinical application of alkaline phosphatase bone isoenzyme determination using acetate foil is investigated in patients with known underlying disease and is compared with diagnostic evaluation of 112 bone-scans. The separation of alkaline phosphatase isoenzymes proves a valuable diagnostic support of bone scintigraphy. Isoenzyme determination moreover reveals primary and secondary bone changes in early stages of the disease and also offers the possibility of quantitative follow-ups.

Adenocarcinoma↗

TSH, T3, rT3 and fT4 in maximal and submaximal physical exercise.

The response of various thyroid hormone parameters to maximal physical exercise (MPE) was investigated in 14 medium and long distance runners and 13 divers. The effects of submaximal long time physical exercise (SMPE) was examined in seven divers. The TSH-level decreases significantly during MPE and slightly rises again after the end of the exercise. In SMPE, however, TSH continuously rises until 15 min after the end of the exercise. The T3 level rises significantly in MPE and falls below the initial value 15 min after the exercise finishes, during SMPE it remains practically unchanged and slightly decreases after the finish. In MPE, the rT3 level does not change and slightly decreases after termination, while the fT4 level continuously decreases from the beginning till 15 min after the exercise period. The latter two parameters do not show any change in SMPE. As possible reasons for the changes of TSH levels a decrease (MPE) or an increase (SMPE) of pituitary secretion might play a role. Furthermore, in MPE the rise in T3 level might be related to hemoconcentration, and the decrease in fT4 level to an elevated cellular utilization.

Adult↗

[Two generations of FT4-radioimmunoassays--results in euthyroid patients and in patients on thyroid hormone therapy].

In accordance with the TRH-test two generations of FT4-immunoassays were checked in order to find a substitute for the free thyroxine index. The euthyroid reference range of FT4 was between 0.69-1.91 ng/dl using GammaCoat (Clinical Assays) and 0.94-2.29 ng/dl using Amerlex (Amersham), respectively. In the euthyroid range, FT4 as measured by Amerlex was, on the average, 47% higher than the value obtained by using GammaCoat. During treatment by thyroid hormones and TSH-suppression following TRH application, Amerlex FT4 values were up to 59% higher than the GammaCoat FT4 values. During replacement therapy, the FT4 values obtained by Amerlex were within the euthyroid reference range so that a differentiation between substitution and suppression appears to be possible by means of determining FT4. An overdose was assessed by simultaneous determination of T3 and FT4. According to our results Amerlex FT4 meets the requirements of a modern radioimmunoassay and is suitable as a substitute for the free thyroxine index. For this purpose the earlier method of determining FT4 (GammaCoat) does not seem suitable.

Adolescent↗

Stereospecific determination of D-thyroxin and L-thyroxin in serum.

A new method for separate determination of D-thyroxin and L-thyroxin in the serum was applied to study the response of serum levels of these isomers and of radioimmunologically determined total T3, total T4, free T4 and TSH upon administration of 2, 4 and 6 mg of a highly purified D-thyroxin preparation in six male patients with diffuse nontoxic goiter. D- and L-thyroxin are determined separately following extraction of the hormone from the serum and formation of diastereomeric dipeptides. The separation and final determination are accomplished by means of ion-pair chromatography on reversed-phase columns using an iodine-selective catalytic detector. A significant decrease in TSH takes place during the 3-days observation period. The values of D-T4, total T3 and free T4 are highest 4 hours after administration of the tablets and get to be to initial values after 24 hours. L-T4 shows no significant change. A direct suppressive effect of D-T4 on the pituitary gland may therefore be assumed as the cause of the suppression of TSH secretion.

Adult↗

Pharmacokinetics and metabolism of 14C-labelled alinidine in man and dogs.

Radioactively labelled alinidine was administered intravenously (10 mg) and orally (40 mg) to 5 healthy volunteers and beagle dogs (3 animals for each administration route: 0.1 mg/kg body weight i.v. and 1 mg/kg body weight p.o.). Alinidine was totally absorbed in both species. Regardless of the route of administration man excreted the drug via the kidneys within 12 hours, almost entirely in the unchanged form. The blood plasma curves in man followed a multiexponential decline (t 1/2 alpha : 35 sec, t 1/2 beta : 44 min, t 1/2 gamma : 210 min). The maximum plasma levels of the drug were recorded in man, 45 min after oral administration. However, the rather slow decline of plasma radioactivity observed in dogs, corresponded well with the delayed urinary excretion of alinidine (50% of the administered dose) in this species. Dogs metabolized the drug extensively; seven different metabolites including the parent compound were isolated from canine urine. considerable interindividual differneces were found concerning the quantitive but not the qualitative metabolic pattern of alinidine in dogs. Structural analysis by mass spectrometry revealed oxidation, hydroxylation, and cleavage products of alinidine, altered in its imidazolin and/or allylic moiety. In both species no traces of clonidine were found, which was a predicted metabolite formed by the removal of the allylic sidechain of alinidine.

Administration, Oral↗

[Determination of serum free thyroxine: normal range, relation to the free thyroxine ratio and total thyroxine (author's transl)].

The validity of a commercially available f-T4 radioimmunoassay was investigated in 122 patients with different thyroid status. The normal range of f-T4 was 0.60-2.20 ng/dl in euthyroid patients from an endemic goiter area. No significant difference was found between normals and a group taking oral contraceptives (mean = 1.37 ng/dl vs. 1.45 nd/dl). In patients on thyroid hormone or antithyroid drug therapy, f-T4-values showed a better correlation with the results of an oral TRH-test than total T4 or the free thyroxine ratio (ETR). Specificity of ETR was better than that of f-T4. Sensitivity of f-T4 was higher in the group with negative TRH-test, but lower in hypothyroidism as compared to ETR. Determination of f-T4 by radioimmunoassay is a simple diagnostic procedure. Since f-T4 RIA is not influenced by changes in TBG-levels its use is particularly recommended in cases where such changes are to be expected such as estrogen application or gravidity.

Antithyroid Agents↗

[Comparison of 100 micrograms TRH intravenously and 40 mg TRH orally in euthyroidism (author's transl)].

Euthyroid in-patients were investigated with 100 micrograms TRH given intravenously and with 40 mg TRH given orally in order to compare the sensitivity of intravenous and oral TRH-test. In all patients (age 15-91 years) maximal TSH-levels 180 min after 40 mg TRH are significantly (p less than 0.01) higher than maximal TSH-levels 30 min after 100 micrograms TRH. In patients under 50 years of age TSH-30 and TSH-180 are identical on average (6.42 +/- 0.29 microunits/ml vs. 6.53 +/- 0.54 microunits/ml/log x +/- SDlog). In patients older than 50 years TSH-30 is significantly lower (p less than 0.02) than in patients aging less than 50 years (2.11 +/- 0.88 microunits/ml vs. 6.42 +/- 0.29 microunits/ml). Both age-related groups demonstrate no significant difference (p greater than 0.2) in TSH-180 after 40 mg TRH (6.53 +/- 0.54 microunits/ml vs. 3.65 +/- 0.74 microunits/ml). 14 cases (34%) are low or non responders to 100 micrograms TRH intravenously, 8 (19.5%) only following 40 mg TRH orally. Patients with complete TSH-suppression (both iv. and oral TRH-test negative) show significant (p less than 0.05) higher ETR, T4 and fT4 than patients with partial TSH-suppression (iv. negative and oral TRH-test positive). The dose of 100 micrograms TRH does not increase the sensitivity of the test, the specificity is decreased in older patients, the dose of 100 micrograms TRH seems to be to low to yield reliable results. 40 mg TRH orally does not show any false positive findings, because TSH-stimulation is longer and more intensive. T3 increase three hours after orally TRH-application indicates an intact feedback mechanism.

Administration, Oral↗