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Biomedical subjects

F S Keck

Publications and source records attributed to F S Keck.

At least 19 recordsLinked to original sources
PubMed1999

Changes in metabolism of TRH in euthyroid sick syndrome.

OBJECTIVE: The aim of this study was to examine the metabolism of a simple dose, intravenously administered TRH bolus of 200 microg, in patients with euthyroid sick syndrome (ESS). PATIENTS AND METHODS: A TRH test was performed on ten ESS patients and ten controls upon admission (d1) and after recovery (d2). Blood samples were collected at 0, 10, 20 and 30min after TRH injection. We analyzed the volume of distribution (V(d)), the plasma clearance rate (PCR), the fractional clearance rate (FCR), the half-life (t(1/2)) and the TSH response to the injection of TRH. RESULTS: All patients had lower tri-iodothyronine (T(3)) levels compared with controls (0.9 +/- 0. 1nmol/l vs 1.9 +/- 0.1 nmol/l; P < 0.0001; mean +/- S.D.; paired t-test). In addition, the V(d) (16.7 +/- 5.9/l vs 30.6 +/- 0.6/l; P < 0.0005) and PCR (2.0 +/- 0.80 l/min vs 3.3 +/- 0.25 l/min; P <0. 0005) were found statistically lowered in patients than in controls, whereas FCR (0.119 +/- 0.01 permin vs 0.110 +/- 0.01 per min; P < 0. 025) was found increased in patients as opposed to controls. The t(1/2) of exogenously administered TRH was increased in ESS compared with controls (7.2 +/- 0.7 min vs 6.3 +/- 0.6 min; P <0.005). TSH response to TRH was found significantly repressed at 10, 20 and 30 min after TRH injection. On d2, these findings had reverted to normal and no changes regarding the kinetics of TRH and the response of TSH could be detected between patients and controls. CONCLUSIONS: The results demonstrate an impairment of TRH metabolism in ESS. The findings may suggest altered enzymatic activity, responsible for TRH degradation in states of acute ESS. These changes might be involved in the pathogenesis of ESS and represent part of an adaptive mechanism to this syndrome.

Adult↗
PubMed1997

Signal-averaged electrocardiogram in patients with insulin-dependent (type 1) diabetes mellitus with and without diabetic neuropathy.

The purpose of this study was to investigate the presence of ventricular late potentials derived from signal-averaged ECG in patients with IDDM with and without diabetic neuropathy. Eighty patients with IDDM but without evidence of cardiac disease and 80 age-matched healthy control subjects were investigated. The corrected QT interval was measured from the standard surface electrocardiogram. Ventricular late potentials were derived from signal-averaged electrocardiogram. Out of the 80 diabetic patients, 20 had an autonomic neuropathy, 20 had an isolated peripheral neuropathy, and 40 had no symptoms of neuropathy. The corrected QT interval was significantly prolonged in patients with an autonomic neuropathy as compared with the control group (436 +/- 23 ms(x 5) vs 384 +/- 23 ms(x 5), p < 0.001). In the other patient groups there was no significant prolongation of the corrected QT interval. Ventricular late potentials were present in 3 diabetic patients with an isolated peripheral neuropathy and in 1 control subject (NS). No diabetic patient with an autonomic neuropathy had ventricular late potentials. Our data did not indicate an increased incidence of ventricular late potentials derived from signal-averaged electrocardiogram in diabetic patients independent of a coexisting diabetic neuropathy or a prolonged corrected QT interval.

Adolescent↗
PubMed1995

Unchanged 5'-deiodinating activity during the induction of a nonthyroidal illness.

We investigated the formation of a "nonthyroidal illness" (NTI) in pigs undergoing ventricular fibrillation (VF) and resuscitation. Seven minutes after VF twenty-one pigs received either Epinephrine (E: 45 micrograms/kg B.W.; n = 7), Norepinephrine (NE: 45 micrograms/kg B.W.; n = 7), or Vasopressin (VP: 0.8 U/kg B.W.; n = 7). We determined the serum concentrations (sc) of total T4 (TT4), FT4, total T3 (TT3) and rT3 120 min before, during (t0), and 5, 15, 60 and 120 min after VF. At the end of the observation period we figured out the in-vitro T3-generation (kM, Vmax), the in-vitro rT3-generation, the in-vitro rT3-decomposition (kM, Vmax) and the content of cytosolic sulfhydryls (total sulfhydryls, non-protein bound sulfhydryls) in liver and kidney specimen. Animals not undergoing VF served as controls (C) for parameters measured in the intracellular compartment. TT4- and TT3-sc decreased to 3.3 +/- 0.6 micrograms/dl (p < 0.05, vs. t0) and 15.2 +/- 4.1 ng/dl (p < 0.05, vs t0), resp. FT4-sc remained stable for five minutes (2.63 +/- 0.41 ng/dl) before declining to 1.8 +/- 0.39 ng/dl (p < 0.05, vs. t0). The rT3-sc raised finally to 46.9 +/- 7.3 ng/dl (p < 0.05, vs t0). Iodothyronine sc did not exhibit differences between E-, NE- and VP-treatment. Neither in-vitro T3-generation, nor in-vitro rT3-generation, nor in-vitro rT3-decomposition nor intracellular sulfhydryl content were affected by the events of VF and resuscitation as compared to the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Systolic ventricular function in acute hypothyroidism: a study using Doppler echocardiography.

The influence of thyroid state on left ventricular systolic function was studied in 11 patients (5 men, 6 women, aged 20-55 years) without cardiac disease, who had undergone total thyroidectomy and radioiodine treatment for thyroid cancer before. Pulsed-wave Doppler echocardiographic measuring of aortic blood flow and two-dimensional/time-motion (2D/M-mode) echocardiography were performed on two occasions once while the patients were mildly hyperthyroid on thyroxine replacement therapy and once when they were hypothyroid. During hypothyroidism left ventricular end-diastolic diameter decreased from 48 +/- 5 mm to 46 +/- 5 mm (p < 0.05). The diameter of the aortic ring, the left ventricular end-systolic diameter, the thickness of the interventricular septum and posterior wall, and fractional shortening did not differ significantly between the two studies. The following parameter of aortic blood flow changed significantly when passing from the hyperthyroid to the hypothyroid state: peak velocity (0.86 +/- 0.15 m/s versus 0.72 +/- 0.15 m/s, p < 0.01); mean velocity (0.49 +/- 0.08 m/s versus 0.44 +/- 0.08 m/s, p < 0.01); time- velocity integral (14.1 +/- 3.0 cm versus 12.3 +/- 3.1 cm, p < 0.05); stroke volume (43.0 +/- 9.7 ml versus 35.2 +/- 8.2 ml, p < 0.05); and preejection period (124 +/- 23 ms versus 147 +/- 21 ms, p < 0.01). Peak acceleration, mean acceleration, acceleration time and left ventricular ejection time did not change when the thyroid state was altered. It is concluded that left ventricular contractile function was not affected by acute hypothyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1994

Doppler echocardiographic evaluation of left ventricular diastolic function in acute hypothyroidism.

OBJECTIVE: Left ventricular diastolic dysfunction is an important cause of symptomatic heart failure. Previous studies suggest that thyroid dysfunction affects left ventricular diastolic function but the underlying mechanisms remain controversial. The study was undertaken to asses the influence of acute hypothyroidism on left ventricular diastolic function and to elucidate possible underlying mechanisms by means of Doppler echocardiography in a group of athyreotic patients, whose thyroid state depended only on external thyroid hormone supply and could therefore easily be controlled. PATIENTS: Eleven patients (5 men, 6 women, aged 20-55 years), who had had total thyroidectomy, were investigated during mild hyperthyroidism and during acute hypothyroidism. Additionally, 11 healthy control subjects aged 25-51 years were included in the study. DESIGN: M-mode echocardiography of the left ventricle and pulsed-wave Doppler echocardiography of the transmitral flow velocity pattern were carried out. RESULTS: Acute hypothyroidism produced a decrease of left ventricular end-diastolic diameter from 48 +/- 5 to 46 +/- 5 mm (mean +/- SD P < 0.05), of peak velocity of early diastolic filling from 0.52 +/- 0.10 to 0.42 +/- 0.05 m/s (P < 0.05), of peak velocity of late diastolic filling from 0.42 +/- 0.10 to 0.36 +/- 0.09 m/s (P < 0.05), and a decreased time-velocity integral of early diastolic filling (6.2 +/- 1.8 vs 5.1 +/- 0.7 cm, P < 0.05). The other M-mode and Doppler echocardiographic parameters did not differ between the hyperthyroid and the hypothyroid states. CONCLUSIONS: The observed changes of the trans-mitral flow velocity pattern during acute hypothyroidism can be attributed to a reduction of pre-load. There is no direct evidence that acute hypothyroidism affects the intrinsic diastolic properties of the left ventricle.

Acute Disease↗
PubMed1994

Effect of corticotropin releasing factor on atrial natriuretic peptide release from the isolated perfused rat heart.

The effect of corticotropin releasing factor (CRF) on atrial natriuretic peptide (ANP) release and its possible modulation by indomethacin, norepinephrine, propranolol and nitro-L-arginine (an inhibitor of the endothelium-derived relaxing factor (EDRF) release) was investigated, using an isolated perfused rat heart preparation. Bolus injection of 5 micrograms CRF, dissolved in 100 microliters perfusion buffer, provoked a significant (p < 0.01 vs. control) short-time increase of ANP release. Indomethacin (3 x 10(-5) mol/l) inhibited the CRF-stimulated increase of ANP release and decreased the basal ANP secretion (p < 0.01 vs. CRF group). Norepinephrine (10(-9) mol/l) slightly, but not significantly, decreased the CRF-stimulated ANP release and did not change the basal ANP output. Propranolol (3 x 10(-6) mol/l) did not alter ANP release. Nitro-L-arginine (3 x 10(-5) mol/l) increased the basal ANP release (p < 0.01 vs. CRF group) and prolonged the CRF-induced rise of the ANP secretion. The present data suggest that prostaglandins are important mediators of basal and CRF-stimulated ANP release and that EDRF might be a physiological inhibitor of ANP release.

Animals↗
PubMed1993

The function of a hydrogen peroxide-detecting electroenzymatic glucose electrode is markedly impaired in human sub-cutaneous tissue and plasma.

Electroenzymatic glucose sensors implanted into sub-cutaneous (s.c.) tissue of human subjects and experimental animals exhibit lower sensitivities to glucose than in buffer solutions before implantation. The mechanism of the decrease of sensitivity is not known. Sensors used in this study were fabricated from platinum wires (diameter 0.125 mm) with covalently bound glucose oxidase at the tip of the wire. After coating the tip with polyurethane, wires were placed into 27 gauge steel needles. Sensors were operated potentiostatically at 700 mV against Ag/AgCl pseudo-reference electrodes. These sensors were implanted s.c. in 6 diabetic patients for 7 h. In 4 patients, sensors were responsive to successive increases of plasma glucose levels. Mean sensitivity to glucose in s.c. tissue was 29% of in vitro sensitivity. In 2 patients there was a sudden decrease of sensor currents, unrelated to glucose, shortly after implantation. Sensors were inhibited in human plasma to a similar extent. When sensors were exposed to native plasma and to plasma ultrafiltrate (mol. wt. < 10 kDa) for 10 h, identical decreases of signals were found. Exposure to dialysed plasma (mol. wt. > 12 kDa) caused much less decrease of sensor signals. Losses of sensor sensitivities to glucose in s.c. tissue and in plasma were totally reversible upon re-exposure of sensors to buffer solutions. We conclude that sensor inactivation in plasma and possibly in s.c. tissue is caused by low molecular weight substances not retained by the polyurethane membrane.

Adult↗
PubMed1993

On line continuous monitoring of subcutaneous tissue glucose is feasible by combining portable glucosensor with microdialysis.

A new method for continuous measurement of subcutaneous tissue glucose content is introduced: by combining the microdialysis technique with a wearable amperometric glucose sensor, a device for continuous glucose measurement in the subcutaneous tissue was obtained. This device was applied to healthy volunteers (n = 10) over the period of an oral glucose load and to type I diabetic patients (n = 10) under the conditions of daily life. Glucose profiles in both healthy and diabetic persons were followed in the subcutaneous tissue up to 27 hours. This technique will certainly open new perspectives of monitoring and treating diabetic patients.

Biosensing Techniques↗
PubMed1993

Evaluation of thyrotropin secretion before and after TRH by third generation chemiluminescent assay. Assessment of subclinical hyperthyroidism.

The recent introduction of third generation assays for TSH has led to a considerable improvement of assay sensitivity. To assess the clinical significance of subnormal basal TSH (b-TSH) values (< 0.2 microU/ml), we investigated b-TSH and TRH-stimulated TSH (r-TSH) by means of a new, highly sensitive immunochemiluminometric assay in 105 euthyroid subjects, 45 patients with overt hyperthyroidism and 18 patients suspected of having subclinical hyperthyroidism. A weak, albeit statistically significant, correlation (r = 0.48) was found between b-TSH and r-TSH and also between b-TSH and delta-TSH (r = 0.31) in euthyroid subjects. Consideration of b-TSH alone correctly identified 90 % of euthyroid subjects in this group; 10 of 105 apparently euthyroid subjects presented delta-TSH suggesting subclinical hyperthyroidism. While b-TSH was detectable (> 0.04 microU/ml) in 8 of 45 (18%) of hyperthyroid patients, all (100%) were abnormal in both b-TSH and r-TSH. 14 of 18 (78%) of patients with subclinical hyperthyroidism exhibited a blunted TSH response to stimulation (delta-TSH < 2 microU/ml). These results suggest that although the new generation of TSH assays can be a valuable addition to the diagnostic arsenal of thyroid function tests, certain limitations must still be accepted. Specifically, b-TSH in the "grey zone" (0.1-0.2 microU/ml) appears to be a less than reliable predictor of thyroid function.

Adult↗
PubMed1992

Serum angiotensin-converting enzyme activity and active renin plasma concentrations in insulin-dependent diabetes mellitus.

We report here the alterations of serum angiotensin-converting enzyme activity (S-ACE) and of active renin plasma concentrations (ARPC) in 41 insulin-dependent diabetes mellitus (IDDM) patients compared with those of 26 control subjects. The IDDM patients had S-ACE activity (54 +/- 16 I.E.) in the upper normal range (controls, 39 +/- 7). When the patients were subclassified according to their diabetic complications, a significant increase of S-ACE within the IDDM group compared to the controls was observed in patients with nephropathy (68 +/- 13, P less than 0.001) with persistent proteinuria and with retinopathy (63 +/- 14, P less than 0.001). A significant correlation was found between proteinuria and S-ACE (r = 0.98, P less than 0.001) and between retinopathy and S-ACE levels (r = 64, P less than 0.001). No correlation between blood pressure and S-ACE or between blood glucose and S-ACE was observed. The ARPC were within the normal range in the IDDM (21 +/- 9 ng/l) and in control (19 +/- 3) groups. No correlations between ARPC and blood pressure or blood glucose or the degree of diabetic complications were registered. These data show that S-ACE activity is elevated in IDDM patients with nephropathy-proteinuria and/or with retinopathy and the circulating renin may not represent the renal renin-angiotensin vascular system.

Adult↗
PubMed1992

Combination of microdialysis and glucosensor permits continuous (on line) SC glucose monitoring in a patient operated device. II. Evaluation in animals.

The microdialysis technique was used for following the glucose content of the extracellular subcutaneous (SC) fluid under varying blood glucose levels in rats. The glucose content in the microdialysis perfusion fluid was continuously analyzed by means of the measuring flow chamber of an ex vivo glucose monitor. In six ChBB rats blood glucose levels were varied between 40 mg/dl and 575 mg/dl by intravenous (IV) infusion of glucose and by SC injections of insulin, respectively. After a running-in period of about half an hour, the glucose content in the perfusion fluid was closely related to the blood glucose concentration (r > 0.92) up to a time period of 6 hrs. The "relative recovery" rate of glucose by the microdialysis probe in the SC tissue varied within the 6 experimental sessions. The relative recovery rate could be shown to be not dependent on the absolute blood glucose levels in the individual rat within the glucose concentration range tested.

Animals↗
PubMed1992

Thyroid status and hepatic thyroxine deiodinating activity under high-dose long-term nitrendipine.

The influence of high doses of oral nitrendipine on the hypophyseal-thyroid axis and on peripheral thyroxine metabolism was studied in baboons. Administration of 320 mg oral nitrendipine per kg body weight (b.wt.) for three months caused a hypothyroid state with decreased values for thyroxine and reverse triiodothyronine, elevated TSH, but unchanged triiodothyronine; the lower doses investigated (24 and 48 mg/kg b.wt.) were without any effect. High doses of nitrendipine concomitantly increased hepatic 5'-deiodinating activity by a rise in Vmax, which could be attributed to an increase in the deiodinating enzyme content. Normal T3 serum levels in the presence of low T4 serum concentrations under high dose nitrendipine can be ascribed, at least in part, to the enhanced peripheral 5'-deiodination.

Administration, Oral↗
PubMed1992

Thyrotropin-releasing hormone: pharmacokinetic and pharmacodynamic properties in chronic renal failure.

The pharmacokinetics of thyrotropin-releasing hormone (TRH) were determined following a single i.v. administration in ten patients with chronic renal failure (CRF) maintained on chronic hemodialysis and in six normal subjects. A TRH-test (200 micrograms) was performed in all subjects on nondialysis days and was followed by sequential venous blood sampling at 0, 2, 5, 10, 20, 30 and 60 min. Plasma TRH and serum concentrations of TSH, T4, FT4 and T3 were measured by specific and sensitive RIA's. Serum thyroid hormone concentrations were lower in the hemodialysis patients than in the normals (p < 0.001). Basal TRH and TSH levels were similar in patients and in controls, however, a blunted response of TSH to TRH in CRF (3.8 +/- 2.4 vs. 11.2 +/- 2.6 mU/l, p < 0.001) was observed. Mean peak TRH concentrations (Cmax) were 34.445 (11.085, SD) fmoles/ml in CRF and only (13,400 (1.020) in the normals 2 min after TRH administration (tmax). The mean elimination half-life (t1/2) of TRH was 16 min in CRF and 6.5 min in normals (p < 0.001). The metabolic clearance rate (MCR) was markedly lowered in CRF, 58.3 (19.1) compared to normals (82.2 [15.3] l/m2/day, p < 0.001). The area under the plasma concentration-time curve (AUC) was 57.529 (28.562) fmoles.ml-1.min in CRF and 37.339 (5.026) (p < 0.005) in normals. These findings indicate that the pharmacokinetic properties of TRH are impaired in CRF. The kidney might be an important catabolic organ for exogenous TRH. Dosing schedules of TRH require possible adaptation to renal function.

Half-Life↗
PubMed1991

Thyrotropin-releasing hormone: further extraction studies and analysis by fast protein liquid chromatography and radioimmunoassay.

We describe the clinical application of a radioimmunoassay combined with fast protein liquid Chromatography (FPLC) for measuring TRH immunoreactivity (TRH-IR) in blood samples extracted previously with methanol or with Sep Pak C18 cartridges. Sensitivity of the RIA was 3 fmol/tube, displacement at 50% B/B0 was achieved by 55 fmol of unlabelled TRH. Our specific antibody K2B7 (km = 2.2 fM) showed no cross reaction with other peptides. No difference was observed between the mean values of TRH-IR in 19 euthyroid, 22 hyperthyroid, 18 hypothyroid and 10 hypophysectomised patients (45 +/- 17.8, 58 +/- 30, 40 +/- 22 and 36 +/- 12 fmol/ml, mean +/- SD, respectively), whereas TRH-IR was significantly lowered (p less than 0.05) in 6 euthyroid pancreatectomised patients (21 +/- 5 fmol/ml). The reversed phase FPLC analysis of the TRH-IR presented in the methanol extracts was shown to have the same retention time as synthetic TRH. TRH could not be measured in unextracted blood samples. TRH added in preincubated (60 min, at 37 C), before extraction, blood samples showed a loss of 83.4% of immunoreactivity. Our results demonstrate that this method is able to detect TRH-IR in human blood by whole methanol extraction and/or by Sep Pak C18 cartridges extraction. Furthermore the findings suggest that the main source of circulating TRH-IR may be of extrahypothalamic (pancreatic?) origin and that the basal peripheral TRH levels are not involved or they do not clearly represent a pathological condition.

Adult↗
PubMed1991

Combination of microdialysis and Glucosensor permits continuous (on line) s.c. glucose monitoring in a patient operated device: I. In vitro evaluation.

A device for continuous glucose monitoring in fluids was obtained by combining the microdialysis technique with a measuring flow chamber of the "Glucosensor Unitec Ulm" using the GOD method for determining amperometrically blood glucose profiles. The in vitro experiments demonstrate that the relative recovery of glucose by this device is inversely related to the flow rate of the microdialysis perfusion fluid, which, in turn, is inversely related to the response time of the device. The glucose signal increases linearly with the area of the microdialysis working membrane (r = 0.98), and with the glucose concentrations of the standard solutions (r greater than 0.95). The variation coefficient for repeated measurements is below 8%. The accuracy of the device as demonstrated by mean measuring deviation ranges between 1 and 3.8%.

Biosensing Techniques↗
PubMed1991

Comparative effects of dopamine and dobutamine on glucoregulation in a rat model.

The influence of dopamine as compared with dobutamine on glucose homeostasis has been assessed in thyroidectomized euthyroid rats. Both sympathomimetic agents were given intravenously over 6 h at four dosages, varying from 2 to 30 micrograms.kg-1.min-1. Immediately before the end of the infusion period, serum concentrations of glucose and insulin as well as plasma glucagon concentrations were measured. Dobutamine infusions did not exert any influence on these parameters. At a dose of 7.5 micrograms.kg-1.min-1, dopamine infusion caused a decrease in glucose concentrations, accompanied by a rise of glucagon and insulin levels. Glucose levels were significantly increased in the presence of unaltered insulin and decreasing glucagon levels at higher dopamine doses. The rise in glucose levels was reversed by 8 micrograms.kg-1.min-1 and inverted to a decrease by 12 micrograms.kg-1.min-1 of the alpha-adrenergic blocking agent phentolamine, simultaneously infused with 15 micrograms.kg-1.min-1 dopamine, while the insulin levels were increased and glucagon levels remained elevated. These findings demonstrate that dopamine acts on glucoregulation divergently, according to the dosage applied. The data suggest that dopamine rather than dobutamine treatment may disturb glucose homeostasis.

Animals↗
PubMed1991

Aspects of chronic oral treatment with thyrotropin-releasing hormone: the hypothalamic-pituitary-thyroid axis in rats. A study with a pharmacological dose of thyrotropin-releasing hormone.

The effects of 16 days of oral treatment with thyrotropin-releasing hormone (TRH, 1 mg/24 h) on serum levels of thyrotropin (TSH), thyroxine (T4) and triiodothyronine (T3) and the kinetics of TRH in the blood were studied in normal rats. A second group of animals served as controls. TRH was dissolved by sonification (10 mg/l) and was stable in tap water. TRH was measured by a radioimmunoassay procedure (normal range: 20-80 pmol/l, antiserum K2B9 1:120,000 final dilution). An increase in basal TSH (7,200 +/- 440 ng/l, mean +/- SD) was found after 2 days of treatment (11,420 +/- 810 ng/l), but a significant increase was observed after 5 days of treatment (12,530 +/- 640 ng/l, p less than 0.001). T4 serum concentrations remained in the normal range during the entire period of study, whereas T3 serum concentrations (0.76 +/- 0.1 micrograms/l) were increased to 1.22 +/- 0.2 micrograms/l on day 5 (p less than 0.001). A subsequent decline of TSH, T4 and T3 up to the end of the study was observed. TRHmax concentrations were registered on day 5 (790 +/- 24 pmol/l). The mean value of TRHmax was 723 +/- 34 pmol/l. To improve the stability of TRH in tap water, 1-ml samples of drinking water with dissolved TRH were measured. The mean TRH concentration in drinking water was 73 +/- 1.5% (SD). No significant correlations were found between the area under the curve of TSH (184,340 ng.l-1.24 h) and that of TRH (14,954 pmol.l-1.24 h).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗