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Biomedical subjects

J Kvetny

Publications and source records attributed to J Kvetny.

At least 19 recordsLinked to original sources
PubMed2005

Subclinical hyperthyroidism in patients with nodular goiter represents a hypermetabolic state.

The aim of the study was to examine the metabolic status in patients with suppressed TSH but values of FT4I and T3 within the reference range (subclinical hyperthyroidism [sH]). Thirteen patients and 13 control persons with nodular goiter were included. The metabolic state was determined by measurements of basal oxygen consumption (VO2), bone mineral density (BMD), and the circadian variation of TSH. Further was the pituitary thyroid axis examined by studying the effect of lowering thyroid hormones by methimazol treatment. The circadian variation of TSH varied from that of normal persons as the night surge was abolished. The basal VO2 was significantly higher and BMD was significantly lower in patients with sH compared to control persons. Restoration of TSH by lowering of thyroid hormone concentrations lead to a normalization of VO2 and restoration of the circadian variation of TSH. The preserved pituitary thyroid axis, the abolished circadian TSH variation, the increased VO2, and decreased BMD in patients with suppressed TSH, but peripheral thyroid hormone concentrations within the reference range, indicate a hyper metabolic state, which might reflect either an altered cellular set point or an increased sensitivity towards thyroid hormones in peripheral cells and in the thyrotrope cells.

Bone Density↗
PubMed2004

Subclinical hypothyroidism is associated with a low-grade inflammation, increased triglyceride levels and predicts cardiovascular disease in males below 50 years.

OBJECTIVE: Mild thyroid failure is associated with an increased risk for development of atherosclerosis, but whether subclinical hypothyroidism is related to risk for cardiovascular disease is controversial. The purpose of the present study was to examine a possible association between subclinical hypothyroidism and cardiovascular disease. DESIGN: Cross-sectional study of a general population. PATIENTS: Twelve hundred and twelve subjects, men and women, between 20 and 69 years old without thyroid disease not treated with drugs interfering with thyroid function or analysis of TSH were included. MEASUREMENTS: Clinical signs of cardiovascular disease based on a questionnaire and medical records and laboratory analysis of lipids, atherothrombotic risk markers, C-reactive protein and TSH. RESULTS: The main findings were a high incidence of subclinical hypothyroidism (19.7%) in a general population. Subclinical hypothyroidism was associated with higher concentrations of triglycerides and C-reactive protein. Below 50 years of age cardiovascular disease was more frequent in males with subclinical hypothyroidism compared to euthyroid males. Subclinical hypothyroidism was a predictor of cardiovascular disease in males below 50 years with an odds ratio of 3.4 (95% confidence interval 1.6-6.8) for developing cardiovascular disease compared to euthyroid age-matched males. CONCLUSION: Our study demonstrates that patients with subclinical hypothyroidism have increased levels of triglycerides and signs of low-grade inflammation (raised C-reactive protein levels) and that subclinical hypothyroidism might be a risk factor for development of cardiovascular disease in younger males.

Adult↗
PubMed2001

Randomized placebo-controlled trial of perindopril in normotensive, normoalbuminuric patients with type 1 diabetes mellitus.

Diabetic nephropathy is one of the leading causes of end-stage renal disease. We examined whether ACE inhibitor treatment may have a nephroprotective effect in normotensive insulin-dependent diabetic patients without microalbuminuria and with normal glomerular filtration rate (GFR), and whether any effect was associated with the ACE genotype. In a prospective double-blind randomized study, normotensive patients with type 1 diabetes mellitus with normal serum creatinine and no microalbuminuria were treated with either placebo or perindopril, an ACE inhibitor. Urine albumine/creatinine ratio (ACR), mean blood pressure (MBP) and index of glomerular filtration rate (GFR) based on S-creatinine were determined. ACE genotype was determined by electrophoresis. ACR was higher in the placebo group than in the perindopril group after 4 months, and continued to increase during the study period. After 36 months of observation, ACR in the placebo group was 1.7+/-1.1 mg/mmol, and 0.6+/-0.2 mg/mmol in the ACE-inhibitor-treated group (p<0.001, Mann-Whitney test). During treatment, a significant increase in ACR in the placebo group (p=0.007), Wilcoxon matched paired test) was observed. There were no differences between the groups regarding MBP or GFR. The nephroprotective effects of ACE inhibitor treatment was not associated with the ACE genotype (II, ID, DD).

Adult↗
PubMed1999

Results from screening for gestational diabetes mellitus in a Danish county.

OBJECTIVE: To examine the complications in gestational diabetes mellitus with special reference to the significance of the threshold for the oral glucose tolerance test (OGTT, plasma glucose > or = 7.8 mmol/l (equivalent to blood glucose 6.9 mmol/l) (WHO criteria) or blood glucose > 6.7 mmol/l (local criteria) after 2 h 75 g oral glucose load). DESIGN: Prospective descriptive study. SETTING: From April 1, 1995 to April 1, 1997 a screening for gestational diabetes mellitus (GDM) according to the recommendations from the Danish board of health was performed in Ribe county. SUBJECTS: Pregnant women in Ribe county (n = 6158). MAIN OUTCOME MEASURES: Complications during pregnancy and the outcome. RESULTS: Two hundred and twenty (3.6%) women had GDM by the local selection criteria and 2.8% according to the WHO criteria. The study revealed a significantly increased frequency of malformations (7.3% vs. 1.2%, p < 0.0001) and preeclampsia (15.5% vs. 1%, p < 0.0001) in the group with GDM independent of selection criteria (obesity vs. family history and glucosuria). The frequency of preeclampsia appeared higher in the group with obesity (p = 0.040). Malformations appeared with identical frequency in the groups with OGGT threshold higher than blood glucose 6.9 mmol/l (plasma glucose 7.8 mmol/l) (WHO criteria) and with blood glucose between 6.7 and 6.9 mmol/l, whereas preeclampsia did not occur with higher frequency in the latter group. CONCLUSION: Complications appear frequently in women with an abnormal OGGT, and obesity predisposes to preeclampsia. The use of the WHO criteria for screening for GDM would miss a number of women with complications.

Adult↗
PubMed1996

Sarcoidosis causes abnormal seasonal variation in 1,25-dihydroxy-cholecalciferol.

OBJECTIVES: The spontaneous seasonal variations in the calcium regulating hormones 1,25-dihydroxy-cholecalciferol (1,25-DHCC) and parathyroid hormone (PTH) were investigated in patients with sarcoidosis. DESIGN: Controlled, prospective observational study with measurements in the winter and summer seasons, respectively. SUBJECTS: Twelve patients (age: median 33, range 21-54 years) with biopsy-verified (n = 8) sarcoidosis were included as well as 11 age-matched healthy control subjects. MAIN OUTCOME MEASURES: Serum values of calcium, ionized calcium, phosphate, chloride, bicarbonate, creatinine, albumin, angiotensin-converting enzyme, alkaline phosphatase, 1,25-DHCC, and PTH. Also, 24-h whole body retention of 99mTc methylene-diphosphonate was assessed. RESULTS: The patient group showed an increased level of 1,25-DHCC in the summer season (w:146 +/- 67, s:198 +/- 73 pmol L-1; P < 0.01) in contrast to the opposite finding among controls (w:161 +/- 34, s:144 +/- 43 pmol L-1; P < 0.05). Comparing the individual seasonal changes between the two groups, the difference was marked (P < 0.001). Compared with controls, total serum calcium was elevated in the summer season in the patient group (P < 0.05), in which the same parameter correlated positively with 1,25-DHCC (r = 0.658; P < 0.01). PTH was increased two to three times above the control values throughout the year (patients: w:0.37 +/- 0.13, s:0.24 +/- 0.08 micrograms L-1; controls: w:0.14 +/- 0.09, s:0.10 +/- 0.04 micrograms L-1; P < 0.001); although, the level of this hormone was still found within the reference interval. 24-h whole body bone scintigraphy failed to show any seasonal variation in bone metabolism. In contrast, serum alkaline phosphatase was found to be increased during the summer season compared with the control group (P < 0.001). Angiotensin-converting enzyme showed no seasonal variation. CONCLUSIONS: In sarcoidosis, 1,25-DHCC is abnormally regulated throughout the year, with a significantly higher serum level in the summer season. Uncontrolled production of 1,25-DHCC in sarcoid pulmonary alveolary macrophages is possibly responsible for hypercalcaemic episodes, and this parameter should be used as a marker of disease activity.

Adult↗
PubMed1996

Severe hypothyroidism masquerading as renal impairment.

A case of severe hypothyroidism in a 51-year old male is presented. The patient was especially complaining of weakness, stiffness and moderate pain in the proximal muscle groups together with rhinorrhea and nasal stenosis. Because of severely elevated S-creatine-kinase combined with reduced creatinine clearance and proteinuria, polymyositis with secondary glomerulopathy was suspected. Meanwhile, biopsies from skin, muscle, and kidney were normal. All symptoms disappeared 3 months after thyroid replacement therapy was initiated. S-TSH should be considered when evaluating patients with renal impairment of unknown etiology.

Creatine Kinase↗
PubMed1994

[Peripheral thyroid hormone resistance].

Peripheral thyroid hormone resistance (PTHR) was first described by Refetoff in 1967, and was characterized by raised serum hormone values of T4 and T3 and in appropriately elevated values of TSH. PTHR has been shown to be caused by a mutation in the TR beta gene resulting in impaired nuclear binding of thyroid hormones or an impaired post receptor hormone effect. The patients are often characterized phenotypically by impairment of bone, heart or cerebral function.

Humans↗
PubMed1993

Relation between phenotype and intra-cellular thyroid hormone effect in patients with altered peripheral thyroid hormone sensitivity.

OBJECTIVE: We wished to ascertain whether different phenotypic appearances in patients with altered cellular sensitivity to thyroid hormones were related to the type of altered intra-cellular thyroid hormone effect. DESIGN: Blood samples were obtained from two members of a family suffering from generalized thyroid hormone resistance (GTHR) for hormone assays and examination of the cellular thyroid hormone effect, and the results compared with results from other families with signs of altered peripheral thyroid hormone sensitivity. PATIENTS: Two members of a family with thyroid hormone resistance and nine normal persons were studied. MEASUREMENTS: Basal thyroid hormone function tests were measured. The thyroid hormone effect on mononuclear blood cells was determined by measuring the thyroid hormone stimulated oxygen consumption and glucose uptake. RESULTS: The two family members appeared phenotypically normal except for nodular goitre. Thyroid hormone stimulated glucose uptake was depressed whereas thyroid hormone stimulated oxygen consumption was normal. CONCLUSION: Comparison of the present results of the cellular examination in two patients with GTHR, with the results obtained in other families with altered peripheral thyroid hormone sensitivity, suggest that the classic GTHR (phenotype: normal or with goitre) is linked to impaired thyroid hormone stimulated glucose uptake, whereas in patients with osteopetrosis, the thyroid hormone insensitivity seems located at the mitochondrial level (impaired thyroid hormone stimulated oxygen consumption.

Adult↗
PubMed1992

3,5-T2 stimulates oxygen consumption, but not glucose uptake in human mononuclear blood cells.

L-thyroxine (T4), L-triiodothyronine (T3) and 3,5-di-iodothyronine (T2) rapidly (within 30 min) stimulated oxygen consumption in human mononuclear blood cells, whereas the D isomers of T4 and T3 and Triac had no stimulatory effect. Oxygen consumption was stimulated by the same magnitude by equimolar concentrations (5-500 nmol/l) of L-T4, L-T3 and 3,5-T2 reaching a plateau at 100 nmol/l of 0.025 umol/mg DNA x h. The stimulatory effects of T4 and T3, but not of T2 were inhibited by PTU. Glucose uptake was stimulated only by L-T4 and L-T3, whereas 3,5-T2, Triac and the D-isomers of T4 and T3 had no effect. The dose response curve reached an apparent maximum at 100 nmol/l of 0.30 mmol/l x mg DNA x h and PTU had no effect on iodothyronine stimulated glucose uptake. We conclude that 3,5-T2 is a significant intracellular stimulator of oxygen consumption, whereas T3 and T4 stimulate glucose uptake.

Adult↗
PubMed1991

Decreased thyroid hormone-stimulated oxygen consumption and glucose uptake in mononuclear blood cells from patients with autosomal dominant osteopetrosis type I.

Nine patients, from four different families, with autosomal dominant osteopetrosis were investigated. They all had roentgenological type I disease, characterized by universal, symmetrical osteosclerosis and enlarged thickness of the cranial vault. All patients appeared clinically euthyroid. Thyroxine (T4) and tri-iodothyronine (T3) induced oxygen consumption and glucose uptake were studied in vitro in mononuclear blood cells from patients and control persons. Unstimulated oxygen consumption from patients and controls did not differ, and no difference in unstimulated glucose uptake was observed. The increase in T4 and T3 stimulated oxygen consumption was significantly lower in cells from patients with osteopetrosis (T4: 0.007 +/- 0.004 mumol/mg DNA per h, T3: 0.011 +/- 0.004 mumol/mg DNA per h) compared with controls (T4: 0.017 +/- 0.003 mumol/mg DNA per h, T3: 0.023 +/- -0.013 mumol/mg DNA per h; p less than 0.05, p less than 0.05). Cellular glucose uptake after T4 and T3 stimulation was significantly lower in patients (T4: 0.032 +/- 0.017 mmol/l per mg DNA per h, T3: 0.02 +/- 0.017 mmol/l per mg DNA per h) compared with controls (T4: 0.09 +/- 0.017 mmol/l per mg DNA per h, T3: 0.08 +/- 0.01 mmol/l per mg DNA per h; p less than 0.05, p less than 0.01). The reduced oxygen consumption and glucose uptake indicate thyroid hormone resistance which may be of pathogenetic importance for the development of autosomal dominant osteopetrosis type I.

Adult↗
PubMed1991

Triiodothyronine (T3)-associated upregulation and downregulation of nuclear T3 binding in the human fibroblast cell (MRC-5)--stimulation of malic enzyme, glucose-6-phosphate-dehydrogenase, and 6-phosphogluconate-dehydrogenase by insulin, but not by T3.

The specific nuclear binding of triiodothyronine (T3) (NBT3) and the activity of malic enzyme (ME), glucose-6-phosphate-dehydrogenase (G6PD), and 6-phosphogluconate-dehydrogenase (6PGD) were studied in the human fibroblast cell (MRC-5). The overall apparent binding affinity (Ka) was 2.7 x 10(9) L.mol-1 estimated from kinetic studies of nuclear T3 binding, and 2.5 x 10(9) L.mol-1 estimated from equilibrium studies. The scatchard plots were curvilinear and composed of a high-affinity binding site with Ka1 3.4 +/- 0.7 x 10(9) L.mol-1 and maximal binding capacity (MBC) MBC1 57.0 +/- 11.9 fmol/mg DNA and a low-affinity binding site with Ka2 2.9 +/- 1.1 x 10(8) L.mol-1 and MBC2 124.7 +/- 22.1 fmol/mg DNA (n = 6). Incubation of cells with 6 nmol/L T3 for 20 hours reduced NBT3 to 62.2% +/- 15.7% (P less than .01, n = 11). The Ka estimated from kinetic studies was reduced to 6.7 x 10(7) L.mol-1, and the scatchard plots were linear, with Ka 4.5 +/- 1.6 x 10(8) L.mol-1 and MBC 137.0 +/- 44.6 fmol/mg DNA (n = 3) of the same magnitude as the low-affinity binding site in cells incubated without T3 (NS). The reduction in NBT3 was reversible and maximal at T3 concentrations saturating the high-affinity binding site and more than 58% of the total nuclear binding sites. The MRC-5 cell cytosol contained ME, G6PD, and 6PGD activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Line↗
PubMed1991

Increased nuclear tri-iodothyronine binding and thyroid hormone-stimulated glucose consumption in mononuclear blood cells from patients with liver cirrhosis.

Nuclear tri-iodothyronine (T3) maximal binding capacity (MBC) and thyroxine- and T3-stimulated cellular oxygen consumption and glucose consumption were examined in mononuclear blood cells from six patients with liver cirrhosis (LC), in six patients with alcoholic hepatitis (AH), and in six healthy control subjects. Serum T3 was decreased in patients with LC. The MBC of T3 was increased significantly (P less than 0.05) in cells from patients with LC compared with patients with AH and controls, whereas the equilibrium association constants did not differ. Unstimulated glucose consumption was slightly increased (P less than 0.05) in cells from patients with AH and LC compared with controls. Thyroid hormone-stimulated glucose consumption was significantly (P less than 0.05) increased in cells from patients with LC compared with controls and patients with AH. Unstimulated oxygen consumption did not differ between the groups, but thyroid hormone-stimulated oxygen consumption was depressed in cells from patients with AC (P less than 0.05) compared with patients with LC and with controls. We conclude that both thyroid hormone-stimulated glucose consumption and T3 nuclear receptor binding in cells from patients with LC are increased, and suggest that the observed changes are responsible for maintenance of euthyroidism in the face of reduced circulating T3.

Adult↗
PubMed1991

Modulation of nuclear T3 binding by T3 in a human hepatocyte cell-line (Chang-liver) - T3 stimulation of cell growth but not of malic enzyme, glucose-6-phosphatdehydrogenase or 6-phosphogluconate-dehydrogenase.

UNLABELLED: The T3 modulation of nuclear T3 binding (NBT3), the T3 effect on cell growth, and the T3 and insulin effects on malic enzyme (ME), glucose-6-phosphat-dehydrogenase (G6PD) and 6-phosphogluconat-dehydrogenase (G6PD) were studied in a human hepatocyte cell-line (Chang-liver). T3 was bound to a high affinity site with (mean +/- SD, n = 7) Ka1 3.0 +/- 0.3 * 10(9) M-1 and maximal binding capacity (MBC1 112.1 +/- 20.7 fmol/mg DNA, and to a low affinity site with (median, (range), n = 7) Ka2 1.4 (0.6 - 2.6) * 10(7) M-1 and MBC2 766 (461-2687) fmol/mg DNA. Incubation of cells with T3 6 nmol/l for 20 hours reduced the area under the T3 binding curves (AUC) to 80.9% +/- 10.0% of AUC in cells incubated without T3 (p < 0.01, n = 7). The downregulation, being reversible and associated with receptor saturation, was caused by a reduction in MBC1 of the high affinity site to 66.6 fmol/mg DNA, whereas Ka1 was unchanged. T3 stimulated cell growth (p < 0.05, n = 8), but had no effect on the activities of ME, G6PD, and 6PGD. Insulin (1 mumol/l) enhanced the activities of ME (p < 0.01, n = 6) and 6PGD (p < 0.05, n = 6). IN CONCLUSION: The cellular effects of T3 in the human hepatocyte cell-line was: 1) a reversible modulation of NBT3 associated to receptor saturation; 2) stimulation of cell growth; 3) contrary to the findings in rat hepatocytes no stimulation of ME, G6PD or 6PGD. Insulin enhanced ME and 6PGD.

Cell Division↗
PubMed1990

[The peripheral effect of thyroid hormones].

Human metabolism depends on not only extracellular processes: TSH production and secretion and thyroid gland secretion of hormones but also intracellular processes: active membrane transport of hormone, specific receptor-binding of hormone and the post-receptor effect. All these processes participate in maintaining a normal thyroid state in normal conditions and in disease. Only serum hormone concentration is routinely examined and it is therefore important to observe patients in which a discrepancy between the clinical condition and serum hormone measurements is evident as treatment with antithyroid drugs or hormone substitution may be irrational.

Antithyroid Agents↗
PubMed1990

Effect of selective blockade of oxygen consumption, glucose transport, and Ca2+ influx on thyroxine action in human mononuclear cells.

The effect of selective blockade of cellular glucose transporters, Ca2+ influx, and mitochondrial oxygen consumption on thyroxine (T4)-stimulated oxygen consumption and glucose uptake was examined in human mononuclear blood cells. Blockade of glucose transporters by cytochalasin B (1 x 10(-5) mol/L) and of Ca2+ influx by alprenolol (1 x 10(-5) mol/L) and verapamil (4 x 10(-4) mol/L) inhibited T4-activated glucose uptaken and reduced T4-stimulated oxygen consumption by 20%. Uncoupling of mitochondrial oxygen consumption by azide (1 x 10(-3) mol/L) inhibited T4-stimulated oxygen consumption, but had no effect on glucose uptake. We conclude that T4-stimulated glucose uptake in human mononuclear blood cells is dependent on intact glucose transporters and Ca2+ influx, but not on mitochondrial oxygen consumption. However, oxygen consumption is, in part, dependent on intact glucose uptake.

Adult↗
PubMed1990

Effect of thyroxine on cellular oxygen-consumption and glucose uptake: evidence of an effect of total T4 and not "free T4".

Recent studies of cellular T4 and T3 uptake have indicated active transport of the hormones into the cell rather than passive diffusion of the non-protein bound fraction. In order to study the significance of the extracellular environment, oxygen consumption and glucose uptake were examined in human mononuclear blood cells. Cells were incubated in protein free medium and in human serum totally depleted of thyroid hormones by resin treatment and fixed amounts of T4 (total T4 = 0-50-100-5000 nmol/l; free T4 = 0-5-11-5600 pmol/l) were added. Thyroxine stimulated glucose uptake and oxygen-consumption in a dose dependent manner but the T4 stimulation was dependent on the total concentration of T4 and did not differ between serum incubation or non-protein containing medium. Addition of ANS (100 mg/l) which inhibits binding of T4 to TBG, did not increase T4 effect in serum. Inhibition of the NaK-ATPase by addition of ouabain (9-72 mg/l) did not inhibit T4 stimulation, thus indicating that the ouabain sensitive NaK-ATPase is not a major component of the processes which initiate the intracellular effects of T4. Therefore the stimulation of uptake of oxygen and glucose in human mononuclear blood cells seems to be dependent on the total concentration of T4 and not on the non-protein bound (free) fraction suggesting active membrane uptake of T4, as the limiting factor for intra-cellular hormone effect.

Anilino Naphthalenesulfonates↗