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Biomedical subjects

K W Wenzel

Publications and source records attributed to K W Wenzel.

At least 55 records · Page 3Linked to original sources
PubMed1987

[Differences in the effectiveness of levothyroxine preparations].

Three proprietary preparations of L-thyroxine were tested for their bioequivalence in a cross-over trial. Comparing the two most commonly prescribed preparations, during administration of preparation B (Euthyrox) serum concentrations of basal thyrotropin (TSH) was significantly higher than with preparation A (L-Thyroxin Henning) in both subgroups and in the cross-over calculation, as well as after stimulation with thyrotropin-releasing hormone (TRH) in one of the subgroups. During administration of a third preparation, C (Levothyroxine, enos), serum concentrations of total thyroxine (T4) and free thyroxine (fT4) were significantly lower than with preparation A, while basal and TRH-stimulated TSH levels were in all measurements highly significantly higher. Although there was the tendency for preparation B to be inferior, a greater effectiveness of preparation A could not be statistically proven for all data. But a markedly reduced bio-availability or effectiveness was demonstrated with respect to preparation C.

Adult↗
PubMed1987

Glycogen phosphorylase isozyme pattern in rat liver and isolated non-parenchymal liver cells.

The isozyme distribution of glycogen phosphorylase (EC 2.4.1.1) was studied in adult rat liver and isolated non-parenchymal liver cells by means of immuno-titration. In adult rat liver, the L-type of glycogen phosphorylase was found to dominate, whereas the heterogeneous non-parenchymal liver cell population apparently contains all three glycogen phosphorylase isozymes.

Animals↗
PubMed1987

Binding and uptake of asialothyroglobulin by isolated rat hepatocytes.

Binding and uptake of asialothyroglobulin by freshly isolated rat hepatocytes were studied in dependence on temperature as well as on the concentrations of the ligand and of calcium ions. The endocytosis of native thyroglobulin occurred as a nonspecific process. The number of galactose-specific receptors on the hepatocyte surface was estimated to be 47,400 per cell. The cells exhibited only a single class of binding sites with an association constant for asialothyroglobulin of Kass = 0.18.10(8)M-1. The internalization of surface-bound asialothyroglobulin appeared to be a first-order process. The rate constant of internalization ki, was estimated to be 0.6.10(-3) s-1. The obtained data provide an explanation of the extreme half-life of asialothyroglobulin in the circulation.

Animals↗
PubMed1986

[Optimization of levothyroxine treatment. Dosage dependence on the existing parenchymal mass, age, body weight and fasting intake].

The requirement of levothyroxine (LT4) was estimated in 310 patients with various thyroid disorders. Criterion of adequate LT4 dosage was a negative TRH test after dose titration in increments of 25 micrograms/d. Dosing with concomitant food intake was tested first and, after 8-10 weeks, compared to drug intake on an empty stomach. Significant correlations to dose levels were detected. LT4 requirement was notably lower in nodular than in diffuse goitre (2.0 vs. 2.2 micrograms/kg X d), probably due to the greater mass of autonomous parenchyma in nodular goitre. This influence of parenchyma mass was demonstrated by the increased LT4 requirement in hypothyroid conditions without goitre (2.3 micrograms/kg X d) and in complete functional loss following thyroidectomy (2.9 micrograms/kg X d). LT4 demands were significantly lower in the elderly of all groups, especially in nodular goitre, obviously again due to increased autonomic hormone production. Drug intake on an empty stomach as compared to LT4 administration with concomitant food intake increased the LT4 absorption rate: switching to drug intake of similar doses on an empty stomach yielded negative TRH test results in 76% of patients and significantly reduced LT4 requirements in patients with goitre. For initiation of therapy, a dosage regimen designed according to age and body weight has proven its value. Individual adjustment of the LT4 dose by TRH testing, however, is indispensible in suppressive therapy.

Adolescent↗
PubMed1985

Purification and some properties of lysosomal alpha-glucosidase of rat liver.

Acid alpha-glucosidase was purified from the lysosomal/mitochondrial fraction of rat liver by acid precipitation, ammonium sulphate precipitation and affinity chromatography on Sephadex G 100, resulting in 17000-fold enrichment from that of the liver homogenate. The molecular weight of the enzyme was estimated to be 125000 from analytical gel filtration experiments. On SDS-polyacrylamide gel electrophoresis the purified enzyme showed only a single band having an apparent molecular weight of about 64000. Based on these results, it is concluded that lysosomal liver alpha-glucosidase consists of two subunits. The discontinuous system of SDS-polyacrylamide gel electrophoresis, however, revealed two closely migrating protein bands suggesting heterogeneity of the enzyme subunits.

Ammonium Sulfate↗
PubMed1984

Similar effects of thionamide drugs and perchlorate on thyroid-stimulating immunoglobulins in Graves' disease: evidence against an immunosuppressive action of thionamide drugs.

Previous studies have shown that serum titers of thyroid-specific antibodies such as thyroid-stimulating immunoglobulins (TSI), TSH-displacing antibodies (TDA), or microsomal antibodies (MAb) decrease in patients with Graves' disease during therapy with thionamide drugs (TD). In keeping with some in vitro results it was postulated that TD have an immunosuppressive action which may be partly responsible for the beneficial effects. To further elucidate this theory, we compared the changes in TSI during treatment with TD such as methimazole (MMI) and propylthiouracil (PTU) as well as with perchlorate (PC), an unrelated compound with a different mode of therapeutic action. Of 69 patients with hyperthyroidism due to Graves' disease, serum from 62 (90%) was positive for TSI, as measured by cAMP accumulation in a thyroid tissue culture assay. Six patients had to be excluded due to noncompliance. Of the remaining 56 patients, those 41 subjects (73%) with good control of the disease were followed up to 24 months during dose-adjusted antithyroid treatment. All patients with an uncomplicated course of treatment had a decline in the initially increased TSI values on either drug regimen. Five of 10 patients receiving PTU and 8 of 13 patients receiving MMI reached normal TSI levels; so did 11 of 18 patients receiving PC. There was no individual correlation between TSI decrease and drug dosages or the serum T4 and T3 levels. In all 3 groups, however, a decrease in mean T4 and T3 levels preceded the fall in TSI. By grouping the patients according to whether they had more than a 20% decrease in the initial TSI values after either 2 months or more than 4 months of treatment, it could be shown that the late responders had significantly higher T4 and T3 levels after 2 months of treatment. The similar patterns of change in TSI during treatment with TD and PC are strong evidence against an immunosuppressive effect of TD. If any direct interference occurs, a toxic effect on intrathyroidal lymphocytes by intrathyroidal drug accumulation could be the cause of the disappearance of TSI with both drug types. On the other hand, the data provide indirect evidence for the theory that the restoration of the euthyroid state is the cause of decreasing TSI levels and normalization of the immune regulation in many patients during treatment with antithyroid drugs.

Adult↗
PubMed1983

Long-term follow-up using serial serum thyroglobulin determinations in patients with differentiated thyroid carcinoma.

Although thyroglobulin is generally recognized as a useful marker for metastases in cases of differentiated thyroid carcinoma, there have been few reports of the use of thyroglobulin determination for long-term follow-up. This report presents the results of long-term follow-up studies carried out for periods of up to 4 years in 18 patients, including 4 patients with local and 14 with distant metastases. After successful treatment, thyroglobulin fell to unmeasurable levels in the four patients with local metastases and in four of six patients with distant metastases. In some patients treated successfully with 131I, the thyroglobulin level remained elevated for several months before falling to within the normal range. Thyroglobulin levels correlated with tumor growth in six of eight patients with tumor progression, remained high with a slight downward trend in one patient, and declined to unmeasurable levels in another case. Only one patient in this group showed radioiodine uptake in the metastases at the end of the observation period. The lack of 131I uptake in the other patients probably reflects the low degree of differentiation of the metastases. The following conclusions regarding the use of thyroglobulin measurement for the long-term follow-up of thyroid carcinoma can be made: (1) Following 131I therapy for metastatic thyroid carcinoma, return of thyroglobulin levels to within the normal range may take several months. The trend observed in serial thyroglobulin determinations is more meaningful than the absolute values for evaluating the success of therapy. (2) Thyroglobulin levels correlate with tumor growth in most cases of tumor progression, even when changes in differentiation may have led to a loss of radioiodine uptake by the metastases. It may be concluded that serial thyroglobulin determinations are therefore useful for the detection of metastases that do not accumulate radioiodine.

Carcinoma↗
PubMed1983

Syndrome of persisting thyroid stimulating immunoglobulins and growth promotion of goiter combined with low thyroxine and high triiodothyronine serum levels in drug treated Graves' disease.

Among 48 Graves' patients treated with antithyroid drugs there were 8 patients with a further growth of an already enlarged goiter and a persistence of thyroid stimulating immunoglobulins (TSI). TSI activity did not persist in a comparison group of patients with less severe initial symptoms and an uncomplicated course during a similar regimen of drug treatment. Thyrotoxicosis was difficult to control in this subgroup of patients as low serum T4 was accompanied by borderline high T3 levels although TSH in serum remained undetectable. In spite of comparable low doses of antithyroid drugs serum T4 in the complicated group remained significantly lower (58 +/= 15 nmol/I SD vs. 97 +/- 19 nmol/I SD, p less than 0,001) and serum T3 stayed significantly higher (3,66 +/- 0,49 nmol/I SD vs. 2,15 +/- 0,50 nmol/I SD, p less than 0,001) than in the group with uncomplicated treatment. It is discussed that the promotion of goiter growth could be due to growth stimulating antibodies, and that a local intrathyroidal iodide depletion during antithyroid drug treatment might cause the shift from T4 to T3 production in this entity of Graves' patients.

Adult↗
PubMed1983

HLA-DR3 and HLA-DR5 associated thyrotoxicosis--two different types of toxic diffuse goiter.

One hundred fifty patients with toxic and scintigraphically diffuse goiter were HLA typed (A, B, C, DR). One group consisted of 101 patients with concomitant Graves' ophthalmopathy and/or TSH-binding inhibiting antibodies (TBIAb). Forty nine patients had neither ophthalmopathy nor TBIAb. The former group showed a higher prevalence of HLA-B8 and DR3 compared to a normal control group. The latter group showed a higher frequency of HLA-DR5, whereas the HLA-B8 and DR3 antigens were slightly below normal prevalence. These data indicate an immunogenetic heterogeneity in patients with toxic diffuse goiter. A group of 47 hyperthyroid patients with single autonomous thyroid adenoma had no increased prevalence of any HLA-antigens. Patients with long term remission did not show an altered prevalence of any of the HLA antigens compared to controls. In contrast, patients with Graves' ophthalmopathy and/or TBIAb activity who relapsed had a significantly higher prevalence of HLA-B8 DR3, whereas patients without TBIAb and eye signs who relapsed had a significantly higher prevalence of HLA-DR5 than the control group.

Graves Disease↗
PubMed1982

Lack of influence of the antidopaminergic drug domperidone on basal and TRH-stimulated TSH-serum levels after oral administration.

Since antidopaminergic drugs are known to elevate basal and TRH-stimulated TSH-serum levels and since this effect was also shown after iv administration of the novel dopamine antagonistic agent domperidone, it was investigated, whether this antiemetic drug could interfere after oral intake with the evaluation of thyroid function. Oral domperidone caused a marked TSH-enhancement of TRH-induced TSH increments in 6 out of 14 euthyroid subjects, with no statistical significance, however. The difference between oral and parenteral influence as well as inter-individual changes are probably due to the varying first pass effect of the drug after oral absorption.

Administration, Oral↗
PubMed1981

[Misdiagnoses and mismanagement in thyroid diseases (author's transl)].

Measures prior to diagnosis and treatment already installed were assessed retrospectively in 8501 patients with suspect thyroid disease between the years 1976 and 1979. In 10.5% of these patients there were 11.2% misdiagnosis or wrong treatment. The most common misdiagnoses were hyperthyroidism in euthyroid patients (1.9%), hypothyroidism in euthyroidism (0.8%), non-recognition or non-aspiration of cold nodules (0.9%), missing a goitre (0.6%). Among diagnostic methods the radio-iodine test was reason for a wrong diagnosis most commonly (66%). The TRH-test proved to be least erroneous, technical reasons being the cause of the 9.6% of misdiagnoses. The most common mismanagements were due to lack of prophylaxis of recurrence after goitre operation (1.5%), external irradiation of the thyroid gland with radium or Roentgen rays (0.7%), and during thyroid hormone treatment of goitre (1.3%). Iatrogenic disease existed mainly as factitious hyperthyroidism (0.7%), non-treated hypothyroidism after treatment with radio-iodine of hyperthyroidism (0.1%), and as goitre recurrence due to lack of prophylaxis of recurrence (0.8% of all patients). As every 10th patient was subjected to misdiagnosis or mismanagement, shifting to endocrinological advisory centers may prevent future mismanagement of thyroid disorders.

Berlin↗
PubMed1981

Pharmacological interference with in vitro tests of thyroid function.

Numerous drugs may cause changes in the serum concentrations of T4 and of T3. If such alterations are not recognized an incorrect diagnosis may result. In moderate degrees of hypo- and hyperthyroidism thyroid hormone levels may be spuriously normal, or the influence of pharmacological substances may lead to false diagnosis of thyroid disease in euthyroid patients. Since prediction of such alterations remains uncertain, it may be necessary to perform additional investigations when a potential artefact is recognized. On the other hand many pharmacological agents, especially those which interact with neurotransmitters, may influence TSH secretion, too. The TRH-test may show an increase or decreased TSH response, although complete suppression is only rarely seen during high-dose glucocorticoid treatment when low TRH doses are applied. Because of TRH-test gives such wide separation between different clinical states false interpretations are generally less likely than with drug-induced changes in T4 and T3 values.

Alpha-Globulins↗