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Biomedical subjects

H Studer

Publications and source records attributed to H Studer.

At least 73 records · Page 4Linked to original sources
PubMed1985

Iodine content and density of thyroglobulin investigated by isopycnic centrifugation.

The density of in vitro iodinated thyroglobulin (Tgb) molecules, measured by isopycnic centrifugation, increases linearly with their iodine content. In contrast, the iodine to density (I:D) regression for differently iodinated native rat Tgbs is not constant but varies, depending on experimental conditions: For LID-fed rats the slope of the individual I:D regression line of each Tgb decreases linearly with the decreasing mean degree of iodination of the sample (r = 0.9104, P less than 0.01). On the other hand, in Tgb samples synthesized by propylthiouracil-blocked glands, the I:D regression is no longer linear. Rather, a bimodal pattern is obtained revealing a preexisting highly iodinated Tgb pool together with newly synthesized, non-iodinated protein. The results indicate: (a) the mean degree of iodination of a native Tgb cannot be estimated accurately if only its mean density is known, and (b) the degree of heterogeneity of iodination is identical for any in vivo produced Tgb sample with the same iodine content.

Animals↗
PubMed1985

Toxic nodular goitre.

Toxic nodular goitre is the late result of a slow growth process generating new daughter follicles from the mother follicles of a normal thyroid gland. Since the normal follicular shell is not built up by monoclonal epithelial cells, but rather by cells with widely variable functional equipment, daughter follicles generated by the preferential replication of particular mother follicular cells endowed with a high growth potential, may be different from mother follicles. For instance, the progeny of follicles may have a higher or lower iodine metabolism than their progenitor follicles. Some of the newly generated follicles have a high autonomous, i.e. TSH-independent, iodine turnover, while some others have a high autonomous growth potential. The degree of autonomous function is entirely independent of that of growth. In the process of goitrogenesis, newly generated follicles may, in addition, acquire new forms of expressing genetic functions. Such new traits, e.g. a particular growth pattern, may become inheritable and are then passed on from mother to daughter cells. The result is the most characteristic of all hallmarks of nodular goitres, which is the heterogeneity of structure and function between two diseased glands and even between closely adjacent follicles of the same gland. Greatly uneven intrinsic replication rates between different follicular cells and equally varying independency on growth stimuli account for regional differences in goitre growth. This, together with a network of fibrous scars interfering with unimpeded expansion of the growing follicle population, invariably produces a nodular growth pattern of the goitre. TSH certainly does not account for the growth of this type of goitre. Instead, a number of thyroid growth factors, including growth-stimulating immunoglobulins akin to those found in Graves' disease, have been discovered in recent years. Once the number of follicular cells with high intrinsic growth potential has become large enough under the impact of extrathyroidal growth stimuli, goitre growth may become autonomous and self-perpetuating. Whether or not a nodular goitre will produce thyrotoxicosis is a function of the number of follicles with high intrinsic iodine turnover which happen to be generated in the course of goitrogenesis. In contrast to thyrotoxicosis in Graves' disease, hyperthyroidism in nodular goitre is a very slowly progressing, insidiously evolving complication.

Autoradiography↗
PubMed1985

Pathogenesis of heterogeneity in human multinodular goiter. A study on growth and function of thyroid tissue transplanted onto nude mice.

Functional and morphologic heterogeneity of human multinodular goiters was investigated in 300 samples from "cold" and "hot" regions of 20 goiters transplanted onto nude mice. Transplants were labeled with [3H]thymidine and radioiodine, while the host's thyroid-stimulating hormone (TSH) secretion was either stimulated or suppressed. Proliferation and function of follicular cells were assessed in whole follicles reconstructed from autoradiographs of serial sections. Hot transplants had a higher autonomous iodine uptake than those of cold tissue in TSH-suppressed hosts. Functional autonomy widely varied among the follicles, but even more so among individual cells. Hot grafts differed from cold ones only by a comparatively larger fraction of autonomous cells. Intercellular differences of iodinating activity were not abolished by TSH. Grafts faithfully reproduced the individual growth pattern of the original tissue. Between 0.5% and 7% of all follicular cells replicated despite suppression of TSH. Up to 70% of these cells were clustered, forming scattered foci of autonomously growing tissue. Other cells only started replicating after long-term TSH stimulation. Thus, goiters contained subsets of cells with high and others with low growth response. Progenies of replicating cells remained clustered, sometimes budding outwards to form new follicles. Autonomy of growth and autonomy of function are independent traits of epithelial cells. Epithelial cells have their individual growth pattern, replication rate, and functional capacity. These traits are passed on from a mother cell to its progeny during follicle neogenesis. To this main mechanism accounting for the morphologic and functional heterogeneity of human goiters, inheritable modifications of gene expression must probably be added.

Animals↗
PubMed1985

Paradoxical effects of thyrotropin on diffusion of thyroglobulin in the colloid of rat thyroid follicles after long term thyroxine treatment.

Autoradiographs of human goiters demonstrate that the speed of diffusion of newly iodinated thyroglobulin (Tgb) molecules through the colloid space may vary widely from one follicle to another. Since the mechanisms which govern the mixing of the colloid are unknown, we investigated the effect of TSH on these processes in rat thyroid glands. Autoradiographs were prepared from thyroids of rats killed 1 h after 125I or 4 h after [3H]leucine injection. In animals treated with T4 for 2 days, 70% of all follicles showed ring labeling of the colloid periphery with both isotopes, indicating slow mixing of newly synthesized and newly iodinated Tgb molecules with preexisting ones. TSH markedly enhanced the mixing process, thereby diminishing the incidence of ring reactions to roughly 10% of all follicles. These results were expected. Unexpected however, was, the nearly total absence of rings in thyroids treated with T4 for 25 days. Semiquantitative autoradiography revealed a higher absolute number of both newly iodinated and newly synthesized Tgb molecules in the core of follicles in chronically suppressed compared to acutely suppressed thyroids. Moreover, after chronic T4 pretreatment, the effect of TSH on diffusion was the opposite of that observed in acutely T4-treated glands, since 0.5 IU TSH injected twice daily between days 21 and 25 caused the reappearance of 125I and [3H]leucine labeled rings in 44% and 33%, respectively, of all follicles. We conclude that acute TSH suppression slows intraluminal diffusion of thyroglobulin molecules and acute TSH injection accelerates the mixing process, whereas, in contrast, chronic TSH suppression improves and acute TSH action on chronically suppressed follicles impairs diffusion. Therefore, the impact of TSH-mediated processes on the hydrodynamic properties of colloid, and thereby on the intraluminal iodination and coupling process, is more complex than hitherto thought.

Animals↗
PubMed1984

[Sodium chloride intake and supply of iodine in the Swiss population].

The controversial salt intake in a representative sample of the Swiss adult population was evaluated by measuring the sodium excretion in the urine of 966 adult probands of different regions in Switzerland. Prior to this study the validity of a widely used and easy method for the analysis of sodium excretion in large scale studies was investigated by determination of the quotient of sodium excretion and creatininuria in a single urine sample and the calculation of the 24-h values. The results with this method were compared to those of determination of effective sodium content in the 24-h urine samples of 43 probands. Similar mean values were demonstrated for both methods. On the other hand, only 53.5% of the individual results were between +/- 30% of the effective values. It is therefore concluded that this method is useful only for large scale studies but not for individual evaluations of sodium excretion. The mean sodium excretion was 176.2 +/- 105.9 mmol/24 h for the 966 probands. This corresponds to a daily salt intake of 10.3 +/- 6.2 g. Determination of the effective sodium excretion in 24-h urine samples of 147 probands, which differed slightly from the whole collective with regard to age and sex distribution, confirmed these data with a mean sodium excretion of 143.2 +/- 62 mmol/24 h, corresponding to a daily salt intake of 8.4 +/- 3,6 g. Iodine excretion in the 24-h urine samples of 112 probands completed the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1984

[Place of nuclear medicine methods in thyroid diagnosis].

Since the introduction of precise and easily accessible methods of measuring the level of T4 and T3 in serum, the use of isotopes to assess thyroid function can no longer be advocated. Moreover, the recent growth in knowledge concerning the pathogenesis of thyroid diseases indicates that not even scintigraphic imaging of the thyroid gland contributes substantially to therapeutic decisions in routine situations such as Graves' disease and most euthyroid and hyperthyroid nodular goiters. The use of isotopes in clinical thyroidology should therefore be restricted to the fairly few cases where it is essential for diagnostic and therapeutic decisions, such as, for example, in planning 131I-therapy of postoperative goiter recurrences. A critical review of the indications is presented. Isotopes continue, however, to expand our knowledge of the pathogenesis of thyroid diseases in clinical research.

Diagnosis, Differential↗
PubMed1984

Malignant follicles of a differentiated thyroid carcinoma releasing iodinated thyroglobulin into the lymphatic vessels.

Serial sections across a follicular thyroid carcinoma taken from a 71-year-old woman with hyperthyroidism and grossly elevated serum thyroglobulin were examined by PAS staining and autoradiographic techniques. PAS positive material, presumably thyroglobulin, was found in the interstitial network between follicles. Some of this material was autoradiographically positive for 125I within 17 h after tracer application. Direct connections between the lumina of tumour follicles and the lymphatic vessels surrounding them were identified. These channels can explain the release of iodinated thyroglobulin by some differentiated carcinomas.

Adenocarcinoma↗
PubMed1984

Does amiodarone affect heart rate by inhibiting the intracellular generation of triiodothyronine from thyroxine?

The hypothesis that the antiarrhythmic drug amiodarone slows down the heart rate by its inhibitory action on the intracellular conversion of thyroxine (T4) to 3,5,3' triiodothyronine (T3) was investigated. For this purpose we compared the effect of amiodarone with that of another potent inhibitor of the T4----T3 conversion, i.e. the radiographic contrast medium iopanoic acid, on the heart rate of unanaesthetized guinea-pigs. Both amiodarone and, to an even greater extent, iopanoic acid induced an increase in serum 3.5',3' triiodothyronine (reverse T3), indicating effective inhibition of T4----T3 conversion. Both amiodarone and iopanoic acid were accumulated in the liver and in the heart (measured as iodine). While amiodarone induced bradycardia, iopanoic acid did not change the heart rate. Supraphysiological amounts of exogenous T3 reverted the amiodarone induced bradycardia to near normal values. A comparable effect was observed with isoprenaline. The intracellular inhibition of the T4----T3 conversion is not the ultimate mode of the action of the amiodarone effect on heart rate. It is thought that amiodarone interacts with T3 at its receptor or somewhere later along the pathway from the T3-receptor interaction to the final effect of T3 on heart rate.

Amiodarone↗
PubMed1983

[Autonomy and heterogeneity of the follicle in euthyroid and hyperthyroid human nodular goiter: answer to old riddles?].

The mechanisms responsible for the transformation of a morphologically and functionally normal thyroid into a heterogeneous eu- or hyperthyroid nodular goitre are summarized. The 3 basic processes of goitre pathogenesis are: 1. Each goitre develops from a normal thyroid gland by generation of new follicles. 2. New follicles are formed by multiplication of preferentially replicating cell clones of the follicular epithelium. Follicles already begin multiplying in response to a goitrogenic stimulus too weak to enhance metabolic functions other than replication. 3. The epithelial cells of normal follicles are not homogeneous and monoclonal, but belong to different populations with different metabolic equipment. Therefore, the daughter follicles may be metabolically different, e.g. in iodinating capacity. A certain degree of autonomous, i.e. TSH-dependent function is inborn to all follicles. The individual degree of autonomy of iodine turnover is not variable during goitrogenesis but determined by the metabolic individuality of the mother cell at the moment of folliculoneogenesis. These three basic processes explain the typical heterogeneity of nodular goitre. From autonomous highly iodinating cell families, autonomous "hot" daughter follicles arise which may be scattered all over the gland either as single follicles or as clusters of varying size (so-called "disseminated autonomy"). Particularly large clusters of "hot" follicles result in scintigraphically visible hot nodules, often called "toxic adenomas". Hyperthyroidism appears when the total joint autonomous hormone production of normal and "hot" follicles exceeds the requirements of the organism. The large majority of goitre nodules, including the so-called "toxic adenoma", are not true monoclonal benign neoplasias. Rather, they are built up by the same polyclonal heterogeneous follicles as extranodular goitre tissue. They have no choice but to expand in nodular fashion because they replicate within a poorly extensible network of connective tissue. This network of fibrous tissue results from scarring of multiple hemorrhagic necrosis occurring episodically during goitre growth.

Adult↗
PubMed1983

Serum concentrations of amiodarone during long term therapy. Relation to dose, efficacy and toxicity.

In 17 patients on long term therapy with amiodarone, serum drug levels measured by HPLC were related to pharmacological effects. At steady state, serum levels were directly proportional to the dose, 5 mg/kg per day leading to an average serum level of approximately 2.5 mumol/l. The non-amiodarone level of iodine averaged 4-times higher than the level of amiodarone iodine. The elimination half-life of amiodarone ranged from 21 to 78 days, and of non-amiodarone iodine from 24 to 160 days. Control of arrhythmias was satisfactory in all 12 evaluable patients, when the serum amiodarone level exceeded 1.5 mumol/l. Deterioration of vision and polyserositis occurred only at amiodarone levels above 4 mumol/l. Tentatively, a therapeutic range of 1.5 to 4 mumol/l is proposed. In contrast, thyroid dysfunction was observed at any amiodarone level. In view of the narrow therapeutic window, therapy with amiodarone may be optimized by monitoring its serum level and in addition, thyroid function should be regularly checked.

Adult↗
PubMed1983

A link between liver microsomal enzyme activity and thyroid hormone metabolism in man.

1 The effect of different combinations of liver microsomal enzyme inducing drugs on thyroidal hormone steady state concentrations was investigated. Three groups of healthy volunteers were given daily either antipyrine 1200 mg together with phenobarbitone 100 mg, antipyrine 1200 mg combined with rifampicin 600 mg or rifampicin 600 mg alone for a period of 14 days. 2 Before and after each treatment the total body clearance of antipyrine, gamma-glutamyl transferase (gamma-GT), 6 beta-OH-cortisol as in vivo parameters of liver microsomal enzyme activity were measured. In addition, thyroxine (T4), free thyroxine (FT4), T3 resin uptake, tri-iodothyronine (T3) reverse T3 (rT3) and TSH were estimated. 3 After rifampicin administration there was a 60% increase in antipyrine clearance while following combinations of antipyrine-phenobarbitone or antipyrine-rifampicin an 80% and 128% increase respectively occurred. 4 A marked decrease of T4, FT4 and rT3 was seen in all groups while T3 remained stable in all groups investigated. This effect may be partly due to an increase in extrathyroidal metabolism of T4 as found previously by a kinetic turnover study using 125I-T4. It also depends on the extent of the liver microsomal enzyme inducing capacity rather than on the nature of the drugs used. The striking disparity of liver enzyme induction of T4 and rT3 disposal on the one hand and T3 metabolism on the other is a unique phenomenon whose pathogenesis is not clear at the present time.

Adult↗
PubMed1983

Acute cerebrovascular accident after treatment with cis-platinum and methylprednisolone.

A 53-year-old woman with recurrent ovarian cancer sustained an intracerebral hemorrhage after the 4th course of a chemotherapy regimen which included cis-platinum (DDP). She received high-dose methylprednisolone as an antiemetic along with the DDP. No metastases or abnormal vascularity were found on histological examination of the right frontal lobe which had been removed surgically. Causes of cerebrovascular accidents during and following chemotherapy are discussed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1983

The site of leakage of intrafollicular thyroglobulin into the blood stream in simple human goiter.

Serum thyroglobulin is increased in many thyroid diseases, including simple goiter. We followed thyroglobulin levels in 19 patients with diffuse and nodular euthyroid goiters by serial measurements of 80 samples over 2 yr. The large intraindividual variations suggested episodic release of thyroglobulin in this thyroid disease. To test the hypothesis that the phenomenon was due to sporadic release of colloid from diseased follicles, we studied 98 multinodular goiters by conventional histological techniques. Sixty-four surgical samples were auto-radiographed. Focal necrosis of single follicles as well as large necrotic areas, involving multiple follicles together with interstitial stroma, were found in 42% of the goiter specimens. The earliest stage of necrosis was focal death of epithelial cells, often followed by hemorrhages. Through the epithelial gaps, colloid leaked out into the interstitial space. In later stages, granulation tissue containing numerous macrophages invaded damaged follicles. Fibrous scars remained as ultimate witness of repair processes. In one chance observation, acute release of highly labeled thyroglobulin from follicular lumina into the interfollicular interstitium was autoradiographically documented. We conclude that the varying concentrations of thyroglobulin in serum of patients with simple goiter may result from episodic necrosis of follicles, permitting leakage of colloid into the interfollicular space.

Epithelium↗
PubMed1983

Thyroglobulin-rich colloid goitres: a result of the combined action of lithium and methimazole on the rat thyroid.

Naturally occurring euthyroid goitres in man and goitres produced in experimental animals by iodine deficiency or goitrogen feeding both have in common a thyroglobulin of low iodine content. The latter experimental goitres are always depleted of colloid and thyroglobulin. In contrast, natural goitres often contain excessive amounts of colloid which may accumulate because of endocytosis becoming refractory to TSH. We tested the hypothesis that minute doses of goitrogens could lower the iodine content of thyroglobulin without colloid depletion. We then examined whether such a low-dose 'classical' goitrogen could induce excessive colloid storage rather than depletion if acting in concert with lithium, a cation which blocks endocytosis. Rats on an adequate iodine intake were fed minimal doses of methimazole either alone or combined with lithium chloride. Chronic minimal-dose methimazole treatment lowered the iodine content of thyroglobulin without changing thyroglobulin content and thyroid weight. In contrast, addition of lithium to methimazole, produced goitres containing supranormal amounts of poorly iodinated thyroglobulin. We conclude that borderline doses of goitrogens can lower iodination of thyroglobulin without causing hyperplasia and colloid depletion. Thyroglobulin-rich goitres can be obtained by adding a second goitrogen which inhibits endocytosis. As an alternative to Marine's hypothesis of colloid goitre formation we suggest that inhibition of endocytosis, e g by goitrogens of the lithium type, could cause colloid and thyroglobulin accumulation in human iodine deficiency goitre.

Animals↗