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Biomedical subjects

H Gerber

Publications and source records attributed to H Gerber.

At least 181 records · Page 10Linked to original sources

[Surgical treatment of hyperthyroid struma: surgery results, postoperative long-term course and study of a factor connected with recurrences].

None of the 335 patients thyroidectomized for hyperthyroidism in our department of surgery between 1972 and 1982 died as a consequence of the operation. Reassessment of 226 of these patients by questionnaire 68 +/- 25 (SD) months after thyroidectomy revealed the following complications: postoperative paresis of the recurrent nerve (9%), persistent change of voice (2%), and persistent hypoparathyroidism (3.5%). 91 patients underwent a follow-up investigation 74 +/- 33 months after thyroidectomy. Only one had recurrent hyperthyroidism but 6 had a recurrence of the goiter. Patients with recurrent goiters had a significantly higher frequency of increased serum thyroglobulin levels than patients without goiters. These results emphasize the effectiveness of surgical therapy in hyperthyroidism, and suggest that serum thyroglobulin might be a useful predictor for goiter recurrence.

Adult↗

Treatment of active rheumatoid arthritis with slow intravenous injections of thymopentin. A double-blind placebo-controlled randomised study.

41 patients with active rheumatoid arthritis entered a placebo-controlled double-blind randomised study in which 21 received slow intravenous injections (given in fractions over 10 min) of thymopentin (TP-5) 50 mg 3 times a week for 3 consecutive weeks and 20 received placebo in the same way. After 3 weeks of treatment the TP-5 group showed improvement (p less than 0.05 or p less than 0.01) in all but one of the clinical variables tested. There was improvement in the number of joints painful at rest, the number of joints painful on motion, scores for tenderness on pressure and swollen joints, severity of pain on awakening and morning stiffness, and right-hand grip strength; left-hand grip strength remained unchanged. In the placebo group, only morning stiffness improved significantly. The intergroup comparisons showed that thymopentin was significantly better than placebo in reducing tenderness, joint swelling, severity of pain on awakening, and disease activity. 4 weeks after the end of the TP-5 therapy, the improvement was still present although there was a trend towards relapses. No significant modifications occurred in any of the laboratory variables tested and only minor side-effects were experienced by either group.

Adult↗

Confirmative study of the effectiveness of thymopentin in active rheumatoid arthritis.

Forty-one patients with active rheumatoid arthritis entered a controlled double-blind randomized study. Of these patients, 21 received prolonged intravenous injections (10 min) of thymopentin 50 mg three times a week for 3 consecutive weeks, whereas 20 received placebo. Both groups were comparable with regard to clinical parameters. No immunological tests were performed. Analysis of the results after 3 weeks showed that the improvement in the thymopentin group was statistically significant (p less than 0.05 or p less than 0.01) for all clinical parameters, except for the left-hand grip strength. On the other hand, no significant improvement was observed for any parameter, except morning stiffness, in the patients on placebo. The intergroup comparison showed statistically significant differences, favoring thymopentin over placebo treatment, in the Ritchie index, the scores of swollen joints, the assessment of severity of pain, and the scores for changes in the activity of the disease. The present placebo-controlled double blind study thus confirms the positive results generated in a similar open study, i.e., the beneficial therapeutic effect of prolonged intravenous injections of thymopentin in patients with severe rheumatoid arthritis. The drug appears to be safe at the dose regimen used.

Adjuvants, Immunologic↗

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↗

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↗

Equine leucocyte antigens in sarcoid-affected horses.

The distribution of equine leucocyte antigens (ELA) in horses affected by equine sarcoid tumours was determined and compared with unaffected controls. ELA-haplotype W3,B1 occurred more frequently in affected riding horses of Irish, Swiss and French background. The combined data for the three breeds resulted in a chi 2 value of 20.35 (P less than 0.0005 after correction). Simultaneously, ELA-specificity W11 was more frequently found in horses of Irish background, while W5 was found in Swiss and French horses with sarcoids. The combined data for haplotype W3,B1 and/or W5 specificity demonstrated, in the genetically closely-related Swiss and French horses, a highly significant difference in the occurrence of these haplotypes between affected horses and healthy controls (chi 2 = 28.69, P less than 0.00001 after correction). Thus, the results strongly suggest that the predisposition of horses to sarcoid is associated with or linked to the major histocompatibility complex.

Animals↗

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↗

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↗

[Postoperative wound infection in the horse].

A systemic investigation of wound infection in the horse after operative treatment of large wounds reveals that the age of the wound is of critical importance. The limit for an uncomplicated healing process lies around four hours. The duration of the operation itself is of little significance, the location of the lesion on the body of the horse, however, plays a major role. The pattern of isolated bacterial organisms is discussed in relation to the duration of hospital treatment. It is concluded that a systemic antibiotic therapy is of no value and that a local antibiotic therapy is only indicated in rare instances. Such a treatment undoubtedly favours the resistance of bacteria against various chemotherapeuticals, which unfavourably influences wound healing.

Animals↗

[Diagnostic significance of blood thyroglobulin determination].

Thyroglobulin (Tg) is a protein which is synthesized in the thyroid. In healthy individuals only minute amounts of Tg can be found in the serum. In patients with thyroid disorders serum Tg levels are usually elevated, but the extent of this increase gives no indication of the nature of the underlying disease. Measurement of serum Tg is an established method in screening for thyroid disorders and in follow-up of patients with differentiated carcinomas of the thyroid. It seems likely that serum Tg determinations will also prove useful for other purposes (e.g. as an aid in deciding whether to treat a simple goiter by thyroid hormone administration or surgery).

Adult↗

Interim results on the clinical effects of i.v. administered thymopentin in active rheumatoid arthritis.

Forty-one patients with active rheumatoid arthritis entered a controlled, double-blind, randomized study; 21 received prolonged i.v. injections (10 min) of thymopentin 50 mg 3 times a week for 3 consecutive weeks; the other 20 received placebo under the same conditions. The groups were comparable at the start of the study. Statistical tests of changes within the treatment groups after 3 weeks showed that the improvement achieved in the thymopentin group was significant (p less than 0.05 or p less than 0.01) for each clinical parameter, except for left-hand grip strength. On the other hand, no significant improvement was observed for any parameter except morning stiffness in the patients on placebo. The intergroup comparison showed significant differences, favouring thymopentin over placebo treatment, in the Ritchie index, scores for swollen joints, assessment of severity of pain and scores for changes in the activity of the disease. Only minor side-effects were experienced in the two treatment groups. The present placebo-controlled double-blind study confirms the previous positive results achieved in open studies, i.e., the beneficial therapeutic effect of prolonged i.v. injections of thymopentin in patients with severe rheumatoid arthritis observed after 3 weeks of therapy. The drug appears to be safe at the dose regimen used.

Arthritis, Rheumatoid↗

[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↗