[Acute graft-versus-host disease following a single transfusion of erythrocytes]. / Akute Graft-versus-Host-Krankheit nach einer einzigen Erythrozytentransfusion.

A 50-year-old severely immunodeficient woman with malignant non-Hodgkin lymphoma died from graft-versus-host disease due to transfusion of a single unit of packed red cells. Three days after this transfusion a maculo-papular rash appeared, followed by generalized erythroderma refractory to therapy and eventually progressing into generalized ulcero-squamous dermatitis. This case, and a review of other similar cases published elsewhere, prompt the authors to recommend prophylactic irradiation of blood products prior to their administration to patients with cellular immunodeficiency, particularly in cases of acute leukaemia or malignant lymphoma where patients receive intensive radio- and/or chemotherapy regimens. To appreciate the degree of cellular immunodeficiency in such risk patients, simple criteria should be developed to assess the efficiency of the cellular immune system.

Effects of fluoride on thyroid hormone biosynthesis. Studies in a highly sensitive test system.

In view of the recommendation that fluoride supplements via drinking water or table salt prevent dental caries, we analyzed whether fluoride had antithyroid properties in a sensitive experimental model. Rats were given either 60 or 200 micrograms/ml fluoride in the drinking water. This raised the serum fluoride concentration from 0.165 to 0.246 in the first and to 0.576 micrograms/ml in the second instance. Although the higher fluoride dose was near the toxic range, no antithyroid effect was observed. Neither organification of iodine, nor any subsequent step of thyroid hormone biosynthesis (transformation of monoiodotyrosine to diiodotyrosine and then to thyroxine) were affected. Fluoride had no effect on thyroglobulin content of the thyroid gland or on the degree of iodination of thyroglobulin.

Fluorine and thyroid gland function: a review of the literature.

The increasing use of fluoride for prevention of dental caries poses the problem as to whether this halogen has antagonistic properties towards iodine, whereby it could hamper the success of iodine prophylaxis of endemic goitre. Review of the literature shows that some authors have found an inhibition by fluoride of various steps of thyroid hormone biosynthesis in animal experiments. By and large, the inhibition was only slight and it was elicited only with fluoride doses greatly in excess of those recommended for caries prevention. The inhibition was not consistently present and other authors could not confirm it in comparable experiments. There is no convincing evidence that fluoride produces true goitres with epithelial hyperplasia in experimental animals. There are some reports based on casual observations that fluoride is goitrogenic in man. On the other hand, several good studies with adequate exposed and control populations failed to detect any goitrogenic effect of fluoride in man. It is noteworthy in particular that fluoride does not potentiate the consequences of iodine deficiency in populations with a borderline or low iodine intake. Published data failed to support the view that fluoride, in doses recommended for caries prevention, adversely affects the thyroid.

Polyneuropathy in Waldenström's macroglobulinaemia: reduction of endoneurial IgM-deposits after treatment with chlorambucil and plasmapheresis.

A case of progressive polyneuropathy associated with Waldenström's macroglobulinaemia is reported. A monoclonal IgM-lambda gradient was detected in the serum and cerebro-spinal fluid. By electro-immunoblot analysis antibodies against myelin-associated glycoprotein were found in the serum and cerebro-spinal fluid. The motor and sensory conduction velocities of several peripheral nerves were markedly decreased, and examination of visual evoked potentials (VEPs) revealed pathological latencies. Sural nerve biopsies before and after treatment with chlorambucil and plasmapheresis showed nerve fibre loss and demyelination. In the pre-treatment biopsy, heavy accumulations of filamentous material were found which stained positively for IgM by immuno-cytochemistry. Such accumulations had disappeared in a biopsy performed after treatment. The morphological findings were correlated with an improvement of clinical and electro-physiological findings.

[Autonomy and heterogeneity of the follicle in euthyroid and hyperthyroid human nodular goiter: answer to old riddles?]. / Autonomie und Heterogenität der Follikel in der euthyreoten und hyperthyreoten menschlichen Knotenstruma: die Lösung alter Rätsel?

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.

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.