Thyroid and bone: macrophage-derived TSH-ß splice variant increases murine osteoblastogenesis.

It is now firmly established that TSH may influence the physiology and patho-physiology of bone by activating osteoblasts and inhibiting osteoclast activity resulting in relative osteoprotection. Whether this influence is directly exerted by pituitary-derived TSH in vivo is less certain, because we have previously reported that the suppression of pituitary TSH does not remove such protection. Here, we have characterized the functional relevance of a novel form of the TSH-ß subunit, designated TSH-ßv, known to be produced by murine bone marrow cells. We found that fresh bone marrow-derived macrophages (MØs) preferentially produced TSH-ßv and, when cocultured with CHO cells engineered to overexpress the full-length TSH receptor, were able to generate the production of intracellular cAMP; a phenomenon not seen in control CHO cells, such results confirmed the bioactivity of the TSH variant. Furthermore, cocultures of MØs and osteoblasts were shown to enhance osteoblastogenesis, and this phenomenon was markedly reduced by antibody to TSH-ß, suggesting direct interaction between MØs and osteoblasts as observed under the electron microscope. These data suggest a new paradigm of local modulation of bone biology by a MØ-derived TSH-like molecule and raise the question of the relative contribution of local vs pituitary-derived TSH in osteoprotection.

A CD40 Kozak sequence polymorphism and susceptibility to antibody-mediated autoimmune conditions: the role of CD40 tissue-specific expression.

Previously, we and others have demonstrated the association of a C/T single nucleotide polymorphism (SNP), in the Kozak sequence of CD40, with Graves' disease (GD). Here, using an expanded data set of patients, we confirm the association of the CD40 SNP with GD (n=210, P=0.002, odds ratio (OR)=1.8). Subset analysis of patients with persistently elevated thyroid peroxidase (TPO) and/or thyroglobulin (Tg) antibodies (Abs), (TPO/Tg Abs), after treatment (n=126), revealed a significantly stronger association of the SNP with disease (P=5.2 x 10(-5), OR=2.5) than in GD patients who were thyroid antibody-negative. However, the CD40 SNP was not associated with TPO/Tg Abs in healthy individuals. Next, we tested the CD40 SNP for association with Myasthenia Gravis (MG), which, like GD is an antibody-mediated autoimmune condition. Analysis of 81 MG patients found no association of the SNP with disease. Functional studies revealed significant expression of CD40 mRNA and protein in the thyroid (target tissue in GD) but not in skeletal muscle (target tissue in MG). Combined, our genetic and tissue expression data suggest that the CD40 Kozak SNP is specific for thyroid antibody production involved in the etiology of GD. Increased thyroidal expression of CD40 driven by the SNP may contribute to this disease specificity.

[Symptomatic surgery]. / Symptomatische Chirurgie.

We can distinguish between symptomatic and aetiological surgery. Symptomatic surgery includes operations, which remove the symptoms of a disease or at least palliate them albeit without removing their underlying pathology. On the other hand aetiological surgery means the curative removal of a pathology. It can be argued that any type of a surgery is symptomatic in nature, but that a part of the symptomatic surgery is curative as well. In addition to symptomatic and curative surgery, we also apply prophylactic surgery. Prophylactic surgery constitutes a controverse chapter. The question is whether an indication for prophylactic surgery does exist. One can argue, that it is difficult to improve the life of a well being patient by operating on him. On the other hand the question is whether it would not be more intelligent to improve the condition of a patient by removing the pathological aspects before symptoms appear. In addition, a pathological situation should not be allowed to progress to the stage where neither surgery nor conservative treatment offer sufficient benefit to patients.

[Mirizzi syndrome: preoperative diagnosis and therapeutic management]. / Mirizzi Syndrom: Präoperative Diagnostik und Therapeutisches Management.

The Mirizzi syndrome describes a benign obstruction of the common hepatic duct due to a stone impacted within the cystic duct or in the Hartman's pouch of the gall bladder. The obstruction is caused either by external compression (Type I) or due to arrosion of the common hepatic wall creating a cholecysto-biliary fistula (Type II-IV). In a period of 16 months we encountered this rare cause of obstructive jaundice four times. We discuss the importance of preoperative diagnosis and a safe surgical management. Ultrasonography together with the laboratory findings of obstructive jaundice may lead to the suspicion of a Mirizzi syndrome. Often the endoscopic retrograde cholangiography confirms the diagnosis. Some authors report the successful treatment of Mirizzi syndrome by laparoscopic surgery. Nevertheless, we propose the open procedure because of the presence of dense inflammatory adhesions at the junction between the gallbladder and the common hepatic duct. Biliary-enteric bypass is often required to establish a sufficient biliary drainage. We consider laparoscopic techniques to be too dangerous.

[Nephroblastoma-like kidney adenoma: case report of an extremely rare kidney tumor]. / Nephroblastomartiges Nierenadenom: Fallbericht über einen extrem seltenen Nierentumor.

The nephroblastoma-like adenoma of the kidney is an extremely rare tumor with similarities to the nephroblastoma (Wilm's tumor) of the adult. In the literature, different terms are applied to these lesions. We present the case of a 64-year-old woman who underwent a nephrectomy for suspicion of renal cell carcinoma. Histologically the tumor consisted of tubular and papillary formations of monomorphic tumor cells without mitoses or cell-atypias and showed no fibrous capsule. The differential diagnosis to the nephroblastoma of the adult was difficult. Immunohistochemically the tumor expressed the embryonic form of the neural cell adhesion molecule (N-CAM) interstitially and not in the epithelial tumor cell as seen in Wilm's tumor. For the biologic tumor-definition it is important to collect and follow these very rare cases.