Results of preoperative ultrasound guided fine needle aspiration biopsy of solitary thyroid nodules as compared with the histology. A retrospective analysis of 538 patients.

AIM: The goal of this study was to assess the accuracy and limitations of ultrasound guided fine-needle aspiration biopsy (ug-FNAB) of solitary thyroid nodules. METHODS: The ug-FNAB results of 538 patients with solitary thyroid nodules, who afterwards underwent thyroid surgery, were compared retrospectively with the histology. Patients with multinodular goiter were excluded from the study. Ug-FNAB was performed on growing and/or hypoechoic and/or hypofunctional nodules. The ug-FNAB results were grouped as follows: group 1: malignant (n = 44); group 2: malignancy cannot be ruled out (n = 173); group 3: non-malignant (n = 296), group 4: inadequate (n = 25). RESULTS: When the cytological results of group 1 and group 2 were interpreted as being malignant and those of group 3 as being benign, sensitivity, specificity and accuracy of ug-FNAB were 96.7%, 65.8% and 69.5% respectively. The 62 thyroid carcinomas (TC) biopsied presented in 59 cases a suspicious or malignant cytology (95.2%). The smallest TC diagnosed by ug-FNAB had a diameter of 0.5 cm and 36.4% of all papillary TC < or = 1 cm displayed stage pT4. The histology verified a TC in 18 cases out of the 173 ug-FNABs in group 2. Non-malignant ug-FNABs were confirmed by histology in 294 patients (99.3%) in group 3. In 4.65% of the ug-FNABs inadequate material was aspirated. CONCLUSION: Nodules with non-suspicious ug-FNAB results can be safely followed-up by sonography, as the cytological diagnoses were verified in more than 99% by histology. Papillary TC can be diagnosed with ug-FNAB very accurately. As stage pT4 was present in more than one third of patients with papillary TC < or = 1 cm, ug-FNAB is also recommended for thyroid nodules 0.5-1 cm in diameter located adjacent to the thyroid capsule. However, microfollicular proliferations remain the limitation of ug-FNAB, as the cytology cannot distinguish between benign adenoma and follicular TC.

A new type of bradykinin B2 receptor antagonists: bradykinin analogs with N-alkyl amino acids at position 2.

It is commonly assumed that bradykinin B2 receptor antagonists bind to a receptor site partially different from that for agonists. Thus, it is likely that there exists more than one key modification to convert bradykinin receptor agonists into antagonists. In this respect, [L-NMePhe2]-BK represents the basic structure of a new type of bradykinin B2 receptor antagonists without any replacement at position 7. This compound inhibits both in vitro bradykinin-induced contraction of the guinea pig lung strip and in vivo bradykinin-induced bronchoconstriction. Furthermore, this analog shows analgesic activity, blocks in a dose-dependent manner the bradykinin-induced Ca2+ release from macrophages and inhibits at a concentration of 10(-13) M the bradykinin-induced cytokine release from mononuclear cells. Combinations with structural modifications previously performed for other B2 receptor antagonists rather reduce than enhance the potency.

Release of cytokines from isolated lung strips by bradykinin.

Bradykinin as an inflammatory mediator was assayed for its ability to release cytokines from isolated lung tissue derived from guinea pigs, mice and in some cases from patients. Bradykinin elicited in concentrations, which were able to induce a contraction of isolated lung strips, a secretion of different cytokines from the tissue into organ baths as well as from lung tissue incubated in petri dishes (4h, 37 degrees C). Using enzyme immuno assays and the tanned erythrocyte electrophoretic mobility (TEEM)-test in combination with monoclonal antibodies the cytokines could be identified preferably as interleukin(IL)-1, IL-2, sIL-2R and IL-6. Tyrode solution as a control and carbachol in a concentration causing also a contraction were not able to release cytokines in a significant amount. The bradykinin B2 receptor antagonist icatebant (HOE 140) inhibited the bradykinin-induced IL-2 and IL-6 release. The results show that bradykinin can elicit the secretion of the cytokine cascade via a receptor-mediated process.

Influence of serotonin on lymphokine secretion in vitro.

It was found that serotonin can induce the secretion of a chemotactic activity for polymorphonuclear granulocytes and the secretion of charge-changing in in lymphocyte cultures derived from guinea pigs and mice. The serotonin antagonists methysergide, pizotiphen, cyproheptadine and ketanserin inhibited the secretion of the serotonin-elicited factors, whereas the histamine-type 2 antagonist metiamide had no inhibitory effect. Moreover, the production of Concanavalin A-induced lymphokines (migration inhibition factor for macrophages, chemotactic factor for polymorphonuclear granulocytes and for thymocytes, charge-changing lymphokines) was suppressed in the presence of serotonin in the lymphocyte cultures. The fractionation of the supernatants derived from the serotonin-stimulated lymphocytes revealed that serotonin produced an activity with a molecular weight of 40 kDa in the presence of which the Con A-elicited response was completely inhibited. These findings support the regulatory role of serotonin with respect to immune reactions.