Neutrophils can promote clotting via FXI and impact clot structure via neutrophil extracellular traps in a distinctive manner in vitro.

Neutrophils and neutrophil extracellular traps (NETs) have been shown to be involved in coagulation. However, the interactions between neutrophils or NETs and fibrin(ogen) in clots, and the mechanisms behind these interactions are not yet fully understood. In this in vitro study, the role of neutrophils or NETs on clot structure, formation and dissolution was studied with a combination of confocal microscopy, turbidity and permeation experiments. Factor (F)XII, FXI and FVII-deficient plasmas were used to investigate which factors may be involved in the procoagulant effects. We found both neutrophils and NETs promote clotting in plasma without the addition of other coagulation triggers, but not in purified fibrinogen, indicating that other factors mediate the interaction. The procoagulant effects of neutrophils and NETs were also observed in FXII- and FVII-deficient plasma. In FXI-deficient plasma, only the procoagulant effects of NETs were observed, but not of neutrophils. NETs increased the density of clots, particularly in the vicinity of the NETs, while neutrophils-induced clots were less stable and more porous. In conclusion, NETs accelerate clotting and contribute to the formation of a denser, more lysis resistant clot architecture. Neutrophils, or their released mediators, may induce clotting in a different manner to NETs, mediated by FXI.

Single-Molecule FRET to Measure Conformational Dynamics of DNA Mismatch Repair Proteins.

Single-molecule FRET measurements have a unique sensitivity to protein conformational dynamics. The FRET signals can either be interpreted quantitatively to provide estimates of absolute distance in a molecule configuration or can be qualitatively interpreted as distinct states, from which quantitative kinetic schemes for conformational transitions can be deduced. Here we describe methods utilizing single-molecule FRET to reveal the conformational dynamics of the proteins responsible for DNA mismatch repair. Experimental details about the proteins, DNA substrates, fluorescent labeling, and data analysis are included. The complementarity of single molecule and ensemble kinetic methods is discussed as well.

Transanal treatment of strictured rectal anastomosis with a circular stapler device: simple and safe.

BACKGROUND: Several methods of treatment for benign anastomotic strictures after low anterior resection have been described. We report and illustrate a simple, safe, and effective method for treating benign rectal anastomotic strictures by means of a transanal circular stapling device. METHODS: Three patients with a clinically significant rectal stricture underwent transanal resection of the fibrous stenosis by a circular stapler device (CEEA stapler 29 or 31 mm calibre; Tyco Co., USA). RESULTS: No complications occurred. Patients were discharged from the hospital on the first postoperative day. After a follow-up period of 8, 12 and 14 months respectively, no recurrence of the stricture was observed. The stool habits of all 3 patients were normal with 1-3 formed, asymptomatic fecal passages per day. CONCLUSION: Transanal reanastomosis by means of a circular stapler device is a simple and effective method. However, a larger number of patients need to be treated with this relatively new method to draw further conclusions.

[Unifocal autonomy and carcinoma of the thyroid gland]. / Unifokale Autonomie und Karzinom der Schilddrüse.

Two cases operated upon with the clinical diagnosis of unifocal autonomous functioning thyroid nodules (AFTN) are reported where the histological diagnosis revealed a well differentiated thyroid carcinoma (follicular, papillary) without metastasis. The pathogenesis of differentiated thyroid carcinomas in cases of AFTN may be coincident. Alternatively it may evolve from thyroid epithelial cells of the hot nodule, resulting in a "hot" well differentiated thyroid carcinoma. These cases show that under the clinical diagnosis of AFTN a differentiated thyroid carcinoma can be hidden occasionally.

[A comparative study of cytological and histological studies of the thyroid gland]. / Vergleichende Untersuchung zytologischer und histologischer Befunde der Schilddrüse.

We compare the results of fine-needle aspiration cytology of the thyroid gland with postoperative histological findings in 533 patients with thyroidectomy operated on between 1987 and 1994. The classification of the cytological preparations followed the proposal of Weiss and Pilz [35] with the groups 0-IV. In group 0 the most frequent findings were cystic changes in multinodular goitre or malpuncture, respectively. The groups I and II contained cases with multinodular goitre, thyroiditis and follicular adenomas, but 4 carcinomas too. The group III comprised particularly follicular adenomas and carcinomas (8 cases). Both cases in group IV were carcinomas. In group III (cytologic group with suspicious findings) there were 65 cases with false positive results of the cytologic investigation resulting in a specificity of 86.4%. 4 out of 14 thyroid carcinomas could not be detected by cytologic preparations corresponding to a sensitivity of 71.4% for carcinomas. The false negative rate for thyroid carcinomas in group II was caused by regression areas in the center of the tumors (3 cases) as well as one microcarcinoma. Preoperative fine-needle aspiration cytology of the thyroid gland reduces the number of patients operated on for multinodular goitre or cold nodules especially in cases suspicious of carcinoma.

[Bromocriptine treatment of hyperprolactinemia]. / Bromocriptin-Behandlung bei Hyperprolaktinämie.

In 36 female patients with microprolactinoma was carried out a primary therapy and in 19 patients (10 males, 9 females) with a postoperatively persisting hyperprolactinaemia a secondary therapy with bromocriptine. In close correlation between the PRL-levels and the bromocriptine dose we achieved a normalisation of the hormone levels in the microprolactinomas. A normalisation of the cycle was observed in 80%, a persisting of the galactorrhoea in about 90% and a conception in nearly two thirds of the women. Also in those patients who underwent a secondary therapy in nearly 80% a decrease of the PRL-levels into the normal region developed. In a longterm therapy with bromocriptine a reduction of the dose may become possible, so that controls of the hormone levels are necessary in larger intervals. Most side effects of a bromocriptine treatment are transitory.

[Operative findings and therapeutic results in patients with primary hyperparathyroidism]. / Operationsbefunde und Therapieergebnisse bei Patienten mit primärem Hyperparathyreoidismus.

In the period from 1976 to September 1982 39 patients with the clinical diagnosis of primary hyperparathyroidism were operated on. Among then were 24 women and 14 men. The most frequent manifestation form is the renal one (n = 26). The proportion of patients with hypercalcaemic crisis was very large (n = 4). Topographically and anatomically the adenomas were most frequently found in the region of the right lower pole of the thyroid gland. 23 patients had a singular adenoma, 11 patients showed multiple adenomas and only 2 had a diffuse hyperplasia. In patients with persisting hyperparathyroidism before a repeated intervention an attempt of localization should be performed by a selective phlebography with taking of blood samples for the determination of PTH. The success of the operation is to be read off most clearly at the behaviour of the post-operative values of serum calcium. In 29 patients a normocalcaemia was achieved. 6 patients showed at first a hypocalcaemia, which however, was only temporary in 4 patients. 3 patients had a persisting hyperparathyroidism. In accordance with the literary data the formation of renal calculi clearly decreased after a successful operation.

[First experiences with short-term lithium therapy in severe thyrotoxicosis]. / Erste Erfahrungen mit der Lithiumkurzzeittherapie bei schwerer thyreotoxikose.

Even nowadays the therapy of severe, particularly of contrast remedy-induced hyperthyroidism is not without any problems. According to reports in literature the application of lithium salts seems to be an expedient from this dilemma. We controlled the effect of a short-term lithium therapy of 7 days in combination with methimazole in comparison to a group with methimazole monotherapy. The examination showed a good effectiveness and tolerability of the lithium methimazole therapy. While the decrease of the thyroxin concentration in the two groups was not different, in the group with combined therapy a more rapid per cent decrease of the triiodothyronine concentration appeared. In primarily strict selection of the therapy severe side-effects are not to be expected. According to the results yielded up to now the described form of therapy is an actual enrichment for selected forms of hyperthyreosis.

[Personal experiences in the diagnosis and treatment of primary hyperparathyroidism]. / Eigene Erfahrungen bei der Diagnostsik und Therapie des primären Hyperparathyreoidismus.

It is reported on an interdisciplinary team consisting of internists, radiologists and urologists which treated twelve patients with suspicion of primary hyperparathyroidism. The diagnostics is performed in form of a three-step progamme. A great importance is still ascribed to hypercalcaemia and therefore it serves as leading symptom. By means of the selective determination of parathormones no clear side classification could be achieved. In ten patients the operation could successfully be finished with the exstirpation of one or more adenomas of the parathyroid glands. A special importance deserves the intensive postoperative control with regular determinations of serum calcium in order to encounter in time a hypocalcaemia with tetanies by applications of calcium. It is referred to the necessity to search for an adenoma of the parathyroid gland at the slightest suspicion of the presence of a primary hyperparathyroidism.

[Interdisciplinary cooperation in the diagnosis and therapy of diseases of the adrenal glands and the parathyroid glands]. / Interdisziplinäre Zusammenarbeit in der Diagnostik und Therapie von Erkrankungen der Nebenniere und Nebenschilddrüse.

It is reported on the interdisciplinary cooperation between internists, radiologists and surgeons in the diagnostics and therapy of endocrinological diseases (suprarenal gland, parathyroid gland). On the basis of instances diagnostic step programmes are represented and first experiences of the cooperation are reported.

[Control of therapy for hyperthyroidism. Comparison of in-vitro and in-vivo methods]. / Therapiekontrolle der Hyperthyreose Vergleich von In-vitro- und In-vivo-Methoden.

55 patients with treated hyperthyroidism (thyreostatics) underwent a T3 suppression test and a TRH stimulation test. 60% of the patients had a positive and 40% a negative T3 suppression test. While patients with a positive T3 suppression test always showed a positive TRH test, the behaviour of the TRH test in negative suppression test was different (68.2% positive, 31.8% negative). These discrepant findings are to be explained from the establishment of different phases of regulation. In negative TRH test the concentrations of hormones were significantly higher. Increased basal TSH values are an expression of an overtreatment with thyreostatics. In positive suppression test and TRH test after a therapy lasting at least one year the medication can be stopped. In negative suppression test, however, the therapy should be changed. The TRH test allows only evidence about the quality of the regulation of therapy. Finally it can be established that the two tests on account of their different working points in the regulatory system are necessary and not changeable between each other.

[Drug therapy of hyperthyroidism]. / Medikaentöse Therapie der Hyperthyreose

The possibilities of the treatment of hyperthyroidism are mentioned, in which cases the author especially deals with the medicamentous therapy, taking into consideration the different chemical groups (imidazol derivations, thiourazil derivations, perchlorates) and their therapeutic mechanisms. The indications and contraindications of this treatment and the possible side effects are compiled in form of a table. The in-vitro-parameters which are necessary for the observation of the course are estimated in their significance. The author deals with the problems of the additional treatment. Taking into consideration indications and contraindications as well as controls of the course of functional parameters the medicamentous therapy concerned is a treatment with a good prognosis. It is promising particularly in such cases, when suitable parameters are used for the solution of the question concerning the end of the therapy. For this purpose nowadays two tests are at our disposal: 1. modified Alexander's test (radioiodine-test and suppression test under thyreostatic therapy) and 2. TRH-test with radioimmunological determination of TSH. The treatment should be carried out in adequate endocrinological dispensaries, as there are certain risks in not optimal therapy.