Ultrasound melted polymer sleeve for improved screw anchorage in trabecular bone--A novel screw augmentation technique.

BACKGROUND: Screw anchorage in osteoporotic bone is still limited and makes treatment of osteoporotic fractures challenging for surgeons. Conventional screws fail in poor bone quality due to loosening at the screw-bone interface. A new technology should help to improve this interface. In a novel constant amelioration process technique, a polymer sleeve is melted by ultrasound in the predrilled screw hole prior to screw insertion. The purpose of this study was to investigate in vitro the effect of the constant amelioration process platform technology on primary screw anchorage. METHODS: Fresh frozen femoral heads (n=6) and vertebrae (n=6) were used to measure the maximum screw insertion torque of reference and constant amelioration process augmented screws. Specimens were cut in cranio-caudal direction, and the screws (reference and constant amelioration process) were implanted in predrilled holes in the trabecular structure on both sides of the cross section. This allowed the pairwise comparison of insertion torque for constant amelioration process and reference screws (femoral heads n=18, vertebrae n=12). Prior to screw insertion, a micro-CT scan was made to ensure comparable bone quality at the screw placement location. FINDINGS: The mean insertion torque for the constant amelioration process augmented screws in both, the femoral heads (44.2 Ncm, SD 14.7) and the vertebral bodies (13.5 Ncm, SD 6.3) was significantly higher than for the reference screws of the femoral heads (31.7 Ncm, SD 9.6, p<0.001) and the vertebral bodies (7.1 Ncm, SD 4.5, p<0.001). INTERPRETATION: The interconnection of the melted polymer sleeve with the surrounding trabecular bone in the constant amelioration process technique resulted in a higher screw insertion torque and can improve screw anchorage in osteoporotic trabecular bone.

Anatomical considerations for transanal minimal-invasive surgery: the caudal to cephalic approach.

AIM: Nerve-sparing surgery during laparoscopic rectal mobilization is still limited by anatomical constraints such as obesity, the narrowness of the male pelvis, an ultra low rectal cancer or all of these. The transanal approach for total mesorectal excision has overcome the shortcomings of limited access to the rectal 'no-man's land' close to the pelvic floor. The aim of this anatomical study was to define a roadmap of anatomical landmarks for the caudal to cephalic approach so as to standardize nerve-sparing rectal mobilization procedures. METHOD: Macroscopic dissections of the pelvis in a caudal to cephalic direction were performed in eight alcohol-glycerol embalmed cadavers. A roadmap of anatomical landmarks was created at different levels of section to demonstrate the sites of nerve injury. RESULTS: Extrinsic autonomic nerves to the urogenital organs and the internal sphincter muscle are closely adjacent to the lowest portion of the rectum above the pelvic diaphragm. CONCLUSION: This anatomical guide for the pelvic surgeon should facilitate a safe and nerve-sparing dissection of the mesorectal plane with a meticulous overview of the lowest autonomic nerve fibres. New anatomical insights by a 'caudal to cephalic' approach to the 'no-man's land' should help overcome anatomical constraints of a narrow, obese and male pelvis during rectal mobilization procedures.

[Organ manifestations of hyperthyroidism]. / Organkomplikationen der Hyperthyreose.

Patients with hyperthyroidism tend to feel well and procrastinate the visit to the doctor and hence diagnosis of the disease. Among a whole variety of more or less distinct symptoms affecting many organs, cardiovascular disease is most prevalent and serious, because it relates to an increase in mortality of patients with hyperthyroidism. Recent epidemiological studies have clearly demonstrated that the disease already begins with the subclinical states of hyperthyroidism and, as a consequence, treatment should also be commenced early on. Novel insights into the mechanisms and actions of thyroid hormones at the pathophysiological level offer a potential for the development and future therapeutic use of selective hormone analogues. Despite the high frequency and importance of thyroid disorders, awareness appears to be decreasing and over-dosage of thyroid hormones in benign thyroid conditions is frequent. This review should emphasize that the thyroid gland affects the structure and function of a multitude of organs and, on the other hand, many symptoms and complaints, related to various organ systems, should raise suspicion of thyroid disease.

[Drug treatment of immune hyperthyroidism (Basedow disease). Patient selection, long-term follow-up and prevention of recurrence]. / Medikamentöse Behandlung der Immunhyperthyreose (Typ Morbus Basedow). Patientenselektion, Langzeitverlauf und Rezidivprophylaxe.

Since theraphy of Graves' disease is not directed towards the cause of the disease, medical theraphy is still the first choice and symptomatically effective in treating hyperthyroidism. Antithyroid drugs are effective in restoring euthyroidism in >90% of the patients durning 4-6 weeks, but 30-50% of the patients experience relapse after withdrawal. Previous prospective randomized studies evaluated prognostic parameters and the use of levothyroxine for prevention of relapse of hyperthyroidism. Recent studies have addressed the period after withdrawal amd focused on the natural course of disease. The results of a recent prospective randomized and controlled multicenter study were as follows: supplementation of levothroxine does not prevent relapse of hyperthyroidism. Basal TSH (4 weeks after withdrawal of antithyroid drugs) is the best prognostic marker. Smoking and positive TSH-receptor-antibodies at the end of antithyroid theraphy are other risk factors.

4D-QSAR analysis of a set of ecdysteroids and a comparison to CoMFA modeling.

The ecdysteroid-responsive Drosophila melanogaster B(II) cell line is a prototypical homologous inducible gene expression system. A training set of 71 ecdysteroids, for which the -log(EC(50)) potencies in the ecdysteroid-responsive B(II) cell line were measured, was used to construct 4D-QSAR models. Four nearly equivalent optimum 4D-QSAR models, for two modestly different alignments, were identified (Q(2) = 0.76-0.80). These four models, together with two CoMFA models, were used in consensus modeling to arrive at a three-dimensional pharmacophore. The C-2 and C-22 hydroxyls are identified as hydrogen-bond acceptor sites which enhance activity. A hydrophobic site near C-12 is consistent with increasing activity. The side-chain substituents at C-17 are predicted to adopt semiextended "active" conformations which could fit into a cylinder-shaped binding pocket lined largely with nonpolar residues for enhanced activity. A test set of 20 ecdysteroids was used to evaluate the QSAR models. Two 4D-QSAR models for one alignment were identified to be superior to the others based on having the smallest average residuals of prediction for the prediction set (0.69 and 1.13 -log[EC(50)] units). The correlation coefficients of the optimum 4D-QSAR models (R(2) = 0.87 and 0.88) are nearly the same as those of the best CoMFA model (R(2) = 0.92) determined for the same training set. However, the cross-validation correlation coefficient of the CoMFA model is less significant (Q(2) = 0.59) than those of the 4D-QSAR models (Q(2) = 0.80 and 0.80).

[Early operation as a treatment measure in thyrotoxic crisis]. / Frühoperation als Behandlungsmassnahme der thyreotoxischen Krise.

INTRODUCTION: Thyroid storm is a rare disease, occurring in less than 1% of all thyrotoxicoses. Diagnosis and therapy still have serious problems. METHODS: We review 14 patients who were operated on between 1992 and 1999 because of thyroid storm. RESULTS: All of the ten women and four men, aged 27 to 77 years, had an underlying thyroid disease. Autonomies were found in seven, Grave's disease in four, and a nodular goiter in three patients. The precipitating events were in five patients an antiarrhythmic therapy with amiodarone, on three occasions application of contrast medium, two times omission of antithyroid drugs and in one patient severe hyperglycemia with acidosis. In three patients no triggering factor was discovered. All patients were treated with high-dose antithyroid therapy. On admission, four patients were graded as stage-one thyroid crisis, three patients had stage-two and seven patients stage-three disease. All patients were operated on within 18 h of admission. Surgical procedure was in seven cases a bilateral subtotal resection, four times thyroidectomy, and in three patients a Dunhill procedure. After the operation, 12 patients improved rapidly. Two 77 and 74-year-old women died 1 or 2 days after the operation, respectively, one from heart failure and the other from multiple organ failure. Both had been diagnosed as thyrotoxic crisis stage three. CONCLUSION: Early operation should be adopted as a standard option in thyroid storm that cannot be controlled medically. Best results are achieved if the operation is done at stage one or two of the disease.

Evaluation of the LIAISON thyroid chemiluminescence immunoassays.

The LIAISON thyroid hormone assays TSH, FT4, FT3, T4 and T3 were evaluated by determining the imprecision, the reference ranges, the functional sensitivity (TSH), the dilution characteristics (accuracy) (FT4, FT3), and the recovery after spiking (TSH, T4, T3). Furthermore, inter-method comparisons were performed with following methods: Elecsys (Roche Diagnostics; TSH), AxSYM (Abbott Diagnostics; TSH, FT4, FT3, T4), ACS:180 (Bayer Diagnostics; all analytes), Amerlex-M (Johnson & Johnson; T4) and LISO-Phase (Techno Genetics; FT4). The fully automated LIAISON random access analyser is based on microparticle immunoassays and chemiluminescence. The coefficients of variation (CV) of intra-assay imprecision were between 0.2-6.0%, except for the control sample with extremely low TSH concentrations and low T3 concentrations. Inter-assay imprecision was performed by measuring controls covering the measuring range over a period of 9 to 20 days, with CVs ranging from 2.3-16.0%. The suitability of the sample material was determined by analysing serum and samples treated with EDTA, citrate or heparin in parallel. The results showed good correlations of the thyroid hormone concentrations between serum and plasma samples except for LIAISON FT3, for which lower results were observed with EDTA-plasma. The regression analysis of correlation studies gave slopes from 0.849 to 0.957 for TSH, from 1.023 to 1.375 for FT4, from 0.670 to 0.911 for FT3, from 0.917 to 1.166 for T4 and 1.00 for T3 depending on the concentration range and the method of comparison. The LIAISON FT4 assay showed a trend towards higher values in the high concentration range when compared with the ACS:180. The ranges of thyroid hormone concentrations determined in serum taken from apparently healthy subjects were found to be in accordance with published data. The clinical sample study confirmed that the LIAISON thyroid hormone assays are sensitive methods for the differentiation of euthyroid subjects and patients with hyper- and hypothyroidism. In conclusion, the automated thyroid hormone immunoassays on the random-access LIAISON immunoassay analyser proved to be very satisfactory, both from the analytical and the clinical point of view.

[Etiology and pathophysiology of Graves' disease]. / Atiopathogenese des Morbus Basedow.

Infectious agents are considered as etiologic factors for the onset of Graves' disease, while psychosocial stress and smoking may amplify the pathogenic cascade. Furthermore, smoking increases the risk of developing Graves' ophthalmopathy. Occasional evidence indicates that the autoimmune process may primarily be induced by foreign antigens, leading to the synthesis of antibodies which, in part, cross-react with thyrocytic TSH receptors. Once initiated, autoimmunity appears sustained within the thyroid by the cooperation of immunomodulated thyrocytes and antigen-presenting dendritic cells, which may, moreover, cause humoral responses against further thyrocytic antigens. Owing to a local increase in cytokine and integrin expression, lymphocytes and monocytes are attracted to the organ. The synthesis of autoantibodies is mainly propagated by T-helper-2 cells, while, at the same time, T-suppressor cells appear to be functionally deficient. Proof for this hypothetical scenario may allow for novel immunotherapeutic onsets in the near future.

[Administration of levothyroxine in the treatment of Basedow disease]. / Gabe von Levothyroxin in der Therapie des Morbus Basedow.

Current therapy of Graves' disease is symptomatically effective in eliminating hyperthyroidism but is not directed towards the immunological cause of the disease. As a result, the majority of patients experience relapse of hyperthyroidism after antithyroid drugs have been discontinued and need to undergo radioiodine treatment or surgery. Improvement of efficacy of antithyroid drug therapy in inducing longlasting remission of Graves' disease has therefore been an elusive goal. A number of recent experimental and clinical trials have addressed the issue of improving and optimizing modalities of antithyroid therapy. In-vitro studies demonstrating direct immunosuppressive effects of thionamide drugs and encouraging results from a Japanese clinical trial suggested that maximum thyroid blockade and supplementation with levothyroxine might be effective in preventing relapse of disease. The superior efficacy of this approach could not be confirmed by others studies. On the other hand, these studies so far lack statistical power to prove a lack of effect of this approach. The issue of levothyroxine supplementation during antithyroid drug treatment should be separated from another issue of levothyroxine prophylaxis following successful treatment outcome. The latter question is currently addressed by a prospective randomized multicenter study.

An extensive ecdysteroid CoMFA.

The ecdysteroid agonist activity of 71 HPLC-purified ecdysteroids was measured in the Drosophila melanogaster BII tumorous blood cell line assay. The resultant log(ED50) values, spanning almost 6 orders of magnitude, were used to construct a comparative molecular field analysis (CoMFA) model in which conformations were selected by homology to the crystal structure of ecdysone. Model A was constructed by utilization of the region-focused electrostatic indicator field (q2 = 0.631, r2 = 0.903, 5 components, 4 outliers). Model B made use of region-focused electrostatic and steric indicator fields along with MlogP (q2 = 0.694, r2 = 0.892, 5 components, 4 outliers). The model and its underlying bioassay data support a pharmacophore hypothesis in which ecdysteroid binding is understood to be due principally to the summation of localized interactions from approximately six specific loci. This is in contrast to previous structure-activity relationship hypotheses which are formulated in terms of the presence or absence of essential functional groups, without which ecdysteroid receptor affinity would be completely absent. The present CoMFA model is utilized to predict the activities of heretofore unknown ecdysteroids.

[Results of selective goiter resection in functional autonomy]. / Ergebnisse der selektiven Strumaresektion bei funktioneller Autonomie.

In the period from 1989 to 1994 a surgical treatment of toxic nodular goiter was performed in 145 patients. An unifocal autonomous adenoma occurred in 69 cases, a multifocal disease 76 times. The operative strategy consisted in a bilateral resection 105 times, and unilateral resection 29 times. An excision of a single node was carried out in ten cases. In one operation a hemithyroidectomy on one side and a subtotal resection of the other lobe was done. In May 1996 an interrogation about the current thyroid function was performed. In 105 (72.4%) patients a re-evaluation was possible. Concerning the postoperative therapy for prevention of recurrent hyperthyroidism or goiter growth, 84 patients (80%) had been treated with thyroxin and/or iodine. Under this therapy, after a mean period of 36 months 94 patients (89.5%) were clinically euthyroid. Nine patients (8.6%) were hypothyroid. Two patients developed a recurrent hyperthyroidism. Both of them belonged to the group of patients with multifocal autonomies, and both had been treated with thyroxin postoperatively. In one case, recurrent goiter growth occurred that did not need a therapeutic intervention. This patient as well had been treated for a multinodular goiter originally. She had not been taking a specific medication postoperatively. We conclude that a functional resection of autonomic tissue in nodular goiters is efficient in controlling the thyroid metabolism. A medical prophylaxis was not able to prevent recurrent hyperthyroidism in two cases.

[Is hemithyroidectomy as standard intervention of suspicious puncture cytology justified?]. / Ist die Hemithyreoidektomie als Standardeingriff bei suspekter Punktionszytologie gerechtfertigt?

Since 1989, the operative treatment of 65 patients with suspicious fine-needle aspiration cytology of solitary thyroid nodules has been decided on individual clinical criteria such as the patient's history and morphology of the remaining thyroid tissue. Finally, 9 carcinomas were seen amongst 37 hemithyroidectomy specimens, out of 28 resected thyroid glands 2 were papillary microcarcinomas, whereas the others were benign specimens up until now. Despite a comparatively low perioperative morbidity of the hemithyroidectomy, we see thyroid resections justified in cases of suspicious cytology.

Heterogeneity of autoantibodies against thyroid peroxidase in autoimmune thyroid disease: evidence against antibodies directly inhibiting peroxidase activity as regulatory factors in thyroid hormone metabolism.

The close relationship between thyroid microsomal antigen and thyroid peroxidase (TPO) is now well established. The present study evaluates the significance of autoantibodies against TPO (anti-TPO-Abs) in the various forms and stages of autoimmune thyroid disease with respect to a possible heterogeneous nature and particularly to their influence on TPO activity. When measured by a RIA using purified human TPO, anti-TPO-Abs were highly correlated with microsomal antibodies determined by enyzme-linked immunosorbant assay (r = 0.96; P less than 0.0001) and with the results of a TPO immunoprecipitation assay using crude microsomal preparations (r = 0.76; P less than 0.001). Relating the results of these assays to the reactivities of patients' sera with thyroid microsomes in immunoblot under nonreducing and reducing conditions, discordant results could be observed in a few cases. Further analysis of these data indicate a heterogeneous nature of anti-TPO-Abs, which react with at least two antigenic domains of the TPO molecule. The comparative analysis of patients with hyperthyroid Graves' disease, patients with Graves' disease in clinical remission, and patients with hypothyroid Hashimoto's thyroiditis revealed no significant differences in the antibody spectrum. When evaluating the direct influence of anti-TPO-Abs on the activity of TPO under a rigorous methodological approach, we found no significant inhibition of the enzymatic activity by any of the sera investigated from patients with autoimmune thyroid disease compared to that in sera from normal controls. In conclusion, the data indicate a heterogeneous nature of anti-TPO-Abs. The spectrum of antigenic epitopes recognized by anti-TPO-Abs seems not to be significantly different in the various forms and stages of autoimmune thyroid disease. The lack of an inhibitory effect of autoantibodies on TPO activity argues against direct binding of autoantibodies to the enzymatic sites of TPO and indicates that they are not important factors in producing thyroid dysfunction in autoimmune thyroid disease.

Highly sensitive determination of TSH in the follow-up of TSH-suppressive therapy of patients with differentiated thyroid cancer.

Basal and TRH-stimulated TSH levels were determined in 72 patients with differentiated thyroid cancer on hormonal treatment, using a highly sensitive immunoradiometric assay (IRMAclon, Henning). 43 patients were under treatment with levothyroxine (T4), 29 patients with triiodothyronine (T3). In 33/43 patients (77%) under T4- and in 18/29 patients (62%) under T3-treatment basal TSH levels were below 0.1 mU/l and levels stimulated with 200 micrograms TRH i.v. were below 0.5 mU/l. 3 patients showed a significant response (to above 0.5 mU/l) in the TRH test despite basal values of less than 0.1 mU/l. In 2 patients with elevated basal TSH levels (0.23 and 0.60 mU/l, resp.) in the IRMAclon, total suppression of TSH secretion was suggested by a failure of TSH to rise after TRH. By retesting these samples in an own TSH IRMA, basal and stimulated TSH values were below 0.1 mU/l. In conclusion, basal and TRH-stimulated TSH levels are well correlated in most patients with thyroid cancer under hormonal treatment. However, in some cases (5/72) determination of basal TSH could not clearly define the degree of thyrotropic suppression. Thus, TRH testing is still necessary to establish definitely complete TSH suppression in patients with thyroid carcinoma under suppressive treatment.