[Are Higher Prices for Larger Femoral Heads in Total Hip Arthroplasty Justified from the Perspective of Health Care Economics? An Analysis of Costs and Effects in Germany]. / Sind höhere Preise für größere Kopfdurchmesser in der Hüftendoprothetik medizinökonomisch vertretbar? Eine Analyse der Kosten und Effekte in Deutschland.

Background: In total hip arthroplasty (THA), femoral head diameter has not been regarded as a key parameter which should be restored when reconstructing joint biomechanics and geometry. Apart from the controversial discussion on the advantages and disadvantages of using larger diameter heads, their higher cost is another important reason that they have only been used to a limited extent. The goal of this study was to analyse the price structure of prosthetic heads in comparison to other components used in THA. A large group of patients with hip endoprostheses were evaluated with respect to the implanted socket diameter and thus the theoretically attainable head diameter. Materials and Methods: The relative prices of various THA components (cups, inserts, stems and ball heads) distributed by two leading German manufacturers were determined and analysed. Special attention was paid to different sizes and varieties in a series of components. A large patient population treated with THA was evaluated with respect to the implanted cup diameter and therefore the theoretically attainable head diameter. Results: The pricing analysis of the THA components of two manufacturers showed identical prices for cups, inserts and stems in a series. In contrast to this, the prices for prosthetic heads with a diameter of 36-44 mm were 11-50 % higher than for 28 mm heads. Identical prices for larger heads were the exception. The distribution of the head diameter in 2719 THA cases showed significant differences between the actually implanted and the theoretically attainable heads. Conclusion: There are proven advantages in using larger diameter ball heads in THA and the remaining problems can be solved. It is therefore desirable to correct the current pricing practice of charging higher prices for larger components. Instead, identical prices should be charged for all head diameters in a series, as is currently established practice for all other THA components. Thus when reconstructing biomechanics and joint geometry in THA, it should be possible to recover not only leg length, femoral offset and antetorsion of the femoral neck, but also to approximately restore the diameter of the femoral head and thereby optimise the functional outcome.

A pilot trial comparing the tear-out behavior in screw-sockets and cemented polyethylene acetabular components - a cadaveric study.

BACKGROUND: The removal of well-fixed acetabular components following THA (total hip arthroplasty) is a difficult operation and could be accompanied by the loss of acetabular bone stock. The optimal method for fixation is still under debate. The aim of this pilot study was to compare the tear-out resistance and failure behavior between osseo-integrated and non-integrated screw cups. Furthermore, we examined whether there are differences in the properties mentioned between screw sockets and cemented polyethylene cups. HYPOTHESIS: Tear-out resistance and related mechanical work required for the tear-out of osseo-integrated screw sockets are higher than in non-integrated screw sockets. PATIENTS AND METHODS: Ten human coxal bones from six cadavers with osseo-integrated screw sockets (n=4), non-integrated (implanted post-mortem, n=3) screw sockets and cemented polyethylene cups (n=3) were used for tear-out testing. The parameters axial failure load and mechanical work for tear-out were introduced as measures for determining the stability of acetabular components following THA. RESULTS: The osseo-integrated screw sockets yielded slightly higher tear-out resistance (1.61±0.26kN) and related mechanical work compared to the non-integrated screw sockets (1.23±0.39kN, P=0.4). The cemented polyethylene cups yielded the lowest tear-out resistance with a failure load of 1.18±0.24kN. Compared to the screw cups implanted while alive, they also differ on a non-significant level (P=0.1). Osseous failure patterns differed especially for the screw sockets compared to the cemented polyethylene cups. DISCUSSION: Osseo-integration did not greatly influence the tear-out stability in cementless screw sockets following axial loading. Furthermore, the strength of the bone-implant-interface of cementless screw sockets appears to be similar to cemented polyethylene cups. However, given the high failure load, high mechanical load and because of the related bone failure patterns, removal should not be performed by means of tear-out but rather by osteotomes or other curved cutting devices to preserve the acetabular bone stock. LEVEL OF EVIDENCE: Level III, case-control-study.

[Larger heads compensate for an increased risk of THA dislocation in high-risk patients]. / Größere Köpfe kompensieren erhöhte Hüft-TEP-Luxationsgefahr bei Hochrisikopatienten.

BACKGROUND: Dislocation is a devastating complication after total hip arthroplasty (THA) and occurs in 2-5% of primary THA cases and 5-10% of revision THA cases. Assuming correct implantation, dislocation risk can be reduced primarily by capsular repair and the use of larger prosthetic heads. However, larger heads are also associated with risks like accelerated wear or implant loosening, which is why heads with a maximum diameter of 36 mm are currently standard in primary THA. In cases with high dislocation risk, the use of 40 mm and 44 mm heads should be considered. OBJECTIVES: This study aimed to quantify THA dislocation risk and retrospectively analyze the course of disease in high-risk patients treated with 40 mm or 44 mm femoral heads after primary or revision THA, concerning dislocation and other complications suffered. MATERIALS AND METHODS: All patients with increased THA dislocation risk, treated from 2009-2014, were evaluated regarding dislocations. The cases with installation of 40 mm or 44 mm prosthetic heads were classified using a self-developed 5-level risk score and retrospectively analyzed. RESULTS: During the observation period, 288 THA interventions with increased dislocation risk were performed. In 278 cases with ball diameters ≤ 36 mm the dislocation rate was 15.1% (n=42). In 10 high dislocation-risk cases (3A to 4B according to recommended scoring system), 40 mm and 44 mm heads were used. After a 22.8 month mean follow-up, no THA dislocations were reported. CONCLUSION: Our results with 40 and 44 mm heads and the existing literature confirm much higher joint stability and, thus, significantly reduced dislocation risk with larger prosthetic heads in THA. Their use is, therefore, justified in high-risk patients and should be considered in future THA.

Evaluation of a navigated and power controlled milling system "navigated control spine" for spinal surgery.

PURPOSE: The aim of this work was the evaluation of a navigated and power controlled milling system for spine surgery (navigated control spine). The navigation is based on a set of intraoperatively taken fluoroscopic images from different angles. A manually planned workspace limits the power of the mill and assures a higher automatisation degree than any other established navigation system for spine surgery. METHODS: Both a technical study in workspace planning from fluoroscopic images and a milling study on a spine phantom were performed with participants with different level of knowledge of spinal surgery. RESULTS: In the region of interest the workspace planning could be performed with a maximum excess of 1.40 mm for surgeons. In the study performing the milling of a standardised workspace the remnant bone after milling had a mean difference from the planned workspace margin of 1.96-2.12 mm in the region of most interest. Accurate handling of the mill still required a certain level of medical knowledge and experience. In both studies the time needed for application of the system proved acceptable for clinical purposes. DISCUSSION: This concept of navigated and power controlled spinal surgery has proven feasible in an experimental study. This navigation system seems therefore promising for clinical application.

[Evaluation of a training system for middle ear surgery with optoelectric detection]. / Evaluation eines Trainingssystems für die Felsenbeinchirurgie mit optoelektrischer Detektion.

PROBLEM: This work presents a new training concept for surgery of the temporal bone. It is based on a model of gypsum plastic with optoelectric detection of risk structures. A prototypical evaluation is given. MATERIAL AND METHODS: The training models are based on high-resolution computed tomographic data of a human skull. The resulting data set was printed by a three-dimensional (3D) printer. A 3D phantom is created from gypsum powder and a bonding agent. Risks structures are the facial nerve, semicircular canal, cochlea, ossicular chain, sigmoid sinus, dura, and internal carotid artery. An electrically conductive metal (Wood's metal) and a fiber-optic cable were used as detection materials for the risk structures. For evaluating the training system, a study was done with eight inexperienced and eight experienced ear surgeons. They were asked to perform temporal bone surgery using two identical training models (group A). In group B, the same surgeons underwent surgical training with human cadavers. In the case of injuries, the number, point in time, degree (facial nerve), and injured structure were documented during the training on the model. In addition, the total time needed was noted. RESULTS: The training systems could be used in all cases. Evaluation of the anatomic accuracy of the models showed results that were between 49.5% and 90% agreement with the anatomic origin. Error detection was evaluated with values between 79% and 100% agreement with the perception of an experienced surgeon. The operating setting was estimated to be better than the previous"gold standard." The possibility of completely replacing the previous training method, which uses cadavers, with the examined training model was affirmed. CONCLUSIONS: This study shows that the examined system fulfills the conditions for a new training concept for temporal bone surgery. The system connects the preliminary work with printed and sintered models with the possibilities of microsystem engineering. In addition, the model's digital database permits a complete virtual representation of the model with appropriate further applications ("look behind the wall," virtual endoscopy).

Synthesis and cytotoxic activity of 5,6-heteroaromatically annulated pyridine-2,4-diamines.

A series of 5,6-heteroaromatically annulated pyridine-2,4-diamines have been synthesized and their in vitro cytotoxic activities evaluated against six human cancer cell lines. Benzo[g] annulated pyrido[2,3-b]indolediamines 7a-b and 8 showed relatively high cytotoxic activity as well as most of the diamines with pyrrolo[2,3-b]pyridine 17, thieno[2,3-b]pyridine and furo[2,3-b]pyridine 26-28, 1,8-naphthyridine 32 and 34 and benzo[h]quinoline 37 skeletons. Surprisingly, pyrido[2,3-b]indolediamines 13 and 14 without benzo[g] annulation were inactive. None of the new compounds were as potent as ellipticine, the reference compound.

Study of the anticancer potential of Yemeni plants used in folk medicine.

The present work evaluated the anticancer activity of methanol extracts from 24 plants used in Yemeni traditional medicine. To evaluate the in vitro cytotoxic potency of the investigated extracts, an established microtiter plate assay based on cellular staining with crystal violet was used with 5 human cancer cell lines: two lung cancer (A-427 and LCLC-103H), two urinary bladder carcinoma (5637 and RT-112) and one breast cancer (MCF-7) line. The methanolic extracts of Dendrosicyos socotrana, Withanina aduensis, Withania riebeckii, Dracena cinnabari and Buxus hildebrandtii exhibited the highest toxicity on all tumor cell lines with IC50 values ranging between 0.29 and 5.54 microg/ml. The extracts of Jatropha unicostata and Punica protopunica showed a moderate potency on the most tumor cell lines.

Surgery on the lateral skull base with the navigated controlled drill employed for a mastoidectomy (pre clinical evaluation).

Patients who are treated with a mastoidectomy usually suffer from an inflammation of the petrosal bone. The intervention is a time consuming landmark based surgery and usually performed with a powered drill. Delicate risk structures must be respected. Navigated Control (NC) describes the control for a power driven instrument which is controlled by a surgeon and additionally controlled according to the position of the instrument relatively to a deliberated position known from a preoperatively segmented work space which excludes risk structures. The force of a drill can be regulated by the principle of NC. Following results were received: 1. Risk structure segmentation is feasible 2. The drill and a phantom can be registered. 3. With NC the resection is faster, more accurate and with no risk structures damage. 4. The phantom is suitable.

[Manipulator assisted endoscope guidance in functional endoscopic sinus surgery: proof of concept]. / Ein Konzept für eine automatisierte Endoskopführung für die Nasennebenhöhlenchirurgie.

BACKGROUND: Functional endoscopic sinus surgery (FESS) is characterized by single-handed preparation and guidance of the endoscope by the nondominant hand. This results in an additional extension of operation time by up to 15% and ergonomic deficits. The aim of this study is the conception of an automated assistance system for FESS in view of the following questions: (1) Which degree of surgical automation is suitable for FESS? (2) Which design is suitable? (3) What are the properties of the technical system (planning, time, accuracy, precision) of the selected system? (4) Does the system offer potential for a clinical application? METHODS: In all 49 FESS were analyzed for surgical workflows. Measurement of the maximum forces within FESS was performed with 40 trials on an anatomical model. Three different mechanical systems were used in ten FESS and evaluated using the ICCAS Human-Machine Evaluation Scale. For realization of automated endoscope guidance an engine-driven and -braked manipulator (PA10-6c, Mitsubishi, Japan) was used. The technical parameters determined were expenditure of time for the preoperative planning of workspace, surgical accuracy and precision of the intraoperative endoscope positioning, maximal forces, and time. RESULTS: Concept-conditioned instrument changes amount to an average of 41.1 and 18.9% (5.21 min) time requirement for each FESS side. Maximum forces on the mucous membrane during a conventional FESS were measured at 9.8 N (5.9-9.8). Usability of the mechanical endoscope holder was estimated in 18 of 20 cases to be inferior to the standard procedure. The time needed for segmenting the intranasal workspace was 15.2 min (10.0-23.0). The maximum deviation of the automatically driven endoscope from a planned position amounted to 0.85 mm (manually 4.64 mm). The maximum force was measured with 1.1 N in the z direction (manually 9.8 N). Automated guidance of the endoscope to an intranasal position needed 7.25 s (6.4-7.9); manually 12.64 s (5.9-43.0). CONCLUSION: Guidance of the endoscope for FESS by an automated motor-driven system is possible. The conception which is based on workflow analysis favors a system with automatic definition of the workspace and a manual movement of the endoscope. The examined system offers a potential for clinical application. Definition of the automation level and development of a man-machine interface is more important than selection or reconstruction of a special manipulator for endoscope guidance in FESS from a surgical point of view.

Synthesis, structure and anticancer activity of novel 2,4-diamino-1,3,5-triazine derivatives.

A series of 2-(4,6-diamino-1,3,5-triazin-2-yl)-2-{[4-(dimethylamino)-phenyl]imino}acetonitriles 19-27 have been synthesized by the reaction of 2-(4-amino-6-alkylamino-1,3,5-triazin-2-yl)acetonitriles 10-15 with p-nitrosodimethylaniline. Unexpectedly, a similar reaction of acetonitriles 10, 14, 15, 17 and 18 with nitrosobenzene led to the formation of 4,6-diamino-N-phenyl-1,3,5-triazine-2-carboxamides 28-32. The in vitro antitumor activity of the compounds obtained has been tested and 2-[4-Amino-6-(4-phenylpiperazin-1-yl)-1,3,5-triazin-2-yl]-2{[4-(dimethylamino)phenyl]imino}acetonitrile (19) having remarkable activity against melanoma MALME-3 M cell line (GI(50)=3.3 x 10(-8) M, TGI=1.1 x 10(-6) M) is a leading candidate for further development.

ElePhant--an anatomical electronic phantom as simulation-system for otologic surgery.

This paper describes the ElePhant (Electronic Phantom)-an anatomical correct simulation system based on 3D rapid prototyping models for the otologic intervention "Mastoidectomy". The anatomical structures of the head are created with plaster as base material using 3D-printing as rapid prototyping technology (RPT). Structures at risk, represented by electrically conductible material and fiber optics, are realized as an electric circuit and can be detected during the simulation of the surgical procedure. An accuracy study of 15 identical RPT-models compared to the 3D reconstructed CT-dataset of the patient showed that the mean accuracy is lower than the reconstructed CT layer thickness of 0.5 mm. An evaluation study of the ElePhant-system for "Mastoidectomy" was performed by 7 ENT-surgeons. The mean value of the study questionnaire (evaluation range from -2 (not at all) to +2 (very good)) was +1.2. The results showed that the ElePhant can simulate "Mastoidectomy" realistically. It is especially suitable for the simulation of the correct representation and position of the anatomical structures, realistic operation setting, and realistic milling properties of the bone structure. Furthermore it is applicable for training of surgeons.

[Genetic differences in enzymes of folic acid metabolism in patients with lip-jaw-palate clefts and their relatives]. / Genetische Unterschiede von Enzymen des Folsäurestoffwechsels bei Patienten mit Lippen-Kiefer-Gaumen-Spalten und ihren Angehörigen.

BACKGROUND: The effectiveness of folic acid supplementation in the periconceptional period for the prevention of cleft lip/cleft lip and palate (CLP) is contradictorily discussed. Genetically determined variants of enzymes of the folic acid metabolism could be part of the key to success or failure of folate supplementation. A mutation of the methylenetetrahydrofolate reductase (MTHFR) gene is suspected to be a risk factor for CLP. METHODS: The blood samples of 66 CLP patients, their 88 relatives (without CLP), and 184 healthy controls were searched by polymerase chain reaction for mutations of MTHFR 677 C:T, MTHFR 1298 A:C and of the arylamine N-acetyltransferase (NAT1) gene [gene type NAT1 degree 4 (wild type) or not]. RESULTS: There was no significant difference in the number of MTHFR gene mutations (for 677 C:T and 1298 A:C) between the three groups (p approximately 0.3), but for the NAT1 genes (p = 0.033). The homozygote mutation was found more than twice as often in CLP patients (10.5%) and their relatives (10.6%) than in the healthy controls (4.35%). DISCUSSION: Our results provide no evidence that the above MTHFR gene mutations are a risk factor for CLP.A NAT1 gene mutation instead could be a risk factor for CLP.

[Foreign body in paranasal sinuses]. / Fremdkörper in den Nasennebenhöhlen.

AIMS: All cases of the last 5 years requiring foreign bodies to be removed from the paranasal sinuses were investigated as to causes, special aspects in diagnostics and therapy, occurrence of pathologic germs and possible sequels. PATIENTS: 68 cases were evaluated: 43 patients were male, 25 female. Average age was 29 years in males and 37 years in females. RESULTS: In our patients foreign bodies in the paranasal sinuses were in more than 60% the result of medical or dental procedures followed by industrial accidents (25%). The maxillary sinus was affected in 75%, the frontal sinus in about 18%. Involvement of the ethmoid or sphenoid sinus was rare. The spectrum of pathologic microbes was dominated by mixed infections, the share of actinomyces and aspergillus was unexpected high. Most important acute complications were bleeding, compression of the optic nerve and liquorrhoe. Late complications consisted mainly of pain--often associated with disturbances of sensibility- and infections. CONCLUSIONS: A smear should be taken whenever the foreign body remained in the sinus for more than 4 days. Foreign bodies jammed in the posterior wall of the sinus require a sufficiently open view since the risk of heavy bleeding is especially high.

New synthetic route to [bis-1,2-(aminomethyl)benzene]dichloroplatinum(II) complexes, screening for cytotoxic activity in cisplatin-sensitive and resistant human cancer cell lines, and reaction with glutathione.

A new synthetic route to [bis-1,2-(aminomethyl)benzene]dichloroplatinum(II) complexes is described. o-Xylene and the 4-methoxy substituted derivative were used as starting points for the synthesis: benzylic bromination with N-bromosuccinamide/benzoylperoxide followed by the substitution of the benzyl bromides for azide and finally a catalytic hydrogenation with Pd/C of the diazides gave the desired diamines ligands. An attempt to synthesize the 4,6-dimethoxy derivative was unsuccessful due to the bromination of the aromatic ring. The diamines were complexed with K2PtCl4 to give the target Pt(II) complexes: [1,2-bis(aminomethyl)benzene]dichloroplatinum(II) (4a) and [1,2-bis(aminomethyl)-4-methoxy-benzene]dichloroplatinum(II) (4b). Screening for cytotoxic activity was done in comparison to cisplatin in a panel of eight human cancer cell lines; in all cases, the 4-methoxy derivative 4b was less active than the unsubstituted analog, 4a. In four cell lines 4a was as potent as cisplatin, while in the other four lines cisplatin was considerably more potent then 4a. The 5637 bladder cancer cell line was made 4-5 fold resistant to either cisplatin or [d,l-trans-1,2-diaminocyclohexane]dichloroplatinum(II); 4a showed some cross resistance (2-3 fold) to both resistant cell lines. The reactivity of 4a towards substitutions with glutathione (GSH), a biological thiol involved in intrinsic and acquired resistance to Pt-complexes, was measured by a RP-HPLC method. It was found that the second-order rate constant for the reaction of 4a with GSH was similar to that that reported for CDDP, indicating that reactivity towards GSH does not explain the different levels of cross resistance.

StAR protein is increased by muscarinic receptor activation in human luteinized granulosa cells.

Cultured human luteinized granulosa cells (GC) are a unique model to study regulation of the human corpus luteum, e.g. by local factors, including acetylcholine (ACh). GC express functional ACh-receptors of the M1-type (M1R). Priming with the cholinergic agonist carbachol for 24 h, followed by a 24 h stimulation with human chorionic gonadotrophin (hCG), significantly increased progesterone levels (up to 2-fold), compared with hCG stimulation alone. This is likely due to the effect of carbachol, observed after 24 h, to increase the levels of steroid acute regulatory (StAR) protein, as found in Western blots. StAR protein was increased (2-10-fold), while P450 side chain cleavage (SCC) enzyme was unaffected. Thus, one role of muscarinic receptor activation in human GC is regulation of StAR protein and, subsequently, progesterone production.

D1-Receptor, DARPP-32, and PP-1 in the primate corpus luteum and luteinized granulosa cells: evidence for phosphorylation of DARPP-32 by dopamine and human chorionic gonadotropin.

The multifunctional phosphoprotein "dopamine and cAMP-related phosphoprotein, M(r) 32,000" (DARPP-32), which is able to act as an intracellular third messenger, was previously found to be present in human luteinized granulosa cells (GCs) and human ovary. DARPP-32 phosphorylation in GCs was increased by dopamine (DA) acting via a DA-1 receptors (D1-R). In the present study, we examined whether the major endocrine signaling molecule for GCs, LH/human CG (hCG), could also affect DARPP-32 phosphorylation. Immunoprecipitation studies showed that hCG, as well as DA, increased phosphorylation of DARPP-32 at threonine residues within 10 min, indicating that the signal transduction pathways of a hormone and a neurotransmitter involve DARPP-32 in GCs. Phosphorylated DARPP-32 is known to inhibit a cellular phosphatase (PP-1), which was also found to be expressed by GCs. Using RT-PCR and sequence analyses we showed that DARPP-32, PP-1, and D1-R genes were not restricted to cultured luteinized GCs, but were expressed in vivo, in the corpus luteum (CL) of the rhesus monkey throughout its entire life span. Whereas hCG increased steroid production in monkey luteinized GCs and in isolated luteal cells, DA failed to affect basal or hCG-stimulated progesterone production. This indicates that, unlike the LH/hCG receptor, the D1-R is not directly linked to steroid production. Although the precise role of D1-R in the CL remains to be shown, the presence of D1-R, DARPP-32, and its target PP-1 in this endocrine tissue, as well as the phosphorylation of DARPP-32 by a gonadotropin and by DA in luteinized GCs, indicate that the signal transduction pathways of the neurotransmitter DA and the gonadotropin hCG/LH involve DARPP-32. The PP-1 inhibitor DARPP-32 may, thus, be a third messenger used by both DA and hCG/LH to exert common regulatory influences on the cells of the CL.

Bilateral epidermoid cysts of the testicle.

An 11-year-old boy presented with bilateral testicular masses that consisted of hyperechoic centers with hypoechoic rims on ultrasound. Surgical exploration revealed bilateral epidermoid cysts. To our knowledge this is the first reported case of bilateral epidermoid cysts in a child. Recognition of this entity requires surgical confirmation but it may obviate removal of the testicle.

[The behavior of various phenylalkylamines in ultraviolet light. 23. Stability of drugs and preparations]. / Zum Verhalten einiger Phenylalkylamine im ultravioletten Licht. 23. Mitteilung: Stabilität von Arzneistoffen und Zubereitungen.

The UV-VIS-spectrophotometry and the DC enable a survey on qualitative changes of the drugs to be tested after lighting. They are components of investigations performed to ascertain the sensitivity of drug solutions. The authors discuss phenylalkylamine changes after lighting.

[The effect of visible light on the stability of isoprenaline, epinephrine and levarterenol solutions in various containers. 86. Problems in the use of plastic containers for liquid preparations. 21. The stability of drugs and preparations]. / Einfluss des sichtbaren Lichtes auf die Haltbarkeit von Isoprenalin-, Epinephrin- und Levarterenollösungen in unterschiedlichen Behältnissen. 86. Mitteilung: Beiträge zur Problematik des Einsatzes von Kunststoffbehältern für flüssige Arzneizubereitungen; 21. Mitteilung: Stabilität von Arzneistoffén und Zubereitungen.

The stability of solutions of phenylalkylamines of the benzcatechine type was investigated in containers of different structure under influence of diffuse day light, direct sun light and artificial visible light. Thereby a combined influence of different the decomposition increasing factors could be observed. The decompositions were slowest in containers of PE-ND with pigment additionals and were increased from PE-HD, PE-ND, colourless glas up to brown glas .