[Principles of management of periprosthetic fractures]. / Prinzipien des Managements periprothetischer Frakturen.

BACKGROUND: The increasing numbers of primary total hip and knee replacements have subsequently led to growing rates of periprosthetic fractures. In many cases geriatric patients with osteopenia or osteoporotic bone quality are affected. The goal of treatment is the retention or reconstruction of joint function using open reduction and internal fixation or a revision prosthesis. OBJECTIVE: The aim of this article is a description of the basic principles of treatment of periprosthetic fractures of the lower extremities. MATERIAL AND METHODS: An exact description of the fracture using current classification systems with imaging diagnostics is mandatory. This also includes an assessment of the stability of the prosthesis. In the case of a stable prosthesis and a good bone stock open reduction and internal fixation should be performed. In these cases locking plates are standard procedure. If fracture reduction is possible minimally invasive procedures can be performed which help to reduce the surgical trauma and accelerate rehabilitation. If the prosthesis is loose it has to be exchanged for a revision implant. If vast bony defects result they can be augmented using wedges. Conservative treatment plays only a subordinate role in selected cases. RESULTS AND CONCLUSION: Periprosthetic fractures show an increasing incidence and occur more frequently in the geriatric patient population. Due to comorbidities and poor bone quality surgical treatment is a challenge. The fracture must be exactly classified using the appropriate classification system in order to clarify if the prosthesis can be retained or if it has to be exchanged.

[Augmentation technique on the proximal humerus]. / Augmentationstechnik am proximalen Humerus.

BACKGROUND AND OBJECTIVES: The treatment of osteoporotic fractures is still a challenge. The advantages of augmentation with respect to primary in vitro stability and the clinical use for the proximal humerus are presented in this article. MATERIAL AND METHODS: In this study six paired human humeri were randomized into an augmented and a non-augmented group. Osteosynthesis was performed with a PHILOS plate (Synthes®). In the augmented group the two screws finding purchase in the weakest cancellous bone were augmented. The specimens were tested in a 3-part fracture model in a varus bending test. RESULTS: The augmented PHILOS plates withstood significantly more load cycles until failure. The correlation to bone mineral density (BMD) showed that augmentation could partially compensate for low BMD. CONCLUSION: The augmentation of the screws in locked plating in a proximal humerus fracture model is effective in improving the primary stability in a cyclic varus bending test. The targeted augmentation of two particular screws in a region of low bone quality within the humeral head was almost as effective as four screws with twice the amount of bone cement. Screw augmentation combined with a knowledge of the local bone quality could be more effective in enhancing the primary stability of a proximal humerus locking plate because the effect of augmentation can be exploited more effectively limiting it to the degree required. The technique of augmentation is simple and can be applied in open and minimally invasive procedures. When the correct procedure is used, complications (cement leakage into the joint) can be avoided.

[Return to Work after Fractures of the Pelvis and the Acetabulum]. / Berufliche Wiedereingliederung nach Becken- und Azetabulumfrakturen.

BACKGROUND AND INTRODUCTION: Pelvic and acetabular fractures are severe injuries with serious consequences that mainly happen to young people. Therefore it is highly interesting to find out to what extent affected patients succeed in returning to work, which is an important factor concerning quality of live. Thus, the objective of this study was to estimate the "return to work" in a two-year follow-up after rehabilitative treatment of patients with pelvic and acetabular fractures and to identify influencing factors. METHODS: A retrospective cohort study was conducted using population-based administrative data of the Baden-Württemberg statutory pension fund. All patients (age 18 to 63 years) who had participated in a rehabilitation programme between 2004 and 2009 due to a pelvic or acetabular fracture were included. Return to work was modelled using multivariate logistic regression analysis. Rehabilitants were classified as "returned" if they have paid at least one monthly contribution due to employment during 13 to 24 months after rehabilitation. Age, gender, diagnostic group, type of rehabilitation programme, fractures of the spine, nerve injuries of the lumbosacral area and/or the lower limb and employment status before the fractures were considered as prognostic covariates. RESULTS: Two-thirds of the 249 researched patients returned to work. This corresponds to a reduction of employment amounting to 16.6 % for patients with a pelvic fracture and 20.8 % for patients with an acetabular fracture. Main predictor for a return to work was the employment status before the fracture. Younger patients had a better chance to return to work than older ones. Patients with fractures of the spine or nerve injuries of the lumbosacral area and/or the lower limb had a 73 % or, respectively, 78 % higher risk of not returning to work. CONCLUSION: Fractures of the pelvis and the acetabulum currently lead in one of five patients to loss of employment. Thereby the trauma threatens the social security of the young patients. Follow-up care should be intensified to increase recovery rates and reduce the burden of long-term work disability.

[Proximal tibia fracture treatment with a new locking device with polyaxial screw placement: technique and early results]. / Frakturversorgung an der proximalen Tibia mit einem neuartigen winkelstabilen Implantat mit polyaxialer Schraubenplatzierung: Technik und erste Ergebnisse.

BACKGROUND: Surgical treatment of tibial head fractures can be challenging due to the close anatomic relationship to the knee joint which can be affected including its intraarticular structures. Frequently, soft tissue damages are present which can have a strong impact on the planning and choice of surgical technique. An important therapeutic requirement is the anatomic reconstruction and high primary stability to allow early functional treatment. The aim of the present study was to describe a recent locking device and its surgical technique and to analyse the early results. MATERIAL AND METHODS: The Non-Contact-Bridging Plate for the proximal tibia (NCB® PT, Zimmer Inc.) features a polyaxial locking mechanism which allows both compression and locking with the same screw. The system can be applied both minimally invasively and open. 36 patients (16 female, 20 male; average age 53 years) with three type A, 21 type B and 12 type C fractures according to the AO classification were treated. In 22 cases the system was applied open and in 14 minimally invasively. Clinical and radiological follow-up was obtained at 6 weeks, 3, 6 and 12 months. RESULTS: The handling of the system turned out to be straightforward after an initial learning curve. Implant failure was not detected in our sample. The minimally invasive technique can be beneficial in cases of severe soft tissue damage, but must not compromise the quality of reduction. The functional result at 1-year follow-up using a knee score was good or very good and comparable to the literature. The rate of general surgical complications was 11 % (haematoma, superficial or deep wound infection). Implant-related complications were not detected. At the 3-months' follow-up 44 % and at the 12-months' 100 % of the fractures were healed on X-ray. CONCLUSION: The NCB PT plate offers a broad variety of treatment options due to the specific locking mechanism and the fact that it can be applied both minimally invasively and open. In cases of intraarticular involvement the application of compression and locking with the same screw turned out to be very beneficial. The primary stability of the system allows early functional treatment. Clinical results and complication rates of the present study are comparable to those in the literature.

[Treatment of peritrochanteric fractures: biomechanical considerations]. / Versorgung pertrochantärer Femurfrakturen: Biomechanische Überlegungen.

Biomechanical considerations are relevant in the treatment of peritrochanteric fractures. Concomitant diseases and osteoporosis place high demands on the primary stability of the operative treatment. In the situation of unstable fractures (AO/ASIF 31-A2 and A3), even normal activities of life can easily exceed the critical limits of stability, which can result in implant failure. Both intramedullary and extramedullary implants are used successfully in the treatment of even unstable fractures. Different variations in the implant design and anchorage of the load carrier of the femoral neck are available and may have different biomechanical characteristics. Biomechanical tests show that new developments of implants can increase stability. Nevertheless, accurate reduction and operative technique is essential to ensure uneventful fracture healing. Although some supportive measures are very promising, such as augmentation, further research is required to increase stability in the unstable and osteoporotic fracture situation.

Side plate fixation vs. intramedullary nailing in an unstable medial femoral neck fracture model: A comparative biomechanical study.

BACKGROUND: The objective of this study was to investigate primary stability of the proximal femoral nailing antirotation for the indication of unstable medial femoral neck fractures. The device was compared to the dynamic hip screw blade, which is a "gold standard" in the treatment of proximal femoral fractures. METHODS: Six pairs of human cadaver femurs were tested in a cyclic loading model with loads up to 200 N, 400 N, 600 N, 800 N, and 1000 N, respectively. Iliotibial tract was simulated by a chain that applied forces on the greater trochanter during loading. In vitro combined axial and bending loads were applied. Angular displacements during loading were recorded in all directions, and loads to failure were recorded. FINDINGS: For the cyclic loading test no statistically significant differences between the two groups could be detected. Specimens fixed with the dynamic hip screw blade showed higher displacements in the varus direction at 400 N and 600 N, in the external rotation at 200 N, 400 N and 600 N, and in the anterior direction at 400 N. Load to failure revealed no statistical difference between the two implants. INTERPRETATION: The proximal femoral nailing antirotation achieves primary stability comparable to the dynamic hip screw blade. The proximal femoral nailing antirotation combines the biomechanical favorable concept of intramedullary fixation with a minimally invasive surgical technique, which theoretically may be advantageous in clinical use. Further biomechanical studies are required to clarify to what extent the results of the present study can be transferred to the clinical situation.

[Biomechanical investigation of fixed-angle plate osteosynthesis of the proximal humerus]. / Biomechanische Untersuchung der winkelstabilen Plattenosteosynthese am proximalen Humerus.

INTRODUCTION: Proximal humeral fractures are common in the elderly population and are often associated with osteoporosis. Fixation of unstable proximal humeral fractures is problematic due to loss of fixation in osteoporotic bone. Fixed-angle devices are intended to provide superior mechanical stability due to the principle of an internal fixator. The NCB(R)-PH (non-contact-bridging proximal humerus) plate is a new fixed-angle device that locks the screws to the plate by secondary insertion of a locking cap. The aim of this study was to investigate if and to what extent NCB-PH plates applied in the locked mode provide higher mechanical stability in a proximal humerus fracture model. METHODS: For this investigation 16 (8 pairs) fresh frozen cadaveric humeri were used. An AO/ASIF 11-B 1 fracture of the proximal humerus was created in each bone and fixed with the NCB-PH plate. In a paired setting one bone was fixed with the plate in the locked mode and the other with the plate in the non-locked mode. The bones were then subjected to 100 cycles of axial loading and interfragmentary motion was measured. Bones surviving this test were subjected to load-to-failure testing and the force at which failure occurred was recorded. RESULTS: Bones fixed with the plate in the locked mode showed a statistically significant lower (51%) interfragmentary rotation compared to bones fixed with the plate in the non-locked mode. There was also a tendency for the bones fixed with the plate in the locked mode to fail first under higher forces (16%) during load-to-failure testing. CONCLUSION: The NCB-PH plate provides superior interfragmentary stability when used in the locked mode in a human cadaveric proximal humerus fracture model. Therefore, we recommend that all screws should be inserted in the locked mode. The results suggest that the NCB-PH plate in the locked mode provides higher primary postoperative stability thus permitting early functional treatment of the patient.

Early results in the treatment of proximal humeral fractures with a polyaxial locking plate.

OBJECTIVES: We report early results using a second generation locking plate, non-contact bridging plate (NCB PH((R)), Zimmer Inc. Warsaw, IN, USA), for the treatment of proximal humeral fractures. The NCB PH combines conventional plating technique with polyaxial screw placement and angular stability. DESIGN: Prospective case series. SETTING: A single level-1 trauma center. PATIENTS: A total of 50 patients with proximal humeral fractures were treated from May 2004 to December 2005. INTERVENTION: Surgery was performed in open technique in all cases. MAIN OUTCOME MEASURES: Implant-related complications, clinical parameters (duration of surgery, range of motion, Constant-Murley Score, subjective patient satisfaction, complications) and radiographic evaluation [union, implant loosening, implant-related complications and avascular necrosis (AVN) of the humeral head] at 6, 12 and 24 weeks. RESULTS: All fractures available to follow-up (48 of 50) went to union within the follow-up period of 6 months. One patient was lost to follow-up, one patient died of a cause unrelated to the trauma, four patients developed AVN with cutout, one patient had implant loosening, three patients experienced cutout and one patient had an axillary nerve lesion (onset unknown). The average age- and gender-related Constant Score (n = 35) was 76. CONCLUSIONS: The NCB PH combines conventional plating technique with polyaxial screw placement and angular stability. Although the complication rate was 19%, with a reoperation rate of 12%, the early results show that the NCB PH is a safe implant for the treatment of proximal humeral fractures.

[Primary hemiarthroplasty of complex fractures of the humeral head - results for different prosthetic designs]. / Primäre Hemiarthroplastik bei Humeruskopfmehrfragmentfrakturen - Ergebnisse in Abhängigkeit der Prothesengeneration.

AIM: Primary hemiarthroplasty of the shoulder is an alternative method for the treatment of complex fractures of the humeral head as compared to humeral head-preserving methods. This study compares the results of two different prosthetic designs. A first generation design, the Neer prosthesis (SGE 1 G) and a third generation design, the Aequalis prosthesis (SGE 3 G) were investigated. METHOD: The data (patients' charts, X-ray, and ultrasound) were collected and analysed in a retrospective manner. Self assessment was performed using the visual analogue scale (VAS), functional outcome was determined using the Constant score. For data analysis, methods of descriptive statistic were applied. RESULTS: 29 patients were treated with the SGE 1 G and 49 patients were treated with the SGE 3 G. Patients' age in the mean was 76 years, more women than men were affected. According to the Neer fracture classification, four-part fractures were the most frequent type of fracture. 64 % of the patients in the Neer (SGE 1 G) group and 68 % in the Aequalis (SGE 3 G) group were satisfied with the result according to VAS. The average Constant score in the Neer group was 50 points and in the Aequalis group 59 points. Better results were detected for the subjective parameters pain and activity than for the objective parameters motion and strength. The postoperative deviation from the age- and sex-related Constant score was smaller in the Aequalis group (5 points) than in the Neer group (17 points). Ultrasound examinations revealed in nearly all patients atrophy of the rotator cuff resulting in disturbances of motion between the corresponding gliding tissues. CONCLUSIONS: The SGE 3 G shows better results in the VAS and Constant score than the SGE 1 G. The advantages of the modular design of SGE 3 G are underlined by the clinical results.

Treatment of periprosthetic femur fractures with the non-contact bridging plate: a new angular stable implant.

OBJECTIVES: We report the application of a new fixed angle plate (NCB DF, Zimmer inc. USA, Warsaw, IN) in the treatment of periprosthetic femur fractures. The NCB DF combines conventional plating technique with polyaxial screw placement and angular stability. DESIGN: Prospective cohort study. SETTING: A single level-1 trauma center. PATIENTS: From May 2003 to December 2005, a total of 24 patients with periprosthetic femur fractures were treated. The NCB DF femur plate was used in all cases. The average follow-up period was 12 months (3-31 months). Twelve patients had a periprosthetic fracture after total knee replacement (TKA) and 12 patients after total hip replacement (THA). The mean period from primary joint replacement to periprosthetic fracture was 8.2 years for the THA group and 7.2 years for the TKA group. INTERVENTION: A combined conventional/locking surgical technique was performed in all the cases. MAIN OUTCOME MEASURES: Union, non-union, mal-union, duration of surgery, range of motion, postoperative mobility, subjective patient satisfaction and complications. RESULTS: The union rate was 90%, the mal-union rate 5% and the re-operation rate 15%. Postoperative mobility reached the preoperative level in all but for two patients. Three complications occurred relating to the implant or the procedure: one fatigue failure of the plate (non-union), one screw breakage, and one wound infection. CONCLUSIONS: The NCB DF combines conventional plating technique with polyaxial screw placement and angular stability. This combination technique shows promising results regarding union and mal-union rates in periprosthetic fractures in elderly and osteoporotic patients.

[The Non-Contact Bridging Plate. A new fixed-angle device for the minimally-invasive treatment of fractures of the proximal humerus--technique and preliminary results]. / Die Non-Contact-Bridging-(NCB-) Platte. Ein neues winkelstabiles System zur minimal-invasiven Versorgung von Frakturen des proximalen Humerus--Technik und erste Ergebnisse.

BACKGROUND: Fractures of the proximal humerus are common in elderly patients, especially in osteoporotic bone. Requirements for surgical treatment are high primary stability to allow early functional physiotherapy. The Non-Contact Bridging (NCB) Plate for the proximal humerus (PH) is a new head locking system for treating fractures of the proximal humerus which allows minimally invasive surgery (MIS). METHODS: In this contribution, the implant and technique are described, as well as the analysis of the first clinical results after 61 procedures. RESULTS: In a mainly elderly patient population (mean: 73 years, range: 50-91 years) 61 minimally-invasive procedures were performed. The placement of screws led to a high primary stability. Primary implant failure occurred in one case (1.69%). The average constant score after 6 months was 62 points (age related mean 72). CONCLUSIONS: Using the MIS-technique, the NCB-PH plate provides high primary stability, allowing functional treatment without postoperative limitations. The first clinical results show a good functional outcome in a mainly elderly patient population.

[Minimally invasive therapy for osteoid osteoma]. / Minimalinvasive Therapie bei Osteoidosteom.

AIM: We describe a minimally invasive procedure for the treatment of osteoidosteoma and present the outcome of the treatment in our collective. Additionally, a review of the literature for minimally invasive therapy for osteoidosteoma was performed. METHODS: Within approximately three years, ten male patients with the clinical and radiological diagnosis of osteoidosteoma were treated. First, during the procedure for the purpose of orientation, a CT scan of the affected area was performed. Then, under CT-guidance, the nidus of the osteoidosteoma was marked with a k-wire and destroyed with a drill, moulding cutter or the k-wire. The patients' charts and films were reviewed in a retrospective manner, all patients participated in a personal telephone interview. RESULTS: In all cases the intraoperative course was free of complications. After surgery 90 % of the patients were free of pain, in 10 % a significant reduction of the pain was reported. Both in those 10 % and the whole collective there were no clinical symptoms of relapse, the average follow-up in all cases was 19 months. Our results are in accord with data in the literature. CONCLUSION: In our collective the CT-guided, percutaneous removal of osteoidosteoma has been shown to be a safe and effective method. Under DRG conditions it can be performed within a short period of hospitalization or in the out-patient clinic.

Peripheral Subcutaneous Electrostimulation for Control of Intractable Post-operative Inguinal Pain: A Case Report Series.

Objective. To present a novel treatment approach for intractable inguinal neuralgia utilizing percutaneous peripheral electrostimulation. Materials and Methods. We report results of peripheral electrostimulation in three patients who experienced onset of inguinal neuralgic pain in the immediate postoperative period following herniorrhaphy. In each case pain was refractory to medical management and caused significant functional impairment. These three patients were first percutaneously trialed and then implanted with dual octipolar peripheral nerve stimulators (Advanced Neuromodulation Systems, Plano, TX) in close proximity to the injured nerve. Results. All three patients responded very favorably (75-100% pain relief at three, 10, and 12 months postimplantation). There were no complications. All three tapered off their pain-related medication, dramatically increased their levels of activity, and discontinued pain-related medical visits. Both patients who were on disability due to inguinal pain have been able to return to full-time employment. Conclusion. These preliminary results suggest that the technique described is effective and safe, and may be cost-effective as well.

Biotests using unicellular algae and ciliates for predicting long-term effects of toxicants.

Test systems for predicting long-term effects with the freshwater algae Chlamydomonas reinhardi and Scenedesmus subspicatus and the ciliate Tetrahymena pyriformis were evaluated with respect to the following reference chemicals: atrazine, bromacil, diuron, methyl parathion, lindane, 3,4-dichloroaniline, pentachlorophenol, cadmium, copper, and the volatile 1,2-dichloropropane. In growth-inhibition tests under static conditions the algae revealed a higher sensitivity to the toxicants than the ciliate except for lindane and methyl parathion. Comparison of the impairment of photosynthetic efficiency (EPR, NOEC 24 hr) with the inhibition of growth (NOEC 72 hr) of S. subspicatus revealed a higher sensitivity of the EPR parameter for inhibitors of the photosynthesis. A flowthrough system was developed for long-term tests and testing of volatile and instable substances. Under flowthrough conditions C. reinhardi was more susceptible to the chemicals than under static test conditions, except for pentachlorophenol. Due to the high volatility, 1,2-dichloropropane was only tested in the flowthrough system. The data obtained from these toxicity tests provide information about effects on organisms representing different levels of the aquatic food web, possessing differences in sensitivity against toxicants. The presented flowthrough system allows the testing of volatile and instable chemicals, problematic in static test systems, and the EPR parameter is suitable for the early characterization of chemicals acting as specific inhibitors of the photosynthetic electron transport chain.

Influence of inorganic and triethyl lead on nuclear migration and ultrastructure of Micrasterias.

Developing cells of three strains of the desmidiacean alga Micrasterias were treated with inorganic and triethyl lead and examined by light and electron microscopy. In the concentration range 12 to 30 microM, triethyl lead disturbed normal development of the algae, caused changed dictyosomal ultrastructure, disturbed the formation of the secondary cell wall, and caused accumulation of lipid material. Cell multiplication was strongly inhibited between 5 and 30 microM TriEL in Micrasterias denticulata, showing complete inhibition at 15 microM and above. In addition, nuclear migration of developing Micrasterias cells was selectively disturbed by growth-inhibiting concentrations of TriEL, resulting in unusual positioning of the post-telophase nucleus. Although inorganic lead proved to be much more poisonous to Micrasterias cells than TriEL and caused bursting of the cells even at the low concentration of 3 microM it did not affect nuclear migration. Electron microscopic observations revealed a complete disassembly of the post-telophase system of microtubules which is involved in nuclear migration by TriEL, but no detectable effect on the isthmus system of microtubules which anchors the nucleus in the isthmus. It is concluded that the disturbance of nuclear migration in Micrasterias by TriEL was due to the selective disassembly of the involved microtubule system.

On the toxic effects of tetraethyl lead and its derivatives on the chrysophyte Poterioochromonas malhamensis. VII. Protective action of thiol compounds, vitamins, trace elements, and other agents.

The influence of 45 different substances on the growth inhibiting effects of triethyl lead chloride (TriEL) in cultures of the unicellular alga Poterioochromonas malhamensis was studied. Ten thiol or disulfide compounds, 9 vitamins, 12 trace elements, 14 miscellaneous agents, and 9 combinations of these agents were tested. The agents were applied to the algal cultures in three different concentrations simultaneously with 10 microM TriEL and incubated for 72 hr. While none of the tested thiol and disulfide compounds remarkably protected the algae from TriEL toxicity, two vitamins (tocopheryl acetate, ascorbic acid), one trace element (zinc), adenosine-5'-triphosphate Na2 salt, cyclic AMP, and concanavalin A as well as combinations of some of these agents were found to suppress markedly the growth inhibiting effects of TriEL. Zinc was the most effective agent; it increased algal growth in TriEL-treated cultures by about 70 times as compared with cultures containing TriEL alone. A combination of 10 essential trace elements was even more protective and almost completely suppressed TriEL toxicity. In contrast to this, some of the other agents potentiated the toxic effects of TriEL (e.g., magnesium, molybdenum, caffeine, deuteriumoxide, chlorpromazine, dimethylsulfoxide) in the tested concentration ranges. The most protective agents Zn, VitC, and VitE did not prevent the inhibitory effects of TriEL on microtubule (MT) assembly in vitro, suggesting that their in vivo protection is based on mechanisms other than direct protecting MTs from the attack of the lead compound. Zn had no direct influence on the stability and half life of TriEL in the growth medium. The lack of protection found by the thiol compounds used suggests that most probably general thiol interaction of TriEL is not its major toxic mechanism of action. It is postulated that the protective action of Zn, VitE, and VitC is directly or indirectly mediated by suppression of TriEL-induced peroxidation processes in the poisoned algae. The protective agents found provide a basis for further screening experiments in order to test their "therapeutic" potency in experimental animals poisoned with organolead.

On the toxic effects of tetraethyl lead and its derivatives on the chrysophyte Poterioochromonas malhamensis. VI. Effects on lorica formation, mitosis, and cytokinesis.

Effects of tetraethyl lead (TEL) and derivatives triethyl lead (TriEL), diethyl lead (DiEL), and inorganic lead (Pb) on lorica formation of the unicellular alga Poterioochromonas malhamensis were investigated by light and electron microscopy. Lorica formation is microtubule (MT)--mediated and disturbed by agents interfering with MTs. TEL, largely ineffective as such, inhibited lorica formation of P. malhamensis when the lead compound was illuminated during or before the experiment. TriEL inhibited most; DiEL produced qualitatively effects similar to those of TriEL at about 10 times higher concentrations. Inorganic lead was even less toxic and did not selectively inhibit lorica formation of the algae. Low concentrations of TriEL (5 to 7.5 microM) selectively disturbed lorica formation, causing formation of numerous stalk-less loricae which exhibited gross and ultrastructural alterations like those induced by the antimitotic drug colchicine. The effects of TriEL on mitosis and cytokinesis of P. malhamensis were also investigated. The most sensitive mitotic phase was metaphase, which, however, accumulated only up to 5% after treatment of the cells with toxic concentrations (10 microM) of TriEL for 24 hr (control, 2%). On the other hand, up to 15% telophases (including binucleated cells) and even multinucleated cells with up to eight nuclei per cell were found, indicating that cytokinesis was considerably more effectively disturbed by TriEL than mitosis. In giant multinucleated algae, mitoses normally proceeded synchronously; some asynchronous mitoses were found. Beside normal-looking mitotic spindles in giant algae, multipolar spindles, disoriented spindles, and metaphase-like chromosome arrays completely lacking MTs were observed by electron microscopy. The effects of TriEL on cytokinesis of the algae were largely reversible. Giant cells spontaneously recovered and underwent cytokinesis after transferred into TriEL-free growth medium. Colchicine acted qualitatively identical to TriEL (accumulation of metaphases and telophases: 5 and 19%, respectively), but TriEL was about 600 times more toxic than colchicine. Unlike colchicine, its derivative, colchicine, which is known not to interfere with MTs, remained without any selective inhibitory influence on mitosis and cytokinesis of the algae, although much more toxic than the parent compound. From the inhibitory effects of TriEL and the close qualitative similarities to the effects of colchicine, it is concluded that TriEL selectively interferes with cytoplasmic and mitotic MTs of the algae, thereby causing the observed inhibitory effects on lorica formation, mitosis, and cytokinesis.

Interaction of triethyl lead chloride with microtubules in vitro and in mammalian cells.

The effects of triethyl lead chloride (TriEL) on the in vitro assembly and disassembly of microtubules (MTs) from porcine brain were studied by turbidometry at 350 nm and by electron microscopy. TriEL inhibited MT assembly at 50 microM concentration and caused an almost complete disassembly of preformed MTs. The drug depolymerized MTs more effectively than colchicine. Concentrations higher than 50 microM TriEL caused an aberrant assembly process. Fibers about 10 nm width were formed in addition to aggregates of amorphous material. In vivo TriEL also caused MT depolymerization in interphase and mitotic PtK-1 and Ehrlich ascites tumor (EAT) cells as monitored by indirect immuno-fluorescent staining of tubulin and electron microscopy. The extent of MT depolymerization was concentration- and time-dependent. Recovery occurred as early as 5 min after removal of the drug. The fluorescent actin pattern in PtK-1 cells typical of stress fibers and subcortical filaments seemed not to be altered by the presence of TriEL. The vimentin intermediate filament system was, however, rearranged as a juxtanuclear complex after TriEL treatment. Furthermore, TriEL effected the inhibition of cellular growth (100% inhibition at about 10(-5) M). Cytokinesis is prevented to a great extent, resulting in the formation of binucleate cells which can additionally possess some micronuclei.

On the toxic effects of tetraethyl lead and its derivatives on the chrysophyte Poterioochromonas malhamensis. IV. Influence of lead antidotes and related agents.

The unicellular alga Poterioochromonas malhamensis was exposed to 12.5 microM of inorganic or triethyl lead and simultaneously treated with lead antidotes and related agents at concentrations of 12.5, 31.25 and 62.5 microM. With increasing concentrations some of the antidotes alone slightly to severely inhibited algal growth (BAL, CaNa2EDTA, EDTA, Na2EDTA), whereas others (DPA, EGTA, DIZO) were non-toxic at the concentrations tested. EGTA and CaNa2EDTA, at all concentrations tested, completely suppressed the growth inhibition caused by inorganic lead; Na2EDTA and EDTA were protective at the lower or medium concentrations, but DIZO, DPA and BAL considerably enhanced lead toxicity with increasing concentrations. None of the tested agents was able to reduce the toxic effects of triethyl lead. All antidotes markedly increased inhibition of algal growth caused by triethyl lead and some were even lethal to the poisoned algae either at the highest (Na2EDTA, EDTA, DPA) or at all concentrations used (DIZO, BAL). P. malhamensis proved to be a highly sensitive and valuable tests system and the results obtained exhibited striking parallels to medical and clinical experience in therapy of human poisoning with inorganic and organic lead compounds.