[Augmented repair as therapy of fresh injury of the posterior cruciate ligament]. / Therapie der frischen Verletzung des hinteren Kreuzbands mit augmentierter Naht.

The discussion about the therapy of the posterior cruciate ligament persists. Conservative treatment, augmented repair, and reconstruction with autografts are discussed. From 1993 to 1997, 49 patients with posterior cruciate ligament rupture had repair Trevira ligament augmentation of 3 mm. There were 21 isolated and 28 combined ruptures. In 5 cases bony avulsions were refixed by screw or additional hook plate. Investigation of 36 patients, in 15 cases with isolated ligamentous ruptures was made. Osseous avulsion had good results in all cases. Isolated posterior cruciate ligament rupture showed good stability in 7 of 15 cases and instability of 2 + in 8 cases. The medial range Lysholm score was 76.8 (+/- 21.6), the OAK score showed 2 very good and 5 good results, 3 fair and 5 bad results. Using the IKDC score led to 3 very good and 4 good results, 2 fair and 6 bad results. Using subjective criteria, 10 patients described results as very good or good, 2 fair and 3 bad. Posterior cruciate ligament rupture with additional knee injury or fracture of the leg showed bad results in 60 % of cases, and good or fair results in only 40 %. We think augmented repair of fresh injury of the posterior cruciate ligament can be used as an alternative therapy to reconstruction with autograft.

[Diagnostic and incidence of the rupture of the posterior cruciate ligament]. / Diagnostik und Inzidenz der Verletzungen des hinteren Kreuzbands.

The purpose of this article is to evaluate the incidence and to give a general review of the examination of the posterior ligament complex. At least ca. 8-10 % of all severe ligament injuries concern the posterior cruciate ligament, which means, that an estimated 4,000-5,000 Germans suffer a PCL rupture every year. Motor-vehicle accidents are the most common cause of the injury, but sports-related traumas (football, skiing) have increased in recent years. The high number of high-energy mechanisms involved (up to 90 %), cause ligament ruptures often to be associated with other injuries, especially fractures of the femur and tibia head. In polytrauma patients PCL ruptures are frequently recognized very late, because the possibility of this kind of injury is often not considered during the clinical examination. The same holds for the diagnosis of monotrauma patients. The initial step in the evaluation is to obtain a thorough history (including the mechanism of injury) and to perform a physical examination. The instability after a PCL rupture may present as an ACL rupture, because the anterior drawer test seems to be positive. The anterior/posterior drawer test must be assessed with other evaluation procedures to distinguish between anterior und posterior instabilities. The posterior sag sign, the quadriceps active test or the reversed pivot-shift may indicate a PCL rupture. A correct roentgenogram can reveal an avulsion of the tibia and can prove posterior instability due to a posterior translation of the tibia. A quantitative examination (clinical or X-ray) of the instability and the indication of combined injury of the posterior cruciate ligament and the posterolateral complex are necessary for the therapeutic decision (operative/conservative). A rupture of the PCL may occur occasionally as a result of a luxation of the knee (reduced spontaneously) before the medical evaluation. A thorough neurovascular examination is essential. Magnetic resonance imaging can be important to the diagnosis of an acute injury, but it is not essential for the choice between operative and non-operative treatment. Arthroscopy has been found to have a high degree of accuracy in the diagnosis of ligament ruptures of the knee, but it is still an operative treatment, so that it can only be used if an operation of repair or reconstruction is planned anyway. Before operative treatment of chronic complex instability, potential osseous abnormalities (varus morphotype) must be revealed; in case of uncertainty, an X-ray control is necessary.

[Determination of torsion angle after shaft fractures of the lower extremity--clinical relevance and measurement techniques]. / Torsionswinkelbestimmung nach Schaftfrakturen der unteren Extremität--klinische Relevanz und Messmethoden.

In the treatment of femoral and tibial fractures the frontal and sagittal planes are controlled and documented by conventional X-ray films. Computed tomography permits exact measurement of the coronal plane. Between June 1993 and December 1997, 161 computed tomographic measurements of femoral torsion and 55 of tibial torsion after shaft fracture were carried out. The results were analyzed in a clinical study. A CT examination was carried out if the clinical examination aroused suspicion of a difference in torsion. 28.5% of the patients examined with femoral fractures and 23.8% of those with tibial fractures and torsion differences of more than 20 degrees. Between June 1993 and June 1997, 30 corrective derotating osteotomies of the femur and 9 of the tibia were carried out. The average preoperative difference of torsion of the femur was 29 degrees and of the tibia 25 degrees. After the operation the average femur difference was 7 degrees and of the lower leg 6.5 degrees, which are inside normal physiological limits. The osteotomies were carried out in the metaphysis near the fracture. Additional corrections in other planes were necessary on the femur in 27% and on the lower leg in 46%. With the aim of avoiding torsion differences, or at least to recognize them at an early stage, CT measurements of torsion after osteosythetic treatment of fresh unilateral femur-shaft fractures were carried out in 49 patients between October 1996 and December 1997. The torsion measurements during the operations had to be carried out clinically. No sufficiently exact method of measurement is available in the operating room. Three patients with increased differences of 28 degrees, 26 degrees or 19 degrees had their osteosyntheses corrected. The measurements after correction were inside the normal spread.

Effect of uric acid and chemical analogues on oxidation of human low density lipoprotein in vitro.

Oxidative modification of low density lipoprotein (LDL) is implicated in the early development of atherosclerosis. In the present study, attention has been focused toward the potential protective effects of uric acid and purine-based chemical analogues in copper-promoted oxidative changes to human LDL in vitro. Between 5-100 mumol/l uric acid protected LDL from oxidative degradation in a concentration dependent manner. However, 5 mumol/l were not capable of inhibiting the consumption of LDLs natural antioxidative components, alpha-tocopherol and beta-carotene, but led to a more than two-fold prolongation, up to 3 h, of the lag phase before onset of polyunsaturated acid (PUFA) oxidation. 100 mumol/l uric acid, which is still below the human serum level of 300 mumol/l, reduced consumption of alpha-tocopherol and beta-carotene by about 50% and largely suppressed PUFA oxidation for up to 4 h. A more lipophilic series of methyl analogues of uric acid exhibited less activity. Neither 1,3-dimethyl uric acid, nor the 1,3,7- or 1,7- or 3,7-methylated compounds, all at 100 mumol/l, exceeded the antioxidative potential of 10 mumol/l uric acid. At concentrations up to 100 mumol/l xanthine and its analogues lacked virtually any protective effects toward the LDL constituents. In conclusion, the present study indicates that uric acid at concentrations similar to its physiological levels, and also related analogues are able to suppress oxidative degradation of LDL components. In view of the various mechanisms underlying atherogenesis in vivo, the protective effect in terms of modulating redox reactions and oxidative events in the blood or at the arterial wall appears of potential importance.

[Management of the anterior cruciate ligament rupture: indications, choice of procedure, timing, concomitant and after-care]. / Versorgung der VKB-Ruptur: Indikation, Verfahrenswahl, Zeitpunkt, Begleit- und Nachbehandlung.

The indication for operative or conservative treatment of the anterior cruciate ligament remains still difficult. Many years of intensive basic and clinical research and a better knowledge of biology, biomechanics and pathology have not been achieved standards of therapy. Therefore varying treatment options exist. In this paper we give an overview on the main indications and common treatments. Untreated ruptures of the ACL result in severe functional impairment. Therefore we find a wide indication for an operative reconstruction. Patient orientated factors (age, activity level, morphotype) and the range of instability are important for the decision-making between operative and conservative treatment. The time of intervention is determined by the chosen treatment. Multidirectional instabilities, ruptures of meniscus or damage of cartilage need an early, isolated injuries of the ACL an early or later (until 4 weeks) surgical therapy. An anatomical ligament reconstruction (so called "suture") is possible only for selected ruptures near the femoral insertion. Operative treatment needs a special suture technic and autologous or allogenous augmentation. In 15 until 25% of all ACL ruptures good results can be obtained in this way. In all other types of ruptures only a reconstruction using autologous material (lig. patellae, semitendinosous tendon) is recommended. Rehabilitation after ACL ruptures depends on the method of treatment (conservative procedure, reconstruction material, fixation technique, associated lesions) and has to be adapted to the biological healing process. Normally an immobilisation (cast, orthesis) has no benefit for ligament healing.

[Fusion of the craniocervical transition with "CerviFix" after survived atlanto-occipital dislocation]. / Die Fusion des craniocervicalen Ubergangs mit dem "CerviFix" nach überlebter atlanto-occipitaler Dislokation.

We report a rare case of a young moped rider who suffered atlanto-occipital dislocation. He survived with tetraplegia. We discuss the accident mechanism, the anatomical particulars, and the clinical features and compare our operative treatment with the cases described in the literature.

[Change in procedure to reamed intramedullary nail in diaphyseal femoral fractures after stabilization with external fixator]. / Der Verfahrenswechsel zum aufgebohrten Marknagel bei diaphysären Femurfrakturen nach Stabilisierung mit Fixateur externe.

Due to the special pathophysiological condition of the polytraumatized patient, intramedullary nailing of the femur is not generally recommended. Fracture treatment by traction is not suitable because of the poor intensive care and the persisting instability. The external fixator is able to stabilize the fracture without additional burden to the patient. The stability is sufficient for the first set of treatment. Stabilization requires a changing procedure to an internal osteosynthesis. It is possible to reduce the danger of pin-tract infections with a differentiated concept. The principle of permanent drainage secures the healing of diaphyseal fractures of the femur. 43 diaphyseal femoral fractures were treated with a changing procedure from external fixator to reamed intramedullary nailing. In 1 case (2.3%) we saw an osteitis. The others healed without severe complications. The occurrence of complications depends on the time of the changing procedure.

The treatment of infected tibial pilon fractures.

A total of 33 patients with infection after pilon fracture were retrospectively reviewed from 1988 to 1992. Twenty patients were transfered from peripheral hospitals with active osteitis, 13 patients were treated primarily in our hospital. Factors inducing infection in this group of patients are discussed critically. All patients underwent radical debridement. Restoration of bone stability was required in 72%. Due to the extent of infection, segmental resection had to be perfomed on 7 patients. Resulting soft tissue defects were closed with free flaps in 11 cases. Infection was controlled in 31 patients (93%), but only 8 could be classified as "cured" (24%). Two patients had amputations after failure of treatment. Despite successful therapy, the functional results are poor. Therefore, avoiding infection, has top priority in the post fracture treatment. The correct form of osteosynthesis adapted to the soft tissue lesion can lower infection rates significantly. Soft tissue defects, resulting from open fractures or after primary treatment, have to be closed by flap transfer within a short period of time. The management of the soft tissue is at least as important as the reconstruction of the bone in the treatment of pilon fractures.

[Surgical treatment of diaphyseal tibial fractures. Choice of procedure and results of treatment of 187 fractures]. / Die operative Behandlung diaphysärer Tibiafrakturen. Verfahrenswahl und Behandlungsergebnisse von 187 Frakturen.

From 1988 to 1990 a total of 187 fractures of the tibia (92 compound, 95 closed fractures) were treated with a primary osteosynthesis. In 102 fractures an external fixation was performed, 85 internal fixations were divided into 58 intramedullary nails and 27 plates. In a follow-up study the fracture healing was analysed, 90% of the patients were examined about 18 months after the accident. The mean healing time was between 12 weeks (internal fixation) and 16 weeks (external fixateur). After primary Fixateur externe 54 were treated by secondary internal fixation, intramedullary nailing was the method of choice. Contamination rate of the tibia, taken by an intraoperative wound swab before nailing was 30%. Infection occurred in 3.2%, non union and refractures in 1.5% and 1%. Over all 80% excellent and good results were found after consolidation. 10% fair and 10% bad results including three amputations after III degrees compound fractures and three death after polytrauma.

Experience with the pinless fixator in the treatment of fractures of the lower leg.

This is a report of the experience we have gathered in the application of the pinless fixator in cases of tibial fracture with soft tissue damage. In the Berufsgenossenschaftlichen Unfallklinik Ludwigshafen (Clinic for Trauma Surgery) 12 diaphyseal fractures of the tibia were stabilized with the pinless fixator in 1991. In all cases, conversion to an intramedullary nail was intended from the very beginning and was performed in 11 cases. In one case, a conventional external fixator had to be selected instead. The injuries included first and second degree open and closed fractures, mostly from group A of the AO classification. At conversion four bacteriological smear tests from the medullary cavity proved positive. In four cases, transitory peroneal deficiencies were diagnosed. When investigating their cause, it seemed that the present geometry of the pinless arms might be responsible for pressure damage to the soft tissues. Possibly this difficulty could be solved by altering the configuration of these arms. The pinless external fixator has definitely proved its usefulness when later conversion to an intramedullary nail is intended since the final fixation can be performed with the pinless device still in place.

Hydrogen peroxide production by red blood cells.

Red blood cells are frequently employed in studies of oxidative stress. Technical difficulties have previously prevented the measurement of H2O2 production by red blood cells, except during exposure to certain drugs or toxicants. We now show that a combination of glutathione depletion and 3-amino-1,2,4-triazole (aminotriazole) treatment can be used to measure the endogenous generation of H2O2 by red blood cells. In our studies, aminotriazole was used as an H2O2 dependent (irreversible) catalase inhibitor, and catalase inhibition was used as an indirect measure of H2O2 production. Our results indicate that H2O2 is generated at a rate of 1.36 +/- 0.2 microM/h (3.9 +/- 0.6 nmol.h-1.g Hb-1), and that the steady-state red blood cell concentration of H2O2 is approximately 2 x 10(-10) M. Kinetic comparisons of H2O2 production and oxyhemoglobin autooxidation (which generates O2.- that dismutases to H2O2) indicate that the latter is probably the main source of H2O2 in red blood cells.

Reduction of sperm whale ferrylmyoglobin by endogenous reducing agents: potential reducible loci of ferrylmyoglobin.

The reactivity of the endogenous antioxidants ascorbate, ergothioneine, and urate toward the high oxidation state of sperm whale myoglobin, ferrylmyoglobin-formed upon oxidation of metmyoglobin by H2O2--was evaluated by optical spectroscopy and SDS-PAGE analysis. Depending on whether these antioxidants were present in the reaction mixture before or after the addition of H2O2 to a metmyoglobin suspension, two different effects were observed: (a) In the former instances, ascorbate, ergothioneine, and urate reduced efficiently the oxoferryl moiety in ferrylmyoglobin to metmyoglobin and prevented dimer formation, a process which requires intermolecular cross-link involving specific tyrosyl residues. In addition, all the reducing compounds inhibited--albeit with different efficiencies--dityorosine-dependent fluorescence build up produced via dimerization of photogenerated tyrosyl radicals. (b) In the latter instances, the antioxidants reduced the preformed sperm whale ferrylmyoglobin to a modified metmyoglobin, the spectral profile of which was characterized by a blue shift of the typical 633 nm absorbance of native metmyoglobin. In addition, under these experimental conditions, the antioxidants did not affect dimer formation, thus indicating the irreversible character of the process. The dimeric form of sperm whale myoglobin--separated from the monomeric form by gel electrophoresis of a solution in which ergothioneine was added to preformed ferrylmyoglobin--revealed optical spectral properties in the visible region identical to that of the modified myoglobin. This suggests that the dimeric form of the hemoprotein is redox active, inasmuch as the oxoferryl complex can be reduced to its ferric form. These results are discussed in terms of the potential reactivity of these endogenous antioxidants toward the reducible loci of ferrylmyoglobin, the oxoferryl moiety, and the apoprotein radical.

Possible mechanism of inhibition of nitrite-induced oxidation of oxyhemoglobin by ergothioneine and uric acid.

The time course of oxyhemoglobin oxidation by nitrite consisted of a kinetic lag followed by a transition phase which progressed into a rapid autocatalytic phase. The imidazolthione and imidazolone derivatives, ergothioneine and uric acid, respectively, caused an increase in the duration of the lag phase in a concentration-dependent manner, without affecting the onset and rate of the autocatalytic phase. Neither compound reacted with H2O2 or nitrite, oxidizing species required in the initiation steps of oxyhemoglobin oxidation. On the other hand, both compounds reduced effectively and at comparable rates the high oxidation state of hemoglobin, i.e., ferrylhemoglobin, which is an intermediate species occurring in the autocatalytic phase. In addition, the rate of ergothioneine oxidation, upon its reaction with ferrylmyoglobin, was accelerated by nitrite, thus suggesting a reaction between the thione and nitrogen dioxide. Nitrogen oxide and ferrylhemoglobin are key species in the free radical chain propagation leading to oxyhemoglobin oxidation by nitrite. These data support the view that ergothioneine and urate delay oxyhemoglobin oxidation by nitrite upon the temporary removal of the propagating species, i.e., nitrogen dioxide and, secondarily, ferrylhemoglobin, and within a mechanism encompassing alterations of the nitrite in equilibrium with nitrogen dioxide and ferrylhemoglobin in equilibrium with methemoglobin redox transitions.

Serum urate as an antioxidant for ascorbic acid.

Urate serves as a potent antioxidant by means of radical scavenging and reducing activities. This antioxidant action is partly manifested by interaction with another powerful antioxidant, ascorbic acid, and is particularly evident in species that lack the ability to synthesize ascorbic acid. Urate not only behaves as a radical scavenger but also stabilizes ascorbate in biological fluids. This stabilizing effect appears to be due to an inhibition of iron-catalyzed oxidation of ascorbate. Ascorbate stabilization is particularly evident in human serum and is largely due to iron chelation by urate. Unlike radical-scavenging reactions, this protective effect of urate is not associated with its depletion because a stable, noncatalytic urate-iron complex is formed. Depletion of serum urate results in rapid subsequent oxidation of ascorbate, which is largely iron dependent. Sequential losses of urate and ascorbate significantly reduce the antioxidant capacity of serum.

Comparative cardiotoxicity of doxorubicin and a morpholino anthracycline derivative (KRN8602).

The toxicities of doxorubicin (DXR) and 3'-deamino-3'-morpholino-13-deoxy-10-hydroxycarcminomycin (KRN8602) were compared in perfused rat heart preparations. In addition, their toxicities in isolated myocytes as well as their abilities to cause oxidation of intracellular reduced glutathione (GSH) were evaluated. Finally, their capacities to initiate oxygen consumption and lipid peroxidation in isolated microsomes were determined. DXR caused a dramatic decrease in left ventricular pressure in the perfused hearts and a leak of lactic acid dehydrogenase (LDH) from isolated myocytes. These effects were not observed with KRN8602 at comparable concentrations although KRN8602 caused oxidation of GSH to oxidized glutathione (GSSG) in the myocytes. Both anthracyclines caused an increase in oxygen consumption and lipid peroxidation in isolated microsomes although these effects were more pronounced with KRN8602. The results of these experiments demonstrate that, despite the high capacity to redox cycle and to generate oxygen-derived oxidants, KRN8602 exhibited no measurable cardiotoxicity. The findings are consistent with a view that, if the formation of such oxidants is central to the cardiotoxicity of DXR, these substances must be formed in cellular compartments, e.g. plasma membranes, where the morpholino derivative (KRN8602) does not accumulate.

Reduction of ferrylmyoglobin in rat diaphragm.

The oxidation of myoglobin was monitored by transmission spectroscopy in isolated, superfused preparations of rat diaphragms. In its deoxygenated form, during anoxia, myoglobin was oxidized by adding hydrogen peroxide (1.0 mM) to its ferryl form (FeIV). On the other hand, peroxide-induced formation of ferrylmyoglobin was not observed when the perfusate contained oxygen. Ferrylmyoglobin was visualized after its derivatization with Na2S to form sulfmyoglobin. Depending on the time of addition, ascorbate (4.0 mM) or ergothioneine (2.0 mM) either prevented the formation of or dissipated ferrylmyoglobin. These agents are known to be reductants of this hypervalent form of myoglobin. In addition to providing the first demonstration of ferrylmyoglobin in skeletal muscle, these observations are consistent with the concept that oxidation of myoglobin to hypervalent states might be an important event in the initiation of muscle damage associated with anoxia and reoxygenation. The rapid reduction of myoglobin would prevent peroxidatic alterations of essential cellular constituents by ferrylmyoglobin.

Ferrylmyoglobin-catalyzed linoleic acid peroxidation.

The addition of linoleic acid (18:2) to a solution containing oxymyoglobin (MbIIO2), metmyoglobin (MbIII), or metmyoglobin-azide complex (MbIII-N3-) resulted in the formation of a common complex with identical absorption spectral properties. The addition of H2O2 to a MbIII/linoleic acid mixture revealed a spectral profile with lambda max at 530 nm and different from that observed in the reaction of MbIII with H2O2 and identical to that of ferrylmyoglobin. This was accompanied by a progressive decrease in the absorption in the visible region, indicating heme degradation during the lipid peroxidation process. The oxidation products of linoleic acid during the MbIII/18:2/H2O2 interaction were assessed by HPLC under anaerobic and aerobic conditions. In both instances, the chromatograms at lambda 234 nm revealed the formation of a main peak with a retention time of 11.1 min, which cochromatographed with a standard of 9-hydroperoxide of linoleic acid. The latter adduct was not degraded by the oxoferryl complex of myoglobin. The conclusions originating from this research are two-fold. On the one hand, the identical spectral properties exhibited by the product originating from the reaction of either MbIIO2 or MbIII with linoleic acid bridge the apparent discrepancy between the different reactivities of MbIIO2 and MbIII toward H2O2 and their ability to promote lipid peroxidation. On the other hand, the pattern of oxidation products of linoleic acid observed during the MbIII/H2O2 interaction, i.e., the formation of a 9-hydroperoxide adduct as a major product, points to a specific binding character and a regioselectivity of the oxoferryl complex in the oxidation of unsaturated fatty acids or a catalytic preference for decomposition of the various isomeric hydroperoxides over that of the 9-hydroperoxide.

The reduction of ferryl myoglobin by ergothioneine: a novel function for ergothioneine.

In this paper, we demonstrate that ergothioneine (ES), a naturally occurring thiolhistidine, reduces ferrylmyoglobin (MbIV) to MbIII when the former (ferryl species) is produced by exposing either deoxy MbII or MbIII to H2O2. The reduction of MbIV to MbIII by ES yields the disulfide of ES which the addition of GSH promptly reduces back to ES. The addition of ES (100 microM) in the perfusion buffer of Langendorff rat heart preparations exposed to a brief period of ischemia prevents the myocardial damage (lactate dehydrogenase release) which accompanies reperfusion. The results of these experiments support a view that ES and its redox couple GSH might function in a Mb redox cycle.