[Treatment of Fractures of the Distal Third of Tibia Diaphysis by MIPO Technique]. / Lécba zlomeniny distální tretiny diafýzy tibie pomocí MIPO techniky.

PURPOSE OF THE STUDY MIPO (Minimally Invasive Plate Osteosynthesis) technique is currently a commonly used method to treat fractures of the distal third of tibia diaphysis. At the same time, it is just like other methods accompanied by a relatively high complication rate. The purpose of this study was to determine whether the use of this technique at our department is effective and whether the complication rate does not differ considerably from values reported by literature. MATERIAL AND METHODS In the period 2014-2016, minimally invasive plate osteosynthesis was performed in a total of 42 patients, who had suffered a fracture of the distal third of tibia diaphysis. They sustained a low-energy trauma. The mean age of patients was 50 years (range 27-86 years) and the mean follow-up period was 11.8 months (range 1.5-38 months). All the patients were treated with a minimally invasive technique with the use of subcutaneous LCP. In 41 patients (98%) it was inserted via anteromedial approach. In one patient only (2%), the LCP was inserted via anterolateral approach due to the unfavourable local finding on the medial side of the distal lower limb. RESULTS Of the total number of operated patients, 35 patients (83%) underwent surgery within 24 hours of injury, including two patients in whom an external fixator was used. The mean operative time was 61 minutes (range of 30-150 minutes). The primary healing occurred in 93% of patients with radiological signs of healing within 5.6 months on average (range of 1.5-16 months). Time to full weight bearing was 4.2 months on average (range of 1.5-16 months). Delayed healing was observed in four patients. In three patients, a non-union developed, necessitating revision surgery. Infectious complications were reported in seven patients, in three of whom deep wound infection developed. In one case, the chronic infection resulted in a lower limb amputation. In five patients mal-union occurred. DISCUSSION The outcomes achieved by the authors in treating fractures of the distal third of tibia diaphysis with a minimally invasive technique do not considerably differ from the outcomes reported by other authors in literature. In terms of the outcomes and the complication rate, the MIPO method is comparable to the treatment of these fractures with the use of nails. Limiting for fracture healing is the vascular supply. Therefore, in treating these injuries it is necessary to proceed with minimum invasiveness and carefulness and to seek to limit any additional trauma to soft tissues, thus also to vascular supply. In case of syndesmosis failure, the concurrent treatment of distal fibula fractures is clearly indicated. In case of intact syndesmosis, fibular osteosynthesis and the sequence of procedures are to be decided by the surgeon. At present, rigid osteosynthesis is being abandoned for potential slower healing up to development of non-unions. CONCLUSIONS The treatment of fractures of the distal third of tibia diaphysis remains an unsolved issue despite the development of stateof-the art materials, implants and surgical techniques. The MIPO technique can be considered an effective method of treatment of these types of fractures, achieving a high success rate of healing and acceptable rate of complications. Key words: minimally invasive plate osteosynthesis (MIPO), distal third of tibia diaphysis, locking compression plate (LCP).

[Results of Surgically Treated Patients for Hip Fracture - Complications, Mortality]. / Výsledky po operacích zlomenin proximálního femuru ­ komplikace, letalita.

PURPOSE OF THE STUDY Our main objective was to evaluate the mortality and complications of patients following surgical treatment of hip fractures and to identify the associated risk factors for postoperative mortality. MATERIAL AND METHODS We retrospectively reviewed all patients over the age of 50 who underwent surgical treatment for femoral neck and peritrochanteric fractures at our institution in 2003 and 2013. Mortality was compared between subgroups classified by age, gender, fracture type, method of treatment. Correlation between mortality and postoperative complications, time to surgery, and blood transfusion need were evaluated. Chi-square was used for categorical variables and two-tailed student's t-test for continuous variables. Survival curves were compared by the log-rank test. Mortality rates were adjusted for patient age and compared to the mortality rates of Prague's population in the given years. RESULTS Altogether 425 patients were surgically treated for proximal femoral fracture in 2013, while 229 patients were treated in 2003. The overall 1-year mortality decreased by 10% over the study period (38% in 2003 and 28% in 2013), despite the higher average age in 2013. Survival was better in all subgroups broken down by diagnosis and method of treatment, statistically relevant in the subgroup of femoral neck fractures, notwithstanding the method of treatment and in the subgroup treated with total hip arthroplasty. The strongest prognostic factor for survival was the advanced age. The mortality rate rises significantly over the age of 75. The largest age group was between 85-89 years, with 1-year mortality rate of 32%. The annual mortality of the general population in Prague aged 85-89 years was 13% and has improved only by 1% in the decade. The reoperative rate was 4% and did not affect mortality. There was no significant relationship between mortality and complications or delay of surgery for up to 4 days. DISCUSSION The factors that might have contributed to better survival are the introduction of guidelines for hip fracture care to our unit, better prophylaxis of venous thromboembolism, improvement of surgical skills due to the growing volume of these cases, and a higher rate of discharges to aftercare units. CONCLUSIONS Mortality has significantly decreased between 2003 and 2013 (p < 0.001). We didn't find a correlation between mortality and delay of surgery up to 4 days. That means that a complicated operation such as hip arthroplasty could be postponed and operated in more comfortable conditions (in superaseptic OR) by orthopedic surgeons. Although we haven't identified any modifiable risk factor, we believe that the reasons for better survival are multifactorial as discussed. Key words: hip fracture, proximal femoral fracture, mortality, complications, time to surgery.

[Operative Treatment for Saddle-Shaped Femoral Heads]. / Operacní resení sedlovité deformity hlavice kosti stehenní.

PURPOSE OF THE STUDY A saddle-shaped deformity of the femoral head has a poor prognosis due to rapid development of secondary changes. A new method of treatment by intra-articular anteromedial wedge reduction osteotomy (AWRO) of the femoral head may preserve the hip for the future. This study was designed to ascertain that this invasive technique was safe and effective and to confirm our hypothesis that AWRO significantly improved functional and radiological parameters of the hip joint. MATERIAL AND METHODS Patients who underwent AWRO between 2010 and 2013 were enrolled in this study. The indication criteria for the procedure included Stulberg grade V hips on AP radiographs, hinged abduction with pain, limping and a limited range of movement. Values of the Stulberg grading, capital diaphyseal index, caput-collum-diaphyseal angle and Harris hip score were recorded before and after surgery and the results were statistically evaluated using the paired t-test. The AWRO procedure was performed from the anterolateral approach after subperiosteal protection of the vessels had been ensured. The central necrotic part of the femoral head was removed, and the medial segment was mobilised and fixed to the intact lateral segment. Either a hip spica cast or bed-rest for six weeks was indicated. Full weight bearing was allowed at 3 months after surgery. RESULTS Twelve patients with an average follow-up of 55 months were evaluated. There were eight boys and four girls with an average age of 14 years at the time of surgery. The average Harris hip score improved from 54.52 before to 73.58 after surgery. The post-operative outcomes according to the Stulberg classification included one grade II hip, seven grade III hips, three grade IV hips and one grade V hip. The average capital-diaphyseal index dropped from 1.56 (1.19-1.92) to 1.28 (0.95-1.67) and the average caput-collum-diaphyseal angle increased from 134 degrees (121-143) to 140 degrees (130-155) after surgery. Avascular necrosis developed in two patients. All the differences were statistically significant. DISCUSSION Reduction osteotomies of the femoral head reported in the literature differ from the AWRO procedure used in this study in both the approach and the performance. The results presented here are in agreement with those published in the relevant literature. They showed no significant deterioration in comparison with the outcomes of our short-term study reported earlier. The outcome of treatment is related to the disease aetiology, functional parameters and previous procedures involving the hip joint. CONCLUSIONS AWRO is a salvage procedure that prolongs the longevity of joints in incongruent hips with very high morbidity. This procedure gave significantly better results in years after surgery, which confirmed our hypothesis. Level of evidence IV Key words: hinge abduction, Perthes disease, Stulberg, femoral head reduction osteotomy, avascular necrosis, arteria circumflexa femoris medialis.

Neuronal Nogo-A upregulation does not contribute to ER stress-associated apoptosis but participates in the regenerative response in the axotomized adult retina.

Nogo-A, an axonal growth inhibitory protein known to be mostly present in CNS myelin, was upregulated in retinal ganglion cells (RGCs) after optic nerve injury in adult mice. Nogo-A increased concomitantly with the endoplasmic reticulum stress (ER stress) marker C/EBP homologous protein (CHOP), but CHOP immunostaining and the apoptosis marker annexin V did not co-localize with Nogo-A in individual RGC cell bodies, suggesting that injury-induced Nogo-A upregulation is not involved in axotomy-induced cell death. Silencing Nogo-A with an adeno-associated virus serotype 2 containing a short hairpin RNA (AAV2.shRNA-Nogo-A) or Nogo-A gene ablation in knock-out (KO) animals had little effect on the lesion-induced cell stress or death. On the other hand, Nogo-A overexpression mediated by AAV2.Nogo-A exacerbated RGC cell death after injury. Strikingly, however, injury-induced sprouting of the cut axons and the expression of growth-associated molecules were markedly reduced by AAV2.shRNA-Nogo-A. The axonal growth in the optic nerve activated by the intraocular injection of the inflammatory molecule Pam3Cys tended to be lower in Nogo-A KO mice than in WT mice. Nogo-A overexpression in RGCs in vivo or in the neuronal cell line F11 in vitro promoted regeneration, demonstrating a positive, cell-autonomous role for neuronal Nogo-A in the modulation of axonal regeneration.

Tic disorders: administrative prevalence and co-occurrence with attention-deficit/hyperactivity disorder in a German community sample.

Coexistence of tics and attention-deficit/hyperactivity disorder (ADHD) has important clinical and scientific implications. Existing data on the co-occurrence of tic disorders, Tourette Syndrome (TS), and ADHD are largely derived from small-scale studies in selected samples and therefore heterogeneous. The Nordbaden project captures the complete outpatient claims data of more than 2.2 million persons, representing 82% of the regional population in 2003. Based upon the number of diagnosed cases of tic disorders, TS, and ADHD, we determined 12-months administrative prevalence rates as well as rates of co-occurrence. Both tic disorders and ADHD were diagnosed most often in the age group 7-12 years (any tic disorder: 0.8%; ADHD: 5.0%). With increasing age, the administrative prevalence difference in favor of males disappeared, with tic disorders being somewhat more frequently reported in females than males in the age groups above 30 years. The highest rate of ADHD co-occurring with tic disorders was found in adolescents (age 13-18 years, 15.1%). Tic disorders were observed in 2.3% of patients with ADHD. Administrative prevalence rates of tic disorders and TS were substantially lower compared to rates found in community-based epidemiological studies, suggesting that a large number of cases remain undetected and untreated under present conditions of routine outpatient care.

[The health economics of attention deficit hyperactivity disorder in Germany. Part 1: Health care utilization and cost of illness]. / Gesundheitsökonomie der Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung in Deutschland Teil 1: Versorgungsepidemiologie und Krankheitskosten.

In the German region of Nordbaden, 5% of children (aged 7-12 years) and 1.3% of adolescents (aged 13-19 years) were diagnosed with attention deficit hyperactivity disorder (ADHD) in 2003. About two thirds of these patients were not seen by a physician specialized in psychiatry. Now the National Association of Statutory Health Insurance Physicians in Germany (Kassenaerztliche Bundesvereinigung, KBV) has developed a proposal for the integrated provision of care for these patients, combining a guidelines-oriented multidisciplinary approach with a system of quality assurance. Against this background, currently available ADHD-related data are presented, covering epidemiology, comorbidity and differential diagnosis, health care utilization, and cost of illness. According to administrative data analyses from Nordbaden, direct medical costs for patients with ADHD, from the perspective of statutory health insurance (SHI), exceed those of matched controls by a factor of >2.5. On this basis, ADHD-related expenditures of the German SHI may be estimated at around EUR 260 million in 2003, and almost certainly will have continued to grow further since. In addition to this, a diagnosis of ADHD is associated with substantial indirect cost. Although the literature on the burden of ADHD is incomplete, it seems plausible that the cost of illness might be comparable to that reported for alcohol and addiction disorders. Thus we anticipate an increasing relevance of formal health economic evaluations of health care programs offered to patients with ADHD.

[The health economics of attention deficit hyperactivity disorder in Germany. Part 2: Therapeutic options and their cost-effectiveness]. / Gesundheitsökonomie der Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung in Deutschland. Teil 2: Therapeutische Optionen und ihre Kosteneffektivität.

Attention deficit hyperactivity disorder (ADHD) has been associated with a continuous increase of health care utilization and thus expenditures. This raises the issue of cost-effectiveness of health care provided for patients with ADHD. Comparative health economic evaluations generate relevant insights and typically report incremental cost-effectiveness ratios (ICERs) of alternatives versus an established standard. Typically, results of cost-effectiveness analyses (CEAs) are reported in terms of incremental cost-effectiveness ratios (ICERs). International evaluations, as well specific adaptations to Germany, indicate an acceptable to attractive cost-effectiveness--according to currently used international benchmarks--of an intense medication management strategy based on stimulants, primarily methylphenidate, with ICERs ranging from 20,000 EUR to 37,000 EUR per quality-adjusted life year (QALY) gained. Economic modeling studies also suggest cost-effectiveness of long-acting modified-release preparations of methylphenidate, owing to improved treatment compliance associated with simplified once daily administration schemes. Atomoxetine, in contrast, appears economically inferior compared to long-acting stimulants, given its higher acquisition costs and at best equal clinical effectiveness. There are currently no data supporting the cost-effectiveness of psychotherapeutic or behavioral interventions. Economic evaluations, which have been published to date, are generally limited by time horizons of up to 1 year and by their prevailing focus on ADHD core symptom improvement only. Therefore, further research into the cost-effectiveness of ADHD treatment strategies seems warranted.

A safer plasma supply from remunerated donors--"The Immuno/Community Bio-Resources experiment".

With the goal of increasing the safety of plasma used in the manufacture of therapeutic products, Immuno and its subsidiary Community Bio-Resources (now a division of Baxter Healthcare Corporation), have developed a comprehensive plasma quality programme. This programme includes four main safety initiatives: a plasma centre location/appearance programme, a Qualified Donor programme, an Inventory Hold, and the PCR testing of plasma pools. Many of these initiatives have been adopted in part by the plasma collection and fractionation industry. Using a statistical model that takes into consideration the unique donation characteristics of remunerated plasma donors, combined with 1998 CBR virus reactive rates, an estimated residual likelihood of an undetected donation entering a plasma pool was determined. These estimates, for each million donations, were 0, 1.64, and 4.68 donations for HIV, HBV, and HCV, respectively, and were far below those previously reported for remunerated or volunteer donations. These estimates were confirmed by subsequent PCR testing, which allowed for the additional removal of positive units before manufacture. The low virus load of this plasma supply, combined with increasingly effective virus removal and inactivation procedures, has resulted in the safest ever supply of plasma derivatives.

Kinetics and thioredoxin specificity of thiol modulation of the chloroplast H+-ATPase.

The kinetics of thiol modulation of the chloroplast H+-ATPase (CF0CF1) in membrana were analyzed by employing thioredoxins that were kept reduced by 0.1 mM dithiothreitol. The kinetics of thiol modulation depend on the extent of the proton gradient. The process is an exponential function of the thioredoxin concentration and reaction time and can be described by an irreversible second order reaction. The results indicate that the formation of the complex between thioredoxin and CF0CF1 is slow compared with the subsequent reduction step. Furthermore we have compared the efficiencies of the Escherichia coli thioredoxin Trx and the two chloroplast thioredoxins Tr-m and Tr-f. The second order rate constants are 0.057 (Tr-f), 0.024 (Trx), and 0.010 s-1 microM-1 (Tr-m) suggesting that Tr-f rather than Tr-m is the physiological reductant for the chloroplast ATPase. The often employed artificial reductant dithiothreitol exhibits a second order rate constant in thiol modulation of 1.02.10(-6) s-1 microM-1.

The H+/ATP coupling ratio of the ATP synthase from thiol-modulated chloroplasts and two cyanobacterial strains is four.

In this paper the authors emphasise that the proton translocating ATP synthase from thiol-modulated chloroplasts and two cyanobacterial strains has a coupling ratio of 4 protons per ATP synthesised or hydrolysed. This ratio is determined by several thermodynamic studies at equilibrium between phosphate potential (Delta Gp) and proton gradient (Delta(mu)H+), and is confirmed by measurement of proton flux during ATP hydrolysis. Ratios lower than 4 H+/ATP that have been published in the past have predominantly been determined with the oxidised chloroplast enzyme. Errors in these measurements will be discussed.

Bacterial stimulation of adventitious rooting on in vitro cultured slash pine (Pinus elliottii Engelm.) seedling explants.

A bacterium has been isolated that initiates adventitious rooting when co-cultured under in vitro conditions with seedling-produced hypocotylary explants of slash pine (Pinus elliottii). Rooting efficiencies produced through bacterial-explant co-culture range from approximately 15% to greater than 90% over non-treated controls. Explant exposure to the root inducing bacterium has produced no obvious pathology in the regenerated plantlets. Seedling explants rooted by bacterial-explant co-culture have been successfully transitioned to ambient greenhouse conditions.

Regional lymph node morphology in malignant melanomas and their prognostic value.

The occurrence of granulomatous epithelioid cell reaction, hyperplasia of lymphatic paracortex and existence of histiocytosis of the intermediary-medullary sinuses observed on sections of lymph nodes of 582 patients suffering from high-risk melanomas, examined during a ten-year period, have been established as reliable indicators of survival. On the other hand, lymphocytic infiltrative processes of the lymph node capsule, medullar plasmocytosis, and hyperplasia of germinal centres have been seen as indicators of a bad prognosis. Lymphocytic paracortical depletion and a predominance of postcapillary venules within the T zone were found to be less important in patients with a low chance of survival. We were able to establish a connection between lymphonodular parameters and the survival rate of the patients. In a multivariate test we found that there were four factors for statistical ascertainment of the prognosis of melanoma patients with lymphadenectomy: mitotic rate of primary tumour, lymphocytic infiltration of the lymph node capsule, existence of paracortical hyperplasia, and sex of the patient.

Multiple shoot production from seedling explants of slash pine (Pinus elliottii, Engelm.).

Hypocotylary explants obtained from 30- to 40-day-old slash pine (Pinus elliottii, Engelm.) seedlings treated with 6-benzylaminopurine produced multiple buds that eventually elongated into axillary shoots. The explants were pulse treated (45-s dip) with 6-benzylaminopurine (22.2, 111, 222 µM) plus a control and cultured on three different basal media containing activated charcoal (0.5% w/v). Hormonal concentration and basal medium were compared for the number and size of axillary shoots induced after 12 and 29 days. The greatest number of axillary shoots was produced by explants that were pulse treated with 111 µM 6-benzylaminopurine and cultured on Gresshoff and Doy medium. The axillary shoots were fewer in number per explant than shoots previously reported resulting from hormonally induced advantitious buds of slash pine, but the axillary shoots developed more rapidly.

Genetic characterization of a mutation that enhances paraquat tolerance in the fern Ceratopteris richardii.

Three nuclear mutations that affect tolerance to the herbicide paraquat have been selected in the fern Ceratopteris richardii. Two of the mutations, pq2 and pq45 are allelic and confer low and moderate tolerance, respectively. A third mutation, pqa6, is not linked to the other two and significantly enhances the level of tolerance when in combination with either pq2 or pq45. The pqa6 mutation does not independently confer tolerance in the absence of the other mutations.

Characterization of (14)C-naphthol uptake in excised root segments of clover (Trifolium pratense L.) and fescue (Festuca arundinaceae Screb.).

An isolated root uptake test (IRUT) was used to characterize the bioaccumulation of (14)C-naphthol in excised root segments obtained from 6-month-old hydroponically grown plants: two varieties of fescue (Festuca arundinaceae Schreb.) and one variety of clover (Trifolium pratense L.). Naphthol uptake rates were directly related to naphthol concentration in the range 0.01 to 0.2 uM. The incubation time required for equilibrium to be reached between naphthol in root tissue and in solution was between 9 and 12 h. Tests using metabolic inhibitors, KCN, NaN3, and DNP, indicated that naphthol uptake may be the result of both passive and active mechanisms. Q10 values for naphthol uptake ranged from 1.05 to 1.16.

Biochemical Studies of Paraquat-Tolerant Mutants of the Fern Ceratopteris richardii.

Enzymes and metabolites associated with mitigation of paraquat toxicity were compared in two paraquat-tolerant mutants and a sensitive wild-type strain of the fern Ceratopteris richardii Brongn. In 21-day-old gametophytes, the specific activities of superoxide dismutase, catalase, peroxidase, glutathione reductase, dehydroascorbate reductase, and ascorbate peroxidase showed no differences that would explain mutant tolerance. Constitutive levels of ascorbate and glutathione also did not differ significantly in the three strains. An experiment testing the inducibility of paraquat tolerance revealed no change in the dose response of mutant or wild type gametophytes after exposure to sublethal concentrations of the herbicide. Uptake of paraquat by whole gametophytes was also equivalent in mutants and wild type. These data suggest that the physiological basis for tolerance in these mutants, unlike several other tolerant biotypes reported, does not lie in the oxygen radical scavenging system, in an inducible stress response, or in a block to whole-plant uptake.

The origin of the Sternberg cell.

The Sternberg cell, the malignant cell of Hodgkin's disease, remains of uncertain nature 80 years after it was first described. Numerous hypotheses have been advanced as to its origin: that it derives from the macrophages, B lymphocyte, T lymphocyte, interdigitating reticulum cell or even from an as yet unidentified cell-line. We here review these various hypotheses, as well as the different techniques used for its study. The morphologic, ultrastructural, histochemical and immunologic studies are discussed in detail.

Plantlet regeneration from mature zygotic embryos of eastern white pine (Pinus strobus L.).

Plants were regenerated from whole embryo explants obtained from eastern white pine (Pinus strobus L.) seeds. Embryos were surgically removed and axenically cultured to induce buds in vitro on a modified Murashige and Skoog medium containing various concentrations of 6-benzylaminopurine. Embryos remained on bud induction medium for 21 days and then were transferred to the same basal medium without 6-benzylaminopurine to promote bud development and subsequent shoot elongation. The medium containing 10 µM 6-benzylaminopurine induced the greatest number of shoots per embryo. Rooting was achieved by direct transfer of the shoots to a non-sterile artificial soil mixture followed by multiple treatments with 15 nM 1-naphthaleneacetic acid. Regenerated seedlings are currently growing under greenhouse conditions.

Report on discussion of paper by P. M. Attiwill.

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