[Total endoprosthetic replacement of femur, humerus and tibia]. / Endoprothetischer Totalersatz von Femur, Humerus und Tibia.

Improvements in diagnostics and effectiveness of chemotherapy have resulted in most patients with primary malignant bone tumours being candidates for limb salvage surgery. Herewith, the use of modern modular tumour endoprostheses allows for the replacement of all big joints and even entire long bones such as the femur, humerus and tibia. In this article, we focus on individual prerequisites for and challenges with performing a total endoprosthetic reconstruction of the above-mentioned anatomic structures. Additionally, data from the literature with regards to functional outcome, problems and complications are presented.

Hepatotoxic combination effects of three azole fungicides in a broad dose range.

Single active substances of pesticides are thoroughly examined for their toxicity before approval. In this context, the liver is frequently found to be the main target organ. Since consumers are generally exposed to multiple residues of different active substances via the diet, it is important to analyse combinations of active substances for potential mixture effects. For the (tri-)azoles, a group of agricultural fungicides and antifungal drugs, combination effects on the liver are likely because of a similar mode of action. Hepatotoxic effects of mixtures of two triazoles (cyproconazole and epoxiconazole) and an imidazole (prochloraz) were investigated in a 28-day feeding study in rats at three dose levels ranging from a typical toxicological reference value to a clear effect dose. Test parameters included organ weights, clinical chemistry, histopathology and morphometry. In addition, molecular parameters were investigated by means of pathway-focused gene expression arrays, quantitative real-time PCR and enzyme activity assays. Effects were compared to those caused by the individual substances as observed at the same dose levels in a previous study. Mixture effects were substantiated by increases in relative and absolute liver weights, histopathological findings and alterations in clinical chemistry parameters at the top dose level. On the molecular level also at lower dose levels, additive effects could be observed for the induction of several cytochrome P 450 enzymes (Cyp1a1, Cyp2b1, Cyp3a2), transporters (Abcb1a, Abcc3) and of genes encoding for enzymes involved in fatty acid or phospholipid metabolism (Ppargc1a, Sc4 mol). In most cases, treatment with mixtures caused a more pronounced effect as compared to the individual substances. However, the assumption of dose additivity was in general sufficiently conservative to cover mixture effects observed under the conditions of the present study.

Synovial aspiration and serological testing in two-stage revision arthroplasty for prosthetic joint infection: evaluation before reconstruction with a mean follow-up of twenty seven months.

INTRODUCTION: The two-stage revision protocol is the gold standard for controlling and treating low-grade prosthetic joint infections of total hip and total knee arthroplasty. The antibiotic pause for diagnostic reasons before reconstruction (stage two) is discussed in relation to the persistence of the infection and the development of resistant bacterial strains. Serological markers and a synovial analysis are commonly used to exclude the persistence of infection. Therefore, we asked (1) is the serological testing of C-reactive protein and leucocytes a valuable tool to predict a persistence of infection? and (2) what is the role of synovial aspiration of Plymethylmethacrylat (PMMA) spacers in hip and knee joints? MATERIALS AND METHODS: One hundred twelve patients who were MSIS criteria-positive for a prosthetic joint infection were studied, including 45 total hip arthroplasties (THA) and 67 total knee artrhoplasties (TKA) patients. All patients were treated with a two-stage-protocol using a mobile PMMA spacer after a 14-day antibiotic-free interval, during which we measured serological markers (C-reactive protein and leucocytes) and performed synovial aspiration (white blood cell count, polymorphonuclear cell percentage, and microbiological culture) in these patients and compared the results with those of their long-term-follow-up (mean follow-up 27 months, range 24-36 months). RESULTS: Of the 112 patients, 89 patients (79.5%; 95% CI 72-86.9) exhibited infection control after a two-stage exchange, and we detected most methicillin-resistant, coagulase-negative Staphylococci (CoNS) in cases of a persistent infection. The mean sensitivity of serum C-reactive protein in the patients was 0.43 (range 0.23-0.64), and the mean specificity was 0.73 (range 0.64-0.82). For serum leucocytes, the mean sensitivity was 0.09 (range 0-0.29), and the mean specificity was 0.81 (range 0.7-0.92). The mean sensitivity for the WBC count in the synovial fluid (PMMA spacer aspiration) was 0.1 (range 0-0.29), and the mean specificity was 0.79 (range 0.68-0.92). For the PMN percentage, the mean sensitivity was 0.1 (range 0-0.29), and the mean specificity was 0.79 (range 0.68-0.92). No cut-off values could be established for C-reactive protein, leucocytes, WBC count and PMN percentage due to the low AUC. CONCLUSION: No reliable markers were identified for the long-term persistence of infection. C-reactive protein and leucocytes were often elevated, even when the infection was controlled. In addition, normalized serum markers did not exclude the persistence of infection during follow-up. The synovial analysis of the WBC count and PMN percentage did not predict the persistence of infection. However, microbiological synovial fluid analysis is often misleading due to false positive microbiological cultures, which results in overtreatment.

[Spindle-cell osteosclerotic bone lesion with MDM2 amplification]. / Spindelzellige osteosklerotische Knochenläsion mit MDM2-Amplifikation.

This case report presents an osteosclerotic bone lesion in a 49-year-old man with MDM2 amplification. The final diagnosis shows metastasis to the bones from stomach cancer. In primary bone tumours, the MDM2 amplifications observed have been described for many other tumour entities as well, and therefore do not exclude bone metastasis from a carcinoma.

[Autologous fibula transplantation for reconstruction of bone defects]. / Die autologe Fibulatransplantation zur Rekonstruktion knöcherner Defekte.

The reconstruction of large bone defects following tumor resection, trauma or infection is difficult and subject to individual preferences of each surgeon. Free autologous fibula grafts are a reliable biological treatment method, whereas both a vascularised and a non-vascularised transplantation is possible. The use of either treatment option - vascularised or non-vascularised - is accompanied by individual advantages and/or disadvantages that should be taken into consideration during the preoperative planning process. Vascularised fibula transplants should be used especially for the reconstruction of large segmental defects and in patients, in whom adjuvant chemo- and/or radiation therapy is to be administered. Non-vascularised fibula grafts - which offer the advantage of a certain regeneration potential at the donor site as well as a shorter operation time - might be beneficial for bridging hemicortical defects and segmental defects with good soft tissue coverage.

Hepatotoxic effects of (tri)azole fungicides in a broad dose range.

The toxicological relevance of effects observed at molecular stage, which occur at dose levels well below classical no-observed adverse effect levels is currently subject to controversial scientific debate. While the importance of molecular effects for the identification of a mode of action or an adverse outcome pathway is undisputed, their impact for other regulatory purposes remains uncertain. Here, we report the results of a 28-day rat-feeding study including three widely used hepatotoxic (tri)azole fungicides (cyproconazole, epoxiconazole and prochloraz) administered individually at five dose levels, ranging from slightly above the reference values to a clear toxic effect dose. Parameters analysed included pathology, histopathology, clinical chemistry and particularly effects on the molecular level. Since azole fungicides are considered to cause liver toxicity by a mechanism involving the constitutive androstane receptor (CAR), a known CAR activator (phenobarbital, PB) was administered to investigate potential similarities between triazoles and PB-mediated liver toxicity by pathway-focused gene expression analysis. Our results show an increase in liver weights and additionally histopathological changes (hepatocellular hypertrophy) for all substances at the top dose levels. The effects on liver weight were most pronounced for cyproconazole by which also the animals receiving the next lower dose were affected. In addition, vacuolisation of hepatocytes was observed at the top dose level. No such findings were obtained with any substance at lower doses to which consumers and operators might be exposed to. In contrast, the expression of sensitive marker genes (like some cytochrome-P-450 isoforms) was significantly affected also at the lower dose levels. While some of these changes, like the induction of genes related to fatty acid and phospholipid metabolism (e.g. Fasn, Fat/Cd36, Ppargc1a) or xenobiotic metabolism (Cyp1a1, Cyp2b1, Cyp3a2), could be associated with high dose effects like hepatocellular vacuolisation or hypertrophy, a histopathological correlate was lacking for others.

The effect of selective inhibition of inducible nitric oxide synthase on cytochrome P450 after liver transplantation in a rat model.

BACKGROUND: Activity levels of cytochrome P450 (CYP) provide markers for liver function and graft rejection episodes after orthotopic liver transplantation (OLT). Some in vitro studies have shown decreased CYP activation of inducible nitric oxide synthase (iNOS) in rejecting liver grafts. The aim of this study was to evaluate CYP isoenzyme activity changes in vivo and to examine histopathologic aspects during inhibition of iNOS after treatment with aminoguanidine (AG) using OLT in the rat. MATERIALS AND METHODS: Thirty DA-(RT1av1) rats that served as donors and LEWIS-(RT(1)) rats as recipients were divided into three groups: group I (controls, syngeneic rats; n = 6), group II (allogeneic rats without immunosupression; n = 11), and group III (allogeneic rats with AG treatment; n = 13). On postoperative days 5, 8, and 10 we performed laboratory investigations and liver biopsies for histopathologic investigations. RESULTS: On postoperative day 5, activities of CYP-1A1 and -3A4 were significantly lower (P = .022) in group III and the activity of CYP-1A2 higher (P < .05) compared with group II. At postoperative days 8 and 10, the activities of all CYP isoenzymes were significant higher in AG-treated rats (group III) in contrast with group II after allogeneic OLT without immunosuppression. Histopathologic findings revealed less distinct rejection signs in group III specimens after AG treatment compared with group II. CONCLUSION: Summarizing our results, we concluded that AG treatment led to increased CYP activity and less distinction of graft rejection after OLT in rats.

[Rare occurrence of fulminant acid burn of the esophagus]. / Seltene Ursache einer fulminanten Säureverätzung des Osophagus.

Peptic ulcer due to Zollinger-Ellison syndrome is a rare entity. In this case report a 55-year-old man had a medical history of esophageal reflux, vomiting, and diarrhea for 10 years. Despite continuous medication with a proton pump inhibitor, no complete recovery from symptoms was achieved. A diagnosis of gastrinoma was at first not considered. After discontinuation of the proton pump inhibitor for only a few days, the strong stimulation of the gastrinoma led to fulminant hydrochloric acid burn of the distal esophagus with iatrogenic or spontaneous perforation at the esophagogastral junction. We describe the operative treatment as a two-stage reconstruction with colon interposition and resection of the primary tumor in the duodenum.

Mixture effects of two plant protection products in liver cell lines.

Pesticide products contain one or more active substances as well as adjuvants, which are added for example as solvents or antioxidants. Nevertheless, only the active substances are evaluated with a comprehensive battery of mammalian toxicity tests. However, in some cases mixture effects of active substances and adjuvants may occur, leading to increased toxicity of the products. To address this issue, we investigated effects of active substances with known hepatotoxicity and two commonly used fungicides: Priori Xtra® and Adexar®. For this purpose, respective active substances individually and in combination as well as the products were applied to two human hepatoma cell lines (HepaRG and HepG2) in a broad dose range. The results of cytotoxicity analysis, nuclear receptor transactivation (AhR, CAR, PXR), mRNA and protein expression of xenobiotic metabolizing enzymes (CYP1A1, CYP2B6 and CYP3A4) allow the conclusion that active substances and plant protection products differ in terms of their in vitro toxicity. The products activate AhR, while the individual active substances as well as the combination of the active substances have no or only minor effects. The present results support the hypothesis that plant protection products may have a modified toxicity as compared to active substances alone, consequently requiring more comprehensive testing.

[Incidental carcinoma of the prostate: can we and should we recommend radical prostatectomy?]. / Inzidentelles Prostatakarzinom: Kann und soll die radikale Prostatektomie danach empfohlen werden?

INTRODUCTION: There is controversy regarding tumor control of incidental prostate cancer (PC). We evaluated in a large cohort if we can recommend radical prostatectomy after TURP. MATERIAL AND METHOD: In 52 (4.3%) from a total of 1207 patients undergoing radical prostatectomy the diagnosis had been made by TURP. In a retrospective analysis we evaluated morbidity, histopathological results, and tumor control of pT1a/b tumors. RESULTS: The number of incidentally detected PC decreased with time. In 5.8% in the TURP group and in 0.5% of the needle biopsy group, there was no residual tumor found (p<0.001). Morbidity was similar +/- TURP with the exception of operation time (206 vs 188 min) and catheter duration (19.3 vs 17.3 days). Postoperative continence was identical. There was no difference in tumor control for local recurrence-free survival and PSA-free survival with and without TURP. CONCLUSIONS: The rate of incidentally detected PC by TURP decreases over time, but in almost all cases we found clinically relevant cancer. TURP is not an adverse prognostic factor and morbidity is similar compared with patients who were diagnosed by needle biopsy. Our data confirm that we should recommend radical prostatectomy to patients who are candidates for further curative therapy.

[Focal proliferations of retinal pigment epithelium. Risk factor in senile macular degeneration]. / Fokale Proliferationen des retinalen Pigmentepithels. Risikofaktor bei der altersabhängigen Makuladegeneration.

BACKGROUND: Clinical studies have demonstrated the relevance of focal RPE proliferations in early AMD as risk factors for visual loss caused by late AMD. Angiographically these focal RPE proliferations are characterized as small hypofluorescent spots with hyperfluorescent rim without leakage. Corresponding to histological and experimental studies they can be interpreted as small areas of occult choroidal neovascularizations covered by proliferated RPE cells. The characterization of the long-term prognosis of these lesions was the aim of the present study. PATIENTS AND METHODS: Ninety-eight patients (52 female, 46 male) were reexamined clinically and angiographically with a follow-up of 2-12 years (mean 6.5 years). RESULTS: Visual loss of two lines or more could be observed in 64.5% of patients with final visual acuity less than 20/100 in 24.5% of patients. Morphologically the changes in visual acuity were related to the progression towards classical choroidal neovascularizations in 32.7% of patients. In addition 11.2% of patients demonstrated a regression of the small occult membrane with the development of small areas of RPE atrophy covering the size of the original occult neovascularization. In 10.2% of the patients enlargement of the lesion was observed, resulting in a large occult choroidal neovascularization without signs of classical membranes, and in 45.9% of patients the clinical and angiographical situation was unchanged. The most important prognostic factor correlating with visual loss was the presence of a disciform lesion in the fellow eye and of multiple drusen in the examined eye. Other factors like the size or location of the focal RPE proliferation and the duration of follow-up did not correspond with visual loss. CONCLUSIONS: Focal RPE proliferations in early AMD interpreted as small occult choroidal neovascularizations are associated with a high risk of visual loss. Especially if these lesions are associated with multiple drusen and a disciform lesion in the fellow eye, nearly all patients are at risk for visual loss. These changes may therefore characterize a special high-risk group for future prophylactic treatments in early AMD, but because of the high risk for the development of classical choroidal neovascularizations in this group, these results are also very important for the planning of prophylactic laser trials for drusen in early AMD.

[Late vision loss after focal hemorrhagic chorioretinopathy]. / Später Visusverlust nach fokaler hämorrhagischer Chorioretinopathie.

Prospective clinical studies about photocoagulation of extrafoveolar choroidal neovascularizations in focal hemorrhagic chorioretinopathy (CR) have demonstrated that the risk of visual loss years after successful treatment is related to the development of retinal pigment epithelium (RPE) atrophy around the laser scar. The reason for this event was thought to be late damage of RPE cells due to the laser treatment. However, because RPE atrophy can also be seen in untreated patients, a prospective study was started to test this pathogenetic hypothesis and to analyze the pathogenetic factors and prognostic importance of RPE atrophy in focal hemorrhagic CR. Eighty-eight patients (52 women, 36 men, 15-45 years old; mean follow-up 62 months; 26 patients treated by photocoagulation) with focal hemorrhagic CR were reexamined. Fifty-two patients (15 treated by photocoagulation and 37 untreated) showed clinically visible RPE atrophy. In these 52 patients the initial and final visual acuity, the amount of initial subretinal fluid (34.6% < 500 microns, 50% 500-750 microns, 15.4% > 750 microns) and the amount RPE atrophy (23.2% < 500 microns, 53.6% 500-750 microns, 23.2% > 750 microns) were analyzed. The development of RPE atrophy was dependent on the time of follow-up (36 patients without RPE atrophy, mean follow-up 29 months; 52 patients with RPE atrophy, mean 84 months, P < 0.001). Of the 52 patients with RPE atrophy, 15 were treated by photocoagulation. The distribution of RPE atrophy was similar to what was found in the 37 untreated patients (P = 0.4). With pronounced RPE atrophy, a decrease in final visual acuity was seen (RPE atrophy < 500 microns, mean visual acuity 0.5; 500-750 microns mean visual acuity 0.3; > 750 microns, mean visual acuity 0.1; P = 0.005). Increased RPE atrophy was also associated with a higher incidence of visual loss (p = 0.009). The amount of RPE atrophy was not dependent on the time of follow-up (P = 0.3), but only correlated with the initial amount of subretinal fluid (atrophy < 500 microns: subretinal fluid < 500 microns 15.4%, 500-750 microns 7.7%, > 750 microns 0%; atrophy 500-750 microns: subretinal fluid < 500 microns 19.2%, 500-750 microns 32.7%, < 750 microns 1.9%; atrophy > 750 microns: subretinal fluid < 500 microns 0%, 500-750 microns 9.6%, > 750 microns 13.5%; P < 0.0001). Because RPE atrophy in focal hemorrhagic CR was seen in patients both with and without photocoagulation therapy, laser treatment cannot be the causative factor. With increased follow-up the risk of the development of RPE atrophy increases in all patients. The resulting amount of RPE atrophy was only dependent on the initial amount of subretinal fluid. If the fovea is included in the exudative detachment, there is a higher risk of long-term visual loss.

[Focal hemorrhagic chorioretinopathy. Clinical differentiation and visual prognosis]. / Fokale hämorrhagische Chorioretinopathie. Klinische Differenzierung und Visusprognose.

Macular choroidal neovascularization in young adults without any known underlying diseases is referred to under the general term of focal hemorrhagic chorioretinopathy. In endemic areas of the USA an infection with Histoplasma capsulatum is thought to be the causative agent, but in Europe the pathogenesis of this condition is unknown. With the aim of finding how European patients with this disease might be detected by clinical examination and to estimate the prognosis for sight in the affected eye and the fellow eye, a follow-up examination (follow up 1-24 years, mean 7 years) of 88 patients (age 15-48 years, mean 33.6 years) was undertaken. Most patients were between 20 and 40 years of age and mildly myopic. The number of chorioatrophic scars associated with the choroidal neovascularization in particular varied widely between patients. Therefore, this characteristic is most useful for clinical differentiation between patients. In contrast, the development of an atrophic conus at the optic disc was predominantly correlated with worsening myopia. One-third of all patients experienced decreased vision during follow-up. In two-thirds of the group, however, the final vision was still 0.1 or better. The initial visual prognosis in the eye affected was predominantly dependent upon the location of the neovascular membrane in relation to the fovea and therefore upon the possibility of photocoagulation treatment. Long-term follow up in these patients revealed visual acuity decreased further only in eyes with increasing atrophy of the retinal pigment epithelium surrounding the disciform or laser scar. One-fifth of the patients also developed choroidal neovascularization in the fellow eye.(ABSTRACT TRUNCATED AT 250 WORDS)

[Volumetry of the human tongue by MRI]. / MR-Volumetrie der Zunge zur Abschätzung der individuellen Zungengrösse.

AIM: The purpose of this study was to determine the volume of the tongue using MRI. The correlation of the individual volume of the tongue and the size of the oral cavity was to be investigated. MATERIAL AND METHODS: To analyze the tongue volume we combined coronal and sagittal data acquisition, which divided the tongue virtually into two lateral and one medial part. This procedure helped to decrease artefacts by partial volume effect. In 20 probands (m/f 7/13, average age of 36.3 years) the volume of the tongue was determined. Imaging protocol: Magnetom 63 SP (Siemens, Erlangen), T1-weighted sequences (TR/TE 500 ms/10 ms), slice thickness 5 mm, matrix 256 x 256, FOV 250 mm. RESULTS: There was a significant linear regression between the tongue volume and height of the mouth cavity. This correlation can be used to calculate the normal volume of a patient's tongue. DISCUSSION: Volumetry of the tongue can be carried out by means of MRI without application of injurious X-rays. It can be employed before as well as after tongue reduction surgeries for therapy control. The individual ideal tongue volume can be determined easily by determination of the height of the oral cavity.

[Craniofacial techniques in traumatology]. / Kraniofaziale Techniken in der Traumatologie.

The coronal incision is a versatile approach to midface or skull base fractures. It allows the open reduction of complex fracture sites and facilitates canthopexy, marginotomy or calvarian bone harvesting. By this method, primary treatment can be optimised and the rate of secondary corrective surgery can be reduced. All trauma patients who underwent this kind of intervention were re-examined to check functional and aesthetic results. The complication rate was low and the advantages of these techniques are evident, so that it is suggested that the indication for this operative approach should be extended.

[Craniofacial techniques in traumatology]. / Kraniofaziale Techniken in der Traumatologie.

The coronal incision is a versatile approach to midface or skull base fractures. It allows the open reduction of complex fracture sites and facilitates canthopexy, marginotomy or calvarian bone harvesting. By this method, primary treatment can be optimised and the rate of secondary corrective surgery can be reduced. All trauma patients who underwent this kind of intervention were re-examined to check functional and aesthetic results. The complication rate was low and the advantages of these techniques are evident, so that it is suggested that the indication for this operative approach should be extended.

[Fluorescence angiography in age-related macular degeneration. Study of the incidence of lesions treatable with coagulation]. / Fluoreszenzangiographie bei der altersabhängigen Makuladegeneration. Studie zur Häufigkeit koagulativ behandelbarer Läsionen.

BACKGROUND: The treatment of late age-related Macular Degeneration (AMD) according to the results of prospective clinical studies is indicated in classical choroidal neovascularisations (NV), which can be delineated from the center of the fovea. To evaluate the effectiveness of this therapy, the knowledge of the frequency of treatable lesions in the spectrum of late AMD is important. PATIENTS AND METHODS: The frequency of different manifestations of late AMD and of lesions treatable with photocoagulation according to the results of prospective clinical studies was recorded in a consecutive series of 2503 fluorescein angiogramms in patients with symptomatic late AMD. RESULTS: Classical choroidal NV could be detected in 35.4% of the patients. In 5.5% of the patients these NV were extra- or juxtafoveolar and therefore laser treatment could be recommended. 10.2% of the patients demonstrated small (< 1 PD) subfoveal classical NV and 20.4% of the patients showed large (> 1 PD) subfoveal NV or membranes associated with large subfoveal, subretinal hemorrhages. Occult choroidal NV could be seen in 41.8% of the patients. These occult NV were larger 1 PD in 21.9% of the patients and small (< 1 PD) in 19.9% of the patients. Pigment epithial detachments (PED) could be seen in 14.6% of the patients (9.9 vascular PED, 3.7% avascular PED, 1.0% rip of the retinal pigment epithelium). Disciform scars were present in 7.2% of the angiogramms. CONCLUSIONS: The spectrum of late AMD can be differentiated in several clinical features. In this consecutive series of 2503 symptomatic AMD patients only appr. 6%% of the patients could be treated with laser treatment according to the results of prospective clinical studies. Because in addition the success of this treatment is very limited, the development of new therapeutic options is one of the major tasks in ophthalmology.