[Flexible flatfoot in children: variation within normal range or need for treatment?]. / Der kindliche Knick-Senk-Fuß: Normvariante oder therapiebedürftige Deformität?

Flexible flatfoot in childhood is a common cause for repetitive consultations and the diagnosis is verified by the clinical examination. In most cases the findings are age-dependent variants of the norm and if asymptomatic there is no need for treatment. In the first decade of life symptomatic flexible flatfoot should initially be treated with shoe inserts. Further diagnostic steps are required once conservative treatment is unsuccessful or a rigid structural deformity is found in the clinical examination. The underlying reasons may be neuropathic or structural anatomical in origin. Lateral column lengthening as described by Evans or minimally invasive arthroereisis are well established surgical options but for arthroereisis the number of long-term studies is low. In general the indications for surgical and conservative therapy have to be judged with caution although parents often see an urgent need for treatment.

New multifunctional prosthetic arm and hand systems.

We are building a new hand with 18 DOF which has all its actuators inside the body of the hand. This hand is in a form suitable for the 50% women but has the strength capabilities of a 50% male.

Low density of sympathetic nerve fibres and increased density of brain derived neurotrophic factor positive cells in RA synovium.

OBJECTIVE: To investigate the correlation between density of nerve fibres and the presence of BDNF(+) cells. METHODS: Densities of nerve fibres and BDNF(+) cells were detected by quantitative immunohistochemistry in fresh synovial tissue from 52 patients with RA, 59 with OA, and 26 controls (Co). BDNF was also detected by in situ hybridisation. RESULTS: Sympathetic nerve fibre density was similar in Co and OA but markedly reduced in RA (p = 0.002), whereas density of substance P positive (SP(+)) sensory nerve fibres was lower in OA than in Co and RA (p = 0.002). The ratio of sympathetic/SP(+) sensory nerve fibre density was highest in OA and Co, followed by RA. The correlation between density of sympathetic nerve fibres and SP(+) sensory nerve fibres in OA (R = 0.425, p = 0.001) was strongly positive, had a positive trend in Co (R = 0.243, NS), but was negative in RA (R = -0.292, p = 0.040). In RA and OA tissue the density of BDNF(+) cells was high in sublining areas but markedly lower in Co (p = 0.001). BDNF(+) cell density correlated positively with the ratio of sympathetic/SP(+) sensory nerve fibre density in Co (R = 0.433, p = 0.045) and in OA (R = 0.613, p = 0.015), but not in RA (R = 0.101, NS). Immunohistochemical double staining demonstrated that some macrophages and fibroblasts were positive for BDNF. CONCLUSIONS: The correlation of density of SP(+) sensory with sympathetic nerve fibres was positive in Co and OA but negative in RA. BDNF may have a stimulatory role on growth of sympathetic in relation to SP(+) sensory nerve fibres in Co and OA, but not in RA.

Homocysteine promotes the LDL oxidase activity of ceruloplasmin.

Ceruloplasmin (CP) oxidises low density lipoprotein (LDL). The oxidising potential depends on the formation of Cu(+)-CP which is redox-cycled during oxidation. Homocysteine (HCY) reduces free Cu(2+), potentiating its cell-damaging property. We show that HCY enhanced LDL oxidation by CP, but did not activate the LDL oxidising potential of Cu(2+)-diamine oxidase. Selective removal of the redox-active Cu(2+) abolished the LDL oxidase activity of CP. However, HCY partially restored the LDL oxidase activity of redox-copper depleted CP, indicating that the remaining six copper atoms in CP may also be involved in the process. Spectroscopic and oxidation inhibition studies using the Cu(+)-reagent bathocuproine revealed that HCY induced Cu(+)-CP formation, thus promoting its LDL oxidase activity.

[Development and trial use of multistep diagnosis of musculoskeletal disorders during a routine physical examination at the workplace]. / Entwicklung und Anwendungserprobung einer Mehrstufendiagnostik für Muskel-Skelett-Erkrankungen bei der arbeitsmedizinischen Routineuntersuchung.

Musculoskeletal disorders represent the main cause for absenteeism. To determine the disorders exactly, a multistep inventory of examinations was developed. The method of diagnostics may be an indicator of the quality of occupational medical management. It may improve the availability of health data related to working conditions and may increase the chances of goal-oriented prevention in the field of working conditions as well as in the field of behavior. In addition, the standardized recording of data provides an opportunity for evaluation in epidemiological studies, which may be organized as longitudinal studies to look for the development of musculoskeletal disorders over time.

[Office workplace at a computer monitor from an occupational-orthopedic view]. / Der Bürobildschirmarbeitsplatz aus orthopädisch-arbeitsmedizinischer Sicht.

Typical back problems as well as complaints in the shoulder-arm-hand system are increasing as the volume of sedentary office work at the computer screen rises. Various legal rules precisely define preventive measures. However, basic orthopedic-biomechanical principles are not being taken into consideration. Orthopedists as well as occupational physicians are equally challenged to enforce those legal guidelines by beginning to raise awareness of the principles and thus contributing towards improvement of working conditions.

A method to assess biochemical activity of liver cells during clinical application of extracorporeal hybrid liver support.

Biochemical activity of a hybrid liver support system based on porcine liver cells was investigated in patients suffering from acute liver failure, coma stage III-IV Patient plasma was drawn systemically and after circulation through the bioreactor at four hour intervals. A method is used that takes into account the rate of plasma flow and the differences in plasma concentration systemically and after circulation through the liver support system to determine the net release or uptake of metabolites such as ammonia, urea and glucose. Urea release (mean 2.28+/-0.37 micromol/h/g cells) and ammonia uptake (mean 0.17+/-0.11 micromol/h/g cells) was seen during treatment, an active role of the system in glucose metabolism was observed. All patients were bridged successfully to liver transplantation.

[The importance of the esophageal-tracheal-double lumen tube for clinical use and emergencies]. / Die Bedeutung des ösophago-trachealen Kombinationstubus in der klinischen Routine und bei Notfällen.

Difficult intubation can unexpectedly occur in clinical practice and emergencies. Oxygenation must be maintained with resumed artificial ventilation. Besides tracheal intubation with an ETT as the "gold standard" of airway management, the esophageal-tracheal Combitube(R) (ETC; Tyco-Healthcare, Neustadt/Donau, Germany; www.combitube.org) is another interesting device that has been used satisfactorily in a variety of circumstances, specially for management of the difficult airway. The ETC has been used during prehospital and hospital emergencies. Now, anesthesiologists have managed the ETC successfully in clinical practice also. The anesthesiological management does not differ from the management in other difficult airway situations. The use of the Combitube needs an appropriate teaching and continuous clinical practice.

Upregulation of vascular endothelial growth factor receptors is associated with advanced neuroblastoma.

BACKGROUND: Angiogenesis is essential for tumor growth and relies on the production of angiogenic factors. Vascular endothelial growth factor (VEGF) is a major regulator of angiogenesis that binds to tyrosine kinase receptors Flt-1 and KDR. The interaction of VEGF and its receptors at gene and protein levels in neuroblastoma remains widely unknown. METHODS: Tumor biopsy specimens and serum were obtained from 37 neuroblastoma patients; adrenal biopsy sections and sera of 7 normal children served as controls. Biopsy specimens were examined by real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blotting; serum was analyzed by enzyme-linked immunosorbent assay (ELISA). VEGF-A(165), B, C, Flt-1, and KDR were analyzed. RESULTS: VEGF isoforms and its receptors' mRNA were expressed in neuroblastoma and control tissues. Whereas the ligands were increased in stages III and IV, the receptors were upregulated in stage III only. At protein level, VEGF-B and C, Flt-1, and KDR were not detectable in tissue lysates, whereas VEGF-A was increased in stages III and IV. Serum VEGF protein levels were upregulated in stage III. CONCLUSIONS: VEGF-A(165) is one of the major angiogenesis regulators among the ligands' family of VEGF, whereas its receptors KDR, and most probably Flt-1, may contribute to a poor prognosis (angiogenic) phenotype, as indicated by their upregulated MRNA levels in stage III neuroblastoma. VEGF-A(165) mainly contributes to increased serum VEGF levels and may serve as a diagnostic tool in advanced-stage neuroblastoma.

Impact of cardiac transplantation on molecular pathology of ET-1, VEGF-C, and mitochondrial metabolism and morphology in dilated versus ischemic cardiomyopathic patients.

Little is known about the long-term impact of cardiac transplantation on activity and modifications of endothelin (ET)-1 system, vascular endothelial growth factor (VEGF), and mitochondrial metabolism and morphology in patients with ischemic cardiomyopathy (ICM) versus dilated cardiomyopathy (DCM). Messenger RNA (mRNA) expression levels of ET-1, endothelin converting enzyme (ECE)-1, VEGF-C, carnitine palmitoyltransferase (CPT)-1, and carnitine acetyltransferase (CARAT), as well as the number of normal, edematous, and degenerated mitochondria were assessed in left ventricular biopsies of 21 patients with DCM and 20 with ICM (New York Heart Association class III-IV) before and up to 3 months after cardiac transplantation. Cardiac samples of donated, nonfailing hearts served as controls (n=10). In cardiac biopsies of both ICM and DCM patients, ET-1, VEGF-C, CPT-1, and CARAT mRNA were up-regulated, whereas ECE-1 mRNA was down-regulated (P<0.05). Degenerated mitochondria had the highest number in both groups, followed by normal and edematous mitochondria. After cardiac transplantation, in ICM patients impaired gene expression levels decreased to, or below, normal levels, and the number of normal mitochondria increased (P<0.05). In implanted hearts of DCM patients, however, up-regulated ET-1 transcript levels persisted and the number of normal mitochondria decreased, whereas the number of degenerated mitochondria increased (P<0.05), and edematous mitochondria remained unchanged in number. These results show that cardiac transplantation corrects the impaired hemodynamic and echocardiographic parameters in both groups, whereas in DCM, the molecular pathology of ET-1 system and mitochondria persists. Therefore, it is more likely that these changes are the cause rather than a consequence of DCM.

"Wiener klinische Wochenschrift": publication patterns 1990-2000.

The impact factor (Institute for Scientific Information, ISI, Philadelphia, PA, USA) is a widespread used and acknowledged source for judging the quality of a researcher. In addition the "Science Citation Index (SCI)" [Institute for Scientific Information (ISI)] provides the scientific community with a citations database indicating the number of cited references in indexed articles. For several reasons, the SCI seems to be more relevant. To evaluate the quality of the journal "Wiener klinische Wochenschrift", we assessed how often contributors to this journal have been cited during the last decade and which contributions have ranked as top papers. Moreover, with the aim of a more objective type of scientific evaluation, we have employed a new score, the "Citation Per Time Score (CPT-Score--the SCI divided by the number of years of observation, starting one year after publication). We have evaluated the total SCI for the years 1990 to 1994 and for the years 1995 to 1999. The number of total citations between the appearance of an article and the year 2000 was analyzed. The highest ranked publication of the whole decade (1990-2000) was a paper by G. Stanek with 40 citations. Furthermore, we have evaluated the "Top Ten Papers" of the journal. Interestingly, a steady increase of the total citation index of the journal "Wiener klinische Wochenschrift" over the last decade could be demonstrated. This study clearly shows that the citation rate of an article is not determined by the impact factor of the journal but rather the quality of the contribution. Moreover, the citation analysis of papers published in the last ten years in the "Wiener klinische Wochenschrift" shows a satisfactory citation rate for articles published in this journal. It is therefore definitely attractive to submit an article to a journal such as the "Wiener klinische Wochenschrift".

Ondansetron attenuates CCK induced satiety and c-fos labeling in the dorsal medulla.

Serotonin 5-HT(3) antagonists have been suggested for treatment of several disorders involving altered gastrointestinal (GI) function. CCK also has well documented GI actions on both food intake and vago-vagal reflexes. To evaluate potential interactions, the effect of a 5-HT(3) antagonist, ondansetron, on exogenous CCK induced satiety and c-fos activation was determined. Ondansetron reduced both actions of CCK by approximately 50%. The reduction in c-fos was localized to a specific subregion of the dorsal medulla, suggesting that a distinct subpopulation of CCK receptive fibers are modulated by 5-HT(3) ligands. Treatments using 5-HT(3) antagonists also may affect endogenous CCK functions.

Cortical representation of the sensory dimension of pain.

It is well accepted that pain is a multidimensional experience, but little is known of how the brain represents these dimensions. We used positron emission tomography (PET) to indirectly measure pain-evoked cerebral activity before and after hypnotic suggestions were given to modulate the perceived intensity of a painful stimulus. These techniques were similar to those of a previous study in which we gave suggestions to modulate the perceived unpleasantness of a noxious stimulus. Ten volunteers were scanned while tonic warm and noxious heat stimuli were presented to the hand during four experimental conditions: alert control, hypnosis control, hypnotic suggestions for increased-pain intensity and hypnotic suggestions for decreased-pain intensity. As shown in previous brain imaging studies, noxious thermal stimuli presented during the alert and hypnosis-control conditions reliably activated contralateral structures, including primary somatosensory cortex (S1), secondary somatosensory cortex (S2), anterior cingulate cortex, and insular cortex. Hypnotic modulation of the intensity of the pain sensation led to significant changes in pain-evoked activity within S1 in contrast to our previous study in which specific modulation of pain unpleasantness (affect), independent of pain intensity, produced specific changes within the ACC. This double dissociation of cortical modulation indicates a relative specialization of the sensory and the classical limbic cortical areas in the processing of the sensory and affective dimensions of pain.

Semicarbazide-sensitive amine oxidase catalyzes endothelial cell-mediated low density lipoprotein oxidation.

OBJECTIVE: Deamination products of semicarbazide-sensitive amine oxidases (SSAO), i.e. aldehydes, superoxide and ammonia have been shown to initiate vascular damage. SSAOs are copper-enzymes, present in endothelial (EC), smooth muscle cells (SMC) and in blood. Transition metals ions (Cu, Fe) mediate the oxidative (atherogenic) modification of LDL by SMC and EC. The physiological source of the active metal ions is still under debate. We hypothesize that SSAOs may catalyze LDL oxidation by endothelial cells via enzyme-complexed Cu++. METHODS: EC isolated from human umbilical veins and cultured in 35 mm wells in RPMI-1640 medium were used as LDL oxidation system. RESULTS: Diamine oxidase (DAO), a SSAO which activity is elevated in tissues and sera of diabetic patients, catalyzes the oxidation of LDL by EC. In the presence of purified DAO (0.07 to 70 U/l) LDL oxidation was increased up to 10-fold as measured by thiobarbituric acid reactive substance (TBARS) formation as well as apoprotein modification of LDL. Chemical blockage of the SSAO substrate binding site did not inhibit the catalytic effect of DAO on LDL oxidation. Denaturation of the enzyme did not destroy the ability of the preparation to facilitate LDL oxidation by EC. The potential of the enzyme to catalyze LDL oxidation was not suppressed in the presence of serum. However, selective removing of enzyme-copper completely abolished the ability of the enzyme to trigger cell-mediated LDL oxidation. CONCLUSION: DAO, beside generating angiopathic deamination products, has the potential to act as a pathophysiological catalyst of LDL atherogenic modification by vascular cells.

Genistein prevents the glucose autoxidation mediated atherogenic modification of low density lipoprotein.

Hyperglycemia has been assumed to be responsible for oxidative stress in diabetes. In this respect, glucose autoxidation and advanced glycation end products (AGE) may play a causal role in the etiology of diabetic complications as e.g. atherosclerosis. There is now growing evidence that the oxidative modification of LDL plays a potential role in atherogenesis. Glucose derived oxidants have been shown to peroxidise LDL. In the present study, genistein, a compound derived from soy with a flavonoid chemical structure (4', 5, 7-trihydroxyisoflavone) has been evaluated for its ability to act as an antioxidant against the atherogenic modification of LDL by glucose autoxidation radical products. Daidzein, (4',7-dihydroxyisoflavone) an other phytoestrogen of soy, was tested in parallel. Genistein--in contrast to daidzein--effectively prevented the glucose mediated LDL oxidation as measured by thiobarbituric acid-reactive substance formation (TBARS), alteration in electrophoretic mobility, lipid hydroperoxides and fluorescence quenching of tryptophan residues of the lipoprotein. In addition the potential of glucose-oxidized LDL to increase tissue factor (TF) synthesis human endothelial cells (HUVEC) was completely inhibited when genistein was present during LDL oxidative modification by glucose. Both phytoestrogens did not influence the nonenzymatic protein glycation reaction as measured by the in vitro formation of glycated LDL. As the protective effect of genistein on LDL atherogenic modification was found at glucose/genistein molar ratios which may occur in vivo, our findings support the suggested beneficial action of a soy diet in preventing chronic vascular diseases and early atherogenic events.

p-Hydroxyphenylacetaldehyde, the major product of tyrosine oxidation by the activated myeloperoxidase system can act as an antioxidant in LDL.

The oxidative modification of low density lipoprotein (LDL) may play a significant role in atherogenesis. HOCl generated by the myeloperoxidase/H2O2/Cl- system of activated neutrophils may be operative in vivo making LDL atherogenic. Tyrosine has been found to be oxidized by HOCl to p-hydroxyphenylacetaldehyde (p-HA) capable of modifying phospholipid amino groups in LDL. As an amphiphatic phenolic compound, p-HA may have the potential to act as an antioxidant in the lipid phase of LDL. The present results show that (a) tyrosine exerts a protective effect on LDL modification by HOCl, (b) p-HA could act as antioxidant associated with the lipoprotein preventing cell- and transition metal ion-mediated LDL oxidation and (c) p-HA was able to scavenge free radicals.

Effects of garlic extract (Allium sativum) on neutrophil migration at the cellular level.

Studies of the effects of garlic extract on oxidative and lipoprotein levels have yielded widely different findings. Leukocytes play an important role during many processes, including inflammation. They migrate from intravascular spaces into tissues and attack microorganisms. In a recent study, the inhibitory effects of the nonsteroidal antiinflammatory drug, ibuprofen, on leukocyte transmigration were demonstrated using an in vitro assay. Little is known about the cellular effects of garlic extracts (Allium sativum). The aim of the current study was to investigate the influence of garlic extract on leukocyte migration through endothelial cell monolayers and thereby evaluate a possible role in inflammatory processes. Human umbilical endothelial cells were cultured on microporous membranes to make an endothelial cell monolayer (ECM). Freshly isolated neutrophils were used in a recently described migration assay. The amount of untreated neutrophils migrating through the untreated ECM was used as control and set at 100%. Neutrophils and/or ECM were pretreated with garlic extract using moderate, higher, and lower concentrations. Moderate plasma concentrations of garlic extract inhibited neutrophil migration through ECM significantly (64 +/- 5.8% standard deviation [SD]; P < 0.05) when both cell types were treated, (a situation that may have clinical relevance). Treating either neutrophils or ECM alone showed significant reductions in migratory rate (neutrophils treated alone: 81 +/- 7.7% SD, P < 0.05; ECM alone: 70 +/- 6.7%, P < 0.05). Thus, garlic extract is identified as a potent inhibitor of leukocyte migration through endothelial cell monolayers. Treatment of both cell types has an additive effect. Endothelial cells seem to be more affected than neutrophils. Further investigations are necessary to understand the potential clinical consequences.

Herbal medicines: current trends in anesthesiology practice--a hospital survey.

STUDY OBJECTIVES: To develop a simple survey to determine the patient population actively utilizing dietary supplements and/or herbs, during the preoperative period. DESIGN: Prospective study, with survey instrument. SETTING: University medical center. PATIENTS: 1,017 patients presenting for preanesthetic evaluation prior to outpatient surgery. INTERVENTIONS: After undergoing preanesthetic evaluation, patients were asked to complete a survey listing which of the nine most popular nutraceuticals currently available on the market they were using. MEASUREMENTS AND MAIN RESULTS: A total of 1017 surveys were submitted over a period of five months, with 32% being poorly completed and thus discarded. Of the remaining 755 valid surveys, 482 patients used at least one nutraceutical agent. 90% of these patients were using vitamins, 43% garlic extracts, 32% Gingko Biloba, 30% St. John's Wort, 18% Ma Huang, 12% Ecchinaceae, 10% Aloe, 8% Cascare, 3% licorice. CONCLUSION: A significant population of patients scheduled for an elective surgical procedure are self-administering nutraceutical agents. Some of these agents have the potential to cause serious drug interactions and hemodynamic instability during surgery. Hence, it may be important to identify patients self-administering these medications, during the preoperative period.

Effects of remifentanil on neutrophil adhesion, transmigration, and intercellular adhesion molecule expression.

BACKGROUND: Anaesthetic drugs are used for pain therapy and anaesthesia. Neutrophils play a significant role during the process of inflammation. The aim of the current study was to investigate the effects of remifentanil and fentanyl on neutrophil migration through endothelial cell monolayers, and on adhesion molecule expression. METHODS: After isolation of polymorphonuclear neutrophils (PMNL) we used a currently described migration assay. PMNL and/or endothelial cell monolayers (ECM) were pre-treated with remifentanil using clinically relevant, as well as higher and lower concentrations or relevant concentrations of fentanyl. RESULTS: Concentrations of remifentanil (50 ng/mL) similar to the relevant plasma concentration were able to inhibit PMNL migration through ECM significantly (migration compared to the control 82+/-7% SD; P<0.05), when both cell types were treated with the synthetic narcotic remifentanil. Fentanyl (30 ng/mL) showed a stronger inhibitory effect (migration compared to the control 67+/-9.2%; P<0.05). Endothelial cell adhesion molecule expression was reduced after either remifentanil or fentanyl. CONCLUSION: The results of the present investigation indicate that remifentanil influences interaction of ECM against human neutrophils. Compared to fentanyl, remifentanil seems to exhibit minor inhibitory effects on neutrophil migration.