Bicycle accidents - do we only see the tip of the iceberg? A prospective multi-centre study in a large German city combining medical and police data.

INTRODUCTION: Bicycles are becoming increasingly popular. In Münster, a German town with a population of 273,000, bicycles were the main method of transportation in 2009, used more often (37.8%) than cars (36.4%). Each day in Münster, bicycles are used around 450,000 times. In 1982, they were only used around 270,000 times a day. However, the increased use of bicycles has also led to an increased number of bicycle accidents. METHODS: Between February 2009 and January 2010, data on bicycle-accidents leading to injuries were collected by the Police of Münster and in all emergency units of the six hospitals in Münster. A systematic acquisition of technical data from the police and the medical data from the hospitals were combined anonymously. None of the forms contained personal data of patients involved, except for patient age and sex as well as time and place of bicycle accidents to match the questionnaires. The data were entered into a central database (MS Access for input/MySQL for data retrieval). RESULTS: 2250 patients were included in this study. For each of these patients either a patient record or a hospital record or a police record or a combination of any of these different records existed in our database. In total, 1767 patients received medical treatment at a hospital and 484 people included in the study did not go to a hospital. Three fatalities occurred as a result of bicycle accidents. Considering reasons for hospital admission, traumatic brain injuries were the leading cause (25.7%). However, the largest resource consumption was attributed to fractures of the upper extremities (36.8%) and lower extremities (29.9%) with major surgery. DISCUSSION: Bicycle accidents occur more frequently than indicated by police records. The results of the Münster Bicycle Study have shown that the actual number of bicycle accidents exceeds the officially reported number by nearly two times. Since bicycle helmets cannot prevent accidents it is recommended not only to focus on helmet use as the only injury prevention method. Other factors, such as weather, pavement and default of traffic, roadworthiness of the bicycles or alcohol/drug abuse also affect the accident rates.

[Accuracy of determination of the hip centre in navigated total knee arthroplasty]. / Genauigkeit der Bestimmung des Hüftgelenkszentrums bei der Kniegelenksnavigation.

AIM: In navigated knee arthroplasty the hip centre is determined by rotary motion of the femur (pivoting). The accuracy of this functional hip centre determination in vivo is unclear. In the following paper the accuracy of pivoting in the determination of the hip centre was examined. METHODS: Navigated (TC-PLUS, Solution, PLUS Orthopedics) total knee arthroplasty (PI Galileo, PLUS Orthopedics) was performed on 25 patients with primary arthritis of the knee joint. The position of the femoral component and the hip centre were postoperatively determined by computer tomography. Through comparison with the intraoperatively documented data, the deviation of the pivoted from the true hip centre in the frontal and sagittal planes was calculated. The degree of arthritis of the hip was determined on plain radiographs according to Kellgren. RESULTS: The mean deviation was determined to 1.0 +/- 0.7 degrees in the frontal plane and 2.5 +/- 1.6 degrees in the sagittal plane (p = 0.002). This corresponds to a mean overall deviation of 20 +/- 10 mm. The data were continuously, non-parametrically distributed without any outliers. A great range of motion (ROM) in the frontal as well as sagittal planes during pivoting resulted in a less accurate determination of the hip centre. There was no correlation to the degree of arthritis of the hip. CONCLUSION: The results indicate a recommendable ROM during pivoting for maximal accuracy of hip centre determination of 20 to 30 degrees in the sagittal plane and 30 to 40 degrees in the frontal plane. Arthritis of the hip is not a contraindication for functional determination of the hip centre.

Randomized phase III study of high-dose fluorouracil given as a weekly 24-hour infusion with or without leucovorin versus bolus fluorouracil plus leucovorin in advanced colorectal cancer: European organization of Research and Treatment of Cancer Gastrointestinal Group Study 40952.

PURPOSE: This trial was conducted to determine whether high-dose fluorouracil (FU) given as a weekly 24-hour infusion is more active than bolus FU + leucovorin (LV), and whether high-dose infusional FU can be modulated by LV. PATIENTS AND METHODS: A total of 497 patients with previously untreated metastatic colorectal cancer were randomly assigned to receive bolus FU 425 mg/m2 intravenously + LV 20 mg/m2 on days 1 to 5 and repeated on day 28 (FU + LV), or FU 2600 mg/m2 as a 24-hour infusion alone (FU24h) or in combination with 500 mg/m2 LV (FU24h + LV)-all given weekly x6 followed by a 2-week rest period. Survival was the major study end point. RESULTS: With a median follow-up of more than 3 years, survival did not differ among the treatment groups (median FU + LV, 11.1 months [95% CI, 10.2 to 15.0 months]; FU24h, 13.0 months [95% CI, 10.4 to 15.4 months]; FU24h + LV, 13.7 months [95% CI, 12.0 to 16.4 months]; P =.724). Progression-free survival (PFS) was significantly longer for FU24h + LV (median FU + LV, 4.0 months [95% CI, 3.4 to 4.9]; FU24h, 4.1 months [95% CI, 3.4 to 5.0]; FU24h + LV 5.6 months [95% CI, 4.4 to 6.7]; P =.029). The response rates in the subgroup of patients with measurable disease were 12%, 10%, and 17% for FU + LV, FU24h, and FU24h + LV, respectively (not significant). Occurrence of grade 3 and 4 diarrhea was higher in the FU24h + LV arm (22%) compared with the FU24h (6%) or FU + LV (9%) arms; however, stomatitis (11% in FU + LV v 3% in FU24h v 5% in FU24h + LV arms) and hematologic toxicity were higher in the bolus FU + LV arm. Global quality of life did not differ within the three arms. CONCLUSION: Neither FU24h + LV nor FU24h prolong survival, relative to bolus FU + LV. Leucovorin increases PFS if added to FU24h, but increases toxicity.

Are endometrial carcinoma cells disseminated at hysteroscopy functionally viable?

OBJECTIVE: The aim of this study was to evaluate the rate of transtubal dissemination of endometrial carcinoma cells by hysteroscopy and the functional viability of disseminated tumor cells by assessing cell adhesion in an in vitro model. METHODS: We studied 24 uteri obtained at TAH+BSO in patients with endometrial carcinoma. Further inclusion criteria were negative peritoneal cytology, no involvement of the uterine serosa or extrauterine disease, and endometrial surface involvement >1 cm in diameter. In vitro fluid hysteroscopy was performed with a 5-mm single-flow rigid hysteroscope. A maximum of 150 ml saline was infused at a maximum pressure of 100 mm Hg for a maximum of 3 min. Fluid running off through the tubes was collected. The cell suspension was enriched by a density gradient centrifugation. The isolated cells had a mean viability of 90% as judged by trypan blue exclusion. Viable cells (5 x 10(4) per 2-cm(2) polyvinyl chloride well plate) were cultured with equal parts of Dulbecco's modified Eagle's minimal essential medium and Ham's F-12 for 24 h. The endpoint of the analysis was the adherence of tumor cells to the polyvinyl chloride well plate, which was taken as a proxy for functional cell viability. Cytological evaluation was performed separately by two cytologists blinded to the source and date of the smears. RESULTS: Transtubal fluid dissemination was seen in 20 of 24 (83%) uteri. Tumor cells were found in 17 specimens (71%). In 10 (42%) specimens the disseminated tumor cells were functionally viable. CONCLUSIONS: Our model suggests that hysteroscopy can cause dissemination of malignant cells into the abdominal cavity from uteri containing endometrial carcinoma and that these cells can be functionally viable and adhere to a matrix.

Differential regulation of chromogranin A, chromogranin B and secretogranin II in rat brain by phencyclidine treatment.

Chromogranin A, chromogranin B and secretogranin II belong to the chromogranin family which consists of large protein molecules that are found in large dense core vesicles. Chromogranins are endoproteolytically processed to smaller peptides. This study was designed to elucidate the regulation of chromgranin expression by acute and subchronic phencyclidine administration. The behavioral syndrome produced by phencyclidine represents a pharmacological model for some aspects of schizophrenia [Jentsch and Roth (1999) Neuropsychopharmacology 20, 201-225]. Tissue concentrations of chromogranins were measured with specific radioimmunoassays. Alterations in secretogranin II gene expression were investigated by in situ hybridization. A single dose of phencyclidine (10mg/kg) led to a transient decrease in secretoneurin tissue levels in the prefrontal cortex after 4h followed by an increase in secretoneurin tissue levels after 12h. Repeated phencyclidine treatment (10mg/kg/day) for five days resulted in elevated secretoneurin levels in cortical areas whereas chromogranin A and chromogranin B tissue levels were unchanged. After the same treatment, a significant increase in the number of secretoneurin containing neurons was found in cortical layers II-III, and V-VI as revealed by immunocytochemistry. The increases in secretoneurin levels were paralleled by an increased number of secretogranin II messenger RNA containing neurons as well as by an increased expression of secretogranin II by individual neurons. The present study shows that secretoneurin II tissue concentration and secretogranin II messenger RNA expression is distinctly altered after acute and subchronic phencyclidine application. From these results we suggest that phencyclidine may induce synaptic alterations in specific brain areas and may contribute to a better understanding of synaptic dysfunction which may also occur in schizophrenia.

Hyperglycaemia in vitro alters the proliferation and mitochondrial activity of the choriocarcinoma cell lines BeWo, JAR and JEG-3 as models for human first-trimester trophoblast.

AIMS/HYPOTHESIS: Early intrauterine growth delay in diabetes could be caused by a reduced growth of the placenta. Our study investigates whether hyperglycaemia in vitro reduces trophoblast proliferation. METHODS: First-trimester trophoblast cell models (BeWo, JAR and JEG-3 choriocarcinoma cells) were cultured for 24 and 48 h with 5.5 mmol/l D-glucose, 25 mmol/1 D-glucose (hyperglycaemia) and with an osmotic control. Cell number, total protein and nucleic acid content and mitochondrial activity (tetrazolium salt assay) were measured, the cell cycle analysed (FACS, cyclin B1 levels) and apoptosis (Annexin-V) measured. RESULTS: In BeWo cells hyperglycaemia reduced cell number, protein, nucleic acid and cyclin B1 levels. The reduced G2/M and increased G0/G1 population after 24 h reflects growth arrest at G0/G1. In JAR cells after 24 h the population was arrested in G0/G1, whereas after 48 h the G0/G1 block was abrogated and the cells were arrested at G2/M. The net effect was an unchanged cell number. In JEG-3 cells hyperglycaemia resulted in fewer cells after 24 h but not after 48 h indicating some adaptation. Mitochondrial activity was either stimulated (BeWo) or reduced (JAR, JEG-3) under hyperglycaemia. Some of these effects were also induced by hyperosmolarity alone. CONCLUSION/INTERPRETATION: Hyperglycaemia has the potential to inhibit the proliferation of first-trimester trophoblast cell models. The mechanisms leading to growth arrest and to changes in mitochondrial activity are complex and depend on differentiation. We hypothesise a hyperglycaemia-induced impairment of placental growth in the first trimester of a poorly controlled diabetic pregnancy.

Antibody reaction patterns in first trimester placenta: implications for trophoblast isolation and purity screening.

The aim of this immunohistochemical and cytochemical study was to select specific antibodies to establish an efficient purification protocol for first trimester trophoblast and for subsequent purity screening of isolated trophoblast cells. The reactivity of antibodies to various cytokeratin filaments, glycoprotein CD9, fibroblast specific antigen (FSA), common leukocyte antigen CD45RB and macrophage antigens CD163, CD68 and CD14 were studied on cryosections of placental tissue. Among the cytokeratins tested, cytokeratin 7 was the only keratin filament type, which was not expressed in placental mesenchymal cells, but in all trophoblast subpopulations. Since anti-CD9, in addition to mesenchymal cells, also strongly labels extravillous cytotrophoblast cells, whereas the antibody to FSA only reacts with mesenchymal cells, anti-FSA is suitable as a depletion antibody for mesenchymal cells. Among the macrophage markers anti-CD163 was the most specific for Hofbauer cells. CD45RB was expressed on maternal and fetal leukocytes as well as on Hofbauer cells. Isolated first trimester placental cell preparations that have been collected from a density gradient contained up to 45 per cent non-trophoblast cells. Immunocytochemistry using antibodies to CK7, FSA, vimentin, CD45RB and CD163 demonstrated that subsequent immunodepletion with antibodies to CD45RB and FSA increased the purity of the trophoblast preparation to greater than 98 per cent. According to this study trophoblasts from first trimester placentae should be identified by cytokeratin antibodies specific for the isoform 7. Purification of isolated trophoblasts by density gradient alone does not result in a sufficient degree of purity.

Endothelin A and B receptors change their expression levels during development of human placental villi.

Endothelin receptors have recently been found in non-vascular tissues including the human placenta. The present study investigated developmental changes in location and expression levels of endothelin A and B receptors (ETA-R, ETB-R) in human placentae and isolated trophoblast by comparing first and third trimester tissues. In the first trimester all cells and tissues were immunolabelled for ETA-R and ETB-R, whereas in third trimester placentae the syncytiotrophoblast (ETA-R, ETB-R) and macrophages (ETA-R) were unstained. Immunoblotting for both receptors revealed up to three bands at 33-35, 50 and 75 kDa, respectively, which were differentially present in the first and third trimester. Pre-adsorption of antibodies with oligopeptides used for antigen-generation weakened the immunoreactions. ETA-R protein levels decreased (P< 0.05) in total villous tissue and isolated trophoblast, whereas ETB-R was unchanged. ETB-R transcripts (RT-PCR) prevailed in both stages and tissues, but in contrast to the protein levels its preponderance decreased from first trimester to term in villous tissue (P< 0.01), because of a four to five-fold increase in ETA-R and only a two-fold (P< 0.05) increase in ETB-R mRNA levels (P< 0.01). We conclude that ET receptor location, intracellular processing and expression levels in human villous tissue change between the first and third trimester. This may reflect changing functions of ET-1 during placental development.

The impact of diets with different magnesium contents on magnesium and calcium in serum and tissues of the rat.

The impact of three different magnesium diets (70, 1,000 and 9,000 ppm) on total, ionized and bound magnesium as well as ionized calcium in serum and total calcium and magnesium in femoral bone, skeletal muscle, heart and liver of male Sprague-Dawley rats was investigated. The percentage of ionized serum magnesium was unproportionally high in rats fed a low magnesium (70 ppm) diet. Femoral magnesium was correlated with ionized and total serum magnesium. In contrast, there was generally no correlation between total serum magnesium and the magnesium fractions in skeletal muscle, heart and liver. In rats fed the magnesium deficient diet, total cardiac concentration of magnesium was even significantly increased along with total calcium content, while there were no effects on total muscle and liver magnesium. Within the single groups, ionized serum calcium was never proportional to dietary magnesium, but in all three magnesium diet groups together, it was inversely correlated with dietary magnesium. Moreover, ionized serum calcium was inversely correlated with both ionized and total serum magnesium. In all 3 groups together, the concentrations of total calcium and magnesium in heart and skeletal muscle were correlated, within the single groups correlation existed only in the 1000 ppm group. Magnesium influx via calcium channels during low magnesium intake has been seen in non cardiac tissues [35,36], but nothing similar is known about non selective channels for divalent cations in the heart [33]. Thus, magnesium uptake by cardiac cells along with calcium seems to be possible, especially at low intracellular magnesium concentrations, but is still poorly investigated. We suggest that the calcium-antagonistic effect of magnesium is related to the turnover rate of magnesium rather than to its tissue concentrations.

[Delirium after vascular surgery interventions. Intermediate-term results of a prospective study]. / Durchgangssyndrome nach gefässchirurgischen Operationen. Zwischenergebnisse einer prospektiven Untersuchung.

INTRODUCTION: Postoperative delirium is a common psychic disturbance occurring acutely after various surgical procedures and typically presenting with a fluctuating course. These patients' recovery takes longer. In this study we analyze the incidence of postoperative delirium in patients undergoing vascular surgery and try to identify risk factors for its development. METHODS: Patients undergoing elective arterial operations were included. Their medical history, the specific vascular diagnosis and operation performed, the medication and laboratory data were monitored. Additionally the patients were preoperatively interviewed by a psychiatrist. Intraoperatively the drugs, infusions, possible transfusions, blood gases and pressures were monitored, as were the times of surgery and anesthesia. Postoperatively patients were seen daily by the psychiatrist and the surgeon for at least 7 days. Postoperative delirium was diagnosed according to DSM IV criteria, and mild, moderate and severe delirium were distinguished. RESULTS: Fifty-four patients entered the study. Twenty-one (38.9%) developed postoperative delirium (11 mild, 2 moderate, 8 severe). Patients with aortic operations developed delirium more frequently than those with non-aortic procedures(55.5 vs 22.2%, n = 27 each). Some preexisting diseases (hearing disturbance) increased the probability of postoperative delirium, while age was not identified as a risk factor. General psychopathological and depressive disturbances increased the likelihood of postoperative delirium. Patients who had a severe intraoperative course developed postoperative delirium more frequently. This was not seen in the absolute time of surgery or anesthesia nor in the intraoperative development of blood pressure or intraarterial gases, which did not differ between patients with and without postoperative delirium. More reliable parameters were an increased intraoperative need for crystalloid volume, intra- or postoperatively decreased hemoglobin values (Hb < 10 g/dl) and the development of acidosis that had to be treated. Patients with delirium had serious complications more often (8/21 = 38.1% vs 6/33 = 18.2%) and needed Intensive Care treatment longer (2.7 vs 2.1 days, only aortic surgery 3.2 vs 2.4 days). CONCLUSIONS: Postoperative delirium after vascular surgery is frequent. Patients undergoing aortic surgery, with specific concomitant medical disease, psychopathological disturbances and a severe intraoperative course, are at risk of developing postoperative delirium.

Neuroendocrine secretory protein 55 (NESP55): alternative splicing onto transcripts of the GNAS gene and posttranslational processing of a maternally expressed protein.

Recent studies established a novel genomically imprinted gene located 45 kb upstream of the human GNAS1 locus. This locus encoded for the Neuroendocrine Secretory Protein with an apparent molecular weight of 55,000 (NESP55), which is transcribed exclusively from the maternal allele. We sequenced rat and human NESP55 and investigated tissue-specific splicing of its mRNA and posttranslational modifications of the protein in various tissues. Alternative mRNA splicing of NESP55 was analyzed by sequencing of cDNA clones, RT-PCR and Northern blotting. Two main splice variants, which were generated in a tissue-specific manner, were identified: The open reading frame encoding NESP55 was spliced onto exons 2-13 of Gsalpha in the adrenal medulla, pituitary and the brain. In addition, in the pituitary a second shorter, prominent mRNA transcript was generated by splicing of NESP55 onto exons 2, 3 and N1 of Gsalpha. Several of the cDNA clones isolated contained inverted repeats of 50-150 bp at their 5' or 3' termini, which might form hairpin stems and thus alter mRNA stability. The NESP55 open reading frame encoded a hydrophilic protein of 28,018 Da (human) and 29,218 Da (rat), respectively, which resembled the class of acidic, neuroendocrine secretory proteins collectively called chromogranins. NESP55 is highly conserved among mammalian species. It is posttranslationally acidified by the addition of keratan sulfate glycosaminoglycan chains and differentially processed by endopeptidases in various endocrine and neuronal tissues.

Elevated levels of serum secretoneurin in patients with therapy resistant carcinoma of the prostate.

PURPOSE: The majority of prostate cancers show some degree of neuroendocrine differentiation. It was previously demonstrated that chromogranin A, a constituent of large dense core vesicles of neuroendocrine cells, is frequently elevated in patients with metastatic prostate cancer. We evaluate the expression of secretoneurin, which is generated by proteolytic processing of secretogranin II (chromogranin C), in patients with prostate disease. MATERIALS AND METHODS: Secretoneurin was measured in sera of 16 healthy men whose blood was drawn for prostate cancer screening (controls), and in 9 patients with prostatitis, 19 with benign prostate hyperplasia and 54 with prostate cancer detected by radioimmunoassay. Therapy resistant disease (clinical stage D3) was noted in 20 prostate cancer cases. Serum prostate specific antigen was measured in all patients and controls. In addition, chromogranin A, prostate acid phosphatase and interleukin-6 were determined in patients with D3 prostate cancer. Molecular properties of secretoneurin immunoreactivity were analyzed by gel filtration chromatography followed by radioimmunoassay. RESULTS: Mean secretoneurin was 58.9+/-8 fmol./ml. in patients with therapy resistant prostate cancer. Levels were significantly higher than those measured in sera from controls and patients with prostatitis, benign prostatic hyperplasia and pT2 or pT3 prostate cancer. There was a statistically significant correlation between secretoneurin and chromogranin A in patients with endocrine therapy failure (r = 0.543, p<0.05). There was no correlation between serum secretoneurin and prostate specific antigen, prostate acid phosphatase or interleukin-6. Gel filtration chromatography analysis of sera of 3 patients with D3 prostate cancer revealed a peak of secretoneurin immunoreactivity where intact secretoneurin elutes, thus showing that the processed peptide is circulating in the blood. CONCLUSIONS: Secretoneurin is elevated in sera of patients with endocrine therapy refractory prostate cancer. Our results support the concept that neuroendocrine differentiation is associated with prostate cancer progression.

Generality and specificity of emotion-recognition deficit in schizophrenic patients with positive and negative symptoms.

Schizophrenic patients with positive and negative symptoms, as well as non-patient control subjects, were asked to recognize emotional stimuli of happy, sad, and neutral facial expressions. Dependent measures were the percentage of correct responses, and the incorrect use of an emotion category owing to false recognition. Schizophrenic patients with negative symptoms exhibited a generalized emotion-recognition deficit, and their use of emotion categories during false recognition was random. Schizophrenic patients with positive symptoms showed a deficit in their recognition of 'sad' emotion and were 'positively biased' to the category 'happy' as reflected by its most frequent usage during false recognition.

Correspondence of emotional self-rating with facial expression.

Emotional processing abilities are difficult to measure psychometrically. Ultimately their quantification has to rely on 'subjective' judgment thereby leaving open the problem of response biases. Assessments of autonomic arousal similarly provide a mere unspecified measurement of a specific emotion. A standardized mood induction procedure capable of obtaining reliable happy and sad mood changes in healthy subjects was used to demonstrate the effectiveness of this procedure. We performed a two-part experiment using a rater-based analysis of facial expressions. This entailed analyzing the emotion portrayed in the faces. The faces of 24 healthy subjects were videotaped during the mood induction procedure of happiness and sadness, respectively. A group of 20 raters naive to the experimental task and conditions rated the facial expressions on six basic emotions. Results showed that ratings corresponded with the facial expressions, which were reflecting the mood of the task condition. Subjects' facial expressions together with self-ratings demonstrate the successful applicability of this standardized mood induction procedure for eliciting happy and sad mood.

Subcortical correlates of differential classical conditioning of aversive emotional reactions in social phobia.

BACKGROUND: Conditioning processes have been proposed to play a role in the development of anxiety disorders. As yet, the neurobiologic correlates of emotional learning have not been fully understood in these patients. Accordingly, brain activity was studied in subcortical and cortical regions involved in the processing of negative affect during differential aversive classical conditioning. METHODS: Twelve patients with social phobia and 12 healthy control subjects were presented with paired conditioned (CS; neutral facial expressions) and unconditioned stimuli (US; negative odor vs unmanipulated air). Functional magnetic resonance imaging (fMRI) was utilized to examine regional cerebral activity during habituation, acquisition,a nd extinction trials. Activity was measured with echo-planar-imaging (EPI), and signal intensity in individually defined anatomic regions were analyzed. RESULTS: Subjective ratings of emotional valence to the CS indicated that behavioral conditioning occurred in both groups. The presentation of CS associated with negative odor led to signal decreases in the amygdala and hippocampus of normal subjects, whereas an opposite increased activation in both regions was observed in patients. Regional differences were not found during habituation and extinction. CONCLUSIONS: Results suggest that conditioned aversive stimuli are processed in subcortical regions, with phobic patients differing from control subjects.

Differential amygdala activation in schizophrenia during sadness.

Several studies have reported impaired emotion processing in schizophrenic patients. However, the corresponding functional cerebral correlates of such impairment have not been fully understood, leaving the neurobiological basis of their affective symptoms unknown. Functional magnetic resonance imaging (fMRI) was utilized to examine brain activity in subcortical and cortical regions of 13 medicated male schizophrenic patients and 13 matched healthy controls during happy and sad mood induction. Results show brain activity in the amygdala of normal controls during negative affect, which is in line with previous neuroimaging findings. Unlike controls, schizophrenic patients have not demonstrated amygdala activation during sadness despite matched ratings to normal controls indicating a similar negative affect. Recognizing that structural abnormalities exist in the amygdala of schizophrenic patients, our results provide new evidence of functional abnormalities in the limbic system.