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Purpose The purpose of this study was to determine the frequency of detection of isthmoceles by ultrasound 6 months after caesarean section (CS) and which symptoms associated with isthmocele formation occur after CS. Subsequently, it was determined how often the ultrasound finding “isthmocele” coincided with the presence of complaints. Methods A prospective multicentre cohort study was conducted with 546 patients from four obstetric centres in Berlin, who gave birth by primary or secondary CS from October 2019 to June 2020. 461 participants were questioned on symptoms 3 months after CS; 329 participants were included in the final follow-up 6 months after CS. The presence of isthmoceles was determined by transvaginal sonography (TVS) 6 months after CS, while symptoms were identified by questionnaire. Results Of the 329 women, 146 (44.4%) displayed an isthmocele in the TVS. There was no statistically significant difference in the manifestation of symptoms between the two groups of women with and without isthmocele; however, when expressed on a scale from 1 to 10 the intensity of both scar pain and lower abdominal pain was significantly higher in the set of women that had shown to have developed an isthmocele (p = 0.014 and p = 0.031, respectively). Conclusion The prevalence of isthmoceles 6 months after CS was 44.4%. Additionally, scar pain and lower abdominal pain were more pronounced when an isthmocele was also observed in the TVS. Trial registration Trial registration number DRKS00024977. Date of registration 17.06.2021, retrospectively registered.

Background: Children generally have a higher nasal resistance than adults. Growth changes the size and different anthropometric parameters of the nose. Logarithmic effective resistance and logarithmic vertex resistance were introduced as physically correct parameters for nasal obstruction. The previously published classification of obstruction derived from 36,500 measurements is missing data for patients aged 7 to 19 years. Methodology: Rhinomanometry was performed before and after decongestion with 9 different anthropometric measurements in 225 children and adolescents. Correlations among age, anthropometric measurements, and logarithmic effective and vertex resistance were determined for both sexes, and regressions were calculated. Results: The highest correlations with the resistance values were found between age, lateral nasal length, and logarithmic effective resistance. A highly significant linear regression between age and logarithmic effective resistance was also found. This was used for adaption of the classification of obstruction in adults to growing patients. The resistance of the nasal airways at the age of 7 years was about twice that in adults. Conclusions: The linear regression equations can be used to suborder obstructions measured by four-phase rhinomanometry into classes for estimation of their severity according to age.

Background: The aim was to analyse the association between severity of complications up to 30 days after surgery and pre-operative nutritional and physical performance parameters. Methods: The participants were a subsample of the previously published PERATECS study (ClinicalTrials.gov: NCT01278537) and included 517 onco-geriatric patients aged 65 years, undergoing thoracoabdominal, gynaecological, or urological surgery. Post-operative complications were classified according to the Clavien Classification System (CCS). Independent risk factors related to the severity of complications, defined as major complications (CCS IIIa-V) and graded complications (CCS grade 0-V), were analysed using logistic and ordinal regression, respectively. Results: In total, 132 patients suffered major post-operative complications. The development of major post-operative complications was independently associated with body mass index (BMI) 20 s, hypoalbuminaemia ( 165 min), and specific tumour sites (upper gastrointestinal, gynaecological) (all P < 0.05). Mini Nutritional Assessment (MNA) scores and weight loss were not independent risk factors for the severity of complications. Conclusion: sNutritional and physical performance risk factors that predicted the severity of complications differed between major and higher-grade post-operative complications, but hypoalbuminaemia independently predicted both. The results support the need for pre-operative risk screening. Due to the explorative nature of the study, further research is required in larger cohorts to corroborate these findings.

Hintergrund: Die Ergebnisse der Untersuchungen der okularen Blutflussregulation (BF-Regulation) von Patienten mit primarem Offenwinkelglaukom (POWG), Normaldruckglaukom (NDG) und okularer Hypertension (OH) im Vergleich zu Gesunden werden beschrieben. Material und Methoden: Mit dem neu entwickelten Ocular Pressure Flow Analyzer OPFA (tpm Luneburg) wurden Untersuchungen bei 92 Patienten mit neu diagnostizierten Glaukomen durchgefuhrt, davon 48 mit POWG, 22 mit NDG und 22 mit OH und mit Gruppen Gesunder verglichen. Die OPFA-Methode verwendet spezielle Saugnapfe zur pneumatischen Ankopplung am Auge zur Aufnahme der okularen Pulse mit hochempfindlichen Transducern und eine Saugpumpe zur simultanen Steigerung des Augeninnendrucks. Nach Tropfanasthesie beider Augen wird der Augeninnendruck kurzzeitig auf suprasystolische Werte erhoht. Wahrend kontinuierlicher Verminderung des intraokularen Druckes werden die okularen Pulse bei steigendem okularen Perfusionsdruck registriert. Durch Vergleich mit einem Kalibrationsvolumen von 1 µl erhalt man intra- und interindividuell reproduzierbare relative okulare Pulsblutvolumina. Die okulare Perfusionsdruck-Pulsblutvolumen-Kurve charakterisiert die individuelle okulare Zirkulation und den systolischen und den diastolischen okularen Perfusionsdruck. Ergebnisse: Die okularen Pulsblutvolumina bleiben bei Gesunden bei Anderung des okularen Perfusionsdrucks uber einen bestimmten Bereich konstant. Nach Uberschreiten eines kritischen Punktes (CP) fallt das okulare Pulsblutvolumen ab. Die Differenz zwischen dem kritischen Punkt und dem Augeninnendruck bezeichnen wir als okulare autoregulatorische Kapazitat (AC). Bei den POWG-Patienten und bei den NDG-Patienten fand sich eine statistisch hoch signifikante Erniedrigung der AC im Vergleich zu der AC der Gesunden. Die ROC-Kurven (ROC: Receiver Operating Characteristic) zeigten bei optimalem Cut-off Value fur das POWG eine Spezifitat von 97,9 %, eine Sensitivitat von 75,0 % und fur das NDG eine Spezifitat von 100 % und eine Sensitivitat von 77,3 %. Die AC bei den OH-Patienten lag dagegen im Bereich der Norm. Die okularen arteriellen Blutdrucke waren bei den POWG- und bei den OH-Patienten erhoht und bei den NDG-Patienten unverandert im Vergleich zu denen Gesunder. Die okularen Perfusionsdrucke waren sowohl bei den Patienten mit POWG und NDG als auch bei denen mit OH statistisch nicht verandert. Schlussfolgerungen: Bei Patienten mit POWG und NDG liegt eine Storung der okularen BF-Regulation vor, die mit hoher Aussagesicherheit mit dem OPFA-Gerat erkannt wird. Durch regulatorische Erhohung des okularen arteriellen Blutdrucks wird der okulare Perfusionsdruck aufrecht zu erhalten versucht zur Sicherung der okularen Perfusion.

Apixaban (Eliquis®) is a direct and competitive inhibitor of factor FXa that is approved for thrombosis prophylaxis after hip and knee replacement surgery, in non-valvular atrial fibrillation and venous thromboembolic events therapy [1]. In cases of severe hemorrhages there is no approved specific antidote available to reverse the effect of apixaban yet. Previous animal and in vitro studies [2, 3] with supratherapeutic concentrations of apixaban (200ng ml-1) have shown that activated prothrombin complex concentrate (aPCC) and recombinant factor VIIa (rFVIIa) have a greater effect in reversing the effect of apixaban than prothrombin complex concentrate (PCC). The effect of these non-specific hemostatic agents for reversal of apixaban concentrations measured in patients after prophylactic doses (maximum observed plasma concentration 62 ng ml-1 [4]) remains unclear.

Completeness of population-based registration systems is recognized to be an important aspect of the quality of information in registries which has to be examined. In this paper a model is presented which was used to estimate completeness of reporting of Down syndrome data notified to the Styrian Malformation registry between 1985-92. The model introduced is based on the two-source capture-recapture method allowing for time-varying parameters. For estimation of the parameters a discrete-time filtering algorithm was developed. For the used data set, an estimate of completeness derived from this model was in good agreement with an independent estimator based on demographic data and maternal age-specific Down syndrome risks whereas the usual two-source capture-recapture method gave a higher estimate.

Background: The production of intraocular antibodies is considered a specific marker for active infectious uveitis. The aim of our study was to evaluate the diagnostic value of aqueous humor analysis in consecutive patients referred to a tertiary clinical center. Methods: We analyzed 91 paired aqueous humor/serum samples from 89 patients with intraocular inflammation. In 71 patients aqueous humor analysis was used as a positive or negative confirmation of the suspected cause, whereas in 18 patients the clinical diagnosis was completely uncertain. A modified micro-ELISA technique was used to detect intraocular IgG production against Toxoplasma gondii, varicella zoster virus, herpes simplex virus and cytomegalovirus. Statistical analysis was performed using the ”Cohen’s kappa” test.Results: Specific intra-ocular antibody production could be detected in 12 (66.7%) of 18 patients with uncertain diagnosis. Subsequently initiated therapy led to clinical improvement in 10 patients, whereas 2 patients remained unchanged. In 2 (2.8%) of 71 patients aqueous humor analysis led to revision of the initially suspected etiology and to a change of therapy. Statistical analysis showed a significant accordance of diagnosis and aqueous humor analysis (P

A central area for induction of anesthesia (CAIA) is supposed to optimize processes of preoperative patient preparation for anesthesia. The purpose of this study was to assess whether the separation of the anesthesia process into anesthesia induction and anesthesia maintenance is associated with residents' job satisfaction. The central area for induction of anesthesia model (CAIA model) was prospectively compared to the conventional model of anesthesia being induced, maintained and ended by the same anesthetist. Quality of senior staff supervision for each day as well as workday satisfaction was additionally graded by a Likert-scale. More than 80% of residents considered their workday as satisfying or very satisfying, regardless of the model applied. Furthermore, work day satisfaction was significantly associated with the quality of supervision provided by the teaching staff. It was concluded that time and attention provided by the teaching staff rather than the anesthesia organisational model were the major determinants of workday satisfaction.

The council of the European Economic Communities has issued a directive (86/469/EEC) for the examination of animals and fresh meat for the presence of residues of several hormones, drugs and environmental pollutants. The purpose of this paper is to compare the method used by the EEC with a Bayesian approach to calculate necessary sample size using prior information in different situations (assuming Beta-, Normal- and Gamma-distribution for the prior distribution). It has been shown that the Bayesian approach requires significantly smaller sample sizes for all levels of inspection. Furthermore, an example is given in the examination of pigs for the presence of residues of drugs in pork.

In order to reduce the incidence of postoperative nausea and vomiting (PONV) a standard operating procedure (SOP) was developed in our department. This consists basically in the administration of one antiemetic intervention for moderate risk (2 risk factors), two interventions for high risk (3-4 risk factors) and no prophylaxis in patients who have no or only one risk factor. The aim of this study was to find out whether PONV prophylaxis according to our SOP was followed and led to a lower incidence of PONV.A total of 2,729 patients were examined in a prospective observational study with post-ad hoc analysis in our department. Inclusion criteria were age over 14 years after general anesthesia and postoperative care in the recovery room. This group was examined in relation to compliance with the SOP.A total of 725 (26.6%), 1050 (38.5%) and 954 (35.0%) patients were grouped according to risk classification into groups with low, medium and high risks, respectively. An SOP compliant regime occurred in 668 patients (92.1%) of the low risk groups, in 373 patients (35.6%) of the moderate risk group and 177 patients (18.6%) of patients at high risk for PONV. In the high risk group 565 patients (59.2%) received at least one antiemetic medication. Patients with PONV were on average cared for 12 min longer in the recovery room (p=0.048).Patients with medium and high risk have a lower incidence of PONV than expected per risk calculation by complying with the SOP. However, the recommended risk-adapted approach was inadequately implemented. Considering this there is room for improvement. Moreover taking into account these implementation issues a general PONV prophylaxis may be beneficial.

Expert panel consensus was used to develop evidence-based process indicators that were independent risk factors for the main clinical outcome parameters of length of stay in the intensive care unit (ICU) and mortality. In a retrospective, matched data analysis of patients from five ICUs at a tertiary university hospital, agreed process indicators (sedation monitoring, pain monitoring, mean arterial pressure [MAP] ≥ 60 mmHg, tidal volume [TV] ≤ 6 ml/kg body weight, peak inspiratory pressure [PIP] ≤ 35 cmH2O and blood glucose [BG] ≥ 80 and ≤ 130 mg/dl) were validated using a prospective dataset of 4445 consecutive patients. After matching for age, sex and ICU, 634 patients were analysed. Logistic regression of the 634 patients showed that monitoring analgesia and sedation, MAP ≥ 60 mmHg and BG ≥ 80 mg/dl were relevant for survival. Linear regression of the 634 patients showed that analgesia monitoring, PIP ≤ 35 cmH2O and TV ≤ 6 ml/kg were associated with reduced length of ICU stay. Linear regression on all 4445 patients showed analgesia, sedation monitoring, MAP ≥ 60 mmHg, BG ≥ 80 mg/dl and ≤ 130 mg/dl, PIP ≤ 35 cmH2O and TV ≤ 6 ml/kg were associated with reduced length of ICU stay, indicating that adherence to evidence-based key process indicators may reduce mortality and length of ICU stay.

To analyze safety issues of regional anaesthesia and analgesia in Germany only a few single center studies are available. Therefore, the German Society for Anaesthesiology and Intensive Care Medicine (Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin, DGAI) and the Professional Association of German Anaesthetists (Berufsverband Deutscher Anästhesisten, BDA) initiated a network for safety in regional anaesthesia. From this the first results on infectious complications will be reported.In a Delphi process the documentation of the setup and maintenance of regional anaesthesia and analgesia was agreed with the participants in a working group from the DGAI. After approval by the officially authorized representative for patient data privacy protection a registry was programmed to collect anonymous data. Up to October 2008 data from 6 centers could be analyzed.After testing for plausibility 8,781 regional anaesthesia procedures (22,112 catheter days) could be analyzed. The 5,057 neuraxial and 3,724 peripheral catheter-based procedures were in place for a median of 2.48 days (range 1.0-3.0 days) and 4 severe, 15 moderate and 128 mild infections were recorded. Diabetics were not found to show a statistically significant increase in risk (2.6% compared to 1.9% for non-diabetics: n.s.). Neuraxial procedures seem to have a higher rate of infections than peripheral procedures (2.7% vs. 1.3%, p0.0001). Multiple punctures of the skin also seem to be associated with a higher infection rate than single skin punctures (4.1% vs. 1.6%, p0.0001).Infectious complications of catheter-based regional anaesthesia are common. Strict hygienic standards must therefore be complied with. More data are necessary to calculate risk factors. The registry provided can also be used as a benchmark to reduce these rates further.

Up to as many as 38,000 people die in German hospitals each year as a result of preventable medical errors. Anesthetic procedures are generally safer than internal medical procedures and the mortality associated with anesthesia is estimated to be 3.3-5 cases per million. However, this is still 10 times higher than the risk associated with civilian aviation for example. Up to 80% of mistakes are attributable to inadequate execution of non-technical skills (NTS) such as communication, teamwork and organization of the working environment. Training in non-technical skills through Anesthesia Crisis Resource Management (ACRM) is an integral part of the Berlin Simulation Training (BeST) curriculum. The aim of this study was to describe the subjective evaluation of change in routine clinical behavior as a result of simulator training using latent outcome variables such as "subjective evaluation of learning outcome", with special emphasis on communication.In total 235 doctors with varying levels of professional experience received BeST training between 2001 and 2004. An anonymous postal questionnaire was sent to 228 of these participants and the response rate was 64% The questionnaire contained 13 questions covering evaluation of the workshop and learning outcome with respect to communication in the operating room (OR), teamwork in the OR and medical knowledge. Following factor analysis 3 latent outcome variables (subjective evaluation of the learning outcome, workshop-related change in perception of the value of communication and general value and relevance) were generated. Logistic regression was used to determine whether there was any relationship between the latent outcome variables and a number of independent factors.It was not possible to demonstrate any relationship between the level of professional training, age or date of the workshop and the variables selected to describe subjective evaluation of behavioral change as a result of the workshop. How realistic the candidates perceived the training scenarios to be (p0.01) and the sex of the candidates (p=0.03) were both significantly related to evaluation and female candidates were more likely to positively evaluate the simulator training. From the candidates' perspective the training significantly altered their perception of the value of NTSs, and in particular communication, during the management of critical incidents in the OR.Well-staged and realistic simulation is associated with better learning outcomes. It may be important to take gender aspects into account in ACRM training.

A new procedure for the discrimination of mixed data is presented. The method allows the application of well-known discriminators after defining new (continuous) variables from the a-posteriori-probabilities. Some outlooks and an example from medical diagnostics are given.

The efficacy control for the treatment of bone metastases in breast cancer is difficult and usually initiated later and with longer time between treatment cycles than the restaging of visceral or soft tissue metastases. The amino-terminal propeptide (PINP) of type I collagen as a biochemical indicator of bone turnover might facilitate early and valid disease surveillance. The utility of total PINP was investigated in metastatic breast cancer patients, with or without bone metastases (for monitoring of therapy). The results were compared to the established markers, osteocalcin and beta-carboxyterminal telopeptide (CTX) or crosslaps concentration.Baseline serum samples of 51 patients with metastastic breast cancer under chemotherapy were investigated. In total, 38 patients had been diagnosed with bone metastases while 13 had no evidence of metastastic spread to the bone. All the patients with bone spread received bisphosphonates in addition to systemic chemotherapy and/or antibody therapy or hormonal treatment. Osteocalcin, CTX and PINP levels were measured on an Elecsys 2010 analyzer (electrochemiluminescence immunoassay--ECLIA). The normal cut-off values were: osteocalcin41.3 pg/ml, CTX1008 pg/ml and PINP95 ng/ml. Based on overall treatment outcome, the patients were grouped as responders (CR/PR), with stable disease (SD) or displaying primary progression (PD).The baseline levels of PINP were significantly higher in patients with bone metastases (median: 92.8 ng/ml) than in those without (median: 63.2 ng/ml, p = 0.044). Patients with more than seven bone metastases had significantly higher PINP levels (median: 149.7 ng/ml) than those with fewer than seven (median: 67.6 ng/ml, p = 0.04). Significant differences were also found for osteocalcin and CTX, at p = 0.02 and p = 0.04, respectively, although the median levels remained under the normal cut-off levels. In terms of response assessment of bone spread, the PINP concentrations decreased in responders from 194.3 ng/ml to 100.4 ng/ml (p = 0.23). In patients with SD, PINP remained at the same level of approximately 70 ng/ml (p = 0.16), but increased in patients with PD from 83.4 ng/ml to 176.5 ng/ml (p = 0.14). These trends rather than statistical difference were probably due to the limited patient cohort. No differences were found for the serum concentrations of PINP, CTX and osteocalcin between post- and pre-menopausal women.The PINP levels of the osseous metastatic breast cancer patients were elevated at baseline in comparison to those without bone involvement; the levels correlated to the number of bone metastases but were independent of the menopausal status. Thus, the levels of PINP under therapy might correlate with the response to therapy. Osteocalcin and CTX did not show similar sensitivity for the surveillance of bone metastases.

To assess the role of allogeneic stem cell transplantation (SCT) after reduced-intensity conditioning (RIC) in acute leukaemias, we retrospectively compared 25 patients with acute lymphoblastic leukaemia or acute myelogenous leukaemia after RIC to a historical group of 50 matched controls after high-dose conditioning. Engraftment, acute GvHD and severe infections were comparable in both groups. During the observation period, 1/25 patients (4%) after RIC and 14/50 (28%) after standard SCT died due to transplant-related causes; cumulative nonrelapse mortality (NRM) was 4% after RIC and 24% after standard SCT (P=0.029). In total, 15/25 patients (60%) relapsed after RIC and 20/50 (40%) after standard SCT; probability of disease-free survival (DFS) at 3 years was 43% after RIC and 49% after standard SCT (NS). Overall survival (OS) was 40% after RIC and 37% after standard SCT (NS). Stage of disease, cytogenetic risk profile, acute and chronic GvHD, chimerism status at day 90 and severe infections after transplantation were risk factors with significant impact on DFS and/or OS. In retrospective analysis, patients with acute leukaemias who receive RIC because of contraindications against standard SCT have a comparable outcome to standard SCT, but the higher relapse rate warrants further studies.

Early detection before scintigraphic appearance of osseous metastatic spread might improve the outcome of breast cancer patients. The amino-terminal propeptide (PINP) of type I collagen as an indicator of bone formation is a very promising candidate among all markers of bone metabolism. We investigated the utility of total PINP in breast cancer patients at different stages of the disease.Precision tests using controls and serum pools were done for total PINP on the Elecsys2010 analyzer (electrochemiluminescence immunoassay - ECLLA). Baseline samples of 51 breast cancer patients with metastatic disease plus 11 patients under neoadjuvant treatment were available. Altogether, 38 patients had been diagnosed with bone metastases while 24 had no evidence of metastatic spread to the bone.For serial precision (intra assay), we found coefficients of variation between 1.2-2%. Total imprecision according to the NCCLS protocol ranged from 1. 7-5.4% only. Retrieval in ring trials was between 94% and 103%. ROC analysis of osseous versus nonosseous metastatic disease revealed an area under the curve (AUC) of 0.72. The sensitivity for the detection of bone lesions was 50% at the preliminary normal cut-off of 95 ng/mL. The baseline levels of the patients with bone metastases were significantly higher than those of patients with visceral of soft tissue spread only (p0.001). PINP concentrations correlated with osseous spread in terms of number and size of the bone lesions. Generally, non-osseous metastases did not produce elevated PINP levels in only 2/24 patients without bone metastases showing minimally elevated PINP concentrations (95 and 112 ng/ml).The Elecsys test for total PINP is highly reproducible. PINP concentrations can discriminate patients with bone metastases from those without osseous spread. The moderate sensitivity for the diagnosis of bone lesions may be biologically related to ineffective bone repair in a certain subset of patients. Further studies must focus on the monitoring of patients with elevated baseline levels and on those patients with low PINP levels in the case of otherwise proven bone metastases.

Tyrosine kinase signal transduction pathways are a focus of interest for therapeutic interventions. The oncoprotein HER-2/neu shows tyrosine kinase activity leading to phosphorylation and activation of numerous second-messenger systems. One target of phosphorylation processes is assumed to be the tumor type M2 isoenzyme of pyruvate kinase (TuM2-PK) which has been shown to be elevated in metastatic breast cancer.We measured the plasma levels of HER-2/neu, TuM2-PK and tyrosine-phosphorylated TuM2-PK (p-TuM2-PK) in 69 patients (pts) with breast cancer and correlated these parameters to each other and to the classical tumor marker CA 27.29. The samples were measured with ELISA assays while CA 27.29 was determined with an automated chemiluminescence assay. For analysis, we formed 5 subgroups according to the plasma HER-2/neu levels (group 1:15 ng/ml, n = 28; group 2: 15or = x50 ng/ml, n = 21; group 3: 50or = x100 ng/ml, n = 9; group 4: 100or = x500 ng/ml, n = 7; group 5:or = 500 ng/ml, n = 4).From the HER-2/neu group 1 to group 5, there was a statistically significant increase of CA 27.29 from 35.8 U/ml to 1095.8 U/ml (p0.001). There was also a trend for increasing TuM2-PK levels with increasing HER-2/neu levels (p = 0.126). From the lowest extinction (0.088) to the highest extinction result (2.167) of p-TuM2-PK we found a 25-fold increase, which was reproducible in spiking and dilution experiments proving that TuM2-PK is phosphorylated at tyrosine residues to a certain extent. However, there was no correlation between plasma HER-2/neu and p-TuM2-PK levels.TuM2-PK is phosphorylated at tyrosine residues in breast cancer patients. Using the shed antigen of HER-2/neu in plasma as a surrogate marker, we did not find any evidence that this phosphorylation is initiated by the oncoprotein HER-2/neu.

Experimental designs in medicine are often characterized by repeated observations on the same patient. In an approach of analysis of variance, you may analyse such data with the help of multivariate analysis of variance for repeated measurements ((1980)).

The amplitude modulation following response (AMFR) has been shown to be a promising tool for objective frequency-specific assessment of hearing thresholds children. AMFR represented in the frequency domain by a single spectral line. This simplifies the objective statistical detection in comparison other responses with a more complex waveform. The aim of the present study is to compare the performance of four known tests (phase coherence (PC), new Hotelling T2 (HT2*), modified PC (PC*), magnitude-squared coherence (MSC)) on the basis of a large sample (n=1484) of AMFR recordings (stimulus level of 30 dB nHL in normally-hearing subjects, and 30 dB SL in hearing-impaired subjects) to find the test best suited for AMFR detection. The decision was made on the basis of the detection rates as well as of the ROC curves. Based on the large data pool, MSC and PC* show equal performance and a small but consistent advantage in objective detection of AMFR over HT2* and PC.

Recently, a high validity correlation of the tumor M2 pyruvate kinase (Tu M2-PK) isoenzyme in comparison to standard tumor markers has been demonstrated in solid tumors. We investigated this marker in 67 patients with advanced breast cancer (ABC) in comparison to healthy controls.Plasma Tu M2-PK was measured using an ELISA assay (ScheBo Tech, Giessen, Germany) while serum CA27.29 was determined using a chemiluminescent immunoassay (Bayer Diagnostics, Tarrytown, USA).In a ROC analysis, the cut-off to discriminate patients from controls was established at 15 U/ml for Tu M2-PK (specificity 85%; positive predictive value 81%) and 30 U/ml for CA27.29 (specificity 91%; positive predictive value 92%). Median ABC baseline levels (ranges) in patients with ABC for Tu M2-PK and CA27.29 were 12.8 U/ml (4.8-252,495) and 130 U/ml (13.3-8130), respectively. Response assessment was done in 45 chemotherapy courses of 38 pts. In 13 out of 19 blocks (68.4%) with PD (progressive disease), an elevated level of Tu M2-PK at baseline or in the follow-up was found. In 17 out of 20 blocks (85%) with SD (stable disease), the Tu M2-PK level was normal at baseline or normalised within 4 weeks of treatment. All 6 patients with disease remission had a normal baseline Tu M2-PK level or the levels decreased promptly.Tu M2-PK gives additional information about ABC, indicating disease activity and sensitivity to chemotherapy while CA27.29 reflects tumor burden.

The assessment of bone metastases by clinical examination or imaging techniques is still considered unreliable. We compared a specific marker of bone resorption, urinary deoxypyridinoline (DPD)-crosslinks, with serum calcium (Ca), alkaline phosphatase (AP) and CA27.29, to evaluate the status of bone metastases in patients with breast cancer.Second morning voided urine was collected from 2 groups of patient (pts), those without evidence of disease (n = 118), and those with bone metastases (n = 85) under specific therapy plus pamidronate. DPD and CA27.29 were measured on the automated ACS180 system (Bayer Diagnostics, Tarrytown, NY, USA). Receiver operating characteristics (ROC) curves were established for each of the 4 biomarkers to determine whether they could distinguish the 2 subsets of pts with clinically sufficient validity, and to establish the corresponding cut-off values.Neither Ca nor AP was useful in discriminating the 2 subgroups. At a DPD cut-off of 13 nmol/mmol, we found a specificity of 69% and a sensitivity of 53% for diagnosing bone metastases. Best results, however, were seen for CA27.29. A cut-off value of 30 U/ml resulted in a specificity of 62% and a sensitivity of 81%.CA27.29 was the best parameter for the discrimination of stage IV breast cancer with bone metastases. The primary advantage of DPD lies in the monitoring of bone metastases under specific therapy.

The objective of our study was to assess the hemodynamic effects of immunoadsorption (IA) and subsequent immunoglobulin G (IgG) substitution in comparison with the effects of conventional medical treatment in patients with dilated cardiomyopathy (DCM).Various circulating cardiac autoantibodies have been detected among patients suffering from DCM. These antibodies are extractable by IA.Patients with DCM (n = 18, New York Heart Association III-IV, left ventricular ejection fraction30%) and who were on stable medication participated in the study. Hemodynamic measurements were performed using a Swan-Ganz thermodilution catheter. The patients were randomly assigned either to the treatment group with IA and subsequent IgG substitution (IA/IgG group, n = 9) or to the control group without IA/IgG (n = 9). In the IA/IgG group, the patients were initially treated in one IA session daily on three consecutive days. After the final IA session, 0.5 g/kg of polyclonal IgG was substituted. At one-month intervals, IA was then repeated for three further courses with one IA session daily on two consecutive days, until the third month.After the first IA course and IgG substitution, cardiac index (CI) increased from 2.1 (+/-0.1) to 2.8 (+/-0.1) L/min/m2 (p0.01) and stroke volume index (SVI) increased from 27.8 (+/-2.3) to 36.2 (+/-2.5) ml/m2 (p0.01). Systemic vascular resistance (SVR) decreased from 1,428 (+/-74) to 997 (+/-55) dyne x s x cm(-5) (p0.01). The improvement in CI, SVI and SVR persisted after three months. In contrast, hemodynamics did not change throughout the three months in the control group.Immunoadsorption and subsequent IgG substitution improves cardiovascular function in DCM.

Morbidity and mortality, disease-free- and overall survival were analysed in an adjuvant high-dose chemotherapy (HDCT) study with ifosfamide and epirubicin for high-risk (or = 10 positive lymph nodes) breast cancer.A total of 21 patients (pts) were treated with 4 cycles of ViEC (vindesine, epirubicin, cyclophosphamide) as standard chemotherapy. After the second cycle, CD34+ stem cells were mobilised with G-CSF. HDCT consisted of epirubicin 100 mg/m2 on days (-5)-(-4) before stem-cell rescue and ifosfamide 5000 mg/m2 on days (-5)-(-2).No therapy-related deaths occurred. Mucositis WHO grade III/IV in 52% and neutropenic fever in 81% were the most relevant toxicities. Nausea and vomiting WHO grades III/IV were found in 62.2%. The median duration of leucopenia grade IV was 7 days (range: 4-11) with a median time to platelet recovery50,000/microliter of 6 days (range: 4-11). After a median follow-up time of 21 months (range: 12-49 months), six of 21 pts (28.6%) relapsed. Two patients died 12 and 18 months after initial diagnosis.Adjuvant HDCT with epirubicin and ifosfamide is safe and shows good tolerability for high-risk breast cancer.

In a previous paper Wernecke, Kalb (1999) applied the multivariate repeated measures analysis of variance (Timm (1980)) as well as the method of data alignment (Hildebrand(1980)) to a cross-over clinical trial. The latter method consists of an adjustment of those factors not regarded in the current analysis and a following rank analysis of variance. However, the precondition of independent groups for this analysis is only valid from a practical point of view (Jones, Kenward(1990) assume the groups as independent, if the wash-out-phases will be large enough). Furthermore, ranking after alignment supposes quantitative scaling.

Urinary deoxypyridinoline (DPD)-crosslinks have been shown to be a highly specific parameter for type I collagen metabolism.In a prospective breast cancer study, urine samples were collected in after-care patients and in patients with bone metastases. DPD-crosslinks were measured every three weeks using a fully automated chemiluminescence immunoassay. Bone metastases were confirmed by bone scan and/or x-ray, and were followed-up over six months. To validate the test, a receiver operating characteristics (ROC)-curve was set up to find the DPD cut-off concentration which separates patients with no evidence of disease (NED) from patients with bone metastases.73 breast cancer patients (41 with NED, 32 with bone metastases) were included into the ROC analysis. At a DPD cut-off value of 8 nmol/mmol creatinine, we found the best sensitivity (84.4%) for the detection of bone metastases with a specificity of 70.7%. Patients with stable bone disease under intravenous pamidronate treatment (90 mg q3w) and specific therapy had a significant (p = 0.007) fall of the DPD-crosslinks in comparison to the progressive subset with 72.7% falling below 8 nmol/mmol.We conclude that the net bone turnover is not increased at a DPD-crosslinks elimination8 nmol/mmol.

The purpose of this investigation was to examine the characteristics of breathing-related fluid flow in the trachea of human fetuses with congenital diaphragmatic hernia in the hopes of developing a standard for the prenatal diagnosis of the degree of severity of the resulting pulmonary hypoplasia. Our ultimate goal is the prediction of postnatal mortality in fetuses with congenital diaphragmatic hernia.The study comprised six cases of isolated congenital diaphragmatic hernia (one on the right side; five on the left) varying in gestational age from 26 to 36 weeks. Four of the patients survived after surgical repair and two died during the neonatal period owing to lung hypoplasia. Color Doppler was used to visualize the fluid displacement in the trachea generated by fetal breathing movements. Spectral Doppler was then used to analyze the fluid flow velocity waveforms. More than 40 continuous breathing cycles (inspiration + expiration) were recorded for each case. We distinguished between regular and irregular patterns.Only the regular breathing phases, defined as five or more consecutive cycles of symmetric appearance, were considered for analysis. The inspiration and expiration times, the peak velocity of inspired and expired fluid and the volume obtained by integration of the tracheal fluid flow displaced during fetal breathing were compared with those of five healthy fetuses for each gestational age. Only the tracheal volume flow was helpful in predicting outcome. In normal pregnancies this parameter increased from 0.21 +/- 0.10 ml/breath (mean +/- SD) at 26 weeks to 1.37 +/- 0.48 ml/breath at 36 weeks of gestation. A significantly low (p0.05) volume flow was found only in the fetuses with congenital diaphragmatic hernia with a lethal postnatal outcome, whereas this parameter was normal in all survivors.Our preliminary observations suggest that the tracheal volume flow during fetal breathing activity is related to lung growth. In fetuses with severe lung hypoplasia one would expect a significant reduction in this parameter as an expression of deficient fetal lung growth. The displaced fluid volume per breath in the trachea of human fetuses as assessed by Doppler ultrasound may be a useful predictor of outcome in cases of isolated congenital diaphragmatic hernia.

A procedure is described for coupling different discriminators to a new (common) decision rule using the corresponding allocation vectors only. This enables one to cope jointly with data of different structure and/or scales of measurement but without strong restrictions on the number of (especially categorical) features. The method is combined with a consequent cross-validation process securing the results reached. Examples from medical diagnostics demonstrate the usefulness of the proposed procedure, especially in comparison with the known linear discriminant analysis as judged from the error rates obtained.

Fur eine exploratorische Auswertung raumbezogener Daten lassen sich neben speziellen Geoinformationssystemen auch Datenanalysesysteme nutzen, sofern sie uber flexible Programmiermoglichkeiten und komfortable Graphik verfugen. Die Datenstruktur des dynamischen Graphiksystems DGS von ISP ist dabei besonders geeignet, Methoden der hochinteraktiven Graphik auf Daten mit geographischem Bezug anzuwenden. Im Beitrag wird gezeigt, wie unter ISP ein “rechnendes” Geoinformationssystem entwickelt werden kann, das sich gut fur die Auswertung von Umwelt- und Gesundheitsdaten nutzen last. Die Moglichkeiten dynamischer Graphik werden am Beispiel der Analyse der Kontaminationung von Trinkwasser gezeigt.

Es wird ein Verfahren vorgestellt, welches die simultane Verarbeitung von Datensatzen behebiger Merkmalsskalierung und/oder Strukturierung (d.h. z.B. unabhangig gewonnene Beobachtungen oder zeitlich zusammenhangende Messungen — Zeitreihen) gestattet.

We describe the new computerized rhinologic diagnostic system "CARIMA", a software-controlled system based on a measuring head and a PC. The currently available software allows active anterior rhinomanometry to be carried out with a special program for the nasal allergen test, as well as active posterior rhinomanometry and the determination of the laryngotracheal resistance in patients with an open tracheostoma. The measurement procedure is controlled by the patient by watching the screen during data collecting. The breaths are averaged after curve correction by splining, introducing a time-referred system into the computerized rhinomanometry. The advantage of the method is a detailed analysis of the increasing and decreasing part of the inspiratory and exspiratory half-wave, allowing clinical conclusions to be made about the nasal valve.

In otological and ophthalmological functional diagnostics it is typical to record for a certain individual several similar biopotentials under different conditions of stimulation and/or to collect various potentials for the same individual. Since the combination of these different data collected from a patient is of interest, coupling of the classification results obtained for each single data set seems desirable. Based on sample classifiers, obtained by linear discriminance analysis, of acoustically or visually evoked potentials from selected patients an algorithm is proposed for their coupling, which logically links the various rules of allocation and is based on the principle of assignment by highest likelihood. Furthermore, the procedure may be modified by inclusion of corresponding confidence intervals for the determined allocation frequencies. The results obtained for the groups of patients investigated show a considerable improvement of classification as judged from the error rates being distinctly reduced after the coupling.

Using covariance analysis as an adjusted regression analysis it is possible, with the assumption of homogeneity and normality of variance, to test several regression functions for homogeneity, if the given groups of data material are independent. This well-known analysis is applied to a number of examination methods of ophthalmology. In the cases of ophthalmo-dynamography (ODG) and ophthalmo-dynamometry (ODM), the paper answers the question to what extent the result of ophthalmologic measurement is influenced by posture (sitting — lying — standing). Contrary to several authors' practice of combining the regression lines for the systolic and diastolic blood-pressure because of the improvement of the correlation coefficient to be achieved in this way, it was possible to show that generally such an approach is not recommendable. Patients suffering from a certain type of arteriosclerosis distinguish themselves by deviations of their ODG data from the normal blood-pressure relation of the arteria carotis interna and the arteria brachialis. These differences can be tested for statistical significance by means of covariance analysis.

Die Einfuhrung der computergestutzten Rhinomanometrie erleichtert nicht nur die Kontrolle der Meswertaufnahme und die Speicherung der gewonnenen Mesergebnisse, sondern fuhrt auch zu einem erweiterten Verstandnis der Physiologie der Nasenatmung. Dies setzt jedoch voraus, das die Mittelwertkurve, welche vereinbarungsgemas die Abhangigkeit zwischen Differenzdruck und Volumenstrom darstellt, nicht als Regressionskurve aus einer Anzahl von Einzelwerten in einer „Punktwolke“ bestimmt wird, sondern das aus einer Anzahl von Atemzyklen zeitbezogen ein „reprasentativer Atemzug“ fur die beiden Mesgrosen berechnet wird, welcher alle 4 Quadranten der sinusahnlichen Kurve getrennt zur Darstellung bringt. Dies wird durch die Einfuhrung der Spline-Interpolation in die Rhinomanometrie erreicht. Da die Druck-Stromungsbeziehung wahrend der an- und abschwellenden in- und exspiratorischen Anteile des Atemzyklus nur zufallig gleich ist, ergibt sich als allgemeine Kurvenform dieser Beziehung eine Schleife (Abb. 1 b) anstelle einer einfachen gebogenen Kurve (Abb. 1 a). Der Abstand zwischen den Schenkeln im in- und exspiratorischen Kurventeil wird durch Phasenverschiebungen zwischen Druck- und Stromungssignal bestimmt.

Many authors consider the nature of the slow acoustically evoked potentials to be partly a specific one. Therefore the AEP-time behavior probably contains more information about the functional state of the acoustical channel than it is got by the usual measurement of only 3 values (N1P2-amplitude, 2 latencies). A test of this hypothesis is possible with a multivariate mathematical procedure, which involves the whole AEP-time behavior. We are using the multivariate variance- and discriminant analysis. For the application of this statistical method random samples of patients with certain otologic diseases are needed. To avoid mistakes in grouping these samples some preliminary investigations had been necessary: This paper reports the results of multivariate investigations concerning age differences of the AEP in normal hearing adults. By means of the multivariate variance analysis the AEP of 3 age groups were examined (group 1: 15--34 years, group 2: 35--44 years, group 3: 45--60 years). At 1000 Hz as well as at 400 Hz significant differences between the group averages were found, which were not detectable by the usual N1P2-amplitude measurement. Furthermore with the discriminant analysis it is possible to perform a relatively reliable differentiation between the individual AEP of the age groups 1 and 3.

By means of the multivariate variance analysis the ratio of intra- and interindividual variability of the AEP--time function was investigated. 90 AEP from 9 normal hearing persons (10 AEP from every person, averaging sessions spread over 10 weeks) were analyzed. The 10 AEP of every person were treated as a random sample. A multivariate pair comparison (single comparison between samples) on the basis of 12 variables (time points) showed only for 1 out of 36 sample pairs no significant differences between the sample averages. By applying the discriminant analysis false classifications resulted only for 7 out of the 90 AEP (approximately 8%). These facts mean, that even throughout the time of 10 weeks the intraindividual differences of the AEP--time behavior are significantly smaller than the interindividual ones.