Mobile App-based documentation of patient-reported outcomes - 3-months results from a proof-of-concept study on modern rheumatology patient management.

BACKGROUND: Mobile medical applications (Apps) offer innovative solutions for patients' self-monitoring and new patient management opportunities. Prior to routine clinical application feasibility and acceptance of disease surveillance using an App that includes electronic (e) patient-reported outcome measures (PROMs) warrant evaluation. Therefore, we performed a proof-of-concept study in which rheumatoid arthritis (RA) patients used an App (RheumaLive) to document their disease. METHODS: Accurate PROM reporting via an App in comparison to paper-based versions was investigated to exclude media bias. Sixty participants recruited from 268 consecutive RA outpatients completed paper-based and electronic PROMs (Hannover Functional Questionnaire/derived HAQ; modified RA disease activity index) using the App at baseline and follow-up visits. Between visits, patients used their App on their own smartphone according to their preferences. The equivalence of PROM data and user experiences from patients and physicians were evaluated. RESULTS: Patients' (78.3% female) mean (SD) age was 50.1 (13.1) years, disease duration 10.5 (9.1) years, and paper-based HAQ 0.78 (0.59). Mean confidence in Apps scored 3.5 (1.1, Likert scale 1 to 6). ePROMs' scores obtained by patients' data entry in the App were equivalent to paper-based ones and preferred by the patients. After 3 months, the App retention rate was 71.7%. Patients' overall satisfaction with the App was 2.2 (0.9, Likert scale 1 to 6). Patients and physicians valued the App, i.e., for patient-physician interaction: 87% reported that it was easier for them to document the course of the disease using the App than "only" answering questions about their current health during routine outpatient visits. Further App use was recommended in 77.3% of the patients, and according to physicians, in seven patients, the App use contributed to an increased adherence to therapy. CONCLUSION: Our study provides an essential basis for the broader implementation of medical Apps in routine care. We demonstrated the feasibility and acceptance of disease surveillance using a smartphone App in RA. App use was convincing as a reliable option to perform continuous, remote monitoring of disease activity and treatment efficacy. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02565225 . Registered on September 16, 2015 (retrospectively registered).

Factors associated with pain coping and catastrophising in patients with systemic lupus erythematosus: a cross-sectional study of the LuLa-cohort.

OBJECTIVE: The aim of this study was to identify factors associated with pain coping and catastrophising in patients with systemic lupus erythematosus. METHODS: All patients were participants of the lupus erythematosus long-term study, which is based on patient-reported data assessed among members of the German Lupus Erythematosus Self-Help Organization. Assessments were performed by means of a questionnaire. Among self-reported clinical data the Pain-Related Self Statements Scale (PRSS) was included. To depict significant differences univariable analyses were carried out using non-parametrical rank tests. To examine factors influencing our outcome variables, we performed a multivariable stepwise regression model including variables that presented significantly in the univariable analysis. RESULTS: 447 cases (94.9% female) were analysed showing a mean catastrophising score of 1.1 (SD 0.8) and a mean coping score of 2.8 (SD 0.9) in the PRSS subscales. Higher catastrophising quartiles went along with higher experienced pain, lupus activity, fatigue, damage and decreased health related quality of life, whereas they presented inversely for coping. In our multivariable model, factors associated with catastrophising were: number of lupus-specific drugs (p value 0.004), pain in the last 7 days (p value 0.034), the Short Form 12 Health Survey Mental Component Summary (p value <0.001) and disease activity measured by the Systemic Lupus Activity Questionnaire (p value 0.042). Social participation reflected by performed leisure activities such as dancing or bowling had a positive association with coping (p value 0.006). In contrast, other health related physical activities and their extent had no impact on coping. A direct association between the amount of pain coping and catastrophising, as well as a great impact of the catastrophising, respectively, coping level on physical and mental functioning could be shown. CONCLUSIONS: Reduction or increase of detected factors might lead to a modification of pain coping and catastrophising and offer an approach to more effective care in patients with SLE.

Regional deep hyperthermia for salvage treatment of children and adolescents with refractory or recurrent non-testicular malignant germ-cell tumours: an open-label, non-randomised, single-institution, phase 2 study.

BACKGROUND: Although the survival of children and adolescents with malignant germ-cell tumours has improved greatly in recent years, the outcome remains poor for those with refractory or recurrent malignant germ-cell tumours. We aimed to determine whether objective tumour response could be achieved in patients with refractory or recurrent malignant germ-cell tumours with PEI-regional deep hyperthermia as salvage treatment. METHODS: Patients with refractory or recurrent non-testicular malignant germ-cell tumours after standard cisplatin-based chemotherapy were treated prospectively with PEI chemotherapy (cisplatin 40 mg/m(2), delivered intravenously on days 1 and 4; etoposide 100 mg/m(2), intravenously on days 1-4; and ifosfamide 1800 mg/m(2), intravenously on days 1-4) plus simultaneous 1-h regional deep hyperthermia (41-43°C) on days 1 and 4. Patients received three to four treatment courses at 21-day intervals until residual tumour resection was possible; they subsequently received one or two additional courses of PEI-regional deep hyperthermia. Local radiotherapy was given for incompletely resected tumours. Chemotherapy and hyperthermia toxic effects were assessed using WHO grading. The primary endpoint was the proportion of patients who had an objective response as assessed with Response Evaluation Criteria in Solid Tumors version 1.0 guidelines. Secondary endpoints were the event-free survival and overall survival after 5 years. This ongoing PEI-regional deep hyperthermia study (Hyper-PEI protocol) is registered at the German Cancer Society, number 50-2732. FINDINGS: 44 patients aged 7 months to 21 years (median 2 years 7 months) with refractory or recurrent malignant germ-cell tumours (nine patients with poor response, 23 patients with first relapse, 12 patients with multiple relapses) were included in this study. We identified 34 yolk sac tumours, eight embryonal carcinomas, one choriocarcinoma, and one dysgerminoma by histology analysis. Of the 35 patients who had sufficient clinical and radiographical data available for response assessment, 30 (86%) had an objective response to treatment (16 patients had complete remission and 14 had partial remission). 5-year event-free survival was 62% (95% CI 45-75), and 5-year overall survival was 72% (95% CI 55-83). The median follow-up of surviving patients was 82 months (range 9-195). WHO grade 3-4 neutropenia and thrombocytopenia occurred in all 181 chemotherapy cycles. Granulocytopenic fever, which required intercurrent hospital admission, was noted in 29 (66%) of 44 patients after 53 (29%) of 181 courses. Five patients experienced treatment-related grade-3 acute renal toxic effects. INTERPRETATION: A multimodal strategy integrating PEI-regional deep hyperthermia and tumour resection with or without radiation can successfully treat children and adolescents with refractory or recurrent malignant non-testicular germ-cell tumours. The long-term prognosis of patients with poor response or after first relapse was almost similar to those receiving first-line treatment. This strategy merits further investigation. FUNDING: Deutsche Krebshilfe eV, Bonn, Elterninitiative Kinderkrebsklinik Düsseldorf eV, the Barbara and Hubertus-Trettnerstiftung, and the Marie Quendt Fund.

Radiological outcome and gait function of SCFE patients after growth arrest.

PURPOSE: Slipped capital femoral epiphysis (SCFE) represents the most common disorder of the hip in adolescents and a preliminary stage of degenerative joint disease. Up to now, functional outcome evaluation measured by objective instruments has been commonly neglected. The present study investigates whether the pathoanatomy of the hip joint after SCFE-analyzed on a standard X-ray-match functional results gained by three-dimensional gait analysis. A variation of functional outcome depending on the radiological findings after growth arrest is hypothesized. METHODS: Thirty-seven SCFE patients after growth arrest [mean age 18.5 years, standard deviation (SD) 4.61] with unilateral affection were included. The pathoanatomy of the hip joint was classified according to the radiological index of Heyman and Herndon and to aspherity. Three-dimensional gait analysis parameters were evaluated and subgroup analysis was performed according to the radiological results. RESULTS: The radiological findings revealed very good results in general (average comprehensive index of Heyman and Herndon 94 ± 9 %, aspherity grade <2). Significant deviations of gait parameters in relation to the radiological result were an increase in step width, sagittal range of motion (ROM) of the pelvis and foot progression for the worse subgroup. CONCLUSIONS: Taken as a whole, the pathoanatomy of the hip joint after SCFE matched the functional results gained by gait analysis. Functional outcome varied slightly depending on the radiological findings after growth arrest. Differences were most pronounced for foot progression. Only with the help of gait analysis was it possible to describe deviations more precisely and objectively. Further studies are required in order to show which alterations are relevant for the development of secondary osteoarthritis.

Thymoma-a clinico-pathological long-term study with emphasis on histology and adjuvant radiotherapy dose.

INTRODUCTION: To evaluate prognostic factors of thymic epithelial tumors (TETs) with particular reference to histology and the dose-response relationship of adjuvant radiotherapy. METHODS: Retrospective study with central pathological review on patients resected for TET between 1966 and 2004 at a single institution. Prognostic factors were identified using Cox regression analysis. RESULTS: From 93 patients with TET, 33.3% relapsed and 47.3% died. Cause of death was known in 64% and attributed to TET in 25%. Myasthenia gravis was associated with superior disease-free survival (DFS) and overall survival (OS). Tumors smaller than 8.5 cm had a significantly better prognosis. With a median follow-up of 9.8 years actuarial OS at 5, 10, and 20 years were 96%, 92%, and 47% in stage I; 85%, 61%, and 53% in stage II; 72%, 39%, and 15% in stage III and IV. Advanced stage and incomplete resection had a negative impact on DFS and OS. According to histology (WHO type A, AB, B1; favorable; versus WHO type B2, B3; intermediate; versus thymic carcinoma, unfavorable) three prognostic groups were discernible. On multivariate analysis, tumor size, and stage emerged as prognostic factors, but neither histology nor myasthenia. Postoperative radiotherapy was administered in 27 patients (median dose 50.8 Gy). Doses in excess of 50 Gy were associated with significantly improved DFS and OS. CONCLUSIONS: Tumor stage, histology, complete resection, and tumor size had a significant impact on survival. Myasthenia may facilitate early detection and is correlated with superior survival. When postoperative radiotherapy is administered, doses above 50 Gy may improve outcome.

The gait function of slipped capital femoral epiphysis in patients after growth arrest and its correlation with the clinical outcome.

PURPOSE: Slipped capital femoral epiphysis (SCFE) represents the preliminary stage of osteoarthritis. Reliable tools for outcome evaluation should be developed to prevent persisting defects. The functional outcome of SCFE-patients after growth arrest is analysed by instrumented 3D-gait analysis (GA). The results are matched to the clinical examination findings. METHODS: A total of 39 SCFE patients after growth arrest (18.8 years; BMI 26.5 kg/m²) with unilateral affection were included. The clinical results were classified according to Harris hip and clinical Heyman Herndon scores. 3D-GA-parameters were evaluated and compared to the sound side and a group of 40 healthy adults (28.0 years; 21.9 kg/m²). The subgroup analysis was performed according to clinical results. RESULTS: The clinical examination revealed very good results. GA could detect even small alterations. Some parameters indicated sustained functional impairments: Compared to the control group patients' walking speed (p = 0.022), step frequency (p < 0.001) and single support of the slip side (p < 0.001) decreased, while step width (p = 0.014), double support (p = 0.004) and stance time of sound side increased (p = 0.001). For kinematics patients, the sagittal range of motion (ROM) of pelvis (p < 0.001) and the external rotation of the ankle on both sides increased (p = 0.011) and sagittal ROM of hip (p = 0.002) and knee flexion of slip side (p < 0.001) decreased. The sagittal ROM of the ankle on the slip side decreased compared to the sound side (p = 0.003). Subgroup analysis revealed a positive correlation between clinically unsatisfying results and GA parameters. CONCLUSIONS: Functional impairments in SCFE-patients can be found even after growth arrest. Alterations are explained partly by the disease and partly by patients' constitution. BMI-matched controls and long-term follow-up are needed.

An ask-the-expert service on a rheumatology web site: who were the users and what did they look for?

OBJECTIVE: To analyze the inquiries sent to an online ask-the-rheumatologist service in order to identify the users' needs and requirements. METHODS: The official web site of the German Competence Network Rheumatology (www.rheumanet.org) provided expert information for patients, relatives, and physicians. We analyzed the content of 1,133 inquiries posted over 5 years and the experts' answers were blinded for analyses. RESULTS: Patients (60.0%), relatives (24.3%), and physicians (15.7%) addressed the experts. Inquiries were predominantly sent by women (62.2%). Distinct rheumatic diseases were mentioned in 40.5% of the inquiries, and 16.3% reported musculoskeletal symptoms without a definite diagnosis. The number of questions ranged from 1-7 per inquiry (mean±SD 1.58±0.9). Of the inquiries, 33.2% contained personal histories, 24.9% searched for a rheumatologist nearby, and 11.6% asked for a "second opinion." The questions covered a wide range of interests, including medication (30.8%), diagnosis-related issues (15.7%), laboratory tests (6.9%), (treatment) guidelines (6.2%), sexual and reproductive health issues (4.1%), and clinical trials (3.4%). In more than 50% of the inquiries, the information requested from the experts was already at least partly published on the web site. The experts' answers covered the users' questions completely in 91.8%, partly in 6.1%, and not at all in 2.1%. CONCLUSION: A standardized medical web site providing tailored and trustworthy information for all user groups gains from an ask-the-expert service. Only such an interactive online application is able to satisfy users' actual demands: searching for specific individualized information on the internet. Therefore, an ask-the-expert service contributes to optimized patient care.

Correlation of functional outcome and X-ray findings after Perthes disease.

PURPOSE: The purpose of this study was to evaluate the functional impairments during gait after Legg-Calvé-Perthes Disease (LCPD) and to correlate these data with the clinical and radiographic outcome. METHODS: In 13 individuals with LCPD in recovery or final stage (mean age 9.5 ± 3.5 years) with unilateral hip involvement the clinical result was graded according to Tönnis and the radiographic outcome according to Heyman and Herndon; the functional impairment during gait was compared to a group of healthy children (n = 30, mean age 8.1 ± 1.2 years). All children underwent computerised three-dimensional gait analysis. RESULTS: The standard physical examination resulted in 69.2% normal range of movement according to Tönnis, but overall analysis of gait revealed that only 30.7% had a normal gait pattern. All children with an excellent or good radiographic (n = 6) outcome walked normally or showed minor deviations. CONCLUSIONS: The results of the standard clinical examination do not reflect the function of the hip joint during gait. Additional information is revealed from gait analysis and should be part of outcome studies in LCPD.

The value of training in communication skills for continuing medical education.

OBJECTIVE: Question arises as to what extent communication skills are considered in continuing medical education (CME). METHODS: Analysis for CME-courses in communication skills in the area of the Chamber of Physicians North Rhine (ÄkNo), Germany. Supply Arm(A): CME events (n = 19,320) certified in 2007 were evaluated. Demand Arm(B): course participation of 850 family physicians in the period 2002-2007 was analyzed (n = 37,724). Tests were calculated to the level 0.05 using Mann-Whitney U-test. RESULTS: (A) 388 (2.0%) events were concerned with the topic communications. 59.3% involved active cooperation of the participants. 0.5% events devoted more than 50% of their duration to the topic communication. Proportions in the subjects of internal medicine, general medicine and pediatrics amounted to 0.2%. (B) 803 (2.1%) events with a focus on communication were identified. Women took part in significantly more events than men (p<0.002) and selected more interactive courses. CONCLUSION: Content on communication training was small. Increasing experience does not automatically improve communication skills but an extent of deliberate praxis seems to be necessary and must be sought and developed. PRACTICE IMPLICATIONS: Communication skills are still insufficiently provided in CME-courses and should be more directed to focus as treatment strategies and scientifically investigated for outcome improvements.

[Supply of and participation in CME activities in the area served the north rhine chamber of physicians in Germany]. / Angebot und Fortbildungsverhalten bei der Continuing Medical Education (CME) im Bereich der Ärztekammer Nordrhein.

INTRODUCTION: the study analyses the supply and the demand for Continuing Medical Education (CME) in the area served by the "Ärztekammer Nordrhein (ÄkNo)", which is one of the biggest regional Chambers of Physicians in Germany. Both the supply of all CME events certified by the ÄkNo in 2007 (n=18,932) and the participation of physicians in CME activities - using the example of family doctors (n=850), ophthalmologists (n=122) and orthopaedists (n=38) in the university towns of Cologne, Bonn and Aachen - was analysed for the period of 2002 to 2007 (n=44,760 events). METHODS: differences between groups were tested by the nonparametric Kruskal-Wallis method; adjustment for other factors was performed using Cochran-Mantel-Haenszel tests. The significance level was chosen to be 0.05. RESULTS: half of the accredited CME activities had been provided in the form of lectures accompanied by discussion. This didactic focus is reflected by the CME choices of the analysed physicians, although interactive, multimedia materials and case based formats have been demonstrated to be advantageous. Family physicians and ophthalmologists participated twice as often in CME events as orthopaedists (p<0.001). Across all the disciplines investigated, female physicians participated significantly more often in CME events than their male colleagues (p<0.03). CONCLUSION: our results show individual, group and gender specific differences in Continuing Medical Education which so far have not been adequately recognised and which warrants more research on CME.

Correlation of viral load of respiratory pathogens and co-infections with disease severity in children hospitalized for lower respiratory tract infection.

BACKGROUND: The clinical significance of viral load and co-infections in children with respiratory infections is not clear. OBJECTIVE: To evaluate the correlation of viral load as well as viral and bacterial co-infections with disease severity in hospitalized children with lower respiratory tract infections (LRTIs). STUDY DESIGN: This is a prospective study conducted in children admitted for LRTIs for two seasons. To determine viral and bacterial load of respiratory pathogens we performed multiplex real-time polymerase chain reaction and semiquantitative bacterial cultures on nasopharyngeal aspirates (NPA). RESULTS: During the study period 244 (60%) children were hospitalized for LRTI with acute virus-induced wheezing and 160 (40%) for radiologic confirmed pneumonia. In the first NPA, viruses were identified in 315 (78%) of the 404 samples and bacteria in 198 (63.3%) of 311 samples. The viral load significantly decreased between the first and second NPA sample in most single and viral co-infections, except rhinovirus and human bocavirus infections. Viral load was inversely related to CRP in RSV infections, whereas a positive correlation was observed in adenovirus infections. Duration of hospitalization was significantly longer in RSV single infections compared to rhinovirus single infections whereas in the latter, leucocytosis and use of systemic steroids was more common. In RSV viral co-infections the presence of fever, leucocytosis, and the use of antibiotics was significantly more frequent. Positive cultures of Haemophilus influenzae dominated in RSV and rhinovirus single infections and Moraxella catarrhalis in RSV viral co-infections. CONCLUSIONS: Specific viral single and co-infections as well as viral load contribute to disease severity in children with LRTIs.

Changing attitudes towards online electronic health records and online patient documentation in rheumatology outpatients.

OBJECTIVES: The Internet supports interactive patient assessments, online documentation and access to online electronic health records (EHRs), but little is known about the acceptance of these features and trends in rheumatology patients. Therefore, we studied patients' attitudes and willingness to participate in online patient (self-)documentation. METHODS: We interviewed 153 consecutive outpatients with rheumatoid arthritis, systemic lupus erythematosus or spondyloarthritis using a paperbased self-administered questionnaire. To detect recent trends in patients' perception we compared our 2006 data to the results of our survey conducted in 2001. P-values provided in the abstract reflect the comparisons from 2001 and 2006. RESULTS: Patients were predominantly female (69.3%; n.s.), mean age was 45.7+/-14.4 years (n.s.), and 68.6% (+18.6% compared to 2001; p<0.001) reported regular Internet use. Confidence in the Internet and reliability of online information were rated unchanged to 2001. Internet users appreciated to access their EHR online in 68.6% (+13.8% compared to 2001; p<0.01), (self-)monitor the course of their disease online in 80.0%, and answer outcome questionnaires online in 67.6%. Internet users considered computers as valuable instruments in the patient-doctor relationship (88.4%), 58.8% were not convinced that computer use influences the relationship positively. CONCLUSIONS: Attitudes of patients with rheumatic disorders (Internet users and non-users) towards online EHRs have improved since 2001, online applications for patient assessments and disease (self-)management in rheumatology seem feasible now. Nevertheless, unchanged low confidence rates in the Internet and in the reliability of medical information derived from the Internet should sound a note of caution regarding the implementation of such services.

Retrospective study of neoadjuvant versus adjuvant radiochemotherapy in locally advanced noninflammatory breast cancer : survival advantage in cT2 category by neoadjuvant radiochemotherapy.

PURPOSE: This retrospective study compares patients treated between 1991 and 1998 with neoadjuvant radiotherapy +/- chemotherapy (RCT) or adjuvant RCT for locally advanced noninflammatory breast cancers (LABC) in terms of pathologic complete response (pCR), 10-year relapse-free (RFS), and overall survival (OS). PATIENTS AND METHODS: Preoperative RCT in 315 and adjuvant RCT in 329 cases consisted in 50 Gy (5 x 2 Gy/week) to the breast and the supra-/infraclavicular lymph nodes. 101 neoadjuvant patients received - in case of breast conservation - a 10-Gy interstitial boost with (192)Ir afterloading before and 214 neoadjuvant patients a preoperative electron boost after external-beam radiotherapy. In the neoadjuvant RCT group, chemotherapy was applied prior to radiotherapy in 192 patients, and simultaneously in 113; ten had no chemotherapy. In the adjuvant RCT group, chemotherapy was applied to 44 patients before surgery and to 166 after surgery; 119 had no chemotherapy. RESULTS: Breast conservation became possible in 50.8% after neoadjuvant RCT for LABC with a pCR rate at surgery of 29.2%. A complete nodal remission (pN0) after RCT was observed in 56% (89/159) of the cN+ (clinically node-positive) neoadjuvant patients. There were trends in favor of preoperative RCT for RFS and OS (hazard ratio [HR] = 0.85; p = 0.09 for RFS; HR = 0.8130; p = 0.1037 for OS). For patients with cT2 tumors the RFS and OS were statistically significantly better (HR = 0.5090; p = 0.0130 for RFS; HR = 0.4390; p = 0.0026 for OS) after neoadjuvant compared to adjuvant RCT. CONCLUSION: Neoadjuvant RCT achieved a pCR rate of 29.2% and a statistically significantly better RFS and OS in patients with cT2-category breast cancer.

Diagnostic of tooth fractures with the Vistascan system.

Compared with conventional films digital radiography allows a wide range of exposure and scanner settings. The aim of this study was to investigate the diagnostic accuracy of the evaluation of tooth fractures depending on variations of exposure dose, scanner settings and surrounding tissues. Extracted human teeth were exposed separately and in a pig bone phantom before and after artificial fracture at 70 kV (Gendex Oralix DC) and three exposure settings using the Vistascan System I at three different resolution settings. Five dental observers evaluated 432 radiographs of 12 adequately fractured teeth under randomized conditions for the existence of a tooth fracture on a five-point scale. The highest value of true ratings (76.7%) with pig bone vicinity was achieved at 56 micro Gy (160 ms) and 20 lp mm(-1), followed by 71.7% at 27 micro Gy (80 ms) and 20 lp mm(-1). The worst diagnostic accuracy of 56.7% true ratings resulted from 6 micro Gy (20 ms) and 10 lp mm(-1). With radiographs of teeth in empty surroundings the rate of true decisions was in some cases significantly higher. For the diagnostics of tooth fractures with the Vistascan System I the diagnostic value seems to depend on, besides radiographic projection, the scanner resolution setting, the surrounding tissues and the exposure dose.

Early conversion from cyclosporine to tacrolimus increases renal graft function in chronic allograft nephropathy at BANFF stages I and II.

Switching from cyclosporine to tacrolimus without steroid pulse was suggested as a therapeutic option in chronic allograft nephropathy (CAN). Thirty-one renal transplant recipients with CAN were prospectively converted from cyclosporine to tacrolimus (group A), in parallel 31 matched cyclosporin A (CsA) patients (group B) without CAN were followed up for 30 months. In six matching patients of groups A and B inulin and para-aminohippurate (PAH)-clearances and mycophenolate were measured over a span of 3 months. Transplant biopsies of group A were scored according to BANFF. While group A presented with transplant dysfunction compared with group B before switching (2.7 +/- 0.16 mg/dl vs. 1.7 +/- 0.09 mg/dl; P < 0.001), transplant function was equal 30 months later: it ameliorated in group A (2.0 +/- 0.18 mg/dl vs. 2.7 +/- 0.16 mg/dl; P < 0.001) and decreased in group B (1.9 +/- 0.13 mg/dl vs. 1.7 +/- 0.09 mg/dl, P < 0.05). Especially, patients with biopsy scores I and II according to BANFF benefited from tacrolimus. Within 3 months, mycophenolate acid (MPA) levels increased under tacrolimus (P < 0.05) whereas inulin and PAH-clearances remained unchanged. At switching, antihypertensive treatment was more intense in group B, but this difference evened out. Adverse side effects were more frequent under tacrolimus. Patients with mild to moderate CAN significantly benefited from switching to tacrolimus. Increased MPA-levels under tacrolimus might have contributed to this effect.

High nerve growth factor receptor (p75NTR) expression is a favourable prognostic factor in paediatric B cell precursor-acute lymphoblastic leukaemia.

Nerve growth factor (NGF) plays a pivotal role in cellular survival/death decisions with the low affinity receptor p75NTR predominately transmitting anti-proliferative signals. In spite of its established role in B-cell function and identification as a prognostically favourable marker in a number of malignancies, little is known about the expression pattern and prognostic significance of p75NTR in B cell precursor-acute lymphoblastic leukaemia (BCP-ALL). p75NTR expression was prospectively studied on primary ALL-blasts in a cohort of paediatric patients with common ALL (n = 86) and preB-ALL (n = 34) treated within the Co-operative study group for childhood acute lymphoblastic leukaemia (CoALL) protocol, CoALL06-97. Flow cytometric analysis showed that almost half of the patients expressed no or negligible amounts of p75NTR (<10%). The median expression in patients expressing p75NTR beyond that threshold was 49% (range 11-100%). In patients classified as low-risk at diagnosis, p75NTR expression was significantly higher than in high-risk patients (P = 0.001). Of note, p75NTR expression was lower in the 21 patients who subsequently developed relapse compared with those remaining in remission (P = 0.038). Accordingly, relapse-free survival was significantly better in patients expressing high surface p75NTR (P = 0.041). Thus, in this prospective analysis, high p75NTR expression was a strong prognostic marker that identified a group of paediatric ALL patients with favourable outcome.

Dynamic breast MR imaging: is parametric mapping superior to image subtraction in lesion detection?

We compared the detection of malignant lesions in two different methods of parametric-guided analysis to the widely used early subtraction images. The parametric colour-coded overlays were defined by the increase of signal intensity after contrast injection and the course of the time signal intensity curve. Exams of 30 patients with histopathological evidence of 32 invasive breast carcinomas were evaluated. Five hundred five areas of additional enhancing tissue were found in the early subtraction images. The sensitivity was 100 in the subtraction images and 100 and 93.8 in the parametric images, respectively, the specificity 67.5, 84.2 and 88.7, respectively. On average 4.4 ROI-measurements were needed to find the highest increase of signal intensity in the subtraction series compared to 1.9 in the parametric images. Properly selected thresholds in parametric imaging may be helpful in the differentiation of enhancing tissue. Furthermore the parametric image-guided ROI selection significantly speeds up the analysis and makes it safer as a lower rate of ROI-measurements is needed to find the strongest enhancement.

Plasma nitrite concentrations reflect the degree of endothelial dysfunction in humans.

A reduced nitric oxide availability is a hallmark of endothelial dysfunction occurring early in atherosclerosis. Recently, we have shown that plasma nitrite mirrors acute changes in endothelial nitric oxide synthase activity in various mammals, including humans. Here, we examined the hypothesis that plasma nitrite levels are reduced in humans with endothelial dysfunction and the decrease is correlated with increasing numbers of cardiovascular risk factors (RF). Plasma nitrite concentrations were quantified by flow-injection analysis. The coefficient of variation for repeated measurements of plasma nitrite was <8%, and heart rate and blood pressure at the time of blood sampling had no significant effect on nitrite values measured (n=10). Baseline levels of plasma nitrite followed a normal distribution in each group studied and decreased progressively with increasing numbers of cardiovascular risk factors (n=351, p<0.001): 351+/-13 (0 RF), 261+/-10 (1 RF), 253+/-11 (2 RF), 222+/-18 (3 RF), and 171+/-29 nmol/L (4 RF). Intima media thickness (IMT) and flow-mediated dilation (FMD) were determined via ultrasound. Plasma nitrite and FMD levels were lower, whereas IMT was greater in individuals with endothelial dysfunction (n=12) compared to healthy volunteers (n=12). Nitrite correlated significantly with FMD (r=0.56, p<0.001) and inversely with IMT (r= -0.49, p<0.01). Plasma nitrite levels are reliably measurable in humans, indicate endothelial dysfunction, and correlate with cardiovascular risk factors. Future studies are necessary to identify the prognostic relevance of plasma nitrite determination in patients suffering from cardiovascular disease.

Computerized gait analysis in Legg Calvé Perthes disease--analysis of the frontal plane.

OBJECTIVE: Current follow-up and outcome studies of Legg Calvé Perthes disease (LCPD) are based on subjective measures of function, clinical parameters and radiological changes [Herring JA, Kim HT, Browne RH. Legg-Calvé-Perthes disease. Part II: prospective multicenter study of the effect of treatment on outcome. J Bone Joint Surg 2004;86A:2121-34; Aksoy MC, Cankus MC, Alanay A, Yazici M, Caglar O, Alpaslan AM. Radiological outcome of proximal femoral varus osteotomy for the treatment of lateral pillar group-C. J Pediatr Orthop 2005;14 B:88-91; Kitakoji T, Hattori T, Kitoh H, Katho M, Ishiguro N. Which is a better method for Perthes' disease: femoral varus or Salter osteotomy? Clin Orthop 2005;430:163-170; Joseph B, Rao N, Mulpuri K, Varghese G, Nair S. How does femoral varus osteotomy alter the natural evolution of Perthes' disease. J Pediatr Orthop 2005;14B:10-5; Ishida A, Kuwajima SS, Laredo FJ, Milani C. Salter innominate osteotomy in the treatment of severe Legg-Calvé-Perthes disease: clinical and radiographic results in 32 patients (37 hips) at skeletal maturity. J Pediatr Orthop 2004;24:257-64.]. The objective of this study was to evaluate the frontal plane kinematics and the effect on hip joint loading on the affected side in children with a radiographic diagnosis of LCPD. MATERIAL AND METHOD: Computerized, three-dimensional gait analysis was performed in 33 individuals aged > or =5 years (mean 8.0+/-2 years) with unilateral LCPD and no history of previous surgery to the hip or any disorder leading to gait abnormality. Frontal plane kinematics and kinetics were compared to a group of healthy children (n=30, mean age 8.1+/-1.2 years). Hip joint loading was estimated as a function of the hip abductor moment. RESULTS: Subjects with LCPD demonstrated two distinct frontal plane gait patterns, both deviating from normal. Type 1 (n=3) was characterized by a pelvic drop of the swinging limb, a trunk lean in relation to the pelvis towards the stance limb and hip adduction during stance phase and corresponded well to the description of Trendelenburg gait caused by abductor insufficiency. Type 2 (n=12) is characterized by a trunk lean toward the affected stance limb with the pelvis stable or elevated on the swinging limb during single stance phase. The abductor moment of the involved side during single stance was significantly reduced in type 2 compared to the controls (p=0.004) indicating a hip-unloading mechanism. These results may influence the physiotherapy regimen, which may require to work towards a hip-unloading gait pattern.

Polymorphism of p16 INK4A and cyclin D1 in adenocarcinomas of the upper gastrointestinal tract.

PURPOSE: We investigated the prevalence of single nucleotide polymorphisms in the p16 gene (C540G) and the cyclin D1 gene (G870A), both known to regulate function in G1 arrest and therefore, may play an important role in carcinogenesis. METHODS: Using PCR based restriction fragment length polymorphism and single strand conformational polymorphism, we determined single nucleotide exchanges in the p16 and cyclin D1 genes among 56 esophageal adenocarcinomas (ADC) arising in Barrett's esophagus, 95 cardiac gastric ADC, and in 191 distal gastric ADC. The allelic frequencies were compared to a control group of 253 healthy blood donors. RESULTS: The C/G genotype of p16 was identified in 10.4% of esophageal carcinomas, 13.3% of cardiac carcinomas, and in 14.1% of gastric carcinomas, compared to 17.4% in the healthy control group. All other cases showed the C/C wildtype, as no homozygous G/G nucleotide exchange was detected in the group of cancer patients or in the control group. In esophageal cancer, cyclin D1 G/G genotype was found 28.6%, A/G in 46.4%, and A/A in 25.0%. In cardiac carcinoma, frequency of cyclin D1 genotype was 27.4% for G/G, 57.9% for A/G, and 14.7% for AA. In distal gastric carcinoma, both homozygous genotypes (G/G and A/A) had a frequency of 15.2% each, while the heterozygous A/G genotype occurred in 69.6% of patients. The control group displayed 24.9% G/G, 53.8% A/G, and 21.3% A/A genotype. CONCLUSIONS: Our results show that frequencies of p16 or cyclin D1 polymorphisms in gastric and esophageal ADC do not differ significantly from the healthy control group. Therefore, these polymorphisms are unlikely to be associated with risk of ADC of the upper gastrointestinal tract.