Medical adherence in patients with systemic lupus erythematosus in Germany: predictors and reasons for non-adherence - a cross-sectional analysis of the LuLa-cohort.

Objective Adherence to medication has a major impact on treatment control and success especially in chronic diseases but often remains unrecognized. Besides clinical, socioeconomic, disease-related and treatment-related parameters, general and personal health beliefs, as well as perception of health, can affect adherence. Our aim was to investigate the adherence to lupus-specific medications in German lupus patients and to assess influencing factors including detrimental or beneficial effects of health perceptions and beliefs. Methods The Lupus Erythematosus (LE) Long-Term Study (LuLa-study) is a nationwide longitudinal study among German Caucasian patients with systemic lupus erythematosus who have been assessed annually using a self-reported questionnaire since 2001. In 2013, we included questions concerning medical adherence (Morisky Medication Adherence Scale; MMAS-4), beliefs about medication prescribed (BMQ), illness perception and about the patients' health locus of control (HLC). We present a cross-sectional analysis to assess predictors of adherence using a multivariable stepwise logistic regression. Results Five hundred and seventy-nine patients participated, 81 of whom did not take any lupus-specific medication and 40 of whom did not complete the MMAS-4 and were therefore omitted. Only 62.7% reported high adherence. Unintentional behaviour for low medical adherence exceeded the intentional behaviour by far. The use of azathioprine (OR: 1.85; 95% CI: 1.02-3.34), prednisone <7.5 mg (OR: 1.56; 95% CI: 0.97-2.49), a higher age (OR: 1.06; 95% CI: 1.03-1.08) and higher external HLC (OR: 1.15; 95% CI: 1.01-1.30) proved conducive for high adherence in our multivariable model. On the contrary, the general perception of medication being harmful or addictive (OR: 0.89; 95% CI: 0.82-0.97) was detrimental. Conclusion A low belief that one's own health is determined by healthcare providers (external HLC) and the belief of the harmfulness of medication were independent predictors of low adherence besides age and the choice of the medical agent. The recognition of these potential obstacles in physician-patient relationships is essential to ameliorate adherence. Provision of sufficient information and education might help to reach the best possible outcome.

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

UNLABELLED: Current follow-up- and outcome-evaluations of Legg-Calvé-Perthes disease (LCPD) are based on subjective measures of function, clinical and radiological parameters. The objective of this study was to evaluate the sagittal plane kinematics and the effect on hip joint loading on the affected hip in children with LCPD. MATERIALS AND METHODS: Computerized gait analysis was performed in 49 LCPD patients aged ≥ 5 years with unilateral hip involvement. Sagittal plane kinematics and kinetics were compared to a group of healthy children (n=30). RESULTS: Kinematics: a significantly increased anterior tilt and range of motion (ROM) of the pelvis combined with a marked reduction of the extension of the involved hip joint compared to the control group was observed. The increased ROM of the contralateral hip results from increased maximum flexion. Power generation: overall significantly decreased on the involved side during florid stage. Global hip function: significantly reduced hip flexor index of the involved hip; 46.2% of the patients in advanced stage, although having no significant changes in kinematics - except increased anterior pelvic tilt - had a pathologic HFI. CONCLUSION: Sagittal plane hip function is significantly impaired in florid and advanced LCPD. The results of this study will lead to further investigations into whether this development can be prevented by conservative or operative treatment thus improving function and long-term prognosis.

[MRI bone marrow findings in 63 patients with type I Gaucher disease]. / MRT der Knochenmarkverändungen bei 63 Patienten mit Morbus Gaucher Typ I.

PURPOSE: To determine whether MR bone marrow findings in Gaucher patients may help to identify patients at high risk of developing severe Gaucher bone complications exemplified by avascular necrosis (AVN) of the femoral head. MATERIALS AND METHODS: MR images were obtained in 63 Type I Gaucher patients through a standard protocol using coronal T 1 and T 2-weighted sequences of the lower extremities. The location and extent of infiltrated marrow was established using a semi-quantitative MRI scoring method (Düsseldorf Gaucher score, DGS) and the morphological pattern of bone marrow involvement determined (whether homogeneous type A or non-homogeneous type B). The active marrow process with bone edema and AVN of the femoral head were also analyzed. RESULTS: Bone marrow involvement was observed in femoral sites more than in tibial sites. A high DGS was significantly correlated with type B morphology and femoral AVN (both p < 0.0001). Splenectomized patients showed a significantly higher Düsseldorf Gaucher score and type B morphology than non-splenectomized patients (both p < 0.05). AVN was seen in 46 % of patients with type B morphology versus 3 % in type A morphology (p < 0.0001). DGS and morphology of bone marrow involvement were not significantly correlated with active marrow processes. CONCLUSION: Type B marrow morphology and extensive marrow packing were significantly associated with AVN of the femoral head (both p < 0.0001). These patterns are considered predictive and may be employed in a disease management context to alert physicians to the need for urgent therapeutic measures.

Self-assessments of patients via Tablet PC in routine patient care: comparison with standardised paper questionnaires.

OBJECTIVE: We evaluated the feasibility of electronic data capture of self-administered patient questionnaires using a Tablet PC for integration in routine patient management; we also compared these data with results received from corresponding paper-pencil versions. METHODS: Standardised patient questionnaires (FFbH/HAQ, BASDAI, SF-36) were implemented in our documentation software. 153 outpatients (rheumatoid arthritis, systemic lupus erythematosus, spondyloarthritis) completed sets of questionnaires as paper-pencil and electronic versions using a Tablet PC. The quality and validity of data obtained using a Tablet PC and the capability of disabled patients to handle it were assigned; patients' experiences, preferences and computer/internet use were also assessed. RESULTS: Scores obtained by direct data entry on the Tablet PC did not differ from the scores obtained by the paper-pencil questionnaires in the complete group and disease subgroups. No major difficulties using the Tablet PC occurred. 62.1% preferred remote data entry in the future. Seven (4.6%) patients felt uncomfortable with the Tablet PC due to their rheumatic disease. CONCLUSIONS: Self-administered questionnaires via Tablet PC are a facile and capable option in patients with rheumatic diseases to monitor disease activity, efficacy and safety assessments continuously. Tablet PC applications offers directly available data for clinical decision-making improves quality of care by effective patient monitoring, and contributes to patients' empowerment.

Interobserver reproducibility of Gleason grading: evaluation using prostate cancer tissue microarrays.

OBJECTIVES: Due to PSA screening and increased awareness, prostate cancer (PCa) is identified earlier resulting in smaller diagnostic samples on prostate needle biopsy. Because Gleason grading plays a critical role in treatment planning, we undertook a controlled study to evaluate interobserver variability among German pathologists to grade small PCas using a series of tissue microarray (TMA) images. METHODS: We have previously demonstrated excellent agreement in Gleason grading using TMAs among expert genitourinary pathologists. In the current study, we identified 331 TMA images (95% PCa and 5% benign) to be evaluated by an expert PCa pathologist and subsequently by practicing pathologists throughout Germany. The images were presented using the Bacus Webslide Browser on a CD-ROM. Evaluations were kept anonymous and participant's scoring was compared to the expert's results. RESULTS: A total of 29 German pathologists analysed an average of 278 images. Mean percentage of TMA images which had been assigned the same Gleason score (GS) as done by the expert was 45.7%. GSs differed by no more than one point (+/-1) in 83.5% of the TMA samples evaluated. The respondents were able to correctly assign a GS into clinically relevant categories (i.e. <7, 7, >7) in 68.3% of cases. A total of 75.9% respondents under-graded the TMA images. Gleason grading agreement with the expert reviewer correlated with the number of biopsies evaluated by the pathologist per week. Years of diagnostic experience, self-description as a urologic pathologist or affiliation with a university hospital did not correlate with the pathologist's performance. CONCLUSION: The vast majority of participants under-graded the small tumors. Clinically relevant GS categories were correctly assigned in 68% of cases. This raises a potentially significant problem for pathologists, who have not had as much experience evaluating small PCas.

Expression of heat shock protein 70 in renal cell carcinoma and its relation to tumor progression and prognosis.

Heat shock proteins (HSPs) play an important role in the cellular response to environmental stress and exert a cytoprotective effect. Especially HSP70 is an effective inhibitor of apoptosis, suggesting a role of HSP70 in carcinogenesis and tumor progression. To explore the relevance of HSP70 in renal cell carcinomas (RCCs), we analyzed nuclear and cytoplasmic HSP70 protein expression in formalin-fixed tissue from 145 clear cell RCCs by immunohistochemistry as well as Western blot analysis. Nuclear HSP70 expression was found in all RCCs and 75% of the tumors also exhibited a cytoplasmic HSP70 staining. Importantly, RCCs showed significantly reduced cytoplasmic (p=0.001) and combined nuclear/cytoplasmic (p=0.0022) HSP70 expression when compared with their cells of origin. A significant (p=0.0176) decrease of nuclear HSP70 expression became evident from well to poorly differentiated clear cell RCCs. Quite similarly, a trend (p=0.0558) for reduced combined nuclear/cytoplasmic HSP70 expression was shown from early (pT1) to advanced (pT3) tumor stages. Nevertheless, no correlation between HSP70 expression and patients survival became evident. In conclusion, our investigation demonstrates a significant decrease of antiapoptotic HSP70 protein expression during carcinogenesis and during progression from well (G1) to poorly (G3) differentiated clear cell RCCs. Our results suggest that HSP70-mediated inhibition of apoptosis seems to be of minor importance for carcinogenesis and tumor progression in RCCs.

Prognostic relevance of increased Rac GTPase expression in prostate carcinomas.

Rac proteins of the Rho-like GTPase family, including the ubiquitous Rac1, the hematopoiesis-specific Rac2, and the least-characterized Rac3 play a major role in oncogenic transformation, tumor invasion and metastasis. However, the prognostic relevance of Rac expression in human tumors has not been investigated yet. In the present study, Rac protein expression was analyzed in benign secretory epithelium, high-grade prostatic intraepithelium neoplasia (HG-PIN), and prostate carcinomas of 60 R0-resected radical prostatectomy specimens by semiquantitative immunohistochemistry. Thus, Rac proteins were significantly strongly expressed in HG-PIN (P < 0.001) and prostate carcinomas (P < 0.001) when compared with benign secretory epithelium. Accordingly, all tumor tissues analyzed by isoform-specific real-time PCR (n = 7) exhibited significantly higher RNA expression levels of Rac (i.e. sum of Rac1 and Rac3 expression levels) than the respective benign counterparts (P = 0.018) and this appeared to result mainly from increased expression of the Rac3 isoform as verified by immunoblotting. Univariate analyses showed statistically significant associations of increased Rac protein expression in prostate cancer (P = 0.045), preoperative prostate-specific antigen levels (P = 0.044), pT stage (P = 0.002), and Gleason score (P = 0.001) with decreased disease-free survival (DFS). This prognostic effect of increased protein expression of Rac remained significant even in a multivariate analysis including all these four factors (relative risk = 3.22, 95% confidence interval = 1.04-10.00; P = 0.043). In conclusion, our data suggest that increased Rac protein expression in prostate cancer relative to the corresponding benign secretory epithelium is an independent predictor of decreased DFS and appears to result mainly from increased expression of the Rac3 isoform.

[Transient elastography for diagnosing liver cirrhosis]. / Transiente Elastografie zur Diagnose der Leberzirrhose.

BACKGROUND AND OBJECTIVE: Detection of liver cirrhosis has numerous implications because of the potential sequelae of cirrhosis. Transient elastography (Fibroscan), was evaluated as a novel, non-invasive means of assessing cirrhosis by measuring liver stiffness. METHODS: 147 consecutive patients with different forms of liver disease and histologically determined stages of liver fibrosis were prospectively studied by transient elastography. 48 patients had liver cirrhosis. RESULTS: The number of transient elastographic measurements per patient was 12+/-4 (range 6 - 30). Valid elastography measurements were available for 135 out of 147 patients (92 %). The results of transient elastography correlated positively with the histological score of liver fibrosis (r = 0.8; 95 % CI: 0.72 - 0.85; p < 0.001). Areas under the receiver operating characteristic curve (AUROC) were 0.91 for > or = F3 fibrosis (95 % CI: 0.85 - 0.96) and 0.94 for cirrhosis (95 % CI: 0.90 - 0.98). Using a cut-off value of 13 kPa for detection of liver cirrhosis a sensitivity of 90 %, a specificity of 82 %, a positive predictive value of 71 % and a negative predictive value of 95 % were obtained. CONCLUSIONS: Measuring liver stiffness by transient elastography proved to be an easy method to assess liver cirrhosis. In combination with clinical signs, ultrasound and biochemical markers noninvasive diagnosis of liver cirrhosis will be further improved.

Prognostic relevance of Tiam1 protein expression in prostate carcinomas.

The Rac-specific guanine nucleotide exchange factor, Tiam1, plays a major role in oncogenicity, tumour invasion and metastasis but its usefulness as a prognostic marker in human cancer has not been tested yet. In the present study, Tiam1 expression was analysed in benign secretory epithelium, pre-neoplastic high-grade prostatic intraepithelium neoplasia (HG-PIN) and prostate carcinomas of 60 R0-resected radical prostatectomy specimens by semiquantitative immunohistochemistry. Tiam1 proved significantly overexpressed in both HG-PIN (P<0.001) and prostate carcinomas (P<0.001) when compared to benign secretory epithelium. Strong Tiam1 overexpression (i.e. > or =3.5-fold) in prostate carcinomas relative to the respective benign prostatic epithelium was statistically significantly associated with disease recurrence (P=0.016), the presence of lymph vessel invasion (P=0.031) and high Gleason scores (GS) (i.e. > or =7) (P=0.044). Univariate analysis showed a statistically significant association of strong Tiam1 overexpression with decreased disease-free survival (DFS) (P=0.03). This prognostic effect of strong Tiam1 overexpression remained significant in multivariate analysis including preoperative prostate-specific antigen levels, pT stage, and GS (relative risk= 3.75, 95% confidence interval=1.06-13.16; P=0.04). Together, our data suggest that strong Tiam1 overexpression relative to the corresponding benign epithelial cells is a new and independent predictor of decreased DFS for patients with prostate cancer.

Avascular osteonecrosis after hyperthermia in children and adolescents with pelvic malignancies: a retrospective analysis of potential risk factors.

PURPOSE: In children with locally advanced or recurrent malignant tumours, prognosis can be improved by regional deep hyperthermia (RHT) in combination with platin-based chemotherapy. However, because of the increasing number of patients that achieve long-time remission with this therapy, it is necessary to evaluate long-term sequelae of thermochemotherapy. During the years 1993-2004 one has observed avascular osteonecrosis (AON) of the femoral head after RHT in seven children with pelvic germ cell tumours or rhabdomyosarcomas. METHODS: Although AON may develop in patients with malignancies treated with chemo- or radiotherapy alone, RHT might nevertheless contribute to the occurrence of AON. In order to determine potential risk factors for AON after RHT, this study analysed the relationship of AON to the patient's age, medical history and treatment parameters such as thermal dose equivalent and power output. RESULTS AND CONCLUSIONS: In the present study AON was associated with young age as well as intensity of hyperthermia indicated by high power levels that exceed 20 W per kg body weight and/or application of eight or more heat sessions as well as additional radiotherapy. Based on this observation, it was assumed that an optimized three dimensional thermal field modelling may be helpful to avoid hazardous temperatures in the femoral heads during RHT treatment and to reduce AON of the femoral heads.

Urinary excretion of deoxypyridinoline in Perthes' disease: a prospective, controlled comparative study in 83 children.

Our aim was to investigate the relationship between urinary excretion of deoxypyridinoline (DPD) as a marker of bone resorption, and Perthes' disease. There were 39 children with Perthes' disease in the florid stage who collected first-morning urine samples at regular intervals of at least three months. The level of urinary DPD was analysed by chemiluminescence immunoassay and was correlated with the radiological stage of the disease as classified by Waldenström, and the severity of epiphyseal involvement according to the classification systems of Catterall and Herring. The urinary DPD levels of a group of 44 healthy children were used as a control. The median urinary DPD/creatinine (CREA) ratio was significantly reduced (p < 0.0001) in the condensation stage and increased to slightly elevated values at the final stage (p = 0.05) when compared with that of the control group. Herring-C patients showed significantly lower median DPD/CREA ratios than Herring-B patients (p = 0.03). The significantly decreased median DPD/CREA ratio in early Perthes' disease indicated a reduced bone turnover and supports the theory of a systemic aetiology. Urinary levels of DPD may therefore be used to monitor the course of Perthes' disease.

Subjective image quality of digitally filtered radiographs acquired by the Dürr Vistascan system compared with conventional radiographs.

OBJECTIVES: To compare the different digital filters implemented in the Dürr Vistascan system with conventional film and to analyze the filter specificity to anatomic structures. STUDY DESIGN: Ten panoramic image pairs and 10 periapical image pairs (1 digital and 1 conventional) were obtained from 20 patients conventionally and digitally. The display quality of different anatomic image structures was rated subjectively on a 5-point scale. The responses were evaluated using ANOVA and Tukey-Kramer post hoc tests. The intraobserver reliability was evaluated by Cohen's kappa statistics. RESULTS: The display quality of anatomic structures was rated higher by using Caries 1 or 2 filters for periapical and Periodontal 1 or 2 filters for panoramic images, whereas nonfiltered and Noise Reduction-filtered images received the lowest scorings compared to all other digital image modalities (P < or = .0097). The superiority of conventional radiographs to the digital ones was statistically significant (P < or = .0039 and P < or = .0152 respectively). CONCLUSIONS: Depending on the diagnostic task, digital images of the Vistascan system should be filtered before examination. Perfect conventional radiographs still remain the gold standard for image quality.

[Differential diagnosis of focal liver lesions using contrast-enhanced MRI with SHU 555 A in comparison with unenhanced MRI and multidetector spiral-CT]. / Dignitätsbeurteilung fokaler Leberläsionen mit der kontrastverstärkten MRT mit SHU 555 A im Vergleich zur nativen MRT und zur Mehrzeilen-Detektor-Spiral-CT.

PURPOSE: To evaluate the ability of contrast-enhanced MRI with SHU 555 A to provide additional information for characterization of focal liver tumors compared with non-enhanced MRI and multislice spiral CT. MATERIALS AND METHODS: In a prospective manner the images of 45 patients who underwent multislice spiral CT, unenhanced MRI alone and unenhanced and SHU 555 A-enhanced MRI including dynamic imaging at a field strength of 1.0 T were analyzed in a blinded reading. The readers had to determine on a scale from 1 to 5 whether a tumor was benign or malignant. Furthermore, the readers had to give a definitive diagnosis for each lesion. A true cut needle biopsy served as gold standard against which all imaging procedures were compared. RESULTS: The sensitivity for differentiation malignant vs. benign lesion was 77 % with spiral CT, 72 % with unenhanced MRI and 94 % with SHU 555 A-enhanced MRI, respectively (p < 0.05). The specificity for spiral CT was 73 %, for unenhanced MRI 83 % and for contrast-enhanced MRI 83 %, respectively (n. s.). Compared with the histopathologic results, the correct diagnosis was made with spiral CT in 25/45 (56 %), unenhanced MRI in 16/45 (36 %) and contrast-enhanced MRI in 32/45 (71 %) of the patients (p < 0.05). For the subgroup of patients with liver cirrhosis, the correct diagnosis was established with spiral CT in 16/23 (70 %), unenhanced MRI in 9/23 (39 %) and contrast-enhanced MRI in 19/23 (83 %) of the patients (p < 0.05). CONCLUSION: Contrast-enhanced MRI with SHU 555 A has the ability to improve the differential diagnosis of focal liver tumors compared with unenhanced MRI and multislice spiral CT.

The G20210A prothrombin-gene mutation and the plasminogen activator inhibitor (PAI-1) 5G/5G genotype are associated with early onset of severe preeclampsia.

Hereditary risk determinants of venous thrombosis have been reported to be associated with severe preeclampsia. So far there are no data to support whether these risk determinants are related to the time of onset of severe preeclampsia. We used a case-control design, studying 97 women with severe preeclampsia in previous pregnancies and 277 normal women, to assess hereditary risk factors of venous thrombosis as risk determinants for severe preeclampsia. A case-only design comprising solely the 97 women with a history of preeclampsia was used to evaluate these risk factors as risk determinants for early onset of severe preeclampsia. Using the case-control design, there was no significant risk association of the hereditary risk factors with severe preeclampsia [factor V Leiden, odds ratio (OR) 0.9, 95% confidence interval (CI) 0.4, 2.2; prothrombin mutation, OR 1.9, 95% CI 0.5, 7.0; methylentetrahydrofolate reductase 677TT genotype, OR 0.8, 95% CI 0.4, 1.8; plasminogen activator inhibitor (PAI-1) 4G/4G genotype, OR 1.2, 95% CI 0.7, 2.1; PAI-1 5G/5G genotype, OR 1.0, 95% CI 0.5, 1.8]. However, the onset of severe preeclampsia was significantly earlier in women with the G20210A prothrombin gene mutation (24.5 weeks vs. 30.1 weeks, P = 0.046) and in women with the PAI-1 5G/5G genotype (25.7 weeks vs. 30.8 weeks, P = 0.024). Hereditary risk factors for venous thrombosis do not predispose for severe preeclampsia. However, women who are carriers of the G20210A prothrombin gene mutation and the PAI-1 5G/5G genotype are at risk for early onset of severe preeclampsia. It appears that these risk factors do not induce the pathomechanism but accelerate the course of preeclampsia.

[Lupus in Germany: analysis within the German lupus self-help organization (LULA)]. / Lupus in Deutschland: Querschnittsanalyse innerhalb der Lupus erythematodes Selbsthilfegemeinschaft (LULA).

During the last few decades, the prognosis for patients with systemic lupus erythematosus (LE) has changed from high early mortality to a more chronic longterm course. Although the prevalence of LE has been estimated at 20-50/100,000, data concerning the situation of LE patients in Germany are sparse. Since 2001, a documentation within the German Lupus Self-Help Organisation scheduled for a period of 10 years (LULA) has been recording at the patient level the actual status and the long-term course of a large group of LE patients. A questionnaire adapted from the German rheumatological database is updated once a year and sent to all members.In 2001, 1033 members participated in the documentation. Of these, 92.2% were women (mean age 45.8 years) with a mean disease duration of 9.9 years. 37.6% were employed, and 24.5% were on early retirement. 50.2% rated their overall health status as "not so good" or "poor". Most were receiving treatment with [hydroxy-]chloroquine (35.2%) or azathioprine (21.9%), while 67.9% were receiving corticosteroids. The most frequent comorbidities reported were hypertension (33%), scarring skin disease (24.4%), osteoarthritis (25.2%), osteoporosis (24%), psychiatric disorders/depression (22.9%) and chronic renal disease (22%). Thromboembolic events were reported in 18.5%, myocardial infarction in 2.3% and stroke in 4.8% of cases. Concerning their main contact person for health care, 63.6% specified the rheumatologist. In comparison with other cohort studies and in particular with the German rheumatological database, the data provided exclusively by patients are feasible. Concerning the severity of their disease, their treatment and their global assessment of health status, LULA participants are comparable with other LE patients and can be seen as representative of LE patients in Germany. Further assessment especially of long-term data are needed to obtain additional insights into the burden of the disease and the need for special medical care.

An approach for cure: PEI-chemotherapy and regional deep hyperthermia in children and adolescents with unresectable malignant tumors.

BACKGROUND: Elevated temperatures of 40 - 44 degrees C increase the actions of various anticancer drugs including N-lost derivatives, cytotoxic antibiotics and platinum analoga. In clinical usage thermochemotherapy (TCH) should facilitate surgical resection and ameliorate local tumor control. PATIENTS AND METHODS: From 07/1993 to 12/2002 a total of 39 patients have been enrolled onto a phase-II study (female = 24, male = 15, age 1 - 37.5 years, median 5.2). Among these, 24 patients had extracranial non-testicular germ cell tumors and 15 patients soft tissue or chondrosarcomas. INDICATION: locoregional relapse (n = 29) or unresectable tumor after neoadjuvant chemotherapy (n = 10). Among these two groups, there were ten patients with poor response or progressive disease under primary or relapse chemotherapy. Ten out of the 29 relapse patients had more than one relapse. Tumor site: pelvis (30), abdomen (4), head and neck (2), proximal leg (2) and lumbar spine (1). Thermochemotherapy (TCH): 1800 - 2000 mg ifosfamide/m (2) and 100 mg etoposide/m (2) on days 1 - 4 and 40 mg cisplatin/m (2) on days 1 + 4 combined with regional deep hyperthermia (42 - 44 degrees C, 1 h) on days 1 + 4. RESULTS: In 39 protocol patients a total of 166 TCH courses (332 heat sessions) were applied. 20 patients achieved complete response, and 10 patients achieved partial response. TCH was followed by surgical tumor resection in 28/39 patients and/or radiotherapy in 13/39 patients. At a median follow-up of 27 months, outcome in this high-risk patient population was 22 NED, 3 AWD, 12 DOD, 2 DOC. Five year event free (EFS) and overall survival (OS) for the whole study cohort was 0.39 +/- 0.11 (20/39 patients) and 0.52 +/- 0.11 (25/39 patients), respectively. CONCLUSION: TCH shows substantial therapeutic efficacy and facilitates complete tumor resection in 14 out of 28 operated patients. Multimodal treatment including TCH, surgical resection and/or radiotherapy leads to sustained remission in the majority of patients with locoregional tumor recurrence. The therapeutic effect is most pronounced, if TCH is administered at first relapse. Due to the clinical and histologic heterogeneity the number of patients eligible for TCH is limited. Therefore, a more valid assessment of treatment efficacy can only be made by a matched-pair comparison in cooperation with the clinical registers.

Prognostic value of tumor size, metastases, extension into bone, and increased tumor marker in children with malignant sacrococcygeal germ cell tumors: a prospective evaluation of 71 patients treated in the German cooperative protocols Maligne Keimzelltumoren (MAKEI) 83/86 and MAKEI 89.

PURPOSE: To evaluate the prognostic value of metastases, extension into bone, and alpha-fetoprotein (AFP) elevation in children with malignant sacrococcygeal germ cell tumors (GCTs) prospectively collected in two cooperative Maligne Keimzelltumoren (MAKEI) protocols (83/86 and 89). PATIENTS AND METHODS: Between October 1983 and October 1995, 76 of 210 registered patients with sacrococcygeal primaries presented either with pure yolk sac tumor, embryonal carcinoma (EC), or yolk sac tumor and EC mixed with immature and mature teratoma elements. Stages T1 and T2 disease were diagnosed in 15 and 61 children, respectively, 41 patients had metastases, and 35 children presented with extension into bone. At diagnosis, 22 children had an AFP elevation of less than 10,000 ng/mL. Thirty-six children showed an AFP level between 10,000 and 100,000 ng/mL, and 12 patients had values of greater than 100,000 ng/mL. Five patients died of complication during treatment and were excluded from further evaluation. Seventy-one patients could be analyzed. RESULTS: The 5-year relapse-free survival rate (RFS, Kaplan-Meier) was 0.76 +/- 0.03 (54 of 71 patients; median observation time, 54 months after diagnosis). The RFS of patients with and without metastases was different, but not significantly so (0.71 v 0.82). The outcome of patients with extension into bone (n = 31) and without this extension (n = 40) was 0.71 versus 0.80 (RFS, 5 years). Above-normal AFP level had no prognostic significance (P =.52). CONCLUSION: In children with malignant sacrococcygeal GCTs treated with an intensive, short-interval, platinum-based regimen, the stage, extent of metastases, extension into bone, and AFP level had no prognostic significance.

Visually detectable resolution of intraoral dental films.

OBJECTIVES: The visually utilizable resolution of intraoral dental films was examined with the naked eye, with two-fold optical magnification and after digitization using a computer display. METHODS: Agfa Dentus M2, Kodak Ektaspeed Plus and Kodak InSight dental films were exposed with a line pair (lp) test pattern providing frequencies up to 16.6 lp mm(-1). Films were developed at 24 degrees C in a Dürr Periomat machine and at 28 degrees C in a Dürr AC245 machine. Forty dental students evaluated the maximum visually detectable resolution with their naked eye, with an X-ray viewer (providing two-fold magnifying lenses and eliminating disturbing light) and following digitization and monitor display examination. RESULTS: The best detectable resolution was achieved through digitization, reaching a mean of up to 16.5 lp mm(-1). With two-fold magnification, a mean of up to 13.3 lp mm(-1) could be resolved, while only 11.7 lp mm(-1)could be resolved with the naked eye. Unlike the other film types, the resolution of Ektaspeed depended on the processing type when viewing digitized images or when viewing with the naked eye. There was a trend for students above 29 years of age to detect a lower resolution with the naked eye, although they performed comparably with students below 29 years when using the X-ray viewer or viewing digitized images. CONCLUSIONS: Film resolution is utilized best through digitization and secondly using a magnifying lens. With the naked eye, a mean of 11 lp mm(-1) with a broad distribution can be resolved. A magnifying lens is recommended if resolution is important or if the viewer's eyesight is reduced. Compared with E-speed films, Kodak Insight was less dependent on processing conditions.

A comparison of conventional panoramic radiographs with volumetric computed tomography images in the preoperative assessment of impacted mandibular third molars.

PURPOSE: In the present study, we evaluated the geometric, topographic, and anatomic reliability of volumetric computed tomography (VCT) images by comparing conventional panoramic radiographs with reconstructed VCT panoramic and paraxial images before performing third molar surgery. PATIENTS AND METHODS: A total of 6 anatomic sites on 10 patients who showed a topographic relationship between the apices of the third molar root and the mandibular canal were preoperatively assessed by 5 oral surgeons using conventional panoramic radiographs; these were complemented and compared with secondary reconstructed paraxial and panoramic VCT images. RESULTS: The position of the apices in relation to the mandibular canal could be revealed on 94% of VCT reconstructed paraxial images. Assessment of VCT paraxial images could be facilitated by using a toolbar marker in 70% of the paraxial images. In 90% of the paraxial images, it was possible to assess the relationship of the mandibular canal and its adjacent anatomy. The visual grading scores for conventional panoramic images were significantly better on all 7 assessed anatomic sites compared with the reconstructed VCT panoramic images. CONCLUSION: The results showed that the VCT paraxial images gave a significantly clearer perception of the mandibular nerve than conventional panoramic radiographs. However, conventional panoramic radiographs were shown to be better than the VCT reconstructed panoramic images and were therefore an invaluable tool in the "expert-derived" assessment and posed the potential for identifying the need for further VCT diagnostic procedures.

Quantification of total abdominal fat volumes using magnetic resonance imaging.

The purpose of this study was to develop a rapid and reliable method for the measurement of total abdominal fat volumes in diabetic patients using magnetic resonance imaging (MRI). Total volume coverage of the abdomen was obtained using T1-weighted images in 37 diabetic patients (age 48 +/- 13 y mean +/-SD). Quantification of intraabdominal (IAF), subcutaneous (SCF), and total abdominal fat volumes (TAF) was performed using a semiautomated computer assisted analysis. The variability of image analysis for fat measurements between two observers and within observers was assessed. Mean volumes (+/- SD) for IAF, SCF and TAF were 10.5 l (+/- 5.0 l), 15.1 l (+/-7.3 l) and 25.7 l (+/-11.5 l), respectively. Reliability of measurements was excellent for both observers (observer I: intraobserver reliability IAF, SCF and TAF: r = 0.999, r = 0.999 r = 1.0, observer II: r = 0.999, r = 0.999 and r = 1.0), as well as between both observers (interobserver reliability IAF, SCF, and TAF: r = 0.999, r = 0.999, r = 1.0). A single computer analysis required about 9 min in addition to 7 min scan time. The developed analysis method of MR images allows a rapid and reliable determination of total intraabdominal, subcutaneous and total fat volumes. This method has the potential to be very valuable in respective studies in patients with diabetes.