Movement disturbances in the differential diagnosis of Creutzfeldt-Jakob disease.

Movement disturbances are common in dementia disorders and are a central feature of the clinical classification criteria of Creutzfeldt-Jakob disease (CJD). Polymorphism at codon 129 of the prion protein gene is known to determine the clinical picture of CJD. The frequency and characteristics of movement disturbances in other dementing disorders, such as Alzheimer's disease (AD), is barely known and leads to misdiagnoses. We investigated the occurrence and characteristics of movement disturbances in 143 patients neuropathologically confirmed with CJD (n = 100), AD (n = 29), dementia with Lewy bodies (DLB) (n = 7), or other diagnoses (n = 7). All patients had been referred with the differential diagnosis of prion disease. Ataxia and dysmetria were significantly more frequent in CJD than in AD or DLB patients, whereas hypokinesia was up to five times more frequent in AD or DLB (P < 0.05). Using an ordered logistic regression to identify constellations of movement disturbances, the diagnosis of CJD was likely in patients presenting ataxia but not hypokinesia. The reverse situation was statistically associated with AD. Ataxia and cogwheel rigidity were associated with valine-homozygosity and akinesia with methionine-homozygosity in the CJD patients. Our results indicate that the careful assessment of movement disturbances may be helpful in the differential diagnosis of Creutzfeldt-Jakob disease.

Negative inotropy of the gastric proton pump inhibitor pantoprazole in myocardium from humans and rabbits: evaluation of mechanisms.

BACKGROUND: Proton pump inhibitors are used extensively for acid-related gastrointestinal diseases. Their effect on cardiac contractility has not been assessed directly. METHODS AND RESULTS: Under physiological conditions (37 degrees C, pH 7.35, 1.25 mmol/L Ca2+), there was a dose-dependent decrease in contractile force in ventricular trabeculae isolated from end-stage failing human hearts superfused with pantoprazole. The concentration leading to 50% maximal response was 17.3+/-1.3 microg/mL. Similar observations were made in trabeculae from human atria, normal rabbit ventricles, and isolated rabbit ventricular myocytes. Real-time polymerase chain reaction demonstrated the expression of gastric H+/K+-adenosine triphosphatase in human and rabbit myocardium. However, measurements with BCECF-loaded rabbit trabeculae did not reveal any significant pantoprazole-dependent changes of pH(i). Ca2+ transients recorded from field-stimulated fluo 3-loaded myocytes (F/F0) were significantly depressed by 10.4+/-2.1% at 40 microg/mL. Intracellular Ca2+ fluxes were assessed in fura 2-loaded, voltage-clamped rabbit ventricular myocytes. Pantoprazole (40 microg/mL) caused an increase in diastolic [Ca2+]i by 33+/-12%, but peak systolic [Ca2+]i was unchanged, resulting in a decreased Ca2+ transient amplitude by 25+/-8%. The amplitude of the L-type Ca2+ current (I(Ca,L)) was reduced by 35+/-5%, and sarcoplasmic reticulum Ca2+ content was reduced by 18+/-6%. Measurements of oxalate-supported sarcoplasmic reticulum Ca2+ uptake in permeabilized cardiomyocytes indicated that pantoprazole decreased Ca2+ sensitivity (Kd) of sarcoplasmic reticulum Ca2+ adenosine triphosphatase: control, Kd=358+/-15 nmol/L; 40 microg/mL pantoprazole, Kd=395+/-12 nmol/L (P<0.05). Pantoprazole also acted on cardiac myofilaments to reduced Ca2+-activated force. CONCLUSIONS: Pantoprazole depresses cardiac contractility in vitro by depression of Ca2+ signaling and myofilament activity. In view of the extensive use of this agent, the effects should be evaluated in vivo.

In vitro cytotoxicity of different desensitizers under simulated pulpal flow conditions.

PURPOSE: To evaluate the cytotoxicity of three desensitizers, one nonrinse, and one etch-and-rinse adhesive system applied on dentin specimens of different thickness. MATERIALS AND METHODS: The test materials (A: Admira Protect, B: Gluma Desensitizer, C: Seal&Protect, D: Clearfil Protect Bond, E: Optibond FL) and a positive control (35% H2O2) were applied on 1.0-, 1.5-, and 2.5-mm-thick bovine dentin specimens (each subgroup n = 5) in a dentin barrier test device. The experiments were performed with perfusion (2 ml/h) of the pulpal part of the chamber. The eluates were obtained before (baseline) and 15, 30, 45, 60, and 120 min after application of the adhesives and pipetted onto L-929 fibroblasts. Cytotoxicity of the materials was determined in relation to the baseline value using the MTT assay (succinic dehydrogenase activity). Statistical analysis was performed using ANOVA and Student's t-test. RESULTS: With regard to 1.0-mm dentin specimens, application of Clearfil Protect Bond (D) decreased enzyme activity significantly, while test materials A to C and E were not cytotoxic. However, cytotoxicity of D was limited to up to 15 min and decreased thereafter. Application of the test materials A to E on 1.5- and 2.5-mm dentin samples exhibited no significant cytotoxic effects within 120 min. Generally, ANOVA found significant interactions between the test materials and dentin thickness. However, only for Admira Protect was a significant increase of enzyme activity with increasing dentin thickness observed. CONCLUSION: Desensitizing agents might exhibit cytotoxic potential when applied on dentin less than 1.0 mm thick. The tested desensitizers and the adhesive systems caused similar effects, in which cytotoxicty might be influenced by the duration of perfusion and dentin thickness.

Impact of fluoride, milk and water rinsing on surface rehardening of acid softened enamel. An in situ study.

PURPOSE: To evaluate the impact of fluoride, milk and water rinsing on surface rehardening of acid softened enamel in situ. METHODS: Ten subjects performed six tests of4 hours each. In each test, three softened enamel samples were attached to intraoral appliances. For softening, samples were immersed extraorally in an acidic beverage for 120 seconds. Subsequently, specimens were worn intraorally for 5 minutes (Tests 1-3) or 30 minutes (Tests 4-6). Thereafter, the volunteers rinsed with a 250 ppm SnF2/Olaflur solution (Tests 1 and 4), milk (Tests 2 and 5) or non-carbonated mineral water (Tests 3 and 6) for 60 seconds. At each test, one sample was covered with tape during intraoral rinsing and thus, served as control. After rinsing, both test and the control samples were exposed to the oral cavity for up to 4 hours after demineralization. Surface microhardness (SMH) of the specimens was assessed at baseline, immediately after softening and 4 hours after softening. For each subject, the secretion rate of resting and stimulated saliva, buffering capacity and pH-value as well as calcium and phosphate concentration of saliva were measured. Statistical analysis was performed by ANCOVA followed by stratified analyses with Bonferroni correction. RESULTS: Baseline Knoop Hardness (mean +/- S.D.) amounted to 403.1 +/- 39.4. Immediately after softening, mean SMH was reduced to 214.4 +/- 24.1 KHN. Rinsing with 250 ppm fluoride, milk or water after 5 minutes or 30 minutes intraoral exposure of softened samples had a significant effect on rehardening. The increase of SMH (DeltaKHN) was highest after rinsing with fluoride (5 minutes: 95.0 +/- 18.3; 30 minutes: 94.2 +/- 24.3) followed by milk (5 minutes: 77.1 +/- 14.1; 30 minutes: 80.3 +/- 18.7) and water (5 minutes: 49.0 +/- 9.9; 30 minutes: 47.0 +/- 14.1), but did not achieve baseline values. It is concluded that a single rinse with a 250 ppm SnF2/Olaflur solution, milk or water increases rehardening of previously acid softened enamel.

T2*-weighted MRI in diagnosis of multiple system atrophy. A practical approach for clinicians.

BACKGROUND: Putaminal iron deposition is a histopathological feature of multiple system atrophy (MSA), which is not observed in patients with idiopathic Parkinson's disease (PD). T2*-weighted magnetic resonance imaging (MRI) gradient echo (GE) sequences are sensitive for paramagnetic susceptibility changes and therefore may support the clinical differential diagnosis between MSA and PD. METHODS: We evaluated putaminal signal intensities on 1.0 Tesla scans of 52 MSA patients, 88 patients with PD and 29 healthy control subjects. RESULTS: The typical finding in T2* GE sequences of MSA patients was a signal loss of the dorsolateral putamen, which showed a high specificity (>0.91), but was present in only a subpopulation of patients (sensitivity 0.64-0.69). The combination of the latter with additional presence of a hyperintense lateral rim in fluid attenuated inversion recovery (FLAIR) sequences increased the specificity to 0.97. Using a quantitative evaluation of putaminal signal intensities in defined regions of interest MSA and PD could be discriminated with a diagnostic accuracy (r) of up to 0.82. CONCLUSION: Although the separation of groups remains incomplete, the use of T2*-weighted GE sequences combined with FLAIR may be helpful for the differential diagnosis of MSA versus PD considering its fast application, easy evaluation, broad availability, the specificity of findings and the presence of putaminal signal loss already at early disease stages.

Subjectivity and examiner experience in diagnosis of residual caries--an in vitro study.

UNLABELLED: The aim was to evaluate subjectivity (using inter- and intraexaminer repeatability), the effect of examiner experience, and residual caries diagnostic accuracy with visual tactile (VT) criteria and using a caries disclosing agent (CD). Thirty teeth with occlusal caries were excavated by a single operator not involved in the diagnostic part of the study. A test area was marked in each cavity. Four dentists with more than five and five dentists with less than five years' experience rated the marked area twice (a week apart) using VT criteria. A week later, the samples were stained using Caries Detector. The same examiners rated the presence or absence of stain in the marked area twice (a week apart). Undecalcified thin slices were examined for bacteria using light microscopy. Overall kappa for inter-examiner repeatability was higher for CD (0.45) than VT (0.31). In the less experienced group the kappa value was higher for CD (0.41) than for VT (0.23). In the experienced group kappa was lower for CD (0.43) than for VT (0.46). Median kappa for intra-examiner repeatability was higher for caries detector (0.77, 0.53) compared to visual tactile (0.52, 0.34) for the more and less experienced examiners respectively. There was no significant difference between the experienced and the inexperienced group in combined sensitivity and specificity (mean) for VT (0.52, 0.53) or CD (0.60, 0.58). IN CONCLUSION: VT was more subjective than CD, except for experienced examiners who had a higher inter-examiner repeatability for VT than CD. Diagnostic accuracy for residual caries does not increase with experience.

Stem cell-coated titanium implants for the partial joint resurfacing of the knee.

The goal of the present study was to evaluate the partial surface replacement of the knee with stem cell-coated titanium implants and to provide a basis for a successful treatment of large osteochondral defects. Mesenchymal stem cells (MSCs) were isolated from bone marrow aspirates of adult sheep. Round titanium implants with a diameter of 2 x 7.3 mm were seeded with autologous MSC and inserted into an osteochondral defect in the medial femoral condyle. As controls, defects received either an uncoated implant or were left untreated. Nine animals with 18 defects were sacrificed after 6 months. Histological evaluation was performed by intravital polychrome fluorescent labelling, intravital perfusion with Indian ink, microradiographs and differential staining with toluidine blue. The quality of regenerated cartilage was assessed by in situ hybridization of collagen type II and immunohistochemistry of collagen types I and II. In 50% of the cases, defects treated with MSC-coated implants showed a complete regeneration of the subchondral bone layer. In these cases collagen type II and only traces of collagen type I were detected. A high level of collagen type II mRNA expression compared to articular cartilage indicates regenerating hyaline-like cartilage. A total of 50% of MSC-coated and uncoated implants failed to osseointegrate and formation of fibrocartilage was observed. Untreated defects as well as defects treated with uncoated implants demonstrated incomplete healing of subchondral bone and formation of fibrous cartilage. A modified histological score according to Wakitani significantly demonstrated better results for cell-coated implants (8.8+/-6.4) than for uncoated implants (5.5+/-3.9) and for untreated defects (2.8+/-2.5). Our results demonstrate that, in a significant number of cases, a partial joint resurfacing of the knee with stem cell-coated titanium implants occur. A slow bone and cartilage regeneration and an incomplete healing in half of the MSC-coated implants are limitations of the presented method. To improve our approach and optimize the experimental parameters, further investigations are needed prior to clinical application.

Transitional cell carcinomas and nonurothelial carcinomas of the urinary bladder differ in the promoter methylation status of the caveolin-1, hDAB2IP and p53 genes, but not in the global methylation of Alu elements.

Tumor suppressor genes play a prominent role in the modification and progression of urinary bladder carcinogenesis as a result of classic genetic alterations. Little is known about the potential significance of epigenetic events, mediated by DNA hypermethylation. This prompted our investigation to explore the global Alu methylation and the promoter methylation of the novel putative tumor suppressor genes caveolin-1 and hDAB2IP, and of p53 in transitional cell carcinomas (TCC), squamous cell carcinomas and undifferentiated small cell carcinomas of the urinary bladder. Quantitative GeneScan analysis revealed that the various histopathological tumor entities showed considerable interindividual variations in the global methylation, but the overall rate did not significantly differ between the various cancer subtypes. With methylation-specific PCR, a high frequency of methylation of the promoter region of the caveolin-1 gene was detected in undifferentiated small cell carcinomas (50%) and in squamous cell carcinomas (25.9%), while TCC were found not to be methylated. By immunohistochemistry, all squamous cell carcinomas showed a strong diffuse overexpression of caveolin-1, whereas undifferentiated small cell cancers lacked any expression. High-grade, high-stage TCC disclosed a higher incidence (60%) and a substantially stronger expression than low-grade, low-stage TCC (42.9%). Our findings suggest that hypermethylation of the caveolin-1 gene and an abnormal protein expression play a crucial role in cell differentiation, and in the phenotypical conversion of TCC into nonurothelial carcinomas. Promoter methylation of the hDAB2IP gene occurred more frequently in advanced muscle invasive (72.7%) than in superficial noninvasive (50%) TCC. DNA hypermethylation of p53 was detected in a quarter of the low-grade, low-stage TCC and undifferentiated small cell carcinomas, but only sporadically in squamous cell carcinomas, and was absent in high-grade, high-stage TCC. In conclusion, aberrant methylation and abnormal protein expression of the caveolin-1-gene is involved in the formation of nonurothelial carcinomas of the urinary bladder and promoter methylation of the hDAB2IP gene in the progression of TCC from a low to a high malignant potential.

Antimicrobial effectiveness of a highly concentrated chlorhexidine varnish treatment in teenagers with fixed orthodontic appliances.

OBJECTIVE: To evaluate the recolonization pattern of Mutans streptococci (ms) on densely colonized teeth with fixed orthodontic appliances after treatment with a highly concentrated (36%) chlorhexidine varnish. MATERIALS AND METHODS: Healthy subjects (n = 19) with fixed orthodontic appliances and high bacterial ms counts in saliva were recruited. In order to establish a baseline registration, plaque adjacent to brackets was sampled and cultivated on Dentocult strips. Following professional tooth cleaning, chlorhexidine varnish was applied on all teeth for 8 minutes. The degree of recolonization with ms was assessed 2 weeks after varnish application in plaque around the brackets. For statistical analysis, the data were subjected to a repeated measures design. RESULTS: After 2 weeks, ms counts were reduced as compared to baseline values. However, the reduction only weakly met statistical significance (P = .049). CONCLUSIONS: The application of a highly concentrated chlorhexidine varnish in patients with fixed orthodontic appliances does not result in a distinct reduction of ms numbers 2 weeks after treatment.

[In vitro cytotoxicity of different self-etching dental adhesive systems]. / N-vitro-Untersuchung zur Zytotoxizität von Self-Etch-Adhäsivsystemen.

The study evaluated the cytotoxicity of five self-etching dentin adhesive systems applied on dentin specimens of different thicknesses. The test materials (A: Adper Prompt-L-Pop, B: Xeno II, C: Clearfil SE Bond, D: One up Bond F, E: Resulcin Aqua Prime & Monobond) and a positive control (35% H202) were applied on 1.0, 1.5 and 2.5 mm thick bovine dentin specimens (each subgroup n = 5) in a dentin barrier test device. The experiments were performed with perfusion (2 ml/h) of the pulpal part of the chamber. The eluates were obtained before (baseline) and 15, 30, 45, 60 and 120 min after application of the adhesives and pipetted onto L-929 fibroblasts. Cytotoxicity of the materials was determined in relation to the baseline value using the MTT assay and statistical analysis was performed by ANOVA. After 15 min perfusion, test materials B-E applied on 1.0 mm and B and E applied on 1.5 mm dentin specimens exhibited cytotoxic potential. However, after 30 min perfusion none of the adhesives showed any toxicity. Cytotoxicity decreased with increasing thickness of the dentin slices and was lower for Adper Prompt-L-Pop compared to adhesives B-E. Self-etching adhesive systems might exhibit cytotoxic potential when applied on dentin of less than 1.5 mm thickness. However, cytotoxicity of the materials decreased with increasing dentin thickness and increasing duration of perfusion.

Disentangling beat perception from sequential learning and examining the influence of attention and musical abilities on ERP responses to rhythm.

Beat perception is the ability to perceive temporal regularity in musical rhythm. When a beat is perceived, predictions about upcoming events can be generated. These predictions can influence processing of subsequent rhythmic events. However, statistical learning of the order of sounds in a sequence can also affect processing of rhythmic events and must be differentiated from beat perception. In the current study, using EEG, we examined the effects of attention and musical abilities on beat perception. To ensure we measured beat perception and not absolute perception of temporal intervals, we used alternating loud and soft tones to create a rhythm with two hierarchical metrical levels. To control for sequential learning of the order of the different sounds, we used temporally regular (isochronous) and jittered rhythmic sequences. The order of sounds was identical in both conditions, but only the regular condition allowed for the perception of a beat. Unexpected intensity decrements were introduced on the beat and offbeat. In the regular condition, both beat perception and sequential learning were expected to enhance detection of these deviants on the beat. In the jittered condition, only sequential learning was expected to affect processing of the deviants. ERP responses to deviants were larger on the beat than offbeat in both conditions. Importantly, this difference was larger in the regular condition than in the jittered condition, suggesting that beat perception influenced responses to rhythmic events in addition to sequential learning. The influence of beat perception was present both with and without attention directed at the rhythm. Moreover, beat perception as measured with ERPs correlated with musical abilities, but only when attention was directed at the stimuli. Our study shows that beat perception is possible when attention is not directed at a rhythm. In addition, our results suggest that attention may mediate the influence of musical abilities on beat perception.

Improved serodiagnosis of Campylobacter jejuni infections using recombinant antigens.

Campylobacter jejuni is a frequent cause of infectious diarrhoea and is increasingly recognized as a trigger for late-onset complications. The poor standardization of commonly used serological tests might explain the conflicting results regarding the frequency of antecedent C. jejuni infections in defined patient groups. In order to obtain reliable epidemiological data as to the role of C. jejuni in causing late-onset complications, a highly specific and sensitive diagnostic tool for the epidemiological investigation of C. jejuni-associated diseases was developed. It was shown that recombinant proteins encoded by the C. jejuni genes cj0017 (P39) and cj0113 (P18) are specifically recognized by antibodies in sera from patients with C. jejuni enteritis. An ELISA using recombinant P18 and P39 as antigens was 91.9% sensitive and 99.0% specific, with positive and negative predictive values of 97.1% and 97.0%, respectively, comparing favourably with the 27.0% sensitivity of a routinely used serological assay.

Nonparametric methods for analysing the accuracy of diagnostic tests with multiple readers.

The evaluation of diagnostic agents or imaging procedures is governed by the same scientific and regulatory rules as that of other medical products. Receiver operating characteristic (ROC) curves, and especially the area under these ROC curves, are indices for the accuracy of a diagnostic test for continuous as well as ordinal data. The methodology of multivariate rank statistics for the nonparametric Behrens-Fisher problem is used to evaluate the accuracy of a diagnostic test in a complex factorial design with repeated measurements. Hypotheses are formulated by means of relative treatment effects and are tested by a multivariate extension of the Mann-Whitney statistic in a heteroscedastic model. The application of this method is demonstrated by the analysis of a data set from a diagnostic clinical trial.

Impact of chronic LDL-apheresis treatment on Achilles tendon affection in patients with severe familial hypercholesterolemia: a clinical and ultrasonographic 3-year follow-up study.

OBJECTIVE: Pain of Achilles tendon (AT) is a common symptom in patients with severe familial hypercholesterolemia (FH) and often associated with AT xanthomas. It is unknown if these changes are potentially reversible during lipid lowering treatment. LDL-apheresis (LA) represents the most effective lipid lowering regimen. Aim of this investigation was to determine clinical and ultrasonographic reduction of AT xanthomas in patients with severe FH undergoing regular LA. METHODS: At baseline, patient history of 22 patients with FH undergoing LA was obtained and their 44 ATs were evaluated clinically and with ultrasound for the presence of xanthomas. Three years later, both examinations of ATs could be repeated at follow-up visits in 16 patients. AT thickness and changes in echo structure were assessed at both points of time and compared to each other as well as to a healthy control group (n = 21). ROC analysis was performed to identify the optimal cut-off in AT thickness between healthy and affected ATs. RESULTS: Twelve of 22 FH patients suffered from AT pain at least once during their life-time. At baseline, AT thickness was significantly increased compared to the healthy control group (mean sagittal diameter 10.1 +/- 3.6 mm). At follow-up, AT thickness was significantly reduced to 8.2 +/- 3.3 mm (mean) under LA, whereas changes in echo structure were less distinct between both visits. Conversely, in the control group, mean AT thickness was 5.2 +/- 0.6 mm. The optimal cut-off between healthy and affected ATs was determined to be 6mm. CONCLUSIONS: Ultrasonographic changes of the AT (thickening and changes in echo structure) are frequent in patients with severe FH, even if xanthomas are not clinically evident. LA treatment has the capability to reduce AT xanthomas and thickness. Ultrasound may give information about diagnosis and follow-up of AT affection in patients with FH.

Significance of isolated tumor cells in lymph nodes among gastric cancer patients.

PURPOSE: To determine the frequency and prognostic impact of isolated tumor cells (ITC) in regional lymph nodes judged to be tumor free in conventional histopathology among gastric cancer patients. METHODS: Among 161 patients who underwent gastrectomy and D2-lymphadenectomy, 56 were staged pN0(35%). Archival paraffin blocks of 1148 resected regional lymph nodes of those pN0 patients were reevaluated for ITC using monoclonal antibody Ber-EP4. Patients with and without ITC were compared with regard to the distribution of various clinicopathological factors. Prognostic impact of ITC was tested in uni- and multivariate analysis. RESULTS: Of 56 pN0 patients, 33 (59%) exhibited single Ber-Ep4 immunoreactive cells or small cell clusters in at least one lymph node. The occurrence of ITC was not dependent on other clinicopathological factors. ITC impaired patients' prognoses significantly in uni- as well as multivariate analyses [estimated 5-year survival rate: 82% for pN0((i-))vs 58% for pN0((i+))(p = 0.059) and 15% for pN1/2 (p = 0.0005 and p < 0.0001, respectively)]. CONCLUSION: ITC are a frequent event in apparently tumor-free lymph nodes of gastric cancer patients and are overlooked by conventional histopathology. They are encountered even in limited stages of disease and impair patients' prognoses. This should be borne in mind when advocating local resection for early gastric cancer.

Real-time reverse transcription-polymerase chain reaction assay for GA733-2 mRNA in the detection of metastatic carcinoma cells in serous effusions.

Cytomorphologic and immunocytologic examination alone provide only limited sensitivity for the detection of metastatic carcinoma cells in many cases of serous effusions. The specificity of conventional reverse transcription-polymerase chain reaction (RT-PCR) methods for detection of epithelial gene transcripts is low owing to the ectopic expression of many such genes in nonepithelial cells. For the detection of metastatic carcinoma cells, we describe a quantitative real-time RT-PCR assay for GA733-2 messenger RNA encoding an epithelial glycoprotein (EGP-2) that binds to the monoclonal antibody BerEP4. With serial dilutions of BerEP4-positive SK-BR-3 breast carcinoma cells, the RT-PCR assay was able to detect 10 carcinoma cells in a background of 10(6) lymphoid cells compared with 10(2) to 10(3) carcinoma cells detectable by immunocytologic examination. We analyzed 51 serous effusions, including 25 malignant metastatic effusions, by the real-time RT-PCR assay. Receiver operating characteristic curve analyses demonstrated a sensitivity of 96% corresponding to a specificity of 98% for a correct diagnosis of metastatic effusions. These results provide evidence that the GA733-2 real-time RT-PCR assay is a specific and sensitive tool for the detection of metastasis of BerEP4-positive primary tumors in serous effusion specimens.

EGFR but not PDGFR-beta expression correlates to the antiproliferative effect of growth factor withdrawal in glioblastoma multiforme cell lines.

BACKGROUND: The aim of the current study was to investigate a putative relationship between (i) growth characteristics (proliferation and tumorigenicity) of nine glioblastoma multiforme (GBM) cell lines under different growth-stimulating conditions in vitro and (ii) their basal expression of a panel of growth factor receptors/autocrine cytokines. MATERIALS AND METHODS: Basal expressions of the epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor-beta (PDGFR-beta), platelet-derived growth factor-AA (PDGF-AA) and PDGF-BB, tumor growth factor-alpha (TGF-alpha) and TGF-beta as well as tumor necrosis factor-alpha (TNF-alpha) were determined by immunocytochemistry at standard cell culture conditions (10% fetal calf serum [FCS]). Proliferation and tumorigenicity at 10% FCS and relative serum starvation (0.5% FCS) were assessed by using Coulter counting and soft agar cloning, respectively. RESULTS: The ratio between cell multiplications at 10% and 0.5% FCS over a 10-day period was defined as a measure of growth factor dependence of cellular proliferation. Expression of EGFR (but not of PDGFR-beta) strongly correlated to this ratio (Spearman rank correlation coefficient R = 0.87). No considerable correlations were present among other appropriate pairs of variables with biologically founded putative relationships. CONCLUSION: Greater expression of EGFR is associated with increased growth factor dependence of cellular proliferation. Our results strengthen the role of EGFR as a rational molecular target of therapeutic intervention in GBM.

Is musculoskeletal ultrasonography an operator-dependent method or a fast and reliably teachable diagnostic tool? Interreader agreements of three ultrasonographers with different training levels.

Objectives. To assess interreader agreements and a learning curve between three (senior, junior, and beginner) different experienced musculoskeletal ultrasonographers. Senior served as the imaging "gold standard". Methods. Clinically dominant joints (finger, shoulder, knee, tibiotalar, and talonavicular) of 15 rheumatoid arthritis (RA) patients were examined by three different experienced ultrasonographers (senior 10 years, junior 10 months, and beginner one month). Each patient's ultrasonographic findings were reported unaware of the other investigators' results. κ coefficients, percentage agreements, sensitivities, and specificities were calculated. Results. 120 joints of 15 RA patients were evaluated. Comparing junior's and beginner's results each to the senior's findings, the overall κ for all examined joints was 0.83 (93%) for junior and 0.43 (76%) for beginner. Regarding the different joints, junior's findings correlate very well with the senior's findings (finger joints: κ = 0.82; shoulder: κ = 0.9; knee: κ = 0.74; tibiotalar joint: κ = 0.84; talonavicular joint: κ = 0.84) while beginner's findings just showed fair to moderate agreements (finger joints: κ = 0.4; shoulder: κ = 0.42; knee: κ = 0.4; tibiotalar joint: κ = 0.59; talonavicular joint: κ = 0.35). In total, beginner's results clearly improved from κ = 0.34 (agreement of 67%) at baseline to κ = 0.78 (agreement of 89%) at the end of the evaluation period. Conclusions. Ultrasonographic evaluation of a ten-month-experienced investigator in comparison to a senior ultrasonographer was of substantial agreement. Agreements between a beginner and a highly experienced ultrasonographer were only fair at the beginning, but during the study including ultrasonographical sessions of 15 RA patients, the beginner clearly improved in musculoskeletal ultrasonography.

Reliability exercise for the polymyalgia rheumatica classification criteria study: the oranjewoud ultrasound substudy.

Objective. A study supported by the EULAR and the ACR being conducted to establish classification criteria for polymyalgia rheumatica (PMR) will include ultrasound examination of the shoulders and hips. Ultrasound (US) depicts glenohumeral joint effusion, biceps tenosynovitis, subdeltoid bursitis, hip joint synovitis, and trochanteric bursitis in PMR. These findings may aid in distinguishing PMR from other diseases. The purpose of this study was to assess standards and US interreader agreement of participants in the PMR classification criteria study. Methods. Sixteen physicians in four groups examined shoulders and hips of 4 patients and 4 healthy adults with ultrasound. Overall agreement and interobserver agreement were calculated. Results. The overall agreement (OA) between groups was 87%. The OA for healthy shoulders was 88.8%, for healthy hips 100%, for shoulders with pathology 85.2%, and 74.3% for hips with pathology, respectively. Conclusion. There was a high degree of agreement found for the examination of healthy shoulders and pathologic hips. Agreement was moderate for pathologic shoulders and perfect for healthy hips. US of shoulder and hips performed by different examiners is a reliable and feasible tool for assessment of PMR related disease pathology and can be incorporated into a classification criteria study.

Computer-aided detection in full-field digital mammography: detection in dependence of the BI-RADS categories.

The object of this study was to determine the performance of a computer-aided detection system in full-field digital mammography (Senographe 2000D, General Electric, Buc, France) in detecting carcinomas in breasts in dependence of the initial Breast Imaging Reporting and Data System (BI-RADS) categories. A total of 226 mediolateral oblique (MLO) and 186 craniocaudal (CC) view mammograms of histologically proven cancers were retrospectively evaluated with a primary digital computer-aided detection system (Image Checker V2.3; R2 Technology, Los Altos, CA). According to BI-RADS of the American College of Radiology (ACR), the lesions were classified in MLO view as BI-RADS 1 in 2 cases, BI-RADS 2 in 11 cases, BI-RADS 3 in 37 cases, BI-RADS 4 in 56 cases, and BI-RADS 5 in 120 cases, and in CC view as BI-RADS 1 in 2 cases, BI-RADS 2 in 8 cases, BI-RADS 3 in 26 cases, BI-RADS 4 in 46 cases, and BI-RADS 5 in 104 cases. The computer-aided detection system shows markers also in mammograms classified as BI-RADS categories 1-3 by the radiologist. Furthermore, BI-RADS categories 4 and 5 in most cases demonstrate masses in mammography. With increasing BI-RADS category, the computer-aided detection system shows decreasing numbers of overlooked carcinomas. In MLO view, no markers were found in 100% (2/2), 81.8% (9/11), 59.5% (22/37), 46.4% (26/56), and 15% (18/120) for BI-RADS categories 1-5, respectively. False-positive markers, however, were seen in 0.5 per image (205/412). In conclusion, the high rate of false-positive markers shows that the specificity of the computer-aided detection system is limited and that improvements are necessary.