Prostate cancer detection among readers with different degree of experience using ultra-high b-value diffusion-weighted Imaging: Is a non-contrast protocol sufficient to detect significant cancer?

AIM: To evaluate the accuracy of a T2-weighted (T2w) - and a parallel transmit zoomed b = 2000 s/mm2 (b2000) - diffusion-weighted imaging sequence among three readers with different degrees of experience for prostate cancer (Pca) detection. METHODS: Ninety-three patients with suspected Pca were enrolled. For b2000 a two-dimensional spatially-selective RF pulse using an echo-planar transmit trajectory was applied, and the field of view (FOV) was reduced to one-third. All three readers (Reader A: 7, B 4 and C <1 years of experience in prostate MRI) independently evaluated b2000 with regard to the presence of suspicious lesions that displayed increased signal. The results were compared to histopathology obtained by real-time MR/ultrasound fusion and systematic biopsy. RESULTS: In 62 patients Pca was confirmed. One significant Pca (Gleason score (GS) 7b) was missed by Reader C. Overall, sensitivity/specificity/positive predictive value/negative predictive value were 90/71/86/79% for Reader A, 87/84/92/76% for Reader B and 85/74/87/72% for Reader C, respectively. Detection rates for significant Pca (GS >7a) were 100/100/94% for Readers A/B/C, respectively. Inter-reader agreement was generally good (Kappa A/B: 0.8; A/C: 0.82; B/C: 0.74). CONCLUSION: B2000 in combination with a T2w could be useful to detect clinically significant Pca. KEY POINTS: • Significant prostate cancer using zoomed ultra-high b-value DWI was detected. • Diagnostic performance among readers with different degrees of experience was good. • mp- MRI of the prostate using a comprehensive non-contrast protocol is clinically feasible.

Precision of MRI/ultrasound-fusion biopsy in prostate cancer diagnosis: an ex vivo comparison of alternative biopsy techniques on prostate phantoms.

PURPOSE: Comparing the accuracy of MRI/ultrasound-guided target-biopsy by transrectal biopsy (TRB) with elastic versus rigid image fusion versus transperineal biopsy (TPB) with rigid image fusion in a standardized setting. METHODS: Target-biopsy of six differently sized and located lesions was performed on customized CIRS 070L prostate phantoms. Lesions were only MRI-visible. After prior MRI for lesion location, one targeted biopsy per lesion was obtained by TRB with elastic image fusion with Artemis™ (Eigen, USA), TRB with rigid image fusion with real-time virtual sonography (Hitachi, Japan) and TPB with rigid image fusion with a brachytherapy approach (Elekta, Sweden), each on a phantom of 50, 100 and 150 ml prostate volume. The needle trajectories were marked by contrast agent and detected in a postinterventional MRI. RESULTS: Overall target detection rate was 79.6% with a slight superiority for the TPB (83.3 vs. 77.8 vs. 77.8%). TRB with elastic image fusion showed the highest overall precision [median distance to lesion center 2.37 mm (0.14-4.18 mm)], independent of prostate volume. Anterior lesions were significantly more precisely hit than transitional and basal lesions (p = 0.034; p = 0.015) with comparable accuracy for TRB with elastic image fusion and TPB. In general, TRB with rigid image fusion was inferior [median 3.15 mm (0.37-10.62 mm)], particularly in small lesions. CONCLUSION: All biopsy techniques allow detection of clinically significant tumors with a median error of 2-3 mm. Elastic image fusion appears to be the most precise technique, independent of prostate volume, target size or location.

Splenomegaly, elevated alkaline phosphatase and mutations in the SRSF2/ASXL1/RUNX1 gene panel are strong adverse prognostic markers in patients with systemic mastocytosis.

We evaluated the impact of clinical and molecular characteristics on overall survival (OS) in 108 patients with indolent (n=41) and advanced systemic mastocytosis (SM) (advSM, n=67). Organomegaly was measured by magnetic resonance imaging-based volumetry of the liver and spleen. In multivariate analysis of all patients, an increased spleen volume ⩾450 ml (hazard ratio (HR), 5.2; 95% confidence interval (CI), (2.1-13.0); P=0.003) and an elevated alkaline phosphatase (AP; HR 5.0 (1.1-22.2); P=0.02) were associated with adverse OS. The 3-year OS was 100, 77, and 39%, respectively (P<0.0001), for patients with 0 (low risk, n=37), 1 (intermediate risk, n=32) or 2 (high risk, n=39) parameters. For advSM patients with fully available clinical and molecular data (n=60), univariate analysis identified splenomegaly ⩾1200 ml, elevated AP and mutations in the SRSF2/ASXL1/RUNX1 (S/A/R) gene panel as significant prognostic markers. In multivariate analysis, mutations in S/A/R (HR 3.2 (1.1-9.6); P=0.01) and elevated AP (HR 2.6 (1.0-7.1); P=0.03) remained predictive adverse prognostic markers for OS. The 3-year OS was 76 and 38%, respectively (P=0.0003), for patients with 0-1 (intermediate risk, n=28) or 2 (high risk, n=32) parameters. We conclude that splenomegaly, elevated AP and mutations in the S/A/R gene panel are independent of the World Health Organization classification and provide the most relevant prognostic information in SM patients.

[Quantitative perfusion imaging in magnetic resonance imaging]. / Quantitative Perfusionsbildgebung in der Magnetresonanztomographie.

CLINICAL/METHODICAL ISSUE: Magnetic resonance imaging (MRI) is recognized for its superior tissue contrast while being non-invasive and free of ionizing radiation. Due to the development of new scanner hardware and fast imaging techniques during the last decades, access to tissue and organ functions became possible. One of these functional imaging techniques is perfusion imaging with which tissue perfusion and capillary permeability can be determined from dynamic imaging data. STANDARD RADIOLOGICAL METHODS: Perfusion imaging by MRI can be performed by two approaches, arterial spin labeling (ASL) and dynamic contrast-enhanced (DCE) MRI. While the first method uses magnetically labelled water protons in arterial blood as an endogenous tracer, the latter involves the injection of a contrast agent, usually gadolinium (Gd), as a tracer for calculating hemodynamic parameters. PERFORMANCE: Studies have demonstrated the potential of perfusion MRI for diagnostics and also for therapy monitoring. ACHIEVEMENTS: The utilization and application of perfusion MRI are still restricted to specialized centers, such as university hospitals. A broad application of the technique has not yet been implemented. PRACTICAL RECOMMENDATIONS: The MRI perfusion technique is a valuable tool that might come broadly available after implementation of standards on European and international levels. Such efforts are being promoted by the respective professional bodies.

Multi-parametric MRI of rectal cancer - do quantitative functional MR measurements correlate with radiologic and pathologic tumor stages?

PURPOSE: The purpose of this study is two-fold. First, to evaluate, whether functional rectal MRI techniques can be analyzed in a reproducible manner by different readers and second, to assess whether different clinical and pathologic T and N stages can be differentiated by functional MRI measurements. MATERIALS AND METHODS: 54 patients (38 men, 16 female; mean age 63.2 ± 12.2 years) with pathologically proven rectal cancer were included in this retrospective IRB-approved study. All patients were referred for a multi-parametric MRI protocol on a 3 Tesla MR-system, consisting of a high-resolution, axial T2 TSE sequence, DWI and perfusion imaging (plasma flow -s PFTumor) prior to any treatment. Two experienced radiologists evaluated the MRI measurements, blinded to clinical data and outcome. Inter-reader correlation and the association of functional MRI parameters with c- and p-staging were analyzed. RESULTS: The inter-reader correlation for lymph node (ρ 0.76-0.94; p<0.0002) and primary tumor (ρ 0.78-0.92; p<0.0001) apparent diffusion coefficient and plasma flow (PF) values was good to very good. PFTumor values decreased with cT stage with significant differences identified between cT2 and cT3 tumors (229 versus 107.6 ml/100ml/min; p=0.05). ADCTumor values did not differ significantly. No substantial discrepancies in lymph node ADCLn values or short axis diameter were found among cN1-3 stages, whereas PFLn values were distinct between cN1 versus cN2 stages (p=0.03). In the patients without neoadjuvant RCT no statistically significant differences in the assessed functional parameters on the basis of pathologic stage were found. CONCLUSION: This study illustrates that ADC as well as MR perfusion values can be analyzed with good interobserver agreement in patients with rectal cancer. Moreover, MR perfusion parameters may allow accurate differentiation of tumor stages. Both findings suggest that functional MRI parameters may help to discriminate T and N stages for clinical decision making.

[Multiparametric prostate MRI for follow-up monitoring after radiation therapy]. / Multiparametrische MRT der Prostata zum Therapiemonitoring nach Strahlentherapie.

CLINICAL/METHODICAL ISSUE: Radiation therapy is a therapeutic option with curative intent for patients with prostate cancer. Monitoring of prostate-specific antigen (PSA) values is the current standard of care in the follow-up. Imaging is recommended only for symptomatic patients and/or for further therapeutic options. STANDARD RADIOLOGICAL METHODS: For detection of local recurrence magnetic resonance imaging (MRI) of the prostate is acknowledged as the method of choice. PERFORMANCE: Good results for primary diagnosis were found especially in combination with functional techniques, whereas in recurrent prostate cancer only few studies with heterogeneous study design are available for prostate MRI. Furthermore, changes in different MRI modalities due to radiation therapy have been insufficiently investigated to date. PRACTICAL RECOMMENDATIONS: As the initial results were promising prostate MRI and available therapeutic options for detection of local recurrence should be considered in patients with increased PSA.

[Comparative findings of balloon kyphoplasty in patients with vertebral fractures due to osteoporosis, metastases and myeloma]. / Vergleichende Befunderhebungen der Ballonkyphoplastie bei Patienten mit Wirbelkörperfrakturen infolge von Osteoporose, Metastasen und Myelomen.

OBJECTIVE: By evaluations of treatment protocols, the documentation of balloon kyphoplasty regarding efficacy, duration of action and safety should be expanded. In addition, the evaluations should help to clarify the differences in balloon kyphoplasty for patients with vertebral fractures concerning efficacy and safety in relation to the underlying diseases: osteoporosis, bone metastases or myeloma. MATERIAL AND METHODS: In order to reposition the endplates of the vertebrae a balloon was inserted after placement of the working channels. After removal of the balloon, the resulting caverns were filled with PMMA. The radiological and clinical follow-up examinations were carried out over a period of up to 3 years. The clinical and radiological findings before and after treatment at specified visits were transferred to a statistical programme and evaluated. RESULTS: The comparisons of the postoperative results according to the initial diagnosis (metastases: n = 222, osteoporosis: n = 122, myeloma: n = 122) demonstrated significant differences with respect to the cement leakage (14 %, 5 %, 7.5 %), but in all cases without any clinical relevance. The small differences related to the reduction in pain intensity (VAS > 50 mm in each group) after surgery were up to 12 months with no clinical significance. Also in the Oswestry score no differences between the 3 groups were registered. In the case of osteoporosis patients, due to the lower starting position a more significant increase of vertebral body height could be achieved by the kyphoplasty than in the comparison groups of patients with metastases or myeloma (∅ 3.1 mm vs. 0.4-0.5 mm; P < 0.001). Consequently, the kyphosis angle decreased in the osteoporotic group also more strongly than in the comparison groups. CONCLUSIONS: It is evident that the pain relief in the vast majority of cases started immediately after surgery. Additionally, a significant improvement in functioning (Oswestry score) was registered. Both clinical parameters - as far as they could be checked - showed a steady degree of improvement over a period of at least 3 years. This comparative analysis led to the conclusion that balloon kyphoplasty can be successfully applied indiscriminately in patients with vertebral fractures as a result of osteoporosis and also to fractures associated with bone metastases or with myeloma.

[Whole-body MRI in preoperative diagnostics of breast cancer--a comparison with [corrected] staging methods according to the S 3 guidelines]. / Ganzkörper-MRT in der präoperativen Diagnostik des Mammakarzinoms--ein Vergleich mit den Stagingmethoden in der S 3-Leitlinie.

PURPOSE: The German Society of Senology (step-3 guidelines for the early recognition of breast cancer in Germany) recommends whole-body staging including chest X-ray, ultrasound of the liver and bone scintigraphy before systemic therapy in patients with breast cancer. The performance of these three examinations is time-consuming and involves radiation exposure. Whole-body MR imaging (WB-MRI) allows staging in a single examination without radiation exposure. The purpose of this study was to compare the diagnostic accuracy of WB-MRI with staging according to the guidelines. MATERIALS AND METHODS: During 04/07 and 06/09, the initial staging in 51 patients (56 ± 12 yrs) with breast cancer (24 patients with lymph node metastases) was performed according to the S 3-guidelines. Additionally, all patients underwent contrast-enhanced WB-MRI (1.5-Tesla-Magnetom Avanto, Siemens, Erlangen). The findings of the different modalities were compared after correlation of the lesions by follow-up. The detection of suspicious findings and the accuracy of prediction of malignancy of the detected lesions were evaluated. RESULTS: Overall, 14 metastases were detected in 4 of 51 patients after completion of the follow-up. By means of WB-MRI, all 14 metastases could be detected, while just 4 of these metastases were identified by the conventional methods. CONCLUSION: The detection of distant metastases has an important impact on patient management. In this study WB-MRI in breast cancer staging has shown promising results in regard to possible clinical implementation as a matter of routine staging.

[Complications of venous port systems : Radiological diagnostics and minimally invasive therapy]. / Komplikationen venöser Portsysteme : Radiologische Diagnostik und minimalinvasive Therapie.

INTRODUCTION: Documentation of a correct port placement is a routine investigation in radiology. This article describes typical complications of port catheters and minimally invasive treatment options which can guarantee further use without complications. MATERIAL AND METHODS: From January 2009 to May 2010 a surgical port placement was carried out on 174 patients at the University Clinic in Mannheim and of these, 52 patients were admitted to our institute for radiological imaging of the port. Minimally invasive treatment options are presented based on the observed port complications. RESULTS: Of the 52 patients 7 (13.5%) received a port catheter lysis. A successful port position correction was carried out in 3 (5.8%) patients with a malpositioned port catheter and port removal was recommended in 2 patients (3.8%) due to extensive arm venous thrombosis. A minimally invasive port catheter treatment allowed further use of the port system without operative revision in the corresponding patients. The measures were tolerated very well by the patients without postinterventional complications.

Assessment of the peripheral hearing system of sport divers.

OBJECTIVE: To investigate the effect of regular scuba diving on the hearing thresholds of sport divers who have no history of noise exposure or ear-related accidents. Comprehensive topographic examination of the peripheral hearing system of sport divers. DESIGN: Cross-sectional study. SETTINGS: General sport diving community. PARTICIPANTS: 81 sport divers with a mean of 300 dives each were compared to a control group of 81 non-divers. MAIN OUTCOME MEASURE: Participants were classified into three age groups. Examination included microscopic otoscopy, tympanometry, pure-tone audiometry (PTA) including air and bone conduction, speech audiometry and otoacoustic emissions (OAE). RESULTS: PTA suggested significant differences of the hearing thresholds at several frequencies between sport divers and non-divers in all age groups, although a Bonferroni correction for multiple testing was applied. Interestingly, the results were contradictory. Divers obtained better hearing results in air conduction, whereas non-divers showed better results in bone conduction. Speech audiometry and OAE did not reveal significant differences. CONCLUSION: There are no published studies of the peripheral cochlear system of divers that have used a combination of PTA, speech audiometry and OAE. All studies suggesting hearing impairment in divers were based on PTA and might have been influenced by a lack of accuracy of PTA. Our results suggest that diving does not adversely affect the hearing system of sport divers. A thorough test battery of audiological methods implying PTA, speech audiometry and OAE may contribute to offer more reliable results to answer the question of whether commercial or military divers are at higher risk for hearing detoriation.

Assessment of the central hearing system of sport divers.

OBJECTIVE: To investigate the effect of regular scuba diving on central processing sequences of sport divers who have no history of noise exposure or ear-related accidents using a comprehensive topographic examination of the central hearing system. DESIGN: Cross-sectional controlled comparison study. SETTINGS: General sports diving community. PARTICIPANTS: 81 sport divers with a mean of 300 dives each were compared with a control group of 81 non-divers. MAIN OUTCOME MEASURE: The participants were classified into three age groups. Hearing test results were combined for both ears. Examination included brainstem evoked response audiometry (BERA), cortical evoked response audiometry (CERA) and dichotic listening tests to screen for retrocochlear and central hearing disorders. Testing of brainstem latencies was performed in a gender-dependent manner. RESULTS: BERA showed a pathological extension of the I-V-latency in one diver. Magnetic tomographic imaging ruled out brainstem lesions. No reason for the measured latency could be detected. All other latencies (I-III, III-V and I-V) in both gender groups were within normal limits. No statistically significant differences between divers and non-divers could be detected. Dichotic listening showed no clinical abnormalities in any of the participants, but in the age group 18-29 years divers performed significantly better than non-divers (p = 0.01). CERA revealed no significant differences between divers and non-divers in the age group 18-29 years and 30-39 years, whereas divers in the age group 41-50 demonstrated significantly better test results (p = 0.045) (difference of the means: 4.18 dB). CONCLUSION: Dichotic listening and CERA did not reveal a significant reduction of central hearing performance in divers. Persistent on-shore BERA wave latency prolongations that were present in one study could not be confirmed in our study group. This first comprehensive topographic examination of the central hearing system of divers showed no abnormalities.

Incidence and time course of intimal plaque formation in the right coronary artery after radiofrequency current application detected by intracoronary ultrasound.

BACKGROUND: Despite the current clinical use of radiofrequency (RF) catheter ablation in infants and children, the late effects of RF current application at immature myocardium remain unclear. The purpose of this study was to investigate incidence and time course of coronary lesions after RF current application at developing myocardium in an animal model. RESULTS: In 10 pigs, 6 weeks of age (13+/-2 kg), RF current (500 kHz) was delivered by temperature guidance (75 degrees C) using a steerable electrode catheter (4 mm tip electrode) over 30-second periods. RF lesions were created at the lateral right atrial wall at the tricuspid valve annulus and the lateral left atrial and ventricular wall at the mitral valve annulus. Subsequent coronary angiography and intracoronary ultrasound (ICUS) of the right coronary artery (RCA) and the left circumflex artery (CX) were performed 3, 6, 9 and 12 months after RF current application. Quantitative coronary angiography did not exhibit any significant stenosis of the vessels during the study period. Intimal lesions of the RCA were documented for the first time at the 6-month study in 3 animals by ICUS (mean plaque area 2.2+/-0.2 mm(2), mean area stenosis 30.4+/-4.0%). There was no significant change in lesion length, area stenosis and plaque area at the 9- and 12-month studies. All 3 coronary artery lesions were confirmed in close proximity to myocardial RF lesions by histological examination 12 months after RF delivery. No intimal plaque formation of the CX was observed. CONCLUSIONS: Affection of the RCA as a late sequel after RF current application at the lateral right atrial wall occurred in 3 out of 8 long-term surviving pigs. Three to six months seem to be the time frame for the development of intimal lesions after RF delivery. In this experimental setting, angiography failed to detect these intimal changes. The potential risk of coronary affection may be important for catheter ablation procedures at the right atrial myocardium in infants and small children.

Endothelial function in patients with peripheral vascular disease: influence of prostaglandin E1.

Peripheral arterial occlusive disease (PAOD) is characterized by atherosclerotic lesions in large vessels and disturbances on the microcirculatory level. In the local regulation of vascular tone and microvascular perfusion, vascular endothelium plays a key role. For many years prostaglandin E1 (PGE1) has been used for the treatment of PAOD. Because PGE1 has only moderate effects on blood flow other mechanisms may be relevant for the therapeutical efficacy. The aim of our pilot study was to evaluate endothelial function in patients with PAOD and to investigate the impact of PGE1 on endothelial-dependent vasodilation in peripheral vesselsIn 8 controls and in 8 patients with PAOD stage II, endothelial-dependent vascular responses of the femoral vessels to increasing doses of acetylcholine (30,60,90 microg/min) were determined by Doppler flow velocity measurements in the common femoral artery. Furthermore, vascular reactivity was evaluated before and immediately after intravenous infusion of 30 microg PGE1/30 min in patients. Endothelial-dependent vasodilation was significantly reduced in patients with PAOD compared to control subjects. Infusion of PGE1 neither increased blood flow in the common femoral artery nor endothelium-dependent vasodilation of peripheral resistance vessels as indicated by unchanged reaction to acetylcholine. In conclusion, endothelial function is impaired in patients with PAOD. Administration of PGE1 did not increase femoral artery blood flow or improve endothelial-dependent reactivity of peripheral resistance vessels in patients with PAOD. Therefore, beneficial effects of PGE1 in peripheral vascular disease cannot be attributed to an increase in blood supply or an improvement of endothelial-dependent vasodilation.

Use of intravascular ultrasound to compare effects of different strategies of lipid-lowering therapy on plaque volume and composition in patients with coronary artery disease.

BACKGROUND: We studied whether lipid-lowering therapy with atorvastatin (target LDL cholesterol [LDL-C] <100 mg/dL) compared with a moderate treatment regimen that used other lipid-lowering drugs led to a lesser progression of atherosclerosis and to different changes in plaque echogenicity in patients with coronary artery disease. METHODS AND RESULTS: This study was a 12-month, open-label, randomized, multicenter trial, which used serial 3D intracoronary ultrasound to calculate plaque volume and plaque echogenicity. After transcatheter therapy, 131 patients were randomized (atorvastatin n=65, usual care n=66). The target plaque had to be a minor lesion (ie, a diameter stenosis of <50% on angiography). After 12 months, mean LDL-C was reduced from 155 to 86 mg/dL in the atorvastatin group and from 166 to 140 mg/dL in the usual care group. Mean absolute plaque volume showed a larger increase in the usual care group compared with the atorvastatin group (usual care 9.6+/-28.1 mm(3), atorvastatin 1.2+/-30.4 mm(3); P=0.191). The hyperechogenicity index of the plaque increased to a larger extent for the atorvastatin group than for the usual care group, with a significant treatment effect for the percent change (atorvastatin 42.2%, usual care 10.1%; P=0.021). CONCLUSIONS: One year of lipid-lowering therapy to <100 mg/dL LDL-C most likely led to a slowdown of plaque growth of minor lesions. The significantly larger increase in plaque hyperechogenicity is most likely due to a change in plaque composition.

Binding of conserved islet peptides by human and murine MHC class II molecules associated with susceptibility to type I diabetes.

The major histocompatibility complex (MHC) is the most important susceptibility locus for type I diabetes in humans and NOD mice. NOD mice express a single MHC class II molecule (I-Ag7) which carries a unique beta chain sequence. In humans, DQ alleles that encode DQ8 and DQ2 confer the highest risk for the disease. Soluble DQ8 and I-Ag7 were used to directly compare the binding specificity of these MHC molecules. Peptides from three islet antigens--insulin, GAD 65 and HSP 60--bound to both CQ8 and I-Ag7. These peptides included epitopes that are immunodominant in NOD mice, namely insulin (9-23), GAD (206-220) and HSP 60 (441-460). All of these peptide sequences are highly conserved between the human and murine antigens. The binding specificity of DQ8 and I-Ag7 was similar, but not identical, since two peptides eluted from splenocytes of NOD mice did not bind to DQ8. DQ8 formed long-lived complexes with the majority of these peptides, indicating that DQ8 is not a poor peptide binder. These results demonstrate functional similarities between human and murine MHC class II molecules that confer susceptibility to type I diabetes.

[Intracoronary ultrasound]. / Intrakoronarer Ultraschall.

IVUS imaging provides a 2-dimensional, cross-sectional view into the lumen and vessel wall structure of coronary arteries; it is superior to angiography with regard to visualization about several aspects of coronary artery disease. IVUS has given important information on the development and progression of coronary atherosclerosis. Moreover, IVUS has improved our understanding of the mechanisms of percutaneous interventions and restenosis. IVUS-guided balloon sizing during PTCA may increase acute lumen gain as compared to conventional angiographic guidance. Optimization of stent implantation by IVUS guidance also results in larger initial lumen gain than with angiographic control; this approach, however, does not reduce restenosis rates. In summary, IVUS is an optional imaging modality that provides clinically useful information in selected patients.

Incomplete expansion of Palmaz-Schatz stents despite high-pressure implantation technique: impact on target lesion revascularization.

Improved expansion of stents using high-pressure implantation technique with subsequent antiplatelet therapy has improved patient outcome regarding the incidence of subacute stent thrombosis, bleeding complications and restenosis. Whether high-pressure implantation per se guarantees adequate stent expansion remains unclear. The aim of the study was to determine (1) stent expansion after high-pressure implantation technique and (2) whether stent expansion influences rate of target lesion revascularization within 6 months of follow-up. One hundred Palmaz-Schatz stents were implanted in 98 lesions (91 native vessels, 7 graft vessels) of 94 patients using high-pressure implantation technique (balloon pressure 12-20 atm). Stent expansion was investigated using intravascular ultrasound imaging (IVUS). Clinical follow-up of the patients was performed for 6 months. After implantation, stent/mean reference ratio was 0.81 +/- 0.16. Noncompliant balloons used for implantation were chosen by angiographic criteria. Mean balloon/reference ratio was 1.08 +/- 0.22; therefore balloons were not undersized. Additional balloon dilataion using higher pressures and/or larger balloons based on IVUS criteria and subsequent IVUS measurements was performed in 52 patients (55%); in these patients, stent expansion improved from 79 +/- 16 to 91 +/- 15% (mean +/- SD) of average reference areas (p < 0.002). Within the 6 months' clinical follow-up, target lesion revascularization was performed in 19 patients (20%). The only prognostic factors for the development of in-stent restenosis requiring target lesion revascularization were the vessel size (p < 0.05) and the extent of plaque distal to the stents (p < 0.05). Implantation of Palmaz-Schatz stents using high-pressure technique does not guarantee adequate stent expansion. Additional dilatation with higher pressures and/or larger balloons improves stent expansion. The size of the stented vessel and the extent of plaque at the distal stent end (residual outflow stenosis) but not the degree of stent expansion were predictors for target lesion revascularization within 6 months' follow-up.

pH-dependent peptide binding properties of the type I diabetes-associated I-Ag7 molecule: rapid release of CLIP at an endosomal pH.

MHC class II molecules and invariant chain assemble at a neutral pH in the endoplasmic reticulum and are transported to a low pH compartment where the invariant chain is trimmed to the class II-associated invariant chain peptide (CLIP). For many major histocompatibility complex class II molecules, DM is required for rapid removal of CLIP, which allows binding of antigenic peptides. Since I-Ag7 confers susceptibility to type I diabetes in NOD mice, the biochemical requirements for peptide loading were examined using soluble I-Ag7 expressed in insect cells. I-Ag7 formed long-lived complexes with naturally processed peptides from transferrin and albumin, whereas several peptides that represent T cell epitopes of islet autoantigens were poor binders. I-Ag7-peptide complexes were not sodium dodecyl sulfate (SDS) resistant, indicating that SDS sensitivity may be an intrinsic property of I-Ag7. Complexes of I-Ag7 and CLIP formed at a neutral pH, but rapidly dissociated at pH 5. This rapid dissociation was due to a poor fit of M98 of CLIP in the P9 pocket of I-Ag7, since substitution of M98 by a negatively charged residue greatly enhanced the stability of the complex. These biochemical properties of I-Ag7 result in the rapid generation of empty molecules at an endosomal pH and have a global effect on peptide binding by I-Ag7.

Intravascular ultrasound and stent implantation: intraobserver and interobserver variability.

BACKGROUND: Intravascular ultrasound (IVUS) imaging can be used to optimize implantation of intracoronary stents; the variability of the measurements, however, remains unclear. Our aim in this study was to determine the intraobserver and interobserver variability of IVUS measurements after stent implantation. METHODS: Ninety-four patients underwent implantation of 100 Palmaz-Schatz stents in 98 lesions (79 de novo and 19 restenotic). IVUS measurements (3.5F, 30 MHz) of proximal and distal reference sections and of the smallest stent lumen were performed by 2 investigators. RESULTS: Intraobserver and interobserver correlations, respectively, were r = 0.96 and 0.93 for the proximal reference, r = 0.94 and 0.92 for the distal reference, and r = 0.97 and 0.97 for minimal stent lumen. Stent expansion (minimal lumen in the stent/mean reference area) showed a variability of r = 0.80 and 0.70. Taking a cutoff point of 90% for adequacy of stent expansion, observers agreed in only 77% whether the stent was adequately or inadequately expanded. CONCLUSIONS: IVUS enables reproducible lumen measurements in stents and reference sections. The degree of stent expansion, however, underlies a high measurement variability that can lead to different therapeutic strategies.