RENEB Inter-Laboratory Comparison 2021: Inter-Assay Comparison of Eight Dosimetry Assays.

Tools for radiation exposure reconstruction are required to support the medical management of radiation victims in radiological or nuclear incidents. Different biological and physical dosimetry assays can be used for various exposure scenarios to estimate the dose of ionizing radiation a person has absorbed. Regular validation of the techniques through inter-laboratory comparisons (ILC) is essential to guarantee high quality results. In the current RENEB inter-laboratory comparison, the performance quality of established cytogenetic assays [dicentric chromosome assay (DCA), cytokinesis-block micronucleus assay (CBMN), stable chromosomal translocation assay (FISH) and premature chromosome condensation assay (PCC)] was tested in comparison to molecular biological assays [gamma-H2AX foci (gH2AX), gene expression (GE)] and physical dosimetry-based assays [electron paramagnetic resonance (EPR), optically or thermally stimulated luminescence (LUM)]. Three blinded coded samples (e.g., blood, enamel or mobiles) were exposed to 0, 1.2 or 3.5 Gy X-ray reference doses (240 kVp, 1 Gy/min). These doses roughly correspond to clinically relevant groups of unexposed to low exposed (0-1 Gy), moderately exposed (1-2 Gy, no severe acute health effects expected) and highly exposed individuals (>2 Gy, requiring early intensive medical care). In the frame of the current RENEB inter-laboratory comparison, samples were sent to 86 specialized teams in 46 organizations from 27 nations for dose estimation and identification of three clinically relevant groups. The time for sending early crude reports and more precise reports was documented for each laboratory and assay where possible. The quality of dose estimates was analyzed with three different levels of granularity, 1. by calculating the frequency of correctly reported clinically relevant dose categories, 2. by determining the number of dose estimates within the uncertainty intervals recommended for triage dosimetry (±0.5 Gy or ±1.0 Gy for doses <2.5 Gy or >2.5 Gy), and 3. by calculating the absolute difference (AD) of estimated doses relative to the reference doses. In total, 554 dose estimates were submitted within the 6-week period given before the exercise was closed. For samples processed with the highest priority, earliest dose estimates/categories were reported within 5-10 h of receipt for GE, gH2AX, LUM, EPR, 2-3 days for DCA, CBMN and within 6-7 days for the FISH assay. For the unirradiated control sample, the categorization in the correct clinically relevant group (0-1 Gy) as well as the allocation to the triage uncertainty interval was, with the exception of a few outliers, successfully performed for all assays. For the 3.5 Gy sample the percentage of correct classifications to the clinically relevant group (≥2 Gy) was between 89-100% for all assays, with the exception of gH2AX. For the 1.2 Gy sample, an exact allocation to the clinically relevant group was more difficult and 0-50% or 0-48% of the estimates were wrongly classified into the lowest or highest dose categories, respectively. For the irradiated samples, the correct allocation to the triage uncertainty intervals varied considerably between assays for the 1.2 Gy (29-76%) and 3.5 Gy (17-100%) samples. While a systematic shift towards higher doses was observed for the cytogenetic-based assays, extreme outliers exceeding the reference doses 2-6 fold were observed for EPR, FISH and GE assays. These outliers were related to a particular material examined (tooth enamel for EPR assay, reported as kerma in enamel, but when converted into the proper quantity, i.e. to kerma in air, expected dose estimates could be recalculated in most cases), the level of experience of the teams (FISH) and methodological uncertainties (GE). This was the first RENEB ILC where everything, from blood sampling to irradiation and shipment of the samples, was organized and realized at the same institution, for several biological and physical retrospective dosimetry assays. Almost all assays appeared comparably applicable for the identification of unexposed and highly exposed individuals and the allocation of medical relevant groups, with the latter requiring medical support for the acute radiation scenario simulated in this exercise. However, extreme outliers or a systematic shift of dose estimates have been observed for some assays. Possible reasons will be discussed in the assay specific papers of this special issue. In summary, this ILC clearly demonstrates the need to conduct regular exercises to identify research needs, but also to identify technical problems and to optimize the design of future ILCs.

Visual and quantitative assessment of hip implant-related metal artifacts at low field MRI: a phantom study comparing a 0.55-T system with 1.5-T and 3-T systems.

BACKGROUND: To investigate hip implant-related metal artifacts on a 0.55-T system compared with 1.5-T and 3-T systems. METHODS: Total hip arthroplasty made of three different alloys were evaluated in a water phantom at 0.55, 1.5, and 3 T using routine protocols. Visually assessment (VA) was performed by three readers using a Likert scale from 0 (no artifacts) to 6 (extremely severe artifacts). Quantitative assessment (QA) was performed using the coefficient of variation (CoV) and the fraction of voxels within a threshold of the mean signal intensity compared to an automatically defined region of interest (FVwT). Agreement was evaluated using intra/inter-class correlation coefficient (ICC). RESULTS: Interreader agreement of VA was strong-to-moderate (ICC 0.74-0.82). At all field strengths (0.55-T/1.5-T/3-T), artifacts were assigned a lower score for titanium (Ti) alloys (2.44/2.9/2.7) than for stainless steel (Fe-Cr) (4.1/3.9/5.1) and cobalt-chromium (Co-Cr) alloys (4.1/4.1/5.2) (p < 0.001 for both). Artifacts were lower for 0.55-T and 1.5-T than for 3-T systems, for all implants (p ≤ 0.049). A strong VA-to-QA correlation was found (r = 0.81; p < 0.001); CoV was lower for Ti alloys than for Fe-Cr and Co-Cr alloys at all field strengths. The FVwT showed a negative correlation with VA (-0.68 < r < -0.84; p < 0.001). CONCLUSIONS: Artifact intensity was lowest for Ti alloys at 0.55 T. For other alloys, it was similar at 0.55 T and 1.5 T, higher at 3 T. Despite an inferior gradient system and a larger bore width, the 0.55-T system showed the same artifact intensity of the 1.5-T system.

Inexpensive High-Throughput Multiplexed Biomarker Detection Using Enzymatic Metallization with Cellphone-Based Computer Vision.

Multiplexed biomarker detection can play a critical role in reliable and comprehensive disease diagnosis and prediction of outcome. Enzyme-linked immunosorbent assay (ELISA) is the gold standard method for immunobinding-based biomarker detection. However, this is currently expensive, limited to centralized laboratories, and usually limited to the detection of a single biomarker at a time. We present a low-cost, smartphone-based portable biosensing platform for high-throughput, multiplexed, sensitive, and quantitative detection of biomarkers from single, low-volume drops (<1 µL) of clinical samples. Biomarker binding to spotted capture antigens is converted, via enzymatic metallization, to the localized surface deposition of amplified, dry-stable, silver metal spots whose darkness is proportional to biomarker concentration. A custom smartphone application is developed, which uses real-time computer vision to enable easy optical detection of the deposited metal spots and sensitive and reproducible quantification of the biomarkers. We demonstrate the use of this platform for high-throughput, multiplexed detection of multiple viral antigen-specific antibodies from convalescent COVID-19 patient serum as well as vaccine-elicited antibody responses from uninfected vaccine-recipient serum and show that distinct multiplexed antibody fingerprints are observed among them.

Image Quality of Lumbar Spine Imaging at 0.55T Low-Field MRI is Comparable to Conventional 1.5T MRI - Initial Observations in Healthy Volunteers.

RATIONALE AND OBJECTIVES: To assess the potential of 0.55T low-field MRI system in lumbar spine imaging with and without the use of additional advanced postprocessing techniques. MATERIALS AND METHODS: The lumbar spine of 14 volunteers (32.9 ± 3.6 years) was imaged both at 0.55T and 1.5T using sequences from clinical routine. On the 0.55T scanner system, additional sequences with simultaneous multi-slice acquisition and artificial intelligence-based postprocessing techniques were acquired. Image quality of all 28 examinations was assessed by three musculoskeletal radiologists with respect to signal/contrast, resolution, and assessability of the spinal canal and neuroforamina using a 5-point Likert scale (1 = non-diagnostic to 5 = perfect quality). Interrater agreement was evaluated with the Intraclass Correlation Coefficient and the Mann-Whitney U test (significance level: p < 0.05). RESULTS: Image quality at 0.55T was rated lower on the 5-point Likert scale compared to 1.5T regarding signal/contrast (mean: 4.16 ± 0.29 vs. 4.54 ± 0.29; p < 0.001), resolution (4.07 ± 0.31 vs. 4.49 ± 0.30; p < 0.001), assessability of the spinal canal (4.28 ± 0.13 vs. 4.73 ± 0.26; p < 0.001) and the neuroforamina (4.14 ± 0.28 vs. 4.70 ± 0.27; p < 0.001). Image quality for the AI-processed sagittal T1 TSE and T2 TSE at 0.55T was also rated slightly lower, but still good to perfect with a concomitant reduction in measurement time. Interrater agreement was good to excellent (range: 0.60-0.91). CONCLUSION: While lumbar spine image quality at 0.55T is perceived inferior to imaging at 1.5T by musculoskeletal radiologists, good overall examination quality was observed with high interrater agreement. Advanced postprocessing techniques may accelerate intrinsically longer acquisition times at 0.55T.

Diagnostics of infrapatellar saphenous neuralgia-a reversible cause of chronic anteromedial pain following knee surgery.

OBJECTIVES: To evaluate the impact of diagnostic nerve block and ultrasound findings on therapeutic choices and predict the outcome after concomitant surgery in patients with suspected neuropathy of the infrapatellar branch of the saphenous nerve (IPBSN). METHODS: Fifty-five patients following knee surgery with suspicion of IPBSN neuralgia were retrospectively included. Ultrasound reports were assessed for neuroma and postsurgical scarring (yes/no). Responders and non-responders were assigned following anesthetic injection of the IPBSN. The type of procedure (neurectomy/interventional pain procedure/other than nerve-associated therapy) and pain score at initial follow-up were recorded and patients were assigned as positive (full pain relief) or negative (partial/no pain relief) to therapeutic nerve treatment. Factors associated with a relevant visual analog scale (VAS) reduction were assessed using uni- and multivariate logistic regression models and chi-square for quantitative and qualitative variables (p ≤ 0.05). RESULTS: Responders (37/55) more often had an entrapment or an evident neuroma of the IPBSN (97% vs. 6%). A positive Hoffmann-Tinel sign (p = 0.002) and the absence of knee joint instability (p = 0.029) predicted a positive response of the diagnostic nerve block (90%; 26/29). In the follow-up after therapeutic nerve treatment, all patients with full pain relief showed neuromas or entrapment of the IPBSN. Patients negatively responding to therapeutic nerve treatment more frequently showed an additional knee joint instability (25% vs. 4%). CONCLUSION: Selective denervation for neuropathic knee pain is beneficial in selected patients with significant VAS reduction after diagnostic nerve block. Non-responders following diagnostic nerve block but sonographic evidence of IPBSN pathologies need to be evaluated for other causes such as knee joint instability. KEY POINTS: • Sonographic diagnosis of neuroma or entrapment of the IPBSN is frequently seen in patients with anteromedial knee pain and leads to a good response to diagnostic nerve block following knee surgery. • The vast majority of patients with clinical signs of IPBSN neuropathy and response to a diagnostic nerve block sustained full pain relief following therapeutic nerve treatment. • Patients not responding to therapeutic IPBSN treatment have to be evaluated for other causes of anteromedial knee pain such as knee joint instability.

Orthopaedic surgeons do not consult radiology reports. Fact or fiction?

PURPOSE: To find out how orthopaedic surgeons handle radiological reports and to identify ways to improve musculoskeletal radiology service and interdisciplinary communication. METHOD: An anonymised 14-question online survey was distributed among 27 orthopaedic departments in German-speaking parts of Europe. It was available to trainees and consultants between 22/10/2020 and 05/06/2021. The questionnaire collected information regarding the participants' habits of consulting radiology reports depending on the imaging modality, reasons for not reading reports and asked for improvement recommendations for the radiology service. RESULTS: 81 orthopaedists participated. 20% would never consult a plain radiograph report. In contrast, only 4% would never consult a CT report and no one claimed to never consult an MRI report. 43%, 67% and 86% would routinely consult radiology reports of radiographs, CT and MRI studies, respectively. Long time to report availability (24%), a general lack of time (19%) and too long texts (17%) were the most popular reasons for not consulting the reports. 62% of participants voted to sometimes disagree with the reports and in cases of opinion discrepancy 51% would always or often contact the radiologist. 64% preferred to be informed directly via phone about relevant unexpected findings. Most popular report improvement recommendations were more rapid report availability (24%), inclusion of significant images (19%) and inclusion of more angle and distance measurements (16%). In the free text column, a desire for direct interdisciplinary discussion of equivocal cases was often stated (30%). CONCLUSIONS: Concluding, this survey showed that orthopaedic surgeons routinely consult radiology reports. The participants expressed a desire for increased, direct interdisciplinary communication to solve equivocal cases and improve patient care.

AI-based detection and classification of distal radius fractures using low-effort data labeling: evaluation of applicability and effect of training set size.

OBJECTIVES: To evaluate the performance of a deep convolutional neural network (DCNN) in detecting and classifying distal radius fractures, metal, and cast on radiographs using labels based on radiology reports. The secondary aim was to evaluate the effect of the training set size on the algorithm's performance. METHODS: A total of 15,775 frontal and lateral radiographs, corresponding radiology reports, and a ResNet18 DCNN were used. Fracture detection and classification models were developed per view and merged. Incrementally sized subsets served to evaluate effects of the training set size. Two musculoskeletal radiologists set the standard of reference on radiographs (test set A). A subset (B) was rated by three radiology residents. For a per-study-based comparison with the radiology residents, the results of the best models were merged. Statistics used were ROC and AUC, Youden's J statistic (J), and Spearman's correlation coefficient (ρ). RESULTS: The models' AUC/J on (A) for metal and cast were 0.99/0.98 and 1.0/1.0. The models' and residents' AUC/J on (B) were similar on fracture (0.98/0.91; 0.98/0.92) and multiple fragments (0.85/0.58; 0.91/0.70). Training set size and AUC correlated on metal (ρ = 0.740), cast (ρ = 0.722), fracture (frontal ρ = 0.947, lateral ρ = 0.946), multiple fragments (frontal ρ = 0.856), and fragment displacement (frontal ρ = 0.595). CONCLUSIONS: The models trained on a DCNN with report-based labels to detect distal radius fractures on radiographs are suitable to aid as a secondary reading tool; models for fracture classification are not ready for clinical use. Bigger training sets lead to better models in all categories except joint affection. KEY POINTS: • Detection of metal and cast on radiographs is excellent using AI and labels extracted from radiology reports. • Automatic detection of distal radius fractures on radiographs is feasible and the performance approximates radiology residents. • Automatic classification of the type of distal radius fracture varies in accuracy and is inferior for joint involvement and fragment displacement.

MR variability of collagen meniscal implant remodelling in patients with good clinical outcome.

PURPOSE: Collagen meniscal implants (CMI) have variable imaging findings on MRI and it remains ambiguous, if alterations may be present in asymptomatic patients. The aim was, to evaluate MR morphological characteristics and volume of CMI in the early, mid- and long-term follow-up. METHODS: Fifty-seven patients (mean age, 43.6±11 years; 41 male/16 female) with good clinical outcome (subjective visual analogue scale for satisfaction < 2 and a Lysholm-score ≥ 84) after CMI were assessed retrospectively using MRI 1, 2 and 3-8 years postoperatively. CMI morphology, signal intensity (SI), homogeneity and size were assessed and a meniscal score was calculated. Chondral defects and bone marrow edema pattern were reported and summarized in a chondral score. Meniscal extrusion and volume were evaluated. Intra- and inter-reader reliabilities were calculated. Spearman and partial correlations were used (p < 0.05). RESULTS: One year postoperatively, the CMI varied in size [10% (4/40) normal, 30% (12/40) small, 60% (24/40) hypertrophic] and was hyperintense and inhomogeneous in all patients. At long-term follow-up, the size of CMI decreased [6% (1/17) resorbed, 18% (3/17) normal, 41% (7/17) small, 35% (6/17) hypertrophic]. The SI of the CMI changed to normal in only 13% (2/16). The majority was still hyperintense [87% (14/16)]. Less meniscal extrusion was present in the follow-up [71% (11/16) versus initially 93% (37/40)]. The meniscal score improved significantly (ρ = 0.28). Over time, full-thickness femoral chondral defects were increasingly present [65% (10/17) versus initially 33% (13/40)] and the chondral score worsened significantly (p = 0.017). CONCLUSION: Abnormal and inhomogeneous SI and irregular margins of the early postoperative CMI on MRI are findings seen in patients with good clinical results and should not necessarily be overcalled when reporting MRI. These features tend to decrease over time. LEVEL OF EVIDENCE: IV.

In vivo 3D tomography of the lumbar spine using a twin robotic X-ray system: quantitative and qualitative evaluation of the lumbar neural foramina in supine and upright position.

OBJECTIVES: Supine lumbar spine examinations underestimate body weight effects on neuroforaminal size. Therefore, our purpose was to evaluate size changes of the lumbar neuroforamina using supine and upright 3D tomography and to initially assess image quality compared with computed tomography (CT). METHODS: The lumbar spines were prospectively scanned in 48 patients in upright (3D tomographic twin robotic X-ray) and supine (30 with 3D tomography, 18 with CT) position. Cross-sectional area (CSA), cranio-caudal (CC), and ventro-dorsal (VD) diameters of foramina were measured by two readers and additionally graded in relation to the intervertebral disc height. Visibility of bone/soft tissue structures and image quality were assessed independently on a 5-point Likert scale for the 18 patients scanned with both modalities. Descriptive statistics, Wilcoxon's signed-rank test (p < 0.05), and interreader reliability were calculated. RESULTS: Neuroforaminal size significantly decreased at all levels for both readers from the supine (normal intervertebral disc height; CSA 1.25 ± 0.32 cm2; CC 1.84 ± 0.24 cm2; VD 0.88 ± 0.16 cm2) to upright position (CSA 1.12 ± 0.34 cm2; CC 1.78 ± 0.24 cm2; VD 0.83 ± 0.16 cm2; each p < 0.001). Decrease in intervertebral disc height correlated with decrease in foraminal size (supine: CSA 0.88 ± 0.34 cm2; CC 1.39 ± 0.33 cm2; VD 0.87 ± 0.26 cm2; upright: CSA 0.83 ± 0.37 cm2, p = 0.010; CC 1.32 ± 0.33 cm2, p = 0.015; VD 0.80 ± 0.21 cm2, p = 0.021). Interreader reliability for area was fair to excellent (0.51-0.89) with a wide range for cranio-caudal (0.32-0.74) and ventro-dorsal (0.03-0.70) distances. Image quality was superior for CT compared with that for 3D tomography (p < 0.001; κ, CT = 0.66-0.92/3D tomography = 0.51-1.00). CONCLUSIONS: The size of the lumbar foramina is smaller in the upright weight-bearing position compared with that in the supine position. Image quality, especially nerve root delineation, is inferior using 3D tomography compared to CT. KEY POINTS: • Weight-bearing examination demonstrates a decrease of the neuroforaminal size. • Patients with higher decrease in intervertebral disc showed a narrower foraminal size. • Image quality is superior with CT compared to 3D tomographic twin robotic X-ray at the lumbar spine.

Comparison of 3D X-ray tomography with computed tomography in patients with distal extremity fractures.

OBJECTIVE: To compare fracture detection, image quality, and radiation dose in patients with distal extremity fractures using 3D tomography and computed tomography (CT). MATERIALS AND METHODS: IRB approval was obtained including informed consent for this prospective study from June to December 2016. Patients diagnosed with an acute fracture at CT were consecutively scanned on the same day using 3D tomography. Anatomical location (effected bone and location within the bone) and morphological characteristics of fractures (avulsion, articular involvement, mono- vs. multifragmented, displacement), visibility of bone/soft tissue structures, and image quality were assessed independently by two blinded readers on a 5-point Likert scale. Dose-length-product (DLP; mGy*cm) was compared between both modalities. Descriptive statistics, Wilcoxon signed rank test (P < 0.05), Student's t test (P < 0.05), and Cohen's kappa (κ) for interreader reliability were calculated. RESULTS: In 46 patients (28 males; 18 females; mean age, 53 ± 20 years) with 28 hand/wrist and 18 foot/ankle examinations, 86 out of 92 fractures were diagnosed with 3D tomography compared with CT. No false-positive finding occurred at 3D tomography. The six missed fractures on 3D tomography were five avulsion fractures of the carpals/metacarpals or tarsals/metatarsals, respectively, and one nondisplaced fracture of the capitate. Interreader agreement of anatomical location and morphological characteristics was substantial to almost perfect for upper (κ = 0.80-0.96) and lower (κ = 0.70-0.97) extremity fractures. Visibility of bone and soft tissue structures and image quality were slightly inferior using 3D tomography compared with CT (upper extremity P < 0.001-0.038 and lower extremity P < 0.001-0.035). DLP of a comparable scan coverage was significantly lower for 3D tomography (P < 0.001) for both upper (3D mean, 19.4 ± 5.9 mGy*cm; estimated CT mean, 336.5 ± 52.2 mGy*cm) and lower extremities (3D mean, 24.1 ± 11.1 mGy*cm; estimated CT mean, 182.9 ± 6.5 mGy*cm). Even the highest DLP with 3D tomography was < 30% of the mean estimated CT dose of a comparable area of coverage. CONCLUSION: Fracture assessment of peripheral extremities is reliable utilizing a low-dose 3D tomography X-ray system, with slightly reduced image quality.

Dose-optimized computed tomography of the cervical spine in patients with shoulder pull-down: Is image quality comparable with a standard dose protocol in an emergency setting?

PURPOSE: Superimposing soft tissue and bony structures in computed tomography (CT) of the cervical spine (C-spine) is a limiting factor in optimizing radiation exposure maintaining an acceptable image quality. Therefore, we assessed image quality of dose-optimized (DO) C-spine CT in patients capable of shoulder pull-down in an emergency setting. METHODS AND MATERIALS: DO-CT (105mAs/120 kVp) of the C-spine in trauma settings was performed in patients with shoulder pull-down if C5 was not superimposed by soft tissue on the lateral topogram, otherwise standard-dose (SD)-CT (195 mAs/120 kVp) was performed. 34 DO (mean age, 68y ±â€¯21; BMI, 24.2 kg/m2 ±â€¯3.2) and 34 SD (mean age 70y ±â€¯19; BMI 25.7 kg/m2 ±â€¯4.4) iterative reconstructed CTs were evaluated at C2/3 and C6/7 by two musculoskeletal radiologists. Qualitative image noise and morphological characteristics of bony structures (cortex, trabeculae) were assessed on a Likert scale. Quantitative image noise was measured and effective dose (ED) was recorded. Parameters were compared using Mann-Whitney-U-test (p < 0.05). RESULTS: At C2/3, DO-CT vs. SD-CT yielded comparable qualitative noise (mean, 1.3 vs. 1.0; p = 0.18) and morphological characteristics, but higher quantitative noise (27.2 ±â€¯8.8HU vs. 19.6 ±â€¯4.5HU; p < 0.001). At C6/7, DO-CT yielded lower subjective noise (1.9; SD-CT 2.2; p = 0.017) and better morphological characteristics with higher visibility scores for cortex (p = 0.001) and trabeculae (p = 0.03). Quantitative noise did not differ (p = 0.24). Radiation dose was 51% lower using DO-CT (EDDO-CT 0.80 ±â€¯0.1 mSv; EDSD-CT 1.63 ±â€¯0.2 mSv; p < 0.001). CONCLUSION: C-spine CT with dose reduction of 51% showed no image quality impairment. Additional pull-down of both shoulders allowed better image quality at lower C-spine segments as compared to a standard protocol.

Two positive tuberculosis cases in the late Nigrovits family, 18th century, Vác, Hungary.

Two mummies of the Hungarian mummy collection from Vác were the subjects of anthropological, paleopathological, radiological, paleomicrobiological, paleohistological and paleoproteomic studies. Both individuals belonged to the same family. The father, József Nigrovits (No 29), died at the age of 55 on the 11th of November 1793; his son, Antal Nigrovits (No 54), died on the 16th of July 1803, at the age of 22. They lived in the 18th century in Vác, a small town in northern Hungary. The macroscopic examination of the son showed a severely deformed neck and back region; the father has no visible mark of any illnesses. As earlier researches showed that tuberculosis was widespread in the community, the etiology of these deformities was examined. The paleomicrobiological results found that both individuals were infected with tuberculosis. Although they suffered from TB, the CT scan data of the bodies and their 3D reconstructions showed no skeletal evidence of tuberculosis. The deformity of the son turned to be a developmental abnormality of unknown origin, but no Pott's gibbus was present.

Effect of short-term unloading on T2 relaxation time in the lumbar intervertebral disc--in vivo magnetic resonance imaging study at 3.0 tesla.

BACKGROUND CONTEXT: Diurnal changes in T2 values, indicative for changes in water content, have been reported in the lumbar intervertebral discs. However, data concerning short-term T2 changes are missing. PURPOSE: The purpose of this study was to investigate the short-term effects of unloading on T2 values in lumbar intervertebral discs in vivo. STUDY DESIGN: Experimental study with repeated measurements of lumbar discs T2 relaxation time during a period of 38 minutes of supine posture. PATIENT SAMPLE: Forty-one patients with acute or chronic low back pain (visual analog scale ≥3). OUTCOME MEASURES: T2 relaxation time in the intervertebral disc, lumbar lordosis angle, and intervertebral disc height. METHODS: Forty-one patients (mean age, 41.6 years) were investigated in the supine position using a 3-tesla magnetic resonance system. Sagittal T2 mapping was performed immediately after unloading and after a mean delay of 38 minutes. No patient movement was allowed between the measurements. One region of interest (ROI) was manually placed in both the anterior and the posterior annulus fibrosus (AF) and three ROIs in the nucleus pulposus (NP). RESULTS: There was a statistically significant decrease in the anterior NP (-2.7 ms; p<.05) and an increase in T2 values in the posterior AF (+3.5 ms; p<.001). Discs with initially low T2 values in the NP showed minor increase in the posterior AF (+1.6 ms; p<.05), whereas a major increase in the posterior AF was found in discs with initially high T2 values in the NP (+6.8 ms; p=.001). Patients examined in the morning showed no differences, but those investigated in the afternoon showed a decrease in the anterior NP (-5.3 ms; p<.05) and an increase in the posterior AF (+7.8 ms; p=.002). No significant differences were observed in other regions. Correlation analysis showed moderate correlations between the time of investigation and T2 changes in the posterior AF (r=0.46; p=.002). CONCLUSIONS: A shift of water from the anterior to the posterior disc regions seems to occur after unloading the lumbar spine in the supine position. The clinical relevance of these changes needs to be investigated.

Consequences of the electrogenic function of the phagocytic NADPH oxidase.

NADPH oxidase of phagocytic cells transfers a single electron from intracellular NADPH to extracellular O2, producing superoxide (O.-2), the precursor to several other reactive oxygen species. The finding that a genetic defect of the enzyme causes chronic granulomatous disease (CGD), characterized by recurrent severe bacterial infections, linked O.-2 generation to destruction of potentially pathogenic micro-organisms. In this review, we focus on the consequences of the electrogenic functioning of NADPH oxidase. We show that enzyme activity depends on the possibilities for compensating charge movements. In resting neutrophils K+ conductance dominates, but upon activation the plasma membrane rapidly depolarizes beyond the opening threshold of voltage-gated H+ channels and H+ efflux becomes the major charge compensating factor. K+ release is likely to contribute to the killing of certain bacteria but complete elimination only occurs if O.-2 production can proceed at full capacity. Finally, the reversed membrane potential of activated neutrophils inhibits Ca2+ entry, thereby preventing overloading the cells with Ca2+. Absence of this limiting mechanism in CGD cells may contribute to the pathogenesis of the disease.

Dual role of phagocytic NADPH oxidase in bacterial killing.

The classical model of bacterial killing by phagocytic cells has been recently challenged by questioning the toxic effect of oxygen products and attributing the fundamental role to K(+) ions in releasing antimicrobial proteins within the phagosome. In the present study we followed O(2)(*-) production, changes of membrane potential, K(+) efflux, and bacterial killing in the presence of increasing concentrations of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor diphenylene iodonium. Efficiency of bacterial killing was assessed on the basis of bacterial survival measured by a new semiautomated method. Very low rates of O(2)(*-) production were accompanied by significant membrane depolarization and K(+) release and parallel improvement of bacterial killing. When O(2)(*-) production exceeded 20% of its maximal capacity, no further change was detected in the membrane potential and only minimal further K(+) efflux occurred, yet bacterial survival decreased parallel to the increase of O(2)(*-) production. The presented results indicate that both electrophysiological changes (depolarization and consequent ion movements) and the chemical effect of reactive oxygen species play a significant role in the killing of certain pathogens. The observation that an increase of membrane depolarization can compensate for decreased O(2)(*-) production may be important for potential therapeutic applications.

Degranulation and superoxide production depend on cholesterol in PLB-985 cells.

The effect of agents disrupting cholesterol-rich microdomains of the cell membrane was studied on the chemoattractant receptor (FPR and FRPL1) coupled effector responses of promyelocytic PLB-985 cells. Both methyl-beta-cyclodextrin (MbetaCD) and filipin III inhibited exocytosis of primary granules and O(2)(.-) production induced by stimulation of either chemotactic receptor. Alteration of calcium homeostasis of MbetaCD-treated cells does not account for the impairment of the effector responses. Disruption of microfilaments by cytochalasin B (CB) partially reverses the inhibitory effect of cholesterol depletion. Our results provide functional support for the involvement of cholesterol-rich membrane domains in the signaling of chemotactic receptors and call the attention to the possible role of microfilaments in the organization of lipid microdomains.

Contribution of phopholipase D and a brefeldin A-sensitive ARF to chemoattractant-induced superoxide production and secretion of human neutrophils.

We show that blockers of phospholipase D (PLD) reduce fMLP-triggered exocytosis of secretory vesicles effectively. In accordance with this, the PLD product phosphatidic acid (PA) was able to induce mobilization of secretory vesicles. Although PLD seems to play a role in the release of all neutrophil granule types, exogenous PA alone was not sufficient to activate the exocytosis of primary and secondary granules, suggesting that in the case of these granules, additional signaling factors are required to initiate the secretory responses. The ADP-ribosylation factor (ARF)-inhibitor brefeldin A (BFA) inhibited the fMLP-stimulated O2*- production strongly, whereas it did not influence any of the exocytic responses, and no significant effect of BFA was detected on the O2*- generation induced by other stimuli. On the basis of these results, we propose that upon chemoattractant stimulation, PLD activity is involved in induction of degranulation and O2*- production, but a BFA-sensitive ARF is only required to the activation of the NADPH oxidase. This ARF action seems to participate exclusively in the signaling pathway between the fMLP receptor and the oxidase.

Corneal transplantation in children.

Authors discuss the special problems related to childhood keratoplasties. They evaluate the results of the keratoplasties carried out in children during the past 10 years in their service. They review the concerning literature and summarize their opinion on the corneal transplantations of this age group.

Penetrating keratoplasty for pseudophakic bullous keratopathy.

Corneal decompensation after cataract surgery and intraocular lens (IOL) implantation has become the leading indication for penetrating keratoplasty during the past decade. We reviewed the clinical course and the surgical management of 212 patients with penetrating keratoplasty for pseudophakic bullous keratopathy treated at our Department during the last 15 years. Corneal transplantation for pseudophakic bullous keratopathy was successful in 76%. One third of the patients achieved a long-term visual acuity of 0.5 and more. At keratoplasty the original IOL was left in place in 129 eyes. We removed from and not replaced the IOL in 37 eyes and we performed IOL exchange in 46 eyes. The secondary IOL was an angle-supported flexible anterior chamber lens in 40 cases, and a suture fixated posterior chamber lens in 8 cases. During the penetrating keratoplasty for pseudophakic bullous keratopathy the most important question is how to manage the previously implanted intraocular lens. We have to decide whether the intraocular lens should be removed or replaced at the time of surgery. The choice of removing, retaining or replacing the intraocular lens at keratoplasty depends on the variable intraocular pathological conditions and each case requires individual evaluation.

Scleral reinforcement in progressive myopia and intraoperative ultrasound control of the cadaver fascia lata strip.

Scleral reinforcement (sustentaculum sclerae) is one of the operations against myopia. During the progression of myopia the eye grows. The chorioretinal layer can only moderately follow the expansion of the sclera, and mostly this is the cause of the complications that can cause permanent visual acuity decrease. The aim of the operation is to strengthen the posterior part of the sclera by implantation of a cadaver fascia lata strip, that slows down or stops the expansion of the eyeball, and this way prevents the development of complications. At our Department we perform the Snyder-Thompson technique. Between 1984 and 1994 343 operations were performed at our Department. We followed up the changes of the axial lengths by ultrasound (A-mode) examinations. The axial length decreased in 43.7% remained unchanged in 22.2% and increased in 34.1% of the cases. We controlled the location of the strip intra- and postoperatively with B-mode ultrasound. Nowadays scleral reinforcement is still the only possibility to stop or slow down the expansion of the eyeball in cases of progressive high myopia.