Selenium-based digital radiography in the detection of bone lesions: preliminary experience with experimentally created defects

PURPOSE: To compare the diagnostic performance of selenium-based digital radiography with that of conventional screen-film radiography and storage phosphor radiography for the detection of bone lesions simulating osteolyses. MATERIALS AND METHODS: Artificial osseous lesions 1.0-3.0 mm in diameter were created in 80 of 160 predefined regions in 16 porcine femoral specimens. Specimens were enclosed in containers filled with paraffin to ensure accurate repositioning and to obtain an absorption condition comparable to that of a human extremity. Imaging was performed with a selenium-based digital radiography system, a conventional screen-film system, and a storage phosphor radiography system with an exposure identical to that used during clinical imaging. The presence of a lesion was assessed with a five-point confidence scale. Receiver operating characteristic (ROC) analysis was performed for a total of 1,440 observations (480 per modality), and diagnostic performance was estimated with the area under the ROC curve (A(z)). Differences in diagnostic performance were assessed with the paired Student t test. RESULTS: ROC analysis results showed A(z) values of 0.656 for selenium-based digital radiography, 0.679 for storage phosphor radiography, and 0.680 for conventional screen-film radiography. Differences between the three modalities were not significant (P =.60-.93). CONCLUSION: Image quality with selenium-based digital radiography was comparable to that with conventional screen-film radiography and storage phosphor radiography.     

Digital radiography of the skeleton using a large-area detector based on amorphous silicon technology: image quality and potential for dose reduction in comparison with screen-film radiography

AIM: The purpose of this study was to evaluate a large-area, flat-panel X-ray detector (FD), based on caesium-iodide (CsI) and amorphous silicon (a-Si) with respect to skeletal radiography. Conventional images were compared with digital radiographs using identical and reduced radiation doses.MATERIALS AND METHODS: Thirty consecutive patients were studied prospectively using conventional screen-film radiography (SFR; detector dose 2.5 microGy). Digital images were taken from the same patients with detector doses of 2.5, 1.25 and 0.625 microGy, respectively. The active-matrix detector had a panel size of 43 x 43 cm, a matrix of 3 x 3K, and a pixel size of 143 microm. All hard copies were presented in a random order to eight independent observers, who rated image quality according to subjective quality criteria. Results were assessed for significance using the Student's t -test (confidence level 95%).RESULTS: A statistically significant preference for digital over conventional images was revealed for all quality criteria, except for over-exposure (detector dose 2.5 microGy). Digital images with a 50% dose showed a small, statistically not significant, inferiority compared with SFR. The FD-technique was significantly inferior to SFR at 75% dose reduction regarding bone cortex and trabecula, contrast and overall impression. No statistically significant differences were found with regard to over- and under-exposure and soft tissue presentation.CONCLUSION: Amorphous silicon-based digital radiography yields good image quality. The potential for dose reduction depends on the clinical query.     

Treatment of metastatic Ewing's sarcoma or primitive neuroectodermal tumor of bone: evaluation of combination ifosfamide and etoposide--a Children's Cancer Group and Pediatric Oncology Group study.

PURPOSE: One hundred twenty patients with metastatic Ewing's sarcoma or primitive neuroectodermal tumor (PNET) of bone were entered onto a randomized trial evaluating whether the addition of ifosfamide and etoposide to vincristine, doxorubicin, cyclophosphamide, and dactinomycin improved outcomes. METHODS: Thirty-two patients had metastases to lungs only, 12 patients had metastases to bone marrow or bones only, 64 patients had metastases in multiple sites, and five patients had metastases in other sites; seven patients could not be assessed precisely. Treatment comprised 9 weeks of chemotherapy before local control and 42 weeks of chemotherapy; thereafter, regimen A consisted of vincristine 2 mg/m(2), cyclophosphamide 1,200 mg/m(2), and either doxorubicin 75 mg/m(2) or dactinomycin 1.25 mg/m(2). Regimen B consisted of regimen A alternating every 3 weeks with ifosfamide 1,800 mg/m(2)/d for 5 days and etoposide 100 mg/m(2)/d for 5 days. RESULTS: Patients treated on regimen B did not have significantly better survival than those treated on regimen A. The event-free survival (EFS) and survival (S) at 8 years were 20% (SE, 5%) and 32% (SE, 6%), respectively, for those treated on regimen A and 20% (SE, 6%) and 29% (SE, 6%), respectively, for those treated on regimen B. Patients who had only lung metastases had EFS and S of 32% (SE, 8%) and 41% (SE, 9%), respectively, at 8 years. There were six toxic deaths (5%), four from cardiac toxicity and two from sepsis (four treated on regimen B and two treated on regimen A). Two had second malignant neoplasms. CONCLUSION: Adding ifosfamide and etoposide to standard therapy does not improve outcomes of patients with Ewing's sarcoma or PNET of bone with metastases at diagnosis.     

Identification and Characterization of Circular Single-Stranded DNA Genomes in Sheep and Goat Milk

In recent years, a variety of circular replicase-encoding single-stranded (CRESS) DNA viruses and unclassified virus-like DNA elements have been discovered in a broad range of animal species and environmental samples. Key questions to be answered concern their presence in the human diet and their potential impact on disease emergence. Especially DNA elements termed bovine meat and milk factors (BMMF) are suspected to act as co-factors in the development of colon and breast cancer. To expand our knowledge on the occurrence of these potential pathogens in human nutrition, a total of 73 sheep and 40 goat milk samples were assayed by combining rolling circle amplification (RCA), PCR and Sanger sequencing. The present study further includes retail milk from the aforementioned species. We recovered 15 single stranded (ss) circular genomes. Of those, nine belong to the family Genomoviridae and six are members of the unclassified group of BMMF. Thus, dairy sheep and goats add to dispersal of CRESS viruses and circular ssDNA elements, which enter the food chain via milk. The presence of these entities is therefore more widespread in Bovidae than initially assumed and seems to be part of the common human nutrition.     

Three T-cell epitopes within the C-terminal 265 amino acids of the matrix protein pp65 of human cytomegalovirus recognized by human lymphocytes

Although a T-cell response in human cytomegalovirus (HCMV)-immune individuals exists against the most abundantly expressed protein pp65 of the virus matrix, less is known about the determinants that evoke this response. The aim of the study was to identify regions within HCMV pp65 (ppUL83) that contain sequences for the cellular immune response by the use of three recombinant overlapping β-galactosidase pp65 fusion proteins (C74, C35, and C47), covering the C-terminal 265 amino acids of the entire pp65 sequence. Two T-cell epitope determinants were recognized by human lymphocytes of healthy, HCMV-seropositive, human leukocyte antigen (HLA)-typed individuals. One T-cell determinant (amino acids [aa] 303–388) was localized in the mid-region of the entire pp65 sequence and a second T-cell determinant (aa 477–561) within the C-terminal region. By fine mapping with synthetic hexadecamer peptides three T-cell epitopes were identified within these two regions: P10-I (aa 361–376) in the mid-region, P3-II (aa) 485–499), and P6-II (aa 509–524) in the C-terminal region. Inhibition studies with monoclonal antibodies to HLA class I or class II revealed a class I restricted response to peptides P10-I or P6-II, respectively. P10-I responders shared the HLA-DR11 allele and P6-II responders the -DR3 allele. Therefore, these T-cell epitopes of HCMV pp65 might be presented in association with particular HLA class II alleles. J. Med. Virol. 52:68–76, 1997. © 1997 Wiley-Liss, Inc.     

Cytokines and the pathogenesis of myasthenia gravis

Myasthenia gravis (MG) and its animal model experimental autoimmune myasthenia gravis (EAMG) are caused by autoantibodies against nicotinic acetylcholine receptor (AChR) in skeletal muscle. The production of anti-AChR antibodies is mediated by cytokines produced by CD4⁺ and CD8⁺ T helper (Th) cells. Emerging investigations of the roles of cytokines in MG and EAMG have revealed that the Th2 cell related cytokine interleukin 4 (IL-4), an efficient growth promoter for B-cell proliferation and differentiation, is important for anti-AChR antibody production. IL-6 and IL-10 have similar effects. The Th1 cytokine IFN-γ is important in inducing B-cell maturation and in helping anti-AChR antibody production and, thereby, for induction of clinical signs and symptoms. Results from studies of time kinetics of cytokines imply that IFN-γ is more agile at the onset of EAMG, probably being one of the initiating factors in the induction of the disease, and IL-4 may be mainly responsible for disease progression and persistance. Even though other Th1 cytokines like IL-2, tumor necrosis factor α (TNF-α), and TNF-β as well as the cytolytic compound perforin do not directly play a role in T-cell-mediated help for anti-AChR antibody production, they are actually involved in the development of both EAMG and MG, probably by acting in concert with other cytokines within the cytokine network. In contrast, transforming growth factor β (TGF-β) exerts immunosuppressive effects which include the down-regulation of both Th1 and Th2 cytokines in MG as well as EAMG. Suppressive effects are also exerted by interferon α (IFN-α). Based on elucidation of the role of cytokines in EAMG and MG, treatments that up-modulate TGF-β or IFN-α and/or suppress cytokines that help B-cell proliferation could be useful to improve the clinical outcome. © 1997 John Wiley & Sons, Inc. Muscle Nerve, 20, 543–551, 1997     

Towards a better understanding of attitudes and beliefs held by traditional healers and recipients of traditional medicine concerning mental health conditions in post-conflict Liberia: a qualitative investigation

BackgroundA better understanding of attitudes and beliefs held by traditional healers and utilizers of traditional medicine concerning mental health conditions in Liberia is important as Liberia seeks to improve its delivery of mental healthcare in the context of scarce resources and recovery from civil war.MethodsA qualitative research design was used to collect data from 24 Liberian traditional healers, and 11 utilizers of Liberian traditional medicine. Participants were queried about mental health problems in Liberia, treatments, and attitudes towards modern healthcare. Qualitative data were probed and aggregated using content analysis.ResultsMental health problems described by study participants included: Open Mole, African Science, Epilepsy, Depression and Mental Illness (trauma/substance use). Mental health problems were often associated with socioeconomic distress, and participants described their attitudes and beliefs concerning mental healthcare, traditional medicine, and modern healthcare.ConclusionTraditional medicine is an important part of mental healthcare in Africa. Mental illness, social factors, and healthcare access were important problems in Liberia. Mental health problems blended local cultural beliefs with Westernized nosology and social factors. Traditional healer''s attitudes towards Western medicine reflected ambivalence. There is a desire for collaboration with ‘modern’ health care providers, but this will require reciprocal trust-building.     

Autoreactive T cell responses and cytokine patterns reflect resistance to experimental autoimmune myasthenia gravis in Wistar Furth rats

Various mouse and rat strains show different susceptibilities to experimental autoimmune myasthenia gravis (EAMG) that can be induced by immunization with acetylcholine receptor (AChR) and Freund's complete adjuvant, and represents a model for the antibody-mediated myasthenia gravis in humans. We examined AChR-induced B and T cell responses and cytokine mRNA expression to study the mechanisms behind susceptibility to EAMG in Lewis rats and resistance in Wistar Furth (WF) rats. Both strains had similarly elevated concentrations and affinities of serum anti-AChR antibodies, and no difference between the two strains for frequencies of cells in lymphoid organs expressing mRNA of the B cell stimulating cytokine interleukin-4 was found. In contrast, T cell responses to AChR measured by proliferation and by enumeration of interferon-γ-expressing cells at both mRNA and protein level were lower in the resistant WF rats. This strain showed, instead, an up-regulation of the anti-inflammatory transforming growth factor-β. Strain-related differences in the susceptibility to actively induced EAMG are thus related to quantitative differences in distribution between pro-inflammatory and anti-inflammatory cytokines.