[Cavitary lesions in multiple sclerosis: multicenter study on twenty patients]. / Formes cavitaires de sclérose en plaques: étude multicentrique sur vingt patients.

INTRODUCTION: Cavitary white matter changes are mainly described in leukodystrophies and especially in vanishing white matter disease. Large cavitary lesions are not typical for multiple sclerosis (MS). METHODS: We studied MS patients with large cavitary brain lesions. Patient characteristics, disease onset/duration/subtype, expanded disability status scale (EDSS), mini mental state (MMS), vanishing white matter disease genetic analysis, and MRI characteristics of the cavitary lesions were analyzed. RESULTS: Twenty patients were analyzed (6 men and 14 women). Mean age at disease onset was 37.6 (range 17-58). Mean disease duration was 10 years (range 2-20). Five patients had initial relapsing-remitting MS and nine patients had primary-progressive MS. Mean EDSS was 5.5 (range 2-8). Mean MMS was 20/30. Vanishing white matter disease genetic analysis was performed and negative in seven patients. Inferior corpus callosum lesions were seen in all patients with available sagittal FLAIR sequences. Cavitary lesions were strictly supratentorial, and located inside the diffuse leukoencephalopathy, with often a posterior predominance. CONCLUSION: MS patients with large cavitary lesions seem to represent a MS subgroup, predominantly women, with relatively late disease onset, predominantly primary-progressive type, relatively high EDSS scores, and severe cognitive dysfunction.

Differential requirements for the induction of interleukin 2 responsiveness in L3T4+ and Lyt-2+ T cell subsets.

Minimal requirements for the induction of interleukin 2 (IL-2) responsiveness in purified subsets of murine T lymphocytes have been investigated. Whereas Lyt-2+ cells could be induced to IL-2-dependent growth by lectin, phorbol ester, or calcium ionophore, none of these stimuli was by itself sufficient for L3T4+ cells. The latter cells could, however, be induced to respond to IL-2 by combinations of lectin plus phorbol ester or ionophore plus phorbol ester (but not lectin plus ionophore). Under optimal conditions, growth of L3T4+ cells (like Lyt-2+ cells) was independent of accessory cells and cell-cell contact.

Contrast-to-noise ratios of liver lesions using subtraction imaging on multiphase 64-detector row CT.

AIM: To measure contrast-to-noise ratios of liver lesions on conventional enhanced and digitally subtracted multidetector row computed tomography (CT) images. MATERIALS/METHODS: This study was approved by our hospital internal review board (IRB) and all collected data were evaluated in a Health Insurance Portability and Accountability Act (HIPAA)-compliant manner. Subtracted datasets, using pixel-by-pixel subtraction of the post-contrast images from the pre-contrast images, were created from the 64 detector-row CT of patients undergoing three-phase examination of the liver (unenhanced, arterial phase, and portal venous phase). Regions of interest were used to calculate the contrast-to-noise ratios between the lesions and the background liver parenchyma on both the post-contrast and subtracted datasets using the following formula: (Lesion mean (HU) - Liver mean (HU))/standard deviation of mean outside patient (HU). These ratios were compared using a mixed linear statistical model. RESULTS: Contrast-to-noise ratios were calculated for 64 lesions in 50 consecutive patients. Of the 64 lesions, 42 were hypervascular and 22 were hypovascular. Subtracted datasets yielded statistically significant higher contrast-to-noise ratios of hypervascular lesions compared to normal liver parenchyma (p<0.0001). Subtraction did not yield a statistically significant improvement in contrast-to-noise ratios for hypovascular liver lesions (p=0.16). CONCLUSION: Post-processed subtraction CT images generate increased contrast-to-noise ratios for hypervascular liver lesions. As this technique is easy to perform and does not involve additional radiation exposure, it should be considered when evaluating for suspected hypervascular lesions.

Valvular heart disease in patients with Parkinson's disease treated with pergolide. Course following treatment modifications.

UNLABELLED: Valvular heart abnormalities have been reported in patients with Parkinson's disease (PD) treated with pergolide. However, the incidence and severity of these abnormalities vary from study to study and their course after drug withdrawal has not been systematically assessed. OBJECTIVES: To estimate the frequency and severity of valvular heart abnormality and its possible reversibility after drug withdrawal in a case-control study. METHODS: All PD patients in the Amiens area treated with pergolide were invited to attend a cardiologic assessment including transthoracic echocardiography. Thirty PD patients participated in the study. A second echocardiography was performed (median interval: 13 months) after pergolide withdrawal (n=10 patients). Controls were age- and sex-matched non-PD patients referred to the cardiology department. RESULTS: Compared to controls, aortic regurgitation (OR: 3.1; 95% IC: 1.1-8.8) and mitral regurgitation (OR: 10.7; 95% IC: 2.1-53) were more frequent in PD patients (tricuspid: NS). The number of affected valves (n=2.4+/-0.7) and the sum of regurgitation grades (n=2.8+/-1.09) were higher (p=0.008 and p=0.006, respectively) in the pergolide group. Severity of regurgitation was not correlated with pergolide cumulative dose. A restrictive pattern of valvular regurgitation, suggestive of the role of pergolide, was observed in 12/30 (40%) patients including two with heart failure. Pergolide was discontinued in 10 patients with valvular heart disease, resulting in a lower regurgitation grade (p=0.01) at the second transthoracic echocardiography and the two patients with heart failure returned to nearly normal clinical examination. This study supports the high frequency of restrictive valve regurgitation in PD patients treated with pergolide and reveals that a significant improvement is usual when the treatment is converted to non-ergot dopamine agonists.

Solitary fibrous tumor of the buccal space: treatment with percutaneous cryoablation.

Solitary fibrous tumors are rare spindle cell neoplasms that typically occur in the thorax but have been described in various locations within the abdomen and head and neck region. The most common extrapleural site is the oral cavity, but these tumors have been also described in the orbit, nasopharynx, paranasal sinuses, salivary glands, and larynx. We describe a case of a solitary fibrous tumor of the buccal space successfully treated with percutaneous CT-guided cryoablation.

Biotinylation of glycan chains in beta2 glycoprotein I induces dimerization of the molecule and its detection by the human autoimmune anti-cardiolipin antibody EY2C9.

Binding of beta2GPI (beta2 glycoprotein I), a human plasma protein, to AnPLs (anionic phospholipids) plays a key role in the formation of antiphospholipid antibodies involved in autoimmune diseases like antiphospholipid syndrome or systemic lupus erythematosus. We recently showed that binding of beta2GPI to AnPLs was enhanced by biotinylation of its glycan chains with biotin-hydrazide. In the present study, we investigated why this chemical modification of beta2GPI increased both its affinity for AnPLs and its recognition by anti-cardiolipin antibodies. Electrophoretic analysis showed that: (i) high molecular mass beta2GPI (dimers and other oligomers) covalently coupled by imine bonds, were present in variable amounts in oxidized beta2GPI and in beta2GPI-bh (beta2GPI-biotin-hydrazide), but were absent in native beta2GPI; (ii) binding of beta2GPI-bh to phosphatidylserine-coated microtitre plates generated high molecular mass polymers in a time-dependent manner. Native beta2GPI did not polymerize in these conditions. These polymers did not bind more strongly to AnPLs than the monomer beta2GPI. However, in solution at 1 microM beta2GPI-bh essentially appeared as a dimer as revealed by light-scattering analysis. SPR (surface plasmon resonance) analysis showed that the increased affinity of beta2GPI-bh for AnPL monolayers was due to a lower dissociation rate constant compared with native beta2GPI. Finally, the monoclonal human aCL (auto-immune anti-cardiolipin antibody) EY2C9 bound to beta2GPI-bh but did not bind to monomeric native and oxidized beta2GPI. It is likely that the dimeric quaternary structure of beta2GPI-bh is in fact responsible for the appearance of the epitopes targeted by the EY2C9 antibody.

Tolerance of autologous and allogeneic bone grafts to therapeutic radiation in humans.

PURPOSE: To examine the effect of perioperative irradiation on bone graft healing and functional integrity. METHODS AND MATERIALS: Fifty-five bone grafts (10 autologous and 45 allogeneic) performed between 1978 and 1995 were evaluated retrospectively. Sixteen received preoperative radiation, 11 received postoperative, and 13 were treated with a combination of pre- and postoperative radiation. Fifteen nonirradiated grafts were randomly selected to serve as controls. Twenty-three of the grafts were placed in patients who received chemotherapy in the perioperative period. Functional graft survival and radiographic healing quality were evaluated. RESULTS: Overall rates of graft survival at 1 year were 89% for autografts and 79% for allografts. Graft survival rates were 86% and 68% at 1 and 5 years for the irradiated group, and 67% and 58% for the control group. No significant difference was seen in the Kaplan-Meier graft survival curves of the two groups. There was a nonsignificant trend toward improved radiographic healing quality in the control group. No significant differences in outcome based on treatment chronology were found with survival rates of 88% for preoperative treatment and 100% for postoperative treatment. No relation between outcome and bone dose (preoperative + postoperative dose), graft dose (postoperative dose), or mean dose/day was found. There was a trend (p = 0.0525) toward worse outcome seen in the Kaplan-Meier curves of patients who received chemotherapy. This difference, however, was not seen in the 1-year survival rates or healing quality. Tobacco use tended toward predicting failure, with 63% graft survival compared to 85% in nonsmokers (p = 0.09). Healing quality was significantly lower in the smoking group. CONCLUSION: The low failure rate of grafts in irradiated sites, overall and compared to controls from this study and relevant literature, as well as the lack of dose and time effects, does not support significant deviation from the indicated treatment regimen for patients who have received or are expected to receive a graft. The trend toward decreased quality of radiographic bone healing, and data published in relevant literature indicating improved healing when radiation is withheld until 3-4 weeks postoperatively suggest this delay should be attempted when not expected to otherwise compromise patient outcome. A nonsignificant trend only for the effect of chemotherapy on bone grafts was seen, thus we do not recommend changes in its use as appropriate for disease management other than a preference against use during the immediate perioperative period.

Radiofrequency treatment of hepatic neoplasms in patients with permanent pacemakers.

Clinicians who provide care for patients with implantable devices for rhythm management, ie, pacemakers and internal cardioverter defibrillators, must be aware of sources of interference that could affect device function. Intracardiac radiofrequency is a recognized source of potential interference. However, radiofrequency to extracardiac sites that are relatively close to the implanted device has not been investigated thoroughly. We present 2 patients with permanent pacemakers undergoing intrahepatic radiofrequency for the treatment of metastatic disease. No interference was documented in either patient. Additional in vitro and in vivo studies are needed to determine definite clinical guidelines for such patients.

Radiofrequency ablation of regional recurrence from well-differentiated thyroid malignancy.

BACKGROUND: Regional recurrence of well-differentiated thyroid cancer (WTC) is primarily detected with ultrasonography (US), and current treatment is surgical. Radiofrequency ablation (RFA) has been used primarily for liver tumors as an alternative to a surgical procedure. We have applied RFA to a group of patients with locally recurrent WTC. METHODS: Eight patients underwent percutaneous RFA for biopsy-proven recurrent WTC in the neck (mean size, 2.4 cm; range, 0.8-4.0 cm) while under intravenous conscious sedation and with US guidance. The RF electrode was inserted into the site of recurrence and treated with the maximum allowable current for between 2 and 12 minutes. Follow-up consisted of US in 8 patients, thyroglobulin levels in 6 patients, biopsy in 4 patients, and surgical treatment in 2 patients. RESULTS: All 8 patients with no bleeding or infectious complications were treated as outpatients. A minor skin burn and 1 vocal cord paralysis occurred. No recurrent disease at the treatment site was detected, with a mean follow-up of 10.3 months. Histological examination showed no evidence of a tumor in the treated lymph nodes in 6 patients. Follow-up US examinations showed disappearance of previously detected color Doppler flow, as well as mass shrinkage and internal cystic change, or both. CONCLUSIONS: US-guided RFA is an exciting new treatment modality that appears to have a future role in treating locally recurrent WTC.

Rheumatoid pericarditis: new immunopathological aspects.

Rheumatoid pericarditis (RP) is a well known extraarticular manifestation of rheumatoid arthritis (RA). It is not frequently diagnosed despite its high reported prevalence in post-mortem studies. There have been no immunohistological studies of its presence in pericardial membranes. Here we report a complete immunohistological study of two RA patients with RP complications, using a panel of monoclonal antibodies (mAbs) for the recognition of B, T, and NK cells. Both cases showed strong and almost exclusive pericardial membrane infiltration of CD8+ T-cells which was correlated with a higher than expected similar increase in the subset of peripheral blood lymphocytes (PBL). These findings suggest an important role for CD8+ T-cells in chronic RA, especially in this extraarticular manifestation of the disease.

Growth factor activity of IL-6 in the synovial fluid of patients with rheumatoid arthritis.

OBJECTIVE: We set out to determine whether the ability of synovial fluids (SF) in patients with rheumatoid arthritis (RA) to facilitate the proliferation of synovial tissue-derived fibroblastic cell lines was related to the presence of growth factors and/or cytokines. METHODS: The growth factor activity of 20 RA SF was measured by their ability to induce anchorage-independent growth of the rat NRK-49F (49F) fibroblastic strain. The presence of transforming growth factor-beta (TGF-beta) and platelet-derived growth factor (PDGF) was also assessed using neutralising anti-TGF-beta or anti-PDGF-AB mAbs. Cytokines were measured by functional assays or ELISA: RESULTS: We observed a correlation between growth factor activity and the IL-6 levels in SF. Both were correlated to the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels in SF and serum. IL-6 (at concentrations above 10(4) U/ml), synergized with growth factors in the induction of the anchorage independent (AI) growth of 49F cells. Pretreatment of SF with a neutralising anti-IL-6 mAb substantially reduced the capacity of these SF to induce AI growth of 49F cells, confirming the growth factor activity of IL-6 in this test. In contrast, IL-6 alone or in association with PDGF, epidermal growth factor (EGF) or TGF-beta had no effect on the anchored growth of synovial tissue-derived fibroblasts, and treatment of SF with a neutralising anti-IL-6 mAb did not affect their ability to increase the growth rate of synovial tissue-derived fibroblasts. CONCLUSIONS: These results strongly suggest that IL-6 is responsible for the observed correlation between the growth factor activity of SF and inflammatory indexes such as ESR and CRP. However, neither IL-6 nor PDGF were responsible for the observed positive effect of SF on synovial fibroblastic cell lines.

Advances in imaging of the acute abdomen.

Over the last 10 years, the most significant advancement in imaging of the acute abdomen has been the development of helical CT imaging. Rapid breath-hold imaging and improved intravascular opacification have enabled radiologists to obtain volumetric data that can be viewed in smaller slice increments. Helical data can also be analyzed utilizing multiplanar and three-dimensional techniques. With its proven ability to diagnose a wide variety of conditions, CT remains the diagnostic modality of choice for imaging the surgical abdomen. There have been considerable improvements in image resolution in US with improvements in transducer technology. Ultrasonography often serves as the first study in evaluating the pediatric or female patient with right lower quadrant or pelvic pain. Computed tomography may be necessary if US is not diagnostic. Despite these technical advances, plain film radiography should be the first imaging study for suspected cases of bowel perforation or obstruction. Magnetic resonance imaging continues to evolve, with improvements in hardware and software design that allow for faster imaging, but current levels of availability in the acute setting preclude its wider use. Whereas further imaging is not necessary for patients presenting with classic signs and symptoms of various acute abdominal diseases, the atypical patient often requires careful diagnostic imaging. Close consultation between the radiologist and surgeon leads to studies appropriately tailored to meet the diagnostic challenge at hand.

Cartilage and subchondral bone thickness distribution with MR imaging.

RATIONALE AND OBJECTIVES: The authors mapped articular cartilage (AC) and subchondral bone (SB) thicknesses in human acetabula in vitro by using magnetic resonance (MR) imaging and validated AC measurements by using light microscopy. MATERIALS AND METHODS: Left and right acetabula from a deceased patient who had undergone left hemiarthroplasty were imaged with fat-suppressed spoiled gradient-recalled acquisition in the steady state (repetition time = 55 msec, echo time = 15 msec, flip angle = 50 degrees, matrix = 256 x 256, field of view = 8 cm). AC and SB thickness maps were generated from image data by using analytic geometry, which enabled correction for thickness overestimation due to oblique sectioning. Cartilage bone plugs were extracted from the acetabula, and light microscopy was used to validate the thickness measurements obtained with MR imaging. RESULTS: Standard errors between thickness measurements obtained with MR imaging and light microscopy were 0.37 and 0.33 mm for the left and right AC, respectively, which is consistent with the voxel resolution of the MR imaging sequence (0.31 x 0.31 x 0.8 mm). SB thickness of the cartilage plugs could not be reliably measured with light microscopy and, therefore, could not be validated. Contour maps showed that SB thickness gradients were rapid and focal compared with the rather smooth gradients in AC thickness; however, thicker AC was accompanied by thicker SB for left (r2 = .261, P = .0001) and right (r2 = .308, P = .0001) acetabula. Average thickness differences between left and right acetabular AC and SB were 0.13 mm (P = .015) and 0.11 mm (P = .026), respectively. Although it was the operated hip that had thicker articular tissues, the differences were within the pixel resolution (< 0.31 mm). CONCLUSION: AC and SB thickness distribution can be accurately determined by combining noninvasive MR imaging and analytic geometry, which may also provide a means for quantitative, longitudinal assessment of focal AC defects.

Quantification of articular cartilage in the knee with three-dimensional MR imaging.

RATIONALE AND OBJECTIVES: To determine the volume of articular cartilage in cadavers, patients, and healthy volunteers by using a volumetric, fat-suppressed spoiled gradient-recalled signal acquisition in the steady state (SPGR) magnetic resonance (MR) sequence. METHODS: Sagittal MR images were obtained with a fat-suppressed SPGR sequence (repetition time, 52 msec; echo time, 10 msec; 60 degrees flip angle; 3.0-3.5-mm partitions, 256 x 192 matrix, two signals acquired). The cartilaginous surfaces of the tibia, femur, and patella were planimetrically defined with a three-dimensional workstation. A three-dimensional model volume was created by threshold segmenting the cartilage from the adjacent tissues. The volume as calculated by using MR imaging was compared with the actual volume of the cartilage specimens. RESULTS: Observed measurements correlated with actual weight and volume displacement measurements with an accuracy of 82%-99% and linear correlation coefficients of 0.99 (P = 2.5e-15) and 0.99 (P = 4.4e-15). Precision of segmentation in healthy volunteers yielded a coefficient of variation of 0.4% for interobserver variability and 0.3% for intraobserver variability. CONCLUSION: This pilot study suggests that accurate volumetric calculations of knee articular cartilage are possible with currently available MR imaging pulse sequences and a commercially available work station.

In vivo three-dimensional evaluation of the tracheobronchial tree.

Traditionally computed axial tomography has had limitations in evaluating diseases that affect the tracheobronchial tree because of respiratory-induced artifacts, with the likelihood of missing lesions as a result of misregistration. Spiral computed tomography (CT) differs from conventional CT in that the entire thorax can be rapidly imaged in the axial plane after a single breath-hold. Five patients underwent non-contrast-enhanced volumetric CT, with emphasis on three-dimensional reconstruction, and endoscopic evaluation with pathologic confirmation. In all cases, there was complete corroboration between volumetric CT and endoscopic evaluation. The use of selective thresholds allowed the air within the tracheobronchial tree to be used as a negative contrast agent. Thus with the integration of selective windowing, detailed three-dimensional tracheobronchial anatomy may be elucidated. The absence of respiratory registration artifact due to the single breath-hold technique raises the confidence that three-dimensional and multiplanar images generated from such studies are accurate representations of the pathologic conditions at hand. By the integration of volumetric CT techniques and rapid three-dimensional display of tracheobronchial structures, volumetric CT bronchography becomes practical.

Cross-sectional imaging of liver transplantation.

Orthotopic liver transplantation is commonly performed at many institutions around the world. The care of these critically ill patients has heavily relied upon cross-sectional imaging. CT, MRI, and ultrasound help enormously in the preoperative assessment of these patients and in the postoperative management of the various complications. This article reviews the role of these cross-sectional modalities and their respective strengths and weaknesses in the adult transplant candidate and recipient.

Noninvasive liver imaging: new techniques and practical strategies.

The goals and expectations of liver imaging have expanded as the treatment options for a range of liver diseases have advanced. Unfortunately, no single modality can yet achieve all the goals that an ideal imaging modality should satisfy. Currently available liver imaging techniques should be considered complementary rather than competitive in their roles, and appropriate utilization of the expanding technical capabilities of cross-sectional imaging depends on many considerations, including patient factors, referring physician expectations and biases, experience and bias of the radiologist, and the availability of state-of-the-art technical capabilities for each modality. This article reviews the advantages, limitations, and roles of fast CT and fast MR liver imaging techniques as well as the complimentary role of ultrasound, and the future of new imaging considerations including the role of contrast agents.

Comparison of magnetic resonance imaging with operative findings in acute traumatic dislocations of the adult knee.

OBJECTIVES: To compare magnetic resonance imaging (MRI) with examination under anesthesia and with surgical findings in evaluating soft tissue injuries in acute traumatic knee dislocations in adults. DESIGN: Retrospective analysis. SETTING: Level I trauma center. PATIENTS: For a single surgeon, all patients who underwent MRI before surgical treatment for knee dislocations (ten individuals). INTERVENTION: Incompetent ligaments were repaired or reconstructed. MAIN OUTCOME MEASUREMENTS: MRI of knee dislocations was compared with clinical examination under anesthesia and with intraoperative findings at arthrotomy in ten cases. Pertinent positive and negative findings were recorded, and accuracy, sensitivity, specificity, and positive and negative predictive values were calculated. RESULTS: Two mid-grade sprains of the anterior cruciate ligament were erroneously read as complete tears. One rupture or avulsion of each the biceps tendon, the lateral collateral ligament, and the posterolateral and posteromedial corners were considered intact on MRI. The MRI studies erroneously identified tears of the lateral collateral ligament and medial meniscus in one case each. Otherwise, the study was highly accurate. CONCLUSIONS: MRI is useful for defining the presence of ligamentous injuries in knee dislocations; however, clinical examination under anesthesia is more accurate.

Evaluation and management of back pain: preventing disability.

Musculoskeletal pain has become a major public health problem with medical, occupational and socioeconomic implications. This paper reviews the problem of musculoskeletal back pain, impairment and implications for disability with specific reference to recent meta-analyses such as those performed by the Agency for Health Care Policy and Research (1994) and the IASP Task Force on Pain in the Workplace (1995). Data from these and other studies are consistent with our clinical findings suggesting that most cases of low back pain are idiopathic with an obscure etiology. As such they should be classified as non-specific low back pain (NSLBP) or back pain of undetermined etiology. The authors suggest that despite a paucity of objective findings many patients receive diagnoses difficult to justify and extensive diagnostic evaluation, some of which may be inappropriate and contribute to iatrogenic disability. Principles for appropriate diagnostic and therapeutic management are discussed with specific attention to risk factors likely to adversely influence treatment outcome and contribute to unnecessary disability.

Synthesis and biological evaluation of cyclic nitrogen mustards based on carnitine framework.

Two series of cyclic nitrogen mustards structurally related to L-carnitine have been prepared. The cytotoxic activity of these compounds was evaluated by using Chlorambucil as a reference. In accordance with earlier report, the cytotoxicity is in direct correlation with the lipophilicity of the introduced alkyl chains. Among the cyclic nitrogen mustards synthesized, the most cytotoxic compounds were the one acylated with a palmitoyl side chain, which showed activities comparable to that of Chlorambucil.