Physical inactivity and knee osteoarthritis in guinea pigs.

OBJECTIVE: To investigate whether and how a sedentary lifestyle contributes to knee osteoarthritis (OA) incidence and severity. DESIGN: An experiment was conducted using Hartley guinea pigs, an established idiopathic knee OA model. To simulate a sedentary lifestyle, growing animals (n = 18) were housed for 22 weeks in small cages that restricted their mobility, while another group of animals (n = 17) received daily treadmill exercise to simulate moderate physical activity. After the experiment, histological assessments, biochemical assays, and mechanical testing were conducted to compare tibial articular cartilage structure, strength, and degree of OA degeneration between sedentary and physically active animals. Groups were also compared based on body weight and composition, as well as gut microbial community composition assessed using fecal 16S rRNA gene sequencing. RESULTS: Prevalence of knee OA was similar between sedentary and physically active animals, but severity of the disease (cartilage lesion depth) was substantially greater in the sedentary group (P = 0.02). In addition, during the experiment, sedentary animals developed cartilage with lower aggrecan quantity (P = 0.03) and accumulated more body weight (P = 0.005) and visceral adiposity (P = 0.007). Groups did not differ greatly, however, in terms of cartilage thickness, collagen quantity, or stiffness, nor in terms of muscle weight, subcutaneous adiposity, or gut microbial community composition. CONCLUSIONS: Our findings indicate that a sedentary lifestyle promotes the development of knee OA, particularly by enhancing disease severity rather than risk of onset, and this potentially occurs through multiple pathways including by engendering growth of functionally deficient joint tissues and the accumulation of excess body weight and adiposity.

Bcl-3 deficiency protects against dextran-sodium sulphate-induced colitis in the mouse.

Bcl-3 is a member of the IκB family of proteins and is an essential negative regulator of Toll-like receptor-induced responses. Recently, a single nucleotide polymorphism associated with reduced Bcl-3 gene expression has been identified as a potential risk factor for Crohn's disease. Here we report that in contrast to the predictions of single nucleotide polymorphism (SNP) analysis, patients with Crohn's disease and ulcerative colitis demonstrate elevated Bcl-3 mRNA expression relative to healthy individuals. To explore further the potential role of Bcl-3 in inflammatory bowel disease (IBD), we used the dextran-sodium sulphate (DSS)-induced model of colitis in Bcl-3(-/-) mice. We found that Bcl-3(-/-) mice were less sensitive to DSS-induced colitis compared to wild-type controls and demonstrated no significant weight loss following treatment. Histological analysis revealed similar levels of oedema and leucocyte infiltration between DSS-treated wild-type and Bcl-3(-/-) mice, but showed that Bcl-3(-/-) mice retained colonic tissue architecture which was absent in wild-type mice following DSS treatment. Analysis of the expression of the proinflammatory cytokines interleukin (IL)-1ß, tumour necrosis factor (TNF)-α and IL-6 revealed no significant differences between DSS-treated Bcl-3(-/-) and wild-type mice. Analysis of intestinal epithelial cell proliferation revealed enhanced proliferation in Bcl-3(-/-) mice, which correlated with preserved tissue architecture. Our results reveal that Bcl-3 has an important role in regulating intestinal epithelial cell proliferation and sensitivity to DSS-induced colitis which is distinct from its role as a negative regulator of inflammation.

MR Imaging Characteristics of Intraocular Perfluoro-n-Octane.

We describe the unique MR imaging characteristics of intraocular perfluoro-n-octane, a liquid used for intraoperative and postoperative tamponade in the context of complex retinal detachment repair, and contrast it with other intraocular pathologies. Because trace amounts of perfluoro-n-octane may be left in the globe postoperatively, it may be confused for other abnormalities, such as foreign bodies or tumors.

Oxidative stress induces caspase-independent retinal apoptosis in vitro.

Apoptosis is the mode of cell death in retinitis pigmentosa (RP), a heterogeneous group of retinal degenerations. The activation of the caspase proteases forms a pivotal step in the initiation and execution phase of apoptosis in many cells. Inhibition of caspases has been reported to prevent apoptosis in many model systems. However, we demonstrate the absence of caspase activation during retinal cell apoptosis in vitro which involves phosphatidylserine (PS) externalisation, DNA nicking and cell shrinkage. In addition, zVAD-fmk, DEVD-CHO and BD-fmk, inhibitors of the caspases, were unable to alter the characteristics or kinetics of apoptosis, implying that retinal cell death in vitro follows a caspase-independent pathway. We have previously demonstrated the ability of reactive oxygen species (ROS) to act as mediators of retinal cell apoptosis in vitro as well as the ability of antioxidants to prevent retinal cell apoptosis. Here we demonstrate the oxidative inactivation of caspases in this model of retinal apoptosis and provide evidence for an oxidative stress driven cell death pathway that does not involve caspase activity and which retains key features of apoptotic cell death. Furthermore, our data indicates that apoptotic events such as PS exposure, DNA nicking and cell shrinkage may occur independently of caspase activity.

Epidemiologic features of asymptomatic cerebral infarction in patients with nonvalvular atrial fibrillation.

We performed unenhanced computed tomographic scans on 141 asymptomatic patients with nonvalvular atrial fibrillation. Thirty-six patients (26%) had hypodense areas consistent with cerebral infarction. The majority of these were small deep infarcts, seen in 29 patients (21%), but 13 patients (9%) had cortical or large deep infarctions. Twelve patients had more than one infarct on computed tomographic scan. Increasing age and increased left atrial diameter were the only clinical features associated with asymptomatic infarction. Patients older than 65 years with a left atrial diameter greater than 5.0 cm (n = 23) had a 52% prevalence of asymptomatic infarction. Patients younger than 65 years with a left atrial diameter less than 5.0 cm (n = 38) had an 11% prevalence of silent infarction. Patients with only one of these risk factors (n = 72) had a 24% prevalence of silent infarction. Infarction was more common in those with chronic (34%) as opposed to intermittent (22%) nonvalvular atrial fibrillation, but this difference was not significant. Hypertension, diabetes, duration of atrial fibrillation, congestive heart failure, history of myocardial infarction, and echocardiographic evidence of left ventricular dysfunction were not associated with asymptomatic infarction. A history of hypertension was present in only 35% of our patients with small-deep asymptomatic infarction, similar to the percentage in patients without stroke. Asymptomatic cerebral infarction is common in nonvalvular atrial fibrillation. The association with enlarged left atria and the lack of correlation with major cerebrovascular risk factors suggests a cardioembolic mechanism. Further study is needed to determine the functional and prognostic significance of these strokes.

Diagnostic performance of teleradiology in cervical spine fracture detection.

This study was done to assess the diagnostic accuracy of high-resolution (5 lp/mm) teleradiology for detecting cervical spine fractures. Single radiographs from 25 patients with and 25 patients without cervical spine fractures were transmitted between two units of our teleradiology system (Dupont DTR 2000) located 5 miles apart. Each image was examined by four readers. Fracture detection accuracy was assessed by generating receiver operating characteristic (ROC) curves and comparing the areas under each reader's curves for original and transmitted images. Two readers had statistically significant better fracture detection using nontransmitted images, whereas two had no significant differences in accuracy. The authors conclude that high resolution in and of itself is not adequate for fracture detection, and that issues concerning image contrast manipulation also will have to be addressed before teleradiology systems can be used for clinical cervical spine fracture screening.

Digital subtraction angiography: applications in otolaryngology--head and neck surgery.

Digital electronic technology has made its most notable contribution to radiology in the form of the CT scanners which have so greatly benefited medical practice. Experience with intravenous angiography using a digital fluoroscopy unit developed at the University of Arizona gives promise of a further major benefit in the area of angiography. The majority of examinations are conducted on an outpatient basis with a risk level comparable to that of an intravenous pyelogram. The authors review their experience with this unit, including it's diagnostic and therapeutic applications to congenital and acquired vascular diseases, neoplasms, and vascular trauma of the head and neck.

Orbital histiocytosis X.

In three patients with histiocytosis X of bone with orbital involvement, CT scans were reviewed. Consistent findings included a destructive lesion of the lateral wall of the orbit with a large soft-tissue component that extended into the extraconal space, the ocular adnexa, and the infratemporal fossa. The greater wing of the sphenoid was eroded in all cases, with epidural extension into the middle cranial fossa. Cavernous sinus involvement and a second bone lesion were seen in two patients.

Orbital and optic pathway sarcoidosis: MR findings.

PURPOSE: To identify and characterize the MR findings of sarcoidosis when it involves the orbit and visual pathways. METHODS: The MR scans of 15 patients, 3 with presumed and 12 with proved orbital or optic pathway sarcoidosis were retrospectively reviewed. RESULTS: Eight patients had MR evidence of optic nerve involvement by sarcoid granuloma. Perineural enhancement was seen in four cases, optic atrophy in one. Three who had had unenhanced scans showed optic nerve enlargement. Nine patients had optic chiasmal involvement. One patient had increased T2 signal in the optic radiations. Three patients had orbital masses that had MR signal characteristics similar to pseudotumor. Five patients had periventricular white matter abnormalities closely resembling multiple sclerosis. CONCLUSIONS: Sarcoidosis should be considered in the differential diagnosis of optic nerve or nerve sheath enhancement on MR. Orbital sarcoidosis has MR characteristics very similar to pseudotumor.

Evaluation of cerebral hemispheric contrast transit with intravenous digital subtraction angiography.

Thirty-six patients with varying degrees of stenosis of one internal carotid artery were studied using intravenous digital subtraction angiography, assessing relative hemispheric washin and washout of contrast medium. Ipsilateral delayed contrast transit was seen in 16 of 18 patients with a 70% or greater carotid artery stenosis. Decreased hemispheric peak contrast density was also seen in most of these patients. With further improvements in the computer program and faster imaging rates, intravenous digital subtraction angiography has the capability of providing valuable physiologic data along with anatomic information in patients with suspected cerebral ischemia.

Digital subtraction angiography of glomus tympanicum and jugulare tumors.

Radiologic procedures used to evaluate patients with suspected glomus tumor have included plain skull radiography, temporal bone tomography, computed tomography, and cerebral angiography. Of these, only angiography has proven reliable as a screening procedure for small glomus tympanicum and jugulare tumors. Digital subtraction angiography was used as the initial examination for suspected paraganglioma in 14 patients. Intravenous digital subtraction angiography proved to be an acceptable screening tool for these highly vascular tumors. Also, intraarterial digital subtraction angiography proved very satisfactory for mapping of tumor blood supply, which greatly simplified preoperative embolization. Effectiveness of therapy was readily ascertained by serial follow-up intravenous digital subtraction angiography.

MR imaging of acute coccidioidal meningitis.

BACKGROUND AND PURPOSE: Our purpose was to describe the MR imaging findings in patients with acute coccidioidal meningitis. METHODS: Fourteen patients (11 men, three women; 22-78 years old; mean age, 47 years) with coccidioidal meningitis underwent neuroimaging within 2 months of diagnosis. Thirteen patients had MR imaging and one had an initial CT study with a follow-up MR examination 5 months later. Initial and follow-up MR images were evaluated for the presence of ventricular dilatation, signal abnormalities, enhancement characteristics, sites of involvement, and evidence of white matter or cortical infarction. The patterns of enhancement were characterized as focal or diffuse. Pathologic specimens were reviewed in two patients. RESULTS: Ten of the 14 images obtained at the time of initial diagnosis showed evidence of meningitis. All of the initially abnormal studies showed enhancement in the basal cisterns, sylvian fissures, or pericallosal region. Subsequent studies, which were available for three of the four patients with normal findings initially, all eventually became abnormal, with focal enhancement seen on the initial abnormal examination. Other abnormalities seen at presentation included ventricular dilatation (six patients) and deep infarcts (four patients). Pathologic specimens in two patients showed focal collections of the organism corresponding to the areas of intense enhancement on MR images. CONCLUSION: Early in its disease course, coccidioidal meningitis may show areas of focal enhancement in the basal cisterns, which may progress to diffuse disease. Pathologically, the areas of enhancement represent focal collections of the organism. Deep infarcts and communicating hydrocephalus are associated findings.

High-dose i.v. contrast in CT scanning of the postoperative lumbar spine.

Evaluation of the postoperative lumbar spine is sometimes difficult because of obliteration of epidural fat by hypertrophic scarring. We examined 70 patients using a high-dose intravenous contrast technique in an attempt to distinguish hypertrophic scarring from herniated disk. The CT interpretation was confirmed in all 17 patients who had follow-up operations. Thirteen had herniated disk material associated with scar and four had hypertrophic scarring only. The latter four patients underwent reoperation because of concomitant foraminal or spinal canal stenosis seen on CT. Twelve of the herniated disks had the expected appearance of a nonenhancing mass surrounded by a rim of enhancing scar tissue. In the 13th patient, homogeneous enhancement of the herniated disk was seen. It is thought that chronically herniated disks, such as this one, may incite enough surrounding scar to give the CT appearance of an enhancing disk. Finally, marginal enhancement in the anulus fibrosus region was seen in over 90% of disk spaces examined. Although an anatomical explanation cannot be given at present, this phenomenon is thought to represent a normal finding.

Conventional vs computed radiography: evaluation of myelography.

A prospective study was performed to compare the diagnostic efficacy of conventional film-screen (FS) imaging with computed radiography (CR) in myelography. Forty examinations were done with both methods. Digital myelography was found to have diagnostic accuracy equal to that of conventional film-screen examinations.

Gadopentetate dimeglumine as a contrast agent in common carotid arteriography.

BACKGROUND AND PURPOSE: Despite improvements in noninvasive imaging, some patients with contraindications to iodine-based contrast material still require angiography for the evaluation of carotid stenosis. Our aim was to assess the utility of gadopentetate dimeglumine as an intraarterial contrast agent in common carotid angiography. METHODS: Twelve patients with suspected carotid artery stenosis were enrolled in the study. In addition to the standard injection sequences with iohexol, common carotid arteriograms were obtained after administration of gadopentetate dimeglumine. Neurologic status and vital signs were monitored during and for 6 hours after the examination. For each injection, five independent observers, blinded to the contrast agent used, measured the percentage of carotid stenosis and assessed their confidence in grading the stenosis, the overall quality of the examination, and, in cases of decreased quality, the reason(s) for it. Statistical analysis was done with paired and unpaired t-tests with equal variances. RESULTS: No patient had an adverse clinical outcome, and measurements of carotid artery stenosis showed no statistically significant differences between the gadopentetate dimeglumine and iohexol examinations. Overall image quality and observer confidence in measurements of stenosis on the gadolinium-based studies were slightly but significantly lower than those of identical iodine-based studies. CONCLUSION: Gadopentetate dimeglumine may be an alternative to iodine in selected patients undergoing carotid angiography. Although overall image quality of the gadolinium studies is slightly inferior to that of the iohexol studies, measurements of carotid artery stenosis are similar for the two examinations.

Disseminated coccidioidomycosis complicated by vasculitis: a cause of fatal subarachnoid hemorrhage in two cases.

We describe two cases of disseminated coccidioidomycosis that were complicated by fatal subarachnoid hemorrhage. In the first case, a left middle cerebral artery aneurysm and long-segment vasculitis occurred. In the second case, MR imaging revealed an enlarging coccidioidal granuloma at the tip of the basilar artery, and the artery subsequently ruptured. Fatal intracranial hemorrhage is a rare complication of disseminated coccidioidomycosis.

Digital subtraction angiography of the arteries of the head and neck.

The advantages and disadvantages of intravenous and intra-arterial digital subtraction angiography of the arteries of the head and neck are discussed. The clinical applications of the two techniques are compared.

Digital video subtraction angiography of the cervical and cerebral vasculature.

A digital video subtraction angiography unit developed at the University of Arizona is described. The system allows the angiographic evaluation of the cervical and cerebral vasculature by means of intravenous injection of contrast material. The procedure is performed on outpatients and is reliable, safe, and economical. The authors have evaluated suspected arterial and venous occlusive disease, certain aneurysms and tumors, and postoperative results of vascular bypass procedures and aneurysm clipping. The clinical application of the technique is shown with appropriate case presentations.

Signalling apoptosis: a radical approach.

Reactive oxygen species (ROS) are frequently associated with cytotoxicity, often being described as damaging, harmful or toxic. It is generally assumed that, under pathological circumstances, ROS elicit wide-spread and random acts of oxidation. This passive attack of cellular components by ROS, in conditions where oxidative stress is the initiating stimulus for apoptosis, is assumed to simply trigger cell death as a result of cumulative oxidative damage. However, accumulating evidence now suggests that ROS may act as signalling molecules for the initiation and execution of the apoptotic death programme in many, if not all, current models of apoptotic cell death. Signalling by ROS would not appear to be random, as previously assumed, but targeted at specific metabolic and signal transduction cellular components. There is also evidence that the enzymatic generation of ROS may not simply be an unwanted by-product of the primary reaction catalysed, but that ROS may be used as signalling molecules to regulate cellular processes including apoptosis. This view of ROS as signalling molecules (as opposed to toxic metabolites) has been further bolstered by the findings that cellular antioxidants such as glutathione and thioredoxin not only serve to regulate ROS levels but also act as reversible redox modifiers of enzyme function. This review will attempt to delineate the involvement of ROS in apoptosis in light of these recent discoveries and provide evidence for a crucial role for ROS in the initiation and execution of the death process.

Bone marrow imaging using STIR at 0.5 and 1.5 T.

We retrospectively examined MR images in 82 patients to evaluate the usefulness of short inversion time inversion recovery (STIR) in bone marrow imaging at 0.5 and 1.5 T. The study included 56 patients at 1.5 T and 26 patients at 0.5 T with a variety of pathologic bone marrow lesions (principally oncological), and compared the contrast and image quality of STIR imaging with spin-echo short repetition time/echo time (TR/TE), long TR/TE, and gradient-echo sequences. The pulse sequences were adjusted for optimal image quality, contrast, and fat nulling. STIR appears especially useful for the evaluation of red marrow (e.g., spine), where contrast between normal and infiltrated marrow is greater than with either gradient-echo or T1-weighted images. STIR is also extremely sensitive for evaluation of osteomyelitis, including soft tissue extent. In more peripheral (yellow) marrow, T1-weighted images are usually as sensitive as STIR. Limitations of STIR include artifacts, in particular motion artifact that at high field strength necessitates motion compensation. At 0.5 T, however, motion compensation is usually not necessary. Also, because of extreme sensitivity to water content, STIR may overstate the margins of a marrow lesion. With these limitations in mind, STIR is a very effective pulse sequence at both 0.5 and 1.5 T for evaluation of marrow abnormalities.