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M A D'Agostino

Publications and source records attributed to M A D'Agostino.

13 recordsLinked to original sources
PubMed2005

Interobserver reliability in musculoskeletal ultrasonography: results from a "Teach the Teachers" rheumatologist course.

OBJECTIVE: To assess the interobserver reliability of the main periarticular and intra-articular ultrasonographic pathologies and to establish the principal disagreements on scanning technique and diagnostic criteria between a group of experts in musculoskeletal ultrasonography. METHODS: The shoulder, wrist/hand, ankle/foot, or knee of 24 patients with rheumatic diseases were evaluated by 23 musculoskeletal ultrasound experts from different European countries randomly assigned to six groups. The participants did not reach consensus on scanning method or diagnostic criteria before the investigation. They were unaware of the patients' clinical and imaging data. The experts from each group undertook a blinded ultrasound examination of the four anatomical regions. The ultrasound investigation included the presence/absence of joint effusion/synovitis, bony cortex abnormalities, tenosynovitis, tendon lesions, bursitis, and power Doppler signal. Afterwards they compared the ultrasound findings and re-examined the patients together while discussing their results. RESULTS: Overall agreements were 91% for joint effusion/synovitis and tendon lesions, 87% for cortical abnormalities, 84% for tenosynovitis, 83.5% for bursitis, and 83% for power Doppler signal; kappa values were good for the wrist/hand and knee (0.61 and 0.60) and fair for the shoulder and ankle/foot (0.50 and 0.54). The principal differences in scanning method and diagnostic criteria between experts were related to dynamic examination, definition of tendon lesions, and pathological v physiological fluid within joints, tendon sheaths, and bursae. CONCLUSIONS: Musculoskeletal ultrasound has a moderate to good interobserver reliability. Further consensus on standardisation of scanning technique and diagnostic criteria is necessary to improve musculoskeletal ultrasonography reproducibility.

Adult↗
PubMed2005

EULAR report on the use of ultrasonography in painful knee osteoarthritis. Part 1: prevalence of inflammation in osteoarthritis.

OBJECTIVES: To assess the prevalence of inflammation in subjects with chronic painful knee osteoarthritis (OA), as determined by the presence of synovitis or joint effusion at ultrasonography (US); and to evaluate the correlation between synovitis, effusion, and clinical parameters. METHODS: A cross sectional, multicentre, European study was conducted under the umbrella of EULAR-ESCISIT. SUBJECTS: had primary chronic knee OA (ACR criteria) with pain during physical activity >or=30 mm for at least 48 hours. Clinical parameters were collected by a rheumatologist and an US examination of the painful knee was performed by a radiologist or rheumatologist within 72 hours of the clinical examination. Ultrasonographic synovitis was defined as synovial thickness >or=4 mm and diffuse or nodular appearance, and a joint effusion was defined as effusion depth >or=4 mm. RESULTS: 600 patients with painful knee OA were analysed. At US 16 (2.7%) had synovitis alone, 85 (14.2%) had both synovitis and effusion, 177 (29.5%) had joint effusion alone, and 322 (53.7%) had no inflammation according to the definitions employed. Multivariate analysis showed that inflammation seen by US correlated statistically with advanced radiographic disease (Kellgren-Lawrence grade >or=3; odds ratio (OR)=2.20 and 1.91 for synovitis and joint effusion, respectively), and with clinical signs and symptoms suggestive of an inflammatory "flare", such as joint effusion on clinical examination (OR=1.97 and 2.70 for synovitis and joint effusion, respectively) or sudden aggravation of knee pain (OR=1.77 for joint effusion). CONCLUSION: US can detect synovial inflammation and effusion in painful knee OA, which correlate significantly with knee synovitis, effusion, and clinical parameters suggestive of an inflammatory "flare".

Aged↗
PubMed2005

EULAR report on the use of ultrasonography in painful knee osteoarthritis. Part 2: exploring decision rules for clinical utility.

BACKGROUND: Synovial inflammation (as defined by hypertrophy and effusion) is common in osteoarthritis (OA) and may be important in both pain and structural progression. OBJECTIVE: To determine if decision rules can be devised from clinical findings and ultrasonography (US) to allow recognition of synovial inflammation in patients with painful knee OA. METHODS: A EULAR-ESCISIT cross sectional, multicentre study enrolled subjects with painful OA knee who had clinical, radiographic, and US evaluations. A classification and regression tree (CART) analysis was performed to find combinations of predictor variables that would provide high sensitivity and specificity for clinically detecting synovitis and effusion in individual subjects. A range of definitions for the two key US variables, synovitis and effusion (using different combinations of synovial thickness, depth, and appearance), were also included in exploratory analyses. RESULTS: 600 patients with knee OA were included in the analysis. For both knee synovitis and joint effusion, the sensitivity and specificity were poor, yielding unsatisfactory likelihood ratios (75% sensitivity, 45% specificity, and positive LR of 1.36 for knee synovitis; 71.6% sensitivity, 43.2% specificity, and positive LR of 1.26 for joint effusion). The exploratory analyses did not improve the sensitivity and specificity (demonstrating positive LRs of between 1.26 and 1.57). CONCLUSION: Although it is possible to determine clinical and radiological predictors of OA inflammation in populations, CART analysis could not be used to devise useful clinical decision rules for an individual subject. Thus sensitive imaging techniques such as US remain the most useful tool for demonstrating synovial inflammation of the knee at the individual level.

Adult↗
PubMed2005

Interobserver reliability of rheumatologists performing musculoskeletal ultrasonography: results from a EULAR "Train the trainers" course.

OBJECTIVE: To evaluate the interobserver reliability among 14 experts in musculoskeletal ultrasonography (US) and to determine the overall agreement about the US results compared with magnetic resonance imaging (MRI), which served as the imaging "gold standard". METHODS: The clinically dominant joint regions (shoulder, knee, ankle/toe, wrist/finger) of four patients with inflammatory rheumatic diseases were ultrasonographically examined by 14 experts. US results were compared with MRI. Overall agreements, sensitivities, specificities, and interobserver reliabilities were assessed. RESULTS: Taking an agreement in US examination of 10 out of 14 experts into account, the overall kappa for all examined joints was 0.76. Calculations for each joint region showed high kappa values for the knee (1), moderate values for the shoulder (0.76) and hand/finger (0.59), and low agreement for ankle/toe joints (0.28). kappa Values for bone lesions, bursitis, and tendon tears were high (kappa = 1). Relatively good agreement for most US findings, compared with MRI, was found for the shoulder (overall agreement 81%, sensitivity 76%, specificity 89%) and knee joint (overall agreement 88%, sensitivity 91%, specificity 88%). Sensitivities were lower for wrist/finger (overall agreement 73%, sensitivity 66%, specificity 88%) and ankle/toe joints (overall agreement 82%, sensitivity 61%, specificity 92%). CONCLUSION: Interobserver reliabilities, sensitivities, and specificities in comparison with MRI were moderate to good. Further standardisation of US scanning techniques and definitions of different pathological US lesions are necessary to increase the interobserver agreement in musculoskeletal US.

Adult↗
PubMed2001

Phenotypic diversity is not determined by independent genetic factors in familial spondylarthropathy.

OBJECTIVE: To analyze the segregation of manifestations belonging to the spectrum of spondylarthropathy (SpA) among patients and unaffected siblings within SpA multiplex families. METHODS: Ninety-five multiplex families have been investigated. The diagnosis of SpA was made according to European Spondylarthropathy Study Group criteria. The prevalence of SpA manifestations was determined in unaffected siblings and compared with their prevalence in patients. RESULTS: We compared 241 SpA patients with 259 unaffected siblings. The prevalence of skeletal and extraarticular features not used as diagnostic criteria, i.e., radiographic sacroiliitis, peripheral enthesitis, uveitis, psoriasis, and inflammatory bowel disease, was significantly increased in patients compared with unaffected siblings. This result was not accounted for by sex or HLA-B27 distribution differences. CONCLUSION: In familial SpA, skeletal and extraarticular manifestations tend to segregate together, implying that all subsets are predominantly determined by a shared component, and that accessory factors must be responsible for phenotype diversity.

Adult↗
PubMed1992

A new chick mitochondrial DNA-binding protein exhibits sequence-specific interaction near heavy-strand replication origin: cleavage activity, stimulation of mtDNA synthesis, and enhancement in transformed fibroblasts.

We have identified a new, double-strand-dependent, mtDNA-binding protein in chick embryo fibroblast (CEF) mitochondria (and inner-membrane-matrix preparations) which demonstrates both an exclusive specific affinity for the displacement loop (D-loop) control region of chick mtDNA and intramitochondrial levels that reflect corresponding changes in mtDNA replication activity both in vivo and in vitro. This approximately 36 kDa protein (designated aMDP1, avian mitochondrial DNA-binding protein 1) was identified by elution and renaturation following SDS-polyacrylamide gel electrophoresis and by direct isolation from specific mtDNA-protein complexes excised from mobility shift gels. Analysis of the entire 16.7-kb mt genome determined that a MDP1 mediates cleavage of chick mtDNA in vitro at three H- and two L-strand sequence-specific target sites located within a 90-bp A + T-rich genomic tract, theoretically capable of forming stable secondary structures, approximately 200 bases upstream from the H-strand origin (OH) of replication. Furthermore, gel-isolated aMDP1 relaxes supercoiled mtDNA, and exogenous addition of the protein, in a permeabilized in vitro system, preferentially stimulates the synthesis of H-strand sequences which hybridize to OH-containing fragments. Oncogenic transformation of CEF by Rous sarcoma viruses results in a threefold elevated level of aMDP1, directly correlating with a similarly increased level of mtDNA replication in vivo. Heterologous chick-human cross-competition experiments showed that aMDP1 also selectively interacts with human (HeLa) D-loop region mtDNA, possibly reflective of an evolutionary importance for aMDP1 interaction in the region. Functionally, we hypothesize that aMDP1 may operate in conjunction with other mtDNA-binding proteins, important in replication and transcription, by potentiating duplex unwinding either prior to or during an initial stage of H-strand synthesis. Together, these results suggest that aMDP1 is a good potential candidate for a nucleus-encoded regulatory protein which communicates with the mt genome during the replication process.

Animals↗
PubMed1983

The effect of retroviral transformation on DNA replication and DNA polymerase-gamma activity in chick embryo fibroblast mitochondria.

The effect of transformation by oncogenic Rous sarcoma viruses on the replication of mitochondrial DNA (mtDNA) in chick embryo fibroblasts (CEF) was investigated, extending our previous report of a three- to five-fold increase in the rate of mtDNA replication, which is strictly linked to the expression of the transformed state, is mitochondria-specific, and is not attributable to virus production per se or different growth rates between normal and transformed CEF. In this paper, in vivo pulse-label and pulse-chase analysis shows an increased specific activity in all the replicative and topological forms of transformed cell mtDNA I, labeled within a 10-min pulse, 30-min chase period, reflecting about the same proportion of total label incorporated into D-loop strands (approximately 9S) relative to full-length closed circular forms (approximately 37S) of mtDNA from both cell types. In contrast to the concomitant changes observed in many other systems with elevated DNA synthesis, neither the estimated intramitochondrial pool size of the labeled DNA precursor (dTTP), nor the total level of the mtDNA-replicating enzyme (mt gamma-polymerase) is increased in the transformed cells. Notably, however, in both cell types the mitochondrial dTTP pools relative to the mtDNA complement are significantly larger than whole-cell pools relative to the nuclear DNA complement, confirming recent reports in HeLa cells. The solubilized mt gamma-polymerases from normal and transformed CEF, respectively, are both precipitated by 50% ammonium sulfate, inhibited by N-ethylmaleimide, have similar sedimentation coefficients, and exhibit optimal activity when poly(rA) . d(pT)10 is used as the template-primer. On the other hand, the transformed cell enzyme demonstrates an altered response to thiol compounds, a decreased tendency to aggregate during sedimentation, and is significantly less tightly attached to the mitochondria than the normal cell enzyme. We conclude that, as a result of transformation, an increased fraction of mtDNA molecules replicate at a given time, and that this increased replication rate in vivo is correlated with the expression of several altered endogenous properties, which possibly include a modified intramitochondrial structural attachment of the mt gamma-polymerase in situ. This experimental system may be well suitable for use in the identification of regulatory factors which function during the replication of the mitochondrial genome in vivo.

Animals↗
PubMed1976

Specific changes in the synthesis of mitochondrial DNA in chick embryo fibroblasts transformed by Rous sarcoma viruses.

In chick-embryo fibroblasts infected with the Schmidt-Ruppin strain of Rous sarcoma virus, subgroup A (wild type), or with a thermosensitive mutant of this virus, T5, the rates of mitochondrial DNA synthesis differ in cells that exhibit normal and malignant phenotypes. In wild type virus-infected cells grown at 36 or 41 degrees C, morphological transformation is expressed, the rate of 2-deoxy-D-[3H]glucose uptake is stimulated, and mitochondrial DNA synthesis in vivo is stimulated three- to fivefold over that in uninfected cells. In T5-infected cells these changes occur only at the permissive temperature (36 degrees C); a shift to the nonpermissive temperature (41 degrees C) causes the reversal of these effects, and the specific activity of purified mitochondrial DNA is characteristic of that from uninfected cells. In contrast, the specific activities of nuclear DNA purified from cells maximally transformed under the permissive conditions do not differ between wild type-infected and uninfected with the T5 virus. In parallel experiments with isolated mitochondria, the rate of mtDNA synthesis in vitro is again greater in mitochondria isolated from transformed cells. In addition, mitochondrial DNA synthesis in vitro in mitochondria from nontransformed and virus-transformed cells exhibits differential sensitivity to inhibition by mercaptoethanol. Furthermore, the ntDNAP polymerase activity in mitochondrial extracts prepared from cells with transformed phenotypes is about sevenfold higher than in extracts from cells with nontransformed phenotypes.

Avian Sarcoma Viruses↗