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Biomedical subjects

Roy D Altman

Publications and source records attributed to Roy D Altman.

13 recordsLinked to original sources
PubMed2006

Reversible posterior leukoencephalopathy in patients with systemic lupus erythematosus.

BACKGROUND: The development of central nervous system (CNS) symptoms in patients with preexisting systemic lupus erythematosus (SLE) evokes a wide differential diagnosis. Reversible posterior leukoencephalopathy (RPLE) is a rapidly evolving neurologic syndrome with characteristic clinical and radiographic features. Conditions commonly associated with RPLE include hypertensive encephalopathy, eclampsia, immunosuppressive drugs, and inflammatory disorders. OBJECTIVES: To describe our experience with RPLE in patients with concomitant SLE and review the literature. METHODS: The details of 5 novel cases and a MEDLINE review of the literature concerning the development of RPLE in association with SLE are presented. RESULTS: All cases included patients with SLE who developed the acute onset of headache, altered mental status, visual changes, and seizures. Neuroimaging demonstrated posterior white matter edema involving the parietal, temporal, and occipital lobes. Complete clinical and radiographic recovery occurred with prompt antihypertensive treatment and supportive care. Literature review identified 16 additional cases of RPLE occurring in patients with active SLE; the majority of these reports was similar in presentation and outcome to our experience. CONCLUSIONS: It is likely that the clinical manifestations and neuroimages in these lupus patients were the result of the RPLE syndrome. Fortunately, this cause of "secondary" CNS symptoms in patients with SLE is readily reversible when diagnosed early and treated with blood pressure control and supportive care.

Adult↗
PubMed2005

Increased radiographic damage scores at the onset of seropositive rheumatoid arthritis in older patients are associated with osteoarthritis of the hands, but not with more rapid progression of damage.

OBJECTIVE: To investigate the impact of patient age at symptom onset on radiographic joint damage at study entry, and on subsequent progression of damage in a cohort of patients with early seropositive rheumatoid arthritis (RA). METHODS: We studied 186 patients with RA of <15 months' duration. All patients had active disease and had not received disease-modifying antirheumatic drugs. At study entry and during followup, total Sharp scores (TSS), RA-associated joint space narrowing (RA-JSN), and erosions were determined on hand and foot radiographs. Baseline radiographs were also scored for osteoarthritis (OA)-related JSN (OA-JSN) and osteophytes. Older patients (>55 years) and younger patients (</=55 years) were compared by t-test, Mann-Whitney U test, chi-square, or Fisher's exact test. Multiple linear regression models were also constructed. RESULTS: The older group (n = 74) had a higher baseline total Sharp score (median 6.21) compared with the younger group (n = 112) (median 2.33) (P = 0.0002). This was mainly due to a higher baseline JSN score in the older group (median 3.96 versus 1.08) and not to differences in erosion score (median 0.91 versus 0.70). Disease activity and duration of RA symptoms were similar in the 2 groups, as were progression rates of the TSS, JSN score, and erosion score. At baseline, 26% of patients had osteophytes, with a prevalence of 13% in the younger age group and 50% in the older group. The presence of OA-JSN was highly correlated with the presence of osteophytes (r = 0.72). Also, increased age and RA-JSN were associated with increased severity of osteophytes and OA-JSN at baseline. Multiple linear regression analysis showed that both age and hand osteophytes contributed to the increase in baseline RA-JSN score and TSS, but not to erosion score. CONCLUSION: In a cohort of patients with early RA, an increase in the baseline RA-JSN score and TSS can be accounted for in part by the presence of hand OA.

Adult↗
PubMed2005

Structure-/disease-modifying agents for osteoarthritis.

OA is the most common articular disease. Age is its most notable risk factor. With the aging of the population of the developed world, there will be a growing need for better understanding of OA and for superior therapies. There is increasing appreciation for the role of inflammation in OA. There also is the realization that OA is not only a disease of cartilage, but of the entire joint. This has led to increasing interest in structure/disease modification as the goal in OA therapy. However, there are no universally proven structure-/ disease-modifying interventions.

Animals↗
PubMed2005

Recommendations for the registration of agents to be used in the prevention and treatment of glucocorticoid-induced osteoporosis: updated recommendations from the Group for the Respect of Ethics and Excellence in Science.

OBJECTIVES: The Group for the Respect and Excellence in Science (GREES) has reviewed and updated their recommendations for clinical trials to evaluate the efficacy and safety of new chemical entities to be used in the treatment and prevention of glucocorticoid-induced osteoporosis (GIOP). METHODS: Consensus discussion of the committee. RESULTS: With the exception of steroid use posttransplantation, there is no need to differentiate between underlying diseases. Prevention and treatment for GIOP are dependent on exposure to glucocorticoids rather than T-scores as in postmenopausal osteoporosis (PMO). If fracture data are obtained for PMO, it need not be repeated for GIOP, relying instead on bone mineral density (BMD) trials of at least 1 year. GREES recommends several changes in the previous guidance for GIOP. The committee saw no need to repeat preclinical studies if those have been previously done to assure bone quality in PMO. Similarly, phase I and phase II trials, if careful dose selection has been done for PMO, should not be repeated. The "prevention" and "treatment" claims should remain. Since the most recent evidence suggests significant increase in fracture risk for daily doses of prednisone of 5 mg/day or equivalent, clinical trials should concentrate on patients receiving at least this daily dosage. The emergence of bisphosphonates as the reference treatment, together with the rapid bone loss and high fracture incidence in glucocorticoid users, necessitates recommending a noninferiority trial design with lumbar spine BMD as the primary endpoint after 1 year. CONCLUSIONS: Registration of new chemical entities to be used in the management of GIOP should be granted, based on a 1-year noninferiority trial, using BMD as primary outcome and alendronate or risedronate as comparator. Demonstration of antifracture efficacy should have been previously demonstrated in PMO.

Clinical Trials as Topic↗
PubMed2004

Quantitative magnetic resonance imaging evaluation of knee osteoarthritis progression over two years and correlation with clinical symptoms and radiologic changes.

OBJECTIVE: To evaluate the change in osteoarthritic (OA) knee cartilage volume over a two-year period with the use of magnetic resonance imaging (MRI) and to correlate the MRI changes with radiologic changes. METHODS: Thirty-two patients with symptomatic knee OA underwent MRI of the knee at baseline and at 6, 12, 18, and 24 months. Loss of cartilage volumes were computed and contrasted with changes in clinical variables for OA and with standardized semiflexed knee radiographs at baseline at 1 and 2 years. RESULTS: Progression of cartilage loss at all followup points was statistically significant (P < 0.0001), with a mean +/- SD of 3.8 +/- 5.1% for global cartilage loss and 4.3 +/- 6.5% for medial compartment cartilage loss at 6 months, 3.6 +/- 5.1% and 4.2 +/- 7.5% at 12 months, and 6.1 +/- 7.2% and 7.6 +/- 8.6% at 24 months. Discriminant function analysis identified 2 groups of patients, those who progressed slowly (<2% of global cartilage loss; n = 21) and those who progressed rapidly (>15% of global cartilage loss; n = 11) over the 2 years of study. At baseline, there was a greater proportion of women (P = 0.001), a lower range of motion (P = 0.01), a greater circumference and higher level of pain (P = 0.05) and stiffness in the study knee, and a higher body mass index in the fast progressor group compared with the slow progressor group. No statistical correlation between loss of cartilage volume and radiographic changes was seen. CONCLUSION: Quantitative MRI can measure the progression of knee OA precisely and can help to identify patients with rapidly progressing disease. These findings indicate that MRI could be helpful in assessing the effects of treatment with structure-modifying agents in OA.

Arthrography↗
PubMed2004

Use of a permanent magnetic field to inhibit the development of canine osteoarthritis.

This study was designed to determine the potential of a permanent magnetic field to inhibit the progression of osteoarthritis (OA) in a canine model. The magnetic field was created by 72 domino-sized ceramic magnets with surface field strength of 1100 G (0.11 T). The magnetic field strength at the surface of the mattress was 450-500 G (45-50 mT) and was equally distributed over the mattress surface. Eighteen animals had closed resection of their right stifle anterior cruciate ligament. Their kennel floors were covered in one of three ways: no floor mattress (OA) (N = 6); a floor mattress with domino-sized ceramic pieces placed between two layers of foam (sham control OA-MAT) (N = 6); or a floor mattress with domino-sized ceramic permanent magnets placed between two layers of foam (OA-MAT-MAG) (N = 6). Animals were kept in their cages except for 4 h of exercise each day. The left stifle of six animals served as the normal control. The stifle joints were examined at 12 weeks for synovial effusion, gross anatomic appearance, microscopic anatomic appearance (Mankin score), and metalloproteinase (MMP)-1 and -3. Macroscopically, the OA-MAT-MAG group appeared to have less synovitis, less synovial effusion, less disruption of the cartilage surface, and less cartilage ulceration than did the OA group or the control mattress group. The mean Mankin score for the OA-MAT-MAG group was less than that for the OA group (4.2 +/- 0.8 vs. 6.7 +/- 0.3; P <.05) and the control mattress group (4.2 +/- 0.8 vs. 5.2 +/- 0.8; P >.05), but greater than that for the normal left group (4.2 +/- 0.8 vs. 1.0 +/- 0.4; P <.05). These scores show a trend of improvement for OA-MAT-MAG group but the difference with the sham control OA-MAT group was not statistically significant. In immunohistochemical studies, the OA-MAT-MAG group cartilage was stained less heavily for MMP-1 and MMP-3 than were the OA group cartilage and the control mattress group cartilage, but did not differ significantly in MMP-1 and MMP-3 from the normal left group cartilage. The OA-MAT-MAG group did not differ from the normal left group in MMP-3 as determined by Western blot analysis. The study suggests that OA of the medial femoral condyle developed in a canine model exposed to a magnetic field may be inhibited beyond the benefit provided by mattress. Further studies are needed to delineate more precisely the effect of the magnetic field in reducing the severity of OA.

Animals↗
PubMed2004

Efficacy and safety of a single intra-articular injection of non-animal stabilized hyaluronic acid (NASHA) in patients with osteoarthritis of the knee.

OBJECTIVE: Non-animal stabilized hyaluronic acid (NASHA) is a novel hyaluronan (HA) preparation with a 4-week intra-articular half-life. This study compared the efficacy of a single injection of NASHA with placebo in patients with osteoarthritis (OA) of the knee. DESIGN: This was a 26-week randomized, double-blind, multicenter study of a single intra-articular knee injection with either NASHA or placebo (saline). Assessments included the Western Ontario McMasters Universities osteoarthritis index (WOMAC, Likert Scale) and patients' overall global disease status. A positive response was defined as a reduction in WOMAC pain score for the study knee of 40% from baseline with a minimum improvement of > or =5 points. RESULTS: A total of 346 (NASHA 172; placebo 174) patients were treated. WOMAC scores and quality of life were improved in both the NASHA and placebo groups. For the overall population, there were no statistically significant between-group differences in response rates for any efficacy parameters. In patients with OA confined to the knee (N=216), a greater response to NASHA than placebo was observed at week 6 (P=0.025). There were few treatment-related events. CONCLUSIONS: NASHA was not superior to placebo for the primary efficacy analysis. However, these data may be confounded by the inclusion of patients with OA at other sites, as significant benefits over placebo were found among patients with OA confined to the knee. Future trials of OA that examine a local therapy might need to consider restricting the study population to those patients having OA of only the signal joint.

Adult↗
PubMed2004

Relapsing polychondritis, chronic hepatitis C virus infection, and mixed cryoglobulemia.

OBJECTIVE: Review of relapsing polychondritis (RP) and its association to chronic hepatitis C virus (HCV) infection and mixed cryoglobulinemia. METHODS: A case of RP associated with HCV infection is reported. The English language medical and scientific literature was reviewed for RP, hepatitis C, and its relation to other connective tissue diseases from February 1966 to January 2003 using MEDLINE. RESULTS: RP is an uncommon, multisystem disease of unknown etiology characterized by recurrent inflammation of cartilaginous and related tissues, being associated with other diseases in 30% to 35% of cases. HCV infection is a systemic illness with a propensity to trigger or exacerbate autoimmune disorders: eg, essential mixed cryoglobulinemia, membranoproliferative glomerulonephritis, and leukocytoclastic and systemic vasculitis. We could find no previous report of an association between RP with HCV and mixed cryoglobulinemia. Treatment with interferon gamma and ribavirin (IR) not only induced an undetectable viral load, but also resolved symptoms of RP. CONCLUSIONS: We report a patient with RP, HCV, and mixed cryoglobulinemia. It is unknown if there is a cause-effect or chance relationship. Treatment with IR improved the symptoms of RP. It is not known whether the effects of IR were directly on the RP or suppressed RP indirectly through the actions on the viral load or active hepatitis.

Aged↗
PubMed2003

Status of hyaluronan supplementation therapy in osteoarthritis.

Hyaluronans are polysaccharide molecules that occur naturally in synovial fluid; they help to create a viscous environment, cushion joints, and maintain normal function. The American College of Rheumatology recommends intra-articular injection of hyaluronans, which are available as several distinct therapeutic products, as an alternative to oral analgesics or nonsteroidal anti-inflammatory drugs for the symptomatic treatment of pain associated with osteoarthritis of the knee. A large body of literature supports the clinical efficacy and safety of this therapeutic class for this indication, although there are differences between the marketed products and they should be evaluated independently. Preliminary work investigating the use of hyaluronans for osteoarthritis in joints other than the knee has also produced promising results. There is growing evidence that hyaluronans, the biology of which is complex, may also have structure-modifying activity. Thus, compared with currently approved nonoperative therapies for osteoarthritis, hyaluronans may also have beneficial effects on the disease process in osteoarthritis.

Adjuvants, Immunologic↗
PubMed2003

Outcome variables for osteoarthritis clinical trials: The OMERACT-OARSI set of responder criteria.

Improvement in analysis and reporting results of osteoarthritis (OA) clinical trials has been recently obtained because of harmonization and standardization of the selection of outcome variables (OMERACT 3 and OARSI). Moreover, OARSI has recently proposed the OARSI responder criteria. This composite index permits presentation of results of symptom modifying clinical trials in OA based on individual patient responses (responder yes/no). The 2 organizations (OMERACT and OARSI) established a task force aimed at evaluating: (1) the variability of observed placebo and active treatment effects using the OARSI responder criteria; and (2) the possibility of proposing a simplified set of criteria. The conclusions of the task force were presented and discussed during the OMERACT 6 conference, where a simplified set of responder criteria (OMERACT-OARSI set of criteria) was proposed.

Clinical Trials, Phase III as Topic↗
PubMed2002

Inhibition of insulin-like growth factor binding protein 5 proteolysis in articular cartilage and joint fluid results in enhanced concentrations of insulin-like growth factor 1 and is associated with improved osteoarthritis.

OBJECTIVE: The complement component C1s is present in dog joint fluid in an activated state. Since C1s degrades insulin-like growth factor binding protein 5 (IGFBP-5), we undertook to determine whether inhibiting C1s in joint fluid would result in an increase in the amount of intact IGFBP-5 and IGF-1 in cartilage and joint fluid, and whether C1s inhibition would be associated with a reduction in cartilage destruction during the development of osteoarthritis (OA). METHODS: Twenty-two dogs were randomized to 3 treatment groups. All dogs underwent anterior cruciate ligament transection and were exercised. Dogs received 1 of 3 treatments: buffer alone (controls; n = 6); PB-145, a peptide derived from the sequence of antithrombin III (n = 9); and pentosan polysulfate (PPS; n = 7). PB-145 or saline was injected into the joint space 3 times per week for 3 weeks. PPS was injected intramuscularly weekly for 3 weeks. RESULTS: Joint histology showed preservation of chondrocytes and a smooth joint surface in the animals treated with PB-145 and PPS. Mankin scoring showed statistically significant reductions in joint destruction with PB-145 and PPS treatments (P < 0.01) compared with buffer control. Mean active collagenase concentrations were decreased by these two treatments. Immunoblotting of joint fluid showed that both treatments increased concentrations of intact IGFBP-5. Direct analysis of IGFBP-3 and IGFBP-5 protease activity showed that IGFBP-5 was degraded more rapidly and that PB-145 and PPS inhibited the degradation of both proteins. Total IGF-1 concentrations in joint fluid were increased 5.6-5.8-fold by these two treatments. Analysis showed that C1s was being activated in joint fluid and that its activation was inhibited by the addition of PB-145 or PPS. CONCLUSION: The findings suggest that direct inhibition of the serine protease C1s results in increased concentrations of intact IGFBP-5 and that proteolysis of IGFBP-3 is also inhibited, probably by the inhibition of some other protease. This increase in concentrations of intact IGFBP-3 and IGFBP-5 leads to an increase in IGF-1 which is associated with an improvement in joint architecture during the development of OA.

Animals↗