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M Weinblatt

Publications and source records attributed to M Weinblatt.

At least 19 recordsLinked to original sources
PubMed2006

Safety of the selective costimulation modulator abatacept in rheumatoid arthritis patients receiving background biologic and nonbiologic disease-modifying antirheumatic drugs: A one-year randomized, placebo-controlled study.

OBJECTIVE: To assess the safety of abatacept, a selective costimulation modulator, in patients with active rheumatoid arthritis (RA) who had been receiving > or =1 traditional nonbiologic and/or biologic disease-modifying antirheumatic drugs (DMARDs) approved for the treatment of RA for at least 3 months prior to entry into the study. METHODS: This was a 1-year, multicenter, randomized, double-blind, placebo-controlled trial. Patients were randomized 2:1 to receive abatacept at a fixed dose approximating 10 mg/kg by weight range, or placebo. RESULTS: The abatacept and placebo groups exhibited similar frequencies of adverse events (90% and 87%, respectively), serious adverse events (13% and 12%, respectively), and discontinuations due to adverse events (5% and 4%, respectively). Five patients (0.5%) in the abatacept group and 4 patients (0.8%) in the placebo group died during the study. Serious infections were more frequent in the abatacept group than in the placebo group (2.9% versus 1.9%). Fewer than 4% of patients in either group experienced a severe or very severe infection. The incidence of neoplasms was 3.5% in both groups. When evaluated according to background therapy, serious adverse events occurred more frequently in the subgroup receiving abatacept plus a biologic agent (22.3%) than in the other subgroups (11.7-12.5%). CONCLUSION: Abatacept in combination with synthetic DMARDs was well tolerated and improved physical function and physician- and patient-reported disease outcomes. However, abatacept in combination with biologic background therapies was associated with an increase in the rate of serious adverse events. Therefore, abatacept is not recommended for use in combination with biologic therapy.

Abatacept↗
PubMed2001

Long-term safety and efficacy of etanercept in patients with rheumatoid arthritis.

OBJECTIVE: Patients with rheumatoid arthritis (RA) treated with etanercept (Enbrel) in controlled studies of 3 to 6 months' duration had rapid and sustained improvement of their disease, with minimal safety issues. In this study, we examine safety and clinical benefit after longer term treatment with etanercept. METHODS: All adult patients with RA with a previously inadequate response to one or more disease modifying antirheumatic drugs, and who received at least one dose of etanercept as monotherapy in controlled or open label clinical trials were evaluated for safety and clinical benefit. Adverse event rates were compared as was evidence of continued benefit over time. RESULTS: Etanercept continued to be safe and well tolerated in 628 adult patients treated for a median of 25 mo (maximum 43 mo; 1109 patient-years). Nine percent of patients withdrew due to lack of efficacy and 7% due to adverse events. Most adverse events were mild, and no statistically significant increases in frequency of events were seen when patients received etanercept over longer periods of time. Clinical benefit was maintained with longterm therapy. A 100% improvement in individual disease activity measures was achieved by 17% to 28% of the patients. Fifty-five percent of patients who were taking corticosteroids (mean dose at baseline 6.6 mg/day) decreased or discontinued corticosteroid therapy while maintaining control of their arthritis symptoms. CONCLUSION: Etanercept continued to be safe and well tolerated, and its clinical benefit was sustained for a median of 25 mo and for as long as 43 mo in patients with RA.

Adolescent↗
PubMed1999

US consensus guidelines for the use of cyclosporin A in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease that often leads to irreversible joint damage and loss of function. Although there are numerous treatment options, it is difficult to manage the disease in most patients. Use of cyclosporin A (CsA) for RA was first reported in 1979, and since that time many trials have investigated CsA use for this disease. Based on clinical evidence, CsA is an efficacious second-line agent for patients with active RA who have not responded adequately to methotrexate (MTX). In addition, CsA has been shown to provide clinical benefit when used in combination with MTX in patients responding inadequately to MTX monotherapy. Side effects associated with CsA treatment are manageable if dosing, monitoring, and intervention guidelines are followed. The purpose of this review is to provide recommendations for the use of CsA in severe RA to physicians experienced in the management of systemic immunosuppressive therapy for RA. Where possible and appropriate, recommendations are based on evidence available in the literature.

Antirheumatic Agents↗
PubMed1998

The chemokine receptors CXCR3 and CCR5 mark subsets of T cells associated with certain inflammatory reactions.

T cells infiltrating inflammatory sites are usually of the activated/memory type. The precise mechanism for the positioning of these cells within tissues is unclear. Adhesion molecules certainly play a role; however, the intricate control of cell migration appears to be mediated by numerous chemokines and their receptors. Particularly important chemokines for activated/memory T cells are the CXCR3 ligands IP-10 and Mig and the CCR5 ligands RANTES, macrophage inflammatory protein-1alpha, and macrophage inflammatory protein-1beta. We raised anti-CXCR3 mAbs and were able to detect high levels of CXCR3 expression on activated T cells. Surprisingly, a proportion of circulating blood T cells, B cells, and natural killer cells also expressed CXCR3. CCR5 showed a similar expression pattern as CXCR3, but was expressed on fewer circulating T cells. Blood T cells expressing CXCR3 (and CCR5) were mostly CD45RO+, and generally expressed high levels of beta1 integrins. This phenotype resembled that of T cells infiltrating inflammatory lesions. Immunostaining of T cells in rheumatoid arthritis synovial fluid confirmed that virtually all such T cells expressed CXCR3 and approximately 80% expressed CCR5, representing high enrichment over levels of CXCR3+ and CCR5+ T cells in blood, 35 and 15%, respectively. Analysis by immunohistochemistry of various inflamed tissues gave comparable findings in that virtually all T cells within the lesions expressed CXCR3, particularly in perivascular regions, whereas far fewer T cells within normal lymph nodes expressed CXCR3 or CCR5. These results demonstrate that the chemokine receptor CXCR3 and CCR5 are markers for T cells associated with certain inflammatory reactions, particularly TH-1 type reactions. Moreover, CXCR3 and CCR5 appear to identify subsets of T cells in blood with a predilection for homing to these sites.

Animals↗
PubMed1998

Posttraumatic stress disorder and family functioning in adolescent cancer.

Twenty three adolescents with a history of cancer, 27 physically abused adolescents, and 23 healthy, nonabused adolescents were administered structured posttraumatic stress disorder (PTSD) interviews and self-report questionnaires regarding family functioning. Thirty five percent of adolescent cancer subjects met criteria for lifetime PTSD as compared to only 7% of the abused adolescents: 17% of the cancer subjects and 11% of the abuse subjects met criteria for current PTSD. Adolescents with cancer viewed their mothers and fathers as significantly more caring and more protective than the comparison and abused adolescents. Cancer subjects who met criteria for lifetime PTSD saw their families as significantly more chaotic than those who did not have PTSD. Eighty three percent of cancer subjects who had lifetime PTSD also had mothers who had PTSD.

Adolescent↗
PubMed1995

Monosomy 7 and activating RAS mutations accompany malignant transformation in patients with congenital neutropenia.

Individuals with severe forms of congenital neutropenia suffer from recurrent infections. The therapeutic use of recombinant human granulocyte colony-stimulating factor (rhG-CSF) to increase the neutrophil count is associated with fewer infections and an improved quality of life. However, the long-term effects of this new therapy are largely unknown. In particular, it is unclear if myeloid leukemia, a known complication of some forms of congenital neutropenia, will occur with increased frequency among patients who receive long-term treatment with hematopoietic growth factors. We report 13 patients with congenital disorders of myelopoiesis who developed leukemic transformation with either myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) and 1 who acquired a clonal cytogenetic abnormality without evidence of MDS or AML while receiving rhG-CSF. The bone marrows of 10 patients showed monosomy 7 and 5 had activating RAS mutations. These abnormalities were not detected in pretreatment bone marrows and cessation of rhG-CSF was not associated with either clinical improvement or cytogenetic remission. We conclude that patients with severe forms of congenital neutropenia are at relatively high risk of developing MDS and AML. The occurrence of monosomy 7 and RAS mutations in these cases suggests that the myeloid progenitors of some patients are genetically predisposed to malignant transformation. The relationship between therapeutic rhG-CSF and leukemogenesis in patients with severe chronic neutropenia is unclear.

Adolescent↗
PubMed1995

Prospective studies of thyroid function in patients receiving gold therapy.

Gold inhibits the Type I deiodinase that provides the bulk of circulating T3 in humans. We prospectively studied thyroid function in patients receiving increasing parenteral cumulative gold doses. Eight consecutive euthyroid patients with rheumatoid or psoriatic arthritis who were initiating intramuscular gold therapy were enrolled. Serum thyroid hormone levels (total T4, T3, and rT3) and TSH were measured for each subject at various levels during gold therapy. For analysis, the free T4 and free T3 indices, TSH concentrations, and T4/T3 ratios were correlated with cumulative gold dose. Neither individual nor pooled linear regressions showed a significant correlation between cumulative gold dose and any of the thyroid function parameters. Thyroid function is not affected in patients receiving up to 1500 mg of gold compounds. The most likely explanation for this is that gold principally accumulates in the Kupffer cells and renal cortex and these cells do not express Type I deiodinase.

Adult↗
PubMed1994

Prenatal evaluation and in utero platelet transfusion for thrombocytopenia absent radii syndrome.

A fetus with absent radii in both forearms was discovered on routine ultrasound examination performed at 18 weeks of pregnancy. No other significant abnormalities were found, and no signs of haemorrhage were detected. Serial ultrasound examinations revealed no evidence of fetal internal bleeding. At 37 weeks of pregnancy, a CBC obtained by cordocentesis under ultrasound guidance confirmed the diagnosis of thrombocytopenia absent radii (TAR) syndrome. Apheresis platelets were transfused into the umbilical vein to correct the thrombocytopenia and was followed by an uncomplicated delivery. No bleeding was encountered during the remainder of the baby's neonatal course. We conclude that TAR syndrome can be readily identified prenatally on sonogram, and if severe thrombocytopenia is confirmed by cordocentesis, platelets should be transfused to diminish the risk of serious internal bleeding during and immediately after delivery.

Adult↗
PubMed1991

an unusual family cancer syndrome manifested in young siblings.

Three siblings whose mother had an ovarian mass excised as a teenager all developed malignancies in late childhood. Two were diagnosed as having malignant germ cell tumors of the ovary, whereas the third was found to have a soft tissue sarcoma. No underlying familial disease or constitutional chromosomal aberration has been detected and no known carcinogenic chemical exposure has been identified. All three children have been successfully treated with chemotherapy and are doing well off treatment. This is the first family cancer syndrome reported to have an association of ovarian germ cell tumors with embryonal sarcoma.

Adolescent↗
PubMed1991

The effects of cyclosporin A on eicosanoid excretion in patients with rheumatoid arthritis.

Alterations in renal eicosanoid levels have been postulated as a factor in cyclosporin A (CSA) nephrotoxicity. The effects of CSA on renal eicosanoid excretion in rheumatoid arthritis were studied over a 24-week period, during which treatment with nonsteroidal antiinflammatory drugs was discontinued. The initial dosage of CSA was 4 mg/kg/day; at week 24, the mean dosage of CSA was 3.9 mg/kg/day. At week 24, the mean (+/- SD) serum creatinine level (1.04 +/- 0.24 mg/dl) was 32% above the baseline value; renal blood flow had decreased by 21% (P less than 0.03) and the glomerular filtration rate had decreased by 16%. There was a significant increase (P less than 0.03) in the 2,3-dinor thromboxane B2 level at week 2, but there was no significant change in the levels of the other eicosanoids. This study demonstrates that after CSA treatment, there is a selective increase in a thromboxane metabolite that parallels an increase in renal vascular resistance, even in the absence of nonsteroidal antiinflammatory drugs, and with unimpaired formation of other vasodilator eicosanoids.

Adult↗
PubMed1990

Marrow hypoplasia associated with congenital neurologic anomalies in two siblings.

Two siblings with congenital neurologic structural anomalies and delayed-onset selective bone marrow hypoplasia in a previously undescribed constellation of symptoms are presented. Differences between these cases and other well known syndromes are discussed. The importance of this association is the implication that children with congenital neurologic abnormalities may be at increased risk for the development of hypoplastic hematopoietic conditions.

Abnormalities, Multiple↗
PubMed1990

Vasculitis with recurrent pulmonary hemorrhage in a long-term survivor after autologous bone marrow transplantation.

We report an unusual vasculitic syndrome in a long-term survivor of autologous bone marrow transplant. Clinical and pathologic studies revealed a cutaneous and pulmonary leukocytoclastic vasculitis complicated by recurrent pulmonary hemorrhage. Serologic studies revealed an elevated anti-neutrophil cytoplasmic antibody titer. The vasculitis has been successfully controlled with prednisone, cyclophosphamide, and trimethoprim/sulfamethoxazole.

Adult↗