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J Isaacs

Publications and source records attributed to J Isaacs.

At least 19 recordsLinked to original sources
PubMed2005

Treatment of stiff person syndrome with rituximab.

This case report is about the novel use of the anti-CD20 antibody, rituximab, in the treatment of a 41 year old woman with stiff person syndrome. She was admitted to hospital as an emergency with prolonged and painful extensor spasms affecting the neck and back, arms, and legs. The disease had progressed despite a favourable initial response to conventional treatment with intravenous immunoglobulin and cytotoxics. Treatment with rituximab induced a lasting clinical remission.

Adult↗
PubMed2004

Longitudinal study of Pelvicol pubovaginal slings using magnetic resonance imaging.

The mechanism of urinary continence is complicated and is poorly understood. One current opinion is that there is an absence or weakness of the endopelvic fascial supports of the urethra. Pubovaginal slings are rapidly becoming the surgical procedure of choice in the management of urodynamic stress incontinence but their method of action is unclear. This study using magnetic resonance imaging shows how a pubovaginal sling can restore the normal anatomy and continence and adds to the global understanding of this condition.

Female↗
PubMed2001

Autologous stem cell transplantation for rheumatoid arthritis--interim report of 6 patients.

We assessed the safety and efficacy of autologous stem cell transplantation (ASCT) using T cell depleted grafts in the treatment of severe rheumatoid arthritis. Methods included mobilization 2 g/m2 cyclophosphamide (Cy) and granulocyte-colony stimulating factor; graft manipulation of positive CD34+ and negative T cell selection; and conditioning by 200 mg/kg Cy. All 6 patients improved according to American College of Rheumatology response criteria (one patient ACR70, 2 ACR50, 3 ACR20), but relapsed at 1.5-9 months when they began cyclosporine A (CSA). Five improved (one patient ACR remission, 2 ACR70, one ACR50, one improved but did not satisfy ACR response criteria). No serious complications occurred during ASCT or up to 30 months' followup. There was prolonged reduction in CD4+ T cells. ASCT is safe and has short term efficacy. T cell purging does not prevent relapse. Five patients responded to CSA when their disease had previously been refractory, suggesting an immunomodulatory effect. No serious infectious complications occurred despite prolonged reduction in CD3+CD4+ lymphocytes.

Adult↗
PubMed2000

Treatment of poor-prognosis early rheumatoid arthritis. A randomized study of treatment with methotrexate, cyclosporin A, and intraarticular corticosteroids compared with sulfasalazine alone.

OBJECTIVE: To determine whether a regimen of methotrexate, cyclosporin A, and corticosteroids introduced at onset in poor-prognosis rheumatoid arthritis (RA) can produce a significant improvement in outcome compared with standard monotherapy with sulfasalazine (SSZ). METHODS: Eighty-two consecutive patients presenting with new, untreated RA of less than 12 months' duration who fulfilled criteria for poor long-term outcome were randomized to receive either combination therapy (n = 40) or SSZ alone (n = 42). The primary outcome measures were remission and American College of Rheumatology (ACR) criteria for 20% improvement at 48 weeks. RESULTS: After 48 weeks, the numbers of patients who met the ACR criteria for 20% improvement were not significantly different between the two groups (combination 58% versus SSZ 45%), and similar numbers of patients had persisting clinical remission (approximately 10% both groups). During the first 3 months, there were significantly greater reductions in parameters of disease activity in the combination group. By 24 weeks, the swollen and tender joint counts, C-reactive protein levels, and erythrocyte sedimentation rates had fallen significantly in both groups, with a greater improvement in the swollen and tender joint count in the combination group. At 48 weeks, the radiographic damage score had increased by a median of 1 (range 0-42.5) in the combination group and 1.25 (range 0-72.5) in the SSZ group (P = 0.28; although there were significant differences in the scores for the right hand). There were significantly fewer withdrawals due to lack of efficacy in the combination group than in the SSZ group (1 of 40 versus 10 of 42; P = 0.007). In the combination group, dose reduction was needed in 22.5% because of hypertension and in 22.5% because of elevated creatinine levels. Over 48 weeks, serum creatinine increased in both groups, but particularly in the combination arm. CONCLUSION: In poor-prognosis RA patients, "aggressive" combination therapy led to more rapid disease suppression but did not result in significantly better ACR response or remission rates. This suggests that in poor-prognosis disease, an approach based on identifying patients with poor treatment responses before extra therapy is added ("step-up" approach) may be more appropriate than the use of combination therapy in all patients from the outset.

Adrenal Cortex Hormones↗
PubMed1999

The relationship between pityriasis rubra pilaris and inflammatory arthritis: case report and response of the arthritis to anti-tumor necrosis factor immunotherapy.

Pityriasis rubra pilaris (PRP) refers to a group of erythematous, scaling dermatologic conditions that have been associated with seronegative arthritis. We report a case of polyarthritis in a young man with PRP in which magnetic resonance imaging suggested an entheseal-based pathology for the joint disease. The arthritis, but not the skin condition, demonstrated dramatic response to anti-tumor necrosis factor immunotherapy.

Adolescent↗
PubMed1999

Undiagnosed maternal phenylketonuria: the need for prenatal selective screening or case finding.

OBJECTIVES: The aims of this article are to report on a review of cases of maternal phenylketonuria in the International Maternal Phenylketonuria Collaborative Study that were initially diagnosed during or after a pregnancy, to alert health care practitioners to the possible existence of women with undiagnosed phenylketonuria whose fetuses are at risk, and to emphasize that not all adults with untreated phenylketonuria are mentally retarded. STUDY DESIGN: The study was conducted through retrospective database review. RESULTS: Of 414 women with live-born infants, 17 fulfilled our criteria. Six had phenylketonuria diagnosed after they had produced >/=1 affected offspring, 2 had phenylketonuria diagnosed as a result of transient postnatal hyperphenylalaninemia in an offspring, and 9 had phenylketonuria diagnosed by prenatal screening. Undiagnosed maternal phenylketonuria in North America and Europe is currently estimated at 1 case/100,000 births; this rate could be higher elsewhere. CONCLUSIONS: Physicians and midwives should consider a protocol of selective prenatal screening or case finding to detect undiagnosed phenylketonuria among their patients.

Adolescent↗
PubMed1999

Shiga toxin-producing Escherichia coli can impair T84 cell structure and function without inducing attaching/effacing lesions.

Enteropathogenic Escherichia coli (EPEC) intimately adhere to epithelial cells producing cytoskeletal rearrangement with typical attaching and effacing lesions and altered epithelial barrier and transport function. Since EPEC and Shiga toxin-producing E. coli (STEC) share similar genes in the "locus for enterocyte effacement" (LEE) thought to cause these changes, it has been assumed that STEC shares similar pathogenic mechanisms with EPEC. The aims of this study were to compare the effects of EPEC and STEC on bacterial-epithelial interactions and to examine changes in epithelial function. T84 monolayers were infected with STEC O157:H7 (wild strain EDL 933 or non-toxin-producing strain 85/170), EPEC (strain E2348/69), or HB101 (nonpathogenic) and studied at various times after infection. EPEC bound more avidly than EDL 933, but both strains exhibited greater binding than HB101. Attaching and effacing lesions and severe disruption to the actin cytoskeleton were observed in EPEC by 3 h postinfection but not in EDL 933 or HB101 at any time point. EPEC and EDL 933 increased monolayer permeability to [(3)H]mannitol 5- to 10-fold. In contrast to EPEC, EDL 933 completely abolished secretagogue-stimulated anion secretion as assessed under voltage clamp conditions in Ussing chambers. Several other STEC strains induced changes similar to those of EDL 933. In conclusion, STEC impairs epithelial barrier function and ion transport without causing major disruption to the actin cytoskeleton. Pathogenic factors other than products of LEE may be operant in STEC.

Bacterial Adhesion↗
PubMed1998

Neutralizing TNF-alpha activity modulates T-cell phenotype and function in experimental autoimmune uveoretinitis.

Inhibiting TNF-alpha activity prevents tissue destruction without inhibiting retinal T cell infiltration in experimental autoimmune uveoretinitis (EAU) in Lewis rats. To further determine the role of TNF-alpha in autoimmune uveitis we characterized T cells isolated from retinae after treatment with a TNF-alpha antagonist. TNF-alpha activity was neutralized in vivo with a p55 TNF-alpha receptor-Ig fusion protein (sTNFr-Ig), administered 8 and 10 days after induction of EAU with heterologous retinal antigens. Retinal T-cell phenotype expression was examined by flow cytometry with respect to OX22 status (CD45RBlow or CD45RBhigh), activation (OX40 and CD25 expression) and rate of T-cell apoptosis (Annexin V+PI- expression). Lymphocyte reactivity was assessed by proliferation responses and cytokine production to retinal antigens. Despite greater than 40% of CD4+ T cells being activated at the height of disease, the proportion of OX22low expression was reduced and T cells exhibited reduced IFN-gamma and elevated IL-4 production. Retinal T cells maintained antigen-specific proliferation and demonstrated a low apoptotic rate. Although in both animal groups, comparable numbers of T cells were isolated, neutralizing TNF activity suppressed Th1 effector mechanisms protecting against target organ damage.

Animals↗
PubMed1998

Expression of the carbohydrate antigen CD15 in rat uterine epithelial cells during the early stages of pregnancy.

The presence and distribution of the carbohydrate antigen CD15 in rat uterine epithelial cells was determined using immunohistochemical localisation at both light and electron microscopical levels. Rat uterine tissue was examined on days 1, 3 and 6 of pregnancy and it was found that expression of CD15 was highly stage specific with negligible detection on days 1 or 3 of pregnancy but very strong expression at both light and electron microscopic levels on day 6. Electron microscopy using ferritin as marker revealed expression in the glycocalyx of the plasma membrane of uterine epithelial cells. This strongly stage-specific expression of CD15 and the extracellular surface localisation suggests an important role for this antigen during the early stages of pregnancy in the rat and implicates the molecule in attachment to the uterine epithelium.

Animals↗
PubMed1998

Why volunteers matter.

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American Hospital Association↗
PubMed1997

A phase 1 study to address the safety and efficacy of granulocyte colony-stimulating factor for the mobilization of hematopoietic progenitor cells in active rheumatoid arthritis.

OBJECTIVE: To examine the safety and efficacy of granulocyte colony-stimulating factor (G-CSF) alone for the mobilization of peripheral blood progenitor cells in patients with resistant active rheumatoid arthritis (RA). METHODS: Five patients with resistant active RA were studied. A dose of 5 microg/kg of G-CSF (Filgrastim) was given subcutaneously each day for 5 days, and the number of stem cells mobilized into the peripheral blood was assessed by daily CD34 counts. RA disease activity was assessed by standard clinical methods. RESULTS: The absolute numbers of peripheral blood CD34+ cells peaked on day 4, with a mean value of 0.025 x 10(9)/liter (range 0.013-0.048 x 10(9)/liter). There was no significant change in disease activity during the study or in the month following therapy. CONCLUSION: Using G-CSF alone, CD34+ progenitor peripheral blood cells were mobilized in numbers suitable for leukopheresis. G-CSF therapy was well-tolerated in patients with active RA, and was not associated with a flare during treatment or in the month following treatment.

Adult↗
PubMed1997

Psychiatric manifestations of normal-pressure hydrocephalus: a short review and unusual case.

Normal-pressure hydrocephalus (NPH) is a common cause of potentially reversible dementia. It can present with psychiatric manifestations that may hinder its diagnosis. A 68-year-old man presented with a paranoid psychosis and mild cognitive impairment, but not neurological signs or classic "triad." Gait disturbance and urinary incontinence developed later in the course of illness after the diagnosis of NPH had already been made on computed tomographic (CT) scanning. A lumbo-peritoneal shunt was performed, followed by full remission of psychotic symptoms, as well as considerable improvement in functioning, continence, and gait. This case demonstrates the need to consider NPH when older patients present with psychotic symptoms, particularly in the presence of cognitive impairment, gait disturbance, or incontinence. The decision whether to perform a shunting operation is often difficult, because selection of patients with good prognosis is still inaccurate. CT scanning of the brain is an important investigation in older patients presenting with both functional and organic disorders.

Aged↗
PubMed1996

Mechanism of first-dose cytokine-release syndrome by CAMPATH 1-H: involvement of CD16 (FcgammaRIII) and CD11a/CD18 (LFA-1) on NK cells.

The administration of the immunosuppressive humanized monoclonal antibody CAMPATH 1-H, which recognizes CD52 on lymphocytes and monocytes, is associated with a first-dose cytokine-release syndrome involving TNFalpha, IFNgamma, and IL-6 clinically. In vitro models have been used to establish the cellular source and mechanism responsible for cytokine release, demonstrating that cytokine release is isotype dependent, with the rat IgG2b and human IgG1 isotype inducing the highest levels of cytokine release, which was inhibited with antibody to CD16, the low affinity Fc-receptor for IgG (FcgammaR). Cross-linking antibody opsonized CD4 T lymphocytes failed to stimulate TNFalpha release, which together with the observation that TNFalpha release by purified natural killer (NK) cells stimulated by fixed autologous CAMPATH 1-H-opsonized targets was inhibited with anti-CD16, indicates that cytokine release results from ligation of CD16 on the NK cells, rather than Fc-receptor (FcR)-dependent cross-linking of CD52 on the targeted cell. Since the hierarchy of isotypes inducing cytokine release in these cultures matches that seen clinically, we conclude that ligation of CD16 on NK cells is also responsible for cytokine release after injection of CAMPATH 1-H in vivo.

Alemtuzumab↗
PubMed1996

Transient increase in symptoms associated with cytokine release in patients with multiple sclerosis.

Fourteen patients with multiple sclerosis were treated with the humanized monoclonal antibody CAMPATH-1H which targets the CD52 antigen present on all lymphocytes and some monocytes; four also received anti-CD4 antibody. Lymphopaenia developed rapidly and was sustained for at least 1 year. In 12 patients, the first infusion of antibody was characterized by significant exacerbation or re- awakening of pre-existing symptoms lasting several hours. These clinical effects of antibody treatment correlated with increased levels of circulating cytokines. Peak levels of tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma occurred at 2 h, whereas the rise in interleukin-6 (IL-6) was significantly delayed and peaked at 4 h after starting antibody treatment. There was a decline in CH50, indicating complement activation. The neurological symptoms could not be attributed directly to pyrexia and were not provoked (in one patient) by an artificial rise in temperature. In the remaining two patients, a single pre-treatment with intravenous methylprednisolone (500 mg) prevented both the transient increase in neurological symptoms and the cytokine release. Our results, involving 14 intensively studied patients treated with humanized monoclonal antibodies, suggested that soluble immune mediators contribute to symptom production in multiple sclerosis; the mechanism remains uncertain but, on the available evidence, we favour the interpretation that cytokines directly affect conduction through partially demyelinated pathways.

Adult↗
PubMed1996

Treatment of refractory Wegener's granulomatosis with humanized monoclonal antibodies.

Conventional immunosuppression for systemic vasculitides is limited by substantial side-effects, cumulative drug toxicity and refractoriness in some patients. Six Wegener's granulomatosis patients who had been refractory to conventional therapy for at least 6 months, were treated with humanized monoclonal antibodies specific to lymphocyte CD52 or CD4 antigens. Diagnosis was on clinicopathological grounds, supported by the presence of autoantibodies to Proteinase 3. Histological evidence of persistent disease activity was obtained for each patient. Humanized monoclonal anti-CD52, with or without anti-CD4, was given intravenously up to 40 mg/day for up to 10 days. Remission, (programmed withdrawal of drug therapy without return of refractory disease) was achieved in all patients. Cytotoxic drugs were discontinued at the time of monoclonal antibody treatment and not used again; steroids were withdrawn gradually. Four patients relapsed at 1.5, 5, 10 and 18 months, and were treated successfully with further monoclonal antibody therapy alone. Three years after the study began, five patients are well; one patient died at surgery whilst in remission. Humanized monoclonal antilymphocyte antibodies may provide an effective treatment in patients with systemic vasculitis which is refractory to steroids or cytotoxic agents, or who are intolerant of these drugs.

Adoptive Transfer↗