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Biomedical subjects

J N Woody

Publications and source records attributed to J N Woody.

At least 19 recordsLinked to original sources
PubMed1998

Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor alpha monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis.

OBJECTIVE: To evaluate the efficacy, pharmacokinetics, immunogenicity, and safety of multiple infusions of a chimeric monoclonal anti-tumor necrosis factor alpha antibody (cA2) (infliximab; Remicade, Centocor, Malvern, PA) given alone or in combination with low-dose methotrexate (MTX) in rheumatoid arthritis (RA) patients. METHODS: In a 26-week, double-blind, placebo-controlled, multicenter trial, 101 patients with active RA exhibiting an incomplete response or flare of disease activity while receiving low-dose MTX were randomized to 1 of 7 groups of 14-15 patients each. The patients received either intravenous cA2 at 1, 3, or 10 mg/kg, with or without MTX 7.5 mg/week, or intravenous placebo plus MTX 7.5 mg/week at weeks 0, 2, 6, 10, and 14 and were followed up through week 26. RESULTS: Approximately 60% of patients receiving cA2 at 3 or 10 mg/kg with or without MTX achieved the 20% Paulus criteria for response to treatment, for a median duration of 10.4 to >18.1 weeks (P < 0.001 versus placebo). Patients receiving cA2 at 1 mg/kg without MTX became unresponsive to repeated infusions of cA2 (median duration 2.6 weeks; P=0.126 versus placebo). However, coadministration of cA2 at 1 mg/kg with MTX appeared to be synergistic, prolonging the duration of the 20% response in >60% of patients to a median of 16.5 weeks (P < 0.001 versus placebo; P=0.006 versus no MTX) and the 50% response to 12.2 weeks (P < 0.001 versus placebo; P=0.002 versus no MTX). Patients receiving placebo infusions plus suboptimal low-dose MTX continued to have active disease, with a Paulus response lasting a median of 0 weeks. A 70-90% reduction in the swollen joint count, tender joint count, and C-reactive protein level was maintained for the entire 26 weeks in patients receiving 10 mg/kg of cA2 with MTX. In general, treatment was well tolerated and stable blood levels of cA2 were achieved in all groups, except for the group receiving 1 mg/kg of cA2 alone, at which dosage antibodies to cA2 were observed in approximately 50% of the patients. CONCLUSION: Multiple infusions of cA2 were effective and well tolerated, with the best results occurring at 3 and 10 mg/kg either alone or in combination with MTX in approximately 60% of patients with active RA despite therapy with low-dose MTX. When cA2 at 1 mg/kg was given with low-dose MTX, synergy was observed. The results of the trial provide a strategy for further evaluation of the efficacy and safety of longer-term treatment with cA2.

Adult↗
PubMed1997

Suppression of fever and the acute-phase response in a patient with juvenile chronic arthritis treated with monoclonal antibody to tumour necrosis factor-alpha (cA2).

Juvenile chronic arthritis (JCA) is the commonest chronic rheumatic disorder of childhood. Although conventional therapy of JCA continues to improve, many patients experience long-term ill health as a result of their disease or treatment. In adult rheumatoid arthritis (RA), similar concerns have led to the development of therapies designed to interfere in key disease processes. One such therapy is cA2, a chimeric neutralizing monoclonal antibody to the inflammatory cytokine, tumour necrosis factor-alpha (TNF-alpha). The administration of cA2 in adult RA has led to impressive short-term suppression of disease, with a good safety profile. Here, we report the first use of cA2 in childhood arthritis, choosing a patient with severe systemic-onset JCA, resistant to conventional therapies. The patient received two i.v. infusions of cA2, each at a dose of 10 mg/kg, separated by 1 week. The treatment was well tolerated and induced rapid control of fever, anorexia and serositis, together with downregulation of interleukin (IL)-6, soluble TNF receptors (sTNFR) and IL-1ra, and the acute-phase proteins C-reactive protein (CRP) and serum amyloid A (SAA). In contrast, we saw no significant improvement in joint pain or tenderness. Our findings suggest that TNF-alpha is a mediator of fever and other systemic aspects of disease in systemic JCA. TNF-alpha blockade as a treatment modality in JCA deserves further study.

Acute-Phase Reaction↗
PubMed1996

Deactivation of vascular endothelium by monoclonal anti-tumor necrosis factor alpha antibody in rheumatoid arthritis.

OBJECTIVE: To assess whether monoclonal antibody to tumor necrosis factor alpha (TNF alpha) reduces endothelial activation in rheumatoid arthritis (RA). METHODS: Levels of serum E-selectin, intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1), and circulating leukocytes (differential counts) were measured in RA patients before and up to 4 weeks after infusion of either placebo or chimeric anti-TNF alpha antibody cA2 (1 or 10 mg/kg). RESULTS: Treatment with anti-TNF alpha decreased serum E-selectin and ICAM-1 levels, with the earliest detectable changes observed on days 1-3 after anti-TNF alpha infusion. No effect on VCAM-1 levels was detected. In parallel, there was a rapid and sustained increase in circulating lymphocytes. The extent of the decrease in serum E-selectin and ICAM-1 levels and the increase in lymphocyte counts was significantly higher (P < or = 0.05) in patients in whom a clinical benefit of anti-TNF alpha was observed ( > or = 20% response, by Paulus criteria, at week 4) compared with that in patients who failed to respond to anti-TNF alpha at this time point. CONCLUSION: We propose that decreased serum levels of adhesion molecules may reflect diminished activation of endothelial cells in the synovial microvasculature, leading to reduced migration of leukocytes into synovial joints, and thus prolonging the therapeutic effect of anti-TNF alpha in RA.

Antibodies, Monoclonal↗
PubMed1996

Inhibition of immunoreactive tumor necrosis factor-alpha by a chimeric antibody in patients infected with human immunodeficiency virus type 1.

Tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine known to stimulate human immunodeficiency virus type 1 (HIV-1) replication, has been implicated in the pathogenesis of HIV-1 infection. Inhibition of TNF-alpha by a chimeric humanized monoclonal antibody, cA2, was investigated in 6 HIV-1-infected patients with CD4 cell counts < 200/mm3. Two consecutive infusions of 10 mg/kg 14 days apart were well tolerated, and a prolonged serum half-life for cA2 (mean, 257 +/- 70 h) was demonstrated. Serum immunoreactive TNF-alpha concentrations fell from a mean prestudy value of 6.4 pg/mL (range, 4.2-7.9) to 1.1 pg/mL (range, 0.5-2.2) 24 h after the first infusion and returned to baseline within 7-14 days. A similar response was seen after the second infusion. No consistent changes in CD4 cell counts or plasma HIV RNA levels were observed over 42 days. Future studies evaluating the therapeutic utility of long-term TNF-alpha suppression using anti-TNF-alpha antibodies are feasible and warranted.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Increased MRI activity and immune activation in two multiple sclerosis patients treated with the monoclonal anti-tumor necrosis factor antibody cA2.

There is evidence that treatment with an antibody to tumor necrosis factor alpha (TNF alpha) improves an animal model of multiple sclerosis (MS) and is beneficial in two systemic inflammatory disease in humans, but there are no reports about anti-TNF treatment of MS. Therefore, we treated two rapidly progressive MS patients with intravenous infusions of a humanized mouse monoclonal anti-TNF antibody (cA2) in an open-label phase I safety trial and monitored their clinical status, gadolinium-enhanced brain magnetic resonance imaging (MRI), and peripheral blood and cerebrospinal fluid (CSF) immunologic status. We did not notice any clinically significant neurologic changes in either patient. The number of gadolinium-enhancing lesions increased transiently after each treatment in both patients. CSF leukocyte counts and IgG index increased after each treatment. The transient increase in the number of gadolinium-enhancing lesions that followed each infusion of cA2 together with the increase in cells and immunoglobulin in the CSF of each patient suggest that the treatment caused immune activation and an increase in disease activity. These results suggest that further use of cA2 in MS is not warranted and that studies of other agents that antagonize TNF alpha should be carried out with frequent monitoring of gadolinium-enhanced MRIs.

Adult↗
PubMed1995

Double-blind, placebo-controlled multicenter trial using chimeric monoclonal anti-CD4 antibody, cM-T412, in rheumatoid arthritis patients receiving concomitant methotrexate.

OBJECTIVE: To evaluate the clinical response to and safety of single and repeat doses of a chimeric anti-CD4 monoclonal antibody, cM-T412, in patients with rheumatoid arthritis (RA) concomitantly treated with a stable regimen of low-dose methotrexate. METHODS: Sixty-four patients with refractory RA, who were already receiving stable doses of methotrexate, were randomized into a multicenter, double-blind, placebo-controlled trial to receive 3 monthly treatments with either a placebo, or 5, 10, or 50 mg cM-T412, given intravenously. RESULTS: Using > or = 50% improvement in swollen joint counts as a criterion for clinical response, 13%, 13%, 18%, and 13% of patients receiving 50, 10, or 5 mg cM-T412, or the placebo, respectively, exhibited a clinical response at 3 months of therapy. Using > or = 50% improvement in tender joint counts as a measure of clinical efficacy at 3 months, 19%, 13%, 12%, and 6% of patients receiving 50, 10, or 5 mg cM-T412, or the placebo, respectively, exhibited a clinical response. "Flu-like" symptoms (fever, chills, rigor) within 24 hours of the infusion occurred more frequently in the groups receiving 50-mg (29%) and 10-mg (31%) doses of cM-T412 than those receiving 5 mg cM-T412 (12%) or the placebo (13%). Significant CD4+ T cell depletion occurred in the 50-mg group (mean of 353 CD4+ T cells/mm3 at 6 months versus 856 CD4+ T cells/mm3 at baseline). All patients were followed up for 12 months after the final treatment; no opportunistic infectious complications occurred. CONCLUSION: Treatment with cM-T412 in this cohort of RA patients who were also taking methotrexate was not associated with clinical efficacy or enhanced toxicity from infectious complications, despite significant peripheral CD4+ T cell depletion.

Adult↗
PubMed1994

Repeated therapy with monoclonal antibody to tumour necrosis factor alpha (cA2) in patients with rheumatoid arthritis.

Our in-vitro, animal, and early clinical data suggest that tumour necrosis factor alpha (TNF alpha) is an important target for specific biological therapy in rheumatoid arthritis. We report the results of repeated treatment with a chimeric monoclonal antibody to TNF alpha (cA2) in patients having disease flares. 7 patients originally enrolled in an open-label trial completed two to four cycles, each of which was followed by a good clinical response, with median improvements in the swollen-joint count and C-reactive protein exceeding 80%. cA2 may be useful therapy in the control of acute disease flares in rheumatoid arthritis and treatment programmes including cA2 may be effective in the long-term management of this disease.

Antibodies, Monoclonal↗
PubMed1994

Etiology of acute diarrhea among United States Embassy personnel and dependents in Cairo, Egypt.

The purpose of this study was to identify the enteropathogens causing acute diarrheal disease in Americans living in the North Africa/Middle East region during a 34-month period from February 12, 1985 to December 30, 1987 to guide preventive and therapeutic measures. Stool specimens were examined and an epidemiologic questionnaire was administered to patients with acute diarrhea at the Outpatient Health Unit of the United States Embassy in Cairo, Egypt. The subjects consisted of 126 American employees and dependents of the U. S. Embassy in Cairo, Egypt with diarrhea of less than two-weeks duration. Subjects received routine medical care administered by the U.S. Embassy Medical staff. A possible etiologic agent was detected in 41% of the subjects. Enteroadherent Escherichia coli was the most commonly isolated enteropathogen. A high degree of antimicrobial resistance was noted among the bacterial isolates, but all were susceptible to the quinolone antibiotics. Episodes of acute diarrhea occurring among American expatriates in Cairo, Egypt were primarily of bacterial etiology, but only a small portion were caused by the bacterial pathogens routinely identified in a standard clinical bacteriology laboratory. Most of the diarrheal episodes were due to noninvasive enteroadherent E. coli that may cause prolonged disease requiring antimicrobial therapy.

Acute Disease↗
PubMed1993

Antilipid a monoclonal antibody HA-1A: immune complex clearance of endotoxin reduces TNF-alpha, IL-1 beta and IL-6 production.

HA-1A is a human monoclonal IgM antibody which recognizes the lipid A component of lipopolysaccharide (LPS). This antibody has reduced mortality in the septic shock syndrome resulting from Gram negative bacteria, in which many of the manifestations are considered to be due to cellular activation and secretion of cytokines, most notably TNF-alpha. However HA-1A does not directly neutralize LPS effectively in vitro, and studies reported to date have not defined its mechanism of action. Here we demonstrate that HA-1A, which in the presence of complement promotes immune adherence, may inhibit LPS action by facilitating its sequestration on red blood cells and clearance to an extent that cytokine production is reduced. Incubation of LPS at clinically significant (pg/ml) does with HA-1A at therapeutic levels (e.g. 10 micrograms/ml) and complement resulted in LPS association with erythrocyte CR1 receptors. This reduced the ability of the residual, free LPS by 50-70% to induce the secretion of TNF-alpha, IL-1 beta and IL-6 from normal blood mononuclear cells. This mechanism is likely to be operative in vivo, and could account for the protective effect of HA-1A, and its reduction of TNF-alpha production in vivo.

Antibodies, Monoclonal↗
PubMed1993

Antilipid A monoclonal antibody HA-1A decreases the capacity of bacterial lipopolysaccharide to activate human vascular endothelial cells by an immune adherence mechanism.

Human monoclonal IgM antibody HA-1A, which recognizes the lipid A component of bacterial lipopolysaccharide (LPS), has been shown to reduce mortality in Gram negative septicemia. The vascular endothelial lining of blood vessels, which controls leucocyte traffic and activation, as well as haemostatic balance, may be one of the primary targets of LPS action during sepsis. In earlier studies we have described HA-1A-induced immune adherence of LPS to complement receptors on erythrocytes, and showed that pre-incubation with HA-1A, in the presence of complement and red blood cells, markedly reduced LPS-induced cytokine production from peripheral blood mononuclear cells. In the present study, we measured the effect of immune adherence of LPS in the presence of HA-1A on the responses of cultured endothelial cells, and found that subsequent expression of adhesion molecules such as E-selectin, ICAM-1 and VCAM-1, and secretion of the cytokines interleukin-6 and granulocyte-macrophage colony stimulating factor were markedly reduced. Moreover, the ability of LPS to increase levels of tissue factor procoagulant activity on endothelial cells was markedly diminished by LPS immune adherence to HA-1A. This decrease in endothelial activation in response to LPS following immune adherence to HA-1A may play a significant role in the protective effect of HA-1A in vivo during the course of Gram negative sepsis.

Antibodies, Monoclonal↗
PubMed1993

Respiratory disease among military personnel in Saudi Arabia during Operation Desert Shield.

OBJECTIVES: The purpose of this study was to determine whether respiratory disease due to crowded living conditions and high levels of suspended and blowing sand had a major adverse impact on US military personnel during Operation Desert Shield. METHODS: A questionnaire survey was administered to 2598 combat troops stationed in Northeast Saudi Arabia for a mean of 102 days. Samples of surface sand from seven different locations were analyzed by scanning electron microscopy and x-ray diffraction. RESULTS: Among surveyed troops, 34.4% reported a sore throat, 43.1% complained of a cough, 15.4% complained of chronic rhinorrhea, and 1.8% were unable to perform their routine duties because of upper respiratory symptoms. Evaluation of sleeping accommodations indicated that complaints of a sore throat and cough were most closely associated with sleeping in air-conditioned buildings; in contrast, complaints of rhinorrhea were associated with exposure to the outdoor environment while living in tents. Sand samples consisted mostly of quartz, with just 0.21% by weight of respirable size (< 10 microns in diameter). CONCLUSIONS: These findings indicate that upper respiratory complaints were frequent among Operation Desert Shield troops and were related both to the troops' housing and to their exposure to the outside environment.

Adolescent↗
PubMed1993

The Navy Forward Laboratory during Operations Desert Shield/Desert Storm.

The Navy Forward Laboratory (NFL) was an advanced infectious disease laboratory which provided a theater-wide reference diagnostic capability during Operations Desert Shield/Storm. During Operation Desert Shield, when massive numbers of troops were being deployed, the NFL primarily supported medical personnel in the diagnosis and treatment of infectious diseases. During the war, the laboratory provided rapid biologic warfare diagnostic support. The NFL demonstrated the benefits of a comprehensive, on-site diagnostic laboratory when large numbers of troops are deployed to high-risk areas and demonstrated the importance of military medical research laboratories for training of scientists and physicians, threat assessment, and product development.

Humans↗
PubMed1992

T-cell-targeted immunotherapy.

The pace of T-cell research is matched only by the speed with which fundamental advances are being developed as new therapies. This report from a recent meeting updates developments in a number of immunointervention strategies.

AIDS Vaccines↗
PubMed1992

Detection of spores of Bacillus anthracis using the polymerase chain reaction.

The polymerase chain reaction (PCR) was used to identify spores of Bacillus anthracis. By using an assay capable of amplifying a 1247-bp fragment from the gene that encodes the edema factor of B. anthracis, as few as 10(3) copies of a plasmid containing the edema factor gene and as few as 2 x 10(4) spores were detected. Subjecting the product of this PCR to a second PCR designed to amplify a 208-bp fragment nested within the 1247-bp product improved detection to a single plasmid copy per PCR and to two spores of B. anthracis per PCR.

Bacillus anthracis↗
PubMed1991

A partnership in epidemiological research.

Four medical research teams completed ten epidemiological investigations in Djibouti and thus provided the country's Ministry of Health with valuable information on infectious disease risks. A major factor contributing to the success of the work was the high degree of cooperation between the Ministry, a United States naval medical research unit, and the World Health Organization as coordinator.

Africa↗
PubMed1991

Travelers' diarrhea among United States military personnel during joint American-Egyptian armed forces exercises in Cairo, Egypt.

A study was conducted of travelers' diarrhea in a United States military population on deployment in Cairo, Egypt, during July and August 1987. Acute diarrhea requiring medical attention developed in 183 (4%) of 4,500 troops. A possible etiologic agent was identified in 49% of all diarrhea cases. Enteric pathogens associated with cases of diarrhea included: Enterotoxigenic Escherichia coli (17% ST-producers, 13% LT-producers, and 3% LT/ST-producers); Shigella (9%); Campylobacter spp. (2%); Salmonella (2%); and Vibrio cholerae non-01 serogroup (2%). Other enteric pathogens isolated from one episode each of diarrhea included Aeromonas hydrophila group, Plesiomonas shigelloides, and Bacillus cereus. Yersinia enterocolitica, enteroinvasive E. coli, intoxications by Clostridium perfringens and Clostridium difficile, and pathogenic enteric parasites were not found in any of the 183 patients with diarrhea. A survey of military personnel not requesting medical care indicated that up to 40% of troops may have had diarrhea during this deployment. Acute gastroenteritis is a potential cause of substantial morbidity in U.S. military personnel deployed to Egypt.

Adolescent↗