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Biomedical subjects

R Herndon

Publications and source records attributed to R Herndon.

6 recordsLinked to original sources
PubMed2004

Identifying and treating patients with suboptimal responses.

Multiple sclerosis (MS) is an immune-mediated neurologic disease in which acute inflammatory events early in the disease course contribute to subsequent neurologic disability. The early relapsing inflammatory phase is followed by a progressive degenerative phase in which the frequency of acute inflammatory attacks diminishes but progressive loss of neurologic function continues. Current immune therapies are most effective in suppressing the acute inflammatory events that characterize the earlier stages of disease. Optimal suppression of these inflammatory events is likely to have the best potential for delaying or preventing loss of axons and decline in neurologic function. In view of these considerations, and because MS is a heterogeneous disease and response to disease-modifying agents (DMA) varies across individuals, it is important to identify suboptimal responders as early as possible to allow therapeutic modification while the opportunity to avert future loss of function remains. At present, no criteria for identifying suboptimal responders have been validated. In January 2004, a group of neurologists from 16 MS centers in the United States met to develop a consensus on criteria for defining suboptimal response for use in compelling clinical situations and to prompt clinical studies to validate the efficacy of these criteria. Consensus criteria included relapse rates of either 1/year or unchanged from pretreatment rates, incomplete recovery from multiple attacks, evolution of polyregional neurologic involvement, recurrent brainstem or spinal cord lesions, and cumulative loss of neurologic function sufficient to disrupt daily activities. The panel then considered the use of mitoxantrone for patients with worsening MS and a suboptimal response to DMA therapy.

Clinical Trials as Topic↗
PubMed1994

Advances in specific therapy for multiple sclerosis.

During the past year, two new agents have been demonstrated to be of value in multiple sclerosis. The first agent, a form of recombinant interferon beta (Betaseron; Berlex Labs, Cedar Knolls, NJ), is effective in reducing relapses and also prevent accumulation of brain lesions over time, but has no demonstrated effect on the accumulation of disability over time. The second agent, methylprednisolone (Solumedrol; The Upjohn Co., Kalamozoo, MI), administered in megadose pulses over several days and followed by an oral prednisone taper, reduces the conversion rate of patients with optic neuritis to multiple sclerosis by approximately 50% over 2 years compared with placebo or oral prednisone alone. The mechanisms by which these agents exert their benefits are incompletely understood, but both have complex, relatively widespread effects on the immune systems. The demonstration of efficacy for both of these agents represent landmarks in the search for an effective treatment for multiple sclerosis; both agents seem to provide prophylaxis against future relapses, and methylprednisolone seems to delay the development of the disease. Their introduction into the clinical environment will undoubtedly have a profound effect on the day-to-day care of multiple sclerosis patients as well as the designs of future basic and clinical research. Other new therapies that have substantial potential for benefit in multiple sclerosis but require further definitive study include intramuscular copolymer 1 for relapsing disease and low-dose oral methotrexate and booster doses of intravenous cyclophosphamide for chronic progressive disease.

Adrenal Cortex Hormones↗
PubMed1993

Intermittent cyclophosphamide pulse therapy in progressive multiple sclerosis: final report of the Northeast Cooperative Multiple Sclerosis Treatment Group.

Previous studies reported that a 2- to 3-week course of IV cyclophosphamide plus adrenocorticotropic hormone (ACTH) induction can temporarily halt progressive MS for a period of 12 months in the majority of patients treated, after which reprogression occurs. The Northeast Cooperative Multiple Sclerosis Treatment Group was formed to determine whether outpatient pulse cyclophosphamide therapy could affect reprogression and whether there were differences between a modified induction regimen and the previously published regimen. Two hundred fifty-six progressive MS patients were randomized into four groups to receive IV cyclophosphamide/ACTH via the previously published versus a modified induction regimen, with or without outpatient IV cyclophosphamide boosters (700 mg/m2 every other month for 2 years). There were blinded evaluations performed every 6 months. Results demonstrate that (1) there were no differences between the modified and the published induction regimens either in terms of initial stabilization or subsequent progression; (2) without boosters, the majority of patients continued to progress; and (3) in patients receiving boosters, there was a statistically significant benefit at 24 months and 30 months (p = 0.04). Time to treatment failure after 1 year was also significantly prolonged in the booster versus the nonbooster group (p = 0.03). Age was the most important variable that correlated with response to therapy in that amelioration of disease progression occurred primarily in patients 40 years of age or younger. Boosters had a significant benefit on time to treatment failure in patients ages 18 to 40, p = 0.003, but not in patients ages 41 to 55, p = 0.97.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1987

Intrathecally administered natural human fibroblast interferon reduces exacerbations of multiple sclerosis. Results of a multicenter, double-blind study.

A randomized, double-blinded, placebo-controlled, two-year multicenter study demonstrated that natural human fibroblast interferon (interferon beta) administered intrathecally (IT) is effective in reducing the exacerbations of exacerbating-remitting multiple sclerosis (MS). The mean reduction in exacerbation rate of 34 patients with MS who received interferon beta administered IT was significantly greater during the study than that of 35 control patients who received placebo. The prestudy exacerbation rates were comparable for both patients who received interferon beta and control patients, but the exacerbation rate of patients receiving interferon beta at the end of the study was significantly lower than that of the control patients. Interferon beta was administered by nine or ten lumbar punctures for the first six months of the study, and observations were continued for two years. In 95% of the recipients, interferon beta therapy was well tolerated, and the side effects experienced were clearly acceptable for the benefits achieved. Low doses of indomethacin dramatically reduced the toxicity of interferon beta therapy and played an important role in successful double blinding. This study confirms a preliminary report on 20 patients that initially suggested that interferon beta administered IT was of benefit in patients with MS. The number of treatments was fewer and the dosage of interferon beta administered was less in the present study than in the preliminary one. It is possible that even fewer treatments with lower doses of interferon beta administered might provide a similar degree of prophylaxis against exacerbations.

Adult↗
PubMedDate not supplied

Multicentre double-blind study of effect of intrathecally administered natural human fibroblast interferon on exacerbations of multiple sclerosis.

In this randomised, double-blind, placebo-controlled, 2-year multicentre study intrathecally administered natural human fibroblast interferon (IFN-B) was effective in reducing exacerbations of multiple sclerosis (MS) in patients with exacerbating/remitting disease. The mean reduction in exacerbation rate of 34 patients who received IFN-B (recipients) was significantly greater during the study than that of 35 patients who received placebo (p less than 0.04). The prestudy exacerbation rates were comparable in recipients and controls, but the rate at the end of the study was significantly lower in recipients than in controls (p less than 0.001). IFN-B was given by nine or ten lumbar punctures over the first 6 months of the study, and patient observations continued for 2 years. IFN-B was well tolerated in 95% of the recipients, and the side-effects experienced were clearly acceptable for the benefits achieved. Low doses of indomethacin reduced the toxicity of IFN-B and played an important role in successful double-blinding.

Clinical Trials as Topic↗