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Biomedical subjects

A D Goodman

Publications and source records attributed to A D Goodman.

At least 19 recordsLinked to original sources
PubMed1999

Quantitative assessment of motor fatigue and strength in MS.

OBJECTIVE: To determine the test-retest reliability of strength and fatigue measurements in patients with MS and in healthy control subjects, and to examine associations among motor fatigue, strength, and ambulatory impairment in MS patients. BACKGROUND: Motor fatigue, defined as the loss of the maximal capacity to generate force during exercise, and weakness are common in patients with MS. METHOD: Twenty ambulatory MS patients and 20 age- and sex-matched healthy control subjects participated in the study. Test-retest reliability was assessed in two identical testing sessions, separated by 3 to 5 days. Maximal voluntary isometric strength was determined by fixed myometry of seven muscle groups on each side. Motor fatigue was assessed using three exercise protocols: sustained maximal contractions (static fatigue), repetitive maximal contractions, and walking as far as 500 m. Four analysis models for static fatigue were examined for their test-retest reliability and their ability to discriminate between normal fatigue and pathologic fatigue from MS. RESULTS: Test-retest reliability in MS patients was excellent for isometric strength and very good for static fatigue. Test-retest reliability was lower for exercise protocols that involved repetitive contractions or ambulation. Compared with healthy control subjects, MS patients were weak in lower extremity muscles, but upper extremity strength was relatively preserved. Fatigue was greater in MS patients, even in muscles that were not clearly weak. There were no significant associations between strength and fatigue in any of the muscles tested. A fatigue analysis model based on the area under the force-versus-time curve gave the best combination of reliability and sensitivity to detect differences between MS patients and healthy control subjects. CONCLUSIONS: Strength and motor fatigue can be measured reliably in patients with MS. MS patients experience more fatigue than healthy control subjects during sustained contractions, repetitive contractions, and ambulation. Motor fatigue appears to be distinct from weakness because the degree of fatigue was not associated with the degree of weakness in individual muscles. Quantitative assessment of strength and fatigue may be useful to monitor changes in motor function over time in MS patients.

Adult↗
PubMed1999

Neuropsychologic status in multiple sclerosis after treatment with glatiramer.

BACKGROUND: Glatiramer acetate (Copaxone) therapy reduces clinical disease activity in relapsing-remitting multiple sclerosis (MS). OBJECTIVE: To study the effect of glatiramer therapy on neuropsychologic function as part of a randomized, placebo-controlled, multicenter trial. METHODS: Two hundred forty-eight patients with relapsing-remitting MS and mild to moderate disability (Expanded Disability Status Scale score, <5.0) were tested before and 12 and 24 months after randomization to administration of glatiramer acetate, 20 mg/d, or matching placebo. Neuropsychologic tests examined 5 cognitive domains most often disrupted in patients with MS: sustained attention, perceptual processing, verbal and visuospatial memory, and semantic retrieval. RESULTS: Baseline neuropsychologic test performance was similar in both treatment groups and was within normal range, except for impaired semantic retrieval. Mean neuropsychologic test scores were higher at 12 and 24 months than at baseline, and no differences were detected between treatment groups over time. No significant interactions were detected between treatment and either time or baseline impairment. CONCLUSIONS: Our 2-year longitudinal study showed no effect of glatiramer therapy on cognitive function in relapsing-remitting MS. Although it is possible that glatiramer therapy has no effect on cognitive function, the lack of measurable decline in cognitive function in both patient groups for 2 years limits the opportunity for glatiramer to demonstrate a therapeutic effect by minimizing such decline. Emerging treatments for MS should continue to be examined for their effect on cognitive impairment because it can be a critical determinant of disability. A greater understanding of the natural history of cognitive decline in MS is essential for a rational design of these drug trials.

Adolescent↗
PubMed1999

Association of human herpesvirus 6 with the demyelinative lesions of progressive multifocal leukoencephalopathy.

Progressive Multifocal Leukoencephalopathy (PML) is a primary demyelinating disease of the central nervous system occurring almost exclusively in individuals with impaired cell-mediated immunity. The JC polyoma virus has been accepted as the etiologic agent ofPML. Using a two-step in-situ polymerase chain reaction procedure to amplify and detect genomic DNA of human herpesvirus-6 (HHV6) in formalin-fixed paraffin-embedded archival brain tissues, a high frequency of infected cells was consistently detected in PML white matter both within and surrounding demyelinative lesions and HHV6 genome was found mainly within oligodendrocytes. Lesser amounts of HHV6 genome were detected in most normal, AIDS, and other neurological disease control tissues. Immunocytochemistry for HHV6 antigens showed actively infected nuclei of swollen oligodendrocytic morphology only within the demyelinative lesions of PML but not in adjacent uninvolved tissue. In addition, no HHV6 antigens were detectable in control tissues including brains of individuals with HIV-1 encephalopathy but without PML. Double immunohistochemical staining for JC virus large T antigen and HHV6 antigens demonstrated co-labeling of many swollen intralesional oligodendrocytes in the PML cases. The evidence suggests that HHV6 activation in conjunction with JC virus infection is associated with the demyelinative lesions of PML.

AIDS Dementia Complex↗
PubMed1997

Autoimmune hyperthyroidism in patients with multiple sclerosis treated with interferon beta-1b.

OBJECTIVE: To report symptomatic autoimmune hyperthyroidism developing in patients with multiple sclerosis (MS) treated with interferon beta-1b (IFN-beta-1b). REPORT OF CASES: A 44-year-old woman experienced gradually worsening fatigue, depression, and motor function several months after beginning therapy with IFN-beta-1b for MS. Graves disease associated with episodic palpitations, shortness of breath, hair loss, increased appetite, weight loss, and insomnia was confirmed with endocrinologic studies. Increased fatigue and weakness developed in a 52-year-old woman several months after starting IFN-beta-1b therapy. She also noted sweats, heat intolerance, palpitations, increased appetite, and irritability, and endocrinologic evaluation supported a diagnosis of Graves disease. CONCLUSIONS: To our knowledge, this is the first report of autoimmune thyroid disease associated with IFN-beta-1b treatment in patients with MS. Psoriasis has also been reported during interferon therapy for MS, and similar phenomena occur during interferon therapy for hepatitis C. Since some symptoms of thyroid dysfunction may be difficult to distinguish from typical MS-related symptoms, thyroid hormone levels should be checked when unexplained constitutional symptoms occur during IFN-beta-1b therapy.

Adjuvants, Immunologic↗
PubMed1997

Quantitative assessment of sustained-release 4-aminopyridine for symptomatic treatment of multiple sclerosis.

OBJECTIVE: To evaluate the efficacy of 4-aminopyridine sustained release (4AP SR) (fampridine, EL-970) using quantitative measures of motor function in multiple sclerosis (MS) patients. BACKGROUND: In vitro, 4AP improves conduction through demyelinated axons. A previous multicenter trial of 4AP SR using the Expanded Disability Status Scale (EDSS) as the primary outcome was unable to establish clinical efficacy. DESIGN/METHODS: Ten MS patients with stable motor deficits (EDSS 6.0-7.5) were given 4AP SR 17.5 mg bid and placebo for 1 week each in a double-blind, placebo-controlled, crossover trial. Time to walk 8 meters, time to climb four stairs, maximum voluntary isometric contraction measured quantitatively (MVICT), manual muscle testing (MMT), grip strength, EDSS, and the patient's global impression were measured. RESULTS: Timed gait was improved on 4AP SR compared with placebo in 9 of 10 subjects (p = 0.02). Timed stair climbing, MVICT, MMT, grip strength, and EDSS showed nonsignificant improvements on 4AP SR. Based on their global impressions, seven subjects preferred 4AP SR over placebo; only one preferred placebo. There were no serious side effects. CONCLUSION: 4AP SR improved motor function in MS patients. The quantitative outcomes used in this study permit more sensitive evaluation of the therapeutic effect and promise to be useful in future trials of symptomatic treatments for MS.

4-Aminopyridine↗
PubMed1997

The measurement of ambulatory impairment in multiple sclerosis.

The objective of this study was to examine the relationships between continuous measures of ambulatory impairment in MS patients and their ordinal counterparts. Much of the disability caused by MS is due to ambulatory impairment. The Expanded Disability Severity Scale (EDSS) and the Ambulation Index (AI) are ordinal measures of MS severity based largely on the maximal distance subjects can walk (Dmax) and the time to walk 8 m (T8), respectively. At EDSS levels 6.0 to 7.0 and AI levels 3 to 6, scores are defined more by the use of ambulatory aids, rather than by Dmax or T8. We determined Dmax (up to 500 m), T8, the EDSS score, and the AI in 237 ambulatory MS patients. The maximal distance subjects could walk and T8 were strongly related to their ordinal counterparts (Spearman r = 0.65 and 0.91, respectively), but the continuous measures showed considerable variability within EDSS and AI levels that the ordinal scales did not reflect. Most of the variability occurred at EDSS levels 6.0 to 7.0 and AI levels 3 to 6. Because the use of an aid did not clearly predict Dmax or T8, many patients in these ranges had better ambulatory function based on the continuous measures than those with less disability according to the ordinal scales. We found that Dmax and T8 provide more precise information about ambulatory impairment in MS than do the EDSS and AI, allowing better discrimination of differences between patients and potentially greater sensitivity to detect therapeutic effects in clinical trials.

Adult↗
PubMed1996

Sporadic corticosteroid pulses and osteoporosis in multiple sclerosis.

BACKGROUND: Bone mineral density is reduced in patients with multiple sclerosis (MS), but the reduction has not been shown to correlate with steroid use retrospectively. OBJECTIVE: To prospectively measure bone density following a single corticosteroid pulse using dual energy x-ray absorptiometry. PATIENTS AND METHODS: Thirty acutely relapsing patients with MS were given 1000 mg of methylprednisolone intravenously daily for 3 days followed by an oral prednisone taper for 2 weeks. The bone density was determined at the lumbar spine and femoral neck prior to treatment. Seventeen patients were reevaluated 2,4, and 6 months following treatment. RESULTS: Prior to treatment, bone density in patients with MS was already reduced at the femoral neck compared with an age-matched reference population, but the degree of this reduction did not correlate with prior steroid exposure. Lumbar density, in contrast, was normal. Following the steroid pulse, lumbar bone density increased, becoming 1.7% greater than baseline 6 months later (P = .02). Femoral bone density did not change on average, but the patients who required a cane or walker for ambulation had a 1.6% decrease in femoral bone density, while those with better ambulation had a 2.9% increase (P = .04). CONCLUSIONS: Bone density is decreased in MS. A single corticosteroid pulse did not reduce bone density in fully ambulatory patients with MS and multiple pulses did not have a cumulative effect on bone density in retrospective analysis. The change in femoral density in poorly ambulatory patients may have been related to inactivity rather than the steroid pulse.

Adrenal Cortex Hormones↗
PubMed1996

Conditioning of cyclophosphamide-induced leukopenia in humans.

This study evaluated whether decrements in peripheral leukocyte counts induced by cyclophosphamide can be conditioned in humans. Ten subjects being treated for multiple sclerosis received four intravenous treatments with cyclophosphamide (unconditioned stimulus) paired with a conditioned stimulus. Subjects received conditioned stimulus plus 10 mg of cyclophosphamide during one of the next two treatments in a double-blind manner. Eight of 10 subjects (P = 0.044) displayed decreased peripheral leukocyte counts following conditioned stimulus. This change may have resulted from classical conditioning processes.

Adult↗
PubMed1995

Frequency of anti-nuclear antibodies in multiple sclerosis.

We found anti-nuclear antibodies (ANA) in 26.7% of 150 relapsing-remitting and in 30.4% of 23 chronic progressive definite multiple sclerosis (MS) patients by retrospective chart review. These patients did not have systemic lupus erythematosus. Since ANA are not pathogenically relevant in MS, they are false-positive, and likely reflect systemic immune dysregulation in MS.

Adult↗
PubMed1994

Clinical diagnosis of multiple sclerosis. The impact of magnetic resonance imaging and ancillary testing. Rochester-Toronto Magnetic Resonance Study Group.

OBJECTIVE: Magnetic resonance imaging, computed tomography, cerebrospinal fluid analysis, and evoked potential testing are used to assist in the diagnosis of patients suspected to have multiple sclerosis (MS). The impact of these tests on a clinician's diagnosis of patients suspected to have MS has not been studied systematically. DESIGN: Clinicians made a diagnosis of each patient following clinical evaluation, again after reviewing the results of magnetic resonance imaging, and finally after reviewing information from other laboratory testing. These diagnoses were compared with the criterion standard of a masked "gold standard" panel reviewing all information after a mean follow-up of 0.9 year. SETTING: The General Neurology Clinic and Multiple Sclerosis Clinic of the University of Rochester (NY). PATIENTS: A consecutive sample of 62 patients diagnosed as having either possible or probable MS following clinical evaluation. MAIN OUTCOME MEASURE: Changes in diagnostic certainty of clinicians following incremental presentation of new laboratory data and the accuracy of such diagnoses. RESULTS: Clinicians used magnetic resonance imaging findings to diagnose definite MS or to eliminate MS from diagnostic consideration in 44% of cases. In these cases, further laboratory testing did not alter clinicians' decisions. In the remaining 56% of cases, in which magnetic resonance imaging did not lead to a diagnosis of definite MS or eliminate MS from diagnostic consideration, further laboratory testing led to such diagnoses in an additional 13% of cases. Gold standard diagnoses were in agreement with the clinician's assessments. CONCLUSIONS: Magnetic resonance imaging aids in the evaluation of patients suspected to have MS; other subsequent studies (computed tomography, cerebrospinal fluid analysis, and evoked potential testing) have less impact. After all studies are performed, about half of such patients still have a tentative diagnosis.

Adult↗
PubMed1994

The clinical evaluation of patients with subclinical hyperthyroidism and free triiodothyronine (free T3) toxicosis.

PURPOSE: To develop a strategy to identify cases of endogenous subclinical hyperthyroidism and free triiodothyronine (free T3) thyrotoxicosis in otherwise healthy ambulatory patients. PATIENTS AND METHODS: In a retrospective study we reviewed the records of ambulatory patients who had thyroid stimulating hormone (TSH) levels determined between October 1, 1991 and August 31, 1992. Each patient also had a simultaneous free thyroxine (free T4) measurement. Patients were excluded from consideration if they had active, concurrent non-thyroidal illness, psychiatric disease, known hypothalamic/pituitary lesions, were under treatment for hyper- or hypothyroidism, were on drugs known to affect TSH levels, or were pregnant. Patients without exclusions were diagnosed with free T3 toxicosis if they had: (1) a markedly subnormal TSH level (less than or equal to 0.1 mU/L), (2) a normal free T4, (3) a normal total T3, (4) evidence of a primary thyroid abnormality (e.g., autonomous function on a thyroid scan), and (5) an elevated free T3 level by tracer equilibrium dialysis. Patients meeting conditions 1-4, but with normal free T3 levels, were considered to have subclinical hyperthyroidism. RESULTS: One thousand twenty-five patients had TSH and simultaneous free T4 determinations, and 148 of these had markedly subnormal TSH but normal free T4 levels. Three patients met the criteria for free T3 toxicosis and three had subclinical hyperthyroidism. All six patients had either multinodular glands or a single nodule on thyroid exam. Four patients were treated with radioactive iodine or surgery, resulting in reversal of the TSH suppression in three cases. CONCLUSION: Apparently healthy ambulatory patients with subnormal TSH levels should be worked up with measurements of free T4 and total T3. If these are normal, a T3 level (by tracer equilibrium dialysis) be obtained to distinguish subclinical hyperthyroidism from overt free T3 toxicosis. A thyroid scan and radioiodine uptake measurement can be obtained to substantiate the diagnosis. Some patients with these conditions will benefit from treatment.

Adult↗
PubMed1993

Perils and pitfalls of magnetic resonance imaging in the diagnosis of multiple sclerosis. The Rochester-Toronto MRI Study Group.

Purpose. Magnetic resonance imaging (MRI) has come to assume a position of major importance in the diagnostic process for multiple sclerosis (MS). The authors believe that a tendency toward overreliance on MRI results in isolation from clinical findings continues to result in both false-positive and false-negative diagnostic errors. Methods. To evaluate this, MRI results in newly referred patients with clinical findings suggestive, but not diagnostic, for MS, were studied prospectively. Results. Of 99 consecutive referrals for suspected MS, there were 3 false-positive diagnoses of MS and 7 false-negatives, when the MRIs were read in isolation from specific clinical data. None of the scans in the false-negative groups were normal. Representative images of both groups are provided. Conclusion. In newly referred patients who fall short of criteria for definite MS, it remains dangerous for both clinicians and radiologists to rely too heavily only on MRI results.

Adult↗
PubMed1992

Rapid onset of severe retinopathy, cataracts and neuropathy in young patients with diabetes mellitus.

It is rare for young diabetic patients to develop severe complications in the first years of their disease. We describe three patients, aged 14-23 years who developed cataracts and severe retinopathy within one to five years of diagnosis of diabetes. During the same period, one patient developed peripheral neuropathy and a second severe autonomic neuropathy. Rapid development of chronic complications in these patients raises the possibility that there may be a subset of patients with unusual susceptibility to complications. We re-emphasize the need for vigilant monitoring for complications in young diabetic patients, even in the first few years of their disease. In particular, young patients with visual complaints should be evaluated carefully for evidence of treatable eye disease.

Adolescent↗
PubMed1990

Suppressive effect of glucose administration on the binding of prolactin by rat liver.

In an attempt to elucidate the physiologic role of the hepatic receptors for prolactin (PRL), we studied the effect of changes in diet on the specific binding of 125I-ovine prolactin (oPRL) by membranes from female rat liver. Specific binding of PRL (SBP) was decreased by over 50% in rats fed 15% glucose ad lib for 2 days, as compared with fasted rats (P less than .01), while serum PRL was similar in both groups. Feeding 20% glucose by tube decreased SBP significantly, but tube-feeding equicaloric amounts of fat or protein-amino acid solution did not. Glucose feeding did not decrease the specific binding of 125I-bovine growth hormone (bGH) to liver, or decrease SBP to membranes of nitrosomethylurea (NMU)-induced mammary carcinomas, indicating that the effect of glucose on hepatic SBP is selective. Administration of glucose decreased SBP significantly in adrenalectomized-ovariectomized rats, in adrenalectomized-chemically sympathectomized rats, and in hypophysectomized rats receiving replacement therapy, including bovine prolactin (bPRL), bGH, hydrocortisone, estrogen, and thyroid hormones. Thus, the effect of glucose is not mediated by a factor from the adrenals, ovaries, or pituitary, and probably not by catecholamines. Administration of insulin to fasted diabetic rats did not alter SBP. Infusion of glucagon for 1 day, at a rate that did not alter serum glucose, increased hepatic SBP 29% (P less than .01). Since glucose administration decreases plasma glucagon, we hypothesize that glucagon may contribute to the maintenance of the hepatic PRL receptors, and that the suppressive effect of glucose on hepatic SBP may be mediated at least in part by suppression of plasma glucagon.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗
PubMed1989

Evidence for the existence of a GTP-dependent factor in hepatic cytosol that stimulates cyclic AMP binding: possible role in the modulation of cyclic AMP action.

GTP, in physiologic concentration (10(-4) mol/L), enhances cAMP binding to an Mr 57,000 binding protein (BP) in hepatic cytosol, which probably is the phosphorylated receptor subunit of protein kinase II (PK II). When we attempted to separate PK II from other hepatic cytosol proteins by DEAE-cellulose chromatography, we observed that GTP caused little stimulation of [3H]cAMP binding in an eluate fraction (110 to 170 mmol/L KCI), which was rich in PK II but did stimulate cAMP binding to the 210 to 325 mmol/L KCI fraction, which also contains PK II. This suggested that the latter fraction might contain a cofactor necessary for GTP stimulation of cAMP binding, which was lacking in the 110 to 170 mmol/L KCI fraction. Cyclic AMP BP in the 210 to 325 mmol/L fraction was removed by absorption onto cAMP agarose in the presence of 325 mmol/L KCI. When an aliquot of the BP-poor fraction, containing the putative cofactor, was added to the 110 to 170 mmol/L fraction containing PK II, the addition of 10(-4) mol/L GTP to the mixture increased [3H]cAMP binding by more than 80%. Cofactor activity could be extracted from the 210 to 325 mmol/L eluate by adsorption onto cAMP agarose in the presence of 10 mmol/L K phosphate, and eluted with 100 mmol/L KCI, suggesting that the cofactor may bind to the cAMP BP under appropriate circumstances. Addition of this eluted cofactor fraction to the 110 to 170 mmol/L fraction in the presence of 10(-4) mol/L GTP, increased the specific binding of [3H] cAMP more than twofold. Pretreatment of the cofactor fraction with trypsin eliminated this effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Virus-specific cytotoxic T lymphocytes in multiple sclerosis: a normal mumps virus response adds support for a distinct impairment in the measles virus response.

An impairment of the measles virus-specific cytotoxic T lymphocyte response in multiple sclerosis was previously reported. This response is predominantly mediated by HLA class II-restricted CD4+ cells. In the present report, virus-specific cytotoxic T lymphocyte responses in multiple sclerosis were further studied by examining the response to mumps virus. No significant difference was detected in the generation of mumps virus-specific cytotoxic T lymphocyte responses between normal individuals and multiple sclerosis patients with impaired measles virus-specific cytotoxicity. A portion of the mumps virus-specific cytotoxic T lymphocyte response could be mediated by HLA class II-restricted CD4+ cells generated from both normal controls and MS patients. This CD4+ cell-mediated portion of the response was similar in both groups. These findings support the view that there is a distinct measles virus-specific impairment in cell-mediated cytotoxicity in multiple sclerosis.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1988

Effects of prolactin and growth hormone on tissue and serum carnitine in the rat.

Previous experimental observations have suggested to us that PRL and GH may be involved in regulating the metabolism of carnitine, a factor that plays a critically important role in fatty acid oxidation and ketogenesis. In the present study we administered bovine PRL (bPRL) or bovine GH (bGH) at a physiologic rate to hypophysectomized female rats for 2-3 days, and observed that bPRL caused a small (16%) increase (P less than 0.01), and bGH a 36% increase (P less than 0.01), in hepatic carnitine, bPRL decreased serum carnitine by 24% (P less than 0.05), and bPRL and bGH each increased the liver/serum carnitine ratio by 58% (P less than 0.01), suggesting that these hormones enhance the active uptake of carnitine from plasma. bPRL and bGH, alone or in combination, did not affect the carnitine content of cardiac or skeletal muscle, but in combination they increased the heart/serum and muscle/serum carnitine ratios by 45-76% (P less than 0.01), thus allowing maintenance of normal cardiac and skeletal muscle carnitine despite a decreased plasma level. In hypophysectomized male rats, bPRL did not affect liver or epididymal carnitine. We hypothesize that PRL and GH may play a role in the regulation of the carnitine concentration of female liver by enhancing hepatic uptake of carnitine from plasma, and through this mechanism may affect hepatic fatty acid oxidation and ketogenesis. The effect of lactogenic and somatogenic hormones on hepatic carnitine and ketogenesis could be of particular physiological importance in late pregnancy and during lactation.

Animals↗