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Biomedical subjects

L A Stone

Publications and source records attributed to L A Stone.

At least 19 recordsLinked to original sources
PubMed1995

The effect of interferon-beta on blood-brain barrier disruptions demonstrated by contrast-enhanced magnetic resonance imaging in relapsing-remitting multiple sclerosis.

Magnetic resonance imaging (MRI) has been a valuable tool to understand the pathophysiology and natural history of multiple sclerosis (MS), and increasing attention is focusing on the use of MRI findings as outcome measures in treatment trials in MS. The recently completed trial of interferon-beta-1b (IFN-beta 1b) demonstrated a decrease in accumulation of diseased tissue on T2-weighted images and a reduction in new lesions on T2-weighted images. To examine the effect of IFN-beta 1b on blood-brain barrier (BBB) breakdown, and to provide additional insights into the usefulness of MRI in the evolution of effectiveness of experimental treatments in MS, we used the contrast-enhanced lesion frequency of 7-month baseline MRIs compared with the enhanced lesion frequency for 6-month treatment period MRIs in 14 relapsing-remitting (RR) MS patients. Longer baselines were also available for analysis in a subset of 8 patients, as these patients had been followed by monthly MRI in a natural history study for up to 4 years prior to the current study. A significant reduction in the total or new enhancing lesion frequency was detected in the patients analyzed as a whole, and 13 of 14 of the patients demonstrated a reduction in enhancing lesion frequency on treatment over the 6 months studied. These findings suggest that IFN-beta has a mechanism of action that at least temporarily inhibits the opening of the BBB in RRMS patients. This trial also illustrates the usefulness of a baseline versus treatment trial design to evaluate the effect of drug therapy in MS.

Adult↗
PubMed1995

Changes in the amount of diseased white matter over time in patients with relapsing-remitting multiple sclerosis.

MRI is a sensitive technique for assessing disease activity in MS. Diseased white matter (WM) can be identified on T2-weighted images, and active disease is reflected by abnormalities in the blood-brain barrier (BBB) shown on T1-weighted images after administration of paramagnetic contrast agents. Active disease may be demonstrated by contrast-enhanced MRI in patients with early, mild relapsing-remitting (RR) MS even during periods of clinical stability, which indicates that MS is an active process even during the early phase of the illness. To examine the amount of abnormal WM at frequent intervals over time, we studied seven mildly affected RRMS patients, all of whom had frequent contrast-enhancing lesions. These RRMS patients were imaged monthly for 26 to 36 months at 1.5 tesla; the area of abnormal increased WM signal was calculated by image-processing software that utilizes both the T2- and T1-weighted images. All patients showed fluctuations over time in amount of abnormal WM signal, which reflected factors such as the amount of BBB breakdown (measured by number or area of enhancing lesions) and measurement error. All seven RRMS patients, however, showed an overall increase in abnormal WM. Because of the fluctuations between individual measurements, the increase was most accurately reflected when the mean of the first 6 months' measurements was compared with the mean of the final 6 months' measurements, or when a linear regression model was applied.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Blood-brain barrier disruption on contrast-enhanced MRI in patients with mild relapsing-remitting multiple sclerosis: relationship to course, gender, and age.

MRI has provided insight into the pathophysiology and course of MS, particularly through the use of a paramagnetic contrast agent that allows visualization of blood-brain barrier (BBB) breakdown. Neither the overall frequency of BBB breakdown in MS patients nor the characteristics associated with BBB breakdown in MS are known. We studied 68 relapsing-remitting MS (RRMS) patients with three monthly MRIs to examine these questions. Seventy-eight percent of the RRMS patients studied had evidence of BBB breakdown on at least one MRI. While there was a great deal of variability among patients in terms of mean enhancing lesion frequency, BBB breakdown was associated with younger age at onset of disease, measured by age at first symptom or age at diagnosis, and more severe disease as measured by Expanded Disability Status Scale scores equal to or greater than 4.0. We found no relationship between BBB breakdown and duration of disease or gender. We conclude that BBB breakdown is a relatively common phenomenon in RRMS patients and may be most commonly found in patients with more aggressive disease and younger onset. These findings have implications for clinical trials that use MRI as an outcome measure.

Adolescent↗
PubMed1994

Correlation of clinical features and findings on cranial magnetic resonance imaging with urinary myelin basic protein-like material in patients with multiple sclerosis.

Immunoreactive material that appears to be a peptide encompassing all or a portion of residues 80 to 89 of myelin basic protein is present in normal unconcentrated urine and is increased in certain patients with multiple sclerosis (MS). Compared with normal controls, urines collected randomly from 158 MS patients or in a clinical research unit from 8 patients with MS had higher mean values of urinary MBP-like material (MBPLM). The level of MBPLM in urine showed no direct relationship to MBPLM in cerebrospinal fluid and did not correlate with clinical relapses of disease. In the other neurological disease control group (26 patients), some patients with other inflammatory diseases, but not stroke or early phase Guillain-Barré syndrome, also showed elevations. Among the subtypes of MS, those with secondary chronic progressive disease had the highest values. Urinary MBPLM showed no definite correlation with or effect of treatment with glucocorticoids and immunosuppressants except that a lower level of urinary MBPLM showed a weak relationship with improvement following treatment with methylprednisolone/prednisone. In a serial study of 8 patients with unenhanced cranial magnetic resonance imaging and 20 patients with gadolinium-enhanced cranial magnetic resonance imaging, urinary MBPLM did not show a direct correlation with new or enhancing lesions. Urinary MBPLM does not parallel acute myelin damage but appears to reflect an ongoing process, possibly linked to attempted efforts at remyelination.

Adult↗
PubMed1994

Serial contrast-enhanced magnetic resonance imaging in patients with early relapsing-remitting multiple sclerosis: implications for treatment trials.

Serial monthly contrast-enhanced MRIs were performed in 10 early relapsing-remitting patients with multiple sclerosis and 2 patients with chronic progressive disease for a period of 12 to 55 months. MRI was performed at 1.5 T using contiguous 5-mm slices with pre- and postgadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) T1-weighted and T2-weighted images. New and total number of Gd-DTPA-enhancing lesions were numbered and counted and lesion areas were correlated to an increase of > or = 0.5 in Expanded Disability Status Scale (EDSS) scores. The frequency of enhancing lesions varied from patient to patient; however, there was a correlation between a burst of enhancing lesion number and area above the individual's mean lesion frequency to an increase in EDSS score. A bootstrap analysis of the lesion count was performed to develop a statistical basis for determining population sizes for treatment trials. These results provide a basis for the potential use of contrast-enhanced MRI as a primary outcome measure in phase II treatment trials involving patients with relapsing-remitting MS.

Adult↗
PubMed1993

Clinical worsening in multiple sclerosis is associated with increased frequency and area of gadopentetate dimeglumine-enhancing magnetic resonance imaging lesions.

It is now well established that clinically stable patients with relapsing-remitting multiple sclerosis have ongoing disease activity when evaluated by serial gadolinium-enhanced (Gd-DTPA) magnetic resonance imaging (MRI) scans. Despite this, the relationship between clinical disease and MRI lesions, though suspected, has not been extensively documented. The relationship between Gd-DTPA MRI lesions and clinical disease was examined in this study of 9 patients with mild relapsing-remitting multiple sclerosis (Expanded Disability Status Scale [EDSS] < 3.5) who had 24 to 37 monthly Gd-DTPA MRI scans, neurological examinations, and EDSS score assignments. The area and frequency of Gd-DTPA lesions were examined during months with and without clinical worsening as measured by EDSS. Forty-one episodes of clinical worsening were noted during the study. A significant association was observed between these periods of clinical worsening and MRI parameters, including increases in total number, number of new lesions, and the total area of enhancement. Logistic regression analysis showed a significant effect of the number and area of Gd-DTPA MRI lesions on both the onset and continuation of clinical worsening, confirming an important relationship between clinical disease and an increase in cerebral Gd-DTPA MRI activity. A relationship with long-term disability was suggested, but cannot be confirmed without longer follow-up of these patients.

Adult↗
PubMed1991

The coexistence of tics and dystonia.

We studied nine patients with motor and phonic tics and other features of Tourette's syndrome, who developed persistent dystonia in addition to their tics. All, except one, were males (mean age, 35.8 years; range, 8 to 59 years), and had onset of tics prior to age 18 years (mean age, 9 years; range, 1.5 to 17 years). None of the patients were treated with neuroleptic drugs prior to the onset of dystonia. Torticollis and blepharospasm were the most common forms of dystonia. Seven patients had a history of tics in first degree relatives. While these patients were seen in a specialized movement disorder clinic and may, therefore, represent a population with atypical and more severe symptoms, the high prevalence rate of dystonia (5.0% of all patients with Tourette's syndrome seen in the clinic) suggests that some patients with tics may have an increased risk for dystonia.

Adolescent↗
PubMed1991

Vitamin D receptors and compensatory tissue growth in spontaneously diabetic BB rats.

Untreated diabetic (BB) rats exhibited compensatory intestinal growth which was associated with hyperplasia and was accompanied by an increase in unoccupied vitamin D receptors. Although vitamin D receptors were increased, low circulating 1,25-dihydroxy-vitamin D3 [1,25(OH)2D3] prevented amplification of the action of 1,25(OH)2D3, as evidenced by reductions in calbindin D-9K and alkaline phosphatase activity in the BB rat intestine compared to control. In the kidney, a lesser degree of compensatory growth was observed which was not associated with hyperplasia, and no significant effect of diabetes on vitamin D receptors or calbindin D-28K was observed. These studies suggest tissue-specific changes in 1,25(OH)2D3 metabolism during spontaneous diabetes which may be related to the hyperplasia which occurs during compensatory tissue growth.

Animals↗
PubMed1990

Vitamin D receptors in intestine, kidney and thymus of streptozotocin diabetic rats.

Our data confirms previous reports of intestinal and kidney compensatory growth, low plasma 1,25(OH)2D3 and up regulation of intestinal VDRs during untreated diabetes. All of these parameters were normalized in diabetic rats treated with exogenous insulin. There were no alterations in VDR numbers in kidneys or thymus of untreated diabetic animals, indicating that up-regulation of VDRs during untreated diabetes did not occur in all vitamin D target tissues. Compensatory growth of the intestine during untreated diabetes was associated with both hypertrophy and hyperplasia, whereas diabetic kidney growth appeared to be associated with hypertrophy without hyperplasia. Diabetes did not affect somatic index of thymus. The data suggests that the up regulation of VDRs during untreated diabetes may be unique to the intestine and further that VDR up regulation may be related to hyperplasia. Calbindin D-9K was significantly lower in diabetic intestine, suggesting that low circulating 1,25(OH)2D3 prevented amplification of 1,25(OH)2D3's action despite up regulation of intestinal VDRs.

Alkaline Phosphatase↗
PubMed1984

Effect of technique variation on sensory nerve conduction characteristics.

The impact of technique variation on the wave-form characteristics of the evoked sensory potential was determined from the median and ulnar nerves of healthy subjects. The conduction characteristics of latency, amplitude, and duration were determined for orthodromic and antidromic techniques of stimulation as measured under each of three recording modes: 1) single evoked response, 2) superimposition, and 3) electronic averaging. Variation in the technique of stimulation significantly affected each of the three wave-form characteristics. Peak latency and duration of the evoked sensory potential were longer in antidromic stimulation. The amplitude of the sensory potential varied significantly with both recording and stimulating techniques. The amplitude of the sensory response was larger in antidromic stimulation than in orthodromic stimulation and also was found to be smaller with electronic averaging than with the other recording modes in both antidromic and orthodromic conduction techniques. This degree of variation requires that standardized techniques of methodology be established with the development of normal values for the particular laboratory.

Adult↗
PubMed1983

Contact dermatitis.

Explore the source record for details and available documents.

Dermatitis, Contact↗
PubMed1975

Multidimensional scaling of pictorial informativeness.

The dimensions used in the judgment of the informativeness of picture sections were investigated by means of a recently proposed methodology, multidimensional similarity analysis. 10 judges (college students) rated the informational similarity of 32 areas within a single picture. The five extracted dimensions accounted for 86% of the judgmental variance and were all readily interpretable. These dimensions were discussed with respect to an earlier study in which eye movements of subjects viewing this picture were recorded.

Adult↗