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Biomedical subjects

C Bever

Publications and source records attributed to C Bever.

7 recordsLinked to original sources

Interferon-beta-1a induces increases in vascular cell adhesion molecule: implications for its mode of action in multiple sclerosis.

We investigated soluble vascular cell adhesion molecule-1 (sVCAM) levels and MRI lesions over 24 weeks in 15 Relapsing Remitting MS (RRMS) patients randomized prospectively to receive once-weekly (qw) IFN-beta-1a 30 mug intramuscularly (IM) (Group I, 8 patients) or three-times-weekly (tiw) IFN-beta-1a 44 mug subcutaneously (SC) (Group II, 7 patients). Both groups demonstrated a significant increase in sVCAM during treatment when compared to pre-treatment levels. Patients on IFN-beta-1a 44 mug SC tiw had a significant (p<0.0001) mean increase in sVCAM of 321.9 ng/ml which was significantly greater (p<0.0001) than with IFN-beta-1a 30 mug IM qw (68.6 ng/ml). There was a negative correlation between combined unique (CU) MRI lesions and sVCAM levels within the IFN-beta-1a 44 mug SC tiw group (slope=-0.00106, p=0.009). We postulate that the mode of action of IFN-beta therapy in MS may involve the induction of an increase in sVCAM. sVCAM could bind VLA-4 on T-cells and intercept their adhesion to the blood brain barrier (BBB). This mechanism is consistent with the observed clinical effect of IFN-beta in reducing MRI contrast enhancing lesions.

Analysis of Variance↗

Comparative tolerance of IFN beta-1a regimens in patients with relapsing multiple sclerosis. The EVIDENCE study.

The EVIDENCE study was a direct comparative study of two dose regimens of interferon (IFN) beta-1a used in the treatment of relapsing-remitting multiple sclerosis (RRMS): 30 mcg intramuscularly once weekly (qw; n=338) and 44 mcg subcutaneously three times weekly (tiw; n=339). The study continued for an average of 64 weeks. The safety population consisted of all patients receiving at least one dose of study drug. Clinical assessments occurred every 4 weeks for 24 weeks and then every 12 weeks. Blood tests for safety were taken at baseline and at weeks 4 and 12, and every 12 weeks thereafter. Overall adverse events were more common with the 44 mcg tiw regimen (p=0.007), and were due predominantly to differences in injection-site reactions. The majority of adverse events were rated mild by investigators. Hepatic and haematological adverse events and asymptomatic laboratory abnormalities were more common with 44 mcg tiw (p<0.001),with no difference seen for severe events. Flu-like symptoms were more common with 30 mcg qw (p=0.031), were more severe and persisted for longer. Serious adverse events were comparable for both groups, as were drug discontinuations. In conclusion, although adverse events were more common with high-dose, high-frequency IFN therapy, differences were primarily for mild events and did not affect treatment adherence. Based on superior clinical and magnetic resonance imaging outcomes over an average of 64 weeks, coupled with modest safety differences, the risk-benefit ratio for IFN therapy in RRMS favours the 44 mcg tiw regimen over this period of time.

Central Nervous System↗

Performance of the dynamic single photon emission computed tomography (dSPECT) method for decreasing or increasing activity changes.

Radionuclide imaging is now widely used whenever functional information is required. We present a new approach to dynamic SPECT imaging (dSPECT method) that uses a single slow rotation of a conventional camera and allows us to reconstruct a series of 3D images corresponding to the radiotracer distribution in the body at various times. Using simulations of various camera configurations and acquisition protocols, we have shown that this method is able to reconstruct washout half-lives with an accuracy greater than 90% when used with triple-head SPECT cameras. Accuracy decreases when using fewer camera heads, but dual-head geometries still give an accuracy greater than 80% for short and 90% for long half-lives and about 50-75% for single-head systems. Dynamic phantom experiments have yielded similar results. Presence of attenuation and background activity does not affect the accuracy of the dSPECT reconstructions. In all situations investigated satisfactory dynamic images were produced. A preliminary normal volunteer study measuring renal function was performed. The reconstructed dynamic images may be presented as a three-dimensional movie showing movement of the tracer through the kidneys and the measurement of the regional renal function can be performed. The time-activity curves determined from this dSPECT data are very similar to those obtained from dynamic planar scans.

Heart↗

Language functions in patients with multiple sclerosis.

Few studies have demonstrated language impairment in patients with multiple sclerosis (MS) compared to healthy controls. The purpose of this investigation was to examine language functions, specifically naming, comprehension, and verbal fluency, in patients with MS and healthy controls to (1) determine if patients with MS demonstrate language impairment, and (2) provide clarification of MS-related language disturbance, particularly in patients with MS of differing courses. Results showed that both chronic-progressive and relapsing-remitting patients with MS performed significantly more poorly than controls on naming, aural comprehension, letter fluency, and category fluency, as well as other language-based cognitive measures. Chronic-progressive patients obtained significantly lower scores than relapsing-remitting patients on the latter three tests. The language disturbance in this MS sample may be partly explained by impairment in other verbal cognitive functions. These findings highlight the importance of assessing language abilities in patients with MS.

Adult↗

Hereditary adult-onset leukodystrophy simulating chronic progressive multiple sclerosis.

We studied a large kindred with a chronic progressive neurologic disorder affecting at least 10 men and 11 women in four generations in a pattern compatible with autosomal dominant inheritance. In 20 of the affected subjects, evaluated before the availability of computerized tomography and without regard to family history, the diagnosis was multiple sclerosis. Symptoms of the neurologic disorder begin in the fourth and fifth decades and include cerebellar, pyramidal, and autonomic abnormalities. The autonomic symptoms, which involve bowel and bladder regulation and orthostatic hypotension, may be the earliest changes but are frequently disregarded. Survival for 20 years after onset is common. The CT scan is striking and shows a symmetrical decrease in white-matter density, beginning in the frontal lobes but extending to all of the centrum ovale and the cerebellar white matter. Limited pathological observation reveals gross white-matter degeneration with microscopic vacuolation, preservation of U fibers and cortical structures, and no inflammatory changes or reactive gliosis. Because of its hereditary basis, the disorder should be susceptible to genetic definition and ultimately to treatment or prevention.

Adult↗