Systemic recombinant human interferon-beta treatment of relapsing-remitting multiple sclerosis: pilot study analysis and six-year follow-up

The role of the spleen in patients with ulcerative colitis and Crohn's disease was assessed by counting pitted erythrocytes with differential interference microscopy and by splenic ultrasound. The findings were compared with those from age- and sex-matched controls and a group of splenectomized patients. The incidence of hyposplenism was lower than previously reported, being found in six of 29 patients with ulcerative colitis (of whom five had relapsed pancolitis and one had quiescent pancolitis) and two of 21 patients with Crohn's disease. Pitted erythrocyte counts were significantly higher in patients with ulcerative colitis compared with age- and sex-matched controls (p < 0.001), but there was no difference in counts between patients with Crohn's disease and controls. Patients with relapsed but not quiescent ulcerative colitis had significantly smaller spleens than controls. Patients with the highest pitted erythrocyte counts had the smallest spleens on ultrasound. More effective medical and surgical therapy may account for the lower incidence of functional hyposplenism observed in this study. Nonetheless, patients may show marked hyposplenism and remain at risk of overwhelming infection and operative complications. Differential interference microscopy is a simple technique that can be used to assess splenic function in patients thought to be susceptible to infection.     

Neuropsychological findings in relapsing-remitting and chronic-progressive multiple sclerosis.

Administered the WAIS and an expanded Halstead-Reitan Neuropsychological Test Battery (HRB) to 100 (mean age 37.38 yrs) patients with relapsing-remitting (n?=?57) or chronic-progressive (n?=?43) courses of multiple sclerosis (MS) and to 100 normal controls to assess neuropsychological functioning in MS Ss. Both MS groups were clinically stable at the times of testing. Results indicate that both MS groups showed significant neuropsychological impairment, relative to controls, but chronic-progressive MS was associated with greater impairment in each major ability domain (cognitive, sensory, and motor) than was relapsing-remitting MS. In particular, only minimal cognitive impairment was noted in relapsing-remitting MS Ss, whereas chronic-progressive Ss showed impairment on the majority of cognitive test measures from the expanded HRB. Degree of neuropsychological impairment was significantly correlated with MS duration but was unrelated to medication status. MS subgroup differences on the test battery could not be attributed to duration of illness, indicating that disease course is an important independent determinant of neuropsychological impairment in MS. Disability ratings from clinical neurological examinations were highly correlated with motor and sensory performances on neuropsychologial testing, but clinical exams were inadequate in predicting Ss' cognitive status. (33 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Possible role of transforming growth factor-beta in relapsing-remitting multiple sclerosis

Cerebrospinal fluid (CSF) and serum levels of transforming growth factor (TGF)-beta and soluble intercellular adhesion molecule-1 (sICAM-1) were evaluated in ten patients with definite multiple sclerosis (MS) of the relapsing-remitting type. CSF TGF-beta levels of MS patients in remission were significantly (p < 0.01) higher than of MS patients in active phase, and there was a significant inverse correlation (p < 0.05) between TGF-beta and slCAM-1 levels in the CSF of patients in both remitting and relapsing type. This is consistent with a possible down-regulation of TGF-beta on ICAM-1 expression and suggests a possible synthesis in the central nervous system of TGF-beta.     

Interferon beta-1b inhibits reactive oxygen species production in peripheral blood monocytes of patients with relapsing-remitting multiple sclerosis

To determine if perforation rate is a function of delayed diagnosis or delayed presentation in childhood acute appendicitis we performed a retrospective casenote review of 101 consecutive children undergoing emergency appendicectomy over a 12-month period. The perforation rate was 7% in those children presenting with symptoms of 1 day or less and was significantly greater (33%, Chi 2 = 9.45, P < 0.01) in those who had had symptoms for more than 1 day at presentation. There was no difference in in-hospital delay between the groups. A high perforation rate was found to be a feature of delayed presentation.     

Wisconsin Card Sorting Test performance in relapsing-remitting and chronic-progressive multiple sclerosis.

The Wisconsin Card Sorting Test (WCST), a measure of concept formation and set-shifting capacity, was administered to two groups of multiple sclerosis (MS) patients defined by relapsing-remitting (n?=?36) or chronic-progressive (n?=?33) clinical courses. The performance of each group was compared with an age and education-matched control group of chronic back pain patients. The chronic-progressive patients achieved fewer conceptual categories due to a significantly greater number of perseverative responses than control patients, whereas the relapsing-remitting group was unimpaired on the WCST relative to the control group. A stepwise multiple regression analysis suggested that these performance differences were related to clinical course and not to length of illness or degree of physical disability. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Incidence of exacerbations in the first 90 days of treatment with recombinant human interferon beta-1b in patients with relapsing-remitting multiple sclerosis

Interferon beta-1b (IFNbeta-1b) is effective in reducing the frequency of exacerbations in patients with relapsing-remitting multiple sclerosis (RRMS). Recently, a study suggested that treatment with IFNbeta-1b may place MS patients at risk of exacerbations by increasing interferon-gamma (IFNgamma)-secreting cells in the blood early after onset of treatment. We conducted a retrospective study in 192 RRMS patients treated with IFNbeta-1b. We did not observe an increase in the frequency of exacerbations early after the onset of treatment and suggest that the IFNgamma-secreting cell surge linked to the onset of treatment with IFNbeta-1b may not be clinically significant.     

Occurrence of thyroid autoimmunity and dysfunction throughout a nine-month follow-up in patients undergoing interferon-beta therapy for multiple sclerosis

Thyroid autoimmunity and dysfunction are a well known side effect of IFN alpha therapy for viral hepatitis and tumors, while the IFN beta effects on the thyroid gland in neurological patients have not been studied. The aim of this longitudinal study was to look for the appearance of thyroid autoimmunity as well as for the occurrence of overt thyroid disease in the patients affected by multiple sclerosis (MS) treated with IFN beta 1b. Eight patients (4 males, 4 females) undergoing r-IFN beta 1b treatment (8 M.U. every other day for 9 months) for relapsing remitting multiple sclerosis entered the study. We have analyzed thyroid function parameters and auto antibody levels before and after 1, 2, 3, 6 and 9 months of therapy. None of them referred to familiar thyroid pathology or presented clinically overt thyroid disease except for one patient (case 4) who showed TPO-Ab pretreatment positivity and another (case 8) who was in therapy with Levothyroxine 100 microg/die for multinodular goiter. The number of patients with appearance of thyroid antibodies has slowly increased, until the third month of therapy with 3 patients out of 7 positive for TPO-Ab. The only case of overt thyroid dysfunction reported by us appeared after nine months of therapy and consisted of a hypothyroidism. Our data suggest that short-term interferon beta treatment is able to induce thyroid autoimmunity (42.8%) and dysfunction (12.5%).     

Influenza vaccination in patients with multiple sclerosis

Vaccination was well tolerated by 93 patients with multiple sclerosis who received a total of 209 doses of influenza vaccine. In one patient, evidence of a new lesion developed after vaccination; the relapse rate was less than would be expected in the natural course of the illness. Toxic and allergic reactions appeared with 7% and 0.5% of the vaccinations, respectively--a rate no higher than that observed in the general population.     

Lipid peroxidation in patients with multiple sclerosis

Questions of lipid metabolism in patients with multiple sclerosis are considered in the light of biomembrane (myelin) pathology. The results of of the study of the lipids fatty acids spectrum in the blood plasma and the secondary product of their spontaneous and NADPhH-dependent peroxidation, malonic dialdehyde, are stated. The dependence of changes in saturation of fatty acids spectrum and dialdehyde concentrations on the stage and heaviness of the multiple sclerosis is shown. Certain dynamics of lipid metabolism indices as a result of treatment was found. The authors also give some recommendations as to the use of drugs at various stages of the disease.     

Determinants of Gd-enhanced MRI response to IFN-beta-1a treatment in relapsing-remitting multiple sclerosis

BACKGROUND: With the prevalence of antibiotic use, the diagnosis and management of Clostridium difficile disease requires assessment. METHODS: In a retrospective review, patients with a positive culture, toxin, or both during 1 year were identified. Recent literature was reviewed. Results of culture and toxin, prior antibiotic use, antibiotic treatment history and cost were analyzed. RESULTS: Of 592 patients tested, 101 were positive; 96 of 101 were available for review. Of those positive tested for both, 45% were positive for toxin and culture. Sixty-two of 96 were treated with antibiotics; metronidazole was used in 90%. Ten of 62 antibiotic treatments were changed (mean 3 days). Ten days of metronidazole is 1/200th the cost of vancomycin. CONCLUSIONS: In 55% of the positive cases in which culture and toxin were obtained, one test was negative. As metronidazole's efficacy and cost compares favorably with vancomycin, metronidazole is the drug of choice. Any changes made to antibiotic regimens occurred prior to the 6 days recommended in the literature.     

Immunoregulatory effects of interferon-beta and interacting cytokines on human vascular endothelial cells. Implications for multiple sclerosis autoimmune diseases

BACKGROUND AND PURPOSE: Radiolabeled immunoglobulin therapy (RIT) can be a selective, effective, low-toxicity outpatient cancer therapy. A consensus on the best approach for the preclinical and clinical development of RIT reagents needs to be developed. We report the M.D. Anderson Cancer Center prior experience in translating RIT from laboratory to clinic for the treatment of Hodgkin's disease and propose a flow diagram for the development of RIT for other malignancies. MATERIAL AND METHODS: Three different animal models are described: nude mice bearing human tumor xenografts, normal beagle dogs, and normal rhesus monkeys. We produced and purified antibodies and prepared chelate-immunoconjugates reactive with six different human tumor-associated antigens. The Igs used were derived from rabbits, mice, and humans (human-derived RIT reagents being less immunogenic in human patients). Eighty patients with refractory Hodgkin's disease were treated with radiolabeled antiferritin. RESULTS: We recommend a two-injection scheme using, (1) an indium-111-labeled radioimmunoconjugate for diagnosis, pharmacokinetic studies, and dosimetry, and (2) a yttrium-90-labeled radioimmunoconjugate for therapy. The animal models provide useful data on tumor targeting, radiotoxicology, and undesirable biodistributions. A 70% response rate is obtained in patients with advanced recurrent Hodgkin's disease. More extensive preclinical testing allows for safer and more effective clinical RIT studies. CONCLUSIONS: We recommend, (1) preclinical optimization of chelation chemistry, Ig size, Ig origin, route of administration, and fractionation, (2) new clinical Phase I-III studies more appropriate for RIT development than the classical Phase I-III studies used for the development of chemotherapeutic agents, and (3) more extensive preclinical testing of RIT reagents.     

Evoked potential abnormality scores are a useful measure of disease burden in relapsing-remitting multiple sclerosis

OBJECTIVES: To identify the incidence and the success of endourologic therapy for symptomatic bladder-related calculi in simultaneous kidney-pancreas (SPK) transplant patients with bladder drainage. METHODS: A retrospective review of 300 SPK transplant patients with bladder drainage, treated at the University of Wisconsin, Madison from December 1985 to November 1995, is presented. A 3% incidence of bladder calculi was identified. All patients underwent cystolitholapaxy using electrohydraulic lithotripsy and endoscopic suture removal. Follow-up ranged from 15 to 86 months. RESULTS: A 100% stone-free rate was achieved after cystolitholapaxy and endoscopic suture removal. Two patients (22%) developed postprocedural urinary tract infections. No pancreaticoduodenocystotomy leaks or further complications were identified. CONCLUSIONS: SPK transplant patients with nonabsorbable sutures used for the duodenocystotomy anastomosis are at an increased risk for bladder calculi. Cystolitholapaxy with electrohydraulic lithotripsy is a safe and effective treatment for these suture-related stones.     

Dichotic listening and corpus callosum magnetic resonance imaging in relapsing-remitting multiple sclerosis with emphasis on sex differences.

Twenty-five early-onset relapsing-remitting multiple sclerosis patients (12 women and 13 men) with mild disability were compared with 25 matched controls in a dichotic listening (DL) test under nonforced and forced attentional-shift conditions. Patients showed left ear impairment and no left ear advantage in the forced-left condition. Four corpus callosum (CC) regions were measured in patients on a rnidsaggital magnetic resonance imaging scan. The right ear score was negatively correlated whereas the left ear score was positively correlated with CC regions (significant only for the nonforced condition). Moreover, in men, the correlations with DL scores were linked mainly to the splenium and posterior isthmus, and in women, they were stronger for anterior isthmus and posterior body. An inverse correlation between months of disease evolution and CC area was found only in women. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Influenza virus vaccination of patients with multiple sclerosis

Our previous data showed that at least five PKC isoforms (alpha, delta, zeta, lambda and tau) were present in the decidualization. In this study, we then localized the PKC alpha and zeta by immunohistochemistry in the decidualized uterine tissues. The decidualized uterine tissues were induced by trauma-stimulation and fixed in formalin. The immunofluorescence were photographed by confocal microscope. The data revealed that the fluorescence of PKC alpha was present in the deciduomata and myometrium. In the deciduomata, PKC alpha was mainly located in the surrounding nuclear. This phenomenon of localization was especially performed on day 2 and 3 of the decidualization, just on the time of higher frequence of cell mitosis. Since the myometrium with hypertrophy did not display the phenomenon of perinuclear localization, these suggested that the expression and localization of PKC alpha may be associated with the cell proliferation. On the other hand, the PKC zeta was also present and distributed broadly in the deciduomata and myometrium. This expression was increased and similar to the previous Western blot studies. Thus, the data confirmed that the various expression and localization of PKC isoforms may be correlated with the development of deciduomata.     

"Summary measure" statistic for assessing the outcome of treatment trials in relapsing-remitting multiple sclerosis

OBJECTIVE: The relation of temperamental dimensions to somatization and panic disorders in women was investigated. METHOD: Eighteen patients with both panic and somatization disorders, 41 patients with panic disorder only, and 22 control subjects were compared on the Tridimensional Personality Questionnaire. RESULTS: The patients with somatization and panic disorders had significantly higher Novelty Seeking values than both the patients with panic only and the control subjects. The only significant correlation was between the number of symptoms of somatization disorder and Novelty Seeking. The presence of other psychiatric conditions, comorbid with panic disorder in the patient group, did not affect significantly the temperamental variables. CONCLUSIONS: A temperamental disposition characterized by extraversion, impulsivity, as well as frequent exploratory activity and pursuit of novel and pleasurable activities may help differentiate women with both somatization and panic disorders from women with panic disorder only.     

The metabolic characteristics of patients with multiple sclerosis

A comprehensive clinical and biochemical evaluation has been carried out in patients with multiple sclerosis (MS). Measured in the patients' blood were levels of cholesterol, triglycerides, malonic dialdehyde, and superoxidedysmutase activity. The interrelationship revealed between the above measures provides a deeper insight into the mechanisms of pathometabolism in MS.     

Bladder cancer in patients with multiple sclerosis treated with cyclophosphamide

PURPOSE: We define the risk of bladder cancer in multiple sclerosis related to the use of indwelling catheters and cyclophosphamide administered as an immunomodulating agent. MATERIALS AND METHODS: We retrospectively reviewed the records of 2,351 patients with multiple sclerosis referred to the National Center for Multiple Sclerosis. RESULTS: Of the 2,351 patients 2 women and 5 men (0.29%) had bladder cancer. Of the 850 chronically catheterized patients the incidence was 0.7%. One patient with cancer performed intermittent catheterization for a rate of 0.23% in this group. In a subgroup of 70 patients treated with cyclophosphamide 5 chronically catheterized patients (5.7%) had bladder cancer. Hematuria was the most common presenting symptom. These data were compared with those in the literature on bladder cancer in spinal cord injury. CONCLUSIONS: These data suggest a possible synergistic role of cyclophosphamide and chronic catheterization in the induction of secondary bladder cancer. Regular cystoscopy is warranted in these patients to allow early detection of bladder tumors. Nitric oxide metabolism may be an important factor in the carcinogenesis of this type of bladder cancer.     

Epilepsy in patients with multiple sclerosis: radiological-clinical correlations

This study was performed to determine whether the stimulatory effect of plasma angiotensin II (ANG II) on arginine vasopressin (AVP) and oxytocin (OT) secretion in humans is mediated by AT1 subtype receptors. For this purpose, the effects of the AT1 receptor antagonist losartan (50 mg orally) or a placebo on the AVP and OT responses to ANG II (intravenous infusion for 60 minutes of successively increasing doses of 4, 8, and 16 ng/kg min; each dose for 20 minutes) administration were evaluated in seven normal men. In additional experiments, the same subjects were tested with losartan (50 mg orally) alone or placebo alone. Neither losartan nor placebo given alone modified the basal levels of AVP and OT. ANG II infusion induced significant increments in both serum AVP and OT levels (mean peaks were 1.55 and 1.41 times higher than baseline, respectively). Both hormonal responses to ANG II were completely abolished by pretreatment with losartan. These data provide evidence of AT1 receptor involvement in mediation of the ANG II-stimulating effect on AVP and OT secretion.