Budesonide prolongs time to relapse in ileal and ileocaecal Crohn's disease. A placebo controlled one year study.

BACKGROUND AND AIMS: To evaluate the efficacy and safety of the topical corticosteroid budesonide, given in an oral controlled release formulation for maintenance of remission in patients with ileal and ileocaecal Crohn's disease (CD). PATIENTS AND METHODS: Out of 176 patients with active CD who had achieved remission (CD activity index score < or = 150) after 10 weeks' treatment with either budesonide or prednisolone, 90 were randomised to continue with once daily treatment of 6 mg budesonide, or 3 mg budesonide or placebo for up to 12 months in a double blind, multicentre trial. Time to symptomatic relapse was calculated using Kaplan-Meier estimates. Morning plasma cortisol was measured at clinic visits and a corticotropin stimulation test was performed after three months of treatment. RESULTS: Thirty two patients were allocated to the 6 mg budesonide group, 31 to the 3 mg group, and 27 to the placebo group. After three months, 19 per cent of the patients in the 6 mg group had relapsed, compared with 45 per cent in the 3 mg group and 44 per cent in the placebo group (p = 0.047). The corresponding results after 12 months was 59 per cent in the 6 mg budesonide group, 74 per cent in the 3 mg group, and 63 per cent in the placebo group (p = 0.44). The median time to relapse or discontinuation was 258 days in the 6 mg group, 139 days in the 3 mg group, and 92 days in the placebo group (p = 0.021). Mean morning plasma cortisol values increased from entry in all three groups with no statistically significant differences at 12 months. All 13 patients remaining in the placebo group after three months had a normal corticotropin stimulation response, compared with 18 of 23 patients in the 6 mg, and 19 of 21 in the 3 mg budesonide groups (p = 0.14). Acne and moon face were slightly more common in the budesonide groups. CONCLUSION: 6 mg budesonide once daily is significantly more efficacious than placebo in prolonging time to relapse in CD, and causes only minor systemic side effects.     

Analysis of the therapeutic efficacy of different doses of budesonide in patients with active Crohn's ileocolitis depending on disease activity and localization

Background and aims The nonsystemic steroid budesonide has been used to treat active ileocecal and ileocolonic Crohn's disease (CD). This study investigated the optimal budesonide dose using a pH-dependent release formulation. The goal of treatment was the remission of CD (CDAI <150) within 6 weeks of treatment.Patients and methods The study was of randomized, double-blind, dose-finding design. Patients with active CD ileocolitis without steroid pretreatment were treated with 3×2 mg (n=39), 3×3 mg (n=33), or 3×6 mg (n=32) oral pH-modified released budesonide daily.Results The remission rates after 6 weeks were 36% with 3×2 mg, 55% with 3×3 mg, and 66% with 3×6 mg. Significantly more patients were in remission while treated with 3× 6mg than with 3×2 mg budesonide/day. Subgroup analyses revealed that patients with high disease activity (CDAI 300) or ileocolonic disease with disease manifestation distal to the transverse colon responded better to the highest budesonide dose.Conclusion Oral pH-modified released budesonide shows a dose-dependent effectiveness in patients with active ileocolonic CD. In the majority of patients 9 mg budesonide per day is sufficient. However, in patients with highly active disease or ileal disease with distal colonic manifestation higher doses of budesonide could increase the therapeutic response     

Immune status in Crohn's disease : 3. Peripheral blood B lymphocytes, enumerated by means of F(ab)2-antibody fragments, Null and T lymphocytes

In the peripheral blood of patients with Crohn's disease (CD) the numerical distribution of the three major B lymphocyte subsets was determined by the identification of surface immunoglobulins using F(ab)₂-antibody fragments. T cell counts were also obtained and the number of null cells was calculated. Twenty-eight patients with Crohn's disease including 14 patients with previously untreated and very short-standing disease (group CD 1) and 14 patients with long-standing and/or previous drug treated disease (group CD 2) were compared with 28 sex and age-matched normals as well as with 13 patients with acute inflammatory bowel disease (group D). Patients in group D and inactive patients of group CD 1 showed a significant absolute lymphocytosis due to an increase in both the three B cell subsets and the T cells, without changes in the null cells. While the proportion of T cells was normal, there was a significant relative B lymphocytosis and a relative null cytopenia in these patients. Active CD 1 patients, however, showed significantly lower absolute lymphocyte and T cell numbers. In group CD 2, there was a significant absolute lymphopenia caused by an equal decrease in B and T cells. Highly active CD 2 patients showed higher absolute null cell counts than inactive patients. With increasing disease duration there was a significant decrease of the relative and absolute B cell concentrations. The data obtained suggest that T and B cell populations in the peripheral blood are reduced in certain patients with Crohn's disease and that this occurs secondarily to activity of disease, chronicity of disease, and the effects of therapy.     

European Cooperative Crohn's Disease Study (ECCDS): colonoscopy

130 patients with Crohn's disease were colonoscopied in a multicenter trial. The obtained data were analyzed with respect to gathering information on the inflammation pattern, as well as on the importance and prognostic value of special lesions in Crohn's colitis. In 52 patients a second endoscopy was performed at the end of the 2-year study period. Ulcerations and aphthous lesions were the most common lesions, followed by pseudopolyps, cobblestone lesions and stenosis. In general, there was an increasing, distal gradient in the frequency of severe lesions. patients with Crohn's colitis alone had more signs of inflammation than patients with additional involvement of the small intestine. A segmental pattern was the most common form of inflammation. The group of patients (14%) with a continuous pattern did not deviate from the whole collective in clinical activity. In patients with previous resections, inflammation near the anastomosis was accompanied more often than not by stenosis. Patients with ulcerations had a rather short time since confirmation of the diagnosis. Cobblestone lesions and pseudopolyps correlated with short symptomatology. During the follow-up of the study, patients taking steroids or a combination with prednisolone and sulfasalazine seem to have better results than those under placebo or sulfasalazine alone, as regards the more severe symptoms.     

Effects of aerobic exercise on cognitive performance and individual psychopathology in depressive and schizophrenia patients

Cognitive deficits are core symptoms in patients with schizophrenia (SZ) and major depressive disorder (MDD), but specific and approved treatments for cognitive deterioration are scarce. Experimental and clinical evidence suggests that aerobic exercise may help to reduce psychopathological symptoms and support cognitive performance, but this has not yet been systematically investigated. In the current study, we examined the effects of aerobic training on cognitive performance and symptom severity in psychiatric inpatients. To our knowledge, to date, no studies have been published that directly compare the effects of exercise across disease groups in order to acquire a better understanding of disease-specific versus general or overlapping effects of physical training intervention. Two disease groups (n = 22 MDD patients, n = 29 SZ patients) that were matched for age, gender, duration of disease and years of education received cognitive training combined either with aerobic physical exercise or with mental relaxation training. The interventions included 12 sessions (3 times a week) over a time period of 4 weeks, lasting each for 75 min (30 min of cognitive training + 45 min of cardio training/mental relaxation training). Cognitive parameters and psychopathology scores of all participants were tested in pre- and post-testing sessions and were then compared with a waiting control group. In the total group of patients, the results indicate an increase in cognitive performance in the domains visual learning, working memory and speed of processing, a decrease in state anxiety and an increase in subjective quality of life between pre- and post-testing. The effects in SZ patients compared with MDD patients were stronger for cognitive performance, whereas there were stronger effects in MDD patients compared with SZ patients in individual psychopathology values. MDD patients showed a significant reduction in depressive symptoms and state anxiety values after the intervention period. SZ patients reduced their negative symptoms severity from pre- to post-testing. In sum, the effects for the combined training were superior to the other forms of treatment. Physical exercise may help to reduce psychopathological symptoms and improve cognitive skills. The intervention routines employed in this study promise to add the current psychopathological and medical treatment options and could aid the transition to a multidisciplinary approach. However, a limitation of the current study is the short time interval for interventions (6 weeks including pre- and post-testing).     

Cellular heterogeneity in the thymus. I. Electrophoretic analysis of lymphoid cell populations from chickens

Micro-cell-electrophoresis has been applied to demonstrate differences and heterogeneities in various lymphocyte populations. The lymphocytes from the blood, spleen, bursa and thymus of young chickens differ significantly in their electrophoretic mobility (EM) pattern. The blood and spleen lymphocytes appear to be homogeneous by this criteria; bursa cells show slight heterogeneity, and thymus lymphocytes contain two clearly distinct subpopulations. One of the two thymocyte subpopulations is absent in neonatally bursectomized and irradiated animals. This bursa-dependent cellular component in the thymus has about the same EM as bursa cells themselves, which may suggest that these cells are, as such, derived from the bursa. The possible role of the bursa-dependent subpopulation is discussed. Within the first months of life, there is a dramatic shift from the predominance of the electrophoretically slower population to its virtually complete disappearence and the subsequent dominance of the other cellular component. Bursectomy plus irradiation provided pure preparations of one of the thymus subpopulations. The other subpopulation could be highly enriched by differential centrifugation in chicken plasma. Both subpopulations are thus separately available for direct immunological tests. The reduction of the EM by neuraminidase show that sialic acid is a major charged component in the cell surface of all lymphocyte preparations tested. The data indicate also that the different EM of the two thymocyte subpopulations is not due to different amounts of neuraminidase labile groups on the cell surface. The high EM of blood lymphocytes, on the other hand, is probably to be explained by a high content of neuraminidase-labile groups, as well as some ribonuclease sensitive material. A substantial reduction of the EM by ribonuclease was observed on blood lymphocytes, but not on lymphocytes from other organs.     

Cognitive and functional deficits are associated with white matter abnormalities in two independent cohorts of patients with schizophrenia

European Archives of Psychiatry and Clinical Neuroscience - Significant evidence links white matter (WM) microstructural abnormalities to cognitive impairment in schizophrenia (SZ), but the...     

Extracellular pH dynamics of retinal horizontal cells examined using electrochemical and fluorometric methods

Extracellular H(+) has been hypothesized to mediate feedback inhibition from horizontal cells onto vertebrate photoreceptors. According to this hypothesis, depolarization of horizontal cells should induce extracellular acidification adjacent to the cell membrane. Experiments testing this hypothesis have produced conflicting results. Studies examining carp and goldfish horizontal cells loaded with the pH-sensitive dye 5-hexadecanoylaminofluorescein (HAF) reported an extracellular acidification on depolarization by glutamate or potassium. However, investigations using H(+)-selective microelectrodes report an extracellular alkalinization on depolarization of skate and catfish horizontal cells. These studies differed in the species and extracellular pH buffer used and the presence or absence of cobalt. We used both techniques to examine H(+) changes from isolated catfish horizontal cells under identical experimental conditions (1 mM HEPES, no cobalt). HAF fluorescence indicated an acidification response to high extracellular potassium or glutamate. However, a clear extracellular alkalinization was found using H(+)-selective microelectrodes under the same conditions. Confocal microscopy revealed that HAF was not localized exclusively to the extracellular surface, but rather was detected throughout the intracellular compartment. A high degree of colocalization between HAF and the mitochondrion-specific dye MitoTracker was observed. When HAF fluorescence was monitored from optical sections from the center of a cell, glutamate produced an intracellular acidification. These results are consistent with a model in which depolarization allows calcium influx, followed by activation of a Ca(2+)/H(+) plasma membrane ATPase. Our results suggest that HAF is reporting intracellular pH changes and that depolarization of horizontal cells induces an extracellular alkalinization, which may relieve H(+)-mediated inhibition of photoreceptor synaptic transmission.