A loading dose does not decrease the time to response in patients with steroid-treated Crohn's disease beginning azathioprine therapy. Steady state of erythrocyte 6-thioguanine nucleotide and complete response occurred earlier than previously reported.

This study aimed to examine the relationship between exposure to rat urinary allergens, atopic status, smoking and the development of allergic symptoms and specific sensitization.It is a case-referent analysis of a cohort of 342 newly employed laboratory animal workers. Cases comprised persons developing symptoms of laboratory animal allergy or a positive skin prick test to rat urinary allergens; each was matched with up to two asymptomatic referents. Subjects were assigned to categories of exposure based on measurements of airborne rat urinary allergens.Of the cases, 80% reported that their symptoms started within 2 yrs of employment. The odds ratio (OR) for development of each symptom type (respiratory, eye or nose and skin) and of an immediate skin test reaction was increased in those with direct contact with rats. A gradient of increasing OR for the development of any such symptom across exposure categories was found; for respiratory symptoms and skin test reactions the OR for subjects in the highest exposure category were lower than those in intermediate categories, a pattern attenuated when the analysis was confined to outcomes developing within 2 yrs of first exposure. Atopy increased the OR of most outcomes as did cigarette smoking, although there was no evidence of a relationship between smoking and the development of a specific skin test reaction.In conclusion, allergen exposure was confirmed as the most important determinant of laboratory animal allergy; by implication, measures to reduce exposure may be the most effective means to reduce its incidence. Eur Respir J 1999; 13: 1139±1143. Allergy to inhalable, animal-derived proteins is a common occupational health problem among employees working with small laboratory animals. In a prospective study of new staff at a large toxicological laboratory with several animal species, the incidence of clinically-diagnosed laboratory-animal allergy in the first year was 9% and that of specific immunoglobulin (Ig)E development~22% [1].Figures from the surveillance of work-related and occupational respiratory disease (SWORD) national surveillance scheme indicate that laboratory animal proteins are the commonest high molecular weight cause of occupational asthma seen by chest and occupational physicians in the UK [2]; the annual incidence of new cases of laboratory animal asthma in the UK, estimated from the same source, is at least 188 per million exposed employees [3].With the development of immunoassays [4] it has become possible to measure directly the relationship between intensity of exposure to airborne animal allergens and sensitization and allergic disease. This relationship has been studied in a cohort with occupational exposure to laboratory rats; in a previous report of the initial, cross-sectional phase [5] weak associations between allergic symptoms and rat urinary aeroallergen exposure, modified by atopic status were described. The present study describes the findings of a full longitudinal study, analysed using a nested case-referent approa...

Alosetron 0.5 mg and 1 mg once daily as well as 1 mg twice daily are effective in providing global improvement in IBS symptoms, adequate relief of IBS pain and discomfort, and improvement in bowel symptoms in women with severe d-IBS. Lower dosing regimens resulted in a decreased constipation rate.

This study was designed to explore the incidence of lupus anticoagulant (LA) and anticardiolipin antibodies (ACA) and their relationship to each other in a healthy population of 499 blood donors. Plasma samples were tested for LA activity and IgG, IgM and polyvalent ACA. Prolongation of the kaolin clotting time of a mixture of 80% normal plasma and 20% test plasma compared to the normal (dKCT) was used to detect LA activity. A normal distribution of dKCT was found with the mean 3.5 seconds +/- SD 10.6 seconds. Forty subjects (8%) were greater than 10% of the normal control; among these, 18 (3.6%) were outside the 95% confidence limits. The median age (29.3) and sex (M = 12, F = 28) of the 40 subjects with prolonged KCT were significantly different (p less than 0.001) from the group as a whole, younger females predominating. The frequency distribution of IgG, IgM and polyvalent ACA was skewed and the majority did not have detectable levels. ACA concentration falling within 95% of the population group were regarded as normal. Applying this definition, abnormal IgG ACA was greater than 4.33 U/ml, IgM ACA greater than 3.55 U/ml and polyvalent ACA greater than 4.55 U/ml with a prevalence of 4.6%, 4.6% and 5.6% respectively. Of the subjects with positive ACA of any class there was no significant association with either age or sex or the presence of LA. Only three plasma samples had both activities. Neither ACA nor LA were associated with antinuclear antibodies (ANA) or rheumatoid factor (Rh factor). Thus, in a healthy population LA is found predominantly in younger females and neither LA or ACA appear to identify subjects with other autoimmune parameters such as ANA or Rh factor or, for that matter, each other.

A total of 801 women were randomized to the alosetron (n = 532) or placebo groups (n = 269). Physicians classified 98% of patients with diarrhea-predominant IBS. Patients treated with alosetron had a significantly greater proportion of days with satisfactory control of urgency compared to placebo for the treatment period (73% vs 57%, p < 0.001). A significantly greater number of patients treated with alosetron were IBS Global Improvement responders compared to placebo at week 12 (76% vs 44%, p < 0.001). IBS Global Improvement responders had more days with satisfactory control of urgency at week 12 (88% vs 48%) as well as firmer stools, fewer stools/day, and fewer days with incomplete evacuation compared with nonresponders. Alosetron-treated patients showed improvements in bowel functions compared to placebo-treated patients. Constipation was the most commonly reported adverse event.

Findings are presented from the initial cross sectional phase of a cohort study of employees exposed to laboratory rats. Of 366 eligible workers at four sites 323 (88%) were surveyed; symptoms assessed by self completed questionnaire and sensitisation measured by the response to skin prick tests were related to intensity of exposure both to total dust and to rat urinary aeroallergen. Among 238 workers, without previous occupational expo--sure to rats, work related symptoms, which started after first employment at the site were related to exposure intensity (expressed either in terms of dust or of aeroallergen) at the time of onset of symptoms. These relations were stronger in atopic subjects but were unrelated to smoking. Positive skin tests to rat urinary extract were also more frequent with increased exposure, a relation found in both atopic subjects and in smokers. There was a strong association between work related symptoms and specific sensitisation. ( information; the current cohort study was designed to correct these deficiencies. We report findings of the initial phase. Subjects and methods SURVEY METHODSFour institutions specialising in small animal research in the United Kingdom were identified: three use a variety of animals including rats; the fourth uses almost exclusively mice and is not described in this paper. All full time employees in occupational groups where exposure to laboratory rats or mice was probable and a group of non-exposed office workers, who had started work at the site from 1 January 1986 onwards and had worked for at least one month, were invited to participate.Members of the cohort still employed at the sites have been surveyed at six-monthly intervals since 1990. We describe the findings from the initial survey. Two visits to each site were made, the second to collect information from those missed at the first visit. Of 366 eligible subjects 323 (88%) were surveyed, with no difference in response rates between the three workforces. Questionnaires were completed by 315 subjects (84%) and skin prick tests by 295

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Studies were performed to determine the cross-reaction rate of the heparin-dependent antibody with Org 10172, a new low molecular weight heparinoid, and to investigate the effect of Org 10172 on platelet activation induced by the antibody. The plasmas of 17 patients with thrombocytopenia induced by standard heparin were shown, by platelet aggregation studies, to contain the heparin-dependent antibody. Of these 17 patient plasmas, only three cross-reacted with the heparinoid, producing a cross-reaction rate of 18%. When Org 10172 was added to a reaction mixture containing normal platelet-rich plasma, patient plasma, and standard heparin with non-cross-reacting plasmas, it inhibited platelet aggregation and thromboxane B2 production induced by the antibody, provided that the ratio of Org 10172 concentration (anti- Xa U/mL) to standard heparin concentration (IU/mL) exceeded 2.5 to 5.0. This inhibitory effect was observed only with platelet activation mediated by the antibody, but not by collagen (2 micrograms/mL) or ADP (5.0 mumol/L). Additionally, three of 17 patients with serious thrombosis, whose plasma showed no cross-reaction with the heparinoid, received Org 10172 treatment with a good response in each case. These findings suggest that Org 10172 may be a useful drug for the treatment of heparin-induced thrombocytopenia.