Predictive factors for an uncomplicated long-term course of Crohn's disease: a retrospective analysis.

BACKGROUND: Predictive factors for a mild course of Crohn's disease (CD) may have therapeutic consequences, but as yet have not been identified. AIMS: To identify baseline factors that predict mild CD and design a predictive scoring system. METHODS: A retrospective, multicenter study of newly diagnosed CD patients allocated to mild CD (no therapy, mesalazine only, or mesalazine with a single initial short course of low-dose prednisone) or moderate CD (all other patients including resected patients). RESULTS: 162 patients (median follow-up 43 months) were analyzed: 47 mild CD and 115 moderate CD. For mild CD versus moderate CD, mean age at first diagnosis was higher (41.1 versus 33.9 years, p=0.02), mean C-reactive protein (CRP) concentration was lower (1.6 versus 3.6 mg/L, p<0.01), and perianal lesions were less frequent (0% versus 10.4%, p=0.02). The combined incidence of complications (stenosis, any type of fistula, extraintestinal complications or fever) was 21.3% in mild CD versus 35.7% in moderate CD (p=0.07). A scoring system based on age, CRP, endoscopic severity (adapted Rutgeert's score), perianal lesions and combined incidence of complications was developed which can predict a mild prognosis at the initial diagnosis, giving patients the chance of simplified therapy and accelerated step-up in the event of treatment failure. CONCLUSIONS: Approximately a third of CD patients experience a mild disease course and require only basic therapy. A possible scoring system to predict mild CD which may avoid overtreatment and unnecessary risks for the patient and costs is suggested.

Clinical status, psychosocial impairments, medical treatment and health care costs for patients with inflammatory bowel disease (IBD) in Germany: an online IBD registry.

BACKGROUND: The aim of this cross-sectional study was to establish an online inflammatory bowel disease (IBD) registry for a first picture of the situation of IBD outpatients' treatment in Germany. METHODS: Between March 2006 and July 2007 IBD outpatients from 24 gastroenterological specialist practices and two hospitals in Germany were enrolled in an Internet-based registry to evaluate the outpatients' clinical status, psychological impairments, provided health care, as well as medical treatment and medication costs. RESULTS: 1032 IBD patients (ulcerative colitis/UC: 519; Crohn's disease/CD: 511; indeterminate colitis: 2) were enrolled in the study (age: 43 ± 14 years/M ± SD). Disease duration of all patients averaged 10 ± 8.5 years. In 519 UC-patients (49% male; 33% pancolitis), 66% were in remission as were 55% of CD patients (37 % male; 41 % active smokers). Associated with higher rates of disease activity (CDAI ≥ 150; CAI>4) were corticosteroids (CD, UC), topical medication (UC), relevant reported depressive symptoms (15%; 6-31%) and impairments in sexuality (21%; 9-42%). Relevant medication groups prescribed were oral aminosalicylates (UC: 70%; CD: 47%); immunosuppressive therapy - mostly azathioprine/6 MP (CD: 47%; UC: 26%), and Infliximab (CD: 8%; UC: 3%). Strongly associated with their clinical disease activity in UC as well as CD patients, 15% (6-31%) reported relevant depressive symptoms and 21% (9-42%) relevant impairments in sexuality. CONCLUSIONS: The registry constitutes a large complemental database for the patient population in Germany. About one third of the IBD patients were not in clinical remission (CDAI ≥150/CAI >4) (CD: 45%; UC: 27%), although high rates of immunosuppressive drugs (CD: 47%; UC 26%) were administered. This study shows a large burden of active disease associated with an unexpectedly high (co)morbidity and high psychosocial impairments, indicating a reduced health state in IBD patients.

Discontinuous and continuous stimulation of FRTL-5 thyroid cells with bTSH cause different cAMP and nuclear proliferation antigen responses.

Pulsatile TSH secretion has been described in man. We investigated the effect of discontinuous TSH stimulation on FRTL-5 thyroid cells. FRTL-5 monolayers were pulsed with TSH in 4 h incubation periods with alternate 4 h TSH-free intervals, or continuously incubated with TSH. The cAMP production of cells was measured in the supernatant of monolayers. Expression of a nuclear proliferation antigen in FRTL-5 monolayers was determined by a monoclonal antibody (Ki-67) using the alkaline phosphatase-anti-alkaline-phosphatase staining method. The TSH concentration in the stimulation series ranged from 0.01 to 1.0 U/l medium. Rhythmic cAMP production was observed in both discontinuous and continuous stimulation. With discontinuous stimulation cAMP production peaked after about 24 and 48 h, while in the continuous presence of TSH peaks were observed at 32-40 and 48 h. At all TSH concentrations the effect of discontinuous stimulation was higher than in continuously stimulated cultures. The discontinuous incubation stimulated nuclear proliferation antigen expression of FRTL-5 more intensely and there was a positive correlation with TSH concentration. We conclude that the rhythmic pattern of cAMP production after TSH stimulation is independent of the TSH pulse. The amplitude of stimulation and proliferation of FRTL-5, however, is increased by discontinuous TSH application.

Increased cellular growth of FRTL-5 thyroid cells mediated by discontinuous stimulation with bTSH.

Previous reports showed pulsatile secretion of TSH in man. Therefore, we investigated the effect of discontinuous versus continuous TSH stimulation on the cellular level of FRTL-5 thyroid cells, namely the expression of a nuclear proliferation antigen (NPAg). The expression of this antigen correlates linearly with the 3H-thymidine incorporation and is a marker for cellular growth. The FRTL-5 cells were stimulated for 4 hours with bTSH (0.01-1.0 U/l). Compared to continuously stimulated cell cultures the discontinuous stimulation of FRTL-5 cells with bTSH showed a significant higher rate of NPAg expression, i.e. cellular growth.

[Clinical relevance of the determination of TSH-binding inhibitory immunoglobulins (TBII) in patients with immunogenic hyperthyroidism in methimazole therapy]. / Klinische Relevanz der Bestimmung von TSH-Bindungs-inhibierenden Immunglobulinen (TBII) bei Patienten mit immunogener Hyperthyreose unter Methimazoltherapie.

In 38 patients with immunogenic hyperthyroidism a follow-up was performed to estimate the value of TBII before, during and after methimazole therapy. Before therapy increased TBII were detectable in 37 patients (94.4%). After 12 months methimazole therapy 25 patients had TSH-receptor antibodies (66%) within the normal range. In 13 patients positive antibody titres were found. In most cases persistence of increased TBII-values during drug treatment was an indicator of the persistence of active hyperthyroidism (10 of 13 patients). In the rule a disappearance of TBII-activity was combined with a functional remission (22 of 25 patients). Prolonged demonstration of TBII-activity in conjunction with persistence of hyperthyroidism should lead to ablative measures. In contrast to this medical therapy should be finished in patients with immunological and functional remission. Though in the further follow-up a recurrence of the immunological base of the disease with a functional and clinical relapse is possible.