Unexpected rhabdomyolysis with myoglobinuria in a patient in the supine position

BACKGROUND: The relapse rate after steroid induced remission in Crohn's disease is high. AIMS: To test whether oral pH modified release budesonide (3 x 1 mg/day) reduces the relapse rate and to identify patient subgroups with an increased risk of relapse. METHODS: In a multicentre, randomised, double blind study, 179 patients with steroid induced remission of Crohn's disease received either 3 x 1 mg budesonide (n = 84) or placebo (n = 95) for one year. The primary study aim was the maintenance of remission of Crohn's disease for one year. RESULTS: Patient characteristics at study entry were similar for both groups. The relapse rate was 67% (56/84) in the budesonide group and 65% (62/95) in the placebo group. The relapse curves in both groups were similar. The mean time to relapse was 93.5 days in the budesonide group and 67.0 days in the placebo group. No prognostic factors allowing prediction of an increased risk for relapse or definition of patient subgroups who derived benefit from low dose budesonide were found. Drug related side effects were mild and no different between the budesonide and the placebo group. CONCLUSION: Oral pH modified release budesonide at a dose of 3 x 1 mg/day is not effective for maintaining steroid induced remission in Crohn's disease.     

A novel metabolic communication between neurons and astrocytes: non-essential amino acid L-serine released from astrocytes is essential for developing hippocampal neurons

BACKGROUND: Daily administration of rectal formulations of mesalazine is effective in preventing relapse of ulcerative proctitis. Maintenance of remission with lower doses would be an advantage. AIM: The efficacy of mesalazine suppositories (Pentasa) 1 g three times a week v placebo to maintain remission in patients with cryptogenetic proctitis was studied. METHODS: Ninety five patients with cryptogenetic proctitis were randomised within two weeks of remission to receive for one year or until relapse three suppositories per week of either Pentasa (n = 48) or placebo (n = 47). In the case of a relapse, the patients received one suppository/day. RESULTS: It was found that 25 of 48 subjects v 18 of 47 remained in remission in the mesalazine and placebo groups respectively. The relapse rate was lower in the mesalazine group for the following time intervals: 0-90 days (19% v 38%, p = 0.035), 0-180 days (29% v 54%, p = 0.017), 0-270 days (38% v 60%, p = 0.031), and 0-365 days (48% v 62%, p = 0.18). Treatment of relapse with one suppository/day induced remission in 11 of 18 and 2 of 26 patients in the mesalazine and placebo groups respectively (p = 0.001). Overall, 61% v 28% patients remained in the protocol and were in remission at one year (p = 0.001). Tolerance was good. CONCLUSION: Mesalazine suppositories 1 g three times a week are effective for preventing relapses of cryptogenetic proctitis. Increasing the dose to 1 g/day is effective in a high proportion of subjects who relapsed.     

Ribonucleases and host defense: identification, localization and gene expression in adherent monocytes in vitro

Modern medical therapy is increasingly based on evidence. The evidence presented here is that budesonide (Entocort, Astra Pharma) 9 mg/day is superior to placebo and equivalent to systemically active glucocorticosteroids in achieving disease remission in patients with active Crohn's disease, and in prolonging the recurrence time of symptomatic disease. Budesonide causes less disturbance to adrenal function than prednisone or prednisolone and may cause fewer steroid-associated symptoms. Thus, budesonide is the safer, more effective steroid of choice to treat patients with Crohn's disease.     

Initial response and subsequent course of Crohn's disease treated with elemental diet or prednisolone

Elemental diet is as effective as corticosteroids in the treatment of previously untreated Crohn's disease. It is unclear whether a poor nutritional state is a prerequisite for efficacy of elemental diet, whether previously treated patients respond as well, or how duration of remission using elemental diet compares with corticosteroid induced remission. Forty two patients with active Crohn's disease were stratified for nutritional state and randomised to receive Vivonex TEN 2.1 l/day for four weeks, or 0.75 mg prednisolone/kg/day for two weeks and subsequent reducing doses. Nine of 22 (41%) patients assigned to nutritional treatment were intolerant of the diet. Thirty patients completed four weeks treatment. Disease activity decreased on elemental diet from mean (SEM) 4.8 (0.9) to 1.7 (0.6), p < 0.05, and on prednisolone from 5.3 (0.5) to 1.9 (0.6), p < 0.05. For each treatment, nourished and malnourished patients responded similarly. Patients with longstanding disease responded as well as newly diagnosed patients. The probability of maintaining remission at six months was 0.67 after prednisolone, 0.28 after elemental diet, and at one year was 0.35 after prednisolone and 0.09 after elemental diet, p < 0.05. When tolerated, elemental diet is as effective in the short term as prednisolone in newly and previously diagnosed Crohn's disease, and its benefit is independent of nutritional state. The subsequent relapse rate after elemental diet induced remission, however, is greater than after treatment with prednisolone.     

Tumour necrosis factor alpha and interleukin 1beta in relapse of Crohn's disease

BACKGROUND: Concentrations of proinflammatory cytokines are increased in the intestinal mucosa of patients with active Crohn's disease. Experimental immunotherapeutic interventions with anticytokine agents in refractory Crohn's disease show that tumour necrosis factor alpha (TNF alpha) may be an important mediator of inflammation. We investigated the relation between production of TNF alpha and interleukin 1beta by mononuclear cells of the colonic lamina propria in patients with remitting Crohn's disease and the risk of relapse. METHODS: We followed up 137 patients with Crohn's disease in steroid-induced remission for 1 year. Secretion of proinflammatory cytokines (tumour necrosis factor alpha [TNF alpha] and interleukin 1beta) was assessed after short-term culture of human lamina propria mononuclear cells. FINDINGS: Increased secretion of TNF alpha and interleukin 1beta were predictive for acute relapses within the next year. Site and extent of disease, baseline demographics, and serum acute-phase proteins had little predictive value. INTERPRETATION: TNF alpha is important as a target molecule for immune interventions in Crohn's disease. The capacity to produce TNF alpha or interleukin 1beta may identify patients who would benefit from anti-inflammatory remission maintenance.     

Long-term management of Crohn's disease with mesalamine capsules (Pentasa). Pentasa Crohn's Disease Compassionate Use Study Group

Current long-term treatment of Crohn's disease is unsatisfactory. Based on the Crohn's Disease Activity Index (CDAI), this multicenter trial enrolled patients with either active Crohn's disease (CDAI > or = 150) or disease in remission (CDAI < 150). The primary measure of therapeutic response was mean change in CDAI from baseline to final visit. All patients began treatment with a dosage of < or = 4 g/day of mesalamine that ranged from 3.7 g at baseline to 3.4 g at final visit. Overall, 467 patients were enrolled: 333 (active disease) and 134 (remission). The median study participation time was 14 months. For patients entering with active disease, the mean reduction in CDAI was 77 points, with 42% (122/289) achieving remission by their final visit. For patients entering in remission, there was an increase in mean CDAI from 90 at baseline to 96 at final visit, with 79% (95/120) of patients in remission at final visit and 72% (31/43) in remission continuously after 12 months of therapy. From baseline to final visit, the mean prednisone dose decreased 5 mg/day in patients with active disease and 11 mg/day in patients in remission. Mesalamine was well tolerated and no adverse laboratory trends were observed. These results suggest that controlled-release mesalamine shows promise as a steroid-sparing agent and as a safe and effective long-term therapy for the induction of and maintenance of remission of mild-to-moderate Crohn's disease.     

Long-term treatment of ulcerative colitis with ciprofloxacin: a prospective, double-blind, placebo-controlled study

BACKGROUND & AIMS: Although bacterial bowel flora may be one of the contributing factors in the pathogenesis of chronic mucosal inflammation, antibiotic treatment has no established role in ulcerative colitis. The aim of the study was to evaluate the role of ciprofloxacin in the induction and maintenance of remission in ulcerative colitis in patients responding poorly to conventional therapy with steroids and mesalamine. METHODS: Ciprofloxacin (n = 38; 500-750 mg twice a day) or placebo (n = 45) was administered for 6 months in a double-blind, randomized study with a high but decreasing dose of prednisone and maintenance treatment with mesalamine including follow-up for the next 6 months. Clinical assessment and colonoscopic evaluation were performed at 0, 3, 6, and 12 months. Treatment failure, the primary end point, was defined as both symptomatic and endoscopic failure to respond. RESULTS: During the first 6 months, the treatment-failure rate was 21% in the ciprofloxacin-treated group and 44% in the placebo group (P = 0.02). Endoscopic and histological findings were used as secondary end points and showed better results in the ciprofloxacin group at 3 months but not at 6 months. CONCLUSIONS: Addition of a 6-month ciprofloxacin treatment for ulcerative colitis improved the results of conventional therapy with mesalamine and prednisone.     

Can fish oil maintain Crohn's disease in remission?

One of the greatest challenges in managing Crohn's disease is to maintain remission. Although pharmacologic approaches to maintaining Crohn's disease in remission have significantly improved, most of the currently available modalities are associated with significant morbidity. Recently, an enteric-coated preparation of fish oil has been shown to be effective in reducing the rate of relapse in patients with Crohn's disease in remission who are at high risk of relapse. Because of minimal side effects, fish oil appears to be an ideal maintenance agent in Crohn's disease. However, until results from studies that compare the therapeutic effect of fish oil to the currently available maintenance agents are available, fish oil supplementation cannot be recommended as a sole maintenance agent at present. It does, however, seem prudent to promote a diet rich in fish oil in patients with Crohn's disease.     

Crohn's disease and acute leukocytoclastic vasculitis of skin

A 39-yr-old white male with a prolonged history of Crohn's disease presented with worsening diarrhea associated with an increasingly painful rash of both lower extremities as well as left ankle swelling. A skin biopsy revealed an acute leukocytoclastic vasculitis. Intravenous hydrocortisone followed by oral prednisone achieved a rapid remission of the both cutaneous and gastrointestinal manifestations. Long-term remission has been maintained with 6-mercaptopurine and mesalamine. The rare association between cutaneous vasculitis and Crohn's disease is discussed and earlier reported cases reviewed.     

Comparison of mesalazine suppositories in proctitis and distal proctosigmoiditis

BACKGROUND: Mesalazine suppositories at 500 mg b.d. are a safe and effective treatment for patients with ulcerative proctitis or distal proctosigmoiditis. Recently a mesalazine 1 g suppository (Pentasa) has been developed. METHODS: Fifty patients with active ulcerative colitis extending not beyond 20 cm from the anus on sigmoidoscopy, participated in a randomized single-blind study comparing the efficacy, tolerance and acceptance of the new Pentasa mesalazine 1 g suppository, given once daily versus Claversal mesalazine 500 mg suppository b.d. RESULTS: After 2 weeks, clinical remission was observed in 16 of 25 (64%) in the Pentasa group and in 7 of 25 (28%) in the Claversal 500 mg b.d. treated group; sigmoidoscopic remission occurred in 13 of 25 (52%) in the Pentasa group and in six of 25 (24%) in the Claversal group (P < 0.01). After 4 weeks, clinical and sigmoidoscopic remission were observed, respectively, in 84 and 76% of patients treated with Pentasa suppositories, and in 80 and 72% of patients treated with Claversal suppositories 500 mg b.d. (P = N.S.). The patients' evaluation for tolerability and practicality showed that the Pentasa suppository was significantly superior to the Claversal suppository. CONCLUSIONS: Pentasa 1 g suppository once daily induces a quicker clinical and sigmoidoscopic remission, and was better tolerated, than the Claversal 500 mg suppository b.d., and it may represent an advance for the topical treatment of distal proctosigmoiditis.     

Long-term follow-up of patients with Crohn's disease treated with azathioprine or 6-mercaptopurine

BACKGROUND: Crohn's ulcerative gastrointestinal disease is presently managed through a variety of medical interventions, including-according to severity of illness-anti-inflammatory, immunosuppressive, and corticosteroid agents; and with remedial surgery to correct anatomical abnormalities caused by disease processes. The immunosuppressant azathioprine (or its metabolite, 6-mercaptopurine) is considered an efficient maintenance therapy for Crohn's, but there is always concern about bone-marrow suppression, liver damage, and other adverse effects. For how long persons with this disease should be given these drugs has not been determined. METHODS: Patients who were treated with azathioprine or 6-mercaptopurine for more than 6 months, and who were in prolonged clinical remission (> 6 months without steroids) were followed. The time-to-relapse was analysed in those on treatment, in those who stopped treatment for reasons other than a relapse, and in the whole sample, taking into account that they could be treated with the drugs or not, as a function of time. The influence of concomitant variables on time-to-relapse rate was examined using the Cox proportional hazard model. FINDINGS: In the 157 patients who continued to take the therapy, cumulative probabilities of relapse at 1 and 5 years were 11% and 32% respectively. Female gender, younger age, and a time for achieving remission more than 6 months were associated with a higher risk of relapse. In 42 patients who stopped therapy, probabilities of relapse at 1 and 5 years were 38% and 75%, respectively. Male gender, younger age and duration of remission less than 4 years were associated with a higher risk of relapse. After 4 years of remission on these drugs, the risk of relapse appeared to be similar, whether the therapy was maintained or stopped. INTERPRETATION: Taking into account the potential risks of long-term immunosuppressive therapy, the usefulness of maintaining azathioprine or 6-mercaptopurine in patients who have been in remission for more than 4 years is questionable.     

Plasma arachidonic acid-rich phospholipids in Crohn's disease: response to treatment

1. Increased concentrations of plasma polyunsaturated fatty acids have been implicated in the pathogenesis of Crohn's disease. However, it is not known whether there are corresponding changes in circulating phospholipids--the major source of fatty acids in the plasma. 2. Fasting plasma samples were obtained from 17 control subjects and 13 patients with active Crohn's disease [Simple Index of Crohn's Disease Activity (SICDA) > 6] before, and 2 and 8 weeks after, treatment with either a peptide diet or oral prednisolone. 3. Before treatment, the Crohn's disease patients had mildly active disease (SICDA 9.9 +/- 0.8, erythrocyte sedimentation rate 26.4 +/- 6.5 mm/h, serum C-reactive protein 2.8 +/- 0.4 mg/l). The proportions of the polyunsaturated phosphatidylcholine species, 16:0-20:4 (10.0 +/- 0.7%) and 16:0-22:6 (7.1 +/- 0.8%), were both significantly higher than those in healthy controls (7.6 +/- 0.5%, P < 0.01 and 5.3 +/- 0.5%, P < 0.05 respectively). 4. After 2 weeks treatment, the SICDA in the Crohn's disease patients decreased to 3.2 +/- 0.6 (P < 0.0001 compared with the pretreatment value), and there were corresponding falls in the erythrocyte sedimentation rate (to 12.6 +/- 2.7 mm/h, P < 0.05) and C-reactive protein concentration (to 1.7 +/- 0.3 mg/l, P < 0.05)--these improvements being maintained at 8 weeks. There was also a fall to normal values in 16:0-20:4 (to 7.7 +/- 0.6%, P < 0.01 compared with the pretreatment value) and in 16:0-22:6 (to 5.7 +/- 0.5%, P not significant), by week 8. 5. The proportions of polyunsaturated phosphatidylcholine molecular species were increased in the plasma of patients with active Crohn's disease, but fell to normal levels during disease remission. These observations are consistent with the theory that, in active Crohn's disease, the mucosal phospholipids containing polyunsaturated fatty acids are increased, contribute to eicosanoid synthesis and 'spill' into the plasma.     

Genomic organization and chromosomal localization of the Itm2a gene

BACKGROUND: Pemphigus vulgaris is a potentially life-threatening autoimmune disease. Although combination therapies with prednisone and azathioprine are usually effective in controlling the disease, some patients either do not respond to this treatment or show early relapses. OBJECTIVE: To find out whether mycophenolate mofetil would be an effective drug in controlling pemphigus vulgaris in patients who failed initial treatment with azathioprine and prednisone. RESULTS: Twelve patients who were initially diagnosed as having pemphigus vulgaris and had relapsed while undergoing treatment with azathioprine (1.5-2 mg/kg of body weight) and prednisolone (2 mg/kg of body weight) subsequently received combination therapy with mycophenolate mofetil (2 x 1 g/d) and prednisolone (2 mg/kg of body weight per day). Eleven of the 12 patients responded to therapy and showed no relapse of their disease even after tapering of the steroid dose. One patient did not respond. Toxic effects were low with only mild gastrointestinal symptoms in 5 patients and mild lymphopenia (World Health Organization grade I) in 9 patients. During the 9- to 12-month follow-up, none of the 11 patients showed reappearance of pemphigus lesions. CONCLUSION: Treatment of pemphigus vulgaris with mycophenolate is a safe and effective treatment.     

Adjuvant post-operative therapy

About 90% of patients with Crohn's disease require surgery at some time in their lives but the clinical recurrence rate after surgery is about 50% within 5 years, with 50% requiring further surgery within 10 years. Endoscopic evidence of relapse can be found in 75% within 12 weeks of resection. There is therefore a major problem to be solved. The solution is less clear. Retrospective studies suggest that smoking is a major factor determining a poor prognosis after surgery and it is most important that patients are encouraged to stop. There is strong evidence linking diet with Crohn's disease but the mechanism and nature of this link remains unclear. A low total fat intake, possibly supplemented with eudragitcoated n-3 fatty acid (fish oil) looks reasonable on current evidence but not proven. Mesalazine and metronidazole are the drugs for which most supportive evidence is available. The individual trials of mesalazine have generally proved inconclusive and meta-analyses have been needed to demonstrate a significant beneficial effect (approximately halving the relapse rate at 1 year). More recent large controlled studies performed after the meta-analyses however have again proved negative and the benefit is probably more modest than the meta-analyses suggested. Metronidazole, 20 mg/day for the first 3 months after surgery, has been shown to reduce relapse by just over one-third with a beneficial effect that was surprisingly sustained throughout a 3 year follow-up period. Peripheral neuropathy is a problem and further studies are needed at lower dosage. Azathioprine, 1.5-2 mg/kg/day is effective as maintenance therapy but there is insufficient evidence to recommend its routine post-operative use, moreover it takes up to 3 months to have an effect. Although budesonide has been shown to delay the time to relapse in non-operated patients it, like other corticosteroids, has been shown to be no better than placebo when maintenance is assessed according to the proportion of patients who remain relapse-free after 1 year. Patients undergoing operation for Crohn's disease should therefore be strongly advised to stop smoking. A 3 month course of oral metronidazole plus continued maintenance with oral mesalazine can be justified on current evidence but further studies are needed.     

Influence of topically and systemically active steroids on circulating leukocytes in Crohn's disease

OBJECTIVE: Budesonide, although only topically active, is effective in the treatment of Crohn's disease. This study was performed to compare the clinical efficacies of budesonide and prednisolone in relation to the activation status of circulating leukocytes. METHODS: Twenty-four patients with active Crohn's disease were randomized to treatment with either budesonide or 6-methylprednisolone. Clinical response was monitored by the Crohn's disease activity index, C-reactive protein, and orosomucoid. Expression of CD25 and CD71 on T cells and CD64 on neutrophils was determined by flow cytometry. The release of TNF-alpha and IL-1beta by peripheral blood mononuclear cells was measured by ELISA. RESULTS: After 2 wk of treatment a clinical response was observed in both groups, but it was more accentuated in patients treated with prednisolone. At baseline an upregulation of CD71 and CD64, but not CD25, was found in active patients. Prednisolone significantly decreased the expression of CD64 and the release of TNF-alpha and IL-1beta, but did not alter the expression of CD25 and CD71. Budesonide treatment failed to exert any effect on circulating leukocytes. CONCLUSIONS: The inability of budesonide to downregulate activated circulating leukocytes may contribute to the somewhat lower clinical efficacy of this topical steroid in the treatment of active Crohn's disease.     

Thrombotic thrombocytopenic purpura in 13 Dutch centres: treatment and longterm follow-up

OBJECTIVE: Analysis of the incidence, treatment modalities and disease course of thrombotic thrombocytopenic purpura (TTP) in the Netherlands. DESIGN: Retrospective follow-up study. SETTING: 13 centres in the Netherlands. METHODS: Regarding all patients admitted between 1-1-1979 and 1-1-1992 to one of 13 Dutch haematological centres, in whom the diagnosis of TTP was made for the first time, information was gathered from the medical records and from the patients own physicians on patient characteristics at presentation and the occurrence of relapse or death. The follow-up period tended on 1-4-1995. RESULTS: A total of 65 patients with newly diagnosed TTP were identified: 0.34 per 1,000,000 persons a year (95% confidence interval (95%-CI): 0.26-0.45), increasing to 0.83 in the last year of the study. Forty-six (95%) patients were treated with fresh frozen plasma: 18 (28%) by plasma infusion and 44 (68%) by plasma exchange; 48 (74%) (additionally) received corticosteroids. All 52 patients (80%) who survived the first four weeks after admission reached complete remission. Twelve patients with relapsing TTP underwent splenectomy in remission. The 5-year survival rate was 77% (95% CI: 66-87) and the 5-year relapse-free survival rate 38% (95% CI: 25-52). Cardiac symptoms, severe thrombocytopenia and a high serum LDH were risk factors for acute mortality, but no risk factors for relapse or late-occurring death could be identified. CONCLUSION: TTP is a rare disease which is increasingly being recognized. Plasma exchange and corticosteroids are the most frequently used therapies. The disease has a high mortality rate in the acute phase of the disease.     

The effects of topical steroids on refractive outcome and corneal haze, thickness, and curvature after photorefractive keratectomy with a 6.0-mm ablation diameter

BACKGROUND AND OBJECTIVE: To study the effect of topical prednisolone acetate after photorefractive keratectomy (PRK) using a 6.0-mm ablation diameter on the refractive and visual outcomes, corneal haze, corneal thickness, and corneal curvature in a prospective, double-masked, randomized manner. PATIENTS AND METHODS: Seventy-two eyes of 36 patients who had excimer laser PRK for correction of myopia ranging from -3.00 to -6.00 D (-4.11 +/- 0.84 D in eyes treated with steroids and -4.38 +/- 0.79 D in eyes treated with placebo; mean +/- SD) were enrolled. PRK procedures were performed using a 193-nm argon-fluoride excimer laser with 180-ml/cm2 fluence, a 10-Hz repetition rate, and a 6.0-mm ablation diameter. One eye of each patient was treated with the steroid (prednisolone acetate) and the other eye with placebo. Patients were observed for at least 12 months after PRK. RESULTS: There was no statistically significant difference between the steroid and the placebo groups with regard to refraction measurements that were taken postoperatively at 3 months (P = .39) and 12 months (P = .51). The corneas showed an increase in thickness after PRK in both groups, but the difference was not statistically significant at 12 months postoperatively (P = .45). The corneal haze score was not statistically different at any stage between groups (P = .30 at 3 months, P = .84 at 12 months). Keratometric data derived from corneal topography did not show any statistically significant difference (P = .85 at 3 months, P = .96 at 12 months). The rate of uncorrected visual acuity of 20/40 or more was 79.4% (27 eyes) in the steroid group and 70.5% (24 eyes) in the placebo group (P = .40). The rate of loss of 2 or more lines in best spectacle-corrected visual acuity was 5.85% (2 eyes) in the steroid group and 8.8% (3 eyes) in the placebo group (P = 1.0). CONCLUSION: Topical prednisolone acetate use for 3 months after PRK with a 6.0-mm ablation diameter has no effect on refractive and visual outcome, corneal haze, corneal thickness, and corneal curvature.     

Effect of sequential implanting with Synovex on steer and heifer performance

Studies were conducted using 72 (Exp. 1) and 248 (Exp. 2) steer and heifer calves from 1 to 2 mo of age through slaughter to determine whether preweaning implants affect postweaning feed conversion of cattle that are rapidly grown and(or) finished in the feedlot. In Exp. 1, treatments were three Synovex (S) implants administered 0, 70, and 140 d postweaning (NSSS) or Synovex-C (C) administered preweaning and three implants administered postweaning (CSSS). In Exp. 2, treatments were no implants (NNNN), implants administered 0, 74, and 148 d postweaning to calves that had either received no preweaning implant (NSSS), or C (CSSS), and CSSS plus trenbolone acetate (TBA) administered with the last S implant (CSSS-TBA). Synovex-S or -H implants were administered postweaning to steers and heifers, respectively. Steer and heifer calves implanted with C in the preweaning phase were 9.0 and 13.0 kg (Exp. 1) and 7.5 and 15.0 kg (Exp. 2) heavier (P < .10), respectively, at weaning than nonimplanted steer and heifer calves. In Exp. 1, preweaning implant had no affect on postweaning performance or quality grade. In Exp. 2, preweaning implants (NSSS vs CSSS) decreased (P < .10) steer postweaning gains, whereas postweaning implants (NSSS vs NNNN) increased (P < .10) DM intake; however, feed:gain ratio was not affected by implant strategy. Heifers in Exp. 2 that received implants had greater postweaning (P < .10) DM intakes and daily gains than heifers not receiving implants (NNNN); however, feed:gain ratios among treatment groups were unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)     

Management and outcome of borderline ovarian tumors incidentally discovered at or after laparoscopy

OBJECTIVE: The optimal antithyroid drug regimen for Graves' disease remains a matter of controversy. The European Multicentre Trial Group has investigated the effects of methimazole drug dose on the long-term outcome of Graves' disease. DESIGN: Extended follow-up of patients from a prospective multicentre trial, designed to study methimazole dose effects on the outcome of Graves' disease. We have reported previously that the relapse rates did not differ after a medication-free observation period of 12 months; the relapse rates were 37% and 38%, respectively. In this paper, we describe the outcome in these patients after a mean observation period of 4.3 +/- 1.3 years and have looked for potential predictors of this outcome. PATIENTS: Three hundred and thirteen patients with Graves' disease were randomized to treatment with a constant dose of 10 or 40 mg of methimazole for 1 year, with levothyroxine supplementation as required. MEASUREMENTS: At the time of inclusion into the trial: thyroid size, T4, T3, TSH-binding inhibiting immunoglobulins, urinary iodide excretion, thyroid uptake, Crook's therapeutic index of hyperthyroidism (a measure of clinical disease severity). At the time of follow-up examination: TSH, T4, T3, thyroid size, thyroid ultrasound, THS-binding inhibiting immunoglobulins. RESULTS: The overall relapse rate was 58%. There was no difference in relapse rates between patients treated with either 10 or 40 mg of methimazole (58.3 vs. 57.8%). Five patients had become spontaneously hypothyroid, without obvious relationship to antithyroid drug dose. Patients who relapsed and patients who remained in remission did not differ with respect to: age, goitre size, ophthalmopathy, median iodine excretion, serum T4 or serum T3, Crook's therapeutic index and thyroid uptake at the time of study entry. Thus, none of these variables was potentially suitable for predicting outcome. This finding was confirmed by Cox's proportional hazard regression. Thyroid volume, measured by ultrasound, did not differ between patients in remission and patients with relapse. There was no difference in the course of endocrine eye signs, in the requirement for steroid and radiotherapy for eye signs, or in thyroid echostructure between patients in the 10 and in the 40 mg group, nor was serum TSH different in patients who had remained in remission (0.8 +/- 0.6 mU/l in the 10 mg group, 1.0 +/- 0.8 mU/l in the 40 mg group). CONCLUSIONS: The dose of methimazole in Graves' disease therapy can safely be kept to the minimal required dose. This will provide the same chance of remission as higher doses, and provide the best balance of risk and benefit.     

Drug treatment of Crohn's disease]

The medical management of Crohn's disease has changed in recent years, but the mainstay of treatment is still prednisone. A substantial fraction of steroid-treated patients are refractory to therapy and addition of azathioprine or methotrexate has a corticosteroid-sparing effect and increases duration of remission. Controlled ileal release budesonide (9 mg daily) induces clinical remission in 60-70% of patients with Crohn's ileitis or right-sided colitis, and continued budesonide treatment has a finite effect on the duration of remission. The efficacy of mesalazine in active Crohn's disease is limited and high doses are required (4000 mg/day). The role of mesalazine in Crohn's disease in remission is disputed, and there is no evidence of a corticosteroid-sparing effect.