Episode Of Ulcerative Colitis Research Articles

Сравнительная оценка качества жизни и уровня тревоги и депрессии у пациентов с язвенным колитом

Aim: To assess the quality of life, the level of anxiety and depression in patients with ulcerative colitis (UC) depending on disease active/inactive status. Design: comparative prospective study. Materials and methods. In 2018–2020, a clinical study was conducted in Prof. S. V. Ochapovskiy Regional Clinical Hospital No. 1, which enrolled 218 patients: 178 patients with UC (139 patients with active disease and 39 patients with inactive disease) and 40 healthy volunteers (control group). In addition to routine examinations and faecal inflammatory markers, all patients underwent a quality-of-life assessment using The Short Form-36 (SF-36) and Inflammatory Bowel Disease Questionnaire (IBDQ), Clinical Activity Index (CAI), anxiety and depression evaluation using the Hospital Anxiety and Depression (HADS) scale. Results. The lowest mean values for SF-36 and the strongest correlations with CAI were observed in UC patients for the following domains: viability scale, overall health and emotional functioning (р < 0.05). Significant differences were recorded for IBDQ in mean values and correlations between the points on the scale and CAI for all domains (р = 0.0001). The strongest correlations were observed for the overall points and the “intestinal factor” domain (р = 0.0001). Lower mean values for SF-36 were in patients with chronic diseases not related to UC; for IBDQ, the situation was opposite — patients with extraintestinal UC signs had lower mean values. We found a correlation between HADS and CAI points which shows severity of an UC episode (r = 0.560; р = 0.01). Conclusions. The results demonstrate the importance of evaluation of the quality of life of patients with UC using both specific and nonspecific questionnaires, since they complement each other and allow personalising therapeutic approaches for patients with UC. Keywords: ulcerative colitis; inflammatory bowel diseases; quality of life; anxiety; depression.

Exploratory Study of the Effectiveness of Granulocyte and Monocyte Adsorptive Apheresis Before Initiation of Steroids in Patients with Active Ulcerative Colitis During the COVID-19 Outbreak (EXPECT Study): A Multicenter Prospective Clinical Trial

Background: During the COVID-19 pandemic, safe treatment of inflammatory bowel disease is required. Granulocyte and monocyte adsorptive apheresis (GMA) has been used for therapy of steroid-dependent/refractory ulcerative colitis (UC) with few adverse events. Therefore, elucidating the effectiveness of GMA without steroids is important in the current situation. The aim of this study was to investigate the effectiveness of GMA in active UC patients who are not receiving steroids. Methods: A single-arm, open-label, and multicenter prospective clinical trial was conducted at ten facilities in Japan.UC patients who had insufficient responses to 5-aminosalicylic acid without steroids received GMA twice a week for five consecutive weeks. The primary and secondary endpoints were the induction of a response and endoscopic mucosal healing in the patients who achieved a response. Findings: A total of 67 patients were enrolled. The response rate of all patients who received GMA ten times was 58·2%. Of the 39 patients who achieved a response, 74·4% achieved endoscopically confirmed mucosal healing. Both the median Mayo score and ulcerative colitis endoscopic index of severity score were significantly decreased in the patients who achieved a response. The response rate of the patients who were suffering from their first episode was significantly higher than that of those with relapse-remitting UC (80·0% [16/20] vs. 48·9% [23/47], p=0·029). Undergoing the first episode of UC (odds ratio [OR]: 4·952, 95% confidence interval [CI]: 1·292-18·981, p>0.001) was defined as an independent predictor of a response. Interpretation: This study strongly suggest that GMA shows promising effectiveness in inducing remission in active UC patients who are not receiving steroid treatment. We expect that GMA can be made available during the COVID-19 pandemic. Trial Registration: UMIN registration No. 000013702 Funding Statement: Health and Labor Sciences Research Grants from the Ministry of Health, Labor and Welfare of Japan (Investigation and Research for intractable Inflammatory Bowel Disease to HN). Declaration of Interests: MM reports personal fees from Janssen Pharmaceutical K.K., and commercial research funding from AbbVie GK. and Nippon Kayaku Co., Ltd. SN reports receiving personal fees from EA Pharma Co., Ltd., AbbVie GK., Mitsubishi Tanabe Pharma Corporation, Janssen Pharmaceutical K.K., Mochida Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd. KH reports receiving research funding from EA Pharma Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Co., Ltd. HN reports receiving personal fees from AbbVie GK., Kissei Pharmaceutical Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Janssen Pharmaceutical K.K., Takeda Pharmaceutical Co., Ltd., Pfizer Lnc., Cell gene Corporation., EA Pharma Co., Ltd., Zeria Pharmaceutical CO., Ltd., Mochida Pharmaceutical Co., Ltd., Nippon Kayaku Co., Ltd., Daiichi Sankyo Company, Limited., JIMRO Co., Ltd., as well as grants for commissioned/joint research from Hoya Group Pentax Medical, Boehringer Ingelheim GmbH, Bristol-Myers Squibb Company. All other authors declare no competing interests. Ethics Approval Statement: The protocol of the clinical trial was approved by the IRB at each institution. Informed consent to participate in the study was obtained from each participant before inclusion.

Health-Related Quality of Life in Patients with Moderate to Severe Ulcerative Colitis: Surgical Intervention versus Immunomodulatory Therapy

Purpose: Ulcerative colitis (UC) can be managed with immunomodulation or surgery. We aimed to understand whether these strategies had a different impact on patients’ health-related quality of life (HRQoL). Methods: This was a retrospective, cross-sectional study: patients who had a moderate to severe UC episode that prompted the utilization of immunomodulatory drugs or surgery were invited to complete a generic (short form [36] health survey [SF-36]) and a disease-specific (inflammatory bowel disease questionnaire [IBDQ]) survey. Results: We included 157 patients, 65 (41.4%) surgically treated. The therapeutic procedure had a minimal impact on HRQoL: only the social dimension of the IBDQ and the physical function component of the SF-36 were significantly different between the study arms – lower for the surgically treated patients. The type of surgery had no impact, but the occurrence of pouchitis, namely, in a chronic form, was associated with a lower HRQoL. Regression analysis confirmed surgery as an independent predictor of lower scores in the social dimension of the IBDQ (–4.646, 95% CI –6.953 to –2.339) and in the physical functioning (–9.622, 95% CI –17.061 to –2.183) and physical role functioning (–3.669, 95% CI –7.339 to 0.001) dimensions of the SF36. Conclusions: Although usually feared by patients, surgery has a limited impact on UC patients HRQoL when compared to medical management with immunomodulatory drugs.

Clostridium difficile in ulcerative colitis; a retrospective study

Aim : To study epidemiology and risk factors of Clostridium difficile infection (CDI) and its association with colectomy rates in patients with ulcerative colitis (UC). Materials and methods : We retrospectively analyzed medical files of 1179 patients with inflammatory bowel disease who had been treated from January 1 to December 31, 2017, in the Loginov Moscow Clinical Scientific Center (Moscow, Russia). UC was diagnosed according to the International Classification of Diseases, v. 10 (ICD10: K51). Final analysis included data from 400 UC patients. Depending on the presence of preliminary CDI diagnosis, the patients were divided into two groups: 79 (19.75%) patients with UC had at least one confirmed CDI episode, whereas 321 (80.25%) patients had no history of CDI. Results : CDI prevalence in UC patients was 19.75%, and 88.6% of the infectious episodes were community-acquired, whereas only 5.1% occurred in the inpatients. Mean (± SD) age at CDI occurrence in patients with inflammatory bowel disease was 37.8 ± 12.9 years. Only 13.4% of the patients with UC and associated CDI had the history of antibiotic therapy, and 40.5% had been previously treated with steroids. Prolonged immunosuppressive therapy in UC patients was associated with CDI: 41.8% of those with CDI had been treated with azathioprine/6-mercaptopurin for a long time, while among those without CDI this treatment had been administered only to 14.6% (p < 0.001). CDI prevalence in the UC patients who had been treated with mesenchymal stromal bone marrow cells was significantly lower than in those who had been treated with genetically engineered biological agents, both with and without immunosuppressants (p < 0.05). Surgery (colectomy) was necessary in 3 out of 4 patients with extremely severe UC associated with CDI, and in 2 out of 18 patients with extremely severe UC exacerbation without CDI. Conclusion : Young UC patients are more susceptible to CDI and often do not have any conventional CDI risk factors. In UC patients, other risk factors than in the general population, may have a significant impact on the CDI occurrence. UC patients with CDI more often have a history of salicylate failure, they more frequently require biological treatments, have lower mean albumin levels and higher activity of the inflammation. Extremely severe UC episode associated with CDI significantly increases the risk of colectomy.

Clinical outcome after discontinuation of infliximab in patients with ulcerative colitis in deep remission

Abstract Introduction Infliximab (IFX) is effective in treating ulcerative colitis (UC) and in achieving mucosal healing (MH). Little is known about the role of mucosal healing (MH) in the subsequent evolution of the disease and the consequences of discontinuing treatment. Aims To evaluate the characteristics and evolution of patients with UC treated with IFX who discontinued treatment after disease remission. Methods Observational, prospective study of patients with moderate to severe UC, corticosteroid-resistant/corticosteroid-dependent, naive to anti-TNF. IFX administration regimen: 5 mg/kg at 0-2-6 weeks and every 8 weeks thereafter until week 54. In patients achieving MH, IFX was discontinued and the patients were followed-up for at least 20 months. Clinical remission (CR): Mayo score Results Of the 21 patients enrolled, 19 completed the study (colectomy, n = 1; non-responder, n = 1). Mean age: 47.8 years. UC: severe (n = 13) and moderate (n = 6); most patients (n = 11) were steroid-resistant; 57.8% received combined treatment with immunosuppressants, and 31.5% intensified treatment. Week 54: 16 patients (84.2%) showed clinical response, 13 (68.4%) showed CR, and 12 (63.2%) deep remission. Of these, 6 (25%) presented a new episode of UC, and in 3 (25%) IFX was restarted within 12 weeks of discontinuation, with all patients responding. Of the total sample, 91.7% remained IFX-free at week 8, and 75% at week 12, with no remission during follow-up. None of the patients required hospitalisation or surgery. Conclusions Half of patients with deep remission of UC with IFX therapy presented a new episode after treatment discontinuation, and in 25% IFX therapy was restarted.

Evolución clínica tras la suspensión de infliximab en pacientes con colitis ulcerosa en remisión profunda

IntroductionInfliximab (IFX) is effective in treating ulcerative colitis (UC) and in achieving mucosal healing (MH). Little is known about the role of mucosal healing (MH) in the subsequent evolution of the disease and the consequences of discontinuing treatment. AimsTo evaluate the characteristics and evolution of patients with UC treated with IFX who discontinued treatment after disease remission. MethodsObservational, prospective study of patients with moderate to severe UC, corticosteroid-resistant/corticosteroid-dependent, naïve to anti-TNF. IFX administration regimen: 5 mg/kg at 0-2-6 weeks and every 8 weeks thereafter until week 54. In patients achieving MH, IFX was discontinued and the patients were followed-up for at least 20 months. Clinical remission (CR): mayo score <2; Clinical response: decrease in mayo score of 3 points; MH: mayo score 0-1; Deep remission: patient with CR and MH. ResultsOf the 21 patients enrolled, 19 completed the study (colectomy, n = 1; non-responder, n = 1). Mean age: 47.8 years. UC: severe (n = 13) and moderate (n = 6); most patients (n = 11) were steroid-resistant; 57.8% received combined treatment with immunosuppressants, and 31.5% intensified treatment. Week 54: 16 patients (84.2%) showed clinical response, 13 (68.4%) showed CR, and 12 (63.2%) deep remission. Of these, 6 (25%) presented a new episode of UC, and in 3 (25%) IFX was restarted within 12 weeks of discontinuation, with all patients responding. Of the total sample, 91.7% remained IFX-free at week 8, and 75% at week 12, with no remission during follow-up. None of the patients required hospitalization or surgery. ConclusionsHalf of patients with deep remission of UC with IFX therapy presented a new episode after treatment discontinuation, and in 25% IFX therapy was restarted.

Factors associated with treatment outcome, and long-term prognosis of patients with ulcerative colitis undergoing selective depletion of myeloid lineage leucocytes: a prospective multicenter study

BackgroundPatients with ulcerative colitis (UC) have elevated/activated myeloid lineage leucocytes and may respond favorably to adsorptive granulocyte/monocyte apheresis (GMA). However, there are patients who respond well to GMA, and patients who do not benefit. Therefore, predictive factors of GMA efficacy need to be defined. MethodsIn a prospective multicenter setting, 200 UC patients at 32 institutes received one GMA session per week over 10 weeks. Patients who achieved remission were followed for 12 months. The Clinical Activity Index (CAI) ≤3 meant remission, and response meant CAI decreased by ≥3. Quality of life was evaluated by the Inflammatory Bowel Disease Questionnaire (IBDQ). ResultsAfter final GMA, remission, response and no response rates were 67.0%, 15.0% and 18%, respectively. The remission group had a significant decrease in myeloid leucocytes and platelets. Corticosteroid dose decreased (P < 0.001); 49 of 97 patients on corticosteroids became steroid-free. Baseline CAI was lower in the remission group versus non-remission (P < 0.01), whereas IBDQ was higher in the remission group versus non-remission (P < 0.05). After 12 months, 52 of 134 patients had maintained remission. Disease duration was longer in the relapsed group versus maintained remission group (P = 0.041). Male gender, first UC episode and corticosteroid responder were significant factors for maintaining remission, whereas corticosteroid dependent UC was associating with relapse. DiscussionSelective myeloid leucocyte depletion was effective for remission induction and improving patients' quality of life. Baseline demographics such as disease activity level, duration and corticosteroid dependency appear to predict response to GMA. Additionally, patients with a first UC episode who were drug naive responded well to GMA and achieved a favorable long-term disease course by avoiding pharmacologics from an early stage of their inflammatory bowel disease. These findings should help to end unnecessary use of medical resources by targeting GMA to patients who may respond well.

Fecal calprotectin and lactoferrin as predictors of relapse in patients with quiescent ulcerative colitis during maintenance therapy

This prospective study was to evaluate the significance of fecal calprotectin and lactoferrin for the prediction of ulcerative colitis (UC) relapse. Eighty UC patients in remission for ≥3 months on mesalamine as maintenance therapy were included. At entry, stool samples were collected for the measurement of calprotectin and lactoferrin. All patients were followed up for the following 12 months. To identify predictive factors for relapse, time-dependent analyses using the Kaplan-Meier graphs and Cox's proportional hazard model were applied. During the 12 months, 21 patients relapsed. Mean calprotectin and lactoferrin levels were significantly higher in patients with relapse than those in remission (calprotectin-173.7 vs 135.5 μg/g, P = 0.02; lactoferrin-165.1 vs 130.7 μg/g, P = 0.03). A cutoff value of 170 μg/g for calprotectin had a sensitivity of 76 % and a specificity of 76 % to predict relapse, while a cutoff value of 140 μg/g for lactoferrin had a sensitivity of 67 % and a specificity of 68 %. In a multivariate analysis, calprotectin (≥170 μg/g) was a predictor of relapse (hazard ratio, 7.23; P = 0.002). None of the following parameters were significantly associated with relapse: age, gender, duration of UC, number of UC episode, severity of the previous episode, extent of UC, extraintestinal manifestation, and lactoferrin level. Fecal calprotectin showed a higher sensitivity and specificity than fecal lactoferrin for predicting UC relapse. Fecal calprotectin level appeared to be a significant predictor of relapse in patients with quiescent UC on mesalamine as maintenance therapy.

Long-term clinical impact of early introduction of granulocyte and monocyte adsorptive apheresis in new onset, moderately active, extensive ulcerative colitis

Background and aimsThe efficacy of granulocyte and monocyte adsorptive apheresis (GMA) for patients with a first episode of ulcerative colitis (UC) has been scarcely reported. This study was to see if the introduction of GMA at an early stage reduces corticosteroid administration and steroid dependency in the long term clinical course of UC. MethodsForty consecutive patients with moderately active symptoms as the first attack of UC were included. Twenty patients were treated with GMA, with or without corticosteroids (GMA group), and the other 20 were given corticosteroids without GMA (steroid group). All patients were monitored for 5years. Relapses were treated in the same manner as the first attack in both groups. The total dose of steroid administered and the appearance of steroid-dependency were to be compared between the two groups. ResultsAll patients in both groups achieved clinical remission after the first attack. The mean number of relapses per patient was 2.8 in the GMA group and 2.9 in the steroid group (P=0.86). During this study, 5 patients in the GMA group did not require corticosteroids. The mean dose of steroid administered during the 5years was 2141mg in the GMA group vs 5443mg in the steroid group (P=0.002). One patient in the GMA group and 7 in the steroid group were steroid-dependent at the end of the study (P=0.048). ConclusionsIn patients with the first UC episode, GMA therapy at an early stage significantly reduces steroid administration and steroid-dependency in the long-term clinical course.

Granulocyte and monocyte adsorptive apheresis in the management of ulcerative colitis

SIRS, We read with interest the systematic review: granulocyte ⁄monocyte adsorptive apheresis for ulcerative colitis by Thanaraj et al. It would appear that a majority of patients included in the reviewed studies were on corticosteroids. The authors found that compared with medical therapy, remission rates with granulocyte ⁄monocyte adsorptive apheresis (GMAA) were higher, and the treatment had significant corticosteroid-sparing effect. However, several uncontrolled studies 3 reported that GMAA was effective for steroid-naive patients or patients with the first episode of ulcerative colitis (UC). Recently, we completed a prospective trial aimed at identifying factors affecting clinical and endoscopic efficacies of GMAA in patients with active UC. The dose of corticosteroids at entry and the cumulative dose of corticosteroids administered before entry were independent significant factors for both clinical and endoscopic remission, negatively impacting the efficacy of GMAA. Such findings suggest that GMAA might have the effect of first-line therapy for steroid-naive patients or patients with the first UC episode. Up to now, the most common medication for UC has been corticosteroids. Most patients experience adverse side effects while on high-dose and long-term corticosteroids, adding to the disease complications and poor quality of life. In contrast, GMAA is favoured by patients for its safety, and patients with active UC can successfully be treated with GMAA without adding corticosteroids. In addition to the reported efficacy outcomes, I feel that the safety profile of GMAA is an attractive feature of this non-drug-based therapeutic intervention because adverse effects often compromise patients’ compliance with the treatment. Another factor, which must be considered when selecting a treatment option, is the treatment cost. When compared with corticosteroids, GMAA is expensive; one treatment session costs approximately €800. With this in mind, if GMAA can spare patients from corticosteroids, hospitalisation and surgery, it should be costeffective.

W1487: Corticosteroid Naive Patients and Patients With the First Ulcerative Colitis Episode and Short Duration of Disease Are Most Likely to Respond Well to Therapeutic Leucocytapheresis With the Adacolumn

The efficacy of infliximab has validated the notion that inflammatory bowel disease (IBD) like ulcerative colitis (UC) is exacerbated and perpetuated by specific cytokines, notably tumour necrosis factor (TNF)-α. Further, patients with active UC often harbour elevated and activated granulocytes/monocytes (GM), which are known to release TNF and other cytokines. Accordingly, several groups have investigated the efficacy of extracorporeal GM adsorption (GMA) in patients with IBD, but have reported unmatched efficacy outcomes, ranging from an impressive 85% (Cohen RD. Gastroenterology 2005;128:235-6) to an insignificant level (Sands BE, et al. Gastroenterology 2008;135:400-9). However, most hitherto studies recruited sub-groups of patients who had failed to respond to conventional medications and made no attempts to identify responders based on patients' baseline characteristics.

Leucocytapheresis for inflammatory bowel disease in the era of biologic therapy

(Table is included in full-text article.)The development of biologicals such as infliximab to intercept TNF-alpha validates the current perception that certain cytokines are major factors in the immunopathogenesis of inflammatory bowel disease (IBD), ulcerative colitis and Crohn's disease. Furthermore, major sources of inflammatory cytokines include activated peripheral granulocytes and monocytes (GM), which in patients with IBD are elevated with increased survival time and are found in vast numbers within the inflamed intestinal mucosa. Hence, elevated GM should be appropriate targets of therapy in IBD. Accordingly, in recent years technologies such as the Adacolumn have been developed for selective depletion of elevated GM by extracorporeal adsorption (GMA). Published data show that GMA in patients with steroid-dependent or steroid-refractory IBD is associated with striking efficacy and tapering or discontinuation of steroids, whereas in steroid-naïve patients GMA spared patients from steroids. Likewise, GMA at appropriate intervals in patients at a high risk of clinical relapse significantly suppressed relapse, thus sparing the patients from the morbidity associated with active IBD. First ulcerative colitis episode, steroid naivety and short disease duration seem to be good predictors of response to GMA and on the basis of our experience, GMA seems to have an excellent safety profile.

A Retrospective Search for Predictors of Clinical Response to Selective Granulocyte and Monocyte Apheresis in Patients With Ulcerative Colitis

Recently, selective granulocytapheresis (Adacolumn) has appeared as a new treatment for patients with inflammatory bowel disease. This study sought to determine predictors of response to this new nonpharmacologic mode of therapy by retrospectively evaluating 28 patients who received granulocytapheresis after experiencing active ulcerative colitis (UC). Between April 2000 and March 2004, 28 consecutive patients received granulocytapheresis for active UC with the Adacolumn, which is filled with cellulose acetate beads as the column leukocytapheresis carriers; the carriers adsorb granulocytes, monocytes/macrophages, and a small fraction of lymphocytes (FcgammaR and complement receptors bearing leukocytes). Each patient could receive up to 10 Adacolumn sessions, at 2 sessions per week. In 2004, clinical response was retrospectively evaluated. Seven days after the last Adacolumn session, 20 of 28 patients had remission (colitis activity index [CAI] < or =4) including all 8 patients who had their first UC episode. The mean duration of UC in the 8 first episode cases was 3.4 months compared with 40.2 months for all 28 patients and 65.4 months for the 8 nonresponders. The response to Adacolumn was independent of basal CAI. The 8 nonresponders were given conventional medication (CM) or cyclosporine (CsA) if the former failed. Two responded to CM, 3 to CsA, and 3 underwent colectomy. First UC episode and short disease duration appear good predictors of response to granulocytapheresis. Selective granulocytapheresis might be an effective first-line treatment.

Positions of selective leukocytapheresis in the medical therapy of ulcerative colitis

Ulcerative colitis (UC) and Crohn's disease (CD) are the major forms of idiopathic inflammatory bowel disease (IBD). Both UC and CD are debilitating chronic disorders that afflict millions of individuals throughout the world with symptoms which impair function and quality of life. The etiology of IBD is inadequately understood and therefore, drug therapy has been empirical instead of being based on sound understanding of IBD pathogenesis. This is a major factor for poor drug efficacy and drug related side effects that often add to the disease complexity. The development of biologicals notably infliximab to intercept tumor necrosis factor (TNF)-alpha reflects some progress, albeit major concern about their side effects and lack of long-term safety and efficacy profiles. However, IBD seems to be perpetuated by inflammatory cytokines like TNF-alpha, interleukin (IL)-1beta, IL-6 and IL-8 for which activated peripheral granulocytes and monocytes/macrophages (GM) are major sources. Further, in IBD, peripheral GMs are elevated with activation behavior, increased survival time and are found in vast numbers within the inflamed intestinal mucosa; they are suspected to be major factors in the immunopathogenesis of IBD. Hence, peripheral blood GMs should be appropriate targets of therapy. The Adacolumn is a medical device developed for selective depletion of GM by receptor-mediated adsorption (GMA). Clinical data show GMA, in patients with steroid dependent or steroid refractory UC, is associated with up to 85% efficacy and tapering or discontinuation of steroids, while in steroid naive patients (the best responders), GMA spares patients from exposure to steroids. Likewise, GMA at appropriate intervals in patients at a high risk of clinical relapse suppresses relapse thus sparing the patients from the morbidity associated with IBD relapse. Further, GMA appears to reduce the number of patients being submitted to colectomy or exposure to unsafe immunosupressants. First UC episode, steroid naivety and short disease duration appear good predictors of response to GMA and based on the available data, GMA seems to have an excellent safety profile.

Triple terapia inmunosupresora en el tratamiento de la colitis ulcerosa grave

Severe episodes of steroid-refractory ulcerative colitis (UC) were considered an indication for surgery until the introduction of new immunosuppressive agents such as cyclosporine. 1) To confirm the efficacy of intravenous cyclosporine in inducing remission in severe episodes of steroid-refractory UC; 2) To analyze the efficacy of triple immunosuppressive therapy with cyclosporine, azathioprine and prednisone in the maintenance of remission induced by intravenous cyclosporine. Fourteen patients diagnosed with a severe episode of steroid-refractory UC were treated with intravenous cyclosporine at a dose of 4 mg/kg/day. In all patients, after response was induced, this regimen was substituted by oral cyclosporine plus azathioprine at a dose of 2-2.5 mg/kg/day and decreasing doses of corticoids. Neoral cyclosporine was progressively reduced until discontinuation within 3 months, coinciding with a simultaneous decrease of oral steroids. All patients showed response to intravenous cyclosporine with a significant reduction in the Truelove index calculated before and after treatment. After remission was induced, all patients followed triple immunosuppressive therapy for 3 months. In the follow-up for a mean of 24 months (range: 14-34) only two patients required admission for a new episode of UC and colectomy was finally indicated in only one. None of the 14 patients treated with cyclosporine showed severe adverse effects attributable to the drug. Intravenous cyclosporine is a safe and effective alternative in the treatment of severe episodes of steroid-refractory UC. Early initiation of oral administration associated with azathioprine is useful in maintaining response, reducing subsequent relapses and the need for colectomy during the follow-up of these patients.

Idiopathic Myelofibrosis Associated with Ulcerative Colitis

A patient with ulcerative colitis (UC) who developed idiopathic myelofibrosis (IM) is reported. The initial diagnosis of UC was established by colonoscopy and large bowel biopsy, performed after a one-month history of abdominal pain and bloody diarrhea. The patient showed a favorable response to prednisone and mesalamine treatment and six months later he developed a new episode of UC, which was successfully controlled with treatment. However, two years later splenomegaly and anemia were observed, with aniso-poikilocytosis, tear-drop cells, immature myeloid precursors in the peripheral blood, and increased serum LDH, arising the suspicion of IM, a diagnosis that was confirmed by bone marrow biopsy. The present case represents a new association of IM with an autoimmune disease and gives support to the hypothesis of a possible immune basis of some IM cases.

Ulcerative colitis in the elderly: clinical patterns and outcome in 51 Greek patients.

In this study, the clinical characteristics and course of all patients with ulcerative colitis in whom diagnosis of the disease was made at or after the age of 60 (older group), were analyzed and compared with those of patients with ulcerative colitis in whom diagnosis of the disease was made before the age of 60 (younger group). The older group consisted of 51 patients (28 men and 23 women; aged 64+/-3.1 years) and the younger group consisted of 362 patients (192 men and 170 women; aged 38.4+/-14.9 years). The mean follow-up times in the two groups were 9.3 and 12.6 years, respectively. No significant differences between the two groups were found as far as the extent of the disease, the severity of the initial episode, and the outcome of the first episode of ulcerative colitis were concerned. However, significantly fewer elderly patients were operated on for their disease compared with younger patients (6.25% vs 22.3%; P = 0.0268). Although some differences in the course of the disease between elderly and younger patients were observed, such as the number of exacerbations and recurrences and the number of patients who developed colorectal cancer, these differences did not reach statistical significance. It is concluded that ulcerative colitis in elderly Greek patients runs a rather similar course to that in younger patients. However, some unique characteristics observed in the elderly patients (lower rate of colectomy, absence of patients with colorectal cancer, and increased death rate) could be attributed either to truly different disease behavior in the elderly people or to factors directly related to their advanced age.

Search for enteric microbial pathogens in patients with ulcerative colitis.

Microbial pathogens were sought in faeces of patients with active ulcerative colitis and again after 3 months treatment. 64 patients were examined during their first episode of ulcerative colitis and 30 with relapse of chronic disease. At presentation, bacterial pathogens were not found; 1 patient had cryptosporidiosis. In 10 patients treatment appeared to result in some loss of colonisation resistance as evidenced by colonisation with beta-haemolytic streptococci, Staphylococcus aureus, candida and Clostridium difficile. Unidentified cytotoxic activity was present in the faeces of 4 patients at presentation and 2 patients during or after treatment. We conclude that enteric infection is an uncommon finding in patients with active ulcerative colitis.

ERGOTISM: REPORT OF A CASE STUDIED ARTERIOGRAPHICALLY.

The symptoms of ergotism in its epidemic form have been well known for centuries. Fortunately, this form, due to the ingestion of spoiled grain, is no longer seen in this country, but the therapeutic use of ergot alkaloids may produce dramatic arteriospastic disorders. With the widespread employment of arteriographic technics in evaluating peripheral arterial insufficiency, the radiologist may be the first to recognize the vasospastic nature of the disorder and suggest the proper diagnosis. Following is a report of a patient in whom acute symptoms of arterial insufficiency of the right arm developed, initially thought to be due to embolic disease. Arteriography of both upper extremities, the clinical course, and the subsequent discovery that the patient had been using ergotamine tartrate suppositories, led to the diagnosis of arterial spasm caused by ergotism. Case Report A 54-year-old married woman was admitted to the Palo Alto-Stanford Hospital, Palo Alto, Calif., on Dec. 26, 1963, because of pain in the right arm and hand of one-week duration. Past history: Since November 1962 several episodes of ulcerative colitis had occurred. These symptoms were now quiescent. Present illness: During the week of Dec. 20, pain and fatigue occurred in the right arm and hand while the patient was washing dishes. With rest, the symptoms would immediately disappear. In the week prior to admission the pain became progressively more severe, and the patient noted the right hand was paler and colder than the left. Pertinent to these complaints is the following history. For several years the patient had suffered recurrent attacks of migraine headache. In September, 1962, she began to use Cafergot suppositories in an undetermined quantity. Her account of this quantity was inconsistent; at times she stated that she required from two suppositories a week to one or two each night. During the six weeks prior to hospitalization, she admitted employing at least six suppositories per week. Physical examination: The patient appeared tense and apprehensive. The fundi revealed Grade I arteriosclerosis. The carotid pulses were symmetrical and full without a bruit. The heart rate was 55 per minute, blood pressure was 130/90 mm Hg (left arm), and the lungs were normal. The pulses were absent on the right distal to the axillary artery and moderately diminished on the left. The Allen test was markedly positive on the right, but normal on the left. The femoral and pedal pulses were diminished bilaterally. Course: On Dec. 30 axillary arteriography was performed with selective injection into the innominate and left subclavian arteries. Gray Ödman catheters were introduced for this purpose through the left femoral artery, with the Seldinger technic.