Ulcerative Colitis: Sawada K

Saniabadi AR, Hanai H, Fukunaga K, Sawada K, Shima C, Bjarnason I, Lofberg R. · JIMRO Laboratories, 351-1 Nishiyokote Machi, Takasaki, Japan. · Transfus Apher Sci. · Pubmed #17974479 No free full text.

Abstract: The inference that granulocytes and monocytes/macrophages (GM) are part of the immunopathogenesis of inflammatory bowel disease (IBD) and hence should be targets of therapy stems from observations of elevated, and activated GM in patients with IBD. The Adacolumn can selectively deplete GM by adsorption (GMA) and in patients with IBD, GMA has been associated with significant clinical efficacy together with sustained suppression of inflammatory cytokine profiles. Additionally, GMA depleted proinflammatory CD14(+)CD16(+) monocytes and was followed by an increase in CD4(+) T lymphocytes including the regulatory CD4(+)CD25(high+)Foxp3 phenotype. Hence, GMA could be a non-pharmacologic therapy for IBD with potential to spare steroids and other unsafe pharmacologic preparations.

Saniabadi AR, Hanai H, Suzuki Y, Ohmori T, Sawada K, Yoshimura N, Saito Y, Takeda Y, Umemura K, Kondo K, Ikeda Y, Fukunaga K, Nakashima M, Beretta A, Bjarnason I, Lofberg R. · Japan Immunoresearch Laboratories, Nishiyokote Machi, Takasaki, Japan. · J Clin Apher. · Pubmed #15892107 No free full text.

Abstract: Inflammatory and/or autoimmune diseases like ulcerative colitis (UC) or Crohn's disease (CD) are debilitating chronic disorders that poorly respond to pharmacological interventions. Further, drug therapy has adverse effects that add to disease complications. The current thinking is that disorders like inflammatory bowel disease (IBD) reflect an over exuberant immune activation driven by cytokines including TNF-alpha. Major sources of cytokines include myeloid leukocytes (granulocytes, monocytes/macrophages), which in IBD are elevated with activation behavior and are found in vast numbers within the inflamed intestinal mucosa. Accordingly, myeloid cells should be the targets of therapy. Adacolumn is filled with cellulose acetate beads that selectively adsorb and deplete myeloid cells and a small fraction of lymphocytes (FcgammaR and complement receptors bearing cells). In one study, 20 steroid naive patients with moderate (n = 14) or severe (n = 6) UC according to Rachmilewitz despite 1.5-2.25 g/day of 5-aminosalicylic acid received 6 to 10 Adacolumn sessions at 2 sessions/week. Efficacy was assessed 1 week after the last session. The majority of patients responded to 6 sessions, 17 (85%) achieved remission. In 2 of the 3 non-responders, CAI was 8 and 12 in 1; all 3 had deep colonic ulcers at study initiation. Decreases were seen in total leukocytes (P = 0.003), % neutrophils (P = 0.003), % monocytes (P = 0.004), an increase in lymphocytes (P = 0.001), decreases in C-reactive protein (P = 0.0002), and rises in blood levels of soluble TNF-alpha receptors I (P = 0.0007), II (P = 0.0045). In a separate study, a case with very severe steroid refractory UC who received up to 11 sessions responded well and avoided colectomy. Further, myeloid cell purging with Adacolumn has been associated with the release of IL-1 receptor antagonist, suppression of TNF-alpha, IL-1beta, IL-6, IL-8, down-modulation of L-selectin and the chemokine receptor CXCR3. In conclusion, selective depletion of myeloid cells appears to induce anti-inflammatory effects and represents a non-pharmacological treatment for patients with active IBD. The treatment has a clear drug-sparing role. Changes in blood levels of inflammatory and anti-inflammatory factors are thought to contribute to the efficacy of this procedure.

Sawada K. · Department of Gastroenterology, Hyogo College of Medicine, 1-1, Mukogawa, Nishinomiya, Hyogo 663-8501, Japan. · Dis Colon Rectum. · Pubmed #14530661 No free full text.

Abstract: Inflammatory bowel disease is characterized by clinical remission and relapse caused by severe intestinal inflammation. Drug therapy for inflammatory bowel disease is associated with unpleasant side effects. Furthermore, efficacy of conventional drugs decreases with chronic use, which can be a major difficulty in the long-term management of this disease. In active inflammatory bowel disease, leukocytes are elevated with activation behavior and increased survival time, and mucosal neutrophil level parallels the severity of intestinal inflammation and predicts relapse. Leukocyte-derived inflammatory cytokines are suspected to be major factors in the initiation and perpetuation of inflammatory bowel disease. Accordingly, leukocytes should be appropriate targets for therapy. To reduce peripheral blood level of leukocytes, centrifugation has been used to deplete peripheral blood leukocytes; this provided the initial evidence that reducing the level of peripheral blood leukocytes can benefit patients with inflammatory disease. To overcome the limitations of centrifugation, membrane filters, such as the Cellsorba trade mark column and leukocyte-adsorbing beads containing column like Adacolumn, have been developed that are direct blood perfusion systems for removing any desired level of leukocytes. In initial independent clinical studies, these two new models have produced striking clinical efficacy, safety, and a marked reduction in the dose of corticosteroids used to induce remission of active inflammatory bowel disease. Leukocytapheresis has been associated with a significant decrease in the amount of several proinflammatory cytokines produced by peripheral blood leukocytes. Accordingly, the Japan Ministry of Health has now approved both methods for the treatment of active ulcerative colitis. Clinical data suggest that leukocytapheresis might be an effective adjunct to therapy for inflammatory bowel disease to promote remission, taper conventional drug dosage, and potentially reduce the number of patients who require colectomy. The results should further understanding of the pathophysiology of inflammatory bowel disease.

Fukunaga K, Sawada K, Chikano S, Ohnishi K, Egashira A, Tanaka J, Nagase K, Satomi M, Shimoyama T. · Department of Internal Medicine IV, Hyogo College of Medicine. · Nippon Rinsho. · Pubmed #10572419 No free full text.

Abstract: Leukocytapheresis(LCAP) and Granulocytapheresis(GCAP) are classified as extracorporeal circulation therapy(ECCT). These therapies are a novel, effective way to treat patients with ulcerative colitis(UC). During 7 weeks of intensive therapy(LCAP weekly, predonisolone(PSL) 30-80 mg/day), UC patients treated with LCAP revealed significant improvements on their subjective and objective symptoms compared to patients treated with PSL intravenous administration. Moreover, LCAP has been recognized as safer than other drugs for UC. In our previous study, only 9.9% out of 1,978 LCAP sessions showed some side effects, and most were mild and temporary. Therefore, LCAP could be the first choice to treat UC patients who resist and/or reveal severe complications against ordinary drug therapies.

Sawada K, Kusugami K, Suzuki Y, Bamba T, Munakata A, Hibi T, Shimoyama T. · Department of Gastroenterology, Hyogo College of Medicine, Nishinomiya, Japan. · Am J Gastroenterol. · Pubmed #15929771 No free full text.

Abstract: OBJECTIVE: Leukocytapheresis (LCAP) is a method of therapeutic apheresis that removes peripheral leukocytes. Previous studies showed that in patients with ulcerative colitis (UC), LCAP was more effective than high-dose steroid therapy, and it had few adverse effects. We investigated LCAP in a multicenter study using active and sham devices in a double-blind study in order to elucidate the placebo effect of extracorporeal treatment including anticoagulant medication. METHODS: Twenty-five patients with active UC of severe or moderately severe grade were enrolled and assigned to the active group or the sham group. Six patients were excluded from the study and 19 (10 in the active group and nine in the sham group) were evaluated. LCAP (treatment using an active device or a sham device) was performed once a week for 5 wk, followed by two additional sessions during the next 4 wk at 2-wk intervals. Steroids and other medications were continued at the same dosage for 4 wk, which included a 2-wk pre-observation period and the first 2 wk after the start of the LCAP treatment. New medications or increase in the dosage of previous medication were prohibited until evaluation was conducted. RESULTS: The clinical activity index (CAI) value of UC, indicated that the active group showed a significantly greater improvement (80%, 8/10) than the sham group (33%, 3/9; p<0.05). Adverse effects were observed in five patients (one in the active group and four in the sham group). None of these effects was severe and none of the sessions was terminated as a consequence of the adverse effects. CONCLUSION: The results confirmed that LCAP is a safe and effective therapeutic option for patients with active UC.

Sawada K, Egashira A, Ohnishi K, Fukunaga K, Kusaka T, Shimoyama T. · Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan. · Dig Dis Sci. · Pubmed #15844716 No free full text.

Abstract: Leukocytapheresis (LCAP) is a method of therapeutic apheresis to remove patients' peripheral leukocytes by extracorporeal circulation. Previous studies showed that LCAP for the treatment of ulcerative colitis (UC) was more effective and had fewer adverse effects compared to high-dose steroid therapy. However, there are no reports on the application of LCAP for UC patients with toxic megacolon (TM). This study reports the effectiveness and safety of LCAP in treating patients with severe or fulminant UC with TM. Six patients were enrolled in this study and LCAP sessions were performed three times per week for 2 weeks, followed by four further times in the next 4 weeks. After completion of therapy, four patients improved in TM and went into the remission stage of UC. The average Rachmilewitz clinical activity index of these four patients improved from 19.5 to 1. The remaining two patients had to undergo colectomy, however, the symptoms had been mitigated by LCAP and the operations were completed without any problems. These results suggest that LCAP is an additional effective and safe option for TM management in preventing colectomy or for bridging to a safer operation.

Sawada K, Muto T, Shimoyama T, Satomi M, Sawada T, Nagawa H, Hiwatashi N, Asakura H, Hibi T. · Dept of Gastroenterology, Hyogo College of Medicine, Nishinomiya, Tokyo, Japan. · Curr Pharm Des. · Pubmed #12570823 No free full text.

Abstract: The administration of steroids is not always effective for the treatment of ulcerative colitis (UC). Their long-term use often causes adverse effects which sometimes result in their stoppage and acute exacerbation. Therefore, an alternative treatment is necessary in order to decrease steroid dosage and avoid the clinical problems associated with steroids. Methods The effectiveness and adverse effects of a leukocytapheresis (LCAP) were investigated in a controlled multicenter trial with randomized assignment of 76 active-stage UC patients in two groups. In the LCAP group (39 patients), LCAP weekly for 5 weeks as an intensive therapy was added to the on-going drug therapy, while steroids were maintained but not increased, and then LCAP was gradually reduced to once every 4 weeks as a maintenance therapy. In the high dose prednisolone (h-PSL) group (37 patients), PSL was added or increased 30 approximately 40 mg/day for moderately severe and 60 approximately 80 mg/day for severe patients and then gradually tapered. Findings The LCAP group showed a significantly higher effectiveness (74% vs. 38%; p=0.005) and lower incidence of adverse effects (24% vs. 68%; p<0.001). The patients were able to continue the trial for a longer period in the LCAP group than the h-PSL group (p=0.012). Clinical activity and endoscopic indexes showed the LCAP group had better improvements than the h-PSL group. Interpretation The results of the trial show that LCAP permits a reduction in total PSL dosage and is more effective and safer than high-dose PSL administration for intensive therapy, and LCAP may maintain remission longer than PSL.

Shimoyama T, Sawada K, Hiwatashi N, Sawada T, Matsueda K, Munakata A, Asakura H, Tanaka T, Kasukawa R, Kimura K, Suzuki Y, Nagamachi Y, Muto T, Nagawa H, Iizuka B, Baba S, Nasu M, Kataoka T, Kashiwagi N, Saniabadi AR. · Department of Internal Medicine IV, Hyogo College of Medicine, Hyogo, Japan. · J Clin Apher. · Pubmed #11309823 No free full text.

Abstract: Active ulcerative colitis (UC) is characterized by activation and infiltration of granulocytes and monocytes/macrophages into the colonic mucosa. The infiltrated leukocytes can cause mucosal damage by releasing degradative proteases, reactive oxygen derivatives, and proinflammatory cytokines. The aim of this trial (conducted in 14 specialist centers) was to assess safety and efficacy of granulocyte and monocyte adsorption apheresis in patients with active UC most of whom were refractory to conventional drug therapy. We used a new adsorptive type extracorporeal column (G-1 Adacolumn) filled with cellulose acetate beads (carriers) of 2 mm in diameter, which selectively adsorb granulocytes and monocytes/macrophages. Patients (n = 53) received five apheresis sessions, each of 60 minutes duration, flow rate 30 ml per minute for 5 consecutive weeks in combination with 24.4 +/- 3.60 mg prednisolone (mean +/- SE per patient per day, baseline dose). During 60 minutes apheresis, 26% of granulocytes, 19.5% of monocytes and 2% of lymphocytes adsorbed to the carriers. At week 7, 58.5% of patients had remission or improved, the dose of prednisolone was reduced to 14.2 +/- 2.25 mg (n = 37). The apheresis treatment was fairly safe, only eight non-severe side effects (in 5 patients) were reported. Based on our results, we believe that in patients with active severe UC, patients who are refractory to conventional drugs, granulocyte and monocyte adsorption apheresis is a useful adjunct to conventional therapy. This procedure should have the potential to allow tapering the dose of corticosteroids, shorten the time to remission and delay relapse.

Sawada K, Ohnishi K, Fukunaga K, Chikano S, Egashira A, Satomi M, Shimoyama T. · Dept. of Internal Medicine IV, Hyogo College of Medicine. · Nihon Rinsho Meneki Gakkai Kaishi. · Pubmed #10726487 No free full text.

Abstract: To solve adverse effects of high dose steroid administration for patients with moderately severe and severe ulcerative colitis (UC), additional use of leukocytapheresis (LCAP) was tried to settle colonic inflammation. We evaluated immunological changes in the treatment of LCAP using leukocyte removal filter for UC patients. We then assessed the clinical effectiveness of LCAP compared with that of high dose of steroid therapy. LCAP removed monocytes, granulocytes, and lymphocytes presenting CD 11 b+, CD 11 c+, and HLADR+, selectively from the patients. Proinflammatory cytokine productions measured such as TNF alpha, IL-1 beta, and IL 8 reduced and IL 10 increased immediately after LCAP compared with before perfusion. Improved rate was about 70% for LCAP group and about 40% for high dose steroid group (Refer J Gastroenterol). Selective removal of granulocyte, monocytes, and activated lymphocytes inhibits proinflammatory cytokine production and increases immune modulating cytokine productions (Refer Therapeutic Apheresis). Then quick inhibition of several inflammatory deteriorated factors simultaneously controls the activity and clinical symptoms of UC with less severe adverse effects. It can be considered one option for treatment of UC.

Sawada K, Takahashi R, Saniabadi AR, Ohdo M, Shimoyama T. · Department of Gastroenterology, Fujimoto Hospital Medicine, 3-15-27 Konda Habikino, Osaka 583-0857, Japan. · World J Gastroenterol. · Pubmed #16570358 links to  free full text

Abstract: AIM: To investigate the role of cryofibrinogen (CF) in active inflammatory bowel disease (IBD). METHODS: CF was assayed in 284 subjects: 61 with active and 63 with inactive ulcerative colitis (UC), 45 who had proctocolectomy, 35 with active and 20 with inactive Crohn's disease (CD), 40 with other diseases and 20 healthy controls. Trypsin inhibitor (TI) and TI antibody (TI-Ab) were measured in plasma and CF complex by ELISA. RESULTS: CF in active UC was strikingly high compared with all other groups (c2<0.001). Similarly, CF was significantly higher in active CD than in inactive CD or in controls (c2<0.01). In UC, high CF and TI-Ab were associated with the need for operations. Further, high CF, CF/fibrinogen ratio, low TI and high TI-Ab in plasma were associated with disease activity or refractoriness to medication. Elevated CF was not associated with acute reactants like C-reactive protein and white blood cell counts except for erythrocyte sedimentation rate, suggesting that elevated CF was not a consequence of acute inflammation. CONCLUSION: Elevated CF in active IBD appears to be morbigenous. CF promotes IBD via two main mechanisms, quenching of TI (an anti-inflammatory substance) and impairing microvascular perfusion by forming protein aggregates. CF may also serve as a biomarker of chronic IBD. Additional studies are warranted to fully evaluate the role of CF in IBD and the outcome should contribute to a better understanding of the pathogenesis of IBD.

Nagase K, Fukunaga K, Ohnishi K, Kusaka T, Matoba Y, Sawada K. · Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan. · Ther Apher Dial. · Pubmed #15128019 No free full text.

Abstract: The aim was to determine whether adverse effects of leukocytapheresis (LCAP) are related to nafamostat mesilate (NM) as an anticoagulant. Anti-NM IgE were detected in inflammatory bowel disease (IBD) patients who were administrated LCAP in our institute. Forty-nine patients (ulcerative colitis (UC)/Crohn's disease (CD): 30/19) were evaluated. Anti-NM IgE was measured by the ELISA method. Total IgE level and eosinophil count was tested concurrently. We retrospectively checked the presence of allergic symptoms and medications used concurrently with LCAP. Anti-NM IgE were present in six symptomatic patients (6/49; 12.2%) whose adverse effects were highly suspected to be from NM. However, 21 patients showed anti NM IgE-negative, in spite of the fact that their adverse effects were also highly suspected to be from NM. Through the detection of anti-NM IgE alone we could not estimate the relevance of NM as an anticoagulant to the adverse effects of LCAP.

Fukunaga K, Sawada K, Fukuda Y, Matoba Y, Natsuaki M, Ohnishi K, Fukui S, Satomi M, Shimoyama T. · Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan. · Ther Apher Dial. · Pubmed #12921128 No free full text.

Abstract: We report an erythema nodosum (EN) patient whose condition became apparent during the clinical course of ulcerative colitis (UC). The patient relapsed frequently in spite of taking a high dose adrenocortical steroid during his morbidity period of UC. Monocyte-granulocytapheresis (M-GCAP) was combined with 5-aminosalicylic acid 2250 mg/day peroral and once a day of steroid enema. Monocyte-granulocytapheresis was performed once a week for 5 weeks, and succeeded in inducing clinical remission for both UC and EN. The immunological and clinical connections between UC and EN have never been fully elucidated. In this case, because the symptoms of UC and EN revealed parallel improvement after his inflammatory reaction had been brought under control by combining M-GCAP therapy, we hypothesize that the onset of EN appeared as a result of the patient's long-term, treatment-resistant immuno-disturbance, which first appeared as symptoms of UC. Immunomodulative effects induced by M-GCAP might help to control other chronic non-specific inflammations not concerned with targeted organ(s).

Fukunaga K, Fukuda Y, Sawada K, Hori K, Matoba Y, Sagayama K, Ohnishi K, Fukui S, Shimoyama T. · Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa, Nishinomiya 663-8501, Japan. · J Gastroenterol. · Pubmed #12898362 No free full text.

Abstract: Both monocyte-granulocytapheresis (M-GCAP) and leukocytapheresis (LCAP) are categorized as extracorporeal leukocyte removal therapies (ECCTs). These therapies have been recognized as efficient adjuncts for patients of steroid-resistant ulcerative colitis (UC). This study aimed to consider the adaptation and the limitation of these new therapies from the clinical standpoint based on a case of UC showing strong resistance to high-dose continuous steroid injection therapy. The patient successfully underwent a scheduled colectomy while maintaining remission after applying M-GCAP and LCAP independently. Surgical therapy was chosen because of a deep ulcer in the patient's sigmoid colon, which was assumed to constitute a future risk for perforation. This case suggests that combining ECCT with steroid therapy can maintain such poorly controlled and high-risk UC patients safely for the scheduled colectomy while improving the prognosis by reducing the dosage of steroid efficiently prior to operation.

Tomomasa T, Kobayashi A, Kaneko H, Mika S, Maisawa S, Chino Y, Syou H, Yoden A, Fujino J, Tanikawa M, Yamashita T, Kimura S, Kanoh M, Sawada K, Morikawa A. · Department of Pediatrics, Gunma University Faculty of Medicine, Maebashi, Japan. · Dig Dis Sci. · Pubmed #12741466 No free full text.

Abstract: Granulocytapheresis (GCAP) has produced efficacy in adult patients with ulcerative colitis (UC) by adsorbing activated granulocytes and monocytes/macrophages. We retrospectively investigated efficacy and safety of GCAP in pediatric patients with active UC. Twelve steroid-refractory children (12.2 +/- 3.1 years old) were treated with GCAP, one session/week for 5-10 consecutive weeks. In 8 patients, clinical symptoms improved after two GCAP sessions. Normal body temperature, stool frequency, and disappearance of blood in stool were seen after 24.3 +/- 11.5 days. The endoscopic grade improved from 2.6 +/- 0.3 to 0.4 +/- 0.2. One patient who initially responded, developed bloody diarrhea later and 2 cases remained unchanged. The dose of steroid was tapered during GCAP therapy by 50%. No serious adverse effects were noted. Four of 8 cases relapsed 3.5 +/- 2.2 months after the last GCAP while on maintenance therapy, the other 4 were in remission up to 22.8 +/- 18.1 months. In conclusion, GCAP appears to be effective and well tolerated in children with steroid-refractory UC.

Tamura K, Fukuda Y, Sashio H, Takeda N, Bamba H, Kosaka T, Fukui S, Sawada K, Tamura K, Satomi M, Yamada T, Yamamura T, Yamamoto Y, Furuyama J, Okamura H, Shimoyama T. · Laboratory of Hereditary Tumor, Institute for Advanced Medical Sciences, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya 663-8501, Japan. · J Gastroenterol. · Pubmed #12572878 No free full text.

Abstract: BACKGROUND: The etiology of inflammatory bowel disease, which includes ulcerative colitis and Crohn's disease, has not yet been made clear. However, inflammatory bowel disease is recognized as a multifactorial disease, and innate genetic factors might contribute to the pathogenesis. Cytokine genes are thought to be important in inflammatory bowel disease. Recently, interleukin 18, cloned as a novel proinflammatory cytokine, has been implicated in inflammatory bowel disease, especially Crohn's disease. METHODS: To identify germline mutations in patients with inflammatory bowel disease, the entire coding region of IL18 was examined using a DNA sequencing procedure. RESULTS: No functional mutations were found, but a novel single nucleotide polymorphism (SNP) was identified as TCA/TCC at codon 35. In patients with Crohn's disease, the frequency of TCC allele carriers was significantly higher than in healthy controls (chi2 = 9.35, P = 0.002229, OR = 2.58, 95% CI = 1.39-4.80). Also, the magnitude of the association was more remarkable in females (chi2 = 16.36, P = 0.000052, OR = 8.17, 95% CI = 2.73-24.41). The TCC allele at codon 35 of IL18 may increase the risk for Crohn's disease, especially in females. CONCLUSIONS: IL18 is probably one of several genes that determine susceptibility to Crohn's disease.

Sashio H, Tamura K, Ito R, Yamamoto Y, Bamba H, Kosaka T, Fukui S, Sawada K, Fukuda Y, Tamura K, Satomi M, Shimoyama T, Furuyama J. · Department of Genetics, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan. · Immunogenetics. · Pubmed #11904678 No free full text.

Abstract: The importance of tumor necrosis factor (TNF)-alpha and the TNF receptor gene polymorphisms in the etipathogenesis of inflammatory bowel disease (IBD) has not been elucidated. DNA from peripheral blood samples was obtained from 124 patients with Crohn's disease (CD), 106 patients with ulcerative colitis (UC), and 111 unrelated healthy controls. We examined two single nucleotide polymorphisms (SNPs) of the TNF-alpha gene, TNF (-308 G/A and -238 G/A), an SNP of the TNF receptor superfamily member 1A gene, TNFRSF1A(also known as TNFR1), at codon 12 in exon 1 (CCA/CCG), and two SNPs of the 1B gene, TNFRSF1B (also known as TNFR2), (1466 A/G and 1493 C/T). There was a difference in the carrier frequency for haplotype AG (-308 A, -238 G) between UC patients and the controls (OR=4.76, 95% CI=1.53-14.74, P<0.01). We found a significant difference in carrier frequency for haplotype AT (1466 A, 1493 T) of the TNFRSF1B gene between CD patients and the controls (OR=2.13, 95% CI=1.08-4.21, P<0.05). The significance proved to be greater in CD patients with both internal and external fistula (OR=4.8, 95% CI=1.73-13.33, P<0.01), and in those who were poor responders ( n=22) to our treatments, which consisted of nutritional therapy, medical therapy and surgical therapy (OR=9.24, 95% CI=3.37-25.36, P<0.001). This study suggests that one of the genes responsible for UC may be the TNF gene, or an adjacent gene, and that TNFRSF1B gene polymorphisms contribute greatly to the increased onset risk of CD and to the disease behavior.

Fukunaga K, Sawada K, Fukuda Y, Matoba Y, Onishi K, Fukui S, Yamamura M, Satomi M, Shimoyama T. · Division of Gastroenterology, Hyogo College of Medicine, Hyogo, Japan. · Ther Apher. · Pubmed #11886584 No free full text.

Abstract: An 18-year-old woman was treated with leukocytapheresis (LCAP) for her combined ulcerative colitis (UC) and aortitis syndrome (AS). Because a close relationship between these two diseases has been suspected based on their etiological and/or pathological findings, we had hypothesized that LCAP, which has satisfactory effects on inflammatory bowel disease such as UC and Crohn's disease might be effective for both her UC and her AS. After informed consent, LCAP therapy was performed once a week for a total of 7 times. Endoscopic remission of the UC was observed. Even though there were no significant improvements in her subjective symptoms of AS such as side-neck pain and dizziness, objective evidence of improvement was obtained when the patient's condition was compared before and after LCAP by angiography, angio-magnetic resonance imaging, and the plethysmogram of her fingertips. These results suggest that LCAP may be valuable as a new adjunct therapy for AS.

Chikano S, Sawada K, Ohnishi K, Fukunaga K, Tanaka J, Shimoyama T. · Internal Medicine, Hyogo College of Medicine, Sasayama Hospital. · Intern Med. · Pubmed #11579949 links to  free full text

Abstract: We report a patient with ulcerative colitis complicated with idiopatic interstitial pneumonia, in whom the etiology of interstitial pneumonia was unknown, but immunological disturbance might have been involved. There are many complications with ulcerative colitis, but interstitial pneumonia is quite rare and its prognosis is quite poor. Antibiotic and steroid treatment were given under respiration supported therapy, but no response could be obtained. In the treatment of patients with ulcerative colitis, we must be mindful of interstitial pneumonia because the prognosis is quite poor.

Sawada K, Ohnishi K, Fukunaga K, Shimoyama T. · No affiliation provided · Am J Gastroenterol. · Pubmed #12526978 No free full text.

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