Immunosuppressive Treatment In Patients Research Articles

Predictive value of conjointly examined IL-1ra, TNF-R I, TNF-R II, and RANTES in patients with primary glomerulonephritis.

Interleukin-1 receptor antagonist (IL-1ra), tumor necrosis factor soluble receptors (sTNF-R) type I and II, and regulated upon activation, normal T-cell expressed and secreted (RANTES) play an important role in the modulation of primary glomerulonephritis (GN) course. The aim of the study was to assess whether pre-treatment measurements of IL-1ra, sTNF-R, and RANTES assessed conjointly may be useful as predicting factors in patients with GN. In 84 patients (45 males and 39 female) serum concentration (pg/mL) and urinary excretion (pg/mgCr) of cytokines were measured. After 12 months of therapy with steroids and cyclophosphamide the patients were divided into two subgroups: Responders (R) and Non-Responders (NR) according to the treatment results. The urinary IL-1ra, TNF-RI and RII were significantly higher in R than NR (1,732 vs 646 with P < 0.001, 13.1 vs 6.3 with P = 0.005, and 33.6 vs 14.4 with P = 0.012). The urinary RANTES excretion was increased in NR (79.6 vs 28.5; P < 0.001). The multivariable analysis showed that if conjointly assessed, only urinary IL-1ra, TNF-R I and R II, RANTES with 85% probability pointed the feature remission (R). In conclusion, the urinary excretion of IL-1ra, TNF-R I and R II, and RANTES examined conjointly are effective in predicting favorable response to immunosuppressive treatment in patients with GN.

Quand peut-on évoquer et comment traiter une parasitose intestinale en France ?

In a compatible context, hypereosinophilia is suggestive of helminthosis. When the count is higher than 1000/mm(3), a primo-invasion syndroma may be considered, especially if allergic signs are present. Below that level, the helminthosis is probably at the adult stage (chronic phase). In a chronic diarrhoea occurring after a journey abroad, "emerging" protozoa (crypto-microsporidia, Isospora, Cyclospora…) are possibly in cause. A presumptive treatment may be considered. A systematic screening for schistosomiasis (serology and stool examination) is recommended in travellers exposed to the risk (contacts with fresh water) and in immigrant from endemic areas (mainly sub-Saharan Africa) since the disease may be asymptomatic. In young children living communally, two courses at 15 days interval against giardiosis or enterobiasis are recommended for both infected and contact persons. In order to avoid disseminated strongyloidiasis, severe and possibly lethal, a systematic course of ivermectine is strongly recommended before any immunosuppressive treatment in patients having stayed in tropical areas even for a short period and even decades ago. Albendazole became the reference drug for intestinal helminthiasis with in addition a good efficacy on giardiasis. Since some intestinal parasites are not pathogenic, a treatment is not necessarily required when a parasite is found in a stool examination.

Hepatitis B Reactivation in a Renal Transplant Patient Due to a Surface Antigen Mutant Strain: A Case Report

Reactivation of hepatitis B virus (HBV) is a complication of immunosuppressive treatment in patients with a history of HBV exposure. Herein we have reported a case of reactivation after renal transplantation in a 52-year-old male chronic HBV carrier who was treated with hepatitis B immunoglobulin (HBIg) prophylaxis immediately after transplantation in addition to cyclosporine, mycophenolate mofetil and prednisolone for maintenance immunosuppression. After application of rituximab, the patient developed clinical hepatitis with a high load of HBV DNA. Sequence analysis of the surface (S) antigen corresponding to the amino acid residues 101-186 (including the a-determinant region) revealed a genotype D mutant strain, subtype ayw3 with a single amino acid substitution D144E within the S gene. This case suggested that immunosuppressive treatment enhanced with rituximab promoted the emergence of an HBV mutant within the determinant region of the S antigen, which escaped HBIg immunoprophylaxis causing HBV reactivation in a kidney transplant recipient.

Sirolimus and Secondary Skin-Cancer Prevention in Kidney Transplantation

BackgroundTransplant recipients in whom cutaneous squamous-cell carcinomas develop are at high risk for multiple subsequent skin cancers. Whether sirolimus is useful in the prevention of secondary skin cancer has not been assessed.MethodsIn this multicenter trial, we randomly assigned transplant recipients who were taking calcineurin inhibitors and had at least one cutaneous squamous-cell carcinoma either to receive sirolimus as a substitute for calcineurin inhibitors (in 64 patients) or to maintain their initial treatment (in 56). The primary end point was survival free of squamous-cell carcinoma at 2 years. Secondary end points included the time until the onset of new squamous-cell carcinomas, occurrence of other skin tumors, graft function, and problems with sirolimus.ResultsSurvival free of cutaneous squamous-cell carcinoma was significantly longer in the sirolimus group than in the calcineurin-inhibitor group. Overall, new squamous-cell carcinomas developed in 14 patients (22%) in the sirolimus group (6 after withdrawal of sirolimus) and in 22 (39%) in the calcineurin-inhibitor group (median time until onset, 15 vs. 7 months; P=0.02), with a relative risk in the sirolimus group of 0.56 (95% confidence interval, 0.32 to 0.98). There were 60 serious adverse events in the sirolimus group, as compared with 14 such events in the calcineurin-inhibitor group (average, 0.938 vs. 0.250). There were twice as many serious adverse events in patients who had been converted to sirolimus with rapid protocols as in those with progressive protocols. In the sirolimus group, 23% of patients discontinued the drug because of adverse events. Graft function remained stable in the two study groups.ConclusionsSwitching from calcineurin inhibitors to sirolimus had an antitumoral effect among kidney-transplant recipients with previous squamous-cell carcinoma. These observations may have implications concerning immunosuppressive treatment of patients with cutaneous squamous-cell carcinomas. (Funded by Hospices Civils de Lyon and others; TUMORAPA ClinicalTrials.gov number, NCT00133887.)

Effect of immunosuppressive treatment on gene expression in muscle from patients with polymyositis and dermatomyositis

BackgroundPolymyositis (PM) and dermatomyositis (DM) muscle tissue is characterised by infiltrating T cells, macrophages and dendritic cells, as well as cytokines, chemokines and lipid mediators forming an inflammatory milieu. Patients...

Immunosuppressive treatment in primary focal segmental glomerulosclerosis

The therapeutic effects of immunosuppressive agents such as cyclosporin A, mycophenolate mofetil, rituximab and sirolimus on primary focal segmental glomerulosclerosis (FSGS) remain controversial. The present study was intended to review and analyze the treatment results of immunosuppressive agents for primary FSGS in child and adult patients. Complete remission rates and partial remission rates were extracted from published articles and analyzed using statistical tests. Cyclosporin A was effective in the treatment of child and adult patients with idiopathic FSGS. Rituximab therapy displayed a higher complete remission and partial remission rate in children than in adult FSGS patients. Multiple-center large-scale rigorous trials should be considered to evaluate the risk-benefit ratio of immunosuppressive treatment in patients with primary FSGS.

Validation Study of the Oxford Classification for IgA Nephropathy in Korean Adults

Validation Study of the Oxford Classification for IgA Nephropathy in Korean Adults

P3 mAb: An Immunogenic Anti-NeuGcGM3 Antibody with Unusual Immunoregulatory Properties

P3 is a murine IgM mAb that recognize N-glycosylated gangliosides, sulfatides, and antigens expressed in melanoma, breast, and lung human tumors. This antibody has the ability to trigger an IgG antibody response in the syngeneic BALB/c model, even when it is administered in the absence of adjuvant or carrier protein. The mechanism by which the P3 mAb, a self-immunoglobulin, induce this immune response in the absence of co-stimulatory or classical danger signals is still unknown. In the present paper we show that the high immunogenicity of P3 mAb depends not only on CD4 but also on CD8+ T cells, since the depletion of CD8+ or CD4+ T cells led to the loss of P3 mAb immunogenicity in the syngeneic model. Furthermore, the immunization with P3 mAb enhanced the recovery of the CD8+ T cell population in mice treated with an anti-CD8a antibody. Additionally, the immunization with P3 mAb restored the capacity of immunosuppressed mice to reject allogeneic tumors, a mechanism mediated by the action of CD8+ T cells. Finally, in mice with cyclophosphamide induced lymphopenia, the administration of P3 mAb accelerated the recovery of both CD4+ and CD8+ T cells. These results show new possibilities for B and CD8+ T cells interactions during the immune response elicited by a self-protein. Furthermore they point to P3 mAb as a potential interesting candidate for the treatment of immunosuppressed patients.

Immunosuppressive Treatment for Patients with Myelodysplastic Syndromes: A Review of 358 Patients

Abstract 1717Scientific and clinical evidence support a role for immune dysregulation in the pathogenesis of myelodysplastic syndromes (MDS) in some patients, and immunosuppressive therapy (IST) is considered a standard treatment for selected patients with MDS. Despite a number of studies showing its efficacy in MDS, IST has not been widely adopted because of uncertainty about therapeutic benefit, perceived toxicities of antibody treatment, and confusion about patient selection. To better define the place of IST in MDS, we reviewed all published clinical trials of IST for adult patients with MDS to determine its therapeutic benefit and treatment-related toxicity. We also sought to define clinical and laboratory predictors for response to IST. IST was defined as T cell directed therapies, including the following drugs administered alone or in combination: cyclosporine A (CsA), rabbit or horse anti-thymocyte globulin (ATG), alemtuzumab, sirolimus, tacrolimus, mycophenolate mofetil, or daclizumab. Electronic databases were scanned for all peer-reviewed clinical trial reports concerning IST for MDS from inception through August 1, 2011. Risk of bias for each study was assessed by two independent investigators using the Cochrane Risk of Bias Tool, and the Newcastle-Ottawa Scale. The searches of MEDLINE, Cochrane Clinical Trials Register, SCOPUS, Web of Science and EMBASE yielded a total of 1950 articles, and 1937 were subsequently discarded based on our a priori exclusion criteria. A total of 13 reports from 13 individual clinical trials enrolling 358 patients met criteria for this review. IST was well tolerated with a treatment-related mortality rate of 1.3%. Hematologic improvements (HI), partial response (PR), and complete response (CR) was defined using International Working Group for MDS criteria. The overall response rate (ORR) to IST was 41% (HI 18%, PR 15%, and CR 8%). ORR according to treatment regimen were alemtuzumab 68% (n= 31 patients), CsA 56% (n=111 patients), h-ATG 35%, (n=83 patients), r-ATG/CsA 30% (n= 20 patients), r-ATG 27%, (n=15 patients), and h-ATG/CSA 25% (n=79 patients). Response rates were higher when patients were treated on protocols incorporating specific selection criteria versus unselected patients (ORR 59% vs 41%, p=0.01). Patients with a hypocellular bone marrow had response rates that were equal to individuals with normal or increased marrow cellularity: ORR 63% vs 63%, (p=0.99); PR 25% vs 23%, (p=0.81); CR 15% vs 11%, (p=0.46). Patients younger than 60 years had significantly higher response rates to IST than older individuals (ORR 59% vs 40%, p=0.004), irrespective of the treatment regimen administered. Patients who were transfusion dependent had response rates equal to those who were transfusion independent at the time of treatment (ORR 60% vs 55%, p=0.57). Response rates in patients with low and intermediate cytogenetic risk groups as defined by the International Prognostic Scoring Scale (IPSS) were 51% and 49%, respectively. Response rates varied according to World Health Organization (WHO) Prognostic Scoring Scale (WPSS) morphology categories, with overall response rates of 57% (n=128 patients), 10% (n=10 patients), and 21% (n=39 patients) in individuals with very low, low, and intermediate morphology categories, respectively. Response rates did not vary according to gender or cell lineages involved. These results indicate that the choice of IST may be critical in optimizing responses and that IST should be considered for MDS patients younger than 60 years old, with low and intermediate risk IPSS cytogenetics and very low WHO morphology categories, regardless of bone marrow cellularity and duration of transfusion dependence.CsAAlemtuzumabhATGhATG/CsArATGrATG/CsASirolimusANOVAResponseR% (range)No.R% (range)No.R% (range)No.R% (range)No.R% (range)No.R% (range)No.R% (range)No.P-valueCR33/111237/3154/83108/79203/15153/2000/190.002(1–8)(10–41)(1–12)(5–19)(4–48)(3–38)—PR2427/111134/311613/8343/7971/15153/20163/190.013(17–33)(4–30)(9–25)(1–11)(0.1–32)(3–38)(3–40)HI2932/1113210/311512/83119/7900/1500/2000/19<0.0001(21–38)(17–51)(8–24)(5–21)———ORR5662/1116821/313529/832520/79274/15306/20163/19<0.00001(46–65)(49–83)(25–46)(16–36)(8–55)(12–54)(3–40) Disclosures:No relevant conflicts of interest to declare.

Mycophenolate mofetil use in refractory juvenile systemic lupus erythematosus

The optimal immunosuppressive treatment in patients with systemic lupus erythematosus (SLE) remains controversial [1]. Mycophenolate mofetil (MMF) has proved to be an efficacious and safe therapy in adult lupus nephritis [2]. Recently, this drug has been suggested as a possible new alternative treatment for juvenile-SLE, especially in cases of lupus nephritis refractory to treatment with corticosteroids, cyclophosphamide azathioprine, methotrexate and/or cyclosporine [3-4]. In this review we describe our experience with six children diagnosed with SLE and treated with MMF.

Bone mass, vitamin D levels and immunosuppressive treatment in patients with liver transplant and risedronate treatment

As bone matures type I collagen undegoes β isomerisation at the DG motif of the CTX epitope. Measurements of αCTX and βCTX allow us to distinguish between bone turnover in newly formed and mature bone, respectively. In states of pathologically high bone turnover such as Paget's and malignant bone diseases, there is a relatively greater increase in the resorption of newly formed bone. Treatment of these with bisphosphonates results in a relatively greater decrease in the resorption of newly formed bone. The aims were to investigate 1) the relative increase in αCTX in postmenopausal osteoporosis and 2) the relative decrease in αCTX with bisphosphonate treatment. We recruited 60 postmenopausal women (mean age 68: range 55-85) with a BMD T-score of <2.5 or <1 and a fracture. They were randomised into 3 treatment groups: ibandronate (n=19), alendronate (n=23) and risedronate (n=18). 75 healthy premenopausal women (mean age 38: range 30-45) were recruited. We measured α and βCTX (Nordic Biosciences Diagnostics, Copenhagen, Denmark) in second morning void urine samples and serum βCTX (Roche Diagnostics, Pensberg, Germany). The median urinary α and βCTX and serum βCTX were significantly lower in healthy premenopausal compared to postmenopausal osteoporotic women at baseline 62%, 110% and 65% respectively (P<0.0001). The median urinary α and βCTX and serum βCTX showed a significant decrease by 68%, 88%, and 79% from baseline respectively (P<0.0001) after 13 weeks of treatment. The α/β CTX ratio increased by 62% (P<0.05). We conclude that resorption of type I collagen in postmenopausal osteoporosis is greater compared to healthy premenopausal women. There is no relative greater increase in the resorption of newly formed bone. With bisphosphonate treatment, the resorption of type I collagen is decreased after 13 weeks of treatment, but there is no greater decrease in the relative resorption of newly formed bone. In fact, there is a preferential decrease in the resorption of mature bone.

Immunosuppressive treatment in patient with pure red cell aplasia associated with chronic myelomonocytic leukemia: harm or benefit?

Acquired pure red cell aplasia (PRCA) can be primary or secondary to other diseases. PRCA association with chronic myelomonocytic leukemia (CMML) is very rarely reported. Although treatment is directed to underlying cause in secondary PRCA treatment, optimal treatment in patients with CMML and PRCA is unknown, because only four case reports are available. In addition, the effect of hypomethylating agents can be detrimental due to myelosuppression, at least in the early phase of treatment. Bone marrow examination of a 66-year-old woman with severe anemia revealed PRCA and was suspicious for CMML. There was no HLA-matched sibling for bone marrow transplantation. The patient received immunosuppressive therapy with steroids and cyclosporine with temporary response in anemia; however, progressed to acute leukemia over 8 months and died. Immunosuppressive therapy in patients with CMML and PRCA should be cautiously used because it may accelerate acute leukemia transformation.

Pathogenicity of the family Legionellaceae

The Legionellae are Gram-negative bacteria able to survive and replicate in a wide range of protozoan hosts in natural environments, but they also occur in man-made aquatic systems, which are the major source of infection. After transmission to humans via aerosols, Legionella spp. can cause pneumonia (Legionnaires' disease) or influenza-like respiratory infections (Pontiac fever). In children, Legionnaires' disease is uncommon and is mainly diagnosed in children with immunosuppression. The clinical picture of Legionella pneumonia does not allow differentiation from pneumonia caused by others pathogens. The key to diagnosis is performing appropriate microbiological testing. The clinical presentation and the natural course of Legionnaires' disease in children are not clear due to an insufficient number of samples, but morbidity and mortality caused by this infection are extremely high. The mortality rate for legionellosis depends on the promptness of an appropriate antibiotic therapy. Fluoroquinolones are the most efficacious drugs against Legionella. A combination of these drugs with macrolides seems to be promising in the treatment of immunosuppressed patients and individuals with severe legionellosis. Although all Legionella species are considered potentially pathogenic for humans, Legionella pneumophila is the etiological agent responsible for most reported cases of community-acquired and nosocomial legionellosis.

Clinical relevance of pretransplant human leukocyte antigen donor-specific antibodies in renal patients waiting for a transplant: A risk factor

The use of highly sensitive solid-phase antibody detection assays, including x-MAP multiple bead-based technology (Luminex), has greatly enhanced our ability to accurately detect and define very low levels of HLA antibodies. These developments have led to patients having increasing lists of antibody specificities (which may not be clinically relevant), resulting in a new “technological barrier” to transplantation in sensitized patients. Alloantibodies play a major role in all types of solid organ rejection; the presence of low-titer donor-specific antigen (DSA) identified pretransplant is associated with an increased risk of antibody-mediated rejection (AMR). However, these low-titer antibodies do not represent an absolute contraindication to transplant. Improvement in the diagnosis and treatment of AMR will allow sensitized patients with DSA to be successfully transplanted in the short term, but extended follow-up is required to ensure acceptable long-term graft survival in this group. These factors must be integrated into the decision algorithms for immunosuppressive treatment in patients at immunologic risk.

Immunosuppressive treatment of patients with amyotrophic lateral sclerosis

Documented treatment for amyotrophic lateral sclerosis (ALS) is not available. Several studies have suggested an immunological etiology and an effect on the course of disease, when ALS-patients were treated with immunosuppressants. The aim of the present study was to evaluate the effect of immunosuppressive therapy in ALS-patients comparing the course of disease in treated patients and in historic controls with ALS; 21 patients were included in the study, 17 men and 4 women. Median age at admission was 54 years for men and 61 years for women. 5 had progressive bulbar palsy, 7 both upper and lower motor neuron affections and 9 progressive muscular atrophy. Patients were treated with prednisolone and azathioprine for 1 year and examined regularly; 12 were treated and followed for more than a year. No definite difference between survival in treated patients and their controls was found.

Sjögren's syndrome – not just Sicca: renal involvement in Sjögren's syndrome

Objective: To present a case of severe interstitial nephritis with proteinuria in primary Sjögren's syndrome (pSS) and review the literature regarding renal disease and its management in pSS, aiming to suggest recommendations for treatment.Methods: A search of MEDLINE (PubMed) was performed for review articles and case reports using the MESH terms: Sjögren syndrome; renal disease; interstitial nephritis (IN); glomerulonephritis (GN).Results: We describe a rare case of pSS presenting with hypokalaemic tetraparesis and proteinuria due to severe IN, successfully treated with high‐dose steroids and azathioprine. Reviewing the literature, we identified 180 reported cases of renal involvement in pSS (selected based on the European criteria for pSS), 89 of which underwent renal biopsies revealing IN in 49 cases, GN in 33 samples, and both IN and GN in seven. Eighteen studies reported treatment experience of renal disease in 32 pSS cases. Seventeen patients were treated with corticosteroids and cyclophosphamide, and 15 patients received only steroids with improvement in the majority of cases.Conclusion: The present case, as well as the limited number of reports in the literature, suggest that renal involvement, including IN, in pSS may improve with immunosuppressive therapy. Further studies are required to determine indications for and dosages of immunosuppressive treatment in patients with renal involvement of pSS.

Herpes simplex virus colitis complicating ulcerative colitis: A case report and brief review on superinfections

In patients with inflammatory bowel disease herpes simplex virus infection has been described as a major cause of morbidity and mortality, especially in immunocompromised individuals. Here we present the case of a 35-year old woman with an exacerbation of ulcerative colitis caused by herlpes simplex virus infection (HSV-2). The diagnosis was confirmed histologically following subtotal colectomy. After intravenous treatment with aciclovir for 2 weeks postoperative hematochezia stopped. Herpes simplex virus colitis is a rare but potentially fatal complication of immunosuppressive treatment in patients with inflammatory bowel disease. Prompt diagnosis and efficient antiviral therapy are mandatory to improve prognosis.

Efficiency of curative and prophylactic treatment with rituximab in ADAMTS13-deficient thrombotic thrombocytopenic purpura: a study of 11 cases

AbstractThrombotic thrombocytopenic purpura (TTP) is a life-threatening disease that occurs mainly in young adults. Acquired cases are usually a result of antibodies directed against ADAMTS13 (a disintegrin-like and metalloprotease [reprolysin type] with thrombospondin type 1 motif 13), a protease that cleaves the von Willebrand factor multimers. Prognosis has been improved by plasma therapy, but some acute severe forms are refractory to this treatment and achieving a sustained remission is still a challenge in chronic relapsing forms. We therefore conducted a multicentric open-label prospective trial to test the efficacy of rituximab, an anti–B-cell monoclonal antibody, as a curative and prophylactic treatment in patients with TTP as a result of anti-ADAMTS13 antibodies. Six patients were included during an acute refractory TTP episode. Five patients with severe relapsing TTP and persistent anti-ADAMTS13 antibodies were prophylactically treated during remission. All patients received 4 weekly infusions of rituximab. The target of treatment was to restore a significant ADAMTS13 plasma activity (> 10%). Treatment with rituximab led to clinical remission in all cases of acute refractory TTP. In all patients, anti-ADAMTS13 antibodies disappeared, and a significant (18%-75%) plasma ADAMTS13 activity was detected following treatment. Tolerance of rituximab was good. Rituximab is a promising first-line immunosuppressive treatment in patients with acute refractory and severe relapsing TTP related to anti-ADAMTS13 antibodies.

Clinical relevance of the expression of P‐glycoprotein on peripheral blood lymphocytes to steroid resistance in patients with systemic lupus erythematosus

P-glycoprotein (P-gp) of membrane transporters leads to drug resistance by the exclusion of intracellular drugs, including corticosteroids. Some patients with highly active systemic lupus erythematosus (SLE) show poor response to corticosteroids; however, the mechanisms of steroid resistance remain unclear. The aim of this study was to elucidate the clinical relevance of P-gp expression on lymphocytes to steroid resistance in patients with active SLE. Flow cytometric analyses of the expression of P-gp on peripheral blood lymphocytes from 20 normal volunteers and 80 SLE patients were performed. Steroid-exclusion analysis of peripheral blood mononuclear cells (PBMCs) was conducted by using radioisotope-labeled dexamethasone. P-gp was expressed at significantly high levels on most of the peripheral blood lymphocytes from SLE patients, whereas normal lymphocytes had only marginal expression. The quantity of P-gp on SLE lymphocytes correlated with the disease activity in each patient, as estimated by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Furthermore, in SLE patients whose SLEDAI scores were >12 despite taking >0.5 mg/kg/day of prednisolone, P-gp expression on lymphocytes was markedly increased, and intracellular dexamethasone in their PBMCs was significantly decreased. However, intensive immunosuppressive treatment in these SLE patients resulted in successful control of disease activity, which occurred in parallel with a marked reduction of P-gp on lymphocytes. The overexpression of P-gp on lymphocytes might lead to exclusion of corticosteroids from lymphocytes, resulting in steroid resistance in patients with highly active SLE. Reduction of P-gp expression achieved by intensive immunosuppressive treatment overcame the steroid resistance. We therefore propose that measurement of P-gp expression on lymphocytes is useful in the assessment of steroid resistance and is a good marker for indicating the need for intensive immunosuppressive treatment in patients with highly active SLE.

Long‐term healing of Crohn's anal fistulas with fibrin glue injection

Injecting fibrin glue has proved to be an effective means of treating anal fistulas (AF). There has been some debate, however, as to whether this technique should be used on the AF often involved in Crohn's disease (CD). To assess the effectiveness of injecting heterologous fibrin glue as a means of treating AF refractory to immunosuppressive treatment in patients with CD. Fourteen CD patients (five men and nine women, average age 42 years) presenting with refractory AFs were included in this study. Heterologous fibrin glue was injected into the fistula tract under general anaesthesia under continuous endosonographic monitoring using a 7.5-MHz blind linear probe. The patients were followed up clinically and ultrasonographically for 3 months after the procedure, and then at regular intervals. Three months after the fibrin glue injection, the fistulas had completely dried up in 10 patients (71%), the leakage had decreased in one patient (7%), and no improvement was observed in the other three patients (21%). Endosonographic findings showed that the fistula tract had completely disappeared in two cases (14%). The fistula tract was found to be non-permeable in eight cases (57%), and no change in the fistula was observed in four patients (29%). At the end of the follow-up period [average 23.4 months (12-26 months)], the leakage had completely dried up in eight of the 14 patients (57%). No side effects were observed. Nearly 2 years after the use of a heterologous fibrin glue to treat an AF, over half of the patients with CD showed clinical signs of remission. Because it is easy to use and harmless as well as being effective, this method provides a good alternative to classical methods of surgical treatment.