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Severe Course (severe + course)
Selected AbstractsSevere Course of Primary Hyperoxaluria and Renal Failure After Domino Hepatic TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2005Alessandro Franchello We report herein a domino orthotopic liver transplantation (LT), from a 38-year-old woman undergoing liver-kidney transplantation (LKT) for primary hyperoxaluria type I (PH1) to a recipient with cirrhosis and hepatocellular carcinoma. Delayed onset of PH1 and renal failure and 10% residual alanine-glyoxylate aminotransferase (AGT) activity in domino liver justified its use for domino procedure. The clinical course after LKT was similar to that described in other series, including ours. Renal function started promptly and maintained despite sustained hyperoxaluria from dissolution of oxalotic deposits. Conversely, the domino recipient manifested severe hyperoxaluria and developed nephrolithiasis and renal insufficiency with rapid progression over 2 months. A new LT resulted in slow decrease of oxaluria and improvement of renal function. Therefore, PH1 behaved quite differently in these two patients, leading us to conclude that domino LT using livers from PH1 patients should be considered very carefully, only as a bridge to definitive LT in recipients with critical clinical conditions. [source] Polyfunctional HCV-specific T-cell responses are associated with effective control of HCV replicationEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 10 2008Donatella Ciuffreda Abstract HCV infection has a severe course of disease in HIV/HCV co-infection and in liver transplant recipients. However, the mechanisms involved remain unclear. Here, we evaluated functional profiles of HCV-specific T-cell responses in 86 HCV mono-infected patients, 48 HIV/HCV co-infected patients and 42 liver transplant recipients. IFN-, and IL-2 production and ability of CD4 and CD8 T cells to proliferate were assessed after stimulation with HCV-derived peptides. We observed that HCV-specific T-cell responses were polyfunctional in HCV mono-infected patients, with presence of proliferating single IL-2-, dual IL-2/IFN-, and single IFN-,-producing CD4+ and dual IL-2/IFN-, and single IFN-,-producing CD8+ cells. In contrast, HCV-specific T-cell responses had an effector profile in HIV/HCV co-infected individuals and liver transplant recipients with absence of single IL-2-producing HCV-specific CD4+ and dual IL-2/IFN-,-producing CD8+ T cells. In addition, HCV-specific proliferation of CD4+ and CD8+ T cells was severely impaired in HIV/HCV co-infected patients and liver transplant recipients. Importantly, "only effector" T-cell responses were associated with significantly higher HCV viral load and more severe liver fibrosis scores. Therefore, the present results suggest that immune-based mechanisms may contribute to explain the accelerated course of HCV infection in conditions of HIV-1 co-infection and liver transplantation. [source] Seronegative myasthenia gravis: disease severity and prognosisEUROPEAN JOURNAL OF NEUROLOGY, Issue 6 2005F. Romi Around 10,20% of myasthenia gravis (MG) patients do not have acetylcholine receptor (AChR) antibodies (seronegative), of whom some have antibodies to a membrane-linked muscle specific kinase (MuSK). To examine MG severity and long-term prognosis in seronegative MG compared with seropositive MG, and to look specifically at anti-AChR antibody negative and anti-MuSK antibody negative patients. Seventeen consecutive seronegative non-thymomatous MG patients and 34 age and sex matched contemporary seropositive non-thymomatous MG controls were included in a retrospective follow-up study for a total period of 40 years. Clinical criteria were assessed each year, and muscle antibodies were assayed. There was no difference in MG severity between seronegative and seropositive MG. However, when thymectomized patients were excluded from the study at the year of thymectomy, seropositive MG patients had more severe course than seronegative (P < 0.001). One seropositive patient died from MG related respiratory insufficiency. The need for thymectomy in seronegative MG was lower than in seropositive MG. None of the seronegative patients had MuSK antibodies. This study shows that the presence of AChR antibodies in MG patients correlates with a more severe MG. With proper treatment, especially early thymectomy for seropositive MG, the outcome and long-term prognosis is good in patients with and without AChR antibodies. [source] Risk factors and characteristics of extent progression in ulcerative colitisINFLAMMATORY BOWEL DISEASES, Issue 9 2009María Josefina Etchevers MD Abstract Background: The main objective was to identify risk factors for extent progression in distal ulcerative colitis. The secondary objective was to determine clinical characteristics of disease at the time of progression. Methods: Data were obtained from a prospective database. Distal colitis was defined as disease limited to rectum and sigmoid colon (n = 178), extensive colitis as involvement of at least the descending colon (n = 179), and colitis with progression when there was a change of category from distal to extensive (n = 63). To study clinical characteristics at the time of progression, a nested case,control study was performed. Results: Compared to distal colitis, colitis with progression was associated to significantly higher prevalence of extraintestinal manifestations (42.9% versus 15.5%) steroid-refractory course (28.0% versus 2.2%), requirement of thiopurines (44.3% versus 17.3%), cyclosporine (25.4% versus 1.9%), infliximab (9.5% versus 1.2%), surgery (20.6% versus 0.6%), and incidence of neoplasia (6.3% versus 0%). However, these differences appeared after disease progression. Regression analysis demonstrated that preexisting independent predictive factors for progression were younger age at diagnosis (hazard ratio [HR] 0.979 95% confidence interval [CI] 0.959,0.999) and presence of sclerosing cholangitis (HR 12.83, 95% CI 1.36,121.10). The nested case,control study showed that at the time of progression the flare was more severe in cases than in matched controls, with significant differences in markers of disease severity, therapeutic requirements, hospitalizations, and surgery. Conclusions: Patients with distal ulcerative colitis diagnosed at a younger age or with associated sclerosing cholangitis are at higher risk for progression. Disease flare associated with progression follows a severe course with high therapeutic requirements. (Inflamm Bowel Dis 2009) [source] Adefovir dipivoxil therapy in liver transplant recipients for recurrence of hepatitis B virus infection despite lamivudine plus hepatitis B immunoglobulin prophylaxisJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 12 2007Murat Akyildiz Abstract Background:, Treatment of post-transplantation recurrence of hepatitis B virus (HBV) infection despite prophylaxis with hepatitis B immunoglobulin (HBIG) and lamivudine combination therapy is not easy. Because HBV reinfection has a severe course and could result in graft failure in liver transplant recipients, prompt medication is essential. Herein is reported the authors' experience with adefovir dipivoxil (AD) therapy in 11 liver transplant recipients who had HBV reinfection despite the administration of lamivudine and HBIG. Method:, Two-hundred and nine patients underwent liver transplantation (100 deceased donor liver transplantations [DDLT], 109 living donor liver transplantation [LDLT]) due to chronic hepatitis B infection between April 1997 and May 2005 in Ege University Medical School, Liver Transplantation Unit. Patients had prophylaxis with lamivudine and low-dose HBIG combination after liver transplantation. Treatment of recurrence consisted of AD 10 mg once a day and lamivudine 300 mg/daily and HBIG was discontinued in those patients. Results:, In total there were 11 HBV recurrences: five occurred in DDLT recipients and six in LDLT recipients, at a median follow up of 18 months (range, 6,48 months). In one of 11 patients, pretransplant HBV-DNA and HBeAg were positive. Three patients had a severe course and one patient had fibrosing cholestatic hepatitis. After AD treatment, HBV-DNA level decreased in all patients and became negative in seven patients. Two patients died due to hepatocellular carcinoma recurrence after 12 and 14 months of follow up. Serum creatinine level increased mildly in one patient and no other side-effect was observed, and all patients continued therapy. Conclusion:, Adefovir dipivoxil is a safe, effective treatment option for post-transplant HBV recurrence even among patients with fibrosing cholestatic hepatitis caused by lamivudine-resistant HBV. [source] Identification and characterization of 20 immunocompetent patients with simultaneous varicella zoster and herpes simplex virus infectionJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 6 2008KA Giehl Abstract Background, It has been shown that varicella zoster virus (VZV) and herpes simplex virus (HSV) can co-localize to the same sensory ganglion. However, only a few case reports on VZV/HSV co-infections exist. Objective,To identify and characterize patients with concurrent VZV and HSV infection at the same body site. Subjects/Methods, In 1718 patients, the presence of VZV and HSV in suspicious skin lesions was investigated by polymerase chain reaction analysis. Clinical characteristics of co-infected patients were compared with matched control patients infected with either VZV or HSV. The data are discussed in the context of an extensive review of the literature. Results, Twenty (1.2%) of 1718 patients were infected with both VZV and HSV at the same body site. The mean age was 54 years (range, 2,83). The clinical diagnosis was zoster in 65%, herpes simplex in 20%, varicella in 10% and erythema multiforme in 5% of cases. The trigeminus region was affected in 60% and the trunk in 25%. Involvement of the head was most commonly associated with a severe course of disease and with older age. Conclusion, Simultaneous VZV/HSV infection is rare but can occur in immunocompetent patients, which is often overlooked. The majority of cases is localized to the trigeminus region and affects elderly people. [source] Cytotoxic CD4+ T cells in viral hepatitisJOURNAL OF VIRAL HEPATITIS, Issue 8 2006N. Aslan Summary., CD4+ T cells are thought to contribute to antiviral immune responses by secretion of cytokines thereby providing help to CD8+ T and B cells. However, perforin-positive cytotoxic CD4+ T cells have been described in human immunodeficiency virus-positive patients suggesting a role not only of CD8+ but also of CD4+ T cells for killing virus-infected cells. We investigated 76 patients with viral hepatitis [15 hepatitis B virus (HBV), 22 HBV/hepatitis D virus and 17 hepatitis C virus (HCV)] for cytotoxic CD4+ T cells. The frequency of perforin-positive CD4+ T cells in viral hepatitis was highly variable ranging from <1% to more than 25%. Perforin-positive CD4+ T cells displayed the phenotype of terminally differentiated effector cells (CD28,, CD27,). The highest frequencies of CD4+ cytotoxic T lymphocytes (CTLs) were found in patients with delta hepatitis (P = 0.04 vs HBV and HCV patients), and the presence of CD4+ CTLs was associated with elevated aspartate aminotransferase levels (P = 0.01) and decreased platelet counts (P = 0.03). Perforin-positive CD4+ T cells decreased in two individuals during spontaneous clearance of acute hepatitis C. Significant associations were found between the frequency of perforin-expressing CD4+ cells and age (P = 0.04), perforin-positive CD8+ cells (P < 0.001) and perforin-positive CD4,/CD8, lymphoid cells (P = 0.002). Differentiated CD27, effector CD4+ CTLs can be detected in patients with viral hepatitis. In particular in patients with more advanced liver disease, the accumulation of perforin-positive T cells with age could be one correlate for the more severe course of viral hepatitis in elderly individuals. [source] Extranodal lymphoid microstructures in inflamed muscle and disease severity of new-onset juvenile dermatomyositis,ARTHRITIS & RHEUMATISM, Issue 4 2009Consuelo M. López De Padilla Objective Juvenile dermatomyositis (DM) is an autoimmune disease of childhood characterized by lesions in skin and muscle that are populated by plasmacytoid dendritic cells (PDCs) and lymphocyte infiltrates. We undertook this study to examine the cellular composition, organization, and molecular milieu of the cellular infiltrates in muscle in juvenile DM and to correlate the infiltrates with clinical disease manifestations. Methods Since PDCs and lymphocyte foci express CCL19 and CCL21, we investigated for in situ formation of lymphoid microstructures that could be sites of extranodal immune activation. Results Analyses of muscle biopsy samples from children with new-onset juvenile DM showed 3 categories of lesions: diffuse infiltrates, lymphocytic aggregates lacking follicle-like organization, and follicle-like structures. The last of these exhibited elements of classic lymphoid follicles, including networks of follicular dendritic cells and high endothelial venules. They also expressed high levels of CXCL13 and lymphotoxins known to support lymphoid organogenesis. There were also resident naive CD45RA+ T cells and maternally derived B cells and PDCs. Patients with diffuse infiltrates or lymphocytic aggregates were responsive to standard therapy with steroids and methotrexate, but those with follicle-like structures tended to have severe disease that required additional agents such as intravenous Ig or rituximab. Conclusion These data suggest that lymphoneogenesis is a component of the early disease process in juvenile DM. Ectopic lymphoid structures could indicate a severe course of disease; their early detection could be a tool for disease management. [source] An overview of recent findings of the Stanley Foundation Bipolar Network (Part I)BIPOLAR DISORDERS, Issue 5 2003Robert M Post Aim and Methods: Selected recent findings of the Stanley Foundation Bipolar Network are briefly reviewed and their clinical implications discussed. Results: Daily prospective ratings on the NIMH-LCM indicate a high degree of residual depressive morbidity (three times that of hypomania or mania) despite active psychopharmacological treatment with a variety of modalities including mood stabilizers, antidepressants, and benzodiazepines, as well as antipsychotics as necessary. The rates of switching into brief to full hypomania or mania during the use of antidepressants is described, and new data suggesting the potential utility of continuing antidepressants in the small group of patients showing an initial acute and persistent response is noted. Bipolar patients with a history of major environmental adversities in childhood have a more severe course of illness and an increased incidence of suicide attempts compared with those without. Preliminary open data suggest useful antidepressant effects of the atypical antipsychotic quetiapine, while a double-blind randomized controlled study failed to show efficacy of omega-3 fatty acids (6 g of eicosapentaenoic acid compared with placebo for 4 months) in the treatment of either acute depression or rapid cycling. The high prevalence of overweight and increased incidence of antithyroid antibodies in patients with bipolar illness is highlighted. Conclusions: Together, these findings suggest a very high degree of comorbidity and treatment resistance in outpatients with bipolar illness treated in academic settings and the need to develop not only new treatment approaches, but also much earlier illness recognition, diagnosis, and intervention in an attempt to reverse or prevent this illness burden. [source] Substance abuse in bipolar disorderBIPOLAR DISORDERS, Issue 4 2001Frederick Cassidy Background: High rates of substance abuse have been reported in the general population, with males more often affected than females. Although high rates of substance abuse have also been reported in bipolar patients, the relationship between substance abuse and bipolar disorder has not been well characterized. Methods: Substance abuse histories were obtained in 392 patients hospitalized for manic or mixed episodes of bipolar disorder and rates of current and lifetime abuse calculated. Analyses comparing sex, subtype (manic vs. mixed) and clinical history variables were conducted. Results: Rates of lifetime substance abuse were high for both alcohol (48.5%) and drugs (43.9%). Nearly 60% of the cohort had a history of some lifetime substance abuse. Males had higher rates of abuse than females, but no differences in substance abuse were observed between subjects in manic and mixed bipolar states. Rates of active substance abuse were lower in older age cohorts. Subjects with a comorbid diagnosis of lifetime substance abuse had more psychiatric hospitalizations. Conclusions: Substance abuse is a major comorbidity in bipolar patients. Although rates decrease in older age groups, substance abuse is still present at clinically important rates in the elderly. Bipolar patients with comorbid substance abuse may have a more severe course. These data underscore the significance of recognition and treatment of substance abuse in bipolar disorder patients. [source] Patients with severe Graves' ophthalmopathy have a higher risk of relapsing hyperthyroidism and are unlikely to remain in remissionCLINICAL ENDOCRINOLOGY, Issue 4 2007Anja K. Eckstein Summary Objective, To evaluate the relationship between severity of Graves' ophthalmopathy (GO) and relapse/remission rate of associated thyroid disease. Patients and methods, One hundred and fifty-eight patients with Graves' disease (GD) were seen within the first 6,12 months after the onset of GO and were followed for at least 18 months. During treatment, GO was classified as mild (n = 65) or severe course (n = 93) by severity and activity scores. All patients received standard anti-thyroid drug (ATD) treatment for 1 year, and in cases of relapse another cycle of ATD, thyroidectomy or radioiodine therapy. Results, Following ATD treatment, 27 patients (42%) with a mild course of GO went into thyroid disease remission, while only seven (8%) patients with a severe course of GO achieved remission (P < 0·0001). Eventually, 32 patients (49%) with a mild course needed definitive thyroid therapy and the remaining 9% preferred another cycle of ATD. However, among patients with a severe GO course, 84% needed definitive therapy (P < 0·0001) and 8% opted for another course of ATD treatment. The probability of relapse could also be predicted by TBII levels 12 months after initiation of ATD therapy, as 96·8% of patients with TBII levels above 7·5 IU/l relapsed (odds ratio 24·3). Conclusion, Patients with severe GO and high TBII are unlikely to go into remission. This allows early decision-making regarding definitive treatment of the thyroid in GD patients with severe GO or very high TBII levels. [source] Human granulocytic ehrlichiosis in EuropeCLINICAL MICROBIOLOGY AND INFECTION, Issue 12 2002J. R. Blanco Ehrlichiosis comprises a group of emerging tick-borne infectious diseases caused by obligate intracellular Gram-negative bacteria that infect leukocytes. Infections caused by members of the genus Ehrlichia have been described in animals and humans, but to date there are no convincing reports of the presence of other types of human ehrlichiosis different from human granulocytic ehrlichiosis (HGE) in Europe. The European vector is the same as that of Lyme borreliosis, the hard tick Ixodes ricinus, and HGE has a similar epidemiology to that of Borrelia burgdorferi infection. Across Europe, I. ricinus is infected to a variable extent (0.4,66.7%) with the causative agent Ehrlichia (Anaplasma) phagocytophila genogroup, and since its first description in Slovenia in 1997, details of 15 patients have been published. Diagnosis requires careful consideration of all circumstances and symptoms (history of tick bite and the presence of a flu-like syndrome with variable degrees of anemia, thrombocytopenia, and leukopenia, and elevated liver enzymes). Some differences can be seen between US and European HGE patients. European HGE cases have a less severe course, and the presence of morulae is uncommon. In Europe, verification of HGE has been based on PCR and immunofluorescence antibody tests, because no isolation from humans has been reported. [source] Group A streptococcal osteomyelitis: severe presentation and courseACTA PAEDIATRICA, Issue 1 2003D Turner Aim: To evaluate the course of group A streptococcal osteomyelitis associated with severe disease nowadays. Methods: Three consecutive cases of severe group A streptococcal disease with osteomyelitis in children that were documented in Beer Sheva, Israel are described in detail. Results: Two of the three cases were postvaricella. Early in the course of the disease, the presentation resembled that of severe cellulitis. All three patients had severe osteomyelitis and required surgery, and one patient developed chronic osteomyelitis. Sepsis was diagnosed in two cases. Conclusion: Our cases are distinguishable from typical haematogenous staphylococcal osteomyelitis by the severe course and the extensive involvement of bone and soft tissues. The increase in severity of invasive group A streptococcal infections documented throughout the world could account for the difference between our complex cases and the previous reports. [source] Clinical trial: cyclophosphamide pulse therapy , a promising therapeutic alternative in refractory Crohn's diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 12 2009K. J. SCHMIDT Summary Background, In severe steroid-refractory Crohn's disease (CD), established therapies fail in a relevant proportion of patients. Recent pilot studies indicated the efficacy of cyclophosphamide pulse therapy in these patients. Aim, To provide further and substantial evidence for the rationale to apply cyclophosphamide pulse therapy as therapeutic option in severe courses of CD. Methods, Fifteen patients with steroid-refractory (n = 13) or steroid-dependent (n = 2) CD received 2,6 (median 3) monthly pulses of 750 mg cyclophosphamide in an open-label fashion. Eleven patients were on concomitant immunosuppression (azathioprine/mercaptopurine n = 9; methotrexate n = 2). Results, Thirteen of 15 patients (87%) had a clinical response (CDAI decrease >100). Ten patients (67%) went into remission (CDAI <150) after 8 weeks. Steroid-free remission was achieved in eight patients (54%). Two patients (13%) failed to respond. Median CDAI decreased from 420 (245,550) to 100 (26,538) at week 8. Remission lasted 16 months (median, range 4,40). In three patients, arthritis, erythema nodosum and episcleritis completely resolved. Cyclophosphamide pulse therapy administration was well tolerated in all subjects. Conclusions, Cyclophosphamide pulse therapy is safe and highly effective for induction and maintenance of remission in steroid-refractory/-dependent CD. There is a strong need for additional experience to improve the setting of the encouraging cyclophosphamide treatment in CD. [source] A scoring system for the classification of ,-thalassemia/Hb E disease severityAMERICAN JOURNAL OF HEMATOLOGY, Issue 6 2008Orapan Sripichai ,-Thalassemia intermediate patients show a remarkable clinical heterogeneity. We examined the phenotypic diversity of 950 ,-thalassemia/Hb E patients in an attempt to construct a system for classifying disease severity. A novel scoring system based on six independent parameters, hemoglobin level, age at disease presentation, age at receiving first blood transfusion, requirement for transfusion, spleen size, and growth and development, was able to separate patients into three distinctive severity categories: mild, moderate, and severe courses. This system, therefore, can increase the accuracy of studies of genotype,phenotype interactions and facilitate decisions for appropriate patient management. Am. J. Hematol. 2008. © 2008 Wiley-Liss, Inc. [source] | ||||||||||