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Milder Disease (milder + disease)
Selected AbstractsClinical and hematological features of codon 17, A-T mutation of ,-thalassemia in Thai patients,EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 2 2001Vichai Laosombat Abstract: Forty-one patients with codon 17, A-T mutation of ,-thalassemia, which is commonly found in Thailand, were studied to determine whether it is possible to predict phenotypic severity from genetic factors. The clinical phenotype of homozygotes for codon 17, A-T and compound heterozygotes for codon 17, A-T and ,+ -thalassemia may be used to predict a severe phenotype with TM. However, the clinical phenotype of compound heterozygotes for codon 17, A-T and ,+ -thalassemia or Hb E were variable and could not be accurately predicted. The association of ,-thalassemia2 and milder disease was and was not evident in patients with codon 17, A-T and Hb E. The association between Hb CS gene or the presence of XmnI- G, polymorphism and a mild clinical phenotype is not apparent, indicating the involvement of other ameliorating determinants or genetic modifications. [source] Hepatitis C virus carriers with persistently normal ALT levels: biological peculiarities and update of the natural history of liver disease at 10 yearsJOURNAL OF VIRAL HEPATITIS, Issue 5 2006M. Persico Summary., Some chronic hepatitis C (CHC) patients exhibit persistently normal alanine aminotransferase (ALT) levels (PNAL). Patients with PNAL experience significantly milder disease. In order to understand the differences between CHC patients with elevated ALT levels compared with those with PNAL better, we compared epidemiological, immunological and histological findings, in particular, the value of proliferating hepatocyte activity (PCNA) between the two groups of patients. We studied 40 chronic hepatitis C virus (HCV) carriers with increased ALT who underwent liver biopsy for histological diagnosis and determination of clinical prognosis, and 24 PNAL patients under follow-up for 10 years. Immunological response to different HCV genomic epitopes was tested in both the control group and in PNAL subjects. PCNA values from liver specimens of all patients as well as liver biopsies of PNAL patients at time points 0 and 5 years were calculated according to Hall et al.Age, sex and body mass index (BMI) were not significantly different between the two groups. The median liver histology stage was significantly higher in HCV carriers vs the PNAL group (2.5, range = 2,6 vs 1.5, range = 1,2; P < 0.01). Among PNAL patients, histological stage was not statistically different at the three time points considered. Interferon (IFN)-gamma production was comparable in the two groups. PCNA was significantly higher in the group with elevated ALT levels vs the PNAL group (8%, range = 4,15%vs 5% range = 3,8%; P < 0.05) and no statistically significant differences were found in PNAL patients at time points 0, 5 and 10 years. This study confirms that progression to cirrhosis is slow or absent in PNAL patients after 10 years of follow-up. Accordingly, the hepatic proliferative activity index is low and seems to be stable over time. [source] Baroreceptor sensitivity and baroreceptor effectiveness index in cirrhosis: the relevance of hepatic venous pressure gradientLIVER INTERNATIONAL, Issue 2 2010Simonetta Genovesi Abstract Background: Autonomic dysfunction has been reported as one of the complications of cirrhosis. Aims: The aim of this study was to test autonomic dysfunction in cirrhotic patients by analysing the baroreflex sensitivity and the baroreceptor effectiveness index (BEI), in order to determine its correlation with the severity and the aetiology of liver disease. Moreover, we explored the relationship between baroreceptor function and mortality in our cohort of patients. Methods: Clinical and laboratory evaluation, hepatic venous pressure gradient (HVPG) and haemodynamic setting and baroreceptor function were assessed in 45 cirrhotic patients (median age 55, range 38,72 years) divided in groups according to the severity of their disease (26 patients Child A, 13 patients Child B and six patients Child C). Results: Baroreceptor sensitivity and BEI were impaired in more advanced cirrhotic patients compared with subjects with milder disease (P<0.001). HVPG was significantly, independently and inversely correlated with baroreceptor sensitivity (P=0.003). More severe impairment of baroreceptor function was associated with a higher mortality (P=0.04) and subjects with alcohol-related cirrhosis presented worse baroreceptor function (P=0.032) and poorer survival (P=0.003) compared with subjects with post-viral liver disease. Conclusions: These data support the hypothesis that liver disease severity and particularly portal hypertension have an important role in the derangement of baroreceptor function. The aetiology of cirrhosis seems to be related to baroreceptor impairment as well. Mortality rate is higher in subjects with a more damaged autonomic system, strengthening the idea of a worse prognosis in cirrhotic patients with autonomic neuropathy. [source] Role of CTA1R7K-COL-DD as a novel therapeutic mucosal tolerance,inducing vector for treatment of collagen-induced arthritisARTHRITIS & RHEUMATISM, Issue 6 2009Annemarie Hasselberg Objective To determine whether a cholera toxin,derived, novel immunomodulating fusion protein, CTA1R7K-COL-DD, carrying the class II major histocompatibility complex H-2q,restricted type II collagen peptide aa 259,274, can induce therapeutic tolerance and prevent collagen-induced arthritis (CIA) when administered intranasally in DBA/1 mice, and to assess whether ADP-ribosylation at the mucosal membranes exerts a regulatory function such that the outcome of tolerance or immune enhancement can be controlled. Methods DBA/1 mice with CIA were treated intranasally with CTA1R7K-COL-DD. The therapeutic effect was monitored for 46 days after the onset of disease. Clinical scoring of disease, histologic examination of inflammation, and bone erosion were assessed, and cytokine levels were determined in the serum or supernatants from splenocytes stimulated with recall antigen. Results The protective effect of CTA1R7K-COL-DD resulted in roughly 60% of the mice having no clinical signs or histologic evidence of disease after treatment, and those with CIA had significantly milder disease with less bone erosion. The protective status was associated with lower serum titers of IgG1, IgG2a, IgG2b, and IgG3 anticollagen and a substantial decrease in the production of interleukin-6 (IL-6), IL-17, and interferon-,, while levels of IL-10 were markedly up-regulated both in the serum and at the T cell level. Conclusion The enzymatically inactive mutant fusion protein CTA1R7K-COL-DD provided substantial therapeutic protection against CIA following intranasal administration. The mechanism behind the effect appears to be mediated by peptide-specific regulatory T cells induced by mucosal exposure to the peptide containing CTA1R7K-COL-DD vector. In addition, ADP-ribosylation at the mucosal membranes acts as a key regulator controlling mucosal tolerance or immunity. [source] The definition and diagnosis of AsthmaCLINICAL & EXPERIMENTAL ALLERGY, Issue 11 2009F. E. Hargreave Summary The diagnosis of asthma depends on what we mean by the word. Its definition continues to be controversial because there is no single genetic or environmental cause. Addressed from a descriptive point of view, the disease components include airway inflammation, symptoms, variable airflow limitation and chronic airflow limitation. The essentialist definition conveys the message that asthma is a separate disease entity, fails to identify a primary defining characteristic which separates it from other diseases and is long winded. These disadvantages are overcome by the nominalist definition of asthma in which the word ,asthma'refers to an abnormality of airway function, specifically to wide variations in airflow limitation over short periods of time. In patients with asthma the other components of airway disease need to be considered. These have separate nominalist definitions and especially include different types of bronchitis for airway inflammation and chronic obstructive pulmonary disease for chronic airflow limitation. What is present will vary between and within patients. The accurate diagnosis of asthma and of other components of disease all require objective measurements. Currently spirometry and airway responsiveness should be available to the general practitioner, who sees milder disease, and additional quantitative sputum cell counts in specialist practice, where moderate to severe disease is more prevalent. Such measurements characterize the patient, identify heterogeneity and allow treatment to be personalized. [source] | ||||||||||