Spontaneous Exacerbation Research Articles

Analysis of PsO & PsA Treatment with a Focus on Biologics

Psoriasis (PsO) is an autoimmune disease where skin cells build up and form scaly, itchy, and dry patches. PsO is a lifelong disease with spontaneous remission and exacerbation. Up to 30% of patients will also have psoriatic arthritis (PsA) which consists of joint inflammation, pain, stiffness, and swelling. Currently, there is no cure for PsO and PsA, so treatments are focused more on alleviating symptoms, reducing disease severity, and improving quality of life. The goal of this article is to examine treatment selections of biologics for patients with moderate-severe PsO and PsA. Most biologics included in this article, with the exception of etanercept, will allow at least 70% of PsO patients to experience a 75% improvement after 3 months and at least 50% of PsA patients to experience at least a 20% improvement after 6 months. The patient’s insurance coverage, comorbidities, and dosing preference are major factors that should be taken into consideration when selecting a biologic.

HEPATITIS B VIRUS AND ITS GENOTYPES CIRCULATING IN INDIA

Hepatitis B virus (HBV), a DNA virus, is responsible for the acute and chronic hepatitis and lever carcinoma. Worldwide, there are 300 to 350 million people are chronically infected with the virus and 6 lac death occur due to chronic hepatitis and HBV associated liver cirrhosis and lever carcinoma. HBV show variable nucleotide diversity in its genome on the basis of which the virus is classied into ten genotypes (A-J). The HBV infection is mainly spread parenterally, and through intimate contacts. HBV infection is manifested as different diseases such as acute hepatitis, chronic hepatitis, acute or spontaneous exacerbation of chronic hepatitis, fulminant hepatitis, liver cirrhosis, hepatocellular carcinoma and hepatic decompensation. The HBV genome is a relaxed circular, partially double stranded DNAof approximately 3,200 base pairs. There are four partially overlapping open reading frames encoding the envelope (pre-S/S), core (pre-core /core), polymerase, and X proteins. The pre-S/S open reading frame encodes the large, middle, and small surface glycoproteins. Pre-core / core open reading frame is translated into pre-core polypeptide which is modied in to a soluble protein, the hepatitis B e antigen (HBeAg), and the nucleocapsid core protein hepatitis B core antigen (HBcAg).

Therapeutic Effects of Plasmapheresis on Acute Exacerbations of Chronic Hepatitis B Infection.

ObjectiveIn this study, we aimed to demonstrate the effectiveness of plasmapheresis therapy in patients with acute exacerbation of chronic Hepatitis B (CHB) infection.MethodsWe selected 48 patients with acute exacerbation of CHB infection who were treated by plasmapheresis in our intensive care unit between 2009 and 2016. The patients' demographic characteristics and biochemical and hematological parameters, which were recorded before and after plasmapheresis, were assessed, and the effect of plasmapheresis on the course of patients' treatment was examined. The patients were also divided into three groups according to their clinical course (discharged: 24; transplanted: six; exitus: eight). The patients were further divided into four groups and compared based on the underlying causes that led to the exacerbation (spontaneous exacerbation: 25; caused by immunosuppressive drugs: nine; hepatotoxic drugs: six; other agents: eight).ResultsWe observed significant improvements in terms of international normalized ratio (INR), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), lactate dehydrogenase (LDH), total bilirubin, direct bilirubin, blood urea nitrogen (BUN), ammonia, and the Model for End-Stage Liver Disease (MELD) score after plasmapheresis therapy. However, there was no significant improvement in hemoglobin (Hb), white blood cell (WBC) count, platelets, albumin, and lactate values. Also, INR, ALP, and ALT values were found to be significantly correlated with transplants and exitus in patients.ConclusionPlasmapheresis therapy is a reliable treatment method that provides clinical recovery and improvement in laboratory parameters in patients with exacerbation of CHB infection.

European Right-Wing Centrism in the Face of the Coronavirus Crisis

The article examines the reaction of European right-centrist politicians to the threats associated with the spread of coronavirus infection. At the same time, the political context of the perception of the problem is analyzed, especially vividly expressed in approaches to understanding the current crisis and its consequences for the European integration project. The close relationship that exists between the actualization of the national-state identity of Europeans and the increasing requirements for their security is stated. According to leading representatives of the European People’s Party, today fear plays a more prominent role in politics, prevailing over other social emotions. In such conditions, the fundamental need for people to identify themselves as part of a larger community through language, religion or a common understanding of history becomes a critical political factor.According to the author of the article, the viral danger acts as a factor of spontaneous exacerbation of contradictions between national sovereignty and loyalty to all-European structures. At the same time, the emergency actions of national governments forced to deal with the viral threat do not pose a direct threat to European institutions, but raise doubts about their effectiveness. The leadership of the European Union will have to find the right solutions and make extraordinary efforts to maintain a common integration vector with the increased relevance of national competencies.

Cyclooxygenase 2 as a Marker of Early Pregnancy Loss in Cytomegalovirus Infection

Background. Increased expression of cyclooxygenase 2 in the placenta plays a significant role in the formation of placental disorders in the pathological course of pregnancy. It was shown that a high level of expression of cyclooxygenase 2 leads to excessive synthesis of prostaglandins, which stimulate the contractile activity of the uterine myometrium and trigger the abortion mechanism. An analysis of modern literature has shown a lack of data proving the involvement of cyclooxygenase 2 in the pathogenesis of early miscarriages in cytomegalovirus infection. Objective. To establish the pathogenetic role of cyclooxygenase 2 in early pregnancy in the course of miscarriage during exacerbation of cytomegalovirus infection. Materials and methods. The study included 86 women with a gestational age of 8–12 weeks, of which 46 women with spontaneous abortion (O03) and exacerbation of cytomegalovirus infection (main group) and 40 women with medical abortion (O04) without cytomegalovirus infection (control group). The material for the study was peripheral blood serum, urine, homogenate of the villous chorion of the placental tissue. The content of cyclooxygenase 2, the level of IgM and IgG antibodies to cytomegalovirus, low-type IgG antibodies to cytomegalovirus (avidity index) were analyzed by enzyme-linked immunosorbent assay; the content of arachidonic acid – by capillary gas-liquid chromatography. Results. During the study, women of the main group found an increase in the concentration of arachidonic acid by 59 % (p < 0.001) and the activity of the lipolytic enzyme cyclooxygenase 2 – by 58 % (p < 0.001) in the placenta villous chorion homogenate. Conclusion. With an exacerbation of cytomegalovirus infection in the homogenate of the villous placenta chorion of pregnant women with spontaneous abortion, an increase in the content of arachidonic acid and the level of cyclooxygenase 2 is observed. An increased level of cyclooxygenase 2 indicates the development of pregnancy complications and can be used as a non-specific marker predictor of pregnancy termination during exacerbation of cytosis.

Comparative Study on the Response of Tenofovir Mono Therapy Versus Tenofovir Plus Telbivudine Dual Therapy in Patients With Hepatitis B Virus Related Acute on Chronic Liver Failure

Background and Aim: Severe acute spontaneous exacerbation of CHB leading to ACLF is extremely poor, with mortality ranging from 30% to 70%. Therefore, early and rapid reduction of HBV DNA is the essence of therapy in ACLF-B. Methods: Patients with spontaneous reactivation of HBV [(ALT >5 × ULN or >2 × baseline) and HBV DNA >20,000 IU/ml] were randomized to Tenofovir mono therapy (300 mg/day) or Tenofovir plus Telbivudine (600 mg/day) dual therapy along with standard medical treatment. Clinical and biochemical parameters were evaluated at baseline, 1 week, 4 weeks and at 3 months. Virological evaluation was done at baseline and at 3 months. End point was reduction of HBV DNA, reduction of liver related complication, therapy related adverse effects and survival at 3 months. Results: 27 patients were enrolled and 15 of them received mono therapy with Tenofovir and 12 patients received dual therapy (Tenofovir plus Telbivudine). Baseline parameters in two groups had no significant difference. Both groups significantly improve bilirubin, ALT, INR, CTP score and MELD score. Only MELD score showed significant improvement in patient with dual therapy at 3 months in comparison of mono therapy. 11 patient on Tenofovir mono therapy showed undetected HBV DNA (91.7%) at 3 month and one patient had detectable HBV DNA. 10 patients on dual therapy had undetectable HBV DNA (100%). Patients receiving dual therapy showed significant improvement in AKI on follow up compared to those on mono therapy. Among 5 deaths, 3 had received mono therapy and 2 had received dual therapy. Predictors of mortality were high S. bilirubin (25.8 ± 7.8), HBV DNA (5.18 ± 1.17 log10 IU/ml), MELD score (33.0 ± 4.2) and CTP score (12.2 ± 0.8) (Table 1).Table 1Comparison of Meld Score and CTP Score Between Two Study Groups After 90 Days (N = 27).Tenofovir Plus Telbivudine (n = 10)Tenofovir (n = 12)P valueNo. (%)No. (%)MELD score<156(60.0%)2(16.7%)0.035s>154(40.0%)10(83.3%)CTP score<86(60.0%)5(41.7%)0.391 ns>84(40.0%)7(58.3%)Data were expressed frequency and percentage.P value reached from Chi-square test, ns = not significant, s = significant. Open table in a new tab Data were expressed frequency and percentage. P value reached from Chi-square test, ns = not significant, s = significant. Conclusion: In ACLF-B combination of Telbivudine plus Tenofovir is potentially safer with less risk of Tenofovir related nephrotoxicity and hence improved outcomes (Figure 1). The authors have none to declare.

Hepatic flares in chronic hepatitis C: spontaneous exacerbation vs hepatotropic viruses superinfection.

The hepatitis C virus (HCV) causes an acute infection that is frequently asymptomatic, but a spontaneous eradication of HCV infection occurs only in one-third of patients. The remaining two-thirds develop a chronic infection that, in most cases, shows an indolent course and a slow progression to the more advanced stages of the illness. Nearly a quarter of cases with chronic hepatitis C (CHC) develop liver cirrhosis with or without hepatocellular carcinoma. The indolent course of the illness may be troubled by the occurrence of a hepatic flare, i.e., a spontaneous acute exacerbation of CHC due to changes in the immune response, immunosuppression and subsequent restoration, and is characterized by an increase in serum aminotransferase values, a frequent deterioration in liver fibrosis and necroinflammation but also a high frequency of sustained viral response to pegylated interferon plus ribavirin treatment. A substantial increase in serum aminotransferase values during the clinical course of CHC may also be a consequence of a superinfection by other hepatotropic viruses, namely hepatitis B virus (HBV), HBV plus hepatitis D virus, hepatitis E virus, cytomegalovirus, particularly in geographical areas with high endemicity levels. The etiology of a hepatic flare in patients with CHC should always be defined to optimize follow-up procedures and clinical and therapeutic decisions.

Orofacial granulomatosis with gingival manifestation – A rare case report

Orofacial granulomatosis (OFG) is uncommon but increasingly recognized chronic inflammatory disorder characterized by persistent and recurrent lip swelling. It also affects gingiva, buccal mucosa, floor of mouth and a number of other sites in the oral cavity. Orofacial granulomatosis may cause significant cosmetic and functional problems which can be prevented if the disease is diagnosed in its infancy and promptly treated.This is a case report of orofacial granulomatosis in 25-year-old female patient with gingival swelling bearing granular appearance lip and cheek swelling with spontaneous exacerbation and remission since 2 years. Histopathological evaluation and treatment modalities with respect to orofacial granulomatosis are discussed.

Acute and Acute Severe (Fulminant) Autoimmune Hepatitis

Autoimmune hepatitis frequently has an abrupt onset of symptoms, and it can present with acute liver failure. The abrupt presentation can indicate spontaneous exacerbation of a pre-existent chronic disease, newly created disease, a superimposed infectious or toxic injury, or new disease after viral infection, drug therapy, or liver transplantation. Deficiencies in the classical phenotype may include a low serum immunoglobulin G level and low or absent titers of the conventional autoantibodies. The original revised diagnostic scoring system of the International Autoimmune Hepatitis Group can guide the diagnostic evaluation, but low scores do not preclude the diagnosis. Liver tissue examination is valuable to exclude viral-related or drug-induced liver injury and support the diagnosis by demonstrating centrilobular necrosis (usually with interface hepatitis), lymphoplasmacytic infiltration, hepatocyte rosettes, and fibrosis. Conventional therapy with prednisone and azathioprine induces clinical and laboratory improvement in 68-75 % of patients with acute presentations, and high dose prednisone or prednisolone (preferred drug) is effective in 20-100 % of patients with acute severe (fulminant) presentations. Failure to improve or worsening of any clinical or laboratory feature within 2 weeks of treatment or worsening of a mathematical model of end-stage liver disease within 7 days justifies liver transplantation in acute liver failure. Liver transplantation for acute severe (fulminant) autoimmune hepatitis is as successful as liver transplantation for autoimmune hepatitis with a chronic presentation and other types of acute liver failure (patient survival >1 year, 80-94 %). Liver transplantation should not be delayed or superseded by protracted corticosteroid therapy or the empiric institution of nonstandard medications.

Osteosarcoma of maxilla mimicking neurofibroma

Osteosarcoma (OS) is a primary malignant bone tumor producing osteoid or bone. It occurs less frequently in the jaws and in maxilla occurrence is rare. Jaws are less affected compared to long bones (4-13%). The mean age of occurrence is third to fourth decade. The histopathologic features of OS are highly variable. Herein, we report a rare case of a 72 year old female patient with a swelling in right posterior maxilla, whose clinical, radiographic findings were non-specific, An initial incisional biopsy confirmed neurofibroma. Later, a wide surgical excision was done as there was a spontaneous exacerbation of the growth, and histopathology report came as chondroblastic osteosarcoma.

Clinical Features, Differential Diagnosis and Treatment of Autoimmune Hepatitis in the Elderly

Autoimmune hepatitis affects all ages, and it is probably under-diagnosed in the elderly. Patients aged >or= 60 years have a higher frequency of cirrhosis at presentation than adults aged <or= 30 years, and they more commonly have HLA DRB1*04. These findings suggest that host factors affect the clinical phenotype by influencing the antigens that are presented to immunocytes and the nature of the immune response. The elderly may have an indolent progressive disease that is asymptomatic or masked by other concurrent rheumatic conditions. An acute, even fulminant, presentation may reflect de novo disease or a spontaneous exacerbation of a pre-existent chronic process. Centrilobular (zone 3) necrosis may reflect an early histological stage that transforms later to classical interface hepatitis. Diagnostic criteria have been codified, and a scoring system allows systemic assessment of all clinical features and quantifies the strength of the diagnosis. Prednisone in combination with azathioprine is the safest effective initial treatment, and all elderly patients with severe disease should be treated vigorously to full resolution of clinical, laboratory and histological features. Adverse effects of treatment occur mainly with protracted treatment (>18 months) and repeated therapies after relapse. Adjustments in the management strategy are warranted for an incomplete response or a need for re-treatment after relapse. Azathioprine (2 mg/kg/day) should be used as a corticosteroid-sparing, long-term maintenance therapy in these instances. Treatment failure is uncommon in the elderly, and age-related changes in the cellular immune response may attenuate the disease and enhance its response to therapy. Concurrent adjuvant therapies must focus on maintenance of bone density.

Hepatitis E virus as an etiology of acute exacerbation of previously unrecognized asymptomatic patients with hepatitis B virus‐related chronic liver disease

Hepatitis E virus (HEV) has recently been implicated in episodes of acute decompensation in patients having underlying chronic liver disease (CLD) of varying etiology. However, HEV as a cause of acute exacerbation of previously asymptomatic and unrecognized hepatitis B virus (HBV)-infected patients is less well described. The aim of the present study was to investigate the etiology of acute exacerbation of previously asymptomatic and unrecognized HBV-infected patients and to evaluate the relative role of HEV. We also investigated the effect of superinfection on the clinical spectrum of underlying HBV infection. Forty-three patients presented with the following were retrospectively analyzed: (i) clinical features suggestive of acute hepatitis; (ii) with hepatitis B surface antigen (HBsAg) (+); (iii) IgM hepatitis B core antibody (IgM anti-HBc) (-); (iv) no previous history of liver disease; (v) no features suggestive of CLD at presentation; (vi) HBsAg remaining (+) for at least 12 months on follow up; and (vii) having a follow-up biopsy during the convalescent phase showing evidence of chronic hepatitis B. Of the 43 patients, 21 were hepatitis e antigen (HBeAg) (+) (Gr.1) and 22 HBeAg (-) (Gr.2) at presentation. In Gr.1, only two (9.5%) had superinfection (both with hepatitis A virus), whereas in Gr.2, 11 (50%) had superinfection (27.3% hepatitis E, 13.6% hepatitis A and 9.1% both) (P = 0.007). In Gr.1, the remaining 19 (90.5%) patients had spontaneous exacerbation (immune clearance with spontaneous seroconversion) whereas in Gr.2, the remaining 11 (50%) had spontaneous exacerbation (due to reactivation). Overall, HEV superinfection contributed to 20% of acute exacerbation episodes and, in particular, 36% of episodes in initially HBeAg (-) patients. Time to alanine aminotransferase normalization was longer in patients with superinfection (n = 13) as compared to spontaneous exacerbation (n = 30) (median [range] 36 [8-48]vs 16 [6-36] weeks, P = 0.001). During convalescence, there was no significant difference between histological activity index score (median [range] 8 [4-11]vs 8 [4-16] weeks, P = 0.629) and fibrosis scores (median [range] 3.5 [1-4]vs 2 [1-4] weeks, P = 0.099] on liver biopsy after recovery among patients with acute exacerbation due to superinfection and spontaneous exacerbation. Acute exacerbations in HBeAg (+) patients are most often due to spontaneous viral activation, while in HBeAg (-) patients, superinfection with non-B hepatitis viruses and spontaneous viral activation are equally common. HEV is an important cause of acute exacerbation in previously asymptomatic and unrecognized patients with HBV-related CLD.

Inhaled fluticasone propionate is effective as well as oral prednisone in reducing sputum eosinophilia during exacerbations of asthma which do not require hospitalization

The aim of this study was to evaluate whether fluticasone propionate (FP) is effective as well as prednisone (P) in reducing sputum eosinophilia and in improving airway obstruction due to asthma exacerbations not requiring hospitalization. We measured, in a parallel-group, double-blind double-dummy, randomized study, sputum and blood inflammatory cell counts and soluble mediators in 37 asthmatic subjects during a spontaneous exacerbation of asthma (Visit 1) and after a 2 week (Visit 2) treatment with inhaled FP (1000 μg bid) (Group A, n = 18 ) or a reducing course of oral P (Group B, n = 19 ). Asthma exacerbation was accompanied by sputum eosinophilia (eosinophils >2%) in almost all patients (95%). FP improved FEV 1 (from 53.9%±16.8 at Visit 1 to 76.4%±21.2 at Visit 2, p = 0.0001 ) and reduced the percentage of sputum eosinophils (from 38%[0–78] to 3%[1–31, p = 0.0008 ) as well as oral P (FEV 1: from 51.5%±14.4 to 83.6%±21.1, p = 0.0001 ; sputum eosinophils: from 52%[1–96] to 11%[0–64], p = 0.0003 ). At Visit 2, sputum eosinophils were significantly lower in Group A than in Group B. P but not FP induced significant decrease in blood and sputum ECP. Oxygen saturation, PEF variability, symptom score and use of rescue medication similarly improved in both groups. We conclude that FP is effective at least as well as P in reducing sputum eosinophilia and in improving airway obstruction due to asthma exacerbation. However, the cost/effectiveness ratio of this option should be further evaluated.

Analysis of Sputum Cell Counts During Spontaneous Moderate Exacerbations of Asthma in Comparison to the Stable Phase

Background. Acute airway inflammation is considered to characterize asthma exacerbations, but its specific cellular pattern has not yet been completely evaluated. Aim. To evaluate the prevalence of sputum eosinophilia during acute asthma exacerbations of moderate severity, compared with a stable phase of the disease, and to assess the concordance between changes in pulmonary function and sputum eosinophilia in the period between exacerbation and post exacerbation. Methods. We compared sputum and blood inflammatory cell counts in 29 asthmatic subjects during a spontaneous moderate exacerbation of asthma (visit 1) with sputum and blood cell counts measured 4 weeks after the resolution of asthma exacerbation (visit 2). At visit 1, all subjects required an appropriate 1 week treatment with oral corticosteroids. Results. At visit 1, all subjects were able to collect spontaneous sputum, whereas at visit 2 sputum was induced by inhalation of hypertonic saline (NaCl 3, 4, and 5%, 10 minutes each) with β2-agonist pretreatment. Asthma exacerbation was accompanied by a significant increase in sputum eosinophil percentages compared with levels after exacerbation [25%(1–78) versus 4%(0–23), p<0.05). Only four subjects showed low sputum eosinophil percentages during exacerbation, and these showed no differences in main clinical findings with respect to subjects with sputum eosinophilia. At visit 2, the stability of asthma was assessed on the basis of PEF, FEV1, symptoms, and use of rescue β2-agonist. Asthma was defined as stable in 21 out of 29 subjects. Sputum eosinophil percentages fell significantly between visit 1 and visit 2 in both stable and unstable patients, but at visit 2 sputum eosinophil percentages were still high in subjects with unstable asthma. In patients who proved to be stable at visit 2, there was a significant correlation between the changes recorded in sputum eosinophil percentages and in FEV1 between the two visits (rho: 0.723, p<0.001). Conclusion. Sputum eosinophil but not neutrophil percentages increase in most asthmatic subjects during moderate exacerbation of asthma. Changes in the degree of airway eosinophilic inflammation are related to changes in the severity of airway obstruction during asthma exacerbation.

Sputum matrix metalloproteinase-9: Tissue inhibitor of metalloproteinase-1 ratio in acute asthma

Background: The ratio of matrix metalloproteinase-9 (MMP-9) and its inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1) may be a marker of the balance between airway tissue destruction and repair. TIMP-1 may potentially contribute to the pathogenesis of increased submucosal extracellular matrix deposition in asthma. Objective: Our purpose was to assess the variation in sputum MMP-9 and TIMP-1 during acute asthma. Methods: We evaluated the MMP-9 and TIMP-1 balance in sputa of 16 asthmatic patients admitted with spontaneous exacerbation, conducting measurement before (day 1) and after methylprednisolone infusion therapy (days 2, 3, 5, and 7), and on remission days. Results: Peak expiratory flow and eosinophilic cationic protein levels were significantly (P < .05) improved within 7 days in all patients. Sputum MMP-9 levels on day 2 tended to be lower than on day 1, but not significantly. Zymography revealed that the main enzyme was identified immunologically as MMP-9, and gelatinase activity on day 1 had a tendency to decrease for the following 7 days. The TIMP-1 levels gradually increased until day 5, were significantly (P < .05) high on day 5, and decreased on day 7. The MMP-9/TIMP-1 molar ratios were significantly (P < .05) decreased on days 2, 3, 5, and 7 compared with day 1. Sputum levels of MMP-9 and TIMP-1 and the MMP-9/TIMP-1 molar ratios on day 1 were significantly higher (P < .02) than those on remission days. Conclusions: An imbalance between MMP-9 and TIMP-1 was present in acute asthma, with an excess of MMP-9 resulting in a high ratio of MMP-9/TIMP-1 before treatment, and over time with glucocorticosteroid the TIMP-1 levels rose, dropping the ratio of MMP-9/TIMP-1. It was suggested that overproduction of MMP-9 and TIMP-1 after asthma exacerbation might contribute significantly to airway tissue remodeling and that TIMP-1 production in acute asthma might not be suppressed by glucocorticosteroid. (J Allergy Clin Immunol 2000;105:900-905.)

Paradoxical inhibition of cardiac lipid peroxidation in cancer patients treated with doxorubicin. Pharmacologic and molecular reappraisal of anthracycline cardiotoxicity.

Anticancer therapy with doxorubicin (DOX) and other quinone anthracyclines is limited by severe cardiotoxicity, reportedly because semiquinone metabolites delocalize Fe(II) from ferritin and generate hydrogen peroxide, thereby promoting hydroxyl radical formation and lipid peroxidation. Cardioprotective interventions with antioxidants or chelators have nevertheless produced conflicting results. To investigate the role and mechanism(s) of cardiac lipid peroxidation in a clinical setting, we measured lipid conjugated dienes (CD) and hydroperoxides in blood plasma samples from the coronary sinus and femoral artery of nine cancer patients undergoing intravenous treatments with DOX. Before treatment, CD were unexpectedly higher in coronary sinus than in femoral artery (342 +/- 131 vs 112 +/- 44 nmol/ml, mean +/- SD; P < 0.01), showing that cardiac tissues were spontaneously involved in lipid peroxidation. This was not observed in ten patients undergoing cardiac catheterization for the diagnosis of arrhythmias or valvular dysfunctions, indicating that myocardial lipid peroxidation was specifically increased by the presence of cancer. The infusion of a standard dose of 60 mg DOX/m(2) rapidly ( approximately 5 min) abolished the difference in CD levels between coronary sinus and femoral artery (134 +/- 95 vs 112 +/- 37 nmol/ml); moreover, dose fractionation studies showed that cardiac release of CD and hydroperoxides decreased by approximately 80% in response to the infusion of as little as 13 mg DOX/m(2). Thus, DOX appeared to inhibit cardiac lipid peroxidation in a rather potent manner. Corollary in vitro experiments were performed using myocardial biopsies from patients undergoing aortocoronary bypass grafting. These experiments suggested that the spontaneous exacerbation of lipid peroxidation probably involved preexisting Fe(II) complexes, which could not be sequestered adequately by cardiac isoferritins and became redox inactive when hydrogen peroxide was included to simulate DOX metabolism and hydroxyl radical formation. Collectively, these in vitro and in vivo studies provide novel evidence for a possible inhibition of cardiac lipid peroxidation in DOX-treated patients. Other processes might therefore contribute to the cardiotoxicity of DOX.

Cold activation of complement in sera from patients with persistent hepatitis C virus infection on interferon therapy.

The loss of haemolytic activity in sera during storage at low temperature (the cold activation of complement) was observed in 136 of 184 (74%) patients with chronic liver disease associated with hepatitis C virus (HCV) infection. This was more frequent than observed in the three of 40 (8%) patients with chronic hepatitis B (P < 0.001) or none in 43 normal controls (P < 0.001). Of 103 patients with chronic hepatitis C who had completed a full course of recombinant interferon-alpha 2a therapy (total dose: 516 x 10(6) U), 40 responded completely and 21 responded partially, as judged by the normalization or decrease of alanine aminotransferase levels 6 months after the completion of therapy; 42 patients did not respond at all. The cold activation of complement persisted in five (13%) complete responders, less often than in 33 (79%) non-responders (P < 0.001). At the completion of interferon therapy, the cold activation of complement persisted in 12 of 54 patients despite the normalization of alanine aminotransferase. Spontaneous exacerbation of hepatitis occurred in seven of 12 (58%) patients with cold activation, which was more frequent than in the four of 42 patients (10%) without it (P < 0.01). The cold activation of complement disappeared along with the loss of HCV-RNA in five of six responders during the 6 month period after the completion of interferon therapy, while both cold activation and HCV-RNA persisted in all eight non-responders. These results indicate that the cold activation of complement may be useful as a marker of HCV viraemia for monitoring the response to interferon in patients with HCV infection.

Hepatic encephalopathy after transjugular intrahepatic portosystemic shunt

Forty-seven consecutive patients were prospectively evaluated to study the incidence of hepatic encephalopathy as well as modifications in the PSE index after TIPS. Various clinical, laboratory, and angiographic parameters were also recorded to identify risk factors for the development of post-TIPS hepatic encephalopathy (HE). Mean follow-up was 17 +/- 7 months. During follow-up, six patients died and one underwent transplantation. All other patients were followed for at least a year. Fifteen patients (32%) experienced 20 acute episodes of precipitated HE (hospitalization was necessary in 10 instances), and five patients (11%) presented a continuous alteration in mental status with frequent spontaneous exacerbation during follow-up. Both precipitated and spontaneous HE occurred more frequently during the first three months of follow-up. Moreover the PSE index was significantly worse than basal values one month after TIPS, thereafter returning to near basal values. HE was successfully treated in all patients but one who required a reduction in the stent/shunt diameter. Increasing age (>65 years) and low portacaval gradient (<10 mm Hg) were predictors of HE after TIPS. A gradual dilation of the stent/shunt should be performed to obtain a portacaval gradient >10 mm Hg to avoid an unacceptable rate of HE after TIPS.

Spontaneous exacerbation of disease activity in patients with chronic delta hepatitis infection: the role of hepatitis B, C or D?

Forty-six patients with chronic hepatitis delta virus infection were followed between 6 and 116 mo (mean = 32.8 mo; median = 24 mo). Nineteen patients (41%) demonstrated clinical courses with episodes of biochemical reactivation (ALT levels greater than or equal to 10 times baseline values [group A]). Twenty-seven patients (59%) had stable clinical courses without biochemical reactivation (group B). Patients in group A were younger than those in group B (30.5 vs. 35.3 yr; p = 0.03), were less likely to be intravenous drug abusers (16% vs. 52%; p = 0.01) and were more likely to be homosexual (58% vs. 22%; p = 0.01). Serum hepatitis B virus DNA, hepatitis delta virus RNA, IgM antibody to HBc, HBeAg, antibody to HBe and IgG and IgM antibody to hepatitis delta virus were measured in all patients. In group A, these markers were studied before and during reactivation and during remission. In group B, these parameters were studied in a random fashion at 7- to 10-mo intervals. The presence of antibodies to human immunodeficiency virus and hepatitis C virus was assessed in all patients. A total of 38 biochemical reactivation episodes was noted among the 19 patients in group A. Eleven had sequential changes in hepatitis delta virus markers, suggesting that the exacerbations were due to hepatitis delta virus. In three, the sequential changes of viral markers were consistent with the exacerbations due to hepatitis B virus. In five other patients, no sequential changes in viral markers could be demonstrated to correlate with the biochemical exacerbations.(ABSTRACT TRUNCATED AT 250 WORDS)

Gastrointestinal and metabolic function in patients with the carcinoid syndrome

We evaluated gastrointestinal absorption in six consecutive patients with metastatic serotonin-secreting carcinoid tumors. One patient had a consistent defect in fat absorption and two other patients malabsorbed fat during spontaneous or dopamine-induced exacerbation of the carcinoid syndrome. The steatorrhea of the patient with the persistent defect in fat absorption was reduced when tumor serotonin production was reduced by the tryptophan hydroxylase inhibitor parachlorophenylalanine. The six patients had normal hemoglobin levels and the serum concentration of the following urinary constituents was normal in most of the patients: albumin, carotene, 25-hydroxycalciferol, parathyroid hormone, calcitonin, calcium, phosphorous, osteogenous alkaline phosphatase, cholesterol, triglycerides, and serum lipoproteins. The excretion of the following urinary constituents was also normal in most of the patients: creatinine clearance, tubular reabsorption of phosphorous, calcium, D-xylose, cyclic 3'5' monophosphate and hydroxyproline. We conclude that patients with the carcinoid syndrome may have steatorrhea, and that their hyperserotoninemia plays a role in this process.