Serum fetuin-A level is independent of Helicobacter pylori postinfection status in systemic lupus erythematosus.

Helicobacter pylori is a common pathogen causing gastric inflammation and malignancy. Fetuin-A is a multifunctional protein that is involved in the regulation of calcification, insulin resistance and inflammation. Reports on serum levels of fetuin-A in acute H. pylori infection are contradictory. We intended to see whether H. pylori post-infection status has a long-term effect on serum fetuin-A levels in a well-characterized series of systemic lupus erythematosus cases. In this cross-sectional study 117 patients with systemic lupus erythematosus were enrolled. Helicobacter infection status and serum fetuin-A concentration were determined by ELISA and radial immunodiffusion, respectively. H. pylori positive patients had higher serum fetuin-A concentration than negative ones: 517 (456-603) vs. 476 (408-544) mg L-1, median (25-75% percentiles), P = 0.020. No other parameters differed between these groups. During univariate regression analysis fetuin-A levels were associated with Erythrocyte sedimentation rate (ESR), White blood cell count (WBC), C-reactive protein (CRP), serum total protein, albumin, and the SLEDAI index at the time of diagnosis but only serum albumin remained a significant determinant in multivariate regression study.

Chloroquine cardiotoxicity mimicking connective tissue disease heart involvement.

The authors report a case of rare chloroquine cardiotoxicity mimicking connective tissue disease heart involvement in a 56-year-old woman with mixed connective tissue disease (MCTD) manifested suddenly as third degree A-V block with QT(c) interval prolongation and short torsade de pointes runs ultimately degenerating into ventricular fibrillation. Immunological tests suggested an MCTD flare, implying that cardiac arrest had resulted from myocardial involvement by MCTD. However, QT(c) prolongation is not a characteristic of cardiomyopathy caused by connective tissue disease, unless anti-Ro/SSA positivity is present, but that was not the case. Therefore, looking for another cause of QT(c) prolongation the possibility of chloroquine cardiotoxicity emerged, which the patient had been receiving for almost two years in supramaximal doses. Biopsy of the deltoid muscle was performed, because in chloroquine toxicity, specific lesions are present both in the skeletal muscle and in the myocardium, and electron microscopy revealed the accumulation of cytoplasmic curvilinear bodies, which are specific to antimalarial-induced myocyte damage and are absent in all other muscle diseases, except neuronal ceroid lipofuscinosis. Thus, the diagnosis of chloroquine cardiotoxicity was established. It might be advisable to supplement the periodic ophthalmological examination, which is currently the only recommendation for patients on long-term chloroquine therapy, with ECG screening.

Bilateral Parsonage-Turner syndrome after COVID-19 vaccination. A case report and review of the literature / Kétoldali Parsonage-Turner-szindróma COVID-19-vakcinációt követoen. Esetismertetés és az irodalom áttekintése

Parsonage---Turner syndrome (PTS; neuralgic amyotrophy) is a generally unilateral neuritis with sudden onset, severe shoulder or upper arm pain. Although the intense pain is usually self-limiting, two-thirds of patients experience pro-gressive motor weakness, narrowed range of motion, reflex changes, dysesthesias and chronic neuropathic pain in the shoulder girdle musculature and proximal upper limb muscles. The aetiology is unclear, in addition to some idiopath-ic cases the most common triggers of PTS are surgery, trauma, infection or vaccination. It is reported after SARS-CoV-2 infection, and unilateral PTS has been described in some cases following different types of COVID-19 vaccines. We are currently presenting the case of a middle-aged woman who developed partial neuralgic amyotrophy on the right shoulder one month after receiving the second dose of the BNT162b2 COVID-19 mRNA vaccine (Pfizer-BioNTech), and seven months later the symptoms appeared in the contralateral upper limb. The diagnosis of PTS was also confirmed by magnetic resonance and electrodiagnostic examination. The PTS is not an uncommon condi-tion, but in the absence of knowledge it is rarely thought of. The purpose of this report is to draw attention to the possibility of PTS in shoulder or upper arm pain following both SARS-CoV-2 infection and COVID-19 vaccination, as early diagnosis and adequate therapy may help to shorten the course of the disease.

Human serum fetuin A/alpha2HS-glycoprotein level is associated with long-term survival in patients with alcoholic liver cirrhosis, comparison with the Child-Pugh and MELD scores.

BACKGROUND: Serum concentration of fetuin A/alpha2HS-glycoprotein (AHSG) is a good indicator of liver cell function and 1-month mortality in patients with alcoholic liver cirrhosis and liver cancer. We intended to determine whether decreased serum AHSG levels are associated with long-term mortality and whether the follow-up of serum AHSG levels can add to the predictive value of the Child-Pugh (CP) and MELD scores. METHODS: We determined serum AHSG concentrations in 89 patients by radial immunodiffusion. Samples were taken at the time of enrollment and in the 1st, 3rd, 6th, and the 12th month thereafter. RESULTS: Forty-one patients died during the 1-year follow-up period, 37 of them had liver failure. Data of these patients were analysed further. Deceased patients had lower baseline AHSG levels than the 52 patients who survived (293 +/- 77 vs. 490 +/- 106 microg/ml, mean +/- SD, p < 0.001). Of all laboratory parameters serum AHSG level, CP and MELD scores showed the greatest difference between deceased and survived patients. The cutoff AHSG level 365 microg/ml could differentiate between deceased and survived patients (AUC: 0.937 +/- 0.025, p < 0.001, sensitivity: 0.865, specificity: 0.942) better than the MELD score of 20 (AUC: 0.739 +/- 0.052, p < 0.001, sensitivity: 0.595, specificity: 0.729). Initial AHSG concentrations < 365 microg/ml were associated with high mortality rate (91.4%, relative risk: 9.874, 95% C.I.: 4.258-22.898, p < 0.001) compared to those with > or = 365 microg/ml (9.3%). Fourteen out of these 37 fatalities occurred during the first month of observation. During months 1-12 low AHSG concentration proved to be a strong indicator of mortality (relative risk: 9.257, 95% C.I.: 3.945-21.724, p < 0.001). Multiple logistic regression analysis indicated that decrease of serum AHSG concentration was independent of all variables that differed between survived and deceased patients during univariate analysis. Multivariate analysis showed that correlation of low serum AHSG levels with mortality was stronger than that with CP and MELD scores. Patients with AHSG < 365 microg/ml had significantly shortened survival both in groups with MELD < 20 and MELD > or = 20 (p < 0.0001 and p = 0.0014, respectively). CONCLUSION: Serum AHSG concentration is a reliable and sensitive indicator of 1-year mortality in patients with alcoholic liver cirrhosis that compares well to the predictive value of CP score and may further improve that of MELD score.

[New possibilities of treating patients with autoimmune disorders]. / Az autoimmun betegségek kezelésének újabb lehetoségei.

Autoimmune diseases vary in a wide range from mild to severe, intractable diseases. A great development of the therapy has been encountered in the past decades, in particular of formerly incapacitating diseases, such as rheumatoid arthritis or Crohn's disease. While biologic therapy, in particular monoclonal antibodies, offered most new solutions in these disorders, the therapy with many conventional drugs has also been rewritten. Old drugs, such as cyclophosphamide or intravenous immunoglobulin, retained their position in severe forms of autoimmunity. An evolving new area of stem cell transplantation offers benefit for the most severe patients suffering from intractable autoimmune diseases.

Human fetuin/alpha2HS-glycoprotein level as a novel indicator of liver cell function and short-term mortality in patients with liver cirrhosis and liver cancer.

OBJECTIVE: Human fetuin/alpha2HS-glycoprotein (AHSG) is synthesized by hepatocytes. We intended to determine whether liver dysfunction or acute phase reaction is dominant in the regulation of its serum concentrations and to see if decreased AHGS levels are associated with short-term mortality. DESIGN: We determined the serum AHSG levels in patients with acute alcoholic, acute A, B, and Epstein-Barr virus hepatitis, alcoholic cirrhosis, and hepatocellular cancer and correlated them to conventional laboratory parameters of inflammation and liver function. Patients were followed for 1 month. METHODS: Serum AHSG was determined by radial immunodiffusion. RESULTS: Compared to controls, significantly lower AHSG levels were found in patients with liver cirrhosis and hepatocellular cancer but not the acute viral hepatitides. Strong positive correlation with serum transferrin, albumin and prothrombin was found. Febrile episodes were not associated with significantly decreased AHSG levels. Concentrations below 300 microg/ml were associated with high mortality rate (52.0%; relative risk, 5.497; 95% confidence interval, 2.472-12.23; P < 0.0001). Of all laboratory parameters studied serum AHSG levels showed the greatest difference between deceased and survived patients with cirrhosis and cancer. Moreover, other acute phase reactants did not differ significantly. The multiple logistic regression analysis indicated that the decrease of serum AHSG is independent of all other variables that were found decreased in deceased patients. CONCLUSIONS: Decreased serum AHSG concentration is due rather to hepatocellular dysfunction than the acute phase reaction and is an outstanding predictor of short-term mortality in patients with liver cirrhosis and liver cancer.

[Effectiveness of mometasone furoate nasal spray in seasonal allergic rhinitis. First experiences in practice after the introduction of the drug in Hungary]. / Mometazon furoat orrspray hatékonyságának vizsgálata. A gyógyszer hazai bevezetését követó elsó pollenszezon gyakorlati tapasztalatai.

INTRODUCTION: The authors appraised the clinical efficacy of mometasone furoate in patients with seasonal allergic rhinitis and rhinoconjunctivitis. PATIENTS AND METHODS: An open, two-week trial was conducted in 89 patients between 1 July and 15 September 2001. A baseline oto-rhinolaryngological examination was performed. Nasal obstruction, rhinorrhea, sneezing, and itching as well as ocular, throat and ear clinical signs and general symptoms including cough and dyspnea were characterized using a symptom score. Mometasone furoate was administered intranasally in 100 micrograms doses into both nostrils. Depending on the severity of symptoms, antiallergic eye drops and systemic antihistamines were also allowed. After two weeks of treatment, a follow-up physical examination was performed and the symptom score was re-evaluated. Potential adverse events that had occurred during the treatment period were recorded. RESULTS: Mometasone furoate nasal spray alleviated all four nasal symptoms promptly and effectively. In particular, treatment resulted in a 93 percent decrease of overall symptom score. None of the participants discontinued treatment due to the occurrence of adverse effects. CONCLUSION: These results demonstrate that mometasone furoate nasal spray is a safe and effective intranasal corticosteroid for the therapy of SAR/SARC seasonal allergic rhinitis and rhinoconjunctivitis.

Hereditary angioedema: a decade of human C1-inhibitor concentrate therapy.

BACKGROUND: C1-inhibitor (C1-INH) is a serine protease inhibitor regulating the complement, kinin-kallikrein, coagulation, and fibrinolytic systems. Hereditary angioedema (HAE) is caused by an inherited deficiency of C1-INH characterized by sudden, recurrent edematous swellings of the subcutaneous or submucosal tissues. The optional therapy for the acute management of HAE is administration of human C1-INH (hC1-INH) concentrate. However, hC1-INH is not available in many countries, in which case fresh frozen plasma is an alternative. OBJECTIVE: To summarize our experience with hC1-INH concentrate in patients with HAE. METHODS: Clinical and laboratory information on the effectiveness and safety of hC1-INH administered to relieve 468 acute edematous attacks in 61 patients with HAE was analyzed. RESULTS: Severe abdominal or subcutaneous attacks and laryngeal edema were consistently relieved by the administration of 500 U hC1-INH concentrate. Symptoms improved within 15 to 60 minutes of administration. Progression of the attacks was never observed, and there were no recurrent attacks within 72 hours. hC1-INH concentrate requirements did not change after repeated use. hC1-INH concentrate proved effective in the management of 94 attacks in 22 children and 6 attacks in 4 pregnant women. Adverse reactions, viral infections, and antibody formation against the purified protein did not occur. CONCLUSION: The administration of hC1-INH concentrate in HAE is highly effective and safe for the treatment of acute attacks and short-term prophylaxis and in pediatric patients and pregnant women. CLINICAL IMPLICATIONS: Human C1-INH concentrate is effective and safe for the treatment of acute HAE attacks as well as for short-term prophylaxis.

Eosinophils and Mast Cells in Helicobacter Pylori Infected Gastric Mucosa.

Although Helicobacter pylori (HP) is frequently associated with chronic active gastritis and peptic ulcers, its exact pathogenic role or the pathomechanism is still unclear. Here, we describe a striking, statistically significant increase of eosinophils in HP infected gastric mucosa compared to HP negative gastritis with similar activity. In both cases, the mean number of the mast cells in the mucosa was comparable, although the individual values showed wide distribution. The source and role of eosinophilia in HP infected mucosa, the potential link between the degree of eosinophilia and the clinical progression, as well as between eosinophils and mast cells require further study.

Immunologic Profile of Patients Suffering from Herpes Simplex Virus (HSV) -Associated Oral Lesions Treated with Natural Human Interferon Alpha (Egiferon).

10 consecutive patients with HSV-associated chronic oral lesions were treated with Egiferon for ten days. There were a statistically significant increase in the Large Granule Lymphocyte (LGL) counts and the number of spontaneous E rosette forming cells by the end of the treatment period. Interferon alpha brought about a preferential expression of CD8, CD11b, CD14, CD25 and CD45RO cell surface molecules without any effect on the expression of CD2, CD3, CD4, CD20 and HLA-DR.

Relationship between the tumor necrosis factor alpha polymorphism and the serum C-reactive protein levels in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract, including ulcerative colitis (UC) and Crohn's disease (CD). The aim of the study was to determine the prevalence of the tumor necrosis factor alpha (TNF-alpha) promoter polymorphisms at positions -238 and -308, and to measure the serum CRP levels in CD and UC patients and in a healthy population. The TNF-alpha gene polymorphisms were determined by the PCR-RFLP method. Samples of 74 CD and 50 UC patients and 138 healthy Hungarian volunteers were examined. The G-->A substitution at position -308 (designated the TNF2 allele) was significantly less frequent among IBD patients than in the control group (P=0.0009); 15% of the CD patients and 18% of the UC patients carried the mentioned allele, which was significantly less frequent compared with the healthy population (33%, P=0.0035 and P=0.036, respectively). No difference in the G-->A substitution at position -238 was observed. We found the median CRP levels to be significantly higher in the active phase of the disease than in the inactive phase among the -308A allele carriers (P=0.002), while this difference was not significant when the CRP levels in the active and inactive phases were compared among the -308GG homozygous patients (P=0.084). The decreased frequency of the TNF2 allele (known to be associated with elevated TNF-alpha production) in IBD may determine the severity of IBD through its interaction with plasma CRP levels, and may modify the pathogenesis of this chronic inflammatory disease.

High normal serum levels of C3 and C1 inhibitor, two acute-phase proteins belonging to the complement system, occur more frequently in patients with Crohn's disease than ulcerative colitis.

Few data are available on measurements of serum concentrations of complement proteins in inflammatory bowel disease (IBD). Therefore we measured serum levels of C3, C4, and C1-esterase inhibitor (C1-INH) as well as C-reactive protein (CRP) in 167 patients with Crohn's disease (CD) and 111 patients with ulcerative colitis (UC). Median serum concentrations of C3 and C1-INH were significantly higher in CD than in UC. According to multiple logistic regression analysis adjusted to age, sex, activity of disease, and presence of extraintestinal manifestations, IBD patients with high-normal (> or = 128%, > or = 75th percentile ) C1-INH concentrations had significantly (0.0275) higher odds ratio to have a diagnosis of CD than UC. Patients with high-normal C3 (> or = 1.40 g/liter) and high (> or =20 mg/liter) CRP concentrations had an even higher odds ratio of a CD diagnosis (P = 0.0132). Our findings indicate that measurement of C3, C1-INH, and CRP can be used as an additional marker to pANCA/ASCA for distinguishing patients with CD and UC.

Impaired humoral immune response against mycobacterial 65-kDa heat shock protein (HSP65) in patients with inflammatory bowel disease.

Since only scarce data are available on the immune response against heat shock proteins (HSP) in inflammatory bowel disease (IBD), we have measured with an ELISA method serum levels of IgG, IgA, and IgM antibodies to mycobacterial HSP65 and human HSP60 in 66 patients with Crohn's disease (CD), 42 patients with ulceratiVe colitis (UC), and 126 age-and gender-matched healthy controls. Serum concentration [median (25th-75th percentiles) of IgG anti-HSP65 antibodies was substantially lower in patients with either CD (P < 0.01) or UC (P < 0.001) than in healthy controls, while no difference was found in the levels of anti-HSP60 antibodies. Low anti-HSP65 antibody levels were measured in patients with active CD and in both active and inactive UC, and only in IBD patients with no extraintestinal manifestations. In conclusion, our present findings indicate that an abnormal immune response to bacterial HSP65 or some epitopes of the protein may contribute to the dysregulation of host defenses against certain intestinal bacteria.

Helicobacter pylori infection in connective tissue disorders is associated with high levels of antibodies to mycobacterial hsp65 but not to human hsp60.

BACKGROUND: To investigate whether the Helicobacter pylori status influences levels of antibodies against mycobacterial heat shock protein (hsp) 65 and human hsp60 in systemic autoimmune diseases and to study the concentration of anti-H. pylori antibodies in autoimmune patients and healthy controls. MATERIALS AND METHODS: Antibodies against human heat-shock protein hsp60, mycobacterial heat-shock protein hsp65 were analyzed by ELISA. Anti-Helicobacter antibodies were determined by enzyme immunoassay. RESULTS: There was a markedly higher prevalence of H. pylori infection in undifferentiated connective tissue disease (82%) (n = 33) and systemic sclerosis (78%) (n = 55) but not in systemic lupus erythematosus (n = 49), polymyositis/dermatomyositis (n = 14), rheumatoid arthritis (n = 21) or primary Raynaud's syndrome (n = 26) compared with controls (59%) (n = 349). In autoimmune diseases H. pylori infection was associated with elevated levels of antihsp65 (p =.008) but not of antihsp60. Anti-hsp65 levels were significantly higher in H. pylori-infected (n = 129) than in uninfected patients (n = 69) (p =.0007). CONCLUSIONS: These findings indicate that in autoimmune diseases the infection with the H. pylori bacterium is associated with increased concentration of antimycobacterial hsp65.

Paradoxical alteration of acute-phase protein levels in patients with chronic hepatitis C treated with IFN-alpha2b.

Previously we observed elevation of the serum concentration of two acute-phase protein (AFP) complement components (C9 and C1-inhibitor) in patients with chronic hepatitis C who responded (R) to IFN-alpha therapy, but not in non-responders (NR). In the present study we investigated the effect of high-dose IFN-alpha therapy on serum concentrations of two positive [orosomucoid (OROSO) and C-reactive protein (CRP)] and two negative [transferrin (TF) and fetuin/alpha2HS-glycoprotein (AHSG)] AFP in an outpatient setting. We investigated blood samples of 40 patients with chronic hepatitis C at the onset and at the end of a 3-month treatment with high-dose IFN-alpha2b (5 MIU/day for 6 weeks, followed by 5 MIU t.i.w.) and of 52 healthy individuals. Serum concentrations of OROSO, TF and AHSG were measured by radial immunodiffusion; CRP levels were determined by immunotubridimetry. Compared to controls, patients with chronic hepatitis C had significantly lower OROSO and CRP, and higher AHSG levels. By the end of treatment, OROSO concentration increased in R (P = 0.0054), but not in NR patients. In contrast, TF levels decreased in R (P = 0.0040), but did not change in NR patients. Similarly, in R patients, AHSG levels tended to decrease (P = 0.0942) following IFN-alpha treatment. We conclude that the acute-phase reaction is suppressed in patients with chronic hepatitis C that may be potentially related to the responsiveness to IFN-alpha therapy.

Hereditary and acquired angioedema: problems and progress: proceedings of the third C1 esterase inhibitor deficiency workshop and beyond.

Hereditary angioedema (HAE), a rare but life-threatening condition, manifests as acute attacks of facial, laryngeal, genital, or peripheral swelling or abdominal pain secondary to intra-abdominal edema. Resulting from mutations affecting C1 esterase inhibitor (C1-INH), inhibitor of the first complement system component, attacks are not histamine-mediated and do not respond to antihistamines or corticosteroids. Low awareness and resemblance to other disorders often delay diagnosis; despite availability of C1-INH replacement in some countries, no approved, safe acute attack therapy exists in the United States. The biennial C1 Esterase Inhibitor Deficiency Workshops resulted from a European initiative for better knowledge and treatment of HAE and related diseases. This supplement contains work presented at the third workshop and expanded content toward a definitive picture of angioedema in the absence of allergy. Most notably, it includes cumulative genetic investigations; multinational laboratory diagnosis recommendations; current pathogenesis hypotheses; suggested prophylaxis and acute attack treatment, including home treatment; future treatment options; and analysis of patient subpopulations, including pediatric patients and patients whose angioedema worsened during pregnancy or hormone administration. Causes and management of acquired angioedema and a new type of angioedema with normal C1-INH are also discussed. Collaborative patient and physician efforts, crucial in rare diseases, are emphasized. This supplement seeks to raise awareness and aid diagnosis of HAE, optimize treatment for all patients, and provide a platform for further research in this rare, partially understood disorder.