bluuebunny/crossref_metadata_2025_split huggingface dataset:
The economic burden of antibiotic treatment of penicillin‐allergic patients in internal medicine wards of a general tertiary care hospital
Authors: Sade K. , Holtzer I. , Levo Y. , Kivity S. 
Published: December 2004

SummaryBackground Penicillin allergy poses a major problem in the management of infectious diseases.Objective We estimated the costs and usage of antibiotic treatment of ‘penicillin‐allergic’ patients in comparison to non‐allergic patients in a tertiary care hospital.Materials and methods The study was based on the records of 118 randomly chosen in‐hospital patients labelled as being ‘allergic to penicillin’ and who were treated with antibiotics. The antibiotic selection and cost of the patients with alleged penicillin allergy were compared to 118 matched patients without an antibiotic allergy (controls).Results During in‐hospital treatment, the mean antibiotic cost for penicillin‐allergic patients was 63% higher than the cost for the controls. In addition, there was a 38% higher cost of the recommended anti‐microbial treatment regimen to be followed upon discharge by the former compared to the latter.Conclusions Penicillin‐allergic patients were more likely to receive broader spectrum antibiotics compared to the non‐allergic ones. Since many of the patients who are labelled as being ‘allergic to penicillin’ are, in fact, not allergic to it, inaccurate reporting of penicillin allergies may have costly economic and epidemiologic repercussions in addition to more toxic effects which can occur when choosing alternative drugs in case of penicillin allergy.
Systemic reactions to immunotherapy: influence of composition and manufacturer
Authors: Gastaminza G. , Algorta J. , Audicana M. , Etxenagusia M. , Fernández E. , Muñoz D. 
Published: December 2004

SummaryBackground Although immunotherapy clearly demonstrated the benefit of reducing allergic symptoms, it has the drawback of adverse events, mainly systemic reactions that could be very inconvenient for patients and even life‐threatening.Objective The aim of the present study was to assess the incidence of systemic reactions to immunotherapy in a large number of patients, and its potential relationship with the characteristics of therapy, such as allergen composition or manufacturing laboratory.Methods This study analysed the administration of specific immunotherapy during a period of 5 years, involving 1212 patients affected by respiratory hypersensitivity or hymenoptera venom anaphylaxis. Commercial extracts were supplied by five different laboratories. All the patients were attended at an out‐clinic immunotherapy unit by the same experienced staff. Immunotherapy was given following a conventional schedule, modified according the usual recommendations.Results A total of 250 adverse reactions have been recorded, resulting in a frequency of 0.84% over the total number of injections. Seventy‐nine of them (32%) were systemic reactions (0.27% SR/injection). The 79 systemic reactions were observed in 60 patients (5% of the patients). The frequency of systemic reactions was significantly lower (P < 0.01) on the group of mites than on the other groups. The frequency of systemic reactions varies according to the manufacturing laboratory. In the case of mite extracts, although one of the laboratories had a lower frequency of adverse systemic reactions, it did not reach the level of statistical significance. However, in relation to pollen extracts, preparations of one of the manufacturers had a significantly lower frequency of systemic reactions. Concerning the time of occurrence, 27% of systemic reactions were delayed, thus they appeared at least 30 min after the vaccine injection, most of them due to pollen extracts.Conclusion This is a preliminary study to evaluate the factors that could facilitate the appearance of systemic reactions demonstrating that not only the composition but also the manufacturer is connected to systemic reactions. Although further studies are needed to clearly establish the influence of manufacturer on frequency and time of appearance of systemic reactions, it seems necessary to reach a wide consensus on allergen extract standardization methods.
Cellular responses to cytomegalovirus in immunosuppressed patients: circulating CD8+ T cells recognizing CMVpp65 are present but display functional impairment
Authors: ENGSTRAND M , LIDEHÄLL A K , TÖTTERMAN T H , HERRMAN B , ERIKSSON B-M , KORSGREN O 
Published: December 2004

SUMMARYThe availability of tetrameric complexes of HLA class I molecules folded with immunodominant peptides makes it possible to utilize flow cytometry for rapid and highly specific visualization of virus specific CD8+ T cells. An alternate technique is to incubate whole blood with specific antigens and to subsequently detect and characterize responding T cells (e.g. by performing intracellular staining of interferon-gamma). By using an HLA-A2 tetramer construct folded with the same immunodominant CMV-peptide as that used for peptide pulsing, we monitored both the presence and functional capacity of CMV-specific CD8+ T cells. In addition T cell activation was assayed by determination of CD38 and CD69 expression. Twelve organ transplant patients and 31 healthy blood donors with latent CMV infection were investigated using CMV pp65 tetramer staining and intracellular staining of interferon-gamma after CMV pp65 peptide pulsing or CMV lysate pulsing. CMV-specific T cells were detected in similar absolute numbers as well as frequencies of T cells in the two groups investigated. However, the CMV-specific CD8+ T cells in immunosuppressed individuals showed a decreased functional response to the CMV-peptide, as evidenced by reduced interferon-gamma production when compared to healthy blood donors (19%; 42%, P &lt; 0·005). In addition, CD38 expression was markedly higher in immunosuppressed patients compared to healthy blood donors (24%; 6%, P &lt; 0·005). In a case report we demonstrate that reactivation of CMV can occur in an immunosuppressed patient with high number of CMV-specific T cells, but without functional capacity. Hence, these findings reflect impaired activation of cytotoxic T cells controlling latent CMV infection in immunosuppressed patients.
High serum vascular endothelial growth factor correlates with disease activity of spondylarthropathies
Authors: DROUART M , SAAS P , BILLOT M , CEDOZ J-P , TIBERGHIEN P , WENDLING D , TOUSSIROT É 
Published: December 2004

SUMMARYAngiogenesis is involved in chronic inflammatory joint diseases such as rheumatoid arthritis (RA). Vascular endothelial growth factor (VEGF) plays a crucial role in angiogenesis. The spondylarthropathies (SpA) are characterized by enthesitis and synovitis, in which blood vessels participate. The objective of this study was to investigate serum VEGF levels and their potential associations with disease activity markers for SpA. Sera were collected from 105 patients with SpA (72 with ankylosing spondylitis (AS), four with psoriatic arthritis (PsA), six with reactive arthritis (ReA), eight with enteropathic arthropathy and 15 with undifferentiated SpA), 50 patients with rheumatoid arthritis (RA) and 64 healthy controls. Disease activity in SpA patients was assessed using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and laboratory parameters of inflammation [erythrocyte sedimentation rate (ESR) and C-reactive protein level (CRP)]. Serum VEGF levels were significantly higher in SpA patients (316·4 ± 215·6 pg/ml) and RA patients (405·2 ± 366·5) than in controls (217·3 ± 145·2) (P = 0·003). In SpA patients, serum VEGF levels correlated with disease activity indices (BASDAI: r = 0·22, P = 0·04; ESR: r = 0·3, P = 0·003; and CRP: r = 0·23, P = 0·02). Serum VEGF levels were not associated with presence of extra-articular manifestations or syndesmophytes or with the grade of sacroiliitis. These results suggest that VEGF and therefore angiogenesis may play a role in SpA pathogenesis and may serve as a disease activity marker in SpAs.
Keratinocyte growth factor (KGF) decreases ICAM-1 and VCAM-1 cell expression on bronchial epithelial cells
Authors: JUST N , TILLIE-LEBLOND I , GUERY B P H , FOURNEAU C , TONNEL A-B , GOSSET P 
Published: December 2004

SUMMARYActivation of leucocytes during airway inflammatory reaction involves adhesion to bronchial epithelial cells (BEC), a process implicating specific interactions between glycoproteins with epithelial cell surface proteins, mainly intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). In this study, the effect of keratinocyte growth factor (KGF), a growth factor involved in pulmonary epithelium repair, was evaluated on adhesion molecule expression with BEAS-2B cells and BEC and granulocyte adherence to BEAS-2B. The modulation by KGF of membrane and mRNA expression of ICAM-1 and VCAM-1 was studied on confluent cells stimulated or not with tumour necrosis factor-α (TNF) (200 UI/ml) or TNF and interleukin (IL)-4 (50 UI/ml and 10 ng/ml). Levels of soluble-(s)ICAM-1 and sVCAM-1 were measured by ELISA. Although moderately, KGF significantly decreased membrane ICAM-1 expression in unstimulated BEAS-2B cells (24% inhibition at 100 ng/ml) or in TNF- or TNF + IL-4-stimulated cells (22·5 and 18·7% inhibition, respectively). Treatment with KGF tended to decrease VCAM-1 expression in TNF- and TNF + IL-4-stimulated BEAS-2B (P = n.s. and P &lt; 0·05, 14 and 15% inhibition, respectively). In primary culture of BEC, adhesion molecule expression was also reduced. ICAM-1 and VCAM-1 mRNA expression were also inhibited by KGF. Levels of sICAM-1 and sVCAM-1 were not significantly increased in supernatants from KGF-treated cells (30% and 24% increase at 100 ng/ml, respectively) compared to controls. Moreover, KGF decreased by 31% the adherence of neutrophils to TNF-activated BEAS-2B. In conclusion, KGF decreases ICAM-1 and VCAM-1 expression and neutrophil adherence in BEC. These suggest its involvement in the resolution of the inflammatory reaction.
Augmented production of proinflammatory cytokines and accelerated allotransplantation reactions in heroin-treated mice
Authors: HOLÁŇ V , ZAJÍCOVÁ A , KRULOVÁ M , BLAHOUTOVÁ V , WILCZEK H 
Published: December 2004

SUMMARYHeroin treatment or abusive drug addiction influences many physiological functions, including the reactions of the immune system. Although suppression of various manifestations of the immune system after heroin (or morphine) administration has been reported, we show here that production of proinflammatory cytokines and nitric oxide (NO) was enhanced and allotransplantation reactions were accelerated significantly in heroin-treated recipients. Mice were treated by a subcutaneous administration of heroin (diacetylmorphine) given in one or repeated daily doses. The ability of spleen cells from treated mice to respond in vitro to alloantigens and to produce IL-2, IL-4, IL-10 and IFN-γ, and the production of IL-1β, IL-12 and NO by peritoneal macrophages, were tested. Within 2 h after heroin administration, proliferative responses to alloantigens and the production of IL-1β, IFN-γ, IL-12 and NO were enhanced significantly. In contrast, the production of anti-inflammatory cytokines IL-4 and IL-10 was at the same time rather decreased. As a consequence, skin allografts in heroin-treated mice were rejected more promptly than in untreated or vehicle-treated recipients. Similarly, the growth of allogeneic tumours induced by high doses of tumour cells was suppressed significantly in heroin-treated mice. The enhancing effects of heroin on the production of proinflammatory cytokines were antagonized by naltrexone, a specific inhibitor of classic opioid receptors. These results show that heroin treatment augments production of proinflammatory cytokines and accelerates allotransplantation reactions. The observations thus illustrate the complexity of the effects of heroin on the immune system and should be taken into account during medical treatment of opiate addicts and in the use of morphine to decrease pain in various clinical situations.
Increased circulating interleukin-12 (IL-12) p40 in pulmonary sarcoidosis
Authors: SHIGEHARA K , SHIJUBO N , OHMICHI M , KAMIGUCHI K , TAKAHASHI R , MORITA-ICHIMURA S , OHCHI T , TATSUNO T , HIRAGA Y , ABE S , SATO N 
Published: December 2004

SUMMARYIn sarcoidosis, a T helper 1 (Th1) response is an essential event and the up-regulation of interleukin-12 (IL-12) has been detected in affected disease sites. In order to investigate the clinical usefulness of circulating IL-12, we measured the serum concentrations of IL-12 by ELISA and performed immunohistochemistry using specific MoAbs for IL-12 in the lungs and scalene lymph nodes of patients with sarcoidosis. The serum concentration of IL-12 p40 was detectable in all 45 patients with pulmonary sarcoidosis and 18 normal controls, whereas that of IL-12 p70 was undetectable. The serum concentrations of IL-12 p40 in pulmonary sarcoidosis were significantly higher than those of the normal controls, especially in cases with abnormal intrathoracic findings detected by chest roentogenogram. The serum concentrations of interferon-γ (IFN-γ) also increased compared with those of normal controls and there was a significant positive correlation between the serum concentrations of IL-12 p40 and IFN-γ. Furthermore, serum angiotensin-converting enzyme (ACE) and lysozyme, which are known to be useful markers for disease activity in sarcoidosis, correlated well with the serum concentrations of IL-12 p40. The positive 67Ga scan group (for lung field) had significantly elevated serum IL-12 p40 levels compared with those of the negative group. No bioactivity of IL-12 p70 was detected in three sarcoid cases sera by using the IL-12 responsive cell line. Finally, the immunohistochemical approach revealed that IL-12 p40 was expressed in the epithelioid cells and macrophages of sarcoid lungs and lymph nodes. We concluded that the production of IL-12 p40 was far greater in the sera and we have demonstrated this to be a useful clinical marker for disease activity and the Th1 response in pulmonary sarcoidosis.
Role of incidental and/or cured intestinal parasitic infections on profile of CD4+ and CD8+ T cell subsets and activation status in HIV-1 infected and uninfected adult Ethiopians
Authors: KASSU A , TSEGAYE A , WOLDAY D , PETROS B , AKLILU M , SANDERS E J , FONTANET A L , VAN BAARLE D , HAMANN D , DE WIT T F RINKE 
Published: December 2004

SUMMARYIntestinal parasitic infections have been suggested to cause persistent immune activation leading to an unbalanced immune state. Such a state has been proposed to be a major factor in the pathogenesis of AIDS in an African context. The present study investigated the effect of incidental parasitic infection and treatment on the profile of T cell differentiation and activation markers on CD4+ and CD8+ T cells from HIV-1 infected and uninfected adult Ethiopians. Cryopreserved PBMCs from 64 subjects (41 HIV-negative and 23 HIV-positive) with follow-up visits at 6-monthly intervals were used to compare the effect of incidental intestinal parasites and their treatment upon T cell subset profiles and activation status. The samples were stained with antibodies to various T cell differentiation and activation markers allowing naive, memory, effector, memory/effector, activated and resting CD4+ and CD8+ T cell subsets to be quantified by triple-colour FACScan. Incidental intestinal parasitic infections resulted in a significant increase in memory CD4+ T cell numbers both in HIV-negative and HIV-positive subjects (P &lt; 0·05). There was also a significant increase in the percentage of CD8+ HLA-DR+ T cells (P &lt; 0·05) in HIV-positive subjects co-infected with parasites. In HIV-negative subjects, a significant decline in activated cells and a significant increase in resting CD8+ T cells (P &lt; 0·05) was observed after treatment for parasites. These data suggest that intestinal parasitic infections could result in the alteration of T cell subset counts and also in the up-regulation of T cell activation markers inperipheral blood. Treatment of parasitic infections showed a tendency to reduce the activation suggesting that, together with other community based intervention strategies, such treatment could be used to down-regulate immune activation and hence protect the host from being easily attacked by HIV.
CpG ODN enhances uptake of bacteria by mouse macrophages
Authors: UTAISINCHAROEN P , KESPICHAYAWATTANA W , ANUNTAGOOL N , CHAISURIYA P , PICHYANGKUL S , KRIEG A M , SIRISINHA S 
Published: December 2004

SUMMARYUnmethylated CpG motif in synthetic oligodeoxynucleotide (CpG ODN) or bacterial DNA is well recognized for its role in innate immunity, including enhancing production of NO and cytokines by macrophages. In the present study, we demonstrated the effect of CpG ODN on the phagocytic uptake of bacteria by macrophages. Flow cytometric analysis of mouse macrophages (RAW 264·7) incubated with fluorescein isothiocyanate (FITC)-labelled Burkholderia pseudomallei, Salmonella enterica serovar Typhi or Escherichia coli showed that CpG ODN increased the uptake of these bacteria by mouse macrophages. The enhancement of bacterial uptake by CpG ODN was concentration-dependent. The increase of bacterial uptake by CpG ODN-activated macrophages shown above is consistent with the result of bacteria internalization study using a standard antibiotic protection assay. There was also an increase in the rate and degree of multi-nucleated giant cell formation, phenomena which have been shown previously to be unique when the cells were infected with B. pseudomallei. These observations may provide significant insights for future investigation into host cell–pathogen interaction.
Glomerular deposition of C1q and anti-C1q antibodies in mice following injection of antimouse C1q antibodies
Authors: TROUW L A , SEELEN M A , DUIJS J M G J , BENEDIKTSSON H , VAN KOOTEN C , DAHA M R 
Published: December 2004

SUMMARY
Anti-C1q autoantibodies are present in the serum of patients with different autoimmune diseases such as systemic lupus erythematosus (SLE). The occurrence of these autoantibodies correlates with renal involvement. In the present study we examined whether injection of rabbit antimouse C1q antibodies in mice leads to deposition in kidneys. Injection of healthy mice with a single dose of rabbit IgG antimouse C1q antibodies resulted in deposition of both C1q and IgG anti-C1q in glomeruli. The pattern of deposition observed in the glomeruli of mice injected with antimouse C1q antibodies both at 24 h and 2 weeks was both glomerular basement membrane (GBM)-associated and mesangial. Injection of control IgG did not have a detectable effect on circulating C1q levels, and no deposition of either C1q or rabbit IgG was seen at 24 h. The deposition of rabbit antimouse C1q and C1q in glomeruli resulted in complement activation, as assessed by C3 deposition, and influx of leucocytes associated with albuminuria in some, but not all mice. In none of the control mice was albuminuria observed. This report is the first to show that anti-C1q antibodies deposit in the healthy glomerulus together with autologous C1q. This deposition is stable for at least 2 weeks, causes complement activation, leucocyte influx and can lead to mild albuminuria.
Anti-cytokine autoantibodies in autoimmunity: preponderance of neutralizing autoantibodies against interferon-alpha, interferon-omega and interleukin-12 in patients with thymoma and/or myasthenia gravis
Authors: MEAGER A , WADHWA M , DILGER P , BIRD C , THORPE R , NEWSOM-DAVIS J , WILLCOX N 
Published: December 2004

SUMMARYWe have screened for spontaneous anticytokine autoantibodies in patients with infections, neoplasms and autoimmune diseases, because of their increasingly reported co-occurrence. We tested for both binding and neutralizing autoantibodies to a range of human cytokines, including interleukin-1alpha (IL-1α), IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-18, interferon-alpha2 (IFN-α2), IFN-ω, IFN-β, IFN-γ, tumour necrosis factor alpha (TNF-α), transforming growth factor beta-1 (TGF-β1) and granulocyte-macrophage colony stimulating factor (GM-CSF), in plasmas or sera. With two notable exceptions described below, we found only occasional, mostly low-titre, non-neutralizing antibodies, mainly to GM-CSF; also to IL-10 in pemphigoid. Strikingly, however, high-titre, mainly IgG, autoantibodies to IFN-α2, IFN-ω and IL-12 were common at diagnosis in patients with late-onset myasthenia gravis (LOMG+), thymoma (T) but no MG (TMG–) and especially with both thymoma and MG together (TMG+). The antibodies recognized other closely related type I IFN-α subtypes, but rarely the distantly related type I IFN-β, and never (detectably) the unrelated type II IFN-γ. Antibodies to IL-12 showed a similar distribution to those against IFN-α2, although prevalences were slightly lower; correlations between individual titres against each were so modest that they appear to be entirely different specificities. Neither showed any obvious correlations with clinical parameters including thymoma histology and HLA type, but they did increase sharply if the tumours recurred. These antibodies neutralized their respective cytokine in bioassays in vitro; although they persisted for years severe infections were surprisingly uncommon, despite the immunosuppressive therapy also used in most cases. These findings must hold valuable clues to autoimmunizing mechanisms in paraneoplastic autoimmunity.
Altered CD8+ T cell responses to selected Epstein–Barr virus immunodominant epitopes in patients with multiple sclerosis
Authors: HÖLLSBERG P , HANSEN H J , HAAHR S 
Published: December 2004

SUMMARYAn increased frequency of antiviral CD8+ T cells is seen in chronic viral infections. During herpes virus infections the expanded CD8+ T cells are thought to control the reactivation of the latent infection. Because multiple sclerosis (MS), a presumed autoimmune disease of the central nervous system, has been associated with a late Epstein–Barr virus (EBV) infection, we wished to examine whether the CD8+ T cell response to EBV epitopes differed between MS patients and healthy controls. Here we report an increased frequency of CD8+ T cells responding to EBV epitopes from nuclear antigen 3 A (HLA-A2/CLG) and latent membrane protein 2 (HLA-B7/RPP) in MS patients. Noticeably, the altered CD8+ T cell response occurred to some but not all EBV epitopes and did not reach the high level seen during acute infection. The responses towards two immunodominant epitopes from human cytomegalovirus (HCMV) were similar in MS patients and normal controls. Together, our data demonstrate the presence of an increased frequency of CD8+ T cells reacting with two epitopes from EBV in patients with MS. The altered response to only two of the tested EBV epitopes would be consistent with the presence of cross-reactive epitopes.