The effects of IgM-enriched immunoglobulin preparations in patients with severe sepsis [ISRCTN28863830]

INTRODUCTION: In this prospective, randomized controlled study, we aimed to evaluate the effect of IgM-enriched immunoglobulin treatment on progression of organ failure and septic shock in patients with severe sepsis. MATERIALS AND METHODS: Forty-two patients with severe sepsis were enrolled in the study. Patients in the study group (n = 21) received an intravenous immunoglobulin preparation (Pentaglobin(®)) in addition to standard therapy. Pentaglobin(®) therapy was commenced on the day of diagnosis of severe sepsis: 5 ml/kg per day Pentaglobin(®) (38 g/l IgG, 6 g/l IgM, and 6 g/l IgA) was infused over 6 hours and repeated for 3 consecutive days. Patients in the control group (n = 18) received standard sepsis therapy, but no immunoglobulin administration. Blood samples for procalcitonin (PCT) measurements were taken daily for 8 days. Severity of critical illness and development of organ failure were assessed by obtaining daily acute physiological and chronic health evaluation (APACHE) II and sequential organ failure assessment (SOFA) scores. RESULTS AND DISCUSSION: Procalcitonin levels showed a statistically significant decrease in the Pentaglobin(®) group (P < 0.001); however, an improvement in SOFA scores could not be demonstrated. Procalcitonin levels and SOFA scores did not change significantly in the control group. Septic shock incidence (38% versus 57%) and 28-day mortality rate (23.8% versus 33.3%) were found to be similar between the Pentaglobin(®) and control groups. The evaluation of serial APACHE II scores did not demonstrate a difference between Pentaglobin(®) and control groups either. CONCLUSION: Present data could not demonstrate any beneficial effects of polyclonal immunoglobulin preparation Pentaglobin(®) on organ morbidity, septic shock incidence and mortality rate in patients with severe sepsis

Undetected HLA-A,B Antigens By Serological Method And Application Of Molecular Methods

Since human leucocyte compatibility has a crucial effect in renal transplantations and there is the need for full-match HLA compatibility between the donor and the recipient for successful bone marrow transplantations. It is clearly evident that HLA system plays a major role in kidney and hone marrow transplantations. Hence, accurate and reliable identification of these antigens is very important. We perform CDC assay for the typing of HLA-A,-B in our EFT accredited laboratories. In case of homozygosity or detection of an ambigious antigen, molecular methods are performed in addition to CDC. The purpose of our study was to demonstrate the comparative results of two methods concerning the cases in which molecular typing was needed in addition to CDC and to list the antigens that could not he identified by CDC hut molecular typing. The study group included 1567 individuals consisting of patients with chronic renal deficiencies (n=646), hematological malignancies (n=646) and their donors (n=275). Samples were typed by CDC and PCR-SSP/SSO methods for HLA-A,-B. The study group was divided into 5 groups as cases with single HLA-A and/or-B and with ambigious HLA-A and/or-B. By molecular methods, 2138 tests were performed. The concordance between CDC assay and molecular methods was 8.8% for HLA-A and 14.2% for HLA-B. The most frequent antigens which could not be identified by CDC but molecular methods were HLA-A32, B15 (7.3, 15.8 %). We believe that performing molecular tissue typing methods at least particularly to patient samples will increase the transplantation success

Characterization of Minor HA-1 in Patients Who Underwent Living Donor Kidney Transplantation

Objectives: The importance of the Human Leukocyte Antigens (HLA) matching is well known in renal transplantation that is one of the best treatment options for end-stage solid organ deficiency. Human Leukocyte Antigens matching between recipient and donor has an influence on graft survey after the renal transplantation. However allogeneic renal transplants between HLA identical siblings might be ended with rejection. Minor histocompatibility antigen (mHag) HA-1 is a nine-amino acid peptide encoded by a diallelic gene on human chromosome 19. mHags have low polymorphisms. Minor histocompatibility antigens are likely to function as potantial risks for graft rejection of HLA-matched solid organ transplantation. In our study, we aimed to investigate the effect of minor HA-1 mismatch on kidney transplant survey

Role of procalcitonin, C-reactive protein, interleukin-6, interleukin-8 and tumor-necrosis factor-alpha in the diagnosis of neonatal sepsis

WOS: 000245874800002PubMed ID: 17479639Diagnosis of neonatal sepsis may be difficult because clinical presentations are often nonspecific, bacterial cultures are time-consuming and other laboratory tests lack sensitivity and specificity. In this study, we aimed to investigate the role of procalcitonin (PCT), C-reactive protein (CRP), interleukin (IL)-6, IL-8 and tumor necrosis factor-alpha (TNF-alpha) in establishing the diagnosis and evaluating the prognosis of neonatal sepsis. Twenty-six neonates with blood-culture positivity and clinical sepsis, hospitalized for clinical suspicion of neonatal sepsis in neonatal intensive care units of Balcali Hospital, Cukurova University and Adana State Hospital between May 2000 and January 2001 (Group I) and 29 healthy neonates followed at the neonatal units and outpatient clinics of these hospitals (Group II) in the same period were studied. Among the septic neonates, 13 had early-onset (Group Ia) and 13 had late-onset (Group Ib) neonatal sepsis, while 14 of the healthy neonates had perinatal risk factors (Group IIa) and 15 of them had no risk factors (Group IIb). The demographic and clinical characteristics of the septic and healthy neonates were recorded, blood samples for determining serum PCT, CRP, IL-6, IL-8 and TNF-alpha were collected from the healthy and the septic neonates before starting treatment, and these investigations were repeated on the 3(rd) and 7(th) days of treatment. In this study, it was found that: (a) pre-treatment mean serum PCT, CRP, IL-6, IL-8 and TNF-alpha levels were significantly higher in the septic neonates than in the healthy ones, (b) compared with the pre-treatment values, serum PCT, IL-6 and TNF-alpha had progressively decreased on the 3rd and 7th days of the treatment in the 17 recovered patients, though they progressively increased in nine patients who died during treatment, (c) the area under the receiver operating characteristic (ROC) curve (AUC) for PCT, TNF-alpha, IL-6, CRP, and IL-8 were 1.00, 1.00, 0.97, 0.90 and 0.68, respectively. For the cut-off value of PCT >= 0.34 ng/ml, the test was found to have a sensitivity of 100%, specificity of 96.5%, positive predictive value of 96.2%, negative predictive value of 100% and diagnostic efficacy of 98.3% for bacterial sepsis in neonates. For the cut-off value of TNF-alpha >= 7.5 pg/ml, sensitivity, specificity, positive predictive value, negative predictive value and diagnostic efficacy were found to be 100%, 96.6%, 96.2%, 96.5% and 98.3%, respectively. it was detected that sensitivity, specificity and diagnostic efficacy values were lower for IL-6, CRP and IL-8. We conclude that PCT and TNF-alpha are the best markers in the diagnosis of neonatal sepsis, and these markers are also valuable in following the effectiveness of treatment and determining the prognosis of the disease

Country data on AMR in Turkiye in the context of community-acquired respiratory tract infections: links between antibiotic susceptibility, local and international antibiotic prescribing guidelines, access to medicine and clinical outcome

Background: Antimicrobial resistance (AMR) is one of the biggest threats to global public health. Selection of resistant bacteria is driven by inappropriate use of antibiotics, amongst other factors. COVID-19 may have exacerbated AMR due to unnecessary antibiotic prescribing. Country-level knowledge is needed to understand options for action

The Relationship Between Minor Histocompatibility Antigens And Graft-Versus-Host Disease After The Allogeneic Hematopoietic Stern Cell Transplantation

The major complication of hematopoetic stem cell transplantation (HSCT) is graft-versus-host disease (GVHD) or graft. HLA incompatibility increases the frequency of GVHD. On the other hand, the risk is still available despite full matched HLAs, which may he related with non-HLAs or minor antigens. One of these minor antigens, HA-1 alelic incompatibility has been shown to be associated with GVHD in HLA-identical sibling transplants. The HA-1 is an HLA-A*0201 restricted non-peptide, winch derives from the cleavage of a protein encoded at clu-omosome 19. There are two :tidies of HA-1 created by a polymorphism at position 504 that results in either Histidine (HA-1.H) or Arginine (HA-1R). The aim a of the study is investigate the relationship between HA-1 and GVHD. We retrospectively examined the HA-1 locus in patients diaDiosed and treated between 1998-2004. We used PLR-SSP for typing HA-1. Forty samples from 20 HLA-A2 positive.HSCT ((BMT, n=3; PBSCT, n=17) recipients and their donors were included in our study. The frequencies of the three possible genotypes RR, RH, HH were 35%, 45% and 20%, respectively, in recipients and 35%, 65% and 0% in donors. Four of the 20 patients (20%) were determined as having evre II or III GVHD. There is HA-1H incompatibility between donor and recipient only in two patients with GVHD. mHAgs were found to be incompatible in 8 out of 20 recipient/donor pairs

Association of HLA-DRB1 Alleles and Autoimmune Hepatitis in Turkish Patients

Objectives: Autoimmune hepatitis (AIH) which is characterized by hypergammaglobulinemia and a wide range of circulating auto antibodies is a necro-inflammatory liver disease of unknown aetiology. Immunogenetic studies have shown the association of autoimmunity with HLA (Human Leukocyte Antigen) alleles. Furthermore, they have shown a decrease in the expression of HLA antigens on lymphocyte surface and a dysregulation of gene expression arranged by HLA. A significant association is found between AIH and HLA-DRB1(star)03, (star)04 and (star)13 alleles in various studies. We performed HLA-DRB1 genotyping in Turkish patients with AIH

IL-10 and TNF-alpha Gene Polymorphisms in Patients with Celiac Disease

Celiac disease (CD) is an autoimmune disorder characterized by intolerance to ingested gluten. HLA-DQ genes are strongly associated with susceptibility to CD. Non-HLA genes are effective in CD pathogenesis as well as HLA genes. TNF-alpha has a single nucleotidepolymorphism (SNP) at position -308 in promoter region, which has been shown to have association with CD in previous studies. The aim of this study is to investigate the association of TNF-alpha and IL-10 cytokine gene polymorphisms with CD and with DQB1*02 status in patients with celiac disease. Thirty three patients and 93 healthy individuals were included in the present study. GG and AA genotypes in position -308 of TNF-alpha gene had a significantly increased frequency in the patient group and in patients with DQB1*02 when compared to the controls. No significant differences could be established for IL-10 gene polymorphisms within the patients and controls. As a result of all these findings, it might be suggested that there is no significant association of IL-10 gene polymorphism with CD and data on TNF-alpha gene polymorphisms are not sufficient enough to clarify the disease pathogenesis thus indicating roles for other genes within or out of MHC gene region

Impact of HLA on the Underlying Primary Diseases in Turkish Patients with End-Stage Renal Disease

The number of patients with end stage renal disease (ESRD) is increasing faster than the number of renal transplantations performed per year worldwide. Of the primary diseases leading to ESRD, diabetic nephropathy is the leading cause. The purpose of the present study is to investigate the association of HLA with the primary diseases leading to ESRD in Turkish patients. A total of 3230 individuals comprising 587 ESRD patients and 2643 healthy controls were enrolled into the study. Class I HLA-A, -B typing was performed by CDC method, while class II HLA-DRB1 typing was performed by low resolution PCR-SSP. We found a significant negative association between almost all A locus antigens and primary disease groups classified as chronic glomerulonephritis and hypertensive nephrosclerosis (p 0.05). HLA-B58 and HLA-DRB1*03 significantly correlated with amyloidosis and diabetic nephropathy, respectively. Determination of HLAs as risk factors for primary diseases leading to ESRD might be beneficial in preventing progression to ESRD and recurrence of the primary disease post-transplantation