Efficacy and quality of life assessment in the use of subcutaneous immunoglobulin treatment for children with primary immunodeficiency disorder.

Summary: Introduction. Most patients with primary and secondary immunodeficiencies need regular Intravenous Immunoglobulin (IVIG) or Subcutaneous Immunoglobulin (SCIG) treatment. This study aimed to evaluate the serum IgG trough levels, frequency of mild and severe infections, frequency and duration of hospitalization, duration of absence of school, and quality of life in patients switching their IVIG therapy to SCIG administration. Materials. Twenty-nine patients with immunodeficiency on regular IVIG treatment and who agreed to receive SCIG treatment were included. Seven patients discontinued treatment after the first SCIG administration. We collected data regarding serum IgG levels, annual numbers of infections, hospital admissions, and adverse events prior to and following SCIG initiation. PedsQL tests such as Scale Total Score (STS), Physical Health Total Score (PHTS), Psychosocial Health Total Score (PsyHTS), emotional functionality, social functionality, school/work problems score were calculated separately for all patients and their parents. Results. In twenty-two cases who were diagnosed as primary immunodeficiency, the most common indication for initiation of SCIG treatment was the long transfusion period of IVIG treatments and the difficulty of access to the hospital. No systemic side effects were noted except local redness, pain, and swelling on the injection site. The median IgG value was 588.9 mg/dl during IVIG treatment and 872 mg/dl one year after SCIG treatment. Annual frequency of infections and absence to school/work decreased significantly in the SCIG group while the annual number of hospitalizations and hospital stay time did not change significantly. There was a significant increase in the "quality of life" scores of the patients and their families. Conclusions. SCIG treatment provides ideal and protective immunoglobulin levels and offers the comfort of treatment in their home environment, thus increasing the patient's satisfaction and quality of life.

The role of oxidative stress in premalignant lesions.

PURPOSE OF INVESTIGATION: The authors aimed to evaluate serum total oxidant status (TOS), total antioxidant status (TAS), and oxida- tive stress index (OSI) in women with abnormal cervical cytology, to determine the association between serum oxidant and antioxidant status of these women, and the progression of abnormal cervical cytology. MATERIALS AND METHODS: A total of 75 women enrolled in the study: 20 women with a determination of atypical squamous cells of undetermined significance (ASCUS), 20 women with low squamous intraepithelial lesions (LSIL), 15 women with high squamous intraepithelial lesions (HSIL) and 20 healthy controls. Serum TOS and TAS were determined and OSI was calculated as the indicator of degree of oxidative stress. RESULTS: Serum TOS levels and OSI were highest in the HSIL group and there was a trend toward increasing serum TOS levels and OSI from ASCUS to HSIL group. CONCLUSION: The authors demonstrated that increased oxidative stress with altered antioxidant level is associated with abnormal cervical cytology. Serum oxidant and antioxidant status may provide guidance as a simple and cost-effective method for follow-up, treatment, and recommendation in all stages of lesions.

Does tamoxifen citrate prevent pulmonary fibrosis due to silica inhalation?

BACKGROUND: As shown in several studies, besides being used in breast cancer, tamoxifen is also known for its antifibrotic effects via reducing the serum TGF-beta levels. We investigated the possible preventive effect of tamoxifen in rats exposed to silica particles depending on the antifibrotic effect. MATERIALS AND METHODS: A total of 102 adult female Wistar Albino rats were divided into five groups. First two groups (control and tmx) were free of silica and the last three groups (slc, tmx1 and tmx 10) were exposed to crystalline silica. The rats in tmx, tmx1 and tmx10 groups received 10 mg/kg, 1 mg/kg and 10 mg/kg of body weight tamoxifen, respectively. On day 84, all rats were sacrified and tissue samples were obtained together with blood samples. The differences in serum TGF-ß levels, histological grades of fibrosis and inflammation in the lung and liver tissues together with addional biochemical markers were calculated between the groups. RESULTS: Silicosis occurred in slc, tmx1 and tmx10 groups in 100%, 91.7% and 52.1%, respectively. Liver fibrosis did not occur. The highest mean lung fibrosis scores were obtained in slc group while the scores were lower in tmx1 group and the lowest in tmx10 within silica-exposed rats. Nevertheless, the inflammation scores were higher in tamoxifen-administered rats in a dose-dependent pattern. CONCLUSION: Silica inhalation did not result in liver fibrosis. Tamoxifen is found to prevent lung fibrosis and reduce serum TGFß-1 levels while increasing lung inflammation (Tab. 3, Fig. 3, Ref. 27).

Anesthetic Management for Left Ventricular Assist Device Implantation Without Using Cardiopulmonary Bypass: Case Series.

PURPOSE: Ventricular assist devices are an alternative to medical treatment in patients with hemodynamic disturbances related to acute or chronic congestive heart failure. In this case series, we present our anesthesia management for implantation of left ventricular assist device (LVAD) with thoracotomy. METHOD: Sixteen patients with end-stage heart failure undergoing LVAD implantation via thoracotomy between November 2012 and August 2014 were analyzed prospectively. Preoperative characteristics, intraoperative hemodynamic and respiratory parameters, use of anesthetic and blood products, and durations of mechanical ventilation, hospital, and intensive care stays were recorded. RESULTS: Sixteen patients (mean age, 54.6 ± 13 years) were investigated. Single-lung ventilation was applied to 2 patients. Cardiopulmonary bypass (CPB) was required in 5 patients. Intraoperative ketamine, midazolam, fentanyl, and rocuronium requirements were 112 ± 63 mg, 5.5 ± 3.5 mg, 438 ± 187 µg, and 179 ± 49 mg, respectively. Requirements of fresh donor blood, fresh frozen plasma, and thrombocyte and erythrocyte suspension were 1.19 ± 1, 1 ± 0.8, 0.44 ± 0.5, and 0.25 ± 0.7 U, respectively. Durations of mechanical ventilation, intensive care unit, and hospital stay were 46 ± 53 hours, 8.2 ± 6.6 days, and 20.5 ± 11.6 days, respectively. Twelve patients were discharged from hospital with full recovery and 2 patients died; 2 patients are still receiving treatment in the hospital. CONCLUSION: A left thoracotomy approach can be used without CPB, because it reduces the incidences of pump complications and blood transfusion. In addition, this case series showed that the implantation of LVAD by thoracotomy can be implemented securely with single-lumen endotracheal tube without single-lung ventilation.

Do elevated serum IgM levels have to be included in probable diagnosis criteria of patients with ataxia-telangiectasia?

Ataxia-telangiectasia (AT) is a rare multisystem, neurodegenerative genetic disorder that is characterised by progressive neurological abnormalities, oculocutaneous telangiectasias and immunodeficiency. Delay in diagnosis or misdiagnosis is probable due to its wide clinical heterogeneity in infancy. Recurrent sinopulmonary infections are often the only presenting symptom and usually patients have decreased immunoglobulins. A total 10% of patients who present with decreased serum immunoglobulin G and A and with normal or elevated immunoglobulin M levels are often misdiagnosed as hyperimmunoglobulin M syndrome. Definitive diagnosis is made if a patient with progressive cerebellar ataxia has a disease causing mutation on the ATM gene. Ataxia-telangiectasia guideline of the European Society for Immunodeficiencies defines the probable diagnosis criteria. We evaluated twenty ataxia-telangiectasia patients (mean age 13.8±4.1 years) retrospectively who were followed-up for a mean of 38.6±27.0 months. Twelve patients had a family history of consanguinity. A total of 80% patients suffered from various infections. Neoplasms occurred in three of them. Patients showed immunological abnormalities as low IgG (45%), low IgA (65%) and elevated IgM (60%) levels. CD3+CD4+ T lymphocyte frequency was low in 45% patients. The mean AFP concentration at the diagnosis was 191.9±140.1 ng/mL and the raised IgM values did not show any statistically significant relationship with high AFP concentrations. Frequency of the elevated IgM concentrations in (60%) patients raises the concerns about thinking this finding has to be accepted as a probable diagnosis criterium.

TLR2 and TLR4 gene polymorphisms in Turkish vitiligo patients.

BACKGROUND: It has been shown that toll like receptors (TLR) may be involved in some inflammatory skin diseases such as psoriasis, atopic dermatitis. Vitiligo is an acquired pigmentation disorder of unknown aetiology. A number of genes playing a role in inflammatory response may be associated with development of vitiligo. OBJECTIVES: To investigate whether there is an association between TLR 2 and TLR4 gene polymorphisms in Turkish patients with vitiligo. METHODS: A total of 100 patients (59 women and 41 men) with vitiligo and 100 controls (58 women and 42 men) were included in the study. The TLR2 gene Arg753Gln and TLR4 gene Asp299Gly and Thr399Ile polymorphisms were genotyped by using polymerase chain reaction and restriction fragment length polymorphism method. The data were analysed by Mann-Whitney U-test, chi-squared test and logistic regression analysis. RESULTS: Significant difference was found in the distribution of TLR2 Arg753Gln genotype and in the allele frequencies TLR2 753Gln between vitiligo patients and healthy subjects (P < 0.05). The distribution of TLR4 Asp299Gly genotype was significantly higher in the patient group (10%) than in the control group (%2) (P < 0.05). The TLR4 Thr399Ile distribution did not show any difference in both vitiligo and healthy groups. CONCLUSIONS: Our findings suggest that Toll-like receptor 2 gene Arg753Gln and Toll-like receptor 4 Asp299Gly gene polymorphisms are associated with vitiligo susceptibility in Turkish patients.

IgG-anti-IgA antibodies: an autoimmune finding in patients with psoriasis vulgaris.

AIM: Psoriasis is thought to be an autoimmune disease caused by inappropriate activation of the cellular immune system. In this study, we aimed to search out IgG-anti-IgA antibody levels, serum immunoglobulins and antinuclear antibodies (ANA). METHODS: The study enrolled 38 psoriasis vulgaris patients and 40 healthy controls. RESULTS: Mean IgG-anti-IgA levels were significantly higher in psoriasis patients. The frequency of positive ANA testing was 21.1%; however, there was no correlation between IgG-anti-IgA antibody levels and ANA positivity. Only one patient had low IgA levels without high IgG-anti-IgA concentrations. CONCLUSION: The data about high IgG-anti-IgA antibody levels are noteworthy for a new evidence of autoimmune mechanism.

Hyper-immunoglobulin M syndrome type 3 with normal CD40 cell surface expression.

Mutations of the CD40 gene have been found in patients with autosomal recessive hyper-immunoglobulin M (HIGM) syndrome type 3. Five patients from four unrelated families with CD40 mutation have been reported so far. Clinical manifestations include recurrent sinopulmonary infections, Pneumocystis carinii pneumonia and Cryptosporidium parvum infection. Affected patients typically have very low levels of IgG and IgA and normal or high levels of IgM. Flow cytometry analysis of these five patients demonstrated that peripheral blood B lymphocytes lacked expression of surface CD40. Herein, we present two siblings from second-degree consanguineous Turkish parents with homozygous CD40 deletion of four nucleotides including the stop codon resulting presumably to a longer protein. Clinical and immunological profile of these patients is similar to the already reported HIGM3 patients except normal CD40 expression on B lymphocytes. This observation emphasizes the requirement of CD40 mutation analysis for definite diagnosis of HIGM3 despite normal flow cytometric expression of CD40, particularly if the immunological and clinical profile is suggestive for HIGM3.

Determination of cut-off titers and agreement between immunofluorescence and immunoblotting methods for detecting antinuclear antibodies in children.

Detection of antinuclear antibodies (ANA) is a diagnostic adjunct in patients with suspected autoimmune connective tissue diseases, and various detection methods are in use. The aim of this study was to analyze the agreement between the ANA immunoflourescence (IF) and immunoblotting (IB) methods and determine cut-off for children subjects in a laboratory setting. We evaluated 729 serum samples that were analyzed by both ANA IF and IB. The results were evaluated by chi(2) test and, for agreement, kappa index was used. Frequencies determined for both 1:40-1:100 cut-off titers of ANA IF in relation to IB testing supported the idea that 1:100 starting dilution should be recommended in children subjects for ANA IF method and antigen specific immunoblot testing was needed, especially for some of the ANA IF negative samples. Agreement between the two methods, especially with homogenous, granular, and nucleolar ANA IF patterns, was statistically significant.

A novel Y331X nonsense mutation in TNFRSF1A gene in two unrelated Turkish families with periodic fever syndrome.

The autoinflammatory disorders differ in severity, as well as age of onset, duration, and manifestations, but they all share some common features: recurring fever peaks, inflammation of serosal membranes, musculoskeletal involvement, varying types of skin rash, amyloidosis as a sequel of the disease. TRAPS is very rare in Turkish population and we present two unrelated Turkish children with similar clinical phenotypes and laboratory findings related with autoinflammatory disorders and with novel p. Y331X mutation in TNFRSF1A gene. Both of the patients were male and they had recurrent fever without abdominal pain and arthralgia. Full cDNA and exon-intron binding regions of TNFRSF1A, MEFV, MVK, CIAS1 genes were analysed by direct DNA sequencing methods in order to differentiate TRAPS, FMF, HIDS, CINCA/MWS/FCAS respectively. We screened ten exons of TNFRSF1A gene, and detected a heterozygous c.1080C>G nucleotide substitution in exon 10 in both of the unrelated patients, resulting p.Y360X nonsense (protein truncated) mutation. According to classical TNFRSF1A gene nomenclature and the agreement of 30th amino acid as the first one, it is accepted as p.Y331X. It was interesting to determine same mutations in fathers of two patients. In one of the cases, E148Q heterozygous mutation, which is one of the disease-causing mutations of MEFV gene, was detected. No nucleotide substitution was identified in exon and exon-intron splicing regions encoding 396 amino acid of MVK gene in both of the patients. In CIAS1 gene, two different nucleotide substitutions resulting synonymous amino acid mutation were detected in exon 3: c.[732G>A] and c.[786A>G] nucleotide substitutions and compatible p.A242A (according to c.DNA p.A244A) and p.R260R (according to c.DNA p.R262R) synonymous amino acid mutations. These nucleotide substitutions were also detected in parents and were reported to be normal variations in Turkish population. In conclusion, in Turkish patients, with dominantly inherited recurrent fever, TRAPS is a diagnosis worthy of attention and novel mutations have to be reported with phenotype associations.

Preparation and application of poly(N,N-dimethylacrylamide-co-acrylamide) and poly(N-isopropylacrylamide-co-acrylamide)/kappa-Carrageenan hydrogels for immobilization of lipase.

In the present of this study, two novel polymeric matrixes that are poly(N,N-dimethylacrylamide-co-acrylamide) and poly(N-isopropylacrylamide-co-acrylamide)/kappa-Carrageenan was synthesized and applied for immobilization of lipase. For the immobilization of enzyme, two different immobilization procedures have been carried out via covalently binding and entrapment methods. On the free and immobilized enzymes activities, optimum pH, temperature, storage and thermal stability was investigated. The optimum temperature for free, covalently immobilized and entrapped enzymes was found to be 30, 35 and 30 degrees C, respectively. Optimum pH for both free and immobilized enzymes was also observed at pH 8. Maximum reaction rate (Vmax) and Michaelis-Menten constant (Km) were determined for free and immobilized lipases. Furthermore, the reuse numbers of immobilized enzymes also studied. It was observed that after 40th use in 5 days, the retained activities for covalently immobilized and entrapped lipases were found as 39% and 22%, respectively. Storage and thermal stability of enzyme was also increased by as a result of immobilization procedures.

Fatal peritonitis due to Trichoderma sp. in a patient undergoing continuous ambulatory peritoneal dialysis.

We describe a rare case of peritonitis caused by an unusual fungus, Trichoderma sp., in a patient on continuous ambulatory peritoneal dialysis. Management of the patient consisted of Tenckhoff catheter removal and antifungal chemotherapy, but the patient died.