CD39 expression on immune cells predicts methotrexate response in rheumatoid arthritis patients.

Background/aim: Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting mostly small joints, such as hand and foot joints symmetrically with irreversible joint destruction. In this study, the relationship between CD39 expression and the treatment response of RA patients was examined to investigate its potential as a biomarker that demonstrates treatment response. Materials and methods: This study included 77 RA patients and 40 healthy controls (HC). The RA patients were divided into 2 groups based on their response to RA treatment, those with a good response to methotrexate (MTX) monotherapy and those with an inadequate response based on the American College of Rheumatology and the European League Against Rheumatism response criteria. Various immunological parameters and Disease Activity Score in 28 Joints (DAS28) were examined between the groups using the Student's t-test. Results: The monocytic myeloid-derived suppressor cell (M-MDSC) percentage was higher in the RA patient group versus the HC group. The CD39 expression in the T lymphocytes were higher in patients that responded well to the MTX compared to those showing inadequate response. Additionally, s negative correlation was found between the DAS28 and CD39 in the T cells. Conclusion: The results showed that the improvement in treatment response to the therapy in RA patients could be because of the enhancement in the CD39/adenosine (ADO) pathway. Therefore, therapies targeting the CD39/ADO pathway in T cells may improve RA treatments.

[Humoral Immune Response in Inactivated SARS-CoV-2 Vaccine: When Should a Booster Dose be Administered?] / Inaktif SARS-CoV-2 Asisi Humoral Immün Yanit: Rapel Doz Ne Zaman Uygulanmalidir?

Vaccination induces the development of long-lasting immunity necessary for a sustained and essential protective antibody response. Understanding how long the humoral immune response induced by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) inactivated vaccine lasts is important to create an effective immunization scheme. This study aimed to detect the first, third, sixth month concentrations and seroconversion rates of the antibodies induced by the inactivated vaccine. The study included 282 healthcare workers who were vaccinated at days 0 and 28 by the inactivated SARS-CoV-2 vaccine (3 µg/0.5ml). Anti-S-RBD-IgG (receptor binding domain) antibody concentrations and seroconversion rates were examined in vaccinated healthcare workers at the first, third and sixth months after the vaccination. MAGLUMI SARS-CoV-2 S-RBD IgG (CLIA) (Snibe Diagnostics, Chinese) kit was used for the detection of antibodies. The mean age of the healthcare workers was 38.93 ± 10.59 (min= 21-max= 64). After the administration of the second vaccine dose, the participants were found to be reactive for anti-SRBD-IgG antibodies by 98.2% and 97.8% at the first and third months, respectively,. The decrease in the mean plasma concentrations of anti-S-RBD IgG was observed as 56.7% in the cohort with only two doses of the vaccine (first month: 42.4 AU/ml versus third month: 18.2 AU/ml). In the cohort with a history of coronavirus disease 2019 (COVID-19) prior to the vaccination, the decrease was observed as 25.1% (first month: 58.29 versus third month: 43.64 AU/ml) and at a mean of 57.4 (0-90) days prior to vaccination, the decrease rate was 43.1% (first month: 55.05 AU/ml versus third month: 31.28 AU/ml), keeping more stable in participants infected at a mean of 183.1 (91-330) days prior to vaccination(a decrease of 5.2%; with 62.34 AU/ml at first and 59.08 AU/ml at third months). At the end of the sixth month, antibodies could not be detected in 16.7% of people who (n= 42) received two doses of the inactivated vaccine, and the amount of anti-S-RDB IgG decreased by an average of 52.5% compared to the third month, and by 74.8% compared to the first month. Antibody concentrations at the first, third, and sixth months after the vaccination with two doses of the inactivated SARS-CoV-2 vaccine were found to be decreased and at the sixth month, the rate of non-reactive people was 16.7%. As participants who had COVID-19 at a mean of 181 (90-330) days before the vaccination presented with a more stable antibody level, it can be concluded that a booster at months 6-12, resulting in a schedule of 0-1-6 months, is recommended for the inactive SARS-CoV-2 vaccination for effective herd immunity.

SARS-COV-2 vaccine: first-month results of a six-month follow-up study.

BACKGROUND: Various COVID-19 vaccines are being developed around the world. Important questions to be answered regarding vaccines are efficacy, safety, and whether antibodies are protective when used in different communities. This study aimed to determine seroconversion rates of the inactivated SARS-CoV-2 vaccine in healthcare workers in a hospital and short-term adverse events due to the vaccine. METHODS: The study carried out in Çukurova University, Turkey, comprised of 282 healthcare workers who received two doses of the inactivated SARS-CoV-2 vaccine administered in two 3 µg doses, 28 days apart. On day 28, after the second dose, antiS-RBD IgG and total anti-spike and anti-nucleocapsid IgM and IgG antibodies against SARS-CoV-2 were detected by using in vitro chemiluminescence immunoassay method. RESULTS: The mean age of participants was 39.06±10.65 (min=21, max=65) with 43.6% males and 56.4% females. On day 28, after the second dose, the seroconversion rates were found to be 92.9% for total anti-spike and anti-nucleocapsid IgG and 15.2% for IgM and 98.2% for anti-S-RBD IgG antibodies and having natural COVID-19 prior to vaccination, age and comorbidity were found to be significant factors for immunogenicity. The incidence of at least one adverse event was found as 29.8% after the first dose and 24.1% after the second dose, with the most common adverse events of having pain at the injection site, weakness, fatigue, and headache.

Determination of the relationship between major histocompatibility complex alleles and childhood onset obsessive-compulsive disorder.

BACKGROUND: About half of the cases of obsessive-compulsive disorder (OCD) occurring in childhood/adolescence occur with similar symptoms both in childhood and adulthood. Immunologic stress is claimed to be a risk factor in the etiology of childhood onset OCD. Our aim was to elucidate the relationship between childhood onset OCD risk and MHC complex I and II alleles. METHODS: MHC alleles of 49 OCD children together with 277 healthy children (aged 4-12) were analyzed by PCR. Results were evaluated by using univariate analysis and multivariate logistic regression analysis. RESULTS: A2, A29, C4, DRB3.1, and DRB1*16 alleles were found to increase the risk of OCD. DISCUSSION: The relationship found between DRB locus and OCD in this study was remarkable since there have been studies on different populations reporting similar relationship between DRB locus and rheumatoid arthritis, which is also an AID. MHC class I and class II alleles were found to increase the risk of OCD in our study, which serves as a suitable model for studies suggesting that MHC genes do not work completely independently. Even though the MHC class I and II genes are considered to have different roles in immune response, in fact they tend to work in cooperation. As in previous studies on AIDs, there is a linear relationship between MHC class II alleles and OCD risk.

Low immunity against vaccine preventable diseases in Turkish HIV cohort

Background/aim: HIV infection increase the risk of serious disease resulting from common vaccine-preventable infections. Vaccinations are particularly important for HIV infected adults. We aimed to investigate the immunity rates against measles, mumps, rubella, hepatitis A, B, and tetanus in newly diagnosed HIV patients. Materials and methods: Patients who admitted to outpatient clinics of three centers with newly diagnosed HIV infection, between 1 January 2015 and 31 June 2017 were included. Measles, mumps, rubella, varicella zoster virus, hepatitis A, hepatitis B, and tetanus antibody levels were measured by commercial diagnostic kits. Demographical and laboratory data of the patients were recorded. Results: Five hundred and twenty-three patients were enrolled in the study. Of the patients 87% were male (n = 455) and the mean age was 38 ± 13 years. Serology was available for measles 74.2% (388/523), mumps 73.8% (386/523), rubella 77.8% (407/523), hepatitis A 88.5% (463/523), hepatitis B 97.7% (511/523), tetanus 8.6% (45/523), and VZV 79.9% (418/523). Seropositivity was 82% for measles, 75.6% for mumps, 92.1% for rubella. Of the patients whom all three of the components of the MMR vaccine was tested, 37.7% (127/337) were susceptible at least one and needed the vaccine. Mean age was lower in patients who are nonimmune to measles and mumps (p = 0.008). Younger patients were also nonimmune for hepatitis A, while older patients were nonimmune for hepatitis B. Conclusion: In our study we found that rates of nonimmunity can increase up to one third of the patients even though there is a national vaccination program. Nonimmune individuals should be detected and vaccinated in line with recent guidelines and response should be monitored because of the possibility of impaired immunity and possible suboptimal response. National campaigns can be launched for adult immunization and physicians should be aware of the importance of adult immunization.

Importance of 14-3-3eta, anti-CarP, and anti-Sa in the diagnosis of seronegative rheumatoid arthritis

Background/aim: Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation. The study aimed to assess serum 14-3-3eta, anti-CarP, and anti-Sa in seronegative RA (SNRA) patients who were treatment-naïve as well as in healthy subjects. This is the first study in the literature to examine these autoantibodies together in SNRA patients. Materials and methods: Forty-five treatment-naïve SNRA patients and 45 healthy subjects were recruited. Drugs change the levels of autoantibodies; therefore, patients who took any medication had been excluded from our study. Anti-carbamylated protein, anti-Sa, and 14-3-3eta were measured by using three different ELISA kits. Results: Median serum concentration of healthy controls in 14-3-3eta was 0.02 (0.02­0.27) ng/mL. Median serum concentration of SNRA patients in 14-3-3eta was 1.00 (0.48­1.28) ng/mL. Data were analyzed with Mann­Whitney U tests; the P-value was <0.001 in 14-3-3eta. Receiver operating characteristic (ROC) curve analysis showed that 14-3-3eta in SNR compared to healthy controls had a significant (P < 0.001) area under the curve (AUC) of 0.90 (95% confidence interval, 0.83­0.96). At a cutoff of ≥0.33 ng/mL, the ROC curve yielded a sensitivity of 88.9%, a specificity of 82.2%, a positive predictive value of 83.3%, and a negative predictive value of 88.1%. Conclusion: We found that 14-3-3eta can be used as a diagnostic marker in SNRA.

Frequency of Celiac Disease in Children with Peptic Ulcers.

AIM: The aim of the present study is to investigate the frequency of celiac disease in children with peptic ulcers and to compare it with that of non-celiac peptic ulcers in terms of clinical and laboratory values. METHODS: Upper gastrointestinal endoscopy was performed in 1769 patients at the Department of Pediatric Gastroenterology, The Faculty of Medicine, Cukurova University, Turkey, between January 2012 and January 2017. These cases consisted of subjects presenting with various GIS symptoms and indicated for endoscopy (with chronic diarrhea, delayed growth and development, abdominal pains, GIS bleeding, etc.). The levels of immunoglobulin A (IgA) serum anti-tissue transglutaminase antibodies, IgA anti-endomysial antibodies (EMA), and IgA serum were estimated in the patients with peptic ulcers. RESULTS: Celiac disease was diagnosed with serology, endoscopy, and histopathology in 250 (14%) of all cases undergoing endoscopy. Peptic ulcers were diagnosed in 74 patients (4.2%) of all cases undergoing endoscopy. tTGA and EMA (+) levels were determined in 22 (29%) of the 74 patients with peptic ulcers, and then the presence of peptic ulcers was investigated in the upper gastrointestinal system using gastrointestinal endoscopy, followed by histopathological confirmation of celiac disease. HP infection was present in 14 (63%) of the patients with celiac disease and in 23 (44%) of non-celiac peptic ulcers; the difference was not statistically significant (p = 0.12). In the total ulcer group, 10.8% (8/74) of patients with celiac peptic ulcers were negative for HP infection, whereas 21% (8/37) of HP-negative patients with ulcers had celiac disease. CONCLUSION: There exists a high risk of celiac disease in children with peptic ulcers. We thus recommend celiac disease to be investigated, particularly in HP-negative patients with peptic ulcers but with no history of NSAID use.

Lean six sigma methodologies improve clinical laboratory efficiency and reduce turnaround times.

BACKGROUND: Organizing work flow is a major task of laboratory management. Recently, clinical laboratories have started to adopt methodologies such as Lean Six Sigma and some successful implementations have been reported. This study used Lean Six Sigma to simplify the laboratory work process and decrease the turnaround time by eliminating non-value-adding steps. METHODS: The five-stage Six Sigma system known as define, measure, analyze, improve, and control (DMAIC) is used to identify and solve problems. The laboratory turnaround time for individual tests, total delay time in the sample reception area, and percentage of steps involving risks of medical errors and biological hazards in the overall process are measured. RESULTS: The pre-analytical process in the reception area was improved by eliminating 3 h and 22.5 min of non-value-adding work. Turnaround time also improved for stat samples from 68 to 59 min after applying Lean. Steps prone to medical errors and posing potential biological hazards to receptionists were reduced from 30% to 3%. CONCLUSION: Successful implementation of Lean Six Sigma significantly improved all of the selected performance metrics. This quality-improvement methodology has the potential to significantly improve clinical laboratories.

Performance comparison of new generation HCV core antigen test versus HCV RNA test in management of hepatitis C virus infection.

The study has evaluated the performance of HCV core antigen (Cag) test by comparing HCV RNA PCR assay which is considered the gold standard for management of HCV infection. Totally, 132 samples sent for HCV RNA (real-time PCR) test were included in the study. Anti-HCV antibody test and HCV Cag test were performed by chemiluminescent enzyme immunoassay (CMEI). Anti-HCV test was positive in all samples. HCV RNA was detected in 112/132 (84.8%) samples, and HCV Cag in 105/132 (79.5%). The most common HCV genotype was genotype 1 (86%). Considering the HCV RNA test as gold standard; the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of Cag test were found to be 93.75%, 100%, 100%, 74.07% and 94.69%, respectively, and paired test results were detected as highly concordant. A high level of correlation was seen between HCV RNA and Cag tests, however, the concordance between the two tests appeared to be disrupted at viral loads lower than 103IU/mL. On the contrary, the correlation reached significance for the values higher than 103IU/mL. Viral loads were in the 17-2500IU/mL range for the negative results for Cag test. Pearson's correlation coefficient revealed a considerably high correlation. The concordance between HCV RNA and Cag tests was disrupted under a viral load lower than 103IU/mL. Therefore, it would be appropriate to consider cost effectiveness, advantages and limitations of the HCV RNA and Cag tests during the decision on which method to use for patient management.

Congenital Toxoplasmosis and Long-term Outcomes

Objective: Congenital toxoplasmosis (CT) can have severe early and late sequelae in children. In this study, we aimed to evaluate the demographic, clinical, treatment characteristics of patients diagnosed with congenital Toxoplasma infection and to highlight the long-term complications of the patients. Methods: Patients with CT were included in this study who were followed between 2010 and 2022 in Cukurova University Medical Faculty Hospital. Demographic, clinical and treatment characteristics were searched retrospectively. In the diagnosis of maternal and CT, Toxoplasma IgM, IgG, IgG avidity, T. gondii polymerase chain reaction tests were used along with clinical and symptoms. Results: Eighteen children (two twins) with CT and their mothers (n=16) were included in the study. Median age was 1 month. Ten (55.5%) of the children were male. CT diagnosis was made during pregnancy in 7 mothers (resulting in 8 babies) and postnatally in 9 mothers (resulting in 10 babies). The mothers of 5 (31.1%) babies with CT received spiramycin treatment during pregnancy. Three (60%) of 5 pregnant women who received spiramycin were diagnosed in the first trimester, 4 (80%) of the babies did not have any sequale and only 1 (20%) had microphthalmia. Ocular involvement was the most common presentation of the disease occured in 10 patients (55.5%), hydrocephalus and intracranial calcification developed in five patients (27.7%). Hearing loss developed in 2 (11.1%) patients. During the follow-up period, seizures developed in 3 patients (16.6%), microcephaly in 2 patients (11.1%), and neurodevolopmental retardation in 7 patients (38.8%), two of the patients had severe mental retardation. One (5.5%) patient with hydrocephalus died at 36 months of age due to complications after ventriculoperitoneal shunt application. Conclusion: In our study, we observed severe sequelae in vision, hearing, and neurodevelopmental aspects in children diagnosed with CT at birth and during follow-ups. Early diagnosis and treatment of infants, along with the detection of Toxoplasma infection during pregnancy, are essential in preventing severe sequelae that may arise due to CT.

Association between pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections disease and tumor necrosis factor-α gene-308 g/a, -850 c/t polymorphisms in 4-12-year-old children in Adana/Turkey.

OBJECTIVES: Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) is a newly defined disease in neuropsychiatry and occurs with an autoimmune mechanism after Group A Beta Hemolytic Streptococcus (GABHS) infection. Tumor necrosis factor (TNF), encoded by TNF-α gene has an important role in the apoptotic mechanisms of autoimmune diseases. Recently, TNF-α polymorphisms and autoimmune/psychiatric disorders have been reported to be related. In this regard, we focused on to investigate a possible relation between the TNF-α gene promoter region-308 G/A and - 850 C/T polymorphisms and PANDAS. MATERIALS AND METHODS: In this study, ages of PANDAS patient and control groups were ranging from 4 years to 12-year-old. Patient group includes childhood onset PANDAS patients (n = 42) and control group includes healthy children (n = 58). Diagnoses have been carried out according to Diagnostic and Statistical Manual of Mental Disorder (DSM-IV) criteria with Affective Disorders and Schizophrenia-Present and Lifetime (KSAD-S-PL) and Children Yale-Brown Obsessive Compulsive Scale Moreover, PANDAS criteria established by the American National Psychiatry Institute have been employed for diagnoses. For identifying polymorphisms; Polymerase Chain Reaction, Restriction Fragment Length Polymorphism and Polyacrylamid Gel Electrophoresis were used. RESULTS AND DISCUSSION: For -308 polymorphism, 37 of 42 PANDAS patients' results and for -850 C/T polymorphism, 38 of 42 PANDAS patients' results were obtained. According to our statistical analysis there is a positive relationship between PANDAS patients for -308 G/A polymorphism but not for -850 C/T polymorphism. There is no positive relationship between -308 G/A polymorphism and antistrep-tolysin O (ASO) titers and no relationship between -850 C/T polymorphism and ASO titers. We found, however, positive relationship between genders of patients (boys) and the disease. According to our results, we propose that the AA polymorphism of -308 G/A polymorphism can be used as a molecular indicator for PANDAS.

Evaluation of pancreatic functions in cases of primary and secondary malnutrition.

BACKGROUND: This study assessed pancreatic functions by investigating fecal elastase-1 (FE-1) levels in stool specimens in children with primary and secondary malnutrition. METHODS: A total of 139 malnourished children who were hospitalized and followed up at a tertiary care pediatrics clinic and 23 healthy children with no known systemic disease or malnutrition were included in this study. Malnourished patients were divided into four groups according to underlying diagnosis including primary malnutrition (N.=51), cystic fibrosis (N.=44), celiac disease (N.=12) and secondary malnutrition (N.=32; remaining patients with various diagnoses). Patient's demographic characteristics and laboratory data were investigated. FE-1 levels of the patients and healthy subjects were evaluated. RESULTS: FE-1 levels in patients with cystic fibrosis, primary malnutrition, and celiac disease, and other patients with secondary malnutrition were significantly lower than those in the control group. CONCLUSIONS: Pancreatic enzymes are used due to pancreatic failure in cases of cystic fibrosis, and patients benefit considerably from treatment. This study shows that pancreatic failure may also occur in cases of primary and secondary malnutrition apart from cystic fibrosis, emphasizing the likelihood of pancreatic enzyme support to be useful in terms of pancreatic failure developing secondarily in cases of primary malnutrition.

Effect of Heterologous Vaccination Strategy on Humoral Response against COVID-19 with CoronaVac plus BNT162b2: A Prospective Cohort Study.

This study aimed to evaluate the mixed and homogeneous application of the inactivated SARS-CoV-2 vaccine CoronaVac (CV) and the mRNA vaccine BNT162b2 (BNT). This prospective cohort study included 235 health care workers who had received two prime shots with CoronaVac. They were divided into three cohorts after the third month: Cohort-I (CV/CV); Cohort-II (CV/CV/CV); and Cohort-III (CV/CV/BNT). Anti-S-RBD-IgG and total anti-spike/anti-nucleocapsid-IgG antibody concentrations were examined in vaccinated health workers at the 1st, 3rd, and 6th months following the second dose of the vaccination. The mean age of 235 health care workers who participated in the project was 39.51 ± 10.39 (min-max: 22-64). At the end of the 6th month, no antibodies were detected in 16.7% of Cohort-I participants, and anti-S-RDB IgG levels showed a decrease of 60% compared to the levels of the 3rd month. The antibody concentrations of the 6th month were found to have increased by an average of 5.13 times compared to the 3rd-month levels in Cohort-II and 20.4 times in Cohort-III. The heterologous vaccination strategy "CoronaVac and BNT162b2 regimen" is able to induce a stronger humoral immune response and it will help remove inequalities in the developing world where CoronaVac was the initial prime.

Protectivity of COVID-19 Vaccines and Its Relationship with Humoral Immune Response and Vaccination Strategy: A One-Year Cohort Study.

This prospective cohort study aimed to evaluate the efficacy of COVID-19 vaccine schemes, homologous versus heterologous vaccine strategies, and vaccine-induced anti-S-RBD-IgG antibody response in preventing COVID-19 among 942 healthcare workers 1 year after vaccination with the inactivated and/or mRNA vaccines. All participants received the first two primary doses of vaccines, 13.6% of them lacked dose 3, 50.5% dose 4, and 90.3% dose 5. Antibody levels increased with the increase in number of vaccine doses and also in heterologous vaccine regimens. In both inactive, mRNA vaccines and mixed vaccination, infection rates were significantly higher in two-dose-receivers, but lower in four- or five-dose receivers and increasing the total number of vaccine doses resulted in more protection against infection: the three-dose regimen yielded 3.67 times more protection, the four-dose 8 times, and five-dose 27.77 times more protection from COVID-19 infection, compared to any two-dose vaccination regimens. Antibody levels at the end of the first year of four- or five-dose-receivers were significantly higher than two- or three-dose receivers. To conclude, an increased number of total vaccine doses and anti-S-RBD antibody levels increased the protection from COVID-19 infection. Therefore, four or more doses are recommended in 1 year for effective protection, especially in risk groups.

Phototoxic effects of topical azelaic acid, benzoyl peroxide and adapalene were not detected when applied immediately before UVB to normal skin.

The enhancing effects on UVB erythema of topical agents applied on sun exposed areas are important due to their increased sunburn risk. Since the lesions in acne vulgaris are seen primarily on the face, the effects of topical agents used in acne treatment on the erythemogenicity of UVB is important. The aim of the present study was to examine whether azelaic acid cream, benzoyl peroxide gel, adapalene gel have the enhancing effects on UVB erythema which are widely used in the topical treatment of acne vulgaris. The minimal erythema dose (MED) was determined with phototest in 30 volunteers and the test was repeated with thin (0.1 cc/25 cm(2)) and thick (0.3 cc/25 cm(2)) azelaic acid cream, benzoyl peroxide gel, adapalene gel. The effects of each agent on MED was determined after 24 hours. MEDs of UVB were unaffected by azelaic acid cream, benzoyl peroxide gel and adapalene gel when applied immediately before irradiation. According to our results azelaic acid, benzoyl peroxide and adapalene do not seem to have enhancing effects on UVB erythema and thus increased sunburn risk.

99mTc tetrofosmin scintigraphy in acute leukaemia: the relationship between marrow uptake of tetrofosmin and P-glycoprotein and chemotherapy response.

BACKGROUND: The non-invasive detection of P-glycoprotein (Pgp) and multidrug resistance related proteins in vivo, will represent the greatest challenge in overcoming multidrug resistance. Although 99mTc tetrofosmin has been used previously as a myocardial perfusion agent, it is now also being used in the imaging of various tumours. In the current study, Tc tetrofosmin was used in the investigation of acute leukaemia. AIM: To show the uptake pattern of 99mTc tetrofosmin in the bone marrow of patients with acute leukaemia, and to ascertain the relationship between 99mTc tetrofosmin uptake and the level of Pgp expression and their relation to the response to chemotherapy. In addition, CD95, which is an indicator of apoptosis (programmed cell death), has also been assessed. MATERIALS AND METHODS: Pgp and CD95 were detected by using flow cytometry. Of the 27 acute leukaemia patients assessed, nine had previously received chemotherapy, and 18 had had an initial diagnosis. All patients had undergone 99mTc tetrofosmin scintigraphy, and their Pgp and CD95 levels had been determined. The same parameters were studied again for 14 patients. The responses to chemotherapy were assessed by patients' clinicians. A control group of 37 patients without bone marrow pathology was also studied in order to provide comparisons for the scintigraphy results. The control images were assessed only qualitatively. RESULTS: In leukaemia patients the uptake of 99mTc tetrofosmin into bone marrow was found to be considerably higher than in control patients (P=0.000). An analysis of the relationship between Pgp, CD95, and the qualitative and quantitative tetrofosmin uptake ratios (URs) showed that there was an inverse correlation only between Pgp and the quantitative uptake ratio (P=0.016, r=-0.461). When the patients were grouped as 'good' and 'poor', as related to the chemotherapy response, there were no meaningful differences between these two groups regarding Pgp, CD95 and tetrofosmin URs (P>0.05). By evaluating the scintigraphic findings of the 'repeated' 14 patients, we showed that if the 99mTc tetrofosmin UR in the second imaging test was reduced by >0.08, the response to chemotherapy tended to be good. This method, based on follow-up scanning with tetrofosmin, showed a sensitivity of 83% and a specificity of 62% in the prediction of a 'good' response, if a decrease of 0.08 was taken into consideration. CONCLUSION: In this study, patients with acute leukaemia showed significant uptake of tetrofosmin into the bone marrow. The addition of basal and repeated 99mTc tetrofosmin scintigraphy to the management protocol for leukaemia could lead to the preferential determination of responses to chemotherapy, by evaluating whole bone marrow non-invasively. This method seems promising, but it needs further support from various similar investigations comprising more patients in order to confirm our results.

Serum IL-1, IL-2, TNFalpha and INFgamma levels of patients with type 1 diabetes mellitus and their siblings.

Type 1 diabetes mellitus (DM) develops as a result of autoimmune destruction of the pancreatic beta-cells. The aim of this study was to explore possible associations between serum levels of cytokines, IL-1, IL-2, TNFalpha and INFgamma and metabolic parameters in children with type 1 DM and their non-diabetic siblings to determine whether these cytokines could be indicators of disordered immune regulation. The study population consisted of 41 children with type 1 DM, 32 non-diabetic siblings, and 28 healthy controls. Children with DM were divided into three subgroups: 1) newly diagnosed patients with diabetic ketoacidosis (ND + DKA), 2) newly diagnosed patients without DKA (ND - DKA), and 3) previously diagnosed patients (PD). The highest serum IL-1alpha level was found in the ND - DKA group, which was significant compared to both the ND + DKA (p < 0.05) and the siblings (S) (p < 0.005). IL-2 levels were similar among all groups. The highest TNFalpha level was observed in the ND + DKA group, which was significant against the ND - DKA (p < 0.05), PD (p < 0.001), S (p < 0.05), and control (C) (p < 0.005) groups. TNFalpha concentration in the PD group was significantly lower than those of S (p< 0.005) and C (p < 0.001) groups. The ND - DKA group had the highest INFgamma and this was statistically significant when compared with the S (p < 0.005) and C (p < 0.05) groups. Both the newly diabetics and all diabetics as a group had statistically significantly higher INFgamma levels than both the S (p < 0.01 for both) and C (p < 0.05 for both) groups. In the diabetics as a whole group, TNFalpha showed correlations with INFgamma (r = 0.370, p < 0.05). IL-1 showed correlation with TNFalpha (r = 0.368, p < 0.05) INFgamma (r = 0.796, p < 0.001) and IL-2 (r = 0.862, p < 0.001) in the all diabetics group. IL-2 was correlated with TNFalpha (r = 0.320, p < 0.05) and INFgamma (r = 0.754, p < 0.01) in the all diabetics group. In conclusion, our results suggest that proinflammatory cytokines TNFalpha, INFgamma, IL-1alpha and IL-2 may play important roles alone or in combination in the pathogenesis of type 1 diabetes mellitus.

Flow cytometric evaluation of bone marrow plasma cells using CD19, CD45, CD56, CD38, and CD138 and correlation with bone marrow infiltration ratio in multiple myeloma patients.

OBJECTIVE: To examine the co-expression of CD19, CD45, CD38, CD56, and CD138 molecules in plasma cells of bone marrow (BM) aspirates and their relation with BM infiltration, and treatment in patients with multiple myeloma by flow cytometry. METHODS: Forty BM aspirate samples were assessed from 40 patients at diagnosis and on follow-up at the Medical Oncology Department, Cukurova University, Balcali Hospital, Turkey, between 2002 and 2004. The mean age was 56.83 +/- 9.1 and male:female ratio was 2.6. All patients received at least 4 courses of VAD(vincristine, adriamycin, dexamethasone) regimens and 20 of them were also treated with high dose melphalan and peripheral autologous stem cell transplantation. The median follow-up period was 19.1 +/- 22.7 months. RESULTS: Using light microscopy the BM smears stained with hematoxylin and eosin from patients on follow up were classified into one of 3 categories, complete remission (CR) (<5%), partial remission (PR) (>5% and <30%), and extensive infiltration (EI) (>30%). According to infiltration ratio 23 were evaluated CR, 2 were PR and 15 were EI. The mean value of CD19 was 6.01 +/- 9.5%, CD56 = 9.9 +/- 6.8%, CD138 = 8.6 +/- 5.6%, CD45 = 84.2 +/- 22.3% and CD38 = 59.5 +/- 25.4%. The flow cytometric analyses revealed that only the mean value of CD38 and CD45 expression were significantly high. We correlated infiltration ratio with each parametric and found statistically significant relations. We also correlated independent variables with each other and found a relation between CD38 and CD19 (p=0.005). We also defined the groups whether treated with peripheral autologous transplantation or not and compared the independent variables between them, in which CD138 was statistically significant (p=0.02). CONCLUSION: We suggest BM plasma cells expressed mainly by CD38 and CD45 may have a role in generation of BM plasma cells and that CD138 expression may be considered in follow-up for minimal residual disease after autologous transplantation in myeloma patients.

Identification of chromosome abnormalities in screening of a family with manic depression and psoriasis: predisposition to aneuploidy.

Cytogenetic analysis is an important stage in understanding the genetic background of manic depression (MD), and may provide a valuable clue to the identification of target loci and successful search for major genes. In order to identify chromosomal regions we aimed to detect the relationships between chromosomal aberrations (CAs) and immunological markers in a family with MD and psoriasis. We used the cell cultivation and conventional G-banding. We found predominantly numerical aberrations. The most common aneuploidy was chromosome 8, followed by chromosome 22, 21, 15, X and Y. However, structural aberrations consisted of duplications, deletions, translocations and breaks, with a focus on: loci on del(1)(q12-q23), del(1)(q21.1-q24), del(1)(q21.1-q23), del(10)(p11.2-pter), der(2)t(2;4)(p25;p12), t(2;22)(p14;p13), t(19;Y)? and dup(10)(q26). The susceptibility genes of MD or psoriasis may be located on these loci. Numerical sex CAs included 4(5.8%) with 45,X, 3(4.3%) with 47,XXY, and 4(5.8%) with structural chromosome X; del(X)(q13); del(X)(p11-pter) del(X)(q21.3) and inv(Y)(q11.2). We also conducted an immunological study. According results of this study, the percentage of CD2+, CD4+ and CD8+ lymphocytes of the father were significantly higher, whereas CD4+ lymphocytes were decreased in the mother, when compared the healthy persons. The percentage of CD4 level of the son was decreased, whereas CD8+ lymphocytes were higher. The CD4/CD8 ratio of the father and the son was found to be significantly high. These results may suggest that MD and psoriasis have a significant impact on both genetic and immunological parameters.

Oxidative stress and apoptosis in relation to exposure to magnetic field.

We investigated the effect of extremely low-frequency electromagnetic field (ELF-EMF) with pulse trains exposure on lipid peroxidation, and, hence, oxidative stress in the rat liver tissue. The parameters that we measured were the levels of plasma alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase as well as plasma albumin, bilirubin, and total protein levels in 30 adult male Wistar rats exposed to ELF. We also determined the percentage of apoptotic and necrotic cells of the kidney extracts from the animals by flow cytometry method. Apoptotic cell death was further characterized by monitoring DNA degradation using gel electrophoresis. The results showed an increase in the levels of oxidative stress indicators, and the flow cytometric data suggested a possible relationship between the exposure to magnetic field and the cell death. We showed significantly lower necrotic cell percentages in experimental animals compared to either unexposed or sham control groups. However, DNA ladder analyses did not differentiate between the groups. Our results were discussed in relation to the response of biological systems to EMF.