Thrombin lag time is increased in children with mild asthma.

BACKGROUND: Inflammation and coagulation are closely linked events. Thrombin is the key enzyme in coagulation system and also has roles in inflammation. OBJECTIVE: The aim of our study was to evaluate thrombin generation in children with mild asthma. METHODS: Forty-two children with mild asthma and 49 healthy children were included in the study. All patients performed spirometry. Thrombin generation tests (TGT) were performed with a calibrated automated thrombogram (CAT) in children without asthma exacerbation during the last six months. During CAT assay thrombogram curves were obtained. The area under the curve showed endogenous thrombin potentials and indicated the total amount of endogenous thrombin generated; the peak height showed the highest thrombin value, thrombin lag time and time to thrombin peak were measured. RESULTS: Thrombin lag time was significantly longer in children with asthma (3.98±1.2min) compared to those in the control group (3.29±0.6min) (p<0.01). Children with asthma also had longer thrombin tail time compared to the control group (19.5±8.9min vs. 16.7±2.9min, p=0.02). Thrombin peak was inversely correlated with FEF 25-75 (r=-0.41, p<0.01). Thrombin lag time was inversely correlated with FEF 25-75 (r=-0.39, p<0.01). CONCLUSION: Inflammation in mild asthma seems to disturb coagulation but this disturbance may not be so strong as to increase thrombin levels and may only affect the initiation phase of thrombin generation.

Clinical comparison of weight- and age-based strategy of dose administration in children receiving intravenous busulfan for hematopoietic stem cell transplantation.

Bu, combined with TDM-guided dosing, is associated with fewer graft failures/relapses and lower toxicity in pediatric HSCT. We aimed this retrospective study for comparison of weight- and age-based dosing in terms of clinical outcomes such as time to engraftment, early complications, EFS, OS, and toxicity profiles in children receiving iv Bu. Sixty-one children who underwent HSCT from April 2010 to February 2013 by means of a Bu-based conditioning regimen and completed 100 days after transplantation at Ankara Children?s Hematology and Oncology Hospital Bone Marrow Transplantation Unit were enrolled in this study. SOS and neutropenic fever occurred more frequently in the weight-based dosing group. We found a statistically significant correlation between Bu dose and the incidence of SOS (r = 0.26, p = 0.04). Multivariate analysis showed only weight-based dosing of Bu was a significant predictor of SOS (HR = 9.46; p = 0.009). However, no relationship was found between two groups in terms of hemorrhagic cystitis, engraftment syndrome, acute or chronic GvHD, time to engraftment, chimerism, TRM, OS, and EFS rates. Weight-based dosing of Bu may cause higher incidence of SOS and early infectious complications at the places where TDM of Bu cannot be performed.

A new approach for the determination of sulphur in food samples by high-resolution continuum source flame atomic absorption spectrometer.

The new approach for the determination of sulphur in foods was developed, and the sulphur concentrations of various fresh and dried food samples determined using a high-resolution continuum source flame atomic absorption spectrometer with an air/acetylene flame. The proposed method was optimised and the validated using standard reference materials, and certified values were found to be within the 95% confidence interval. The sulphur content of foods ranged from less than the LOD to 1.5mgg(-1). The method is accurate, fast, simple and sensitive.

Functional characterization of a novel missense mutation identified in a Turkish patient affected by severe coagulation factor V deficiency.

Factor V (FV) deficiency is a rare coagulation disorder, characterized by a bleeding phenotype varying from mild to severe. To date, 115 mutations have been described along the gene encoding for FV (F5) but only few of them have been functionally characterized. Aim of this study was the identification and the molecular characterization of genetic defects underlying severe FV deficiency in a 7-month-old Turkish patient. Mutation detection was performed by sequencing the whole F5 coding region, exon-intron boundaries and about 300 bp of the promoter region. Functional analysis of the identified missense mutation was conducted by transient expression of wild-type and mutant FV recombinant molecules in COS-1 cells. Two novel mutations: a missense (Pro132Arg) and a 1-bp deletion (Ile1890TyrfsX19) were identified in the F5 gene. While the frameshift mutation is responsible for the introduction of a premature stop codon, likely triggering F5 mRNA to nonsense-mediated mRNA degradation, the demonstration of the pathogenic role of the Pro132Arg mutation required an experimental validation. Expression experiments showed that the missense mutation causes a significant reduction in FV secretion and in the specific activity of the residual secreted molecule (77% and 78% decrease, respectively). This paper reports the identification of two novel mutations responsible for FV deficiency, thus widening the mutational spectrum of the F5 gene. The Pro132Arg mutation adds to the only other two functionally characterized missense defects in the FV A1 domain.

Protective effect of lycopene against radiation-induced hepatic toxicity in rats.

The radioprotective effect of lycopene against liver damage was investigated in 80 female Sprague Dawley rats (10 per group). Early-group rats included: controls (group 1), lycopene (group 2), radiotherapy alone (group 3), and lycopene + radiotherapy (group 4). Lycopene (5 mg/kg per day) was administered orally for 7 days; single-fraction 8 Gy abdominopelvic radiotherapy was administered on day 8. Early-group rats were sacrificed on day 10. Late-group rats (groups 5-8) underwent treatment with the same regimens but, in groups 6 and 8, lycopene was administered until all rats were sacrificed, 60 days postradiotherapy. Liver malondialdehyde levels increased significantly and glutathione (GSH) levels, GSH-peroxidase (GSH-Px) and superoxide dismutase (SOD) activity decreased significantly in radiotherapy versus control groups. In lycopene + radiotherapy groups, malondialdehyde levels decreased significantly and GSH levels, GSH-Px and SOD activity increased significantly compared with radiotherapy groups. No significant between-group histo pathological differences were observed in early groups; in late groups, histopathological changes increased significantly in the radiotherapy group versus control group. A significant decrease in histopathological changes occurred in the lycopene + radiotherapy group compared with the radiotherapy group. Lycopene supplementation significantly reduced radiotherapy-induced oxidative liver injury.

Multiple primary malignant neoplasms from the black sea region of Turkey.

Long-term cancer survival is increasing and, as a consequence, so is the prevalence of secondary malignancies. This study evaluated the patient and tumour characteristics of 117 patients with multiple primary malignant neoplasms (MPMN). The incidence of MPMN in children and adults was 0.28% and 1.23%, respectively. The male : female ratio was 1.7 : 1. The mean ± SE age at tumour diagnosis was 60.56 ± 1.18 years. Overall, the top three tumour sites were the larynx, bladder and breast. Among secondary tumours, lung cancer was the most frequent, followed by breast and colon cancer. Among males, the leading primary and secondary tumour sites were the larynx (30.1%) and lung (50.7%), respectively. Among females, the breasts were both the leading primary (32.6%) and secondary (37.2%) cancer site. The mean ± SE overall survival was 97.2 ± 15.0 months. During follow-up, the brain was the most commonly observed site of metastasis. The occurrence and characteristics of MPMN reported in the literature are also reviewed. The present study contributes towards increasing understanding and treatment of MPMN in a different population group.

Awareness of glucose-6 phosphate-dehydrogenase deficiency in celiac disease.

UNLABELLED: Individuals with celiac disease (CD) are predisposed to a number of haematological abnormalities including anaemia secondary to malabsorption of iron, vitamin B12 or folate; anaemia of chronic disease and coagulopathy secondary to vitamin K deficiency. Correction of coagulopathy with vitamin K is necessary before endoscopic biopsy in patients with suspected CD. However, vitamin K causes haemolysis in glucose-6 phosphate-dehydrogenase deficiency. CONCLUSION: When vitamin K administration becomes necessary for correction of coagulopathy in patients with CD; glucose-6 phosphate-dehydrogenase deficiency should be considered.

Gaucher disease with communicating hydrocephalus and cardiac involvement.

A 14-year-old female with Gaucher disease presented with hydrocephalus, corneal opacities, cirrhosis, and cardiac valvular involvement. A homozygous D409H mutation was identified. She underwent surgery for aortic and mitral valve replacement. Because of severe calcification of the aortic root, no successful valve replacement was performed. She died on the third day after the explorative cardiac surgery. Cardiac abnormalities represent a life-threatening presentation of the homozygous D409H mutation. Identification of this type is essential prior to initiating appropriate therapy with enzyme replacement and cardiac corrective surgery.

Comparison of IL10 and IL2 genotypes of Turkish population with other populations.

The human genome has been shaped by evolutionary and historical forces. Therefore, genetic polymorphisms are useful tools not only to understand the susceptibility to disease in modern populations, but the history of ancestral populations as well. For this purpose, data on genetic polymorphisms such as human leucocyte antigen, mitochondrial DNA sequence variability and the frequencies of TAP1 and TAP2 gene variants in Turkey have been reported previously. Here we have used interleukin (IL)-10 (-592C/A, -819T/C, -1082G/A) and IL-2 (-330T/G) as genetic markers to study the relationship between Turkish population and other populations.

Prognostic value of the PAI-1 4G/5G polymorphism in invasive ductal carcinoma of the breast.

The study group was derived from the archive materials of 55 invasive ductal breast cancer (IDC) patients who had undergone breast-preserving surgery (partial mastectomy/ axillary dissection). All patients included in the study had clinically T(1)-2, N0-M0 invasive ductal carcinoma. Genomic DNA species were extracted from paraffin-embedded blocks, and plasminogen activator inhibitor type-1 (PAI-1) gene 4G/5G genotyping was done by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). Patient demographics, axillary metastasis status, metastatic lymph nodi/total dissected lymph nodes from axilla, histopathologic characteristics of tumors, local recurrences, and survival ratio were assessed. PAI-1 4G/5G genotype frequencies were 4G/4G (64%), 4G/5G (31%), and 5G/5G (5%) in the patient group. According to the results based on frequencies, the demographics were not different. Five-year local recurrence rate of 4G/5G patients was the lowest (2/17, 12%) (P = 0.02). Also five-year distant metastases ratio of 4G/5G patients was the highest (18%) (P = 0.01). Five- and 10-year disease-free survival rates for the 4G/4G, 4G/5G, and 5G/5G groups were 97% and 94%, 82% and 77%, and 100% and 94%, respectively (P = 0.004). The results of this study indicate that the 4G allele in the PAI 1 gene had a negative impact on local recurrence and disease-free survival of patients with clinical T(1)-2N0M0 IDC.

Relationship between small-for-gestational age births and maternal thrombophilic mutations.

Small gestational age (SGA) is one of the major causes of fetal mortality and morbidity. Altered maternal homeostasis as a result of point mutations in the coagulation cascade has been reported as an important risk factor for this adverse pregnancy outcome. This study aims to investigate the relationship between mother's thrombophilic mutations and SGA deliveries in our population. The study group was consisted of sixty-six women who gave birth to one or more SGA babies. 104 women who gave birth to appropriate-for-gestational age (AGA) babies were sampled for the control group. Restriction fragment size analysis were performed by visualizing digested PCR products for Factor V Leiden (G1691A), Factor V Cambridge (A1090G), Factor V A1299G, prothrombin G20210A, methylene tetrahydropholate reductase C677T, A1298C and T1317C mutations. The results of this study indicate that maternal C677T (p=0.01) and A1298C (p<0.01) mutations in MTHFR gene may be suggested as risk factors for SGA outcome in our population. Therefore, maternal screening of these two mutations in the first trimester of pregnancy could help in the assessment of patients.

Complete blood count parameters for healthy, small-for-gestational-age, full-term newborns.

No previous study has investigated the full range of complete blood count (CBC) parameters in small-for-gestational-age (SGA) newborns. The main aim of this study was to compare CBC and peripheral smear parameters in term, healthy SGA neonates and appropriate-for-gestational-age (AGA) neonates, and to establish CBC reference values for full-term SGA newborns. One hundred thirty-two healthy, term newborns (73 SGA and 59 AGA) were included. On day 1, we obtained 109 samples and on day 7 we obtained 77 samples. A CBC and peripheral smear were analyzed for each sample collected and group data were compared. We observed higher mean values for normoblast count, hemoglobin, hematocrit, and red blood cell (RBC) count in the SGA babies than in the AGA babies on day 1. The mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration values for the SGA babies were decreased because of the relatively high RBC count and relatively high mean corpuscular volume we observed in this group. Of the SGA newborns, 21.9% had neutropenia and 4.7% had absolute neutrophil counts lower than 1500/microl on day 1. On both day 1 and day 7, the SGA newborns had higher mean absolute metamyelocyte counts and higher mean I : T (immature : total neutrophil ratio) values than the AGA group. The SGA babies had a lower mean absolute lymphocyte count on day 7 than the AGA group. We detected thrombocytopenia in almost one-third of the 64 SGA newborns tested on day 1. In summary, our study clearly demonstrates that CBC parameters for healthy, full-term, SGA newborns are different from those of healthy, term AGA newborns. This is the first study that has documented different mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, metamyelocyte counts, lymphocyte counts, and I : T in SGA babies compared with AGA babies.

A very unusual presentation of Niemann-Pick disease type B in an infant: similar findings to congenital lobar emphysema.

The main features of Niemann-Pick disease type B (NPD-B) are enlargement of the liver and spleen, and mild pulmonary involvement. Recurrent respiratory tract infection and progressive decline in pulmonary function are major contributors to morbidity and mortality in this patient group. Massive pulmonary involvement in early life is extremely rare. The most common finding on chest X-rays of NPD-B patients is reticular or nodular infiltration of the lungs. This article describes a very rare presentation of NPD-B in an infant who had suffered recurrent respiratory tract infections. Massive emphysema and marked infiltrative parenchymal changes (infiltration of the parenchyma) were initially attributed to congenital lobar emphysema and its compressive effects. However, NPD was suspected when a lung biopsy showed foamy cells and sea-blue histiocytes were detected in a bone marrow biopsy. The definitive diagnosis was established with an enzyme study for sphingomyelinase.

The effect of pre-operative conventional and hyperfractionated radiotherapy schedules on wound healing and tensile strength in rats: an experimental study.

We examined the effects of pre-operative conventional and hyperfractionated radiotherapy schedules on wound healing and tensile strength in 90 female Wistar rats weighing between 182 and 240 g. The animals were randomized into three groups (n = 30 each). Group I was sham-irradiated. Group II (conventional) received 20 daily fractions of 200 cGy, to a total dose of 4000 cGy. Group III (hyperfractionated) received 40 fractions of 120 cGy, twice daily, to a total dose of 4800 cGy. Four weeks after radiotherapy, incision and primary repair with simple suturing was performed on one side of the neck. Twenty-one days after wounding, all the rats were sacrificed. Non-parametric Kruskal-Wallis and Mann-Whitney U-tests were used for the statistical analysis of wound tensile strength. The chi-squared test was used for the statistical analysis of the histopathologic findings. The hyperfractionated group had a significantly lower tensile strength than that of the control group (P = 0.03, z = -2.18). According to the histopathologic findings, fibrosis was increased significantly in the hyperfractionated group as compared to the other groups (P = 0.038, chi2 = 6.52). Hyperfractionated radiotherapy significantly reduced the wound tensile strength in the early evaluation period as compared to the control group.

Successful use of recombinant factor VIIa (NovoSeven) during cardiac surgery in a pediatric patient with Glanzmann thrombasthenia.

Glanzmann thrombasthenia is a rare, hereditary, congenital disorder of platelet function characterized by inappropriate bleeding that is difficult to control. Recombinant activated factor VII (rFVIIa) is a new treatment that is used to stop bleeding and provide surgical support for these patients. This report describes the use of rFVIIa to prevent serious bleeding during and after open-heart surgery in a child with Glanzmann thrombasthenia.

Captopril-induced pancytopenia in a premature newborn.

A preterm infant with renovascular hypertension who developed significant trilineage bone marrow suppression after receiving captopril is reported. Captopril-associated pancytopenia is a very rare complication that was thought to be dose-related and usually caused by accumulation of the drug through defective renal tubular excretion. In our patient, it appears that the combination of renal artery stenosis and renal tubular dysfunction of prematurity might have led to pancytopenia. Captopril should be used with caution especially in premature babies and newborns with underlying renal or renovascular disease even if they do not have overt renal dysfunction. Monitorization of these babies with creatinine clearance or free serum captopril levels may help to establish accumulation of the drug before causing pancytopenia.

Prognostic significance of seizure in patients with glioblastoma multiforme.

BACKGROUND: Several prognostic factors have been described but there are few studies evaluating the prognostic importance of seizure in patients with glioblastoma multiforme (GBM). AIMS: To evaluate the prognostic importance of seizure at the time of the diagnosis of glioblastoma multiforme (GBM) and compare it with other known prognostic factors. SETTINGS AND DESIGN: Between January 1994 and December 2000, 81 patients underwent irradiation for intracranial GBM at our institution. The criteria for inclusion in this study were biopsy-proven GBM, being treated for primary disease. Seventy-six patients were retrospectively evaluated and the remaining five patients could not be enrolled due to lack of details. MATERIAL AND METHODS: The prognostic importance of age, sex, performance status, a history of seizure at diagnosis, extent of surgery, radiotherapy field and dose were studied. STATISTICAL ANALYSIS: The Kaplan-Meier method, the Log rank test, the Cox proportional hazard model and the Mann-Whitney U test were used for statistical analysis. RESULTS: Survival at first and second years was 19.74% and 4.81%, respectively. Univariate analysis revealed age, performance status, history of seizure, and radiotherapy dose as significant prognostic factors and with multivariate analysis age, history of seizure and radiotherapy dose were positive prognostic factors. CONCLUSION: This study concluded that in GBM, history of seizure prior to diagnosis of GBM was a positive prognostic factor.

Purpura fulminans in a child with combined heterozygous prothrombin G20210A and factor V Leiden mutations.

Although thrombosis is relatively rare in children, reports of young patients with thrombosis are becoming more frequent with time. Activated protein C resistance and prothrombin 20210 A mutation are results of point mutations described in the last decade. This article highlights a case of a child with severe arterial thrombosis who was heterozygous for the factor V Leiden (FVL) and prothrombin G20210A mutations. The patient diagnosed with purpura fulminans was an 8-year-old boy who was referred to our hospital with purpuric lesions on the extremities and necrosis of the penis. We believe that the coexistence of more than one thrombophilic mutation contributed to the occurrence of severe thrombosis at a young age in this patient.

Significant differences between capillary and venous complete blood counts in the neonatal period.

The normal capillary and venous hematologic values for neonates have not been defined clearly. It is well known that capillary blood has higher hemoglobin (Hb) and hematocrit (Hct) values than venous blood. In a recent study, we reported differences between capillary and venous complete blood counts (CBC) in healthy term neonates on day 1 of life. The aim of this study was to extend our previous investigation. Term neonates (n=141) were stratified into four groups by days of postnatal age: group 2 (day 7, n=38), group 3 (day 14, n=35), group 4 (day 21, n=32) and, group 5 (day 28, n=36). Data from our previous study were included in the statistical analysis as group 1 (day 1, n=95). A CBC and differential count were carried out on each capillary and venous sample drawn simultaneously. Within each group, the mean and standard deviation for each parameter in capillary and venous blood were calculated and then compared using the paired sample t-test. In all groups, the capillary blood samples had higher Hb, Hct, red blood cell (RBC), white blood cell (WBC), and lymphocyte counts. In each group, venous platelet counts were significantly higher than the corresponding capillary values. There was also a trend toward higher venous mean corpuscular volume, higher capillary polymorphonuclear leukocyte (PML) count and mean platelet volume in all groups. In both capillary and venous blood, Hb, Hct, RBC, MCV values and WBC, lymphocyte, PML counts decreased and platelet counts increased steadily during neonatal period. This study reveals that CBC parameters and differential counts may differ depending on the blood sampling used. The findings underline the importance of considering the sample source when using hematologic reference ranges for healthy or septic neonates. When interpreting results, the term 'peripheral blood' should be replaced with 'capillary blood' or 'venous blood' so that an accurate assessment can be made.