Efficacy of FEIBA for acute bleeding and surgical haemostasis in haemophilia A patients with inhibitors: a multicentre registry in Turkey.

Long used in established industrialized nations to treat patients with haemophilia and inhibitors, factor eight inhibitor bypassing activity (FEIBA) has, in recent years, been introduced into more geographically diverse settings. Data are needed on how successfully FEIBA therapy has been implemented in new regions. To determine the efficacy and safety of FEIBA for the treatment of acute bleeding and surgical haemostasis in a newly industrialized country. A multicentre registry of haemophilia A patients with inhibitors receiving FEIBA treatment was established in Turkey. With a standardized case report form, data were collected retrospectively on: patient demographics; characteristics of acute bleeding episodes and surgical interventions; FEIBA regimen; and treatment outcomes. Thirty-seven patients received a total of 112 FEIBA treatment courses, 90 for acute bleeding and 22 for surgical haemostasis. The median FEIBA dose per infusion for acute bleeding was 50 IU kg(-1), and for surgery was 100 IU kg(-1). For both acute joint and muscle/soft tissue bleeding and in surgery, haemostasis was attained in a median of two FEIBA infusions. FEIBA was judged effective in 92% of treatment courses for acute bleeding, with a 95% confidence interval (CI) of 85-97%. Rates of haemostatic efficacy did not differ significantly between anatomical sites of acute bleeding. The haemostatic efficacy rate of FEIBA in surgery was 86% (CI, 65-97%). No thromboembolic complications or other adverse events occurred during any treatment course. FEIBA has been successfully integrated into clinical practice in Turkey, with rates of haemostatic efficacy comparable to those reported in countries with a longer history of FEIBA usage.

Central nervous system involvement in a case of familial hemophagocytic lymphohistiocytosis with perforin mutation.

Familial hemophagocytic lymphohistiocytosis (FHL) is a rare autosomal recessive lethal condition characterized by fever, cytopenia, hepatosplenomegaly and hemophagocytosis. The presence of central nervous system involvement has a profound impact on the prognosis, treatment, and clinical outcome of the disease. Therefore, the identification of the clinical manifestations of the disease and the characterization of the accompanying neurological symptoms are of prime importance for the rapid diagnosis and subsequent clinical management of the disease. Herein, we report a case of FHL with homozygosity for perforin gene mutation, who presented with central nervous system involvement in the absence of systemic findings.

Ceftriaxone induced thrombocytopenia in a child.

A variety of diseases, hereditary conditions, toxins and drugs may cause thrombocytopenia. Thrombocytopenia induced by ceftriaxone has been rarely reported. In this case, ceftriaxone-induced thrombocytopenia is presented in a 2-year-old girl due to rare presentation (Ref. 10). Full Text in free PDF www.bmj.sk.

Serosurveillance study on transmission of H5N1 virus during a 2006 avian influenza epidemic.

In 2006 an outbreak of avian influenza A(H5N1) in Turkey caused 12 human infections, including four deaths. We conducted a serological survey to determine the extent of subclinical infection caused by the outbreak. Single serum samples were collected from five individuals with avian influenza whose nasopharyngeal swabs tested positive for H5 RNA by polymerase chain reaction, 28 family contacts of the cases, 95 poultry cullers, 75 individuals known to have had contact with diseased chickens and 81 individuals living in the region with no known contact with infected chickens and/or patients. Paired serum samples were collected from 97 healthcare workers. All sera were tested for the presence of neutralizing antibodies by enzyme-linked immunoassay, haemagglutination inhibition and microneutralization assays. Only one serum sample, from a parent of an avian influenza patient, tested positive for H5N1 by microneutralization assay. This survey shows that there was minimal subclinical H5N1 infection among contacts of human cases and infected poultry in Turkey in 2006. Further, the low rate of subclinical infection following contact with diseased poultry gave further support to the reported low infectivity of the virus.

The frequency of consanguineous marriage in eastern Turkey.

UNLABELLED: The frequency of consanguineous marriage in Eastern Turkey: OBJECTIVE: The rate of consanguineous marriage (CM) varies depended on different factors such as race, characteristics of population, and religion and moral features in different countries. Gene frequency and genetic structure are changed by CMs. The aim of the present study is to assess the prevalence of CM and its effects on miscarriage, stillbirth, congenital malformation and ratio of newborn death. METHODS: This study was performed in Van region, Eastern Turkey, between September 2005 and April 2006. A total of 650 families from 24 districts chosen in accordance with the number of inhabitants were included in this study. First cousin marriages were accepted as a first degree CMs, sesquialter and second cousin marriages as second degree and marriages between distant relatives were accepted as a third degree CM. Monthly income of the families was classified in accordance with minimum wage determined by government. RESULTS: Of all families, 224 (34.4%) had CM, and 168 (75%) had first-degree consanguinity. A lower CM rate was found in mothers who graduated from secondary school or upgrading (p < 0.01). However, no relationship was found between CM and fathers' education level. While a low CM rate was found in families who had two or less children (p < 0.01), high rate was observed in families who had five or more children. In addition, a high rate of miscarriage, stillbirth and mental-motor retardation was found in families with CM (p < 0.05). The rate of child mortality between the aged 0-2 years was found to be higher in families with CM (p < 0.01). The higher CM rate was observed in families who married due to pressure or insistence of their families than married voluntarily (p < 0.05). CONCLUSION: Our study showed that CM rate was very high, 34.4%, in our region Eastern Turkey.

Evaluation of lymphocyte subgroups in children with subacute sclerosing panencephalitis.

The aetiology of subacute sclerosing panencephalitis (SSPE) remains to be fully elucidated, although it follows infection with a hypermutant defective M-protein measles virus. This study analysed peripheral blood lymphocyte subgroups to determine their role in the pathophysiology of SSPE. It included 22 children with SSPE aged 2 - 15 years (patient group) and 22 age- and gender-matched healthy children (control group). In children < 6 years old, there were no statistically significant differences between the two groups in the proportions of lymphocytes expressing the surface markers CD3, CD8, CD19 or CD16/56, or in CD4/CD8 ratio. The proportion of CD4(+) lymphocytes in SSPE patients < 6 years of age was significantly lower compared with the control group. In children >or= 6 years old, there were no significant differences in the lymphocyte subgroups. In conclusion, these findings suggest that a low CD4(+) lymphocyte count might be responsible for SSPE in younger children.

Benefit of high-dose methylprednisolone in comparison with conventional-dose prednisolone during remission induction therapy in childhood acute lymphoblastic leukemia for long-term follow-up.

Eight-year event-free survival (EFS) was evaluated in 205 patients with acute lymphoblastic leukemia (ALL), to consider the efficacy of high-dose methylprednisolone (HDMP) given during remission induction chemotherapy between 1 and 29 days. The St Jude Total XI Study protocol was used after some minor modifications in this trial. Patients were randomized into two groups. Group A (n = 108) received conventional dose (60 mg/m(2)/day orally) prednisolone and group B (n = 97) received HDMP (Prednol-L, 900-600 mg/m(2) orally) during remission induction chemotherapy. Complete remission was obtained in 95% of the 205 patients who were followed-up for 11 years; median follow-up was 72 months (range 60-129) and 8-year EFS rate was 60% overall (53% in group A, 66% in group B). The EFS rate of group B was significantly higher than of group A (P = 0.05). The 8-year EFS rate of groups A and B in the high-risk groups was 39% vs 63% (P = 0.002). When we compared 8-year EFS rate in groups A and B in the high-risk subgroup for both ages together /=10 years, it was 44% vs 74%, respectively. Among patients in the high-risk subgroup with a WBC count >/=50 x 10(9)/l, the 8-year EFS was 38% in group A vs58% in group B. During the 11-year follow-up period, a total of 64 relapses occurred in 205 patients. In group A relapses were higher (39%) than in group B (23%) (P = 0.05). These results suggest that HDMP during remission-induction chemotherapy improves the EFS rate significantly for high-risk patients in terms of the chances of cure.

Acute respiratory distress syndrome due to overdose desferrioxamine: report of a child.

In this article, we present an 18-month-old girl with acute iron poisoning who died from acute respiratory distress syndrome due to overdose of desferrioxamine. Our purpose is to emphasize the importance of close follow-up children with acute iron poisoning for desferrioxamine toxicity.

Changes of hemostatic factors in children with acute lymphoblastic leukemia receiving combined chemotherapy including high dose methylprednisolone and L-asparaginase.

In this study, protein C (PC), protein S (PS), heparin cofactor II (HCFII), prothrombin fragment 1+2 (PF 1,2), thrombin-antithrombin III complex (TAT), von Willebrand factor (vWF) and thrombomodulin (TM) were investigated in 19 patients with acute lymphoblastic leukemia, (ALL) receiving combined chemotherapy including L-asparaginase (L-ASP) and high dose methylprednisolone (HDMP). HDMP was administered in doses of 30 mg/kg/day for 7 days, and 20 mg/kg/day for another 7 days. In order to evaluate the effect of HDMP on the hemostatic system, the 8 patients studied here received HDMP (30 mg/kg/day) therapy for 4 days before the combined chemotherapy. These parameters were also studied in 12 healthy children as a control group. PC levels were normal in the patients while PS levels were decreased both before and after combined chemotherapies. Patients with ALL have laboratory signs of coagulation activation such as PF 1,2, TAT prior to initiation of chemotherapy. With combined chemotherapy, TAT levels were found to be normal while PF1,2 were not. TM levels were found to be increased both before and after therapies whereas HCFII and vWF levels were not different from those of the control group. The short course of HDMP therapy did not prominently influence these hemostatic parameters. These results indicate that both the malignant process and the drugs used in combined chemotherapy cause a decrease in natural inhibitors and an increase in procoagulant activity and endothelial injury. These hemostatic changes may contribute to a thrombotic tendency in the patients with ALL.

Thrombomodulin levels in Behçet's disease with and without the factor V Leiden mutation.

The plasma levels of thrombomodulin (TM) in 34 patients with Behçet's disease and 79 healthy control subjects were studied. Eight patients had the factor V Leiden (FVL) mutation. The TM level was significantly lower in patients with the FVL mutation than in patients without the mutation and in the healthy controls (p < 0.05 and p < 0.01). However, there was no difference in overall mean plasma TM concentration between the patients without the mutation and the healthy controls.

Diminished platelet aggregation in patients with iron deficiency anemia.

To evaluate platelet function in iron deficiency anemia, using impedance (in whole blood) and optic (in platelet-rich plasma methods, platelet aggregation analyses were performed in 42 children with iron deficiency anemia at the time of diagnosis and after iron therapy. Collagen-induced platelet aggregation was decreased in patients before therapy compared to after therapy and control levels as indicated by the two methods while adenosine diphosphate (ADP)-induced platelet aggregation was decreased only by the whole blood method. Platelet aggregation with epinephrine, performed only by the optic method, was not altered in patients with iron deficiency anemia. Platelet counts were found to be increased in patients with iron deficiency anemia, and decreased with therapy. These results indicate that some platelet functions are decreased in patients with iron deficiency anemia. These decreased functions may be compensated by increased platelet numbers.

Platelet functions in patients with protein-energy malnutrition.

Protein-energy malnutrition (PEM) has been known to cause several organ damages or dysfunctions. In this study, using optic method, platelet aggregation (PA) analyses were performed in patients with PEM. Adenosine diphosphate (ADP)- and collagen-induced PA were significantly decreased in the patients with PEM. The low values reached normal when the patients caught up the optimal growing curve for their age. PA with ristocetin and epinephrine were not significantly altered in the patients. Conversely, mean platelet count was increased at the beginning compared to those of after therapy and to the control. These results indicate that some platelet functions (ADP- and collagen-induced platelet aggregations), as well as other body functions, have been decreased in PEM.

Application of electrical impedance tomography in diagnosis of emphysema--a clinical study.

In this paper, electrical impedance tomography (EIT) ventilation images from a group of 12 patients (11 patients with emphysema and one patient with only chronic obstructive pulmonary disease (COPD) (chronic bronchitis) and a group of 15 normal subjects were acquired using a Sheffield mark 1 EIT system, at the levels of second, fourth and sixth intercostal spaces. Patients were diagnosed based on CT scans of the thorax, pulmonary function tests and posteroanterior x-ray graphs. One of the patients with emphysema has also a malignant lung tumour. Ventilation-related conductivity changes at total lung capacity (TLC) relative to residual volume were measured quantitatively in EIT images. These quantitative values demonstrate marked differences compared to those values obtained from the EIT images of 15 normal subjects. The EIT images of the patients were also compared with the CT images. In addition to the visual examination of the EIT images a statistical confidence test is applied to compare the images of the patients with the images of the normal subjects. Prior to statistical analysis all images are normalized with TLC to minimize the effect of mismatch between the TLC of different subjects. A normal mean image is created by averaging the normalized images from the normal subjects, at each intercostal space level. Than a 95% confidence interval is defined for each normal mean image. For each image of the patients, a confidence test image, which represents the deviations from the 95% confidence interval of the normal mean image, is created. The regions with emphysematous bulla and parencyhma are detectable in the confidence test images as regions of positive and negative deviations from the confidence interval of the normal mean, respectively. In the test images, it is possible to differentiate emphysematous parenchyma from emphysematous bulla, tumour structure, and COPD. However, the emphysematous bulla, the tumour structure, and COPD result in the same type of defect in the test images and are therefore indistinguishable from each other. In some case, off-plane contributions in the EIT images may result in underestimation of the defects. EIT may be a useful screening device in detecting emphysema rather than a diagnostic tool.

Splenic abscess, pleural effusion and severe anemia caused by Salmonella typhi.

Various complications related to gastrointestinal system, central nervous system, and skeletal system may be observed during typhoid fever, but splenic abscess and pleural effusion are rarely encountered. A 12-year-old boy was admitted with fever, fatigue and pallor. On examination he had hepatosplenomegaly and severe anemia. He was diagnosed as having Salmonella typhi infection complicating with splenic abscess, pleural effusion and severe anemia, and successfully treated with percutaneous drainage with ultrasonography and antibiotics. In conclusion we would like to emphasize that typhoid fever should also be considered in patients with hepatosplenomegaly and severe anemia, and percutaneous drainage with ultrasonography may successfully be used in management of splenic abscess in typhoid fever.

Cerebrospinal fluid pleocytosis in acute lymphoblastic leukemia without central nervous system relapse: a report of three cases.

Three patients with acute lymphoblastic leukemia (ALL) developed mononuclear cells in the cerebrospinal fluid (CSF) after a flu-like history during maintenance treatment. None of the patients showed evidence of central nervous system (CNS) involvement by either clinical or laboratory follow-up. Although the presence of > 5 mononuclear cells/microl in the CSF is important, it may not necessarily indicate CNS disease. Clinical findings, history and cell morphology must be evaluated before deciding on further treatment.

Changes of hemostatic factors in patients with hemoglobinopathies.

In this study, protein C (PC), protein S (PS), heparin cofactor II (HCFII), prothrombin fragment 1+2(PF1,2), thrombin-antithrombin III complex (TAT), von Willebrand factor (vWF) and thrombomodulin (TM) were investigated in 13 patients with beta thalassemia intermedia (TI) not requiring transfusion, six patients with sickle cell disease (SCD), and seven patients with HbS-beta thalassemia (S-BT) who were not in crisis. These hemostatic parameters were also studied in 12 healthy children assigned as a control group. Protein C and Protein S (PC-PS) were found to be decreased in TI patients and normal in S-BT patients. PC was decreased in SCD patients. In the patients with TI and SCD, the mean PF1,2 level was elevated, whereas the TAT level was not statistically different from that of the control group. These results suggested that in patients with hemoglobinopathies: a) decreased natural anticoagulants and b) enhanced procoagulant activation have been encountered. Other unexpected and interesting results of this study are the decreased vWF and elevated HCFII levels in all three patient groups.

Ophthalmo-acromelic syndrome in a Turkish infant: case report.

Ophthalmo-acromelic syndrome (OAS) is an extremely rare autosomal recessive disorder characterised by eye malformations ranging from true anophthalmia to mild microophthalmia and acromelic malformations. In this article, we report a newborn infant with OAS because of its rare presentation. He was the fourth sibling affected in the family. The parents were healthy but there was a close blood relationship between the parents. Physical examination revealed bilateral true anophthalmia and oligodactyly (bilateral four toes) on the feet. He had no other additional abnormalities. We consider that this rare syndrome could be relatively more common in our country because six Turkish cases of OAS have been reported in the English literature to date.

Perforated gastric ulcer in children. Case report.

12-year-old boy in whom a benign gastric ulcer perforated into the free abdominal cavity is reported. He has underwent emergency operation with a preoperative diagnosis of acute peritonitis due to perforation of peptic ulcer. Gastric ulcer is a rare disease of childhood. The illness was discussed in view of the literature.

Serum immunoglobulins and immunoglobulin G subclasses with recurrent wheezing.

In this study serum immunoglobulins (Ig) and IgG subclasses were measured in 42 patients (ranging 9 month-6 year) with recurrent wheezing and in 37 healthy children determined the relationship between serum Igs and recurrent wheezing. Patients were divided into two groups according to the age [9 month-2 year (n: 15), and 2-6 year (n: 27)]. In the patients placed in 9-24 month age group, serum IgG4 level was found to be lower than controls (p < 0.05). But there was not a significant difference in mean serum concentrations of total IgG, IgA, IgM, IgE, IgG1, IgG2 and IgG3 subclasses between the groups (P > 0.05). In the 25 month-6 year age group the mean IgE level was increased compared to the control while IgG3 and IgG4 levels were decreased (p < 0.05). On the other hand, in the 9-24 month age group there was no significant difference between the patients and controls for IgG subclasses deficiency (P > 0.05). However, significant difference in IgG subclasses deficiency was present between the patients and controls in the 25 month-6 year group (P < 0.001). In conclusion, our findings suggest that wheezing in childhood may be associated with low IgG3 and/or IgG4, and in older children high IgE level may be a part of pathogenetic mechanism in patients with recurrent wheezing.

Beta-Thalassemia Mutations in the East of Turkey.

This study was planned to determine the frequency of ß-thalassemia trait and mutations in Van Lake region, which is in the eastern part of Turkey, surrounded by Iran in the east and by Iraq in the south. This study consist of 1014 healthy students, between the age of 12 and 18 years who are studying in boarding schools in Van city and cities surrounding Van Lake that includes Van, Agri, Hakkari, Bitlis, Mus and Siirt. The students were randomly selected according to their school numbers. Their origin was not taken into consideration in selection. Complete blood counts were performed on all donors. The accepted lower limit of mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) were 78 fL and 27 pg respectively. HbA2 was measured by DE-52 microcolumn chromatography method. ß-thalassemia trait with high HbA2 was found in 6 children. ß-thalassemia homozygous form of -30 (T-A) mutation was determined in one child and HbD-Los Angeles heterozygous in another. The ß-thalassemia homozygous individual was accepted as two cases in prevalence calculation. We found that the prevalence of ß-thalassemia trait was 0.78% in this area. In DNA analyses, there were ß-thalassemia gene mutations of FSC 8/9 (+G), -30 (T-A), IVS I-110 (G-A), IVS II-1 (G-A) and IVS I-130 (G-A) in 3, 2, 1, 1 and 1 individuals, respectively. We conclude that although five different ß-thalassemia mutation exist in Van Lake region, ß-thalassemia is not a potential risk in the east of Turkey.