New αIIbß3 variants in 28 Turkish Glanzmann patients; structural hypothesis for complex activation by residues variations in I-EGF domains.

Glanzmann thrombasthenia (GT) is a rare autosomal recessive bleeding disorder characterized by impaired platelet aggregation due to defects in integrin αIIbß3, a fibrinogen receptor. Platelet phenotypes and allelic variations in 28 Turkish GT patients are reported. Platelets αIIbß3 expression was evaluated by flow cytometry. Sequence analyzes of ITGA2B and ITGB3 genes allowed identifying nine variants. Non-sense variation effect on αIIbß3 expression was studied by using transfected cell lines. 3D molecular dynamics (MDs) simulations allowed characterizing structural alterations. Five new alleles were described. αIIb:p.Gly423Asp, p.Asp560Ala and p.Tyr784Cys substitutions impaired αIIbß3 expression. The αIIb:p.Gly128Val substitution allowed normal expression; however, the corresponding NM_000419.3:c.476G>T variation would create a cryptic donor splicing site altering mRNA processing. The ß3:p.Gly540Asp substitution allowed αIIbß3 expression in HEK-293 cells but induced its constitutive activation likely by impairing αIIb and ß3 legs interaction. The substitution alters the ß3 I-EGF-3 domain flexibility as shown by MDs simulations. GT variations are mostly unique although the NM_000419.3:c.1752 + 2 T > C and NM_000212.2:c.1697 G > A variations identified in 4 and 8 families, respectively, might be a current cause of GT in Turkey. MD simulations suggested how some subtle structural variations in the ß3 I-EGF domains might induce constitutive activation of αIIbß3 without altering the global domain structure.

A Significant Association in Paediatric Emergency Department, Cerebral Sinovenous Thrombosis and Ulcerative Colitis: Review of Literature

ABSTRACT Objective: To discuss cerebral sinovenous thrombosis (CSVT), an important mortality and morbidity factor, developing in the progression of ulcerative colitis (UC) in childhood age, in the light of the literature. Methods: A search of PubMed and Google Scholar database was conducted on April 2014. This study retrospectively investigates the cases diagnosed with UC with complication of CSVT below 18 years of age between years 1971 and 2014. The cases were analysed with respect to age, gender, disease duration and treatment, potential risk factors, clinical findings, location of thrombosis, thrombolytic therapeutical applications, and clinical progressions. Results: Twenty-four paediatric patients aged 5 and 18 years were included in the study. Cerebral sinovenous thrombosis had developed during active disease period in 23 (95.8%) patients. The most common complaints were headache (79.1%) and emesis (29.1%). The most frequently detected risk factors for CSVT were anaemia (58.3%) and thrombocytosis (45.8%). Inherited thrombotic disorders were encountered in 10 (41.6%) of the cases. The most common location sites for CSVT were the transverse (33.3%) and the sigmoid (33.3%) sinuses. It had been discovered that 19 (79.2%) of the cases were healed completely without a sequelae, whereas neurological sequelae remained in three (12.5%) of the cases and two (8.3%) of the cases died. Conclusion: In the presence of a prior diagnosis of UC and emergency presentation with emesis, headache, mood changes and particularly seizure, the presence of CSVT should certainly be considered.

Comparison between electronic method and conventional method recording and follow-up of general surgery ward-round notes taken.

AIM: Patient anamneses and ward-rounds notes taken are two key elements which have been and will be used to ensure accurate and reliable sustainability at surgery services. In this study, we aimed to find a new method which is capable of better addressing the needs in this process, simplifying it and also saving time. We also targeted to compare this new method used by us with the method, also known as conventional method, having been used for years. METHODS: Thirty patients were included in the study. The prehospitalization anamneses of the patients were taken using the two methods and the durations were recorded separately for the two methods. Thereafter, the patients were visited by two methods in the morning on each day of their stay. The durations were recorded daily and separately for the two methods. The durations were statistically evaluated separately for the anamneses and ward-round notes taken. RESULTS: Evaluations showed that the method using hand terminal (1.2250 minutes) is more advantageous in terms of duration in recording ward-round scores than the conventional method (1.3853 minutes). It was founded that in regard to the duration, the average duration of manual anamnesis taking (16.3350 minutes) is higher than that of taking anamnesis by means of hand terminal (15.4733 minutes). Furthermore, it was also seen that the use of this new technique eliminated the problems previously experienced in data transfer, access to historical data etc. CONCLUSION: In conclusion, this method that is tested by use of hand terminal is more advantageous than the conventional method in terms of time saving and accurate data transfer. It is our opinion that it will provide advantages in many more aspects if it is worked on.

Serum prealbumin levels in hepatotoxicity of chemotherapy in children with cancer.

OBJECTIVE: To evaluate serum prealbumin levels in chemotherapy-induced hepatotoxicity and to compare them with the other tests that are routinely used in children with cancer. MATERIALS AND METHODS: We studied serum prealbumin levels before and 1, 3, 7, and 21 days after chemotherapy in addition to other tests (AST, ALT, ALP, total protein, albumin, total and direct bilirubin) in twenty-eight children with cancer receiving various combinations of chemotherapeutics. Serum ALT, AST, ALP, albumin and total and direct bilirubin were determined by enzymatic and photometric methods. Prealbumin was determined by an immunonephelometric method. RESULTS: Total protein and albumin were decreased, AST, ALT, ALP, and total and direct bilirubin levels were increased after chemotherapy and returned to the normal levels on the 21st day of chemotherapy, but these changes were not statistically significant. Prealbumin levels were significantly decreased on the first day of chemotherapy and returned to normal on the 21st day (p=0.001). The sensitivity and specificity of prealbumin were 28.5 % and 66.6 % on the third day and 40.0 % and 73.9 % on the seventh day, respectively. The positive and negative predictive values were 22.2 % and 73.6 % on the third day and 25.0 % and 85.0 % on the seventh day, respectively. CONCLUSION: Serum prealbumin levels seem not to be a good marker of chemotherapy-induced hepatotoxicity in respect to the other biochemical markers. On the other hand, hepatotoxicity of chemotherapy which may be fatal in severe cases and cessation of the ongoing chemotherapy may be warranted with the early decrease of prealbumin levels but it should be evaluated in larger group of patients before this conclusion (Tab. 4, Fig. 1, Ref. 18).

Crimean-Congo haemorrhagic fever: peritoneal and pleural effusion.

In Crimean-Congo haemorrhagic fever (CCHF), haemorrhagic manifestations are usually petechiae and ecchymoses on mucous membranes and skin. Rarely, there is bleeding from the nose, gingiva, gastro-intestinal tract, genito-urinary tract, brain and lungs. A 13-year-old boy with CCHF presented with gastro-intestinal bleeding and developed peritoneal and pleural effusion. He made a complete recovery with supportive treatment and ribavirin, without requiring chest or peritoneal fluid drainage. To our knowledge, this is the first report of CCHF associated with peritoneal and pleural fluid.

Can remifentanil be a better choice than propofol for colonoscopy during monitored anesthesia care?

BACKGROUND AND OBJECTIVE: This prospective, randomized trial was designed to test the hypothesis that continuous infusion of low-dose remifentanil can provide effective analgesia, sedation, amnesia, patient comfort and stable recovery profile without respiratory depression when compared with propofol infusion during colonoscopy. METHODS: One hundred patients were randomly assigned to receive either remifentanil (group R, 0.5 microg/kg followed by 0.05 microg/kg/min, n = 50) or propofol (group P, 0.5 mg/kg followed by 50 microg/kg/min, n = 50). Supplemental doses of remifentanil 12.5 microg in group R and propofol 10 mg in group P were given to treat complaints of moderate to severe pain and discomfort. Hemodynamic and respiratory data, pain, discomfort and sedation scores, patient and gastroenterologist satisfaction and recovery profiles were recorded. RESULTS: The duration of colonoscopy was longer in group P. The mean arterial pressure, heart rate and end-tidal CO2 remained stable during the procedure and were comparable between the groups. After bolus injection of the study drugs, the respiratory rate and oxygen saturation values were lower in group R than in group P. Only one patient in group R required airway support. Pain and discomfort scores were better in group R than in group P. Sedation levels were higher in group P than in group R. Group P needed more supplemental doses than group R. The time to reach an Aldrete score of nine or more was shorter in group R, but discharge times were similar in the two groups. Amnesia was better in group P. Nausea and vomiting were more frequent in group R during the recovery phase. CONCLUSION: Low-dose remifentanil infusion with intermittent bolus injections can provide adequate sedation, amnesia and better analgesia than propofol infusion during colonoscopy. However, remifentanil-induced nausea and vomiting may be a problem during the recovery phase.

Visceral childhood leishmaniasis in Turkey.

UNLABELLED: Between 1981 and 2001, we retrospectively analysed 40 cases of visceral leishmaniasis (VL) admitted to the Paediatric Infection Unit of Ondokuz Mayis University Hospital, in the middle Black Sea region of Turkey. Median age at presentation was 3 y. Fever and splenomegaly were found in all patients. Bone marrow smear examination resulted in the diagnosis of VL in 95% of cases. All patients were treated initially with meglumine antimonate and 95% of them were cured with this therapy. The remaining patients were cured with liposomal amphotericin B. CONCLUSIONS: VL should be considered in patients with fever and splenomegaly, particularly those residing in the Mediterranean region. Meglumine antimonate seems to be the first choice of treatment in childhood.

Effects of high-dose methotrexate on the hemostatic system in childhood acute lymphoblastic leukemia.

BACKGROUND: Thromboembolic and hemorrhagic complications are significant causes of death in patients with malignancy. These are well-known with the use of certain drugs. This study was planned to investigate whether there was any effect of high-dose methotrexate on the hemostatic system in childhood acute lymphoblastic leukemia. PROCEDURE: To evaluate the hemostatic system, we investigated coagulation screening tests (prothrombin time, activated partial thromboplastin time, and fibrinogen), coagulation inhibitors (protein C, protein S, and antithrombin III), and fibrinolytic system (fibrin degradation products and tissue plasminogen activator). These parameters were measured in 35 cycles of high dose-methotrexate (3 g/m(2)) of 20 childhood acute lymphoblastic leukemia cases at baseline and on days 1 and 7 after the therapy. RESULTS: We found that high-dose methotrexate administration adversely affected both the coagulation system (prolonged prothrombin time and activated partial thromboplastin time and decreased fibrinogen levels) and coagulation inhibitors (decreased protein C, protein S, antithrombin III) on day 1 after chemotherapy compared to the baseline values. The hemostatic parameters began to improve on day 7 after chemotherapy, except for fibrin degradation products. Tissue plasminogen activator levels were not changed with the therapy. CONCLUSIONS: Coagulation cascade (prolonged prothrombin time and activated partial thromboplastin time and decreased fibrinogen) and coagulation inhibitors (decreased protein C, protein S, and antithrombin III levels) have been found to be affected by high-dose methotrexate therapy, but these transient changes did not cause clinical thromboembolic or hemorrhagic complications.

Middle cerebral arterial occlusion in a child with osteopetrosis major.

Osteopetrosis major (infantile autosomal recessive type) usually presents with pathological fractures, bone marrow failure and some neurological deficits due to remodelling defect of the bone and narrowed bonny channel of the blood supply. Herein we present a case of osteopetrosis major with neurological deficits not attributed to the narrowed carotid channel of the petrous bone, but due to middle cerebral arterial occlusion 2 cm distal to narrowed channel.

Rapid Identification of Family-Specific Mutations in the Factor VIII Gene by One-Step DGGE.

A one-step denaturing gradient gel electrophoresis (DGGE) strategy for the rapid detection of mutations in the factor VIII gene of haemophilia A patients is described. All coding (except the middle part of exon 14) and flanking intronic regions of the gene corresponding to approximately 6.6 kb were amplified in 27 fragments using four PCR programs. Heteroduplex formation was performed for each fragment. A common denaturant gradient gel (35-65%) was chosen that allowed the simultaneous analysis of all PCR amplified regions on a single gel and run for 3.5 h at 160 V. This method was implemented for a patient whose family was seeking carrier determinations. An abnormal pattern was detected in exon 23 and the family-specific mutation was found by subsequent DNA sequencing. One-step DGGE is a promising rapid method for the carrier detection and prenatal diagnosis in haemophilia A families when immediate results are required and when polymorphic markers fail to give information.

Electronic Excited States of the CP29 Antenna Complex of Green Plants: A Model Based on Exciton Calculations.

We have suggested a model for the electronic excited states of the minorplant antenna, CP29, by incorporating a considerable part of the currentinformation offered by structure determination, site-directed mutagenesis,and spectroscopy in the modeling.We have assumed that the electronic excited states of the complex havebeen decided by the chlorophyll-chlorophyll (Chl) and Chl-proteininteractions and have modeled the Coulombic interaction between a pairof Chls in the point-dipole approximation and the Chl-protein interactionsare treated as empirical fit parameters.We have suggested the Q(y) dipole moment orientations and the siteenergies for all the chlorophylls in the complex through a simultaneoussimulation of the absorption and linear dichroism spectra.The assignments proposed have been discussed to yield a satisfactoryreproduction of all prominent features of the absorption, linear and circulardichroism spectra as well as the key spectral and temporal characteristics ofthe energy transfer processes among the chlorophylls.The orientations and the spectral assignments obtained by relatively simpleexciton calculations have been necessary to provide a good point ofdeparture for more detailed treatments of structure-function relationship inCP29. Moreover, it has been discussed that the CP29 model suggested canguide the studies for a better understanding of the structure-functionrelationship in the major plant antenna, LHCII.

The incidence of gallbladder stones and gallbladder function in beta-thalassemic children.

PURPOSE: To determine gallbladder motor function and gallstone prevalence in beta-thalassemic children. Abnormalities in gallbladder function or bile acid metabolism may contribute to gallstone formation in these patients. MATERIAL AND METHODS: In 17 beta-thalassemic patients and 12 normal healthy children with similar age, sex and weight, gallbladder size was measured using real-time US, and volume was calculated using the ellipsoid method. RESULTS: In the beta-thalassemic patients, cholelithiasis was present in 2 patients (11.8%). Sludge, which can be a predisposing factor for cholelithiasis and cholecystitis when it persists, was detected in 5 patients (29.4%). One of the patients had both cholelithiasis and sludge. Compared with the control group, beta-thalassemic children had larger fasting volume, residual volume, and smaller contraction index. CONCLUSION: Beta-thalassemic patients have enlarged gallbladders that retain an increased residual volume of bile. Gallbladder enlargement, bile stasis, and impaired emptying of sludge may be important events in the pathogenesis of pigment gallstones in beta-thalassemic patients.

Intracranial haemorrhage due to factor V deficiency.

Factor V deficiency is a rare coagulation disorder which is inherited autosomal recessively. Factor V deficiency should be considered in infants with bleeding disorders and prolonged prothrombin and activated partial thromboplastin times if bleeding continues in spite of vitamin K injection. In this article, the case of an infant with an intracranial haemorrhage due to congenital factor V deficiency is reported.

Osteopetrosis--improvement of hematologic findings with age.

A three months old girl was admitted to the hospital for evaluation of pallor and abdominal distension. There was anemia, thrombocytopenia and extramedullary hematopoiesis. In the long bone roentgenogram medullary areas could not be distinguished and bone densities were increased. The patient was diagnosed for osteopetrosis with these findings and prednisolone treatment was begun and then discontinued since it was not effective. In the follow up, the need for blood transfusions decreased and then disappeared. We present a case which was diagnosed as osteopetrosis and followed up by blood transfusions and of which hematologic findings improved with age.

Chronic nephrotic syndrome and chronic renal failure by amyloidosis secondary to xanthogranulomatous pyelonephritis.

The association of xanthogranulomatous pyelonephritis (XPN) and systemic amyloidosis is extremely rare. This association has been described in only six cases. We present a 4-year-old male admitted with a history of anuria and abdominal pain. Investigations revealed multiple calculi in both kidneys. A right pyelolithotomy and left nephrectomy were performed. Histological examination demonstrated XPN and amyloidosis. At discharge serum creatinine had dropped to 1.1 mg/dl but after being lost to follow up for 9 years, the child was readmitted because of edema. Laboratory examination revealed a nephrotic syndrome and serum creatinine of 2.3 mg/dl. Rectal biopsy showed the presence of amyloid. A treatment by colchicine was unsuccessful. Fifteen months later, at the age of 15 years, the patient developed terminal renal failure (serum creatinine 14 mg/dl).

Oral high-dose methylprednisolone and intravenous immunoglobulin treatments in adult chronic idiopathic thrombocytopenic purpura.

Ten adult patient of chronic idiopathic thrombocytopenic purpura (CITP) used oral prednisone and were treated with seven doses of oral high-dose methylprednisolone (30 mg/kg). Nine of ten patients responded after HDMP treatment (plt > 150 x 10(9)/L). Two patients having 8 and 10 years of history achieved long-term remission after first HDMP treatment. One unresponsive and one responsive patients did not accept IVIG treatment as second therapy and lost the follow-up. The remaining six patients received IVIG (0.5 mg/kg for 5 days) as second therapy after 3 months. Platelet count increased above 150 x 10(9)/L in 4 patients and between 60-80 x 10(9)/L in 2 patients. The peak platelet counts of both therapy users were higher under HDMP than IVIG therapy (252 +/- 110.4 vs 174.2 +/- 83.7 x 10(9)/L), but the difference was not significant. Responses were transient and returned to pretreatment values at 14-30 days, excluding long-term remission of 2 (2/10) patients after HDMP treatment. No side effect was observed. Thus, oral HDMP appears a good initial therapy for continuous remission in a small ratio of patients and a good security for emergency situations and prior to surgery in adult CITP patients.