The Role of FLT3-ITD and CCAAT-Enhancer-Binding Protein α Mutations on Prognosis of Acute Lymphoblastic Leukaemia in Turkish Patients

ABSTRACT Background: Acute lymphoblastic leukaemia (ALL) is the most common malignancy in childhood. Although some prognostic factors have been defined to date, the estimation of prognosis is currently not perfect. Previous studies had shown an association of FLT3 with poor prognosis and CCAAT-enhancer-binding protein α (CEBPA) mutation with the development of acute myeloid leukaemia (AML). Here, we aimed to evaluate the prognostic value of FLT3-ITD and CEBPA mutations in ALL. Methods: Sixty-one patients with ALL were included in the study. The patients were divided into three risk groups according to BFM risk classification. All of the patients were examined for FLT3-ITD mutations and 45 of them for CEBPA mutations. Mutation positive and negative patients were compared in terms of their risk groups, translocations and cell lineage. The clinical courses of the patients were appraised. Results: FLT3-ITD mutation was detected in 3 of the 61 patients, and CEBPA mutations were detected in 11 of the 45 patients. The incidence of established prognostic indicators including BFM risk classification, t(9; 22); BCR-ABL, t(1; 19); E2A-PBX1, t(12; 21); TEL-AML1, t(4; 11); MLL-AF4 were similar between FLT3-ITD and CEBPA positive and negative patients. A patient with an FLT3-ITD mutation was very susceptible to pancytopenia after maintenance treatment and two other patients with FLT3-ITD mutations were more prone to febrile neutropenia. Conclusion: Our results suggested that CEBPA or FLT3-ITD mutations might not be related to ALL prognosis in the sampled Turkish patients. However, FLT3-ITD mutation might have an influence on the response of bone marrow to chemotherapy.

Vasodilator Effect of Glucagon: Receptorial Crosstalk Among Glucagon, GLP-1, and Receptor for Glucagon and GLP-1.

Glucagon is known for its insulin-antagonist effect in the blood glucose homeostasis, while it also reduces vascular resistance. The mechanism of the vasoactive effect of glucagon has not been studied before; thereby we aimed to investigate the mediators involved in the vasodilatation induced by glucagon. The vasoactive effect of glucagon, insulin, and glucagon-like peptide-1 was studied on isolated rat thoracic aortic rings using a wire myograph. To investigate the mechanism of the vasodilatation caused by glucagon, we determined the role of the receptor for glucagon and the receptor for GLP-1, and studied also the effect of various inhibitors of gasotransmitters, inhibitors of reactive oxygen species formation, NADPH oxidase, prostaglandin synthesis, protein kinases, potassium channels, and an inhibitor of the Na(+)/Ca(2+)-exchanger. Glucagon causes dose-dependent relaxation in the rat thoracic aorta, which is as potent as that of insulin but greater than that of GLP-1 (7-36) amide. Vasodilatation by GLP-1 is partially mediated by the glucagon receptor. The vasodilatation due to glucagon evokes via the glucagon-receptor, but also via the receptor for GLP-1, and it is endothelium-independent. Contribution of gasotransmitters, prostaglandins, the NADPH oxidase enzyme, free radicals, potassium channels, and the Na(+)/Ca(2+)-exchanger is also significant. Glucagon causes dose-dependent relaxation of rat thoracic aorta in vitro, via the receptor for glucagon and the receptor for GLP-1, while the vasodilatation evoked by GLP-1 also evolves partially via the receptor for glucagon, thereby, a possible crosstalk between the 2 hormones and receptors could occur.

Tissue compliance meter is a more reproducible method of measuring radiation-induced fibrosis than late effects of normal tissue-subjective objective management analytical in patients treated with intracavitary brachytherapy accelerated partial breast irradiation: results of a prospective trial.

Identification of radiation-induced fibrosis (RIF) remains a challenge with Late Effects of Normal Tissue-Subjective Objective Management Analytical (LENT-SOMA). Tissue compliance meter (TCM), a non-invasive applicator, may render a more reproducible tool for measuring RIF. In this study, we prospectively quantify RIF after intracavitary brachytherapy (IB) accelerated partial breast irradiation (APBI) with TCM and compare it with LENT-SOMA. Thirty-nine women with American Joint Committee on Cancer Stages 0-I breast cancer, treated with lumpectomy and intracavitary brachytherapy delivered by accelerated partial breast irradiation (IBAPBI), were evaluated by two raters in a prospective manner pre-IBAPBI and every 6 months post-IBAPBI for development of RIF, using TCM and LENT-SOMA. TCM classification scale grades RIF as 0 = none, 1 = mild, 2 = moderate, and 3 = severe, corresponding to a change in TCM (ΔTCM) between the IBAPBI and nonirradiated breasts of ≤2.9, 3.0-5.9, 6.0-8.9, ≥9.0 mm, respectively. LENT-SOMA scale employs clinical palpation to grade RIF as 0 = none, 1 = mild, 2 = moderate, and 3 = severe. Correlation coefficients-Intraclass (ICC), Pearson (r), and Cohen's kappa (κ)-were employed to assess reliability of TCM and LENT-SOMA. Multivariate and univariate linear models explored the relationship between RIF and anatomical parameters [bra cup size], antihormonal therapy, and dosimetric factors [balloon diameter, skin-to-balloon distance (SBD), V150, and V200]. Median time to follow-up from completion of IBAPBI is 3.6 years (range, 0.8-4.9 years). Median age is 69 years (range, 47-82 years). Median breast cup size is 39D (range, 34B-44DDD). Median balloon size is 41.2 cc (range, 37.6-50.0 cc), and median SBD is 1.4 cm (range, 0.2-5.5 cm). At pre-IBAPBI, TCM measurements demonstrate high interobserver agreement between two raters in all four quadrants of both breasts ICC ≥ 0.997 (95% CI 0.994-1.000). After 36 months, RIF is graded by TCM scale as 0, 1, 2, and 3 in 10/39 (26%), 17/39 (43%), 9/39 (23%), and 3/39 (8%) of patients, respectively. ΔTCM ≥6 mm (moderate-severe RIF) is statistically different from ΔTCM ≤3 mm (none-mild RIF) (p < 0.05). At 36 months post-IBAPBI, TCM measurements for two raters render ICC = 0.992 (95% CI 0.987-0.995) and r = 0.983 (p < 0.0001), whereas LENT-SOMA demonstrates κ = 0.45 (95% CI 0.18-0.80). SBD and V150 are the only factors closest to 0.05 significance of contributing to RIF. This prospective study indicates that TCM is a more reproducible method than LENT-SOMA in measuring RIF in patients treated with IBAPBI. This tool renders a promising future application in assessing RIF.

Slow phase relaxation as a route to quantum computing beyond the quantum chaos border.

We reveal that phase memory can be much longer than energy relaxation in systems with exponentially large dimensions of Hilbert space; this finding is documented by 50 years of nuclear experiments, though the information is somewhat hidden. For quantum computers Hilbert spaces of dimension 2(100) or larger will be typical and therefore this effect may contribute significantly to reduce the problems of scaling of quantum computers to a useful number of qubits.

Home ventilator low-pressure alarms fail to detect accidental decannulation with pediatric tracheostomy tubes.

BACKGROUND: Positive-pressure ventilators are equipped with low-inspiratory-pressure alarms to protect patients from hypoventilation. Small uncuffed tracheostomy tubes have a high resistance, and may not trigger these alarms during decannulation. STUDY OBJECTIVE: To determine whether ventilator low-inspiratory-pressure alarms are effective in detecting tracheostomy decannulation. DESIGN: We connected tracheostomy tubes of varying inner diameters (3.0 to 6.0 mm) to a home ventilator and simulated decannulation using low (tidal volume [VT], 600 mL; peak inspiratory pressure [PIP], 25 cm H(2)O), medium (VT, 800 mL; PIP, 30 cm H(2)O), and high (VT, 1,000 mL; PIP, 35 cm H(2)O) ventilator settings. RESULTS: When the ventilator low-inspiratory-pressure alarm was set at 4 cm H(2)O below the desired PIP, it failed to alarm for simulated decannulation of tracheostomy tubes < 4.5 mm on low and medium settings, and < 4.0 mm on high settings. When the ventilator low-inspiratory-pressure alarm was set at 10 cm H(2)O below the desired PIP, it failed to alarm with tracheostomy tubes < 6.0 mm. CONCLUSION: We conclude that ventilator low-inspiratory-pressure alarms fail to alarm during simulated decannulation with small tracheostomy tubes commonly used in children. We speculate that low-inspiratory-pressure alarms set at 4 cm H(2)O below the desired PIP will detect more decannulation than when set at 10 cm H(2)O below the desired PIP.

Effects of sample geometry and electrode configuration on measured electrical resistivity of skeletal muscle.

Over the past 40 years, researchers from a variety of scientific backgrounds have been using Rush's equations to analyze results of their electrophysiological studies. A lack of understanding of the constraints and the domain in which these equations are valid, often results in situations in which it is challenging to evaluate and compare results obtained by different investigators. In this paper, we reanalyzed the conditions for which Rush's equations were derived, and using mathematical modeling, computer simulation and in vitro measurements, we delineated areas of their appropriate application. Our studies showed that both sample geometry and test electrode configuration affect the measured tissue electrical resistivities: 1) The sample can be considered semi-infinite only if its dimensions are > 50 inter-electrode separation distances (IESD), and thickness > 2.5 IESD, 2) smaller sample sizes increase the transversally measured resistivity, 3) semi-infinite samples thinner than 2.5 IESD, and samples tested with needle electrodes demonstrate reduced anisotropy, and 4) when surface-spot electrodes are longitudinally aligned, as the IESD/tissue thickness ratio decreases, the measured resistivity increases. Our conclusion is that in most experimental situations, it is necessary to use modeling techniques to decouple the electrode configuration/sample geometry influence from the measured tissue resistivity.

Severe combined immunodeficiency: otolaryngological presentation and management.

In order to increase the awareness of otolaryngologists of severe combined immunodeficiency syndrome (SCIDS) so they may contribute to an earlier diagnosis of this disorder, we performed a retrospective chart review of a multicenter series from 2 children's hospital medical centers. Eighteen cases were identified, and 14 had an otolaryngological presentation. The average age of presentation was 3.3 months, and 72% were males. Most cases were inherited in an X-linked fashion. Five patients had thrush; 4 had recurrent otitis media. Other otolaryngological presentations included cough, mouth ulcers, pharyngitis, mastoiditis, and bilateral neck abscess. The most severe form of immunodeficiency, SCIDS is a rare condition that involves a disorder in both T and B cell functions. The manifestations involving the head and neck include recurrent upper respiratory tract infections, otitis media, thrush, oral ulcers, and abscesses. It is important that SCIDS be considered in any infant with recurrences of these common infections.

Real-time extraction of tissue impedance model parameters for electrical impedance spectrometer.

This paper presents a new algorithm for real-time extraction of tissue electrical impedance model parameters from in vivo electrical impedance spectroscopic measurements. This algorithm was developed as a part of a system for muscle tissue ischemia measurements using electrical impedance spectroscopy. An iterative least square fitting method, biased with a priori knowledge of the impedance model was developed. It simultaneously uses both the real and imaginary impedance spectra to calculate tissue parameters R0, R infinity, alpha and tau. The algorithm was tested with simulated data, and during real-time in vivo ischemia experiments. Experimental results were achieved with standard deviations of sigma R0 = 0.80%, sigma R infinity = 0.84%, sigma alpha = 0.72%, and sigma tau = 1.26%. On a Pentium II based PC, the algorithm converges to within 0.1% of the results in 17 ms. The results show that the algorithm possesses excellent parameter extraction capabilities, repeatability, speed and noise rejection.

Selection of measurement frequencies for optimal extraction of tissue impedance model parameters.

The results are presented of a study performed to determine the measurement frequencies that provide optimal extraction of tissue impedance model parameters from in vivo measured electrical impedance spectra. Measurement frequency sets that are logarithmic and quasi-linear, and frequency sets that produce angularly equidistant points on the Nyquist loci are used to test the parametric fitting algorithm that calculates R0, R infinity, alpha and tau tissue parameters from complex impedance spectra. Simulated data, calculated in the presence of < or = 5% measurement noise, and in vivo experiments indicate that the quality of the fitted parameters depends upon the selection of measurement frequencies. The results show that, if measurements are performed with a system that has a realistic measurement bandwidth, then, for the best estimation of: R0, the measurement frequencies should include the decade from 100 Hz-1 kHz; R infinity, the algorithm should not include frequencies under 1 kHz; alpha and tau, the measurement frequencies should be equidistantly spaced on the Nyquist locus.

In-vitro and in-vivo comparative analysis of four tissue pH monitoring systems.

The purpose of this investigation was to identify the type of pH-reference electrode combination that is the most suitable and reliable in clinical applications involving long-term postoperative monitoring of microvascular reconstructive transplants and diagnosis of compartment syndrome. Four types of pH-sensing devices were chosen for the study: a standard glass pH electrode, a polymer-based pH electrode, an ISFET pH sensor, and a fiberoptic pH sensor. Various combinations of electrodes were tested in vitro for typically four days. The glass and polymer electrodes maintained stable pH readings, averaging drifts of 0.14 +/- 0.07 and 0.14 +/- 0.08 pH units per 96 hours, respectively. The fiberoptic sensors displayed an average drift of 0.20 +/- 0.15 pH units per 96 hours. ISFET sensors displayed nearly linear drifts, averaging 1.36 +/- 0.54 pH units per 96 hours. When placed in healthy animal tissue, glass and polymer electrode pH readings followed the arterial blood pH values, measured by a blood gas analyzer. In compromised tissue, both glass and polymer electrodes recorded falling pH levels correctly, indicating ischemic conditions. Generally, ISFET sensors in healthy tissue produced pH readings that did not correlate well with arterial blood pH values. Fiberoptic sensors monitored healthy-tissue pH correctly; however, mechanical disturbances of the fiberoptic sensor and occasional discontinuation of computer operation would shift the pH output significantly (at times by 0.2 pH units), resulting in subsequent inaccurate pH readings. The glass electrode was the only sensor evaluated clinically. It correctly indicated tissue viability in all clinical cases, involving both healthy and ischemic tissue. The authors conclude that the glass pH electrode has the best combination of characteristics for clinical tissue pH measurements.

Multiplane Transesophageal and Intracardiac Echocardiography in Large Swine: Imaging Technique, Normal Values, and Research Applications.

Transthoracic echocardiographic imaging has been difficult to attain in the swine model. This study: (1) compares multiplane transesophageal echocardiography (TEE) with single plane TEE and intracardiac catheter echocardiography (ICE) for imaging of the swine cardiovascular system; and (2) defines normal values using these techniques in a closed chest large swine model (n = 24, body weight 50-114 kg). Multiplane TEE increased success rate over the single plane (the variable plane array only at 0 degrees ) TEE (P < 0.01) for imaging the left ventricular (LV) long-axis view (100% vs 50%), LV outflow tract (100% vs 33%), right atrium and its appendage (79% vs 33%), ascending aorta (100% vs 58%), and aortic arch (100% vs 17%). TEE-derived normal values at end-diastole (ED) and end-systole (ES) were: LV internal diameter (ID) = 49 +/- 3 mm (ED) and 33 +/- 4 mm (ES); LV wall thickness = 7 +/- 1 mm (ED); right ventricular (RV) ID = 24 +/- 4 mm (ED); RV wall thickness = 4 +/- 2 mm (ED); left atrial ID = 48 +/- 6 mm (ES); aortic root ID = 26 +/- 3 mm (ES); LV volume = 157 +/- 49 ml (ED) and 57 +/- 22 ml (ES). Baseline LV ejection fraction (64% +/- 6%), Doppler-derived stroke volume (86 +/- 14 ml), and cardiac index (107 ml/min per kg) were determined. Basal normal values, except for an elevated cardiac index in swine, are comparable to those reported for human adults. Multiplane TEE provided better overall cardiac imaging than did single plane TEE. ICE provided higher resolution imaging of individual cardiac chambers and structures when the ultrasound catheter was introduced into the right or left heart, but whole heart imaging was limited by ultrasound penetration at 12.5 MHz. Normal indices of chamber size and function provide a reference for the physiological significance of induced pathological states in this relevant animal model.

Conductance volumetric model of an eccentrically positioned catheter within a three-compartment ellipsoidal ventricle.

This paper presents a mathematical model of the electric field generated and resistance measured by a conductance catheter within a three-compartment ellipsoidal approximation of a cardiac ventricle. The model is based on a novel combination of analytical and numerical techniques. The numerical component of the model predicts displacement of the catheter along the central longitudinal ventricular axis, as well as eccentric positions off that axis. The analytical component of the model enables interactive definition of model parameters during simulation. This versatile combination enables performance of validation studies that include simulations of various catheter movements within a ventricle of changing geometry. The results of our simulation studies agree with the results of previous investigators studying ex-vivo systems.

Preoperative thyroid scanning in presumed thyroglossal duct cysts.

The purpose of this study was to determine if preoperative thyroid scans are essential in the workup of presumed thyroglossal duct cysts. Questionnaires were sent to pediatric otolaryngologists and pediatric general surgeons with a 65% response rate. Fifty-seven percent of the physicians have encountered ectopic thyroid. In 58% of these, this was the only functioning thyroid tissue. Twenty eight percent of pediatric surgeons vs 65% of pediatric otolaryngologists routinely order scans. Two of the physicians encountering ectopic thyroid volunteered that they had successful litigation directed against them for removing the sole functioning thyroid and creating permanent hypothyroidism. There is a likelihood of encountering ectopic thyroid during the course of one's practice. A case of ectopic thyroid is presented, and management strategies are discussed.

Telephone assessment of parents' knowledge of home-care treatments and readmission outcomes for high-risk infants and toddlers.

Medical technology is enabling many high-risk infants and toddlers to be cared for at home. However, techniques for evaluation of home-care and discharge-planning outcomes have not been well documented. Using 60 subjects, we performed telephone assessment of home-care givers' knowledge base in basic knowledge of treatment, operation and maintenance of supplies and equipment, and vendor information, using standard questions, 48 hours following discharge from the hospital. Families giving apnea monitoring or Broviac catheter care as a single treatment scored 100% in all three areas. However, the scores for care givers providing gastrostomy care (54%, 100%, and 91%), tracheostomy care (80%, 70%, and 50%), or total parenteral nutrition (88%, 50%, and 100%) as single treatments were lower. Care givers providing multiple home-care treatments had the lowest scores (65%, 65%, and 76%). However, care givers of patients who were subsequently readmitted scored well (80%, 85%, and 85%), and none of the readmissions were due to a failure of home-care management. Telephone assessment 48 hours after discharge can be used to document home-care and discharge-planning outcomes for high-risk infants and toddlers.

Isolation and reconstitution of the RNA replicase of the cytoplasmic polyhedrosis virus of silkworm,Bombyx mori.

After irradiation of the virus particles of CPV, the RNA replicase associated with the virion was isolated in the form of a genome-replicase complex with DEAE-Sephadex A-25 chromatography. This complex was then treated with Triton X-100 and purified by phosphocellulose column chromatography. The RNA replicase reconstituted with the doublestranded RNA of CPV showed both the enzyme activity of RNA polymerase and methyltransferase. The single-stranded RNA could not serve as the template for the RNA replicase. The role of the RNA replicase of CPV is discussed.