THE ROLE GENE EXPRESSION OF PD-1 AND PD-L1 IN NEWELY DIAGNOSED AND TREATED PATIENTS WITH ACUTE MYELOID LEUKEMIA.

Acute myeloid leukemia (AML) is a myeloid malignancy in which hematopoietic progenitor cells are blocked early in development, causing the development of abnormal cells. The most common type of adult leukemia is AML. The most significant developments in the treatment of cancer over the past ten years have been made possible by programmed death protein 1 and anti-programmed ligand 1 (PD-L1) which are examples of immune checkpoint (IC) inhibitors. This study involved two groups: the patient group, consisting of 80 samples, and the control group, consisting of 40 samples. The participants' age range was 18-85 years, and the samples were obtained from at Baghdad Teaching Hospital - Medical City in Baghdad, Iraq. Patients were categorized into the FAB according to AML Subtype including the FAB (M3), FAB (non- M3). The age group did not show a significant difference (P≥0.05) in patients with AML compared to the control group. Furthermore, The mean age of patients was 42.83 years, and control age mean 40.4 years. The aim of this study was to evaluate the effect of Acute myeloid leukemia on the levels of certain immunological parameters. The results of the QRT-PCR technique for immunological tests showed the PD-1 expression in patients with AML statistically has high significant difference (P≤0.0001). and the PD-L1 expression also had a highly significant difference (P<0.0001) in PD-1, PD-L1 genes, compared to the control group. These findings suggest that AML infection may influence immunological responses.

Inherited thrombophilia in mechanical valve malfunction.

Mechanical valve malfunction due to thrombosis is an important and life-threatening complication in patients with prosthetic valves. Our study was performed to determine the prevalence of thrombophilia genes among patients with acute thrombosis of the mechanical pulmonary valves despite acceptable anticoagulation levels. In this cross-sectional comparative study thirthy two consecutive patients with acute thrombosis of pulmonary mechanical valve who had international normalized ratio (INR) levels for prothrombin time of at least 2 at the time of presentation and in the preceding three months were enrolled and the prevalence rates of thrombophilia factor genes among them was assessed. The results showed that 24 patients (75%) had thrombophilia gene mutations. The affected patients had mutations in one gene in 37.5% of cases, two genes in 31.3%, and three genes in 6.3%. Prevalence rate of Factor V Leiden (FVL), prothrombin (PTH), Plasminogen activator inhibitor-1 (PAI-I), Methylenetetrahydrofolate Reductase (MTHFR), and endothelial protein C receptor (EPCR) gene mutations was 3.1%, 6.3%, 50%, 37.5%, and 25%, respectively. In our study the prevalence of thrombophilia factor gene mutations of patients with acute thrombosis of pulmonary valve was higher than that reported in the general population.

Spatial accessibility of the population to urban health centres in Kermanshah, Islamic Republic of Iran: a geographic information systems analysis.

Geographic information systems (GIS) analysis has not been widely used in underdeveloped countries to ensure that vulnerable populations have accessibility to primary health-care services. This study applied GIS methods to analyse the spatial accessibility to urban primary-care centres of the population in Kermanshah city, Islamic Republic of Iran, by age and sex groups. In a descriptive-analytical study over 3 time periods, network analysis, mean centre and standard distance methods were applied using ArcGIS 9.3. The analysis was based on a standard radius of 750 m distance from health centres, walking speed of 1 m/s and desired access time to health centres of 12.5 mins. The proportion of the population with inadequate geographical access to health centres rose from 47.3% in 1997 to 58.4% in 2012. The mean centre and standard distance mapping showed that the spatial distribution of health centres in Kermanshah needed to be adjusted to changes in population distribution.

Comparison of microtensile bond strength of a resin composite to enamel conditioned by acid etching and Er,Cr:YSGG laser in human primary teeth.

AIM: This study was designed to compare the bond strength of composite resin restorations on the buccal surface of primary human canine after conditioning by conventional acid etching and Er,Cr:YSGG laser. METHODS: Twenty sound primary canines were cut buccolingually into two halves and each half was randomly placed in Er,Cr:YSGG laser or acid etch group. The samples in the acid etch group were etched with 37% phosphoric acid for 30 s. The samples in the laser group were prepared by Er,Cr:YSGG laser. The G6-Tips and 600 µm diameter were used with a 1.5 W of power output, pulse duration of 140 µs and repetition rate of 20 Hz. The bonding agent was applied on the buccal surface of each sample and layers of resin composite were placed. The samples' bond strengths were evaluated by a microtensile test instrument. RESULTS: The mean of microtensile bond strength was 18.55±6.41 in the laser group and 24.62±5.56 in acid etch group. Microtensile bond strength achieved by laser conditioning was significantly lower than microtensile bond strength achieved by the conventional acid etching. Statistics To compare the results between the acid etch and laser group, the paired t test was performed (p value<0.001). CONCLUSION: Conditioning enamel in primary teeth by Er,Cr:YSGG laser, cannot be used as an alternative method for acid etching and cannot substitute this conventional method.

Spatial accessibility of the population to urban health centres in Kermanshah, Islamic Republic of Iran:a geographic information systems analysis

إن تحليل نظم المعلومات الجغرافية لم يستخدم على نطاق واسع في البلدان النامية للتأكد من إمكانية وصول الفئات الضعيفة من السكان إلى خدمات الرعاية الصحية الأولية. إن هذه الدراسة طبقت طرق نظم المعلومات الجغرافية لتحليل إمكانية الوصول إلى مراكز الرعاية الصحية الأولية الحضرية بالنسبة للسكان الذين يعيشون في مدينة كرمنشاه بجمهورية إيران الإسلامية، وذلك بحسب الفئات العمرية والجنس. ففي دراسة وصفية تحليلية على مدى 3 فترات زمنية تم تطبيق طريقة تحليل الشبكات وطريقة المركز الوسطي وطريقة المسافة القياسية باستخدام نظام ArcGIS 9.3.وكان التحليل يستند إلى دائرة ذات نصف قطر قياسي يبعد 750 متراً عن المراكز الصحية، وسرعة مشي تبلغ 1 متراً واحداً لكل ثانية، وزمن وصول منشود إلى المراكز الصحية مقداره 12.5 دقيقة. إن نسبة السكان الذين يصعب عليهم الوصول الجغرافي إلى المراكز الصحية ارتفعت من 47.3% في عام 1997 إلى 58.4% في عام 2012.ولقد أظهر رسم خرائط المركز الوسطي والمسافة القياسية أن التوزيع المكاني للمراكز الصحية في كرمنشاه يحتاج إلى تعديل يتناسب مع التغيرات في توزيع السكان

Geographic information systems (GIS) analysis has not been widely used in underdeveloped countries to ensure that vulnerable populations have accessibility to primary health-care services. This study applied GIS methods to analyse the spatial accessibility to urban primary-care centres of the population in Kermanshah city, Islamic Republic of Iran, by age and sex groups. In a descriptive-analytical study over 3 time periods, network analysis, mean centre and standard distance methods were applied using ArcGIS 9.3. The analysis was based on a standard radius of 750 m distance from health centres, walking speed of 1 m/s and desired access time to health centres of 12.5 mins. The proportion of the population with inadequate geographical access to health centres rose from 47.3% in 1997 to 58.4% in 2012. The mean centre and standard distance mapping showed that the spatial distribution of health centres in Kermanshah needed to be adjusted to changes in population distribution.

L'analyse des systèmes d'information géographique n'a pas été très utilisée dans les pays en développement pour garantir que les populations vulnérables ont accès aux services de soins de santé primaires.La présente étude a appliqué des méthodes des systèmes d'information géographique pour analyser l'accessibilitéspatiale aux centres de soins de santé primaires urbains pour la population de la ville de Kermanshah (République islamique d'Iran) par tranche d'âge et par sexe. Dans une étude analytique-descriptive sur trois périodes, une analyse des réseaux et des méthodes de mesure des distances moyenne et standard jusqu'aux centres ont été appliquées à l'aide du logiciel d'information géographique ArcGIS 9.3. L'analyse reposait sur un rayon standard de 750 mètres de distance à partir des centres de soins, à une vitesse de marche d'un mètre par seconde et untemps d'accès souhaité aux centres de soins de santé de 12,5 minutes. La proportion de la population ayant un accès géographique inadéquat aux centres de soins a augmenté, passant de 47,3 % en 1997 à 58,4 % en 2012. Lacartographie de la distance moyenne et standard jusqu'aux centres a révélé que la répartition spatiale des centres de soins de santé à Kermanshah devait être ajustée aux changements dans la répartition de la population.

Evidence of a critical period of airway instability during central apneas in preterm infants.

The timing and magnitude of airway narrowing in central apneas is unknown. We have developed a method of apnea classification that relies on the transmission of cardiac airflow oscillation to indicate airway patency. Using a theoretical model, we showed that the amplitude of the cardiac airflow oscillation is proportional to airway diameter for small lumens. While in the majority of central apneas the amplitude of the cardiac airflow oscillation remains nearly constant, in a subset of events the waveform decreases with time, suggesting airway narrowing. We hypothesized that this is not a random occurrence but reflects a critical period of airway instability during central apnea. To test this hypothesis we studied 41 preterm infants. Of 4,456 central apneas, 585 had a decrease in the amplitude of the cardiac oscillation. The amplitude of the cardiac airflow oscillation during an apnea was recorded to provide a dynamic measure of changes in airway diameter with time. To allow for comparisons between patients the amplitude of each cardiac airflow oscillation was expressed as a proportion of the maximum amplitude observed in each infant. We then compared the amplitude at multiple successive 0.5 s intervals with the amplitude of the cardiac airflow oscillation observed at the apnea outset using ANOVA. We found a significant decrease in cardiac airflow oscillation after only 1 s irrespective of the apnea duration (3 to 16 s). We conclude that airway narrowing during central apnea is not a random occurrence but appears shortly after the onset of the apnea. We speculate that the phenomenon is secondary to passive airway relaxation.

Prolonged apnea in the preterm infant is not a random event.

We tested the hypothesis that in preterm infants, prolonged apneas (apneas > or = 20 sec) are not random events but are preceded by frequent and progressively longer respiratory pauses associated with changes in ventilatory variables. We studied 36 preterm infants with apnea [birth weight 1190 +/- 60 g (mean +/- SEM), study weight 1300 +/- 60 g, gestational age 28 +/- 1 weeks, and postnatal age 23 +/- 2 days]. A nosepiece with a flow-through system was used to measure ventilation and alveolar gases. Throughout the monitoring period for each infant we established 10-min moving "window of observation" followed by a 1-min interval examined for the detection of a prolonged apnea. Within the 10-min window, three variables were defined: the number of apneic episodes, the maximum length of a single apneic episode, and the total duration of apneic time. During the following minute (eleventh) the presence or absence of a prolonged apnea was determined. Chi-square test for a linear-trend in the rate of prolonged apnea and multiple logistic regression analysis showed that the relative risk of a prolonged apnea increases significantly from preceding periods without apnea to preceding periods containing the potential predictors of prolonged apnea. The strongest predictor was total duration of apneic time in the previous 10 min. When the 1 min before prolonged apnea was compared with the 1 min of similar sleep state not having prolonged apnea, minute ventilation decreased, primarily due to a decrease in respiratory frequency. Oxygen saturation decreased and alveolar PCO2 did not change. These findings suggest that prolonged apnea is not a random event but is preceded by a disturbance of the respiratory control system characterized by (1) frequent apneas of progressive duration, (2) decrease in respiratory minute volume and frequency, and (3) decreased O2 saturation.

Preliminary characterization of a placental factor inhibiting breathing in fetal sheep.

Previous studies have revealed a placental extract that inhibits breathing in fetal sheep. In the present study of 29 chronically instrumented sheep at 132+/-1 days of gestation, infusion of the 1-10 kDa extract inhibited breathing in 76% of the experiments whereas Krebs' solution inhibited it in 24%. It retained this activity after 6 months of freezing, after lyophilization, and upon lowering the pH during purification from 8.0 to 4.0, but it inhibited breathing in only 35% when the pH was lowered to 2.0. A significant dose-dependent effect was observed from a 16-fold dilution to a 4-fold concentration. Treatment of the extract with proteinase K or boiling reduced the activity to 30% or 26% inhibition, respectively. The activity was not adsorbed to an ion-exchange column at pH 7.0 or 8.0, but it was at pH 9.0 and it eluted with increasing NaCl concentrations. On a polyacrylamide gel the activity was eluted at a K(av) of 0.66 (82% inhibition), corresponding to between 2.5 and 4.5 kDa. These findings suggest that a peptide produced by the placenta, with a molecular mass between 2.5 and 4.5 kDa, inhibits fetal breathing.

Use of tolazoline to counteract vasospasm in peripheral arterial catheters in neonates.

Arterial access for blood sampling and continuous blood pressure monitoring is the cornerstone of modern neonatal intensive care. Although umbilical arterial catheters have traditionally been utilized for arterial access, they are associated with potentially devastating complications. Consequently, there has been an increase in the use of peripheral arterial catheters. Unfortunately, these catheters have a limited useful lifespan secondary to vasospasm, intimal damage and/or thrombus formation. In this report, we describe the use of tolazoline (0.02 to 0.2 mg/kg/h) to counteract local arterial vasospasm in five critically ill neonates, where arterial access was vital for care but difficult to maintain.

Spinal cord infarct after arterial switch associated with an umbilical artery catheter.

Paraplegia after an open heart operation in a neonate is a rare complication. We report a case of a infant in whom paraplegia developed after a successful arterial switch operation for transposition of the great arteries. The infant was monitored and resuscitated in the preoperative period with umbilical arterial and venous catheter tips located in the midthoracic region. He likely suffered a clinically silent thromboembolic event predisposing him to a localized hemorrhagic infarction during the repair.

Use of a magnified cardiac airflow oscillation to classify neonatal apnea.

Currently the classification of neonatal apnea relies upon an inference of airway closure based upon the presence of breathing efforts against such an obstruction. In this study we evaluate a new method of classification which utilizes the presence or absence of cardiac airflow oscillation to detect airway closure. Specifically, this evaluation consisted of an examination of the transmission characteristics of an artificially produced airflow oscillation through discrete airway narrowing in a model system; a confirmation that voluntary upper airway occlusion in adult volunteers uniformly induces complete loss of the oscillation; and a comparison of the cardiac oscillation method with the traditional method of apnea classification in a cohort of 4,309 apneas in 32 infants. We determined that the amplitude of the oscillation is negatively correlated with resistance (r = 0.97) and positively with the radius (r = 0.98) of narrowing in a model system, and that voluntary airway obstruction in adult subjects uniformly results in loss of transmitted cardiac oscillations. Moreover, although there was similarity in the frequency distribution of central, obstructive, and mixed apneas in our infants, there were statistically significantly greater obstructive events detected by the cardiac oscillation method. In addition, the cardiac oscillation method had the additional advantage of providing information regarding the timing of airway obstruction during apnea.

Low baseline oxygenation predisposes preterm infants to mixed apneas during inhalation of 100% oxygen.

We have shown previously that administration of 100% O2 to preterm infants induces an apnea which in about 20% of cases has an obstructive component. The obstruction occurred during the longer apneas. In the present study, we tested the hypothesis that the appearance of obstruction in longer apneas depends on the baseline oxygenation. Sixteen preterm infants were studied in quiet sleep (birthweight 1435 +/- 93 g [mean +/- SEM], study weight 1711 +/- 90 g, gestational age 30 +/- 1 weeks, and postnatal age 26 +/- 5 days) at various baseline oxygenations. A flow-through system was used to measure ventilation and alveolar gases. Respiratory efforts in the absence of flow were detected using chest and abdominal displacements or diaphragmatic electromyography. Each infant inhaled 15%, 21%, or 25% O2 for 5 minutes (control period) followed by 100% O, for 2 minutes. Baseline alveolar PO2, O2 saturation and transcutaneous PO2 increased during inhalation of 15%, 21%, and 25% O2, respectively. The immediate decrease in ventilation with 100% O2 was 52% on 15% O2, 20% on 21% O2, and 16% on 25% O2 (p < 0.001); this was associated with an apnea in all cases. The mean length of apneas during 100% O2 was 37 seconds on 15% O2, 19 seconds on 21%, and 11 seconds on 25% (p < 0.01). Twelve infants (75%) developed mixed obstructive apneas in response to 100% O2 when breathing 15% O2 during control period, three (19%) when breathing 21% O2, and none had mixed apnea when breathing 25% O2 during control period (p < 0.05). These findings suggest that lower baseline oxygenation predisposes to long mixed apneas. We speculate that the peripheral chemoreceptors, uniquely active in the small preterm infant with relatively low O2 tension, when suppressed by an increase in oxygen tension, trigger a central inhibition with loss of upper airway muscle tone. This is more pronounced when the baseline oxygen tension is lower, leading to more prolonged apnea and increased probability of obstruction.

Subarachnoid fluid collections: a cause of macrocrania in preterm infants.

We report the outcome of 12 very low birth weight infants with macrocrania caused by subarachnoid fluid collections. By the age of 15 to 18 months, head growth had stabilized along a curve above and parallel to the 95th percentile. No infant required neurosurgical intervention, nor was cerebral palsy or mental retardation diagnosed in any of the infants.

Screening for congenital adrenal hyperplasia: the Delfia Screening Test overestimates serum 17-hydroxyprogesterone in preterm infants.

OBJECTIVE: To compare 17-hydroxyprogesterone (17-OHP) levels measured by quantitative serum radioimmunoassay (RIA), including an extraction step, and by screening fluoroimmunoassay (FIA) on blood spots in preterm infants. METHODS: Subjects were 39 healthy infants born at less than 31 weeks' gestational age. Each infant had weekly blood sampling, and RIA and FIA were performed on each sample. RESULTS: Two hundred twenty-seven samples were taken at 28 to 41 weeks' postconceptional age. Mean +/- SD 17-OHP measured by RIA was 11.4 +/- 11.1 nmol/L (0.4 +/- 0.4 micrograms/dL), and decreased over time. Mean +/- SD 17-OHP measured by FIA was 38.96 +/- 37.3 nmol/L, greater than 17-OHP (RIA). Log(delta FIA-RIA) was inversely related to postconceptional age (R2 = .39). CONCLUSION: Screening FIA of blood spots overestimates levels of 17-OHP in preterm infants and should not be used to determine the likelihood of congenital adrenal hyperplasia in this population. We have abandoned FIA screening for congenital adrenal hyperplasia in infants weighing less than 1500 g.

Effect of baseline oxygenation on the ventilatory response to inhaled 100% oxygen in preterm infants.

We tested the hypothesis that the immediate (< 1 min) ventilatory response to 100% O2 in preterm infants, a test of peripheral chemoreceptor activity characterized by a decrease in ventilation due to apnea, is more pronounced at lower baseline O2 concentrations. We studied 12 healthy preterm infants [birth weight 1,425 +/- 103 (SE) g; study weight 1,670 +/- 93 g; gestational age 30 +/- 1 wk; postnatal age 27 +/- 7 days] during quiet sleep. The infants inhaled 15, 21, 25, 30, 35, 40, and 45% O2 for 5 min in a randomized manner (control period), followed by 100% O2 for 2 min, and then the same initial O2 concentration again for 2 min (recovery period). A nose piece and a flow-through system were used to measure ventilation. The immediate decrease in ventilation with 100% O2 was 46% on 15% O2, 24% on 21% O2, 11% on 25% O2, 8% on 30% O2, 12% on 35% O2, and 8% on 40% O2; there was no decrease on 45% O2 (P < 0.01). The corresponding mean duration of apnea was 29 s during 15% O2, 18 s during 21% O2, 8 s during 25% O2, 9 s during 30 and 35% O2, and 3 s during 40% O2; only one infant developed a 5-s apnea during 45% O2 (P < 0.001). The findings suggest that 1) the ventilatory decrease in response to 100% O2 is dependent on the baseline oxygenation, being more pronounced the lower the baseline O2 concentration; and 2) this ventilatory decrease is entirely related to more prolonged apneas observed with lower baseline O2 concentrations. We speculate that the peripheral chemoreceptors, being so active in the small preterm infant with relatively low arterial PO2, are highly susceptible to changes in PO2, and this makes them prone to irregular or periodic breathing, especially during sleep.