TALIJANSKI DOPRINOS TURSKOJ PEDIJATRIJI ZA OSMANSKOG CARSTVA

The Ottoman Empire maintained close relations with the neighbouring Italian city states in the 16th and 17th century. Yacub Pasha (1425-1481), personal physician of Mehmed II the Conqueror, was an Italian Jew who advanced to the title of pasha and vizier. Domenico Hierosolimitano (ca. 1552–1622), the third physician to Sultan Murad III, was a Jerusalemite rabbi. His book is an important source about everyday life and medical practice in Istanbul at the time. Nuh bin Abd al-Mennab (1627-1707), also of Italian stock, was the Chief Physician of the Ottoman Empire, who translated a pharmacopoeia into Turkish. In the same century, two Italians, Israel Conegliano (Conian) and Tobia Cohen became private physicians to leading Ottoman pashas and the Grand Vizier. A. Vuccino (1829-1893) and Antoine Calleja Pasha (1806-1893) taught at the Istanbul Medical School. Italy was a favoured country for medical education during the early period of Ottoman westernisation. Sanizade Mehmet Ataullah Efendi (1771-1826) translated the first medical book printed in the Ottoman Empire from Italian into Turkish. Mustafa Behcet Efendi (1774-1833), chief physician to the Sultan and the founder of the first western medical school in Turkey, translated several medical books from Italian into Turkish. The first printed pharmacopeia in the Ottoman Empire was also originally Italian In the 19th century, Edouard Ottoni and his son Giuseppe Ottoni were well-known military pharmacists, both under the name of Faik Pasha. Probably the most influential physician of Italian origin was Giovanni Battista Violi (1849-1928), who had practiced paediatrics in Turkey for more than fifty years. Violi was the founder of the first children’s hospital, the first vaccine institute, and the first paediatric journal in the Ottoman Empire.U XVI. i XVII. stoljeću Osmansko je Carstvo bilo u bliskim odnosima sa susjednim talijanskim gradovima-državama. Osobni liječnik Mehmeda II. Osvajača, Jakub Paša (1425.– 1481.), bio je talijanski Židov koji je napredovao do titule paše, a poslije i vezira. Domenico Hierosolimitano (oko 1552.–1622.), treći liječnik sultana Murada III., bio je jeruzalemski rabin. Njegova je knjiga važan izvor saznanja o svakodnevnom životu u Istanbulu, koja opisuje i medicinsku praksu toga vremena. Nuh bin Abd al-Mennab (1627.–1707.), također talijanskog podrijetla, bio je glavni liječnik Osmanskog Carstva, koji je farmakopeju preveo na turski. U istom su stoljeću dva Talijana, Israel Conegliano (Conian) i Tobia Cohen, postali osobni liječnici najvećih turskih paša i velikog vezira. A. Vuccino (1829.–1893.) i Antoine Calleja Paša (1806.–1893.) predavali su na Medicinskom fakultetu u Istanbulu. Kad se Osmansko Carstvo počelo okretati Zapadu, Italija je bila najomiljenije odredište za medicinsko obrazovanje. Sanizade Mehmed Ataulah Efendi (1771.–1826.) preveo je s talijanskoga prvi medicinski udžbenik tiskan u Osmanskom Carstvu. Mustafa Behcet Efendi (1774.–1833.), glavni sultanov liječnik i osnivač prvoga medicinskog fakulteta zapadnoga tipa u Turskoj, preveo je nekoliko medicinskih udžbenika s talijanskog na turski. Prva tiskana osmanska farmakopeja također je prevedena s talijanskog. U XIX. su se stoljeću Edouard Ottoni i njegov sin Giuseppe Ottoni, obojica pod imenom Faik Paša, proslavili kao vojni ljekarnici. Vjerojatno najutjecajniji liječnik talijanskog podrijetla bio je Giovanni Battista Violi (1849.–1928.) koji je u Turskoj više od pola stoljeća držao pedijatrijsku praksu te osnovao prvu pedijatrijsku bolnicu i imunološki zavod te prvi pedijatrijski časopis

Immune thrombocytopenia in the newborn

The leading cause of moderate or severe thrombocytopenia in otherwise healthy appearing neonates is immune thrombocytopenia. Immune thrombocytopenia in the fetus or newborn may result from platelet alloantibodies against paternal antigens inherited by the fetus (alloimmune thrombocytopenia) or platelet autoantibodies in the mother with immune thrombocytopenic purpura (ITP). Only 10% of human platelet antigen (HPA)-1a negative mothers who are exposed to HPA-1a positive fetal platelets during pregnancy develop HPA-1a alloantibodies, and 30% of fetuses/neonates will develop thrombocytopenia and 20% of these cases being severe. The most serious complication of severe fetal and neonatal alloimmune thrombocytopenia (FNAIT) is intracranial hemorrhage (ICH), which is detected in 10-20% of affected fetuses/neonates, with most cases occurring antenatally. ICH leads to neurological sequelae in 20%, and deaths in 5-10% cases. There is no evidence-based optimal treatment strategy. Platelet antibody titration in maternal plasma is not helpful for decision-making. The best indicator for current pregnancy is the outcome of the previous pregnancy. The risk of recurrence among subsequent HPA-positive sibling is close to 100% where the previous sibling was affected with antenatal intracranial ICH. The risk of ICH becomes higher with more severe and earlier onset in each subsequent pregnancy. Serial platelet counts should be obtained for the first 5-7 days of delivery to keep the platelet counts higher than 30,000/µL without active bleeding and higher that 50,000-100,000/µL with active bleeding. Intravenous immunoglobulin (IVIG) is not alternative to platelet transfusions, since platelet counts don’t rise before 24-48 h. In platelet- transfused patients, IVIG can be given to potentially prolong the survival of the incompatible platelets. ITP during pregnancy is not considered a serious risk of perinatal bleeding, but may cause a moderate thrombocytopenia in neonate. In mothers with ITP, the risk of thrombocytopenia is only 10%, with no more than 1% risk of in utero ICH

Surfactant therapy in late preterm infants

Late preterm (LPT) neonates are at a high risk for respiratory distress soon after birth due to respiratory distress syndrome (RDS), transient tachypnea of the newborn, persistent pulmonary hypertension, and pneumonia along with an increased need for surfactant replacement therapy, continuous positive airway pressure, and ventilator support when compared with the term neonates. In the past, studies on outcomes of infants with respiratory distress have primarily focused on extremely premature infants, leading to a gap in knowledge and understanding of the developmental biology and mechanism of pulmonary diseases in LPT neonates. Surfactant deficiency is the most frequent etiology of RDS in very preterm and moderately preterm infants, while cesarean section and lung infection play major roles in RDS development in LPT infants. The clinical presentation and the response to surfactant therapy in LPT infants may be different than that seen in very preterm infants. Incidence of pneumonia and occurrence of pneumothorax are significantly higher in LPT and term infants. High rates of pneumonia in these infants may result in direct injury to the type II alveolar cells of the lung with decreasing synthesis, release, and processing of surfactant. Increased permeability of the alveolar capillary membrane to both fluid and solutes is known to result in entry of plasma proteins into the alveolar hypophase, further inhibiting the surface properties of surfactant. However, the oxygenation index value do not change dramatically after ventilation or surfactant administration in LPT infants with RDS compared to very preterm infants. These finding may indicate a different pathogenesis of RDS in late preterm and term infants. In conclusion, surfactant therapy may be of significant benefit in LPT infants with serious respiratory failure secondary to a number of insults. However, optimal timing and dose of administration are not so clear in this group. Additional randomized, controlled studies and evidence-based guidelines are needed for optimal surfactant therapy in these infants.   Proceedings of the 9th International Workshop on Neonatology · Cagliari (Italy) · October 23rd-26th, 2013 · Learned lessons, changing practice and cutting-edge researc

Non-immune hydrops fetalis

Non-immune hydrops fetalis (NIHF) refers to hydrops in the absence of maternal circulating red-cell antibodies, and constitutes up to 90% of all described hydrops fetalis cases. One-third of hydropic fetuses are discovered incidentally during prenatal sonography in the first or second trimester of gestation. Although hydrops is a fetal condition, in many cases there are associated maternal findings, such as preeclampsia, polyhydramnios, and mirror syndrome (generalized maternal edema, that ‘mirrors’ the edema of the hydropic fetus and placenta). NIHF should be seen as a symptom or clinical phenotype rather than as a disorder, and considered as a non-specific, end-stage status of a wide variety of disorders. Numerous disorders including fetal disorders, maternal diseases (e.g., severe maternal anemia, diabetes and maternal indomethacin use) and placental/cord abnormalities have been associated with NIHF. Despite extensive investigations, the etiology on NIHF may remain unknown in 15% to 25% of patients, even after an autopsy has been performed. Chromosomal abnormalities are the cause of NIHF in 25-70% of the cases. Therefore, fetal or neonatal chromosome analysis is indicated in all cases of NIHF. Abnormalities of the cardiovascular system are responsible for as many as 40% of cases of NIHF. Thoracic abnormalities increase intrathoracic pressure and can obstruct venous return to the heart, leading to peripheral venous congestion, or they may obstruct the lymphatic duct, resulting in lymphedema. Fetal anemia accounts for 10-27% of hydrops. To evaluate the risk of fetal anemia, Doppler measurement of the middle cerebral artery peak systolic velocity should be performed in all hydropic fetuses after 16 weeks of gestation. Parvovirus B19 is the most common infectious agent associated with hydrops. Even in persistent severe anemia, the prognosis is generally good if the fetus is supported by intrauterine fetal transfusions. The development of hydrops in fetuses with a TORCH infection is a poor prognostic indicator. Although hypoproteinemia is frequently proposed as one of the causes of hydrops fetalis, recent studies show that hypoalbuminemia is unlikely to cause the initial development of hydrops. However, it seems to occur as a secondary effect in the cascade of hydrops, and might be the trigger for mild hydrops to evolve into severe hydrops. In addition, not all infants with hypoproteinemia become hydropic, and hydrops fetalis is uncommon in congenital nephrotic syndrome and congenital analbuminemia. In the pathogenesis, inherited metabolic disorders, especially lysosomal storage diseases, are more common than previously thought. Inherited metabolic disorders must be always thought when investigating cases of recurrent NIHF in the same family. It is very important to examine the placenta carefully in cases where hydrops or ascites are present at birth or detected by ultrasound, especially in the transient form. Even if a family does not agree to autopsy, placental examination may be done. Proceedings of the 10th International Workshop on Neonatology · Cagliari (Italy) · October 22nd-25th, 2014 · The last ten years, the next ten years in Neonatology Guest Editors: Vassilios Fanos, Michele Mussap, Gavino Faa, Apostolos Papageorgio

Eryngium kotschyi Boiss.’in izole rat ileum ve idrar kesesi düz kasında kastırıcı etkisi

Bu çalışmada, ülkemizdeki endemik bitkilerden Eryngium kotschyi Boiss.’in toprak altı (EKTA) ve toprak üstü (EKTU) kısımlarının izole sıçan ileum ve idrar kesesi kasında farmakolojik etkinliği araştırıldı. Bitki ekstrelerinin dokulardaki etkinliği tek, agonist (asetilkolin) ve antagonist (atropin, verapamil, oksibutinin-idrar kesesi, papaverin-ileum) varlığında ve kalsiyumsuz ortamda Ca 2+ uygulamaları ile birlikte değerlendirildi. Bitkinin her iki kısmı doku türü, ekstre dozu ve uygulama protokolüne bağlı değişiklik gösterecek şekilde kontraksiyon oluştururken; bu kasılmaların EKTU ve EKTA tek uygulamalarında doza bağımlı, kümülatif uygulamalarında ise dozdan bağımsız olduğu görüldü. Oluşan kasılmaların test edilen antagonistler ile değiştiği; dolayısıyla kontraktil etkinliğin kalsiyum iyonu ve kalsiyum kanallarının uyarılması gibi nonspesifik yolaklara özellikle bağlı olabileceği görüşüne varıldı.The pharmacological activity of the aerial (EKA) and root (EKR) parts of the endemic plant, Eryngium kotschyi Boiss., on rat isolated ileum and detrusor muscle was investigated. Plant extracts alone and with the presence of agonist (acethylcholine) and antagonist (atropin, verapamile, oxybutinine-detrusor muscle, and papaverine-ileum) drugs, along with Ca 2+ applications on calcium-free medium, were applied. Plant extracts induced contraction in ileum and detrusor muscle where the contractions were concentration dependant for EKA and EKR single dose applications in detrusor muscle and concentration-free contractions were observed in cumulative applications for both tissues. Aerial and root parts of Eryngium extracts induced contractions in dose, tissue and protocol dependent manner where the contractions were afected by the tested antagonists, which could be attributed to non-specific pathways including calcium ions and calcium channel stimulations

Comparison of different types of twin pregnancies in terms of obstetric and perinatal outcomes: association of vanished twins with methylenetetrahydrofolate reductase (MTHFR) polymorphism(s).

Vanished twin (VT) has been associated with poor perinatal outcomes. Our research aimed to investigate the outcomes of pregnancies with vanished twin and its possible association with methylenetetrahydrofolate reductase (MTHFR) polymorphisms

Development and validation of machine learning-based clinical decision support tool for identifying malnutrition in NICU patients

Abstract Hospitalized newborns have an increased risk of malnutrition and, especially preterm infants, often experience malnutrition-related extrauterine growth restriction (EUGR). The aim of this study was to predict the discharge weight and the presence of weight gain at discharge with machine learning (ML) algorithms. The demographic and clinical parameters were used to develop the models using fivefold cross-validation in the software-R with a neonatal nutritional screening tool (NNST). A total of 512 NICU patients were prospectively included in the study. Length of hospital stay (LOS), parenteral nutrition treatment (PN), postnatal age (PNA), surgery, and sodium were the most important variables in predicting the presence of weight gain at discharge with a random forest classification (AUROC:0.847). The AUROC of NNST-Plus, which was improved by adding LOS, PN, PNA, surgery, and sodium to NNST, increased by 16.5%. In addition, weight at admission, LOS, gestation-adjusted age at admission (> 40 weeks), sex, gestational age, birth weight, PNA, SGA, complications of labor and delivery, multiple birth, serum creatinine, and PN treatment were the most important variables in predicting discharge weight with an elastic net regression (R2 = 0.748). This is the first study on the early prediction of EUGR with promising clinical performance based on ML algorithms. It is estimated that the incidence of EUGR can be improved with the implementation of this ML-based web tool ( http://www.softmed.hacettepe.edu.tr/NEO-DEER/ ) in clinical practice

Lead and Mercury Levels in Preterm Infants Before and After Blood Transfusions.

Very low birth weight (VLBW) infants usually receive packed red blood cell unit (pRBC) transfusions. Heavy metal transfer via pRBCs is not widely discussed before. This study aimed to determine pre-/post-transfusion erythrocyte lead and mercury levels in infants and to correlate these levels to heavy metal concentrations in pRBCs. VLBW infants (n = 80), needing pRBC transfusion for the first time, were enrolled. Erythrocyte heavy metal levels were determined in pre-/post-transfusion blood samples and also in pRBC units. Mean lead and mercury levels in the pRBCs were found to be 16.3 ± 10.8 and 3.75 ± 3.23 μg/L, respectively. Of the infants, 69.7% received lead above reference dose. Erythrocyte lead levels increased significantly after transfusions (10.6 ± 10.3 vs. 13 ± 8.5, p  0.05). There was a significant correlation between mean difference of mercury levels after transfusion and amount of mercury delivered by pRBCs (r = 0.28). Infants can be subject to high levels of lead and mercury through pRBC transfusions

Congenital central nervous system anomalies

Objective: Our goal was to highlight the prenatal diagnosis and management of central nervous system (CNS) anomalies through sharing our clinic’s experience. Material and Methods: We evaluated prenatal findings and postnatal outcomes of neonates who had a CNS anomaly diagnosis in our clinic over a ten-year period. A total of 183 cases with various CNS anomalies were included in the study. Birth or termination preferences of mothers were recorded in all cases, and postnatal diagnosis concordance and prognosis after surgical procedures were evaluated in mothers who chose to continue the pregnancy. Results: The mean maternal age was 28.2±5.5 years, mean gravida was 2.2±1.3, and the mean gestational age at diagnosis was 30.5±5.5 weeks. Seventy-five out of 183 (41%) patients chose to terminate their pregnancy. Twenty babies (26.6%) in the termination of pregnancy group had additional anomalies. One hundred eight patients gave birth at our institution. The mean birth weight was 3060±647.5 g, the mean gestational week at delivery was 37.9±1.7 weeks, and mean APGAR score (5th minute) was 8.8±2.3. Four neonates died on the postpartum first day. The postnatal diagnosis of 60 of the 108 (55.5%) patients who gave birth was concordant with the prenatal diagnosis, and 32 of the 108 (29.6%) babies underwent surgical interventions. Conclusion: CNS anomalies have a broad spectrum and variable prognoses. This study highlights the limitations of prenatal diagnoses, and the need for parents to have this information in order to determine the course of their pregnancy and prepare themselves for the postnatal challenging treatment/rehabilitation process.PubMedWoSScopu

Why Infants with Some Inherited Metabolic Diseases do not Develop Neonatal Indirect Hyperbilirubinemia ? An Overlooked Detail

Aim: Although indirect hyperbilirubinemia is the most common neonatal problem in term newborns, it is rarely observed in newborns with some inherited metabolic diseases. Therefore, we aimed to compare the frequency of indirect hyperbilirubinemia in newborns with these diagnoses and compare them with healthy newborns. Materials and Methods: In the study group, term newborns with inherited metabolic diseases characterized by metabolic acidosis and/or hyperammonemia were included retrospectively and prospectively between January 1st, 2001, and December 31st, 2014. Healthy-term newborn infants were prospectively included in the control group. Results: In the study group (n=106), 63.2% of the patients had organic acidemia, 20.8% urea cycle disorders, 4.7% mitochondrial diseases, 5.7% fatty acid oxidation disorders, and 5.7% other diseases, while the control group included 126 healthy term newborns. Mean serum indirect bilirubin levels were significantly lower in the study group compared to the control group (5.8±5.4 mg/dL vs 13.9±4.1 mg/dL, p0.05). Conclusion: This was the first epidemiological study aiming to determine a very low incidence of neonatal jaundice in newborns with inherited metabolic diseases characterized by metabolic acidosis and/or hyperammonemia. The exact pathophysiological mechanism of this strikingly low incidence of indirect hyperbilirubinaemia in these newborns should be investigated with prospective biochemical, enzymatic, molecular, and genetic studies