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Biomedical subjects

O Dagan

Publications and source records attributed to O Dagan.

34 records · Page 2Linked to original sources

[First year's experience of the Post-Operative Cardiac Care Unit, Schneider Children's Medical Center].

In the past 10 years there has been a growing preference for early, complete correction of congenital heart disease. The first year of operation of this cardiac unit is described. 216 operations were performed: 15% in the neonatal age group and 35% in the newborn to 1-year-old groups; 2% were palliative procedures. Mortality was 4.9%. Average stay in the ICU was 3.2 days, with a median of 2.25. Average length of ventilation was 35 hours, with a median of 17.5. Complications were: diaphragm paralysis in 13 (6%), 2/3 of which were recurrent operations; in 2 patients (0.9%) we had to plicate the diaphragm. There was severe neurological damage in 2 which deteriorated to brain death in 1. There was peripheral, reversible neurological damage in 4 (1.8%), and acute renal failure in 3%, with half of them requiring dialysis. 75% of these children died and there was superficial infection in 4.1%, deep wound infection in 1.3%, bacteremia in 4.1%, superior vena cava syndrome in 3 (1.3%) and chylothorax in 2 of them (0.9%). 1 patient (0.45%) required a ventricle-peritoneal shunt after acute viral meningitis. We are encouraged by our results to offer early complete correction to all children with congenital heart disease.

Child↗

Chest reconstruction in asphyxiating thoracic dystrophy.

Asphyxiating thoracic dystrophy is a rare, complex malformation with a broad spectrum of clinical expression. Surgery is indicated only in severe cases in which failure to intervene will result in progressive pulmonary damage and eventual death. Conventional surgical techniques for expanding the thoracic cage diameter by sternotomy and the insertion of a metal prosthesis for anterior chest wall stability usually provide these patients with the time needed for thoracic cage growth. However, some of the most severe cases may require a two-stage approach. Hence, management should be directed toward resolving immediate ventilatory problems and minimizing secondary damage to the lungs caused by prolonged ventilatory support.

Asphyxia Neonatorum↗

MRI in acute poliomyelitis.

MRI can be used in the diagnosis of anterior horn infection and for assessing the extent of disease. There are no specific MRI signs to differentiate between the various possible pathogens. This is demonstrated in the present case of poliomyelitis, in which MRI of the spine played an important role in establishing the diagnosis.

Anterior Horn Cells↗

A comparison between continuous central venous pressure measurement from right atrium and abdominal vena cava or common iliac vein.

OBJECTIVE: To determine the accuracy of mean continuous central venous pressure (CVP) measurements in the abdominal vena cava. DESIGN: We simultaneously measured the CVP at the superior vena cava or right atrium and at the abdominal vena cava or common iliac vein. The study was conducted at the pediatric intensive care unit of a major university-affiliated medical center. PATIENTS: Nine patients, aged 6 months to 14 years, were included in our study. MEASUREMENTS AND RESULTS: Eleven continuous recordings of 12 to 68 min were taken, eight of them while the children were mechanically ventilated. Mean overall CVP ranged from 3 to 30 mmHg. A total of 519 simultaneous recordings were made, of which 515 (99.2%) were within the accepted limits of agreement of +/- 2 mmHg: 301 (58%) with delta CVP of +/- 0 mmHg, 189 (36,4%) with delta CVP of +/- 1 mmHg, and 25 (4.8%) with delta CVP of +/- 2 mmHg. The mean pressure difference was -0.22 +/- 1.52 mmHg. Accuracy was maintained within all ranges of CVP (3-10, 11-20, and 21-30 mmHg) and was not influenced by mechanical ventilation or abdominal fluid collection. CONCLUSION: In children with no obstruction of blood flow from the abdominal vena cava to the right atrium, the pressure in the abdominal vena cava or common iliac vein accurately reflects the pressure in the right atrium.

Adolescent↗

Radiologic features of gastric outlet obstruction in infants after long-term prostaglandin administration.

Long-term prostaglandin (PG) therapy has recently been associated with gastric mucosal hyperplasia. We reviewed the clinical and radiologic (especially sonographic) records of eight patients with complex congenital heart disease who were on PG therapy. Feeding problems, vomiting, and abdominal distension were present in six patients. Barium meal revealed antral narrowing in three patients, suggestive of hypertrophic pyloric stenosis in two. Sonography showed a variable degree of increased gastric mucosal lobulation often accompanied by a marked polypoid or lobular appearance. Cortical hyperostosis related to PG therapy was seen in three patients. PG-associated gastric mucosal hyperplasia can cause feeding problems and pronounced gastric lobulation.

Alprostadil↗

Pyoderma gangrenosum and sterile multifocal osteomyelitis preceding the appearance of Takayasu arteritis.

A 9-month-old infant had pyoderma gangrenosum (PG) and sterile osteomyelitis. Three years later the patient developed Takayasu arteritis (TA). Sterile osteomyelitis was reported in approximately 30 patients with different skin lesions, but never together with pyoderma gangrenosum. The association of PG and TA has been reported rarely, and then mainly in adults or in children over age 9 years. This rare association should alert physicians with a case of infantile PG of unknown etiology to consider the possible diagnosis of TA.

Dose-Response Relationship, Drug↗

Effects of extracorporeal membrane oxygenation on morphine pharmacokinetics in infants.

OBJECTIVES: To study the effect of extracorporeal membrane oxygenation (ECMO) on the pharmacokinetics of morphine in infants. DESIGN: A prospective, comparative study of morphine pharmacokinetics during and after ECMO. SETTING: The pediatric intensive care unit at a children's hospital. PATIENTS: Seven infants, aged 1 day to 12 months, requiring ECMO. INTERVENTION: Infusion of morphine. MEASUREMENT AND MAIN RESULTS: Steady-state concentrations of morphine were used to generate a morphine clearance rate. Plasma clearance rate of morphine increased from 0.574 +/- 0.3 L/kg/hr to 1.058 +/- 0.727 L/kg/hr after discontinuation of ECMO (p < .01). Two infants experienced a clinical picture consistent with opioid withdrawal. CONCLUSION: Infants requiring morphine after ECMO may require higher dose rates to maintain adequate sedation.

Extracorporeal Membrane Oxygenation↗

Morphine pharmacokinetics in children following cardiac surgery: effects of disease and inotropic support.

The pharmacokinetics of morphine have not been previously studied in children following cardiac surgery for tetralogy of Fallot (TOF) or transposition of the great arteries (TGA). Morphine steady-state pharmacokinetics were studied in 21 children undergoing repair of TOF, TGA, or atrio-ventricular septal defects (AVSD). Children with TOF or TGA had increased right-sided pressures with no differences between the groups. Children with TOF had significantly faster clearance rates of morphine (1.39 +/- 0.37 L/kg/h) than children following the Fontan procedure (0.86 +/- 0.31 L/kg/h, P < 0.01). When stratifying children by their postsurgical needs for inotropic support, those needing epinephrine, dopamine, or dobutamine at more than 10 micrograms/kg/min had significantly slower clearance rates (0.73 +/- 0.3 L/kg/h) when compared to the rest of the patients (1.5 +/- 0.41 L/kg/h, P < 0.05). Because most children needing inotropic support underwent the Fontan procedure, it is conceivable that their cardiovascular status had a major impact on morphine metabolism. These results suggest a 50% reduction in morphine dosage in children requiring inotropic support following cardiac surgery.

Blood Pressure↗

Preliminary studies of the effects of extracorporeal membrane oxygenator on the disposition of common pediatric drugs.

There is an increased use of extracorporeal membrane oxygenation (ECMO) in the last 15 years for critically ill neonates. While receiving ECMO therapy, the critically ill infant needs various medications. We performed an in vitro study to evaluate the potential effect of the membrane oxygenator on drug extraction. Two closed ECMO circuits were set up at rates of 320 ml/min. One circuit was new and the other was used clinically for 5 days. Morphine at 8 ng/ml, gentamicin 10 micrograms/ml, vancomycin 40 micrograms/ml, phenobarbital 20 micrograms/ml, and phenytoin 20 micrograms/ml were injected into the circuit at 1-h intervals. Blood samples were drawn from the circuit at 10, 30, 60, and 240 minutes after injection. In the new circuit, drugs were eliminated as follows: vancomycin 36%, gentamicin 10%, phenobarbital 17%, phenytoin 43%, morphine 36%. In the used system, levels fell to a much smaller extent: vancomycin 11%, phenobarbital 6%, gentamicin 0%, phenytoin 0%, and morphine 16%. In a child receiving 20 micrograms/kg/h infusion of morphine, steady-state concentrations of 68.2 ng/ml fell to 11.6 ng/ml after changing the membrane. Our data indicate that the ECMO is associated with lowering of the concentrations of commonly used medications and that this process may depend partially on how new the membrane is. Before these changes may lead to new dosing guidelines for small children receiving ECMO, more experiments with new and used systems are warranted, as well as with different types of ECMO.

Anti-Bacterial Agents↗

Prostaglandin-induced antral hyperplasia in neonates: clinical experience and dose-response characteristics.

Antral hyperplasia (AH) induced by prostaglandins (PG) has been described by us recently in 5 infants with cyanotic heart disease receiving the drug. The purpose of the present study was to analyze 14 infants diagnosed as having AH either sonographically or pathologically in an attempt to characterize the dose-response characteristics of this adverse drug reaction, its clinical course and its optimal management. Infants with AH exhibiting large gastric aspirates have received a significantly lower cumulative dose (1,633 +/- 1,266 micrograms/kg) than those presented also with a palpable mass (3,458 +/- 1,703 micrograms/kg), (p < 0.01). While in general there is a dose-related clinical toxicity, variability in the location of the hyperplasia can explain cases of no apparent obstruction despite large cumulative doses of PG. In asymptomatic cases the antral hyperplasia, although visualized, it did not result in gastric outlet obstruction. In all cases followed by us to date, discontinuation of the PG has resulted in resolution of the clinical and sonographic findings. Nasojejunal tube was successfully attempted in several cases, preventing surgery in these very-high-risk infants.

Dose-Response Relationship, Drug↗

Gastric-outlet obstruction induced by prostaglandin therapy in neonates.

BACKGROUND: An infusion of prostaglandin E1 is widely used to maintain patency of the ductus arteriosus in neonates with congenital heart disease. After gastric-outlet obstruction was recognized in several infants who received prostaglandin E1, we studied the association between the drug and this complication. METHODS: We evaluated all neonates who received prostaglandin E1 in our hospital between October 1, 1989, and September 30, 1991, for clinical, radiologic, or pathological evidence of acute gastric-outlet obstruction. RESULTS: Of the 74 neonates evaluated, 65 had no signs of gastric obstruction and were considered normal; 5 had clinical and radiologic or pathological evidence of gastric obstruction consistent with the presence of antral mucosal hyperplasia. The remaining four neonates had clinical signs of gastric obstruction, but no radiologic or pathological examinations were performed. The 5 neonates with antral hyperplasia had received prostaglandin E1 for longer periods (mean [+/- SD] duration, 569 +/- 341 hours) than the 65 normal neonates (54 +/- 58 hours, P less than 0.001) or the 4 neonates with clinical signs of gastric obstruction (119 +/- 60 hours, P less than 0.05). The cumulative dose of prostaglandin E1 was higher in the neonates with antral hyperplasia (2982 +/- 1392 micrograms per kilogram of body weight) than in the normal neonates (279 +/- 270 micrograms per kilogram, P less than 0.001) or the neonates with signs of gastric obstruction (528 +/- 306 micrograms per kilogram, P less than 0.01). In two neonates with antral hyperplasia, the cessation of therapy lessened the gastric-outlet obstruction. CONCLUSIONS: The administration of prostaglandin E1 to neonates can cause gastric-outlet obstruction due to antral hyperplasia. Neonates who receive prostaglandin E1 at recommended doses for more than 120 hours should be closely monitored for evidence of antral hyperplasia.

Alprostadil↗

Computerized algorithms and pediatricians' management of common problems in a community clinic.

In 1987, a microcomputer clinical algorithm (CA) system for constructing and using CAs for patient care was designed and implemented for six common primary care pediatrics problems. Six community clinic pediatricians agreed to use the system for several months. Length of patient's visit, completeness of data collection, antibiotic use, and appropriateness of clinical plan were measured before the computers were introduced (without CAs) and after the computers were introduced (both with and without CAs). All performance measures improved after the introduction of CAs. However, CA implementation had to be discontinued after five weeks because the CAs were too tedious for the physicians to follow during routine care. The authors conclude that CAs cannot be successfully sustained with physicians for common problems, even though their design and use can significantly improve the process of care.

Adolescent↗

Ciprofloxacin inhibits human hematopoietic cell growth: synergism with tumor necrosis factor and interferon.

The cytokines tumor necrosis factor (TNF) and interferon (IFN) induce antiproliferative and cytotoxic activity in a variety of cell types. Ciprofloxacin (CFN)--a new fluoroquinolone antibiotic--has also been described, at high concentrations, to suppress hematopoietic cell growth and to affect cytokine production. This study examines the possible relationship between TNF alpha and IFN gamma, as components of host defense mechanisms, and CFN. To investigate the effect of CFN, either alone or combined with TNF or IFN, on normal human hematopoiesis, we examined in vitro changes in hematopoietic progenitor cell growth. We also studied the effect of CFN on human cytokine production by determining TNF, IFN, and colony-stimulating factor (CSF) production by human mononuclear leukocytes (MNC). Granulocyte and monocyte colony formation (granulocyte-macrophage colony-forming cells, GM-CFC) as well as erythroid burst formation (erythroid burst-forming units, BFU-E) were inhibited only by high nontherapeutic levels of CFN. Lower CFN concentrations, however, were inhibitory in the presence of low, noninhibitory concentrations of human recombinant (r)IFN gamma or rTNF alpha. CFN induced a striking dose-dependent increase in IFN gamma production and a decrease in CSF production by mitogen-stimulated MNC. No effect was observed, however, on TNF production by stimulated MNC. The synergistic inhibition of hematopoietic progenitor cell proliferation, achieved by combining low doses of CFN and of antiproliferative cytokines, may explain the occasional case of leukopenia or anemia observed in infected patients receiving CFN. This effect may also indicate the applicability of such a combination against malignant cell growth.

Cell Division↗

Effect of anesthesia on the immune system: suppression of the immunogenic capacity of macrophages and of lymphocyte transformation.

Experiments were carried out aimed at investigating the effects of anesthesia without surgery on certain functional components of the immune system. We observed that the immunogenic antigen-presenting capacity of mouse peritoneal macrophages was significantly reduced one week post-anesthesia, with either injected or inhaled anesthetic drugs. On the other hand, an augmentation of the phagocytic activities of these macrophages was manifested. Hence, the impaired immunogenic potency could not be attributed to a reduced antigen uptake. Lymphocyte transformations, i.e., response to PHA and Con A were suppressed, whereas the response to LPS was augmented.

Anesthesia↗

Human sphingolipid activator protein-1 and sphingolipid activator protein-2 are encoded by the same gene.

Mixed oligonucleotide primers complementary to the translation product of the sphingolipid activator protein (SAP)-2 were used to generate a 144-base pair (bp) complementary DNA (cDNA). This cDNA probe was used to isolate a 2,649-nucleotide-long cDNA that was sequenced and found to contain coding sequences for two known activators of lysosomal enzymes, namely, the sphingolipid activator protein (SAP)-1 and SAP-2. The cDNA contains an open reading frame of 1,482 nucleotides and 1,167 nucleotides of 3'-nontranslated region, followed by a stretch of 24 residues of adenylic acid. At 20 nucleotides upstream from the poly(A) tail there is a consensus AATAAA polyadenylation signal that is preceded by another potential polyadenylation signal. The cDNA, designed SAP-1/SAP-2 cDNA, hybridizes with two human mRNA species of approximately 3 kb in length, which most probably arise from polyadenylation at different sites. There are higher amounts of steady-state RNA levels of the SAP-1/SAP-2 mRNA in skin fibroblasts in comparison to B cells. The steady-state SAP-1/SAP-2 mRNA levels in Gaucher B cells are higher than in their normal counterparts. There is one human SAP-1/SAP-2 gene that has been cloned and is localized on two approximately 5 kb BamHI fragments.

Amino Acid Sequence↗

Thiamine deficiency in children with congenital heart disease before and after corrective surgery.

BACKGROUND: Malnutrition is common in children with congenital heart disease, while thiamine deficiency (TD) is common in malnutrition, in critically ill children, and in adults with congestive heart failure treated with loop diuretics. Our goal was to determine whether children with congenital heart disease had TD and whether treatment with loop diuretics is related to TD in these patients. METHODS: Twelve children with ventricular septal defect (VSD) treated with furosemide, and 10 children with tetralogy of Fallot (TOF) referred for corrective surgery were consecutively enrolled into a prospective study. Data were collected 24 hours before surgery and 5 days after surgery for nutrition evaluation, medications used, anthropometric measurements, and laboratory markers of malnutrition. Thiamine and pyridoxine deficiencies were evaluated using activated enzyme assays. RESULTS: Seven children (32% of patients) did not meet the recommended daily allowance (RDA) for calories and 18% of patients did not meet the RDA for thiamine intake. Anthropometric measurements were low in both groups, more so in those with VSD, although the difference did not reach statistical significance. Overall, 18% (1/12 with VSD and 3/10 with TOF) of children with congenital heart disease had thiamine deficiency before surgery. Three of the four children with TD had adequate intake of thiamine. Six children (27%) had TD 5 days postsurgery (3 children with VSD and 3 children with TOF). CONCLUSIONS: TD is common in children with congenital heart disease (CHD) referred for corrective surgery both before and after surgery. Our results suggest that neither diuretic treatment nor malnutrition can fully explain the development of TD in these children.

Anthropometry↗