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Biomedical subjects

I R Makhoul

Publications and source records attributed to I R Makhoul.

At least 19 recordsLinked to original sources
PubMed2003

Congenital limb deficiencies in newborn infants: prevalence, characteristics and prenatal diagnosis.

Congenital limb deficiency (CLD) occurs in 0.54 to 0.59/1000 live-born infants and varies according to its anatomic location, type and cause. Our aim was to present a fetus with a prenatal ultrasonographic diagnosis of CLD (transverse reduction deficiency of the left upper limb), and to determine the prevalence and clinical characteristics of CLD at a tertiary medical centre in Israel. Among 78 500 live-born infants, there were 24 cases of CLD (0.31/1000): 45.8% of the CLD cases with affected upper limbs, 45.8% with affected lower limbs, and 8.4% with both limbs affected; 88.4% of the limb deficiencies were longitudinal and 11.6% were transverse; and, 33.3% (8/24) of the affected newborn infants had additional congenital anomalies. We conclude that CLD is not an infrequent finding in live-born infants. Comprehensive ultrasonography of the fetus allows early prenatal diagnosis of CLD and provides the parents with important information and helps them in their decision regarding the fate of the pregnancy.

Adult↗
PubMed2003

Insulin in human milk: postpartum changes and effect of gestational age.

OBJECTIVE: To determine if human milk insulin (HMI) concentrations are affected by gestational age and postnatal age. DESIGN AND SETTING: An observational study carried out in a level III neonatal intensive care unit. Insulin concentrations were determined in human milk of 90 parturient mothers who delivered between 30 and 41 weeks gestation. Samples were collected on days 3 and 10 after delivery. RESULTS: HMI concentrations for mothers of preterm infants were not significantly different from those of full term infants, on either day 3 or 10 post partum. When results for all 90 mothers were pooled, regardless of gestational age, HMI concentration fell significantly from day 3 to day 10 (50.1 (34.6) v 41.1 (28.5) microU/ml; p = 0.01; mean (SD)). However, this decrease was only significant for mothers delivering at term (37-41 weeks). CONCLUSIONS: HMI concentrations were not influenced by gestational age at delivery. They decreased post partum, mainly in mothers of term infants. The postnatal changes in HMI concentrations and the effects of oral insulin on the immature intestinal mucosa warrant further investigation.

Female↗
PubMed2003

Neonatal lenticulostriate vasculopathy: further characterisation.

BACKGROUND: Lenticulostriate vasculopathy (LSV) is sometimes detected on routine brain ultrasonography in neonates, and is often associated with various perinatal and neonatal abnormalities. However, most reports on LSV are retrospective with no controls. OBJECTIVES: To compare the perinatal and neonatal clinical characteristics of neonates with LSV with matched controls and to summarise all published reports of LSV. DESIGN: A prospective study that summarises the clinical, laboratory, and neurosonographic data of neonates with LSV. METHODS: Of 1184 neonates admitted to the neonatal intensive care unit (NICU) during a three year period, 857 had a routine head ultrasound examination. Twenty one had LSV, and were compared with 42 matched controls with regard to gestational, perinatal, neonatal, laboratory, and neurosonographic characteristics. RESULTS: LSV was detected in 21 of the 857 (2.45%) neonates. It was bilateral in 10 of the 21 cases and located in the thalamus (n = 14) and basal ganglia (n = 7). Infants with LSV were not significantly different from matched controls in most tested variables. However, compared with the control group, the LSV group included significantly more multiple births and more disturbances in amniotic fluid volume, but less meconial amniotic fluid. In addition, the patients with LSV required fewer blood transfusions and less phototherapy. CONCLUSIONS: Except for more multiple births, neonates with LSV did not display more adverse findings than their matched controls.

Basal Ganglia Cerebrovascular Disease↗
PubMed2003

Neonatologists are using much less dexamethasone.

Two historical cohorts (1993-1994 and 2001) of preterm infants ventilated for respiratory distress syndrome were compared. Dexamethasone administration fell from 22% to 6%. Chronic lung disease in survivors rose slightly from 13% to 17%, and mortality fell from 21% to 15% (other causes). The effect of restriction of dexamethasone use on chronic lung disease and mortality remains to be seen.

Birth Weight↗
PubMed2001

Caudal dysplasia sequence with penile enlargement: case report and a potential pathogenic hypothesis.

The clinical spectrum of caudal dysplasia sequence (CDS) is noted for its diversity. The origin of CDS remains unknown, though poorly controlled gestational diabetes has been implicated in some cases. Here we describe the case of a newborn with CDS associated with penile enlargement (PE). The main anomalies included anal atresia, agenesis of the kidneys and of the sacrococcygeal vertebrae, dysgenesis of lumbar vertebrae, and bilateral cryptorchidism. Penile enlargement (7 cm), a rather unusual finding, has so far not been reported in association with CDS. Chromosomal analysis failed, and the neonate died 30 min after birth. Comparative genomic hybridization analysis using stored DNA showed a balanced normal male DNA content, which negates chromosomal losses or gains as a cause of CDS and/or PE. PE due to virilizing-type adrenal hyperplasia, caused by common mutations in the genes encoding for the adrenal enzymes 21-hydroxylase and 11-hydroxylase, was ruled out. We report on a previously unpublished case of the coexistence of PE and severe CDS and propose a possible pathogenetic hypothesis of this association.

Abnormalities, Multiple↗
PubMed2001

Transient mega-esophagus in a neonate with congenital diaphragmatic hernia.

Esophageal dilatation (ED) in neonates is rare. In the present case, ED was detected in a chest radiograph following repair of congenital diaphragmatic hernia (CDH) in a term neonate. A roentgenographic swallow study on the seventh day of life demonstrated ED and a sub-diaphragmatic stomach. The infant thrived adequately on enteral feeding. A swallow study on the twentieth day of life showed a normal-width esophagus with gastroesophageal reflux and small hiatus hernia. The longstanding herniated stomach in the fetus apparently caused kinking, edema, and obstruction of the gastroesophageal junction. This led to a significant ED and concealment of gastroesophageal reflux. We aim to arouse awareness about the occurrence of ED with CDH, and about its benign course under conservative management.

Esophageal Achalasia↗
PubMed2001

Review of 49 neonates with acquired fungal sepsis: further characterization.

BACKGROUND: Neonatal acquired fungal sepsis (AFS) is a risky condition that warrants every effort for early diagnosis and management. METHODS: We retrospectively reviewed the medical charts of all 4445 neonatal intensive care unit (NICU) admissions in the past 10 years and detected 49 neonates with AFS. We then compared their data with those of 49 matched control neonates who did not have AFS. The following details were collected: gestational, perinatal and neonatal courses; bacterial sepsis; antibacterial therapy; laboratory and imaging investigations; and antifungal therapy and its complications. RESULTS: The incidence of AFS was.4 to 2 cases per 1000 live-births and 3.8% to 12.9% of very low birth weight (VLBW) infants. Compared with 1989 through 1992, between 1993 and 1995 the rate of AFS in VLBW neonates significantly increased (3. 8%-5.6% --> 9.6%-12.9%), along with a significant increase of NICU admission rate (369-410 --> 496-510 admissions/year). Compared with controls, AFS neonates had significantly longer hospitalizations, higher rates of mechanical ventilation, umbilical vein catheterization, and previous treatment with broad-spectrum antibacterial agents (amikacin, vancomycin, ceftazidime, or imipenem). At the onset of AFS, 42.8% of patients had hyperthermia and 40.9% had normal white blood cell count. Causative fungi were as follows: Candida albicans-42.8% of cases, Candida parapsilosis-26.5%, and Candida tropicalis-20.4%. Fungal dissemination was rare, complications of antifungal therapy were infrequent, and no deaths occurred. CONCLUSIONS: First, non-albicans Candida have become more frequent in neonatal AFS. Second, mechanical ventilation and antibacterial agents are significant risk factors for AFS. Third, hyperthermia is a frequent presenting sign of AFS. Fourth, a normal white blood cell count does not rule out AFS. Fifth, meningeal involvement in neonatal AFS should be ruled out before initiation of antifungal therapy. Sixth, the policy of empiric antifungal therapy for AFS should be considered on an individual NICU basis.newborn infant, fungal sepsis, clinical signs, risk factors.

Abdomen↗
PubMed2001

Staphylococcal scalded-skin syndrome in a very low birth weight premature infant.

Exfoliative skin diseases are rare in neonates. When caused by coagulase-positive Staphylococcus aureus, scalded-skin diseases such as staphylococcal scalded-skin syndrome (SSSS), bullous impetigo, and staphylococcal scarlet fever may develop. These diseases might cause significant complications and mortality. SSSS is caused by staphylococcal exfoliative toxins A or B, which split the granular layer of the skin, induce proteolysis, and might exhibit superantigen activities, such as epidermolysis and lymphocyte mitogenicity. We describe a 1378-g premature male infant who was born at 29 weeks' gestation and developed SSSS on day 3 of life, with no clinical signs of neonatal sepsis. After cultures from the lesion and bloodstream were obtained, intravenous cloxacillin therapy was started. Infection control measures were implemented instantly and included isolation of the infected infant, personnel handwashing with hexachlorophene, and placement of exposed neonates into a cohort. The initial lesion expanded and additional lesions appeared, but 12 hours after initiation of antibacterial therapy, the lesions ceased to proliferate. Cultures from scalded-skin lesions grew coagulase-positive Staphylococcus aureus, whereas the bloodstream culture was sterile. The lesions resolved completely within 6 days, and the infant's subsequent course was uneventful. No similar skin lesions were noticed in other infants in the neonatal intensive care unit. We discuss recent advances in understanding the pathogenesis of neonatal SSSS, highlight the importance of early diagnosis and treatment, and stress the need for new adjunctive therapies for this disease.

Coagulase↗
PubMed2001

Congenital subependymal pseudocysts: own data and meta-analysis of the literature.

BACKGROUND: Congenital subependymal pseudocysts are incidental findings that are found in 0.5-5.2% of neonates during postmortem examination or head ultrasonography. In our institution we detected 10 neonates with CSEPC. OBJECTIVE: To investigate associated etiological factors, morphologic characteristics and outcome of CSEPC. METHODS: We performed a meta-analysis of the literature on CSEPC (1967-98), including our 10 cases. RESULTS: A total of 256 cases of CSEPC were analyzed. Ultrasound diagnosed 77.6% of CSEPC; 48.8% were bilateral and 53.4% were located in the caudothalamic groove or head of caudate nucleus. Altogether, 93.5% resolved during 1-12 months of ultrasonographic follow-up. Compared to the general neonatal population, the following features were more prevalent in the CSEPC population: prematurity, maternal vaginal bleeding, preeclamptic toxemia, intrauterine growth restriction, asphyxia, fetal cytomegalovirus and rubella infections, congenital malformations, chromosomal aberrations, infant mortality, and neurodevelopmental handicap. The risk for neurodevelopmental handicap was significantly higher when CSEPC were associated with fetal infections, IUGR, malformations and chromosomal aberrations, or persistence of CSEPC during follow-up. CSEPC infants without any of these four conditions had a low risk for neurodevelopmental handicap. CONCLUSIONS: CSEPC are morphologic features of various underlying conditions encountered in the fetus. Association of CSEPC with IUGR, fetal infections, malformations and chromosomal aberrations or persistence of CSEPC indicates a higher risk for future neurodevelopmental handicaps, probably because of the deleterious effects on the fetal brain that are inherent in these conditions. A favorable outcome is expected in the absence of these risk factors.

Asphyxia Neonatorum↗
PubMed2000

Cytokine response during hyperoxia: sequential production of pulmonary tumor necrosis factor and interleukin-6 in neonatal rats.

BACKGROUND: Exposure of newborn animals to high concentrations of oxygen leads to diffuse alveolar damage similar to that seen in bronchopulmonary dysplasia in human infants. Therefore, neonatal rats are a suitable practical model of hyperoxic lung damage in human infants. OBJECTIVE: To determine the involvement of tumor necrosis factor-alpha and interleukin-6 in lung injury in neonatal rats exposed to 100% O2 concentration. METHODS: A randomized controlled study was designed in which litters of term Sprague-Dawley rat pups were assigned to experimental or control groups. The pups in the experimental group were placed in 100% O2 from birth for 9 days, while the control pups were placed in room air. Twelve to 15 pups from each group were sacrificed on day 1, 3, 6, 9 and 13 after birth for bronchoalveolar lavage collection and lung histologic study. The bronchoalveolar lavage fluid was assayed for TNF alpha and IL-6. RESULTS: Newborn rats exposed to 100% O2 for the first 9 days of life showed severe pulmonary edema and hypercellularity on days 1 and 3, which then improved to nearly complete resolution on days 6 and 9. Pulmonary TNF alpha was produced early on O2 exposure (day 3) and pulmonary IL-6 later (days 6 and 9). CONCLUSIONS: Hyperoxia induces sequential production of pulmonary TNF alpha and IL-6, which corresponds to the severity of the pathological findings and the known inflammatory and anti-inflammatory role of these cytokines.

Animals↗
PubMed1999

Congenital hypothyroidism and nonimmune hydrops fetalis: associated?

Hydrops fetalis (HF) consists of an abnormal accumulation of fluid in two or more fetal compartments, including ascites, pleural effusion, pericardial effusion, and skin edema. Almost all observed cases of HF are of the nonimmune type, the causes of which remain undetermined in 15% of patients. We report a newborn infant with nonimmune hydrops fetalis (NIHF) and congenital hypothyroidism. The infant's mother was healthy and there were no malformations of the placenta or umbilical cord. The infant did not show any structural abnormalities of his central nervous, cardiovascular, gastrointestinal, or urinary tract systems, and there was no evidence of anemia, infectious disease, or inborn error of metabolism. An immune-based process was unlikely, because the blood group of the mother and infant was A-positive and results of an indirect Coombs test in the mother and a direct Coombs test in the infant were negative. The patient's condition gradually improved with mechanical ventilation, repeated thoracocentesis, and total parenteral nutrition. By day 5 of age the skin edema, pericardial effusion, and ascites disappeared, but accumulation of significant amounts of chylous pleural fluid persisted. Because of lethargy, FT4 and thyroid-stimulating hormone levels were obtained and showed hypothyroidism. Thyroid hormone supplementation was then started, and within 4 days the infant became more vigorous and was weaned from mechanical ventilation. After 7 days, the chylothorax resolved completely as the serum thyroxine level normalized. No reaccumulation of pleural effusion was noticed. The infant started to gain weight and was discharged from the hospital at 35 days of age. A possible pathophysiologic association between congenital hypothyroidism and NIHF is discussed. NIHF may be caused by lymphatic congestion attributable to an impairment of lymphatic flow and a delayed return of lymph to the vascular compartment. There could be a possibility that because of thyroid hormone deficiency in this patient, there was reduced adrenergic stimulation of the lymphatic system. This could result in a sluggish flow of the lymph with engorgement of the lymphatic system, leakage of lymph into the pleura and the interstitial spaces, and the production of chylothorax with NIHF. Animal studies demonstrate a direct relationship between lymph flow rate or lung liquid clearance and adrenergic receptor activity in the lymphatic system. These observations support our hypothesis that deficient adrenergic activity in congenital hypothyroidism might lead to chylothorax with NIHF in the fetus. We speculate that thyroid hormone may play a role in the regulation of adrenergic receptors in the lymphatic system and lungs, thus modulating both the lymphatic flow rate and lung liquid clearance, and facilitating the resolution of chylothorax. Examination of thyroid functions should be included in the investigation of fetuses and neonates with NIHF of an obscure origin.

Congenital Hypothyroidism↗
PubMed1995

Prenatal diagnosis of congenital diaphragmatic hernia: timing of visceral herniation and outcome.

Ultrasonographic prenatal diagnosis of congenital diaphragmatic hernia is well established, but the correlation of prenatal detection with clinical outcome remains unclear. We report our experience with 15 cases of prenatally diagnosed congenital diaphragmatic hernia. Seven fetuses were detected at 14-16 weeks' gestation; two with a normal sonographic study at 15 and 16 weeks' gestation showed visceral herniation at 21 and 23 weeks, respectively. In the remaining six cases, a diaphragmatic hernia was found at ultrasonography after 24 weeks' gestation, while previous sonographic studies had been normal. All seven fetuses in whom a diaphragmatic hernia was diagnosed before 16 weeks' gestation were aborted; four of them had severe malformations or karyotype abnormalities. The two neonates who were diagnosed at 21 and 23 weeks' gestation died after surgical repair. In contrast, all six infants whose visceral herniation was diagnosed after 24 weeks of gestation, and whose sonographic studies at 15-23 weeks had been normal, are alive and well after corrective surgery. The results of this series suggest that the timing of visceral herniation into the thoracic cavity is a major indicator of the prognosis of these fetuses and that herniation that occurs after 25 weeks of gestation carries a favourable clinical outcome. Normal sonographic studies during the first half of pregnancy do not exclude the subsequent development of congenital diaphragmatic hernia, raising questions about the advisability of repeat examinations at later stages of gestation.

Congenital Abnormalities↗
PubMed1995

Intratracheal pulmonary ventilation versus conventional mechanical ventilation in a rabbit model of surfactant deficiency.

Intratracheal pulmonary ventilation (ITPV) enhances the clearance of CO2 from dead space and lungs by a bias flow of gas administered in the distal trachea. ITPV flow is continuously administered through a separate catheter placed within an endotracheal tube (ETT). After exiting from catheter's tip in the distal trachea, the flow of gas is redirected outward away from the lungs. We hypothesized that, compared with conventional mechanical ventilation (CMV), ITPV may increase minute CO2 clearance (VCO2), reduce the partial pressure of CO2 dioxide in arterial gas (PaCO2), and reduce distal tracheal peak inspiratory pressure (dPIP). We induced surfactant deficiency in 15 adult rabbits by lung lavage with 10 mL/kg normal saline. Animals were ventilated through a double-lumen 4.0 ETT, inserted through a tracheotomy incision. dPIP, distal positive end expiratory pressure, and distal mean airway pressure were monitored, and the mean exhaled CO2 concentration was measured. For ventilator rates (respiratory rate) of 30, 45, and 70 breaths/min, the study included two phases: phase I compared CO2 clearance and PaCO2 between ITPV and CMV using similar ventilatory pressures; phase II evaluated the effectiveness of ITPV in reducing dPIP and tidal volume (Vt), compared with CMV, while maintaining eucapnea. When comparing ITPV and CMV, the following results (mean +/- SD) were achieved at respiratory rate of 30, 45, and 70 breaths/min, respectively. Phase I ITPV resulted in mean percent reduction of PaCO2 by 31.4 +/- 10%, 37.1 +/- 9.7% and 38.3 +/- 9%; mean percent increase in VCO2 by 61.3 +/- 29%, 56 +/- 23, and 98 +/- 40%, compared with CMV. Phase II ITPV resulted in mean percent reduction of dPIP by 35.5 +/- 14%, 38 +/- 10.8%, and 37.2 +/- 13.7%, and mean percent reduction in Vt by 34.7 +/- 12.9%, 36.4 +/- 15%, and 52.7 +/- 10.7%, compared with CMV. The changes in PaCO2, VCO2 (phase I), and dPIP and Vt (phase II) were all significantly more than 25% (p < 0.05). Oxygenation and pH were not significantly different between ITPV and CMV. We conclude that, in a surfactant deficiency rabbit model, ITPV is an efficient mode of assisted ventilation that increases CO2 clearance and reduces ventilator pressures required for adequate ventilation. We speculate that ITPV can minimize lung barotrauma associated with mechanical ventilation.

Animals↗
PubMed1993

Antibiotic treatment of experimental Pseudomonas aeruginosa pneumonia in guinea pigs: comparison of aerosol and systemic administration.

Pseudomonas aeruginosa pneumonia is associated with high mortality despite appropriate systemic antibacterial therapy. To examine the effects of aerosolized tobramycin on experimental P. aeruginosa pneumonia, guinea pigs were assigned to two main groups: a study group, in which P. aeruginosa was instilled into the tracheal lumen, and a control group, in which normal saline was instilled. Each group was then subdivided according to treatment: normal saline or tobramycin by intramuscular injection, normal saline or tobramycin by aerosol, or normal saline or tobramycin via both aerosol and intramuscular injection. Compared with either intramuscular or aerosolized tobramycin, the combination of aerosol plus intramuscular tobramycin achieved slightly higher survival, total eradication of P. aeruginosa from lungs, and a significant further reduction of lung inflammatory changes. Adding aerosolized tobramycin to systemic tobramycin in the treatment of experimental P. aeruginosa pneumonia enhanced eradication of P. aeruginosa and mitigated pulmonary inflammatory changes.

Aerosols↗
PubMedDate not supplied

Neonatal transverse cerebellar diameter in normal and growth-restricted infants.

OBJECTIVE: To assess the transverse cerebellar diameter (TCD) in preterm and term neonates with normal growth or growth restriction. METHODS: TCD was sonographically measured after birth in 404 neonates born between 23 and 42 weeks of gestation. The study included two groups: Group 1: 334 appropriately grown for gestational age (AGA) neonates (both birthweight (BW) and head circumference (HC) were between the 3rd and 97th centiles), which were subdivided into two subgroups according to the HC measurements. Group 2: 70 small for gestational age (SGA) neonates (BW <3rd centile), were further divided into three subgroups according to HC measurements. RESULTS: In Group 1 of AGA neonates, a linear growth function was observed between the TCD and GA (R = 0.914, P < 0.00001, TCD = 0.279 + 0.142 X GA), and between TCD and HC (R = 0.886, P < 0.00001, TCD = -0.333 + 1.777 X HC). The percentage of neonates with normal TCD (> or =10th centile) was more than 85% of the AGA and asymmetric SGA subgroups, and 60.7% of the microcephalic SGA subgroup (P < 0.02). CONCLUSIONS: This study provides normative data of neonatal TCD across gestational age. TCD measurement via sonography is a new adjunctive criterion for objectively assessing gestational age in infants when a precise determination of gestational age is necessary. This is very important since utility of the TCD is effective for both AGA and asymmetric SGA infants.

Cephalometry↗
PubMedDate not supplied

Predictors of neonatal mortality in 1,500-1,999 g premature infants with respiratory failure. Basis for ECMO Therapeutic Trial.

Despite the introduction of new ventilation techniques and surfactant therapy, some premature infants still experience severe respiratory failure and either die or survive with severe bronchopulmonary dysplasia. Extracorporeal membrane oxygenation is currently not offered for preterm infants with a birth weight less than 2,000 g, mainly because of the potential high risk for intracranial hemorrhage. The aim of this study was to determine risk predictors for mortality alone and for mortality or major lung morbidity in 1,500-1,999 g premature infants with respiratory failure. We reviewed the medical records of all preterm infants (n = 459) with respiratory failure and a birth weight of 1,500-1,999 g treated at five medical centers from 1989 to 1991. Of those infants, 23 (5%) had severe respiratory failure, defined as a requirement for ventilatory support with the fraction of inspired oxygen > or = 0.8 or peak inspiratory pressure > or = 30 cmH2O for > or = 3 hr in the 1st week of life. A mortality of > or = 75% was associated with a single arterial/alveolar oxygen ratio < or = 0.04; pulmonary air leak alone or pulmonary air leak with a mean airway pressure > or = 12 cmH2O; and arterial oxygen tension < or = 50 mmHg. These risk predictors may provide a basis for the selection of patients for future clinical trials of extracorporeal membrane oxygenation in this high-risk group of 1,500-1,999 g premature infants with severe respiratory failure.

Body Weight↗