Mazen Al-Essa

A C597→A Polymorphism in the Norrie Disease Gene Is Associated with Advanced Retinopathy of Prematurity in Premature Kuwaiti Infants

Retinopathy of prematurity (ROP) is a retinal vascular disease which occurs in infants with a short gestational age and low birth weight and may lead to retinal detachment and blindness. In some premature infants, ROP progresses to advanced stages despite rigorous intervention, but in the majority, it spontaneously regresses before the threshold stage. Genetic factors, e.g. mutations in the Norrie disease (ND) gene, have been implicated in determining the progression of ROP to advanced stages. We have identified a novel C597A polymorphism of the ND gene; we screened this and another mutation in the ND gene, C110G, in 210 premature Kuwaiti infants using PCR-RFLP, DNA sequence analysis and DNA enzyme immunoassay hybridization to investigate their association with advanced-stage ROP. In this cohort of premature Kuwaiti newborns, 115 of 210 babies had no eye problems and served as controls, while 95 were found to have ROP. In 71 of the 95 ROP cases, the disease spontaneously regressed at or before stage 3, while in 24 of 95 ROP cases, the disease progressed to advanced stages 4 or 5. The incidence of the AA genotype of the C597A polymorphism was considerably higher in advanced-stage ROP cases (83.3%) compared to spontaneously regressing ROP cases (0%) and the normal controls (10.4%) (p < 0.0001). For the other genotypes, no significant difference was detected between the controls and ROP cases. In the case of the C110G mutation in the ND gene, no significant differences were detected between the controls and ROP cases, and the majority of subjects had a CC genotype in all three groups.

Missense Mutations in Norrie Disease Gene Are Not Associated with Advanced Stages of Retinopathy of Prematurity in Kuwaiti Arabs

Retinopathy of prematurity (ROP) is a disease characterized by retinal neovascularization, possibly leading to retinal detachment and finally blindness. In a proportion of ROP cases, the disease progresses to advanced stages despite rigorous intervention. Missense mutations of the Norrie disease (ND) gene have been associated with progression of the disease in ROP cases from the USA. We have investigated the presence of ND gene mutations in 102 premature newborns of Kuwaiti Arab origin to replicate this finding in a different population/racial group. 56 (55%) of these newborns had normal eyes and served as controls. In 35 (34%) cases, the ROP regressed spontaneously during stage 1–3. In 11 (11%) cases, ROP progressed to advanced stages. A PCR-RFLP method was used to detect the mutations in exon 3 of the ND gene and confirmed the DNA sequence by direct sequencing of the PCR product. The [R121W] mutation of the ND gene was not detected in the premature newborns screened from our Kuwaiti population/group. For the second mutation [L108P], a genotype (PP) was present in 98% of the premature newborns screened and only in 1 of 56 normal infants was the (LL) genotype detected. Our population is genetically homogenous in that genotype (PP) was detected at codon 108 in almost all controls and ROP cases. We did not find an association between the presence or absence of missense mutations of the ND gene and the risk of severe ROP.

Angiotensin-Converting Enzyme Gene Insertion/Deletion Polymorphism in Kuwaiti Children with Retinopathy of Prematurity

Retinopathy of prematurity (ROP) is a disease characterized by neovascularization which occurs in infants with short gestational age and low birth weight and can lead to retinal detachment and blindness. In a proportion of ROP cases, the disease progresses to advanced stages despite rigorous intervention. The genotypes for angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism were determined in 181 premature Kuwaiti infants using a polymerase chain reaction (PCR) method. The incidence of different I/D genotypes was compared in ROP cases (n = 74) and non-ROP controls (n = 107) and within 2 subgroups of ROP patients: (1) in which ROP regressed spontaneously (stages 1–3, n = 53), and (2) in which ROP progressed to advanced stages (stages 4 and 5, n = 21). When the ROP cases were considered collectively as one group, the incidence of the DD genotype was almost identical to that of non-ROP controls. The incidence of heterozygous ID genotype was higher in non-ROP controls. The incidence of the II genotype was higher in ROP cases compared to non-ROP controls (p < 0.01). In contrast to this, when ROP cases were divided in 2 subgroups the incidence of the DD genotype was significantly higher in advanced stage ROP cases compared to spontaneously regressing ROP cases (p < 0.04). The incidences of ID and II genotypes were not significantly different amongst the 2 subgroups of ROP patients.

Retinopathy of prematurity: Mutations in the Norrie disease gene and the risk of progression to advanced stages

Abstract Background : Retinopathy of prematurity (ROP) is a retinal vascular disease that occurs in infants with short gestational age and low birth weight and may lead to retinal detachment and blindness. Missense mutations in the Norrie disease (ND) gene have been associated with the risk of progression to advanced stages in cases of ROP from the US and also in clinically similar ND and familial exudative vitreoretinopathy.

Rate of and Risk Factors Associated with Retinopathy of Prematurity: A Prospective Study from Kuwait

Objective: To determine the rate of retinopathy of prematurity (ROP) among a population of preterm infants in Kuwait, and to review the risk factors associated with the disease. Methodology: A prospective cohort study of all preterm infants of less than 2,000 g birth weight and/or 36 weeks gestational age who were screened for ROP during 1995 at the neonatal unit of the Maternity Hospital in Kuwait. The rate of and some of the possible risk factors associated with the disease were determined. Results: A total of 130 babies were screened of which 59 (45.4%) developed some stage of ROP. The frequency of blindness was 3 (2.3%). Low birth weight, oxygen therapy, patent ductus arteriosus, intraventricular hemorrhage and blood transfusion were the risk factors found to be associated with the disease. However, with logistic regression analysis, only low birth weight and oxygen were independently associated with ROP. Conclusion: The rate of ROP in our unit is not different from that of the other centers, and low birth weight and oxygen therapy are the main risk factors associated with the disease.

Double-Catheter Technique for the Proper Insertion of Umbilical Venous Catheters in Newborns

Objectives: To document the usefulness and safety of inserting a second umbilical venous catheter in ill neonates, while a previously misplaced first catheter was still in its place. Subjects and Methods:The case series involved 25 newborn babies who were admitted to the Neonatal Intensive Care Unit, Maternity Hospital, Kuwait, over a 3-year period from 1999 to 2002. The umbilical venous catheter of the babies was misplaced and diverted to the liver, necessitating insertion of a second catheter while the previous one was still in place. The characteristics of the babies and possible catheter-related complications were recorded. Results:Of the 25 babies, 19 had the second catheter properly placed in the right atrium, while in the remaining 6 neonates, the catheter was still misplaced. Misplacement occurred mostly in full-term babies or the catheter was inserted at a later stage. No life-threatening complication was observed during the procedure. Conclusion:Insertion of a second umbilical venous catheter with the misplaced first catheter in situ is a useful and safe procedure.

Threshold stage of retinopathy of prematurity: maternal and neonatal risk factors.

BACKGROUND The aim of this study was to review the maternal and neonatal risk factors associated with retinopathy of prematurity (ROP) and the threshold stage of the disease. PATIENTS AND METHODS In this prospective cohort study, all preterm infants of less than 1501 g birth weight were screened for ROP between January 1996 and December 1997 at the neonatal unit of the Maternity Hospital in Kuwait. The rate of the threshold stage of ROP, as well as risk factors associated with the disease, were identified. RESULTS A total of 234 babies were screened for ROP, of which 151 (64.5%) developed the disease and 34 (14.5%) had the threshold stage of ROP. Several factors were found to be associated with ROP and threshold ROP. Stepwise regression analysis revealed that low birth weight (P<0.002) and exposure to high oxygen concentration (P<0.0001) were independently associated with ROP. In addition, low birth weight (P<0.006), high oxygen concentration (P<0.003), and culture-proven sepsis (P<0.04) were found to be independent predictors of threshold ROP. CONCLUSION Apart from low birth weight and exposure to high oxygen therapy, which are well-documented risk factors of ROP, septicemia was also found to be associated with the threshold stage of ROP.

Impaired NADPH oxidase activity in peripheral blood lymphocytes of galactosemia patients

Galactosemia is an autosomal recessive disorder with a wide range of clinical abnormalities. Cellular oxidative stress is considered as one of the pathogenic mechanisms of galactosemia. In this study, we examined the activity of NADPH oxidase (NOX), a major superoxide-generating enzyme system, in peripheral blood lymphocytes (PBL) from galactosemia patients. PBL were isolated from galactosemia patients and healthy control subjects and used for cell culture studies and biochemical assays. PBL were cultured in the presence or absence of galactose or galactose-1-phosphate (Gal-1-P), and enzyme activities and/or gene expression of NOX, catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPx) were measured in the cell homogenates. PBL isolated from galactosemia patients showed significantly reduced (P < 0.01) activities of catalase and GPx; however SOD activity remained unaltered. Galactosemia patients were found to have significantly (P < 0.01) increased levels of malondialdehyde (MDA) in blood lymphocytes. Enzymatic activity of NOX was significantly (P < 0.001) reduced in galactosemia patients; however, Western blotting revealed that NOX-1 protein was not significantly altered. Interestingly, levels of NOX activity in lymphocytes isolated from galactosemia patients significantly increased but remained subnormal when cultured in galactose-deficient medium for two weeks, indicating a galactose-mediated inhibition of NOX. Lymphocytes isolated from control subjects were found to have significantly (P < 0.01) reduced NOX activity when cultured in the presence of galactose or Gal-1-P for two weeks. These results show that galactose-induced cellular oxidative stress is not NOX mediated. However, impairment of the NOX system might be responsible for some of the clinical complications in galactosemia patients.

Use of palivizumab with other infection control measures to control respiratory syncytial virus outbreaks in neonatal care units

OBJECTIVE No guidelines exist on the use of palivizumab during outbreaks of Respiratory Syncytial Virus (RSV) in Neonatal Intensive Care Units (NICUs). We aimed to describe an outbreak of RSV in NICU settings and the role of palivizumab in controlling the outbreak. METHODS The index case was a 30-day-old premature infant. During the outbreak, 13 cases of RSV were confirmed by RT-PCR. All infants in the NICU received palivizumab after RSV diagnosis. RESULTS Of the 13 cases, seven were male; and the median (interquartile) of birth weight was 1585 (IQR: 1480-1705) g. All cases were premature under 34-weeks-gestation. Age at onset of disease varies between 10 and 160 days. Only four cases occurred after administering palivizumab and applying other infection control measures. CONCLUSION During nosocomial outbreaks of RSV, administration of palivizumab to all infants in NICU appears to be rational and may help contain outbreaks.

Lipoprotein A profiles in Arab newborns

Abstract Background: Lipoprotein A (LpA) is an intriguing lipoprotein with unquestionable genetic determination which is expressed early in life. The increasing interest in LpA is due to its established recognition as an important independent risk factor for premature atherosclerosis in cardiovascular diseases. Coronary heart disease is a major cause of morbidity and premature mortality in Kuwait. The present study was designed to measure serum LpA concentrations in Arab newborns to establish reference values for LpA in newborns and its relationship to factors present in the mother and baby.