Rosemary D. Higgins

Candida Sepsis and Association With Retinopathy of Prematurity

Objective. To assess the association of Candida sepsis with retinopathy of prematurity (ROP) in extremely low birth weight infants. Methods. We prospectively identified 253 infants admitted to the Critical Care Nursery at Georgetown University Hospital with birth weights ≤1000 g born between January 1, 1994, and June 30, 1996. Of these 253 infants, 62 died and 55 were transferred to other institutions before ophthalmologic screening for ROP. Clinical data on 98% (133/136) infants were reviewed. Candida sepsis was defined as a positive blood culture for Candida species. Severity of ROP was staged by the International Classification for ROP. Data were analyzed using the χ2 test for nominal data, unpaired t test for continuous data, Mann-WhitneyU test for ordinal data, and logistic regression. Results. The mean birth weight (±SD) of the population studied was 777 g (±136 g), and the mean gestational age at birth was 26.0 weeks (±1.8 weeks). The overall incidence of ROP was 74%, and it correlated significantly with birth weight, gestational age, days on supplemental oxygen, and 5-minute Apgar scores. The incidence of ROP was significantly higher in the infants who hadCandida sepsis (21/22 [95%]) compared with those who did not (77/111 [69%]). Using logistic regression to control for the influence of birth weight, gestational age, days on supplemental oxygen, and 5-minute Apgar scores, Candida sepsis was an independent predictor of stage 3 or worse ROP. In addition, 9 (41%) of 22 infants with Candida sepsis required laser surgery compared with 10 (9%) of 111 infants without Candidasepsis. This difference was significant independent of birth weight, gestational age, days on supplemental oxygen, and 5-minute Apgar scores. Conclusions. Candida sepsis is independently associated with increased severity of ROP and the need for laser surgery in extremely low birth weight infants.

Race, Candida Sepsis, and Retinopathy of Prematurity

The objective of this observational cohort study at Georgetown University Hospital from January 1, 1994 through December 31, 1997 was to investigate race, Candida sepsis, and duration of oxygen exposure in infants with retinopathy of prematurity (ROP) with birth weight ≤1,000 g. The incidence of ROP was 70.8% (114/161). The incidence of stage III or greater ROP in the Caucasian infants was significantly higher at 46.7% (14/30) than in the African-American infants at 23.8% (20/84) with p < 0.02. In addition, the incidence of threshold disease was higher in Caucasian infants 33.3% (10/30) when compared to African-American infants 9.5% (8/84) with p < 0.002. Using multiple logistic regression, African-American race was found to be an independent protective factor against developing severe ROP [adjusted odds ratio 0.39; 95% confidence interval (UCI) 0.16–0.97]. Extremely-low-birth-weight African-American infants with comparable severity of illness (including birth weight, gestational age, duration of supplemental oxygen exposure, and Candida sepsis) are less likely to develop severe ROP than Caucasian infants.

Neuropeptide Y expression in a mouse model of oxygen-induced retinopathy

Background: Neuropeptide Y (NPY) is a potent vasoconstrictor and angiogenic agent that is found in the retina. The goal of this study was to determine the expression of NPY and its receptors, NPY Y1 and NPY Y2, in a mouse model of oxygen‐induced retinopathy.

Ibuprofen improves oxygen-induced retinopathy in a mouse model

Purpose. Retinopathy of prematurity is a developmental vascular anomaly occurring in the incompletely vascularized retina of the premature infant. Ibuprofen is a nonsteroidal anti-inflammatory agent similar to indomethacin, but with less pronounced side-effects. The goal of the study was to test the hypothesis that ibuprofen would improve oxygen-induced retinopathy in a mouse model. Methods. C57BL6 mice pups were exposed to 75% oxygen from postnatal day 7 through postnatal day 12. Ibuprofen was administered along with oxygen exposure as a single subcutaneous dose of 40 mg/kg/day for 5 days. Animals were sacrificed on postnatal day 17 through postnatal day 20. The severity of retinopathy was assessed by a retinopathy scoring system of fluorescein-conjugated dextran-perfused retinal flat mounts and by quantitation of extra-retinal nuclei by use of periodic acid-Schiff-stained retinal sections. Results. Animals that received ibuprofen during hyperoxia exposure had a significantly lower median (25 th, 75 th quartile) retinopathy score of 6 (5, 7.5) compared with animals that received oxygen only, with a score of 12 (10.5, 12.5), with p < 0.005. Animals given ibuprofen during hyperoxia exposure had a significantly lower extra-retinal nuclei count per section (14.2 ± 3.6) compared with animals that were only exposed to oxygen (26.8 ± 5.8), with p < 0.005. Ibuprofen did not affect the growth of the animals. Conclusion. Ibuprofen improves oxygen-induced retinopathy when administered concurrently with the injury phase without affecting the normal retinal development of the animals.

Captopril and vascular endothelial growth factor in a mouse model of retinopathy

Purpose. Angiotensin converting enzyme (ACE) inhibition has been shown in animal models of retinopathy and in patients with diabetes to improve retinal neovascularization. The mechanism is not clearly identified, but could potentially be mediated via vascular endothelial growth factor modification. The objective of this study was to determine the effect of captopril, an angiotensin converting enzyme (ACE) inhibitor, on retinal VEGF, VEGF-R1, and VEGF-R2 expression in a mouse model of oxygen induced retinopathy (OIR). Methods. A mouse model of OIR was used and retinal tissue was obtained at P7, prior to oxygen exposure, at P12, just after oxygen exposure, and at P17, the time of maximal retinal neovascularization for VEGF, VEGF-R1 and VEGF-R2 assessment. A group of animals were treated with captopril (0.5 mg/kg/d SC from P7 for five days). Results. Captopril plus OIR treated animals had higher levels of retinal VEGF mRNA and protein at P12 (p < 0.05) and lower levels at P17 (p < 0.05) than OIR animals. VEGF-R1 mRNA expression increased 16 fold from P7 to P17 (p < 0.05) in room air reared animals. VEGF-R1 mRNA expression was unaffected by OIR and/or captopril treatment. VEGF-R2 mRNA expression decreased from P7 to P17 by 1.5-fold in room air reared animals (p = 0.001). Retinal VEGF-R2 mRNA and protein expression were significantly higher at P12 in OIR plus captopril treated animals than OIR animals (p = 0.01). Conclusions. In summary, captopril maintains VEGF and increases VEGF-R2 expression during the period of hyperoxia when VEGF expression is normally suppressed. Captopril treatment during oxygen exposure is associated with a reduction in the angiogenic response at day 17 as manifested by decreased VEGF and VEGF-R2 expression in retinal tissue. Angiotensin converting enzyme inhibition is associated with changes in expression of VEGF and VEGF-R2 in the evolution of retinal neovascularization in the mouse model of retinopathy.

Lack of effect of gender on retinopathy in the mouse.

Background: The reported effect of gender on retinopathy of prematurity has been controversial. The goal of this study was to determine the effect of gender on oxygen‐induced retinopathy in a mouse model.

Perinatal vascular development

See article by Boels et al. [3] (pages 140–150) in this issue. During transition to the extrauterine environment, the newborn infant must accomplish complex cardiorespiratory adjustments. Dramatic changes in pulmonary and systemic vascular resistance must occur within minutes, followed by more gradual changes over the succeeding days. A host of mediators of vascular tone are involved in these processes and these have been the focus of extensive study. Differential responses from different vascular beds contribute to these circulatory changes; a variety of exogenous and endogenous factors affect the responsiveness of vascular beds to vasoactive mediators. When these critical circulatory changes are not accomplished successfully, the life-threatening disorder known as persistent pulmonary hypertension of the newborn may result [1]. In older subjects, pulmonary hypertension associated with the acute respiratory distress syndrome, congenital heart disease with left-to-right shunt, and primary pulmonary hypertension remain baffling challenges for … *Corresponding author. Tel.: +1-202-687-8569; fax: +1-202-784-4747