Perinatal bacterial colonization and neonatal early-onset sepsis: A case-control study.

BACKGROUND: The utility of determining maternal-neonatal surface colonization as detected by standard microbiological cultures around the time of birth is unclear. The aim of this study is to evaluate the association between maternal and neonatal surface colonization at birth and neonatal early onset sepsis (EOS). OBJECTIVE: To investigate the association of white matter hyperintensities (WMHs) present in the brain with AD CSF biomarker levels. METHODS: We conducted a case-control study of newborns admitted to the neonatal department of a referral women's and children's hospital from 2009 to 2017. Cases were infants with blood-culture-confirmed EOS (<3 days of life), and controls were infants without EOS randomly chosen based on the cases' date of birth. Maternal genitourinary and neonatal ear swab cultures were used to determine bacterial surface colonization status. RESULTS: Fifty-one infants were diagnosed with EOS during the study period, where Escherichia coli (45%), and Group B Streptococcus (23%) accounted for 68% of infecting organisms. Compared to infants without EOS, those infected were more likely to have surface colonization of the mothers (60% vs 40%, p = 0.048) and infants (90% vs 11%, p < 0.001). In univariate analysis, chorioamnionitis [7.1 (95% CI 2.9, 16.8)], small-for-gestational-age [OR 0.08 (95% CI 0.02, 0.4)], exposure to antibiotics around time of birth [2.3 (95% CI 1.0, 5.1)], maternal surface colonization [2.2 (95% CI 1.0, 4.9)] and neonatal surface colonization [23.5 (95% CI 7.3, 76.1)] were significantly associated with EOS. Adjusting for potential confounders, neonatal colonization remained significantly associated with neonatal EOS [AOR 15.0 (95% CI 3.5, 64.2), p < 0.001]. CONCLUSION: In our setting with predominant Gram-negative EOS, neonatal colonization but not maternal colonization was significantly associated with EOS in the newborn.

Dwell time and risk of central-line-associated bloodstream infection in neonates.

BACKGROUND: Umbilical venous catheters (UVCs) or peripherally inserted central catheters (PICCs), widely used in high-risk neonates, may have a threshold dwell time for subsequent increased risk of central-line-associated bloodstream infection (CLABSI). AIM: To evaluate the CLABSI risks in neonates having either UVC, PICC, or those having both sequentially. METHODS: The study included 3985 infants who had UVC or PICC inserted between 2007 and 2009 cared for in 10 regional neonatal intensive care units: 1392 having UVC only (group 1), 1317 PICC only (group 2), and 1276 both UVC and PICC (group 3). FINDINGS: There were 403 CLABSIs among 6000 venous catheters inserted, totalling 43,302 catheter-days. CLABSI rates were higher in group 3 infants who were of lowest gestation (16.9 per 1000 UVC-days and 12.5 per 1000 PICC-days; median: 28 weeks) when compared with group 1 (3.3 per 1000 UVC-days; 37 weeks) and group 2 (4.8 per 1000 PICC-days; 30 weeks). Life table and Kaplan-Meier hazard analysis showed that UVC CLABSI rate increased stepwise to 42 per 1000 UVC-days by day 10, with the highest rate in group 3 (85 per 1000 UVC-days). PICC CLABSI rates remained relatively stable at 12-20 per 1000 PICC-days. Compared to PICC, UVC had a higher adjusted CLABSI risk controlled for dwell time. Among group 3, replacing UVC electively before day 4 may have a trend of lower CLABSI risk than late replacement. CONCLUSION: There was no cut-off duration beyond which PICC should be removed electively. Early UVC removal and replacement by PICC before day 4 might be considered.

Elastic cord-related ocular injury.

We report a case of an elastic cord-related ocular injury, to increase the public's awareness of the seriousness of this type of injury. A 43-year-old Chinese postman presented with decreased visual acuity in the left eye after being hit by an elastic cord at work. Slit lamp examination revealed pupillary sphincter rupture with iridodonesis and phacodonesis. There was also a traumatic nuclear cataract, gross hyphaema and vitreous haemorrhage. The patient was started on topical steroids and antibiotics. His visual acuity and vitreous haemorrhage improved during subsequent visits. Elastic cord-related ocular injuries have potential sight-threatening consequences. The public should be aware of the possible danger of using elastic cords.

Causes and management of Descemet's membrane detachment associated with cataract surgery--not always a benign problem.

INTRODUCTION: Detachments of Descemet's membrane (DM) occur with not uncommon frequency during cataract surgery. The figure for extracapsular cataract extraction (ECCE) is 2.6%, and that for phacoemulsification is 0.5%. Most detachments are small and of little visual consequence. Large detachments are rare but can lead to loss of vision. Early recognition and appropriate management is the key to a favourable outcome. This review provides cataract surgeons with guidelines to the management of this problem. METHODS: A review of reported studies on the subject was made using a MEDLINE search. A summary of the reviewed data is presented. RESULTS: The problem is fairly widespread, given the number of cataract operations done today. The important points with regard to aetiology, classification, recognition and appropriate management are presented in this article. CONCLUSION: DM detachment should not be taken lightly because of the potential for serious visual outcome. It may be avoided in a large majority of cases. Appropriate and prompt management may prevent the patient from suffering visual loss should it occur.

Asymptomatic QTc prolongation associated with quetiapine fumarate overdose in a patient being treated with risperidone.

We report a patient who ingested a 2000-mg overdose of quetiapine fumarate (Seroquel). Her maintenance medications also included risperidone, venlafaxine, topiramate, and clonazepam. On presentation, she was drowsy, but had no other significant CNS signs and no cardiac symptoms or abnormal physical signs. Approximately 2 h after the quetiapine ingestion, an electrocardiogram (ECG) showed normal sinus rhythm at 95 beats/min with a corrected QT (QTc) interval of 537 ms (upper limit of normal = 440 ms). Plasma quetiapine concentration at that time was 1800 ng/ml. Continuous ECG monitoring for the subsequent 18 h did not reveal any episode of ventricular tachycardia. A 12-lead ECG 18 h post-overdose was normal with a QTc interval of 401 ms and the corresponding plasma quetiapine concentration was 160 ng/ml. She made an uneventful medical recovery from the toxic ingestion. This case suggests that when patients overdose on quetiapine while taking therapeutic doses of risperidone, such overdoses, even if not massive, can cause considerable QTc interval prolongation. We recommend that quetiapine overdose patients undergo continuous ECG monitoring for 12-18 h post-ingestion.

Glycated proteins in diabetes.

The term nonenzymatic glycation (of protein) refers to a wide variety of spontaneous reactions between reducing sugars and protein-bound amines. This reaction has been documented in humans and plays a role in the development of diabetic complications and perhaps in some of the degenerative processes of aging. In addition to the monocarbonyl sugars and their derivatives, an additional source of glycation is alpha-dicarbonyls. Over time, nonenzymatic glycation leads to the formation of irreversible terminal products known collectively as advanced glycation end-products (AGE) and extensive data on the role of AGEs in the etiology of diabetic complications exist. Our improved ability to measure alpha-dicarbonyls and specific AGEs may provide new and more powerful tools to monitor diabetes and predict diabetic complications in the future.

Diabetic retinopathy and serum lipids.

The association between serum lipid levels and diabetic retinopathy has been investigated in many studies. Some studies show a positive relationship between serum cholesterol and low-density lipoprotein levels and retinal hard exudation. Other studies show serum triglyceride levels as being important in the progression of retinopathy. Certain other studies show no relationship between serum lipid levels and diabetic retinopathy. We review the literature on this subject and illustrate this report with an example of a diabetic with severe diabetic maculopathy and high serum lipid levels.

Performance of the enhanced Abbott AxSYM cardiac troponin I reagent in patients with heterophilic antibodies.

The presence of heterophilic antibodies in the serum of a small subpopulation of individuals continues to cause false results for modern-day immunoassays. In order to determine the frequency of heterophilic antibody (HA)-related false positives within our population of positive cardiac troponin I (cTnI) patients, we assayed 200 samples using the original in-house cTnI assay (Abbott AxSYM) and the Bayer ACS:180 cTnI, which we had previously observed to be more effective at blocking HA interference. Four samples were identified as false positives based on discordant results between the two assays, as well as the correction of the false positives by treatment of the samples with heterophilic antibody blocking reagent (HBR). An 'enhanced' version of the AxSYM cTnI reagent was designed to greatly reduce or eliminate HA interference, and has now replaced the original reagents. The present study shows that the enhanced reagent significantly reduced or eliminated much of the HA interference. Comparative studies between the enhanced cTnI reagent and the original Abbott AxSYM cTnI reagent showed excellent correlation and equivalent diagnostic concordance, when HA samples were excluded from the analysis.

A study of defaulters of treatment for diabetic retinopathy.

BACKGROUND AND AIM OF STUDY: Diabetic retinopathy needing Argon Laser Photocoagulation requires multiple sessions of treatment and follow-up. It is not uncommon for patients to default laser treatment for various social, economic or medical reasons. This paper aims to examine the common reasons for defaulting and to evaluate the effectiveness of a "no-show" compliance programme in reducing the rate of defaultment. MATERIALS AND METHODS: A "no-show" defaulters' compliance programme was introduced in July 1994. It was designed to recall defaulters for counselling and further laser treatment. We examined retrospectively a group of 1377 patients scheduled for Argon Laser Photocoagulation treatment at the Singapore National Eye Centre in the period July-December 1994 and compared it to another group of 1332 patients scheduled in the corresponding period in 1995 to assess the effectiveness of this programme. The common reasons for defaulting for the two periods were also reviewed and compared. RESULTS: The results were analysed using the Chi-square test and there was a significant decrease in the default rate in 1995; p < 0.01. CONCLUSION: The results showed that the "no-show" programme significantly decreased the number of defaulters over the period under study. In time, this will result in a decrease in diabetic blindness.

Trends in the pattern of blindness and major ocular diseases in Singapore and Asia.

This article details the changing trends in the major causes of blindness and visual impairment in Singapore over the past four decades. A comprehensive review of existing data from published and unpublished sources on ocular disease studies and surveys in Singapore was conducted. The rates of blindness and visual impairment from cataract, age-related macular degeneration, glaucoma, diabetic retinopathy and refractive errors, as well as other major diseases are described and compared with other Asian countries. Such epidemiological data on the blinding conditions in our population are vital in the understanding of trends in ocular diseases, as well as in prioritizing current health services and preventive programmes.

Anaemia--more than meets the eye.

Anaemia is a commonly encountered medical condition, although associated ophthalmic manifestations are not often sought or recognised. The authors present a case report of a patient with severe vitamin B12 deficiency anaemia with florid retinal changes classical of anaemic retinopathy. A review of the ocular involvement in anaemia is also presented.

Reactive oxygen intermediates increase vascular endothelial growth factor expression in vitro and in vivo.

Elevated vascular endothelial growth factor (VEGF) levels are required for ocular and tumor angiogenesis in animal models. Ischemic hypoxia is strongly correlated with increased VEGF expression in these systems and is considered a physiologically relevant stimulus. Because ischemic hypoxia is often followed by reperfusion and reactive oxygen intermediate (ROI) generation, we examined the potential role of ROI in the control of VEGF gene expression. Human retinal pigment epithelial cells exposed to superoxide or hydrogen peroxide rapidly increased VEGF mRNA levels. Superoxide-associated mRNA increases were dose dependent, blocked by antioxidants, and associated with elevated VEGF protein levels in conditioned media. Increases in VEGF mRNA levels were also observed in cultured human melanoma and rat glioblastoma cells with superoxide or hydrogen peroxide. Cycloheximide prevented the ROI-associated increases in VEGF mRNA. Transcriptional inhibition with actinomycin D revealed an inducible increase in VEGF mRNA half-life, but nuclear run-on experiments showed no increase in VEGF transcriptional rate. Reoxygenation of human retinal pigment epithelial cells in vitro and ocular reperfusion in vivo increased retinal VEGF mRNA levels. Antioxidants prevented the reperfusion-associated VEGF mRNA increases in retina. We conclude that ROIs increase VEGF gene expression in vitro and during the reperfusion of ischemic retina in vivo. The ROI-associated increases are mediated largely through increases in VEGF mRNA stability.

Up-regulation of vascular endothelial growth factor production by iron chelators.

Agents that modulate cellular iron availability have been studied for their antitumor activity. Based on encouraging in vitro studies, the iron chelator deferoxamine (DFO) has been used in clinical studies to treat cancer patients. The observation that DFO induced macular edema in several cancer patients led to the present investigation of vascular endothelial growth factor (VEGF) as a possible mediator of the encountered side effects. Both normal and malignant cell lines were incubated with DFO and a variety of other iron chelators. DFO, at concentrations achievable in humans, induced a 3-5-fold increase in VEGF mRNA expression in all cell lines studied. This increased VEGF mRNA expression was dose and time dependent. A panel of structurally different iron chelators induced an even more potent increase in VEGF mRNA expression. The DFO-induced increase in VEGF mRNA expression translated into 6- and 4-fold increases in VEGF protein secretion in conditioned media of retinal pigment epithelial and C6 glioblastoma cells, respectively. These findings suggest that VEGF may act as a mediator of the side effects induced by iron chelation therapy. In addition, because VEGF is an important regulator of angiogenesis, iron chelators should be given with caution to cancer patients.

Increased hyaluronan at sites of attachment to mesentery by CD44-positive mouse ovarian and breast tumor cells.

The mouse ovarian ascites tumor, MOT, and mammary ascites tumor, TA3/St, served as models to follow changes in hyaluronan levels during tumor growth, attachment, and invasion. Subsequent to introduction of tumor cells into the peritoneal cavity, hyaluronan accumulated intraperitoneally and at the initial sites of attachment of tumor cells and cell clumps to the mesenteric surface; the latter co-localized with sites of fibrin deposition as reported earlier. Subsequently, high levels of hyaluronan accumulated throughout the interior of the mesentery. Because neither tumor cell line synthesized substantial amounts of hyaluronan in culture, the large accumulations observed in the mesenteries and ascites fluid of tumor-bearing animals most likely resulted from increased synthesis and secretion by peritoneal-lining mesothelial cells and/or fibroblasts in response to stimulation by the tumor cells or their products. TA3/St tumor cells were universally positive for the hyaluronan receptor, CD44, whereas approximately 90% of MOT tumor cells were CD44-negative. However, the great majority of MOT or TA3/St cells that initially attached to the mesentery were strongly CD44 positive. We propose that hyaluronan-rich matrix is involved in tumor cell attachment to the mesentery possibly via interaction with tumor cell surface CD44.

Vascular permeability factor and vascular endothelial growth factor in ovarian hyperstimulation syndrome: a preliminary report.

OBJECTIVE: To determine whether serum levels of vascular permeability factor (VPF) are elevated in patients with ovarian hyperstimulation syndrome (OHSS) and to determine if luteinizing granulosa cells may be a source of VPF. DESIGN: Prospective observational study. SETTING: University IVF and GIFT program. PATIENTS: Eight consecutive IVF and GIFT patients at high risk for OHSS. MAIN OUTCOME MEASURES: Vascular permeability factor concentration in serum and follicular fluid. RESULTS: Serum VPF was significantly higher (15.2 +/- 4.0 pM; mean +/- SEM) on day +14 in the group who developed severe OHSS compared with those who did not. Follicular fluid VPF (171.5 +/- 18.5 pM) was approximately 100-fold greater than serum (1.7 +/- 1.3 pM) or peritoneal fluid (2.5 +/- 1.3 pM) 36 hours after hCG administration. CONCLUSION: Vascular permeability factor is elevated in patients with severe OHSS and the ovary may be a source of VPF secretion.

Expression of vascular permeability factor/vascular endothelial growth factor by melanoma cells increases tumor growth, angiogenesis, and experimental metastasis.

Vascular permeability factor (VPF)/vascular endothelial growth factor (VEGF) is an angiogenic cytokine expressed by many human and animal tumors. Hypoxia often up-regulates VPF/VEGF expression further. To better define the role of VPF/VEGF in tumor biology, we screened tumorigenic lines for those expressing minimal constitutive and hypoxia-inducible VPF/VEGF. Human melanoma SK-MEL-2 cells best fit these criteria and formed small, poorly vascularized tumors in immunodeficient mice. We transfected SK-MEL-2 cells stably with sense or antisense mouse VPF/VEGF cDNA or with vector alone. Cells transfected with sense VPF/VEGF (V+) expressed and secreted large amounts of mouse VPF/VEGF and formed well-vascularized tumors with hyperpermeable blood vessels and minimal necrosis in nude/SCID mice. Antisense-transfected VPF/VEGF (V-) cells expressed reduced constitutive VPF/VEGF and no detectable mouse VPF/VEGF, and formed small, minimally vascularized tumors exhibiting extensive necrosis. Vector-alone transfectants (N1 cells) behaved like parental cells. V+ cells formed numerous lung tumor colonies in SCID mice, approximately 50-fold more than N1 cells, whereas V- cells formed few or none. These experiments demonstrate that VPF/VEGF promotes melanoma growth by stimulating angiogenesis and that constitutive VPF/VEGF expression dramatically promotes tumor colonization in the lung.

Elevated serum levels of vascular endothelial growth factor in patients with preeclampsia.

OBJECTIVE: To determine whether altered levels of vascular endothelial growth factor (VEGF) may be implicated in the pathogenesis of preeclampsia, and whether VEGF mediates the endothelial cell activation that is involved in the pathogenesis of the clinical syndrome. METHODS: In a cross-sectional study, maternal serum samples in late pregnancy (at the time of clinical disease) were collected from 78 nulliparous women. These subjects were subdivided into those with preeclampsia (n = 27), nonproteinuric pregnancy-induced hypertension (n = 15), and normal pregnant women (n = 36). In a nested case-control study, in addition to samples taken before delivery, samples were obtained in early pregnancy (before clinical disease) and 24-48 hours postpartum from 12 of the patients with preeclampsia, 12 of those with nonproteinuric pregnancy-induced hypertension, and 12 of the normal pregnant subjects. Umbilical cord blood was sampled from 14 of the preeclamptic and 16 of the normal pregnant subjects. We measured VEGF levels in all samples using an immunofluorometric assay. RESULTS: In most samples collected before delivery, VEGF levels were below the lower limit of detection. However, the proportion of detectable levels was higher in the preeclampsia group (seven of 27) than in the normotensive group (one of 36, P < .05). The proportion in the nonproteinuric pregnancy-induced hypertension group (two of 15) did not differ significantly from the other groups. Levels in the patients with preeclampsia were not elevated before clinical disease. Levels of VEGF in umbilical blood samples were higher than in maternal venous blood, although there were no significant differences between groups. CONCLUSION: Serum VEGF levels were elevated in patients with preeclampsia, which suggests that the growth factor has a role in the endothelial cell activation that occurs in the disease.

Mass screening for diabetic retinopathy--a report on diabetic retinal screening in primary care clinics in Singapore.

INTRODUCTION: Mass screening for diabetic retinopathy is expensive and inaccessible if done by institutional ophthalmalogists. Most diabetics are seen in primary care. Hence it is logical to provide mass screening in primary care clinics. In Singapore, government polyclinics are ideal centres of screening as they are well organised and accessible to the community. SCREENING METHOD: An effective mass screening strategy must provide wide coverage, be low cost and have the ability to assess diabetic eyes accurately and quickly. Non-mydriatic fundal photography was used as the screening method. Mass coverage was achieved by rotating two cameras around six government polyclinics. Cost was reduced by training existing staff and organising the programme to provide a high turnover of screenees. The photographs were read by ophthalmologists in a government-owned hospital. Patients that required referral were referred to specialist eye clinics. RESULTS: A total of 13,296 patients were screened or rescreened during a period of 2 years (25 months). 2,911 patients or 21.8% of the total screened were found to have diabetic retinopathy. About half of these (10.8%) had sight threatening retinopathy. The most common sight threatening retinopathy was maculopathy (8.0%). Twenty-two percent of cases screened were referred. These include referral for other ocular conditions detected during the screening. CONCLUSION: Non-mydriatic fundal photography has proven to be both accessible and effective in screening diabetic eyes in urban Singapore and can be recommended for mass screening of diabetic eyes in the community.