The impact of diabetic ketoacidosis and age on behavior six months post-diagnosis in children with type 1 diabetes

Objectives: Children with type 1 diabetes mellitus (DM1) may be at increased risk of psychosocial and adjustment difficulties. We examined behavioral outcomes six months post-diagnosis in a group of children with newly diagnosed DM1. Methods: This study formed part of a larger longitudinal project examining pathophysiology and neuropsychological outcomes in diabetic patients with or without diabetic ketoacidosis (DKA). Participants were 61 children (mean age 11.8 years, SD 2.7 years) who presented with a new diagnosis of DM1 at the Royal Children’s Hospital, Melbourne. Twenty-three (11 female) presented in DKA and 38 (14 female) without DKA. Parents completed the behavior assessment system for children, second edition six months post-diagnosis. Results: There was a non-linear relationship between age and behavior. Internalising problems (i.e. anxiety depression, withdrawal) peaked in the transition from childhood to adolescence; children aged 10–13 years had elevated rates relative to the normal population (t = 2.55, P = 0.018). There was a non-significant trend for children under 10 to display internalising problems (P = 0.052), but rates were not elevated in children over 13 (P = 0.538). Externalising problems were not significantly elevated in any age group. Interestingly, children who presented in DKA were at lower risk of internalising problems than children without DKA (t = 3.83, P < 0.001). There was no effect of DKA on externalising behaviors. Conclusions: Children transitioning from childhood to adolescence are at significant risk for developing internalising problems such as anxiety and lowered mood after diagnosis of DM1. Somewhat counter-intuitively, parents of children presenting in DKA reported fewer internalising symptoms than parents of children without DKA. These results highlight the importance of monitoring and supporting psychosocial adjustment in newly diagnosed children even when they seem physically well.

Doctors' knowledge of the law on withholding and withdrawing life-sustaining medical treatment

Objectives To examine the level of knowledge of doctors about the law on withholding and withdrawing life-sustaining treatment from adults who lack decision-making capacity, and factors associated with a higher level of knowledge. Design, setting and participants Postal survey of all specialists in emergency medicine, geriatric medicine, intensive care, medical oncology, palliative medicine, renal medicine and respiratory medicine on the AMPCo Direct database in New South Wales, Victoria and Queensland. Survey initially posted to participants on 18 July 2012 and closed on 31 January 2013. Main outcome measures Medical specialists’ levels of knowledge about the law, based on their responses to two survey questions. Results Overall response rate was 32%. For the seven statements contained in the two questions about the law, the mean knowledge score was 3.26 out of 7. State and specialty were the strongest predictors of legal knowledge. Conclusions Among doctors who practise in the end-of-life field, there are some significant knowledge gaps about the law on withholding and withdrawing life-sustaining treatment from adults who lack decision-making capacity. Significant consequences for both patients and doctors can flow from a failure to comply with the law. Steps should be taken to improve doctors’ legal knowledge in this area and to harmonise the law across Australia.

Acute injuries in track and field athletes: A 3-year observational study at the Penn Relays Carnival with epidemiology and medical coverage implications

Background Few studies have examined acute injuries in track and field in both elite and sub-elite athletes. Purpose To observe the absolute and relative rates of injury in track and field athletes across a wide range of competition levels and ages during three years of the Penn Relays Carnival to assist with future medical coverage planning and injury prevention strategies. Study design: Descriptive epidemiology study. Methods Over a 3-year period all injuries treated by the medical staff were recorded on a standardised injury report form. Absolute injury rates (absolute number of injuries) and relative injury rates (number of injuries per 1000 participants) were determined and odds ratios (OR) of injury rates were calculated between sexes, competition levels and events. Injuries were also broken down into major or minor medical or orthopedic injuries. Results Throughout the study period 48,473 competing athletes participated in the Penn Relays Carnival, and 436 injuries were sustained. For medical coverage purposes, the relative rate of injury subtypes was greatest for minor orthopedic injuries (5.71 injuries per 1000 participants), followed by minor medical injuries (3.42 injuries per 1000 participants), major medical injuries (0.69 injuries per 1000 participants) and major orthopedic injuries (0.18 injuries per 1000 participants). College/elite level athletes displayed the lowest relative injury rate (7.99 injuries per 1000 participants), which was significantly less than high school (9.87 injuries per 1000 participants) and masters level athletes (16.33 injuries per 1000 participants). Males displayed a greater likelihood of suffering a minor orthopedic injury compared to females (OR = 1.36, 95% CI = 1.06 to 1.75; χ2 = 5.73, p = 0.017) but were less likely to sustain a major medical injury (OR = 0.33, 95% CI = 0.15 to 0.75; χ2 = 7.75, p = 0.005). Of the three most heavily participated in events, the 4 x 400m relay displayed the greatest relative injury rate (13.6 injuries per 1000 participants) compared to the 4 x 100 and 4 x 200m relay. Conclusions Medical coverage teams for future large scale track and field events need to plan for at least two major orthopedic and seven major medical injuries per 1000 participants. Male track and field athletes, particularly masters level male athletes, are at greater risk of injury compared to other genders and competition levels.

Incidence and fatality of serious suicide attempts in a predominantly rural population in Shandong, China : a public health surveillance study

Objectives To estimate the incidence of serious suicide attempts (SSAs, defined as suicide attempts resulting in either death or hospitalisation) and to examine factors associated with fatality among these attempters. Design A surveillance study of incidence and mortality. Linked data from two public health surveillance systems were analysed. Setting Three selected counties in Shandong, China. Participants All residents in the three selected counties. Outcome measures Incidence rate ( per 100 000 person-years) and case fatality rate (%). Methods Records of suicide deaths and hospitalisations that occurred among residents in selected counties during 2009–2011 (5 623 323 person-years) were extracted from electronic databases of the Disease Surveillance Points (DSP) system and the Injury Surveillance System (ISS) and were linked by name, sex, residence and time of suicide attempt. A multiple logistic regression model was developed to examine the factors associated with a higher or lower fatality rate. Results The incidence of SSAs was estimated to be 46 (95% CI 44 to 48) per 100 000 person-years, which was 1.5 times higher in rural versus urban areas, slightly higher among females, and increased with age. Among all SSAs, 51% were hospitalised and survived, 9% were hospitalised but later died and 40% died with no hospitalisation. Most suicide deaths (81%) were not hospitalised and most hospitalised SSAs (85%) survived. The fatality rate was 49% overall, but was significantly higher among attempters living in rural areas, who were male, older, with lower education or with a farming occupation. With regard to the method of suicide, fatality was lowest for non-pesticide poisons (7%) and highest for hanging (97%). Conclusions The incidence of serious suicide attempts is substantially higher in rural areas than in urban areas of China. The risk of death is influenced by the attempter’s sex, age, education level, occupation, method used and season of year.

Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990-2010: A systematic analysis for the Global Burden of Disease Study 2010

BACKGROUND Measuring disease and injury burden in populations requires a composite metric that captures both premature mortality and the prevalence and severity of ill-health. The 1990 Global Burden of Disease study proposed disability-adjusted life years (DALYs) to measure disease burden. No comprehensive update of disease burden worldwide incorporating a systematic reassessment of disease and injury-specific epidemiology has been done since the 1990 study. We aimed to calculate disease burden worldwide and for 21 regions for 1990, 2005, and 2010 with methods to enable meaningful comparisons over time. METHODS We calculated DALYs as the sum of years of life lost (YLLs) and years lived with disability (YLDs). DALYs were calculated for 291 causes, 20 age groups, both sexes, and for 187 countries, and aggregated to regional and global estimates of disease burden for three points in time with strictly comparable definitions and methods. YLLs were calculated from age-sex-country-time-specific estimates of mortality by cause, with death by standardised lost life expectancy at each age. YLDs were calculated as prevalence of 1160 disabling sequelae, by age, sex, and cause, and weighted by new disability weights for each health state. Neither YLLs nor YLDs were age-weighted or discounted. Uncertainty around cause-specific DALYs was calculated incorporating uncertainty in levels of all-cause mortality, cause-specific mortality, prevalence, and disability weights. FINDINGS Global DALYs remained stable from 1990 (2·503 billion) to 2010 (2·490 billion). Crude DALYs per 1000 decreased by 23% (472 per 1000 to 361 per 1000). An important shift has occurred in DALY composition with the contribution of deaths and disability among children (younger than 5 years of age) declining from 41% of global DALYs in 1990 to 25% in 2010. YLLs typically account for about half of disease burden in more developed regions (high-income Asia Pacific, western Europe, high-income North America, and Australasia), rising to over 80% of DALYs in sub-Saharan Africa. In 1990, 47% of DALYs worldwide were from communicable, maternal, neonatal, and nutritional disorders, 43% from non-communicable diseases, and 10% from injuries. By 2010, this had shifted to 35%, 54%, and 11%, respectively. Ischaemic heart disease was the leading cause of DALYs worldwide in 2010 (up from fourth rank in 1990, increasing by 29%), followed by lower respiratory infections (top rank in 1990; 44% decline in DALYs), stroke (fifth in 1990; 19% increase), diarrhoeal diseases (second in 1990; 51% decrease), and HIV/AIDS (33rd in 1990; 351% increase). Major depressive disorder increased from 15th to 11th rank (37% increase) and road injury from 12th to 10th rank (34% increase). Substantial heterogeneity exists in rankings of leading causes of disease burden among regions. INTERPRETATION Global disease burden has continued to shift away from communicable to non-communicable diseases and from premature death to years lived with disability. In sub-Saharan Africa, however, many communicable, maternal, neonatal, and nutritional disorders remain the dominant causes of disease burden. The rising burden from mental and behavioural disorders, musculoskeletal disorders, and diabetes will impose new challenges on health systems. Regional heterogeneity highlights the importance of understanding local burden of disease and setting goals and targets for the post-2015 agenda taking such patterns into account. Because of improved definitions, methods, and data, these results for 1990 and 2010 supersede all previously published Global Burden of Disease results.

To increase or decrease dosage of antimicrobials in septic patients during continuous renal replacement therapy: the eternal doubt

Critical illness, acute renal failure and continuous renal replacement therapy (CRRT) are associated with changes in pharmacokinetics. Initial antibiotic dose should be based on published volume of distribution and generally be at least the standard dose, as volume of distribution is usually unchanged or increased. Subsequent doses should be based on total clearance. Total clearance varies with the CRRT clearance which mainly depends on effluent flow rate, sieving coefficient/saturation coefficient. As antibiotic clearance by healthy kidneys is usually higher than clearance by CRRT, except for colistin, subsequent doses should generally be lower than given to patients without renal dysfunction. In the future therapeutic drug monitoring, together with sophisticated pharmacokinetic models taking into account the pharmacokinetic variability, may enable more appropriate individualized dosing.

A Mouse Model of Early-Onset Renal Failure Due to a Xanthine Dehydrogenase Nonsense Mutation

Chronic kidney disease (CKD) is characterized by renal fibrosis that can lead to end-stage renal failure, and studies have supported a strong genetic influence on the risk of developing CKD. However, investigations of the underlying molecular mechanisms are hampered by the lack of suitable hereditary models in animals. We therefore sought to establish hereditary mouse models for CKD and renal fibrosis by investigating mice treated with the chemical mutagen N-ethyl-N-nitrosourea, and identified a mouse with autosomal recessive renal failure, designated RENF. Three-week old RENF mice were smaller than their littermates, whereas at birth they had been of similar size. RENF mice, at 4-weeks of age, had elevated concentrations of plasma urea and creatinine, indicating renal failure, which was associated with small and irregularly shaped kidneys. Genetic studies using DNA from 10 affected mice and 91 single nucleotide polymorphisms mapped the Renf locus to a 5.8Mbp region on chromosome 17E1.3. DNA sequencing of the xanthine dehydrogenase (Xdh) gene revealed a nonsense mutation at codon 26 that co-segregated with affected RENF mice. The Xdh mutation resulted in loss of hepatic XDH and renal Cyclooxygenase-2 (COX-2) expression. XDH mutations in man cause xanthinuria with undetectable plasma uric acid levels and three RENF mice had plasma uric acid levels below the limit of detection. Histological analysis of RENF kidney sections revealed abnormal arrangement of glomeruli, intratubular casts, cellular infiltration in the interstitial space, and interstitial fibrosis. TUNEL analysis of RENF kidney sections showed extensive apoptosis predominantly affecting the tubules. Thus, we have established a mouse model for autosomal recessive early-onset renal failure due to a nonsense mutation in Xdh that is a model for xanthinuria in man. This mouse model could help to increase our understanding of the molecular mechanisms associated with renal fibrosis and the specific roles of XDH and uric acid. © 2012 Piret et al.

Psychological distress and pain reporting in Australian coal miners

BACKGROUND: Coal mining is of significant economic importance to the Australian economy. Despite this fact, the related workforce is subjected to a number of psychosocial risks and musculoskeletal injury, and various psychological disorders are common among this population group. Because only limited research has been conducted in this population group, we sought to examine the relationship between physical (pain) and psychological (distress) factors, as well as the effects of various demographic, lifestyle, and fatigue indicators on this relationship. METHODS: Coal miners (N = 231) participated in a survey of musculoskeletal pain and distress on-site during their work shifts. Participants also provided demographic information (job type, age, experience in the industry, and body mass index) and responded to questions about exercise and sleep quality (on- and off-shift) as well as physical and mental tiredness after work. RESULTS: A total of 177 workers (80.5%) reported experiencing pain in at least one region of their body. The majority of the sample population (61.9%) was classified as having low-level distress, 28.4% had scores indicating mild to moderate distress, and 9.6% had scores indicating high levels of distress. Both number of pain regions and job type (being an operator) significantly predicted distress. Higher distress score was also associated with greater absenteeism in workers who reported lower back pain. In addition, perceived sleep quality during work periods partially mediated the relationship between pain and distress. CONCLUSION: The study findings support the existence of widespread musculoskeletal pain among the coal-mining workforce, and this pain is associated with increased psychological distress. Operators (truck drivers) and workers reporting poor sleep quality during work periods are most likely to report increased distress, which highlights the importance of supporting the mining workforce for sustained productivity.

Biceps femoris architecture and strength in athletes with a prior ACL reconstruction

Purpose To determine if limbs with a history of anterior cruciate ligament (ACL) injury reconstructed from the semitendinosus (ST) display different biceps femoris long head (BFlh) architecture and eccentric strength, assessed during the Nordic hamstring exercise, compared to the contralateral uninjured limb. Methods The architectural characteristics of the BFlh were assessed at rest and at 25% of a maximal voluntary isometric contraction (MVIC) in the control (n=52) and previous ACL injury group (n=15) using two-dimensional ultrasonography. Eccentric knee-flexor strength was assessed during the Nordic hamstring exercise. Results Fascicle length was shorter (p=0.001; d range: 0.90 to 1.31) and pennation angle (p range: 0.001 to 0.006: d range: 0.87 to 0.93) was greater in the BFlh of the ACL injured limb when compared to the contralateral uninjured limb at rest and during 25% of MVIC. Eccentric strength was significantly lower in the ACL injured limb than the contralateral uninjured limb (-13.7%; -42.9N; 95% CI = -78.7 to -7.2; p=0.021; d=0.51). Fascicle length, MVIC and eccentric strength were not different between the left and right limb in the control group. Conclusions Limbs with a history of ACL injury reconstructed from the ST have shorter fascicles and greater pennation angles in the BFlh compared to the contralateral uninjured side. Eccentric strength during the Nordic hamstring exercise of the ACL injured limb is significantly lower than the contralateral side. These findings have implications for ACL rehabilitation and hamstring injury prevention practices which should consider altered architectural characteristics.

Communicating consequences with costs: A commentary on Corso et al's cost of injury

Estimating the economic burden of injuries is important for setting priorities, allocating scarce health resources and planning cost-effective prevention activities. As a metric of burden, costs account for multiple injury consequences—death, severity, disability, body region, nature of injury—in a single unit of measurement. In a 1989 landmark report to the US Congress, Rice et al1 estimated the lifetime costs of injuries in the USA in 1985. By 2000, the epidemiology and burden of injuries had changed enough that the US Congress mandated an update, resulting in a book on the incidence and economic burden of injury in the USA.2 To make these findings more accessible to the larger realm of scientists and practitioners and to provide a template for conducting the same economic burden analyses in other countries and settings, a summary3 was published in Injury Prevention. Corso et al reported that, between 1985 and 2000, injury rates declined roughly 15%. The estimated lifetime cost of these injuries declined 20%, totalling US$406 billion, including US$80 billion in medical costs and US$326 billion in lost productivity. While incidence reflects problem size, the relative burden of injury is better expressed using costs.

Proposed vehicle impact speed: Severe injury probability relationships for selected crash types

Speed is recognised as a key contributor to crash likelihood and severity, and to road safety performance in general. Its fundamental role has been recognised by making Safe Speeds one of the four pillars of the Safe System. In this context, impact speeds above which humans are likely to sustain fatal injuries have been accepted as a reference in many Safe System infrastructure policy and planning discussions. To date, there have been no proposed relationships for impact speeds above which humans are likely to sustain fatal or serious (severe) injury, a more relevant Safe System measure. A research project on Safe System intersection design required a critical review of published literature on the relationship between impact speed and probability of injury. This has led to a number of questions being raised about the origins, accuracy and appropriateness of the currently accepted impact speed–fatality probability relationships (Wramborg 2005) in many policy documents. The literature review identified alternative, more recent and more precise relationships derived from the US crash reconstruction databases (NASS/CDS). The paper proposes for discussion a set of alternative relationships between vehicle impact speed and probability of MAIS3+ (fatal and serious) injury for selected common crash types. Proposed Safe System critical impact speed values are also proposed for use in road infrastructure assessment. The paper presents the methodology and assumptions used in developing these relationships. It identifies further research needed to confirm and refine these relationships. Such relationships would form valuable inputs into future road safety policies in Australia and New Zealand.

Doctors’ perspectives on law and life-sustaining treatment: Survey design and recruitment strategies for a challenging cohort

- Background Palliative medicine and other specialists play significant legal roles in decisions to withhold and withdraw life-sustaining treatment at the end of life. Yet little is known about their knowledge of or attitudes to the law, and the role they think it should play in medical practice. Consideration of doctors’ views is critical to optimizing patient outcomes at the end of life. However, doctors are difficult to engage as participants in empirical research, presenting challenges for researchers seeking to understand doctors’ experiences and perspectives. - Aims To determine how to engage doctors involved in end-of-life care in empirical research about knowledge of the law and the role it plays in medical practice at the end of life. - Methods Postal survey of all specialists in palliative medicine, emergency medicine, geriatric medicine, intensive care, medical oncology, renal medicine, and respiratory medicine in three Australian states: New South Wales, Victoria, and Queensland. The survey was sent in hard copy with two reminders and a follow up reminder letter was also sent to the directors of hospital emergency departments. Awareness was further promoted through engagement with the relevant medical colleges and publications in professional journals; various incentives to respond were also used. The key measure is the response rate of doctors to the survey. - Results Thirty-two percent of doctors in the main study completed their survey with response rate by specialty ranging from 52% (palliative care) to 24% (medical oncology). This overall response rate was twice that of the reweighted pilot study (16%). - Conclusions Doctors remain a difficult cohort to engage in survey research but strategic recruitment efforts can be effective in increasing response rate. Collaboration with doctors and their professional bodies in both the development of the survey instrument and recruitment of participants is essential.

Short and long term mortality rates after a lower limb amputation

Objective To determine mortality rates after a first lower limb amputation and explore the rates for different subpopulations. Methods Retrospective cohort study of all people who underwent a first amputation at or proximal to transtibial level, in an area of 1.7 million people. Analysis with Kaplan-Meier curves and Log Rank tests for univariate associations of psycho-social and health variables. Logistic regression for odds of death at 30-days, 1-year and 5-years. Results 299 people were included. Median time to death was 20.3 months (95%CI: 13.1; 27.5). 30-day mortality = 22%; odds of death 2.3 times higher in people with history of cerebrovascular disease (95%CI: 1.2; 4.7, P = 0.016). 1 year mortality = 44%; odds of death 3.5 times higher for people with renal disease (95%CI: 1.8; 7.0, P < 0.001). 5-years mortality = 77%; odds of death 5.4 times higher for people with renal disease (95%CI: 1.8; 16.0,P = 0.003). Variation in mortality rates was most apparent in different age groups; people 75–84 years having better short term outcomes than those younger and older. Conclusions Mortality rates demonstrated the frailty of this population, with almost one quarter of people dying within 30-days, and almost half at 1 year. People with cerebrovascular had higher odds of death at 30 days, and those with renal disease and 1 and 5 years, respectively.

Missing-In-Metastasis (MIM) regulates cell morphology by promoting plasma membrane and actin cytoskeleton dynamics

The cells of multicellular organisms have differentiated to carry out specific functions that are often accompanied by distinct cell morphology. The actin cytoskeleton is one of the key regulators of cell shape subsequently controlling multiple cellular events including cell migration, cell division, endo- and exocytosis. A large set of actin regulating proteins has evolved to achieve and tightly coordinate this wide range of functions. Some actin regulator proteins have so-called house keeping roles and are essential for all eukaryotic cells, but some have evolved to meet the requirements of more specialized cell-types found in higher organisms enabling complex functions of differentiated organs, such as liver, kidney and brain. Often processes mediated by the actin cytoskeleton, like formation of cellular protrusions during cell migration, are intimately linked to plasma membrane remodeling. Thus, a close cooperation between these two cellular compartments is necessary, yet not much is known about the underlying molecular mechanisms. This study focused on a vertebrate-specific protein called missing-in-metastasis (MIM), which was originally characterized as a metastasis suppressor of bladder cancer. We demonstrated that MIM regulates the dynamics of actin cytoskeleton via its WH2 domain, and is expressed in a cell-type specific manner. Interestingly, further examination showed that the IM-domain of MIM displays a novel membrane tubulation activity, which induces formation of filopodia in cells. Following studies demonstrated that this membrane deformation activity is crucial for cell protrusions driven by MIM. In mammals, there are five members of IM-domain protein family. Functions and expression patterns of these family members have remained poorly characterized. To understand the physiological functions of MIM, we generated MIM knockout mice. MIM-deficient mice display no apparent developmental defects, but instead suffer from progressive renal disease and increased susceptibility to tumors. This indicates that MIM plays a role in the maintenance of specific physiological functions associated with distinct cell morphologies. Taken together, these studies implicate MIM both in the regulation of the actin cytoskeleton and the plasma membrane. Our results thus suggest that members of MIM/IRSp53 protein family coordinate the actin cytoskeleton:plasma membrane interface to control cell and tissue morphogenesis in multicellular organisms.

Balance of growth factors in the human perinatal lung : Implications for physiological lung development and link to bronchopulmonary dysplasia

The aims of this Thesis was to evaluate the role of proangiogenic placental growth factor (PlGF), antiangiogenic endostatin and lymphangiogenic vascular endothelial growth factor (VEGF) -C as well as the receptors vascular endothelial growth factor receptor (VEGFR) -2 and VEGFR-3 during lung development and in development of lung injury in preterm infants. The studied growth factors were selected due to a close relationship with VEGF-A; a proangiogenic growth factor important in normal lung angiogenesis and lung injury in preterm infants. The thesis study consists of three analyses. I: Lung samples from fetuses, preterm and term infants without lung injury, as well as preterm infants with acute and chronic lung injury were stained by immunohistochemistry for PlGF, endostatin, VEGF-C, VEGFR-2 and VEGFR-3. II: Tracheal aspirate fluid (TAF) was collected in the early postnatal period from a patient population consisting of 59 preterm infants, half developing bronchopulmonary dysplasia (BPD) and half without BPD. PlGF, endostatin and VEGF-C concentrations were measured by commercial enzyme-linked immunosorbent assay (ELISA). III: Cord plasma was collected from very low birth weight (VLBW) (n=92) and term (n=48) infants in conjuncture with birth and endostatin concentrations were measured by ELISA. I: All growth factors and receptors studied were consistently stained in immunohistochemistry throughout development. For endostatin in early respiratory distress syndrome (RDS), no alveolar epithelial or macrophage staining was seen, whereas in late RDS and BPD groups, both alveolar epithelium and macrophages stained positively in approximately half of the samples. VEGFR-2 staining was fairly consistent, except for the fact that capillary endothelial staining in the BPD group was significantly decreased. II: During the first postnatal week in TAF mean PlGF concentrations were stable whereas mean endostatin and VEGF-C concentrations decreased. Higher concentrations of endostatin and VEGF-C correlated with lower birth weight (BW) and associated with administration of antenatal betamethasone. Parameters reflecting prenatal lung inflammation associated with lower PlGF, endostatin and VEGF-C concentrations. A higher mean supplemental fraction of inspired oxygen during the first 2 postnatal weeks (FiO2) correlated with higher endostatin concentrations. III: Endostatin concentrations in term infants were significantly higher than in VLBW infants. In VLBW infants higher endostatin concentrations associated with the development of BPD, this association remained significant after logistic regression analysis. We conclude that PlGF, endostatin and VEGF-C all have a physiological role in the developing lung. Also, the VEGFR-2 expression profile seems to reflect the ongoing differentiation of endothelia during development. Both endostatin and VEGFR-2 seem to be important in the development of BPD. During the latter part of the first postnatal week, preterm infants developing BPD have lower concentrations of VEGF-A in TAF. Our findings of disrupted VEGFR-2 staining in capillary and septal endothelium seen in the BPD group, as well as the increase in endostatin concentrations both in TAF and cord plasma associated with BPD, seem to strengthen the notion that there is a shift in the angiogenic balance towards a more antiangiogenic environment in BPD. These findings support the vascular hypothesis of BPD.