Recent advances in diagnosis and management of pulmonary hypertension in chronic lung disease

Pulmonary hypertension with elevated pulmonary vascular resistance is a common cardiovascular complication associated with increased morbidity and mortality in preterm infants with chronic lung disease. Injury to the developing pulmonary circulation results in structural and functional abnormalities of the pulmonary vasculature. Animal studies have demonstrated that disruption of angiogenesis may contribute to the failure of normal alveolarisation in chronic lung disease. Levels of vascular endothelial growth factor in bronchoalveolar lavage fluid are lower in infants with chronic lung disease compared to preterm controls. Supplemental oxygen is commonly used to prevent and treat pulmonary hypertension, although optimal arterial oxygen saturation levels remain uncertain. Other vasodilators such as inhaled nitric oxide appear promising, but as yet have not been evaluated in the form of randomised controlled trials. Further studies are required to investigate the long-term effectiveness of pulmonary vasodilator therapy.     

Right Ventricular Performance in Hypotensive Preterm Neonates Treated with Dopamine

Systemic hypotension with left ventricular dysfunction is a common complication of neonatal respiratory distress syndrome and is often treated with inotropic agents. Although pulmonary hypertension with elevated pulmonary vascular resistance is also an important pathophysiological finding in respiratory distress syndrome, the effect of inotropes on the right ventricle has not been studied. The aim of this study was to assess changes in right ventricular dimensions and function with inotropic therapy in hypotensive preterm infants. Hypotensive neonates with respiratory distress syndrome were studied before and 1 hour after the initiation of a dopamine infusion. Right ventricular performance was assessed by two-dimensional echocardiography using the ellipsoid approximation method. Eight hypotensive neonates were recruited with a median (interquartile range) gestation of 27 weeks (26 to 27 weeks). Right ventricular end systolic volume decreased significantly from a median (interquartile range) of 1.06 ml/kg (0.81-1.50 ml/kg) to 0.73 ml/kg (0.51-0.99 ml/kg) (p < 0.01) 1 hour following dopamine therapy. Right ventricular end diastolic volume did not change significantly. Right ventricular ejection fraction increased significantly from 0.36 (0.29-0.46) to 0.51 (0.43-0.53) ( p < 0.01). There was a trend toward an increase in right ventricular output from 90 ml/kg/min (67-115 ml/kg/min) to 112 ml/kg/min-143 ml/kg/min) (p=0.07). Dopamine increases right ventricular ejection fraction through a reduction in right ventricular end systolic volume.     

Identification of the cell types in the rostral pars distalis of the pituitary gland of the catfish, Clarias batrachus (Linn)

The cells in the rostral pars distalis (RPD) of the hypophysis of the catfish, Clarias batrachus were distinguished into 2 types by tinctorial affinities, and their functional significance was ascertained experimentally. The lead haematoxylin (PbH)-positive cells of the RPD, herein referred to as the cell type 1, are in the form of a 3-8 cell layer thick palisade along the border between the neurohypophysis (NH) and the RPD. Administration of metopirone caused significant stimulatory changes in these cells, whereas injection of ACTH, hydrocortisone or dexamethasone resulted in marked regression suggesting their ACTH-secreting nature. The type 2 cells constitute a major part of the RPD and are erythrosinophilic in nature. They showed regressive changes after immersion of the catfish in sodium chloride solution and distilled water, and a similar change was observed after injection of prolactin which indicates their prolactin-secreting nature.     

Neuropeptide Y in the forebrain of the adult male cichlid fish Oreochromis mossambicus: distribution, effects of castration and testosterone replacement

We studied the organization of the neuropeptide Y (NPY)-immunoreactive system in the forebrain of adult male cichlid fish Oreochromis mossambicus and its response to castration and testosterone replacement by using morphometric methods. Immunoreactivity for NPY was widely distributed in the forebrain, and the pattern generally resembled that in other teleosts. Whereas immunoreactivity was conspicuous in the ganglia of nervus terminalis (NT; or nucleus olfactoretinalis), a weak reaction was detected in some granule cells in the olfactory bulb and in the cells of area ventralis telencephali pars lateralis (Vl). Moderately to intensely immunoreactive cells were distinctly seen in the nucleus entopeduncularis (NE), nucleus preopticus (NPO), nucleus lateralis tuberis (NLT), paraventricular organ (PVO), and midbrain tegmentum (MT). NPY fibers were widely distributed in the forebrain. Castration for 10/15 days resulted in a drastic loss of immunoreactivity in the cells of NE (P<0.001) and a significant decrease (P<0.01) in their cell nuclear size. However, cell nuclei of the NT neurons showed a significant increase in size. A highly significant reduction in the NPY-immunoreactive fiber density (P<0.001) was observed in several areas of the forebrain. Although testosterone replacement reversed these changes, fibers in some areas showed supranormal responses. Immunoreactive cells in Vl, NPO, NLT, PVO, and MT and fiber density in some other areas did not respond to castration. We suggest that the NPY-immunoreactive elements that respond to castration and testosterone replacement may serve as the substrate for processing the positive feedback action of the steroid hormone.     

Concentrations of cardiac troponin T in neonates with and without respiratory distress

AIMS: To establish a practical postnatal reference range for cardiac troponin T in neonates and to investigate concentrations in neonates with respiratory distress. METHODS: Prospective investigation in a tertiary neonatal unit, recruiting infants with and without respiratory distress (sick and healthy infants respectively). Concentrations of cardiac troponin T were compared between sick and healthy infants, accounting for confounding variables. RESULTS: A total of 162 neonates (113 healthy and 49 sick infants) had samples taken. The median (interquartile range) cardiac troponin T concentration in the healthy infants was 0.025 (0.01-0.062) ng/ml, and the 95th centile was 0.153 ng/ml. There were no significant relations between cardiac troponin T and various variables. The median (interquartile range) cardiac troponin T concentration in the sick infants was 0.159 (0.075-0.308) ng/ml. This was significantly higher (p < 0.0001) than in the healthy infants. In a linear regression model, the use of inotropes and oxygen requirement were significant associations independent of other basic and clinical variables in explaining the variation in cardiac troponin T concentrations. CONCLUSIONS: Cardiac troponin T is detectable in the blood of many healthy neonates, but no relation with important basic and clinical variables was found. Sick infants have significantly higher concentrations than healthy infants. The variations in cardiac troponin T concentration were significantly associated with oxygen requirement or the use of inotropic support in a regression model. Cardiac troponin T may be a useful marker of neonatal and cardiorespiratory morbidity.     

Risk factors for invasive fungal infection in neonates

Invasive fungal infection is an uncommon, but increasing cause of morbidity and mortality in neonates. There are few controlled studies defining risk factors for the development of fungal infection in a contemporary neonatal population. This retrospective case-control study was undertaken to investigate antenatal, demographic and postnatal variables that may be potentially important in the development of fungal infection. Two gestation-matched controls were identified for each index case. Information about perinatal and demographic variables, as well as important neonatal outcomes, was obtained from case notes. Microbiological data collected included the presence of fungal colonization, and organisms responsible for invasive fungal infection. Over a 5-y period, 24 infants with invasive fungal infection and 48 controls were identified. Candida albicans was the organism identified in 75% of cases of fungal septicaemia, and in all cases complicated by fungal meningitis. Preceding fungal colonization, pulmonary haemorrhage and intrauterine growth restriction were factors significantly and independently associated with invasive fungal infection. Fifty-four percent of infants with invasive fungal infection died, and 82% of survivors developed chronic lung disease.

Conclusion : Some new and potentially important risk factors for the development of invasive fungal infection in a contemporary population of infants admitted to a neonatal intensive care were identified.