The pattern of cerebral injury in a primate model of preterm birth and neonatal intensive care

Survivors of very premature birth face an increased risk of adverse motor, cognitive, and behavior sequelae. In order to understand the pathogenesis of these adverse outcomes, an animal model of premature birth and neonatal care in a species with a close similarity to the human infant is sought. In this histological and immunohistochemical study we have defined the pattern of cerebral injury in a premature baboon model undergoing similar neonatal intensive care to that of the human premature infant. Sixteen baboons were delivered at 125 days gestation (dg; term approximately184 dg) with 14 days neonatal intensive care and were compared with gestational control brains at 125, 140, and 160 dg. The premature baboons undergoing neonatal intensive care sustained a spectrum of neuropathologies including white matter injury, hemorrhage, and ventriculomegaly, which resemble lesions frequently observed in the human premature infant. These data suggest that the premature baboon is a model with similarities in maturation and pattern of cerebral injury to the human infant that may provide useful insights of relevance to the human preterm infant.     

Posthaemorrhagic ventricular dilatation in the premature infant: natural history and predictors of outcome

OBJECTIVE: To investigate the natural history and predictors of outcome of posthaemorrhagic ventriculomegaly in the very low birthweight (VLBW) infant. METHODS: All VLBW infants admitted between September 1994 and September 1997 to the neonatal intensive care units of Brigham and Women's Hospital (Boston), Children's Hospital (Boston), and Christchurch Women's Hospital (New Zealand) with germinal matrix intraventricular haemorrhage (IVH) were identified. All charts and ultrasound scans were reviewed to define the natural history and perinatal and/or postnatal factors of value in prediction of the course of posthaemorrhagic ventriculomegaly. Progressive ventricular dilatation (PVD) was defined from the results of serial cranial ultrasound scans. RESULTS: A total of 248 VLBW infants had evidence of IVH (22% of all VLBW infants, mean (SD) gestational age 26.8 (2.6) weeks). A quarter of the infants exhibited PVD. Spontaneous arrest of PVD occurred without treatment in 38% of infants with PVD. Of the remaining 62% with persistent PVD, 48% received non-surgical treatment only (pharmacological and/or drainage of cerebrospinal fluid by serial lumbar punctures), 34% received surgical treatment with insertion of a ventriculoperitoneal reservoir and/or shunt, and 18% died. The development of PVD after IVH and adverse short term outcome, such as the requirement for surgery, were predicted most strongly by the severity of IVH. CONCLUSIONS: These data reflect the natural history of PVD in the 1990s and show that, despite a slight reduction in its overall incidence, there appears to be a more aggressive course, with appreciable mortality and morbidity in the extremely premature infant. The major predictor of adverse short term outcome, defined as death or need for surgical intervention, was the severity of IVH. These findings may be valuable for the management of very small premature infants.     

Efficacy and Safety of Terazosin to Improve Voiding in Spinal Cord Injury Patients

Abstract

A total of 28 male spinal cord injury (SCI) patients were enrolled in an open label study to evaluate the efficacy and safety of terazosin to improve voiding. All patients were started on 1 mg daily dose at bedtime. The dosage was gradually increased to 1–2 mg twice daily, depending upon patient tolerance and a minimum acceptable systolic blood pressure of 90 mm Hg. Urodynamic evaluation was done in 24 patients prior to and one week after a maximum tolerated dose was established for at least 48 hours. The maximum dose varied from 1 to 5 mg daily. Subjective improvement in voiding was noticed in 50 percent of patients. Objective assessment with urodynamics showed a mean drop in maximum voiding pressure of 35 cm H2O (range 9–65 cm H2O) in only 42 percent of patients. Subjective improvement in voiding occurred in 14 of 17 patients with absent detrusor sphincter dyssynergia. The drug was discontinued in three patients with side effects of syncope in one patient, lethargy in another and body rash in the third. Because the tolerance dose of terazosin is variable and the therapeutic response is unpredictable, urodynamic monitoring is recommended to accomplish a useful outcome. (J Spinal Cord Med; 18:236–239)     

An Update on Cardiac Troponins as Circulating Biomarkers in Heart Failure

Circulating troponins and natriuretic peptides are the only biomarkers specifically released from cardiac myocytes that can be determined with robust and sensitive analytical methods, even in healthy subjects. These intracellular proteins are released from reversibly or irreversibly damaged cardiac myocytes into the bloodstream by mechanisms that are not entirely clear. The recent introduction of a new generation of highly sensitive assays of cardiac troponin I or T has not only improved the early diagnosis of acute myocardial infarction but also suggested that there are several causes for troponin release other than acute coronary syndromes. Circulating troponins are elevated in patients with acute or chronic heart failure and are strongly associated with outcome, independently of natriuretic peptides, the benchmark biomarkers in heart failure. In the absence of further experimental evidences, the pathophysiologic basis for the elevation of circulating cardiac troponins in patients with stable chronic heart failure remains speculative.     

Reproducibility of noninvasive cardiac output during arm exercise in spinal cord injury

The carbon dioxide (CO(2)) rebreathing method is a noninvasive technique to estimate cardiac output during exercise, but few data are available on the validity and reliability of this measure in individuals with spinal cord injury (SCI). Sixteen male subjects with SCI (mean age 45 +/- 9, seven paraplegic and nine tetraplegic) underwent three submaximal steady state arm ergometer exercise tests. We estimated cardiac output using the exponential CO(2) rebreathing technique at an individualized exercise intensity approximating 50% of peak oxygen uptake. Mean values for the cardiac output measurements were 13.0 +/- 2.4, 13.3 +/- 2.0, and 13.4 +/- 1.7 L/min; the difference among the trials was not significant (p = 0.54). The typical error was 1.80 +/- 0.85 L/min, the limits of agreement were 11.3 to 15.3 L/min, the coefficient of variation was 5.4% +/- 3.4%, and the intraclass correlation coefficient was 0.85 (95% confidence interval = 0.70-0.94). The test-to-test variation in estimated cardiac output during arm ergometry in individuals with SCI is similar to that observed in studies that used this technique in ambulatory persons. The 5% relative variation between tests suggests that the CO(2) rebreathing technique for estimating cardiac output can be performed in SCI individuals with acceptable reproducibility.