Sequelae associated with cerebral candidiasis in two premature infants

This study reports on two premature infants who developed cerebral candidiasis and survived. Both were found to have significant handicaps on follow-up.     

Plasma L-arginine concentration, oxygenation index, and systemic blood pressure in premature infants

OBJECTIVE: To determine the relationships between plasma L-arginine concentrations and the severity of respiratory distress syndrome (RDS) or systemic blood pressure in premature infants. DESIGN: Prospective, observational study. SETTING: Neonatal intensive care, tertiary referral hospital. SUBJECTS: Fifty-three premature infants. INTERVENTIONS: We measured arginine and nutritional intake, plasma arginine concentration, total amino acid concentrations, and blood pressure on days 3, 7, 14, and 21 of life. In 33 infants who received assisted ventilation, oxygenation index could be calculated to reflect the severity of RDS. The relationships between plasma arginine and oxygenation index or blood pressure were analyzed using multiple linear regression. MEASUREMENTS AND MAIN RESULTS: On day 3, plasma arginine concentrations were decreased compared with normal published values. Arginine concentrations increased with the day of life of measurement (p < .001) and with arginine intake (p < .001). After adjusting for arginine intake and day of life, an inverse relationship was found between oxygenation index and plasma arginine concentrations: (p = .025). No similar relationship was found between oxygenation index and the concentration of total amino acids. A weak positive relationship was found between plasma arginine concentration and systemic blood pressure. CONCLUSIONS: Increments in the oxygenation index, reflective of an increased severity of RDS, are associated with a decrease in plasma arginine concentration. This finding may reflect arginine consumption by the nitric oxide synthase pathway in the lungs of premature infants with RDS, or may be explained by increased arginine catabolism. The lack of a similar relationship between total plasma amino acids and oxygenation index supports the first interpretation.     

Antenatal ambroxol treatment does not prevent the respiratory distress syndrome in premature infants

The effectiveness of ambroxol in the prevention of neonatal respiratory distress syndrome and in reducing the need for intermittent mandatory ventilation and oxygen therapy was studied in 88 mothers whose infants was born between 24 and 34 weeks of gestation and who were randomized either for treatment with ambroxol (group A = 42) or served as control (group B = 46). There were no significant differences in the mean gestational age, birth weight or Apgar score between the two groups. We found no significant differences in occurrence of respiratory distress syndrome (55% vs 45%), in support by intermittent mandatory ventilation (71% vs 72%) or oxygen therapy (74% vs 75%) at 12 h of age between groups A and B. CONCLUSION: This study does not suggest the efficacy of antenatal ambroxol treatment both for the prevention of neonatal respiratory distress syndrome and for the reduction of its severity.     

Antenatal steroids, condition at birth and respiratory morbidity and mortality in very preterm infants

The study purpose was to compare the effect of exercise training on serum lipid and apolipoprotein concentrations and the activities of intravascular enzymes related to lipid transport in previously untrained eumenorrheic, premenopausal (PRM) women (n = 21; mean age, 36 +/- 3 years) and estrogen-free postmenopausal (POM) women (n = 16; mean age, 68 +/- 8 years). Subjects trained at a progressive intensity and duration (50% to 75% maximal O2 consumption [VO2max], 200 to 300 kcal/session) 4 d/wk for 12 weeks. Before and after training, VO2max, body weight, relative body fat, and fasting blood samples were obtained following 2 weeks on a standardized diet designed to maintain body weight and during the early follicular stage for the PRM group. Blood samples were analyzed for serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), the cholesterol content of the HDL3 subfraction, apolipoprotein (apo)A-I and apoB, lipoprotein(a), and the activity of lecithin:cholesterol acyltransferase (LCAT). Total and hepatic triglyceride lipase activity (HTGLA) were determined from plasma samples obtained after heparin administration. The cholesterol content of the low-density lipoprotein (LDL) and HDL2 subfractions and endothelial-bound lipoprotein lipase activity (LPLA) were calculated. A two (group) x two (time) multivariate ANOVA (MANOVA), with repeated measures for time indicated that the exercise-induced changes in physiological measurements, serum lipid or apolipoprotein concentrations, or enzyme activities did not differ between groups. Serum concentrations of TC, LDL-C, and HDL3 cholesterol, TG, and apo A-I and apoB were higher in POM women compared with the PRM group (P < .05 for all). For the combined groups, body weight and relative body fat did not change with training, but VO2max increased an average of 18.5% (P < .05). LPLA, HTGLA, and LCAT activity were unaltered with exercise training. Except for a small but significant decrease in HDL-C (-5.5%) and an elevation in apoB (4.3%; P < .05 for both), the concentrations of serum lipids and apolipoproteins did not change over the training period. We conclude that in previously untrained women, menopausal status does not influence the exercise training response of serum lipids or apolipoproteins or activities of intravascular enzymes related to lipid transport.     

The need for inotropic support in a subgroup of infants with severe life-threatening respiratory syncytial viral infection

BACKGROUND: We experienced an unusual complication of life-threatening respiratory syncytial viral disease cardiovascular compromise. Life-threatening respiratory syncytial virus (RSV) infection has predominancy involved with ventilatory support for respiratory distress and/or failure. We performed a retrospective chart review of 20 consecutive infants admitted to the pediatric intensive care unit (PICU) for impending respiratory failure. METHODS: Seventeen required ventilatory support. As part of the infants' initial assessment, blood pressure, distal perfusion [capillary refill time (CRT) > or = 3 sec], decreased peripheral pulses, and peripheral mottling were used to determine cardiovascular compromise. These infants received volume resuscitation either at the referring facility or the PICU until euvolemia was obtained, as determined by central venous pressure (CVP) monitoring (between 3 to 7 cm H20). Nine of the 20 infants did not respond to volume resuscitation alone and required vasopressor support in the form of: Dopamine (7 patients, 5-10 micrograms/kg/min), Dobutamine (2 patients, 5-7 micrograms/kg/min), and one who expired required both Epinephrine (600 ng/kg/min) and Dopamine (10 micrograms/kg/min). The mean ages of these 9 patients were 6.2 +/- 3.4 weeks (range 3-12 weeks), the mean duration of ventilation was 7.2 +/- 4.1 days (range 4-12 days). The mean duration of pharmacologic support was 69.7 +/- 47 hours (range 14-168 hours). The mean ages of RSV+ infants not requiring inotropic support was 19.4 +/- 27.4 weeks (range 1-90 weeks), and mean duration of ventilation was 5.5 +/- 5.9 days (range 2-20 days). RESULTS: The inotrope treated patients were weaned from pharmacologic support prior to extubation, without any hemodynamic deficits. Our experience with this rather high incidence of hemodynamic complications during this RSV epidemic was unexpected. CONCLUSION: These results substantiate the fact that younger patients with RSV disease are at both greater risk for pulmonary complications and cardiovascular deterioration and may thus benefit from pharmacologic support.     

Antenatal and delivery risk factors simultaneously associated with neonatal death and cerebral palsy in preterm infants

Apomorphine is a powerful agonist of dopaminergic receptors which several years ago was introduced into the therapy of Parkinson's Disease. The pharmacological activity of apomorphine already appears significant at low doses. Unfortunately, the difficulty in determining the drug in plasma at low concentrations hampers the completion of accurate pharmacokinetic studies in humans. Considering the analogy of apomorphine with the molecular structure of catecholamines, the extraction of the drug from plasma was optimized by using adsorption on alumina, a technique widely used for noradrenaline and adrenaline analysis in clinical chemistry laboratories. This method proved particularly efficient and selective in apomorphine extraction from plasma prior to high-performance liquid chromatographic analysis. After pretreatment of 200 microliters of plasma sample with 40 mg of alumina and 10 microliters of tris buffer (pH 8.6), the drug was eluted with 200 microliters of an acidic-organic solution. One volume of the supernatant was mixed with two volumes of phosphate buffer (pH 3.6), and 100 microliters of the obtained mixture were injected into the HPLC system. The chromatograph was equipped with a C18 reversed-phase column and with an electrochemical coulometric detector fitted with a high-sensitivity cell (first electrode 0.00 volts, second electrode +0.35 volts). Sensitivity (20 pg of injected drug), precision (CV within assay and between assays of 3.7% and 5.6%, respectively) and accuracy were comparable to more complex analytical procedures. The miniaturisation of the entire sample pretreatment proved very advantageous for pharmacokinetics studies and, in principle, for therapeutic drug monitoring and toxicological investigations.     

Craniotomy procedures are associated with less analgesic requirements than other surgical procedures

NorA is a membrane-associated multidrug efflux protein that can decrease susceptibility to fluoroquinolones in Staphylococcus aureus. To determine the effect of NorA inhibition on the pharmacodynamics of fluoroquinolones, we evaluated the activities of levofloxacin, ciprofloxacin, and norfloxacin with and without various NorA inhibitors against three genetically related strains of S. aureus (SA 1199, the wild-type; SA 1199B, a NorA hyperproducer with a grlA mutation; and SA 1199-3, a strain that inducibly hyperproduces NorA) using susceptibility testing, time-kill curves, and postantibiotic effect (PAE) methods. Levofloxacin had the most potent activity against all three strains and was minimally affected by addition of NorA inhibitors. In contrast, reserpine, omeprazole, and lansoprazole produced 4-fold decreases in ciprofloxacin and norfloxacin MICs and MBCs for SA 1199 and 4- to 16-fold decreases for both SA 1199B and SA 1199-3. In time-kill experiments reserpine, omeprazole, or lansoprazole increased levofloxacin activity against SA 1199-3 alone by 2 log10 CFU/ml and increased norfloxacin and ciprofloxacin activities against all three strains by 0.5 to 4 log10 CFU/ml. Reserpine and omeprazole increased norfloxacin PAEs on SA 1199, SA 1199B, and SA 1199-3 from 0.9, 0.6, and 0.2 h to 2.5 to 4.5, 1.1 to 1.3, and 0.4 to 1.1 h, respectively; similar effects were observed with ciprofloxacin. Reserpine and omeprazole increased the levofloxacin PAE only on SA 1199B (from 1.6 to 5.0 and 3.1 h, respectively). In conclusion, the NorA inhibitors dramatically improved the activities of the more hydrophilic fluoroquinolones (norfloxacin and ciprofloxacin). These compounds may restore the activities of these fluoroquinolones against resistant strains of S. aureus or may potentially enhance their activities against sensitive strains.     

Arterial blood pressure measurement with oscillometric instruments in newborns and infants

Non-invasive blood pressure measurements by the auscultatory method do not provide reliable, reproducible blood pressure values in many neonates because the Korottkoff sounds are often very difficult to detect. This resulted in the development of many alternative indirect methods. Devices utilizing the Doppler ultrasound technique have not found wide acceptance. Since the introduction of automated oscillometric blood pressure monitors, arterial blood pressure has been increasingly brought into discussion as an indicator of the circulatory state. This is the first study to investigate the similarity and reproducibility of the data obtained with five oscillometric devices for measurement of blood pressure in neonates. MATERIALS AND METHODS. Since investigations on the technical performance are not practical in the clinical setting of a neonatal or pediatric ward, we used two simulators, the CuffLink (Dynatech, Nevada, USA) and a device developed by the PTB (Physikalisch-Technische Bundesanstalt). While the latter uses oscillations originally obtained from neonates, the CuffLink uses artificial and therefore ideal signals for the blood pressure monitors. The signals used for the PTB simulator were obtained from three neonates with an average age of 2 months and a weight of 3.5 kg, 4.4 kg, and 7.8 kg. The following blood pressure monitors were studied: Hoyer/Colin, BP-1001; Datex, Cardiocap II; SpaceLabs, model no. 90426; Hewlett-Packard, NBP M1008A; Critikon, Dinamap 1846. Before the measurements were started, the cuff pressure display of each monitor was checked according to a verification procedure. Although the 4 mmHg margin of error was not exceeded, the results were corrected. RESULTS. The results of the measurements show significant differences between the blood pressure monitors from the various manufacturers, with the differences for the ideal signals of the CuffLink-Simulator being less pronounced than those for the PTB simulator. Direct comparison of results is therefore often impossible. The standard deviation, taken from 20 measurements per monitor and simulation, is below 4 mmHg for both simulators. We can therefore conclude that the reproducibility of data is satisfactory and the emerging trend is reliable. DISCUSSION. The difference between the results of the PTB simulator and the CuffLink are probably due to the method of evaluation and the identification of artifacts of each blood pressure monitor. This is also confirmed by the studies of Mieke et al. The manufacturers should provide devices that display comparative results and improve the algorithms for detection of artefacts, increasing the accuracy of their blood pressure monitors. This could be done with the help of simulators. Considering the pathophysiological characteristics of neonates and infants, the systematic differences between the five monitors have to be regarded as serious.     

Production of endothelin-1 induced by blood transfusion in premature infants

We demonstrated a relationship between blood transfusion and plasma ET-1 levels in 10 premature infants with anemia. Changes in plasma ET-1 and lipoperoxide levels, blood pressure and available oxygen before and after the blood transfusion were determined. Plasma ET-1 levels were significantly elevated after blood transfusion (before: 8.0 +/- 2.8; after: 15.7 +/- 5.4 pg/ml, p < 0.01). A positive correlation was observed between plasma ET-1 levels and lipoperoxide levels (r = 0.887, p < 0.01). There was a significant correlation between plasma ET-1 levels and transfused blood volumes (r = 0.758, p < 0.01). No positive correlation was observed between plasma ET-1 levels and available oxygen. These results suggest that blood transfusion may be a stimulator of ET-1 overproduction and that it may lead to tissue injury through an endothelin-induced oxygen radical formation system.     

Soluble L-selectin plasma concentrations in infants undergoing heart surgery: no association with capillary leak syndrome or need for respiratory support

OBJECTIVE: In critical care patients at risk of developing the acute respiratory distress syndrome (ARDS), low soluble L-selectin (sCD62L) plasma concentrations have been shown to be associated with progression to ARDS and prolonged subsequent mechanical ventilation. This study aimed to determine the usefulness of sCD62L plasma concentrations to identify infants undergoing cardiovascular surgery who are at risk for postoperative pulmonary dysfunction and capillary leaks. DESIGN: Serial measurements of sCD62L plasma concentrations in a cohort of infants with congenital heart disease before, during, and after surgery for 4 consecutive days. SETTING AND PATIENTS: Infants aged 3-337 days undergoing cardiovascular surgery with (N = 27) or without (N = 12) cardiopulmonary bypass in a tertiary care center. RESULTS: sCD62L concentrations before surgery showed a strong correlation with the infant's age (r = 0.77, p < 0.001). During surgery, sCD62L levels dropped from 9.0 +/- 0.7 to 5.6 +/- 0.4 nmol/l (mean +/- SEM; p < 0.001). The minimum sCD62L concentration during and after surgery did not differ between infants operated upon with or without cardiopulmonary bypass (p > 0.1) or in infants who did (N = 10) or did not (N = 29) develop capillary leak syndrome. Whereas capillary leak syndrome was associated with prolonged mechanical ventilation (p < 0.01), there was no relationship between sCD62L concentrations at baseline or at any time thereafter and number of hours on the ventilator(p > 0.1). CONCLUSION: sCD62L concentrations before or after surgery are not apt to identify infants at increased risk of prolonged mechanical ventilation.     

Early changes in plasma brain and atrial natriuretic peptides in premature infants: correlation with pulmonary arterial pressure

To define the change in plasma natriuretic peptides in newborns, we prospectively studied 10 premature infants. They were followed sequentially during the first week of extrauterine life by two-dimensional and pulsed Doppler echocardiography, and studied for atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). We estimated mean pulmonary arterial pressure (MPAP) and measured blood pressure on days 1, 2, 3, 5, 7, respectively. Plasma ANP levels were 81.7 +/- 11.4 pg/ml on day 1 and 67.9 +/- 6.0 pg/ml on day 7, respectively. Between day 2 and day 7, there was a fall in MPAP, i.e. from 37 +/- 4 mmHg to 22 +/- 2 mmHg (P < 0.01), which was associated with a significant decrease in plasma BNP (41.8 +/- 10.1 pg/ml on day 2 vs. 10.4 +/- 0.9 pg/ml on day 7, P < 0.01). There was a positive correlation between MPAP and plasma BNP level (r = 0.643, P < 0.0001), but there was no correlation between MPAP and plasma ANP level. These data suggest that the pattern of secretion of BNP is different from that of ANP and that BNP levels reflect the changes of pulmonary arterial pressure in the neonatal period in premature infants.     

Elevated blood lead levels in children are associated with lower erythropoietin concentrations

PURPOSE: We investigated the incidence of well-directed violent behavior and suicide attempts in patients with temporal lobe epilepsy, with special attention to postictal psychosis. METHODS: We compared 57 episodes of postictal psychosis with 62 episodes of acute interictal (or alternative) psychosis and with 134 complex partial seizures. All patients were matched for age and for age at onset of seizures. RESULTS: The incidence of well-directed violent behavior against human beings was significantly higher (23%) during postictal psychotic episodes than during acute interictal episodes (5%) and postictal confusion (1%). Suicide attempts were also more frequent during postictal psychosis (7%) than during either acute interictal psychosis (2%) or postictal confusion (0%). CONCLUSIONS: Our study showed that well-directed violent and self-destructive behavior was not a feature of epileptic psychosis in general but a specific hallmark of postictal psychosis.     

Xanthine oxidase activity associated with arterial blood pressure in spontaneously hypertensive rats

Recent evidence in vivo indicates that spontaneously hypertensive rats (SHR) exhibit an increase in oxyradical production in and around microvascular endothelium. This study is aimed to examine whether xanthine oxidase plays a role in overproduction of oxidants and thereby may contribute to hypertensive states as a consequence of the increasing microvascular tone. The xanthine oxidase activity in SHR was inhibited by dietary supplement of tungsten (0.7 g/kg) that depletes molybdenum as a cofactor for the enzyme activity as well as by administration of (-)BOF4272 [(-)-8-(3-methoxy-4-phenylsulfinylphenyl)pyrazolo(1,5-alpha)-1,3, 5-triazine-4-monohydrate], a synthetic inhibitor of the enzyme. The characteristic elevation of mean arterial pressure in SHR was normalized by the tungsten diet, whereas Wistar Koto (WKY) rats displayed no significant alteration in the pressure. Multifunctional intravital videomicroscopy in mesentery microvessels with hydroethidine, an oxidant-sensitive fluoroprobe, showed that SHR endothelium exhibited overproduction of oxyradicals that coincided with the elevated arteriolar tone as compared with WKY rats. The tungsten diet significantly repressed these changes toward the levels observed in WKY rats. The activity of oxyradical-producing form of xanthine oxidase in the mesenteric tissue of SHR was approximately 3-fold greater than that of WKY rats, and pretreatment with the tungsten diet eliminated detectable levels of the enzyme activity. The inhibitory effects of the tungsten diet on the increasing blood pressure and arteriolar tone in SHR were also reproducible by administration of (-)BOF4272. These results suggest that xanthine oxidase accounts for a putative source of oxyradical generation that is associated with an increasing arteriolar tone in this form of hypertension.     

The risk factors for early anemia in premature infants

The following items were the main risk factors for development of early anemia of prematurity (EAP): profound prematurity, prenatal hypotrophy, multiple pregnancy, gestosis, anemia of pregnancy, cardiovascular disorders in the mother. Hence, prevention of failing to bear, timely detection and treatment of anemia of pregnancy, of gestosis, health promotion in women of child-bearing age are all considered essential measures to be instituted in EAP prophylaxis.     

Influence of infection on patent ductus arteriosus and chronic lung disease in premature infants weighing 1000 grams or less

OBJECTIVES: To test the hypotheses that (1) infection increases ductal dilatory prostaglandins and inflammatory mediators that may influence the closure of a patent ductus arteriosus (PDA), increasing the incidence of late episodes of PDA (after 7 days) and the rate of closure failures, and (2) the concurrence of PDA and infection increases the risk of chronic lung disease (CLD). METHODS: One hundred fourteen premature infants (birth weight, 500 to 1000 gm) were prospectively assessed for PDA and infection. Serum levels of 6-ketoprostaglandin F1 alpha and tumor necrosis factor alpha were measured routinely in all infants and when PDA or infection was present. Multivariate assessment of risk factors for PDA closure failure and for CLD was done by logistic regression, and expressed as an odds ratio and as 95% confidence intervals. RESULTS: Late PDA episodes were more frequent in infants with infection than in those without infection. A temporally related infection (<5 days between both diagnoses) was associated with an increased risk of PDA closure failure (odds ratio, 19.1 (confidence interval, 4 to 90)). In addition to birth weight and the severity of initial respiratory failure, PDA and infection increased the risk of CLD (odds ratio, 11.7 (confidence interval, 1.7 to 81) for PDA; odds ration, 3.1 (confidence interval, 1 to 11) for infection). Furthermore, when both factors were temporally related, they further increased the risk of CLD (odds ratio, 29.6 (confidence interval, 4.5 to >100)). Infants with infection and those with PDA had higher levels of 6-ketoprostaglandin F1 alpha than did control subjects. Levels of tumor necrosis factor alpha were also elevated in infants with infection and in those with late PDA. CONCLUSIONS: Infection adversely influences PDA outcome by increasing the risk of late ductal reopening and PDA closure failures. Increased levels of prostaglandins and tumor necrosis factor alpha in infants with infection may explain the poor PDA outcome. The concurrence of PDA and infection potentiates their negative effects on the risk of CLD.     

Evaluation of hypothalamic-pituitary-adrenal axis in premature infants treated with dexamethasone

Results of a national survey of the current use of steroids in newborns in 1993 showed that 95% of the neonatologists in the United States have used dexamethasone for neonates at risk for chronic lung disease. Dexamethasone therapy for a period of a week or longer is associated with suppression of the hypothalamic-pituitary-adrenal axis (HPAA) in a substantial number of premature infants. A review of our current understanding of the biochemical tests evaluating HPAA function in premature infants and suggested guidelines for HPAA evaluation and management following dexamethasone therapy are presented.     

24 hour monitoring of blood pressure in premature and full-term new born babies

Using a 24 hour monitoring of the systo-diastolic blood pressure, 127 new born babies were studied in the first five days of life. 45 of these new born babies were premature (35 +/- 1 week) and 82 full-term. The results showed an overlap in the systo-diastolic blood pressure in the 2 groups of subjects with a rise and fall in pressure in the 24 hour period and no fall in pressure during the night typical to a healthy adult.