Heart rate characteristics and neurodevelopmental outcome in very low birth weight infants.

BACKGROUND: Sepsis in very low birth weight (VLBW) infants has been associated with an increased risk of adverse developmental outcome. We have identified abnormal heart rate characteristics (HRCs) that are predictive of impending sepsis, and we have developed a summary measure of an infant's abnormal HRCs during the neonatal hospitalization that we refer to as the cumulative HRC score (cHRC). OBJECTIVE: In this study, we tested the hypothesis that increasing cHRC is associated with an increasing risk of adverse neurodevelopmental outcome in VLBW infants. METHOD: Data were collected on 65 VLBW infants whose HRCs were monitored while in the neonatal intensive care unit and who were examined at 12 to 18 months adjusted age. Using the Bayley Scale of Infant Development-II, we identified delays in early cognitive function (i.e., Mental Developmental Index <70) and psychomotor development (i.e., Psychomotor Developmental Index <70). Cerebral palsy (CP) was diagnosed using a standard neurological examination. RESULT: Increasing cHRC score was associated with an increased risk of CP (odds ratio per 1 standard deviation increase in cHRC: 2.6, 95% confidence limits: 1.42, 5.1) and delayed early cognitive development [odds ratio: 2.3 (1.3; 4.3)]. These associations remain statistically significant when adjusted for major cranial ultrasound abnormality. There was an association of increasing cHRC and delayed psychomotor development, which did not reach statistical significance [odds ratio: 1.7 (1.0, 3.0)]. CONCLUSION: Among VLBW infants, the cumulative frequency of abnormal HRCs, which can be assessed non-invasively in the neonatal intensive care unit, is associated with an increased risk of adverse neurodevelopmental outcome.

Discharge outcomes of extremely low birth weight infants with spontaneous intestinal perforations.

OBJECTIVE: To examine discharge outcomes of extremely low birth weight infants (ELBW) with spontaneous intestinal perforation (SIP). STUDY DESIGN: A single-center retrospective cohort study of all ELBW infants admitted to the University of Virginia neonatal intensive care unit between July 1996 and June 2004. RESULTS: We found 35 patients with SIP (incidence 8.4%). The median gestational age was 25 weeks, median birth weight was 722 g, and 71% of the infants were male. Most infants (n=28) with SIP were diagnosed secondary to pneumoperitoneum; however, one-third (7) of infants<25 weeks had occult presentations without pneumoperitoneum. When controlled for gestational age, gender, multiple gestation, indomethacin, and glucocorticoid exposure, infants with SIP have a higher risk of PVL and death than infants without perforation. SUMMARY: Periventricular leukomalacia and death are significantly associated with SIP in ELBW after adjusting for gestational age, multiple gestation, indomethacin, and glucocorticoid exposure.

MRI based diffusion and perfusion predictive model to estimate stroke evolution.

In this study we present a novel automated strategy for predicting infarct evolution, based on MR diffusion and perfusion images acquired in the acute stage of stroke. The validity of this methodology was tested on novel patient data including data acquired from an independent stroke clinic. Regions-of-interest (ROIs) defining the initial diffusion lesion and tissue with abnormal hemodynamic function as defined by the mean transit time (MTT) abnormality were automatically extracted from DWI/PI maps. Quantitative measures of cerebral blood flow (CBF) and volume (CBV) along with ratio measures defined relative to the contralateral hemisphere (r(a)CBF and r(a)CBV) were calculated for the MTT ROIs. A parametric normal classifier algorithm incorporating these measures was used to predict infarct growth. The mean r(a)CBF and r(a)CBV values for eventually infarcted MTT tissue were 0.70 +/- 0.19 and 1.20 +/- 0.36. For recovered tissue the mean values were 0.99 +/- 0.25 and 1.87 +/- 0.71, respectively. There was a significant difference between these two regions for both measures (p < 0.003 and p < 0.001, respectively). Mean absolute measures of CBF (ml/100g/min) and CBV (ml/100g) for the total infarcted territory were 33.9 +/- 9.7 and 4.2 +/- 1.9. For recovered MTT tissue, the mean values were 41.5 +/- 7.2 and 5.3 +/- 1.2, respectively. A significant difference was also found for these regions (p < 0.009 and p < 0.036, respectively). The mean measures of sensitivity, specificity, positive and negative predictive values for modeling infarct evolution for the validation patient data were 0.72 +/- 0.05, 0.97 +/- 0.02, 0.68 +/- 0.07 and 0.97 +/- 0.02. We propose that this automated strategy may allow possible guided therapeutic intervention to stroke patients and evaluation of efficacy of novel stroke compounds in clinical drug trials.

Comparison and clinical application of frequency domain methods in analysis of neonatal heart rate time series.

The frequency content of the heart rate (HR) series contains information regarding the state of the autonomic nervous system. Of particular importance is respiratory sinus arrhythmia (RSA), the high-frequency fluctuation in HR attributable to respiration. The unevenly sampled nature of heart rate data, however, presents a problem for the discrete Fourier transform. Interpolation of the HR series allows even sampling, but filters high-frequency content. The Lomb periodogram (LP) is a regression-based method that addresses these issues. To evaluate the efficacy of the LP and Fourier techniques in detecting RSA, we compared the spectrum of intervals, the spectrum of HR samples, and the LP of simulated and clinical neonatal time series. We found the LP was superior to the spectrum of intervals and the spectrum of HR samples in analysis near the critical frequency of one half the average sampling rate. Applying the LP to clinical data, we found (1) evidence of stochastic resonance, an enhancement of periodicity with the addition of small amounts of noise, and (2) reduced power at all frequencies prior to clinical diagnosis of neonatal sepsis.

Toward the early diagnosis of neonatal sepsis and sepsis-like illness using novel heart rate analysis.

BACKGROUND AND OBJECTIVE: Abrupt clinical deterioration because of sepsis is a major cause of morbidity and mortality in neonates, and earlier diagnosis should improve therapy of this potentially catastrophic illness. In practice, clinical signs and laboratory data have not been perceived as sensitive or specific for early stages of sepsis. Because heart rate characteristics (HRC) are abnormal during fetal distress and neonatal illness, we hypothesized that abnormal HRC might precede the clinical diagnosis of neonatal sepsis, adding independent information to standard clinical parameters. METHODS: In the neonatal intensive care unit at the University of Virginia, we prospectively studied infants admitted from August 1995 to April 1999 who were at risk for developing sepsis. Infants in the sepsis (culture-positive) and sepsis-like illness (culture-negative) groups had an abrupt clinical deterioration that raised clinical suspicion of infection and prompted physicians to obtain blood cultures and start antibiotic therapy. Infants without sepsis raised no clinical suspicion of illness and had no cultures obtained. We measured novel characteristics-moments and percentiles-of normalized heart rate (HR) time series for 5 days before and 3 days after sepsis, sepsis-like illness, or a random time in controls. We also calculated the Score for Neonatal Acute Physiology (SNAP) and the Neonatal Therapeutic Intervention Scoring System (NTISS) as clinical scores of the severity of illness. RESULTS: There were 46 episodes of culture-positive sepsis in 40 patients and 27 episodes of culture-negative sepsis-like illness in 23 patients. We analyzed 29 control periods in 26 patients. Infants with sepsis and sepsis-like illness had lower birth weights and gestational ages and higher SNAP and NTISS scores than did infants without sepsis. The most important new finding was that the infants in the sepsis and sepsis-like illness groups had increasingly abnormal HRC for up to 24 hours preceding their abrupt clinical deterioration. The abnormal HRC were reduced baseline variability and short-lived decelerations in HR. These abnormalities led to significant changes in HRC measures, for example, the third moment (skewness:.59 +/-.10 for sepsis and.51 +/-. 12 for sepsis-like illness, compared with -.10 +/-.13 for control over the 6 hours before abrupt deterioration). Culture-positive and culture-negative patients had similar HRC and clinical scores, including a significant rise in SNAP in the 24 hours before the event. Multivariable logistic regression analysis showed that HRC and clinical scores independently added information in distinguishing infants with sepsis and sepsis-like illness from control patients in the 24 hours before abrupt deterioration. CONCLUSIONS: Newborn infants who had abrupt clinical deterioration as a result of sepsis and sepsis-like illness had abnormal HRC and SNAP that worsened over 24 hours before the clinical suspicion of sepsis. A strategy for monitoring these parameters in infants at risk for sepsis and sepsis-like illness might lead to earlier diagnosis and more effective therapy.heart rate variability, neonatal sepsis, Score for Neonatal Acute Physiology, Neonatal Therapeutic Intervention Scoring System, newborn.

Can the elimination of lactose from formula improve feeding tolerance in premature infants?

OBJECTIVE: To determine whether a low-lactose formula (LLF, <5% lactose) would ameliorate feeding intolerance in premature infants. STUDY DESIGN: Prospective, randomized, controlled trial involving 306 infants <36 weeks' gestation and weighing <1800 g who received either lactose-containing formula (LCF) 24 kcal/oz or a specially prepared LLF, which was comparable to the LCF except for the functional replacement of lactose with maltose. We examined outcome variables of feeding intolerance and cases of necrotizing enterocolitis (NEC) and suspected NEC. RESULTS: One hundred forty-nine infants were assigned to receive LCF, of which 99 infants received LCF only. One hundred fifty infants were assigned to receive LLF, of which 102 infants received LLF only. The remaining infants received LCF or LLF plus some quantity of human milk or human milk alone. Infants receiving LLF had improved enteral caloric intake and weight gain, reached full feeds faster, had less gastric residual, spent less time without oral intake, and had fewer feedings stopped than the LCF group. The number of cases of NEC and suspected NEC was similar in both groups. CONCLUSION: Low-lactose premature infant formula improved feeding tolerance. There was no evidence that LLF altered the incidence of NEC, but the incidence of NEC in this study was too low to draw conclusions.

Multivariate examination of data from gait analysis of persons with stroke.

BACKGROUND AND PURPOSE: Gait analyses yield redundant information that often is difficult to interpret. The purpose of this study was to show how principal-component analysis can provide insight into gait data obtained from persons with stroke. SUBJECTS: Twenty male and 11 female adults who were ambulatory were studied (mean age = 60.5 years, SD = 11.8, range = 24-79; mean time since stroke = 11.4 months, SD = 15.4, range = 2.0-88.0). METHODS: Spatial data were used in a 4-segment link-segment model to calculate the kinematic and kinetic variables of gait. Principal components were constructed on the averages for 40 variables. RESULTS: The first principal component was related to speed and accounted for 40.8% of the variance. The second principal component was related to differences between the 2 limbs (symmetry) and accounted for 12.8% of the variance. The third principal component was related to adoption of a postural flexion bias and accounted for 10.2% of the variance. The fourth principal component, which was not interpretable, accounted for 6.8% of the variance. CONCLUSION AND DISCUSSION: The principal-component analysis allowed clustering of related variables and simplified the complex picture presented by the large number of variables resulting from gait analysis. Examination of variables closely related to each principal component yielded insight into the nature of the strategies used in walking and their interrelationships. The method has potential for insight into similarities and differences in gait performances arising from different pathologies and for comparing the progress of individuals with similar pathologies.

Probing the order within neonatal heart rate variability.

The mechanism by which heart rate variability (HRV) changes during neonatal illness is not known. One possibility is that reduced HRV is merely a diminished or scaled-down version of normal. Another possibility is that there is a fundamental change in the mechanism underlying HRV, resulting in a change in the ordering of RR intervals. We investigated the nature and extents of order in RR interval time series from 25 Neonatal Intensive Care Unit patients with a spectrum of clinical illness severity and HRV. We measured predictability (deviation of predicted intervals from observed), and regularity (measured as approximate entropy) of RR interval time series showing different degrees of HRV. In RR interval time series where the effects of scaling were removed, we found 1) records showing normal HRV had more order than those showing low HRV; 2) the nature of the order was more like that of a periodic process with frequencies over a large range (time series whose log-log power spectrum had a 1/f distribution) than that of chaotic one (logistic map); and 3) the nature of order did not change greatly as HRV fell. We conclude that neonatal RR interval time series are ordered by periodic processes with frequencies over a large range, and that the extent of order is less during illness when HRV is low.

Role for anions in pulmonary endothelial permeability.

beta-Adrenergic stimulation reduces albumin permeation across pulmonary artery endothelial monolayers and induces changes in cell morphology that are mediated by Cl- flux. We tested the hypothesis that anion-mediated changes in endothelial cells result in changes in endothelial permeability. We measured permeation of radiolabeled albumin across bovine pulmonary arterial endothelial monolayers when the extracellular anion was Cl-, Br-, I-, F-, acetate (Ac-), gluconate (G-), and propionate (Pr-). Permeability to albumin (Palbumin) was calculated before and after addition of 0.2 mM of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX), which reduces permeability. In Cl-, the Palbumin was 3.05 +/- 0.86 x 10(-6) cm/s and fell by 70% with the addition of IBMX. The initial Palbumin was lowest for Pr- and Ac-. Initial Palbumin was higher in Br-, I-, G-, and F- than in Cl-. A permeability ratio was calculated to examine the IBMX effect. The greatest IBMX effect was seen when Cl- was the extracellular anion, and the order among halide anions was Cl- > Br- > I- > F-. Although the level of extracellular Ca2+ concentration ([Ca2+]o) varied over a wide range in the anion solutions, [Ca2+]o did not systematically affect endothelial permeability in this system. When Cl- was the extracellular anion, varying [Ca2+]o from 0.2 to 2.8 mM caused a change in initial Palbumin but no change in the IBMX effect. The anion channel blockers 4-acetamido-4'-isothiocyanotostilbene-2, 2'-disulfonic acid (0.25 mM) and anthracene-9-carboxylic acid (0.5 mM) significantly altered initial Palbumin and the IBMX effect. The anion transport blockers bumetanide (0.2 mM) and furosemide (1 mM) had no such effects. We conclude that extracellular anions influence bovine pulmonary arterial endothelial permeability and that the pharmacological profile fits better with the activity of anion channels than with other anion transport processes.

Bone hardness testing in the trabecular bone of the human patella.

Bone hardness of 10 human patellas in 15 regions and at three depths was measured through in situ indentation tests. Indentation tests were performed perpendicular to the three articular surfaces (lateral and medial facets, and central ridge area) and, thus, parallel to the trabeculae. Multiple regression analysis demonstrated a significant reduction of bone hardness with depth. In addition, the lateral facet had a higher bone hardness than the medial facet, and the proximal and central regions demonstrated higher bone hardness than the distal region. Overall, the proximolateral region of the patella exhibited the highest hardness compared with other regions. As bone hardness is indicative of load bearing, these results may have important consequences for patellar resurfacing and patellar component design.

Cutaneous sparganosis.

Sparganosis is an infection caused by migrating larvae of the cestode genus Spirometra. There have been approximately 62 cases of sparganosis reported in the United States. Although a subcutaneous mass is the most common manifestation, sparganosis is not well-described in the dermatology literature. We present a case of cutaneous sparganosis in a 52-year-old Filipino American woman. Histologically, the sections showed a granulomatous panniculitis and dermatitis containing a section of a sparganum. A transverse section of an intact sparganum reveals an eosinophilic cuticle, loose stroma, calcareous bodies, and smooth muscle fibers.

Unitary anion currents through phospholemman channel molecules.

Phospholemman (PLM) is a 72-amino-acid peptide with a single transmembrane domain, the expression of which induces chloride currents in Xenopus oocytes. It has remained unknown whether PLM is an ion channel or acts as a channel regulator. Here we show, by measuring unitary anion currents across planar phospholipid bilayers to which immunoaffinity-purified recombinant PLM was added, that it does indeed form ion channels. Excised patches of oocytes expressing PLM had similar currents. Of the ions tested, the sulphonic amino acid taurine was the most permeant, and expression of PLM increased fluxes of radiolabelled taurine in oocytes. Phospholemman is the smallest protein in cell membranes known to form an ion channel and the taurine selectivity suggests that it is involved in cell volume regulation.

Exercise, posture, and back pain during pregnancy.

One of the expected benefits of exercise programmes for pregnant women is to reduce or prevent back pain by improving posture. The aim of this project was to evaluate the effect of fitness classes for pregnant women on posture and back pain. In this article, postural aspects are reported. Sixty five pregnant volunteers were included in the study, of whom 27 were enrolled in exercise classes designed according to Canadian guidelines and 38 acted as sedentary controls. Posture was assessed every 4 weeks during pregnancy and 4 months postpartum by measuring curvatures of the lumbar and thoracic spines in a standard relaxed standing position from lateral photographs. Laxity of knee ligaments was also monitored using a clinical arthrometer. Weight gain could explain part of lordosis increase during pregnancy but the effect was not very strong. No effect of exercise on posture was detected. RELEVANCE: This study showed that fitness classes for pregnant women designed according to Canadian guidelines had no detectable effect on posture during pregnancy.

Exercise, posture, and back pain during pregnancy.

In this article the effect of exercise on pregnancy-related back pain is reported. Sixty five pregnant volunteers were included in the study, of whom 27 were enrolled in exercise classes designed according to Canadian guidelines, and 38 acted as sedentary controls. Back pain and functional limitations were assessed every 4 weeks during pregnancy and 4 months postpartum by questionnaires. No significant differences in back pain or functional limitations reported by the two groups were found. The biomechanical factors measured in this study, weight, back posture, and laxity, were unable to explain most of the variation in pain reported. RELEVANCE: This study showed that fitness classes for pregnant women designed according to Canadian guidelines had no detectable effect on back pain during pregnancy. If prevention of pregnancy-related back pain is sought through exercise, design of fitness programmes for pregnant women should be reconsidered.

Patterns of knee arthrosis and patellar subluxation.

This study was based on the unexpected observation of lateral patellofemoral subluxation in the varus osteoarthritic knee. Standardized radiographs of 109 knees (65 patients with osteoarthritis) were selected randomly from the authors' database and retrospectively reviewed. Hip-knee-ankle alignment data were correlated with patellofemoral subluxation and tilt, as well as with radiographic patellofemoral grades for arthrosis. The amount and site of patellofemoral arthrosis were correlated with patellar position and limb alignment. Patellae that were located centrally in the trochlear groove had the lowest radiographic score for arthrosis. Subluxation of the patella, either medially or laterally, was correlated with increased radiographic scores. Limb alignment was not correlated with the radiographic score. A significant percentage of varus knees (28%) had unexpected lateral subluxation of the patella. This observation has not been reported previously. It may have an impact on surgical decision-making for total knee arthroplasty and osteotomy.

Temporal, kinematic, and kinetic variables related to gait speed in subjects with hemiplegia: a regression approach.

BACKGROUND AND PURPOSE: The gait speed that a patient selects is a well-known indicator of overall gait performance. The purpose of this study was to use multiple linear regression to assess the strength of association of temporal, kinematic, and kinetic gait variables with high walking speeds in patients with hemiplegia. SUBJECTS: Thirty-two subjects (20 male, 12 female) with an average age of 61 years took part in a sagittal-plane gait study of both sides of the body. METHODS: Data from cinematographic film and a force plate obtained during multiple walking trials were used in a seven-segment link-segment kinetic model of the walking subject to yield temporal, kinematic, and kinetic variables. RESULTS: Variables correlating significantly with self-selected speed included the maximum hip extension angle and the maximum hip flexion moment on the affected side, and the maximum ankle and hip powers on both sides. A stepwise regression identified variables most useful in predicting stride speed. For the affected side, these variables were the hip flexion moment, the ankle moment range, the knee moment range, and the proportion of double support. Together these variables explained 94% of the variation in gait speed. On the unaffected side, the variables were the percentage of stance phase, the maximum ankle power (push-off), and the maximum hip power (pull-off). They explained 92% of the variation in gait speed. CONCLUSION AND DISCUSSION: These results suggest that experimental studies are needed to assess the effects of treatment aimed at increasing ankle power and hip power and at decreasing the stance time on the affected side, and that these studies should be directed at obtaining a larger hip flexion moment and a larger ankle moment range on the unaffected side.

pH and temperature modulate norepinephrine-dependent changes in endothelial permeability.

To evaluate the role of pH and temperature in norepinephrine (NE)-mediated decreases in endothelial permeability, we studied bovine pulmonary arterial endothelial monolayers at pH values of 4-9 and at temperatures of 35-39 degrees C. Only extremes of pH-modulated endothelial permeability and temperature had no effect. Although both NE and 3-isobutyl-1-methylxanthine decreased endothelial permeability, their effects were diminished by low pH and high temperature. Fever and acidosis may contribute to the edema seen in septic shock by a novel mechanism: attenuation of the barrier-improving function of NE.

The dynamic range of neonatal heart rate variability.

INTRODUCTION: Although it is generally appreciated that heart rate variability is low during severe illness, the extent, time course, and mathematical characteristics of heart rate variability during transitions between health and illness have not been systematically examined. The purpose of this study was to analyze heart rate variability in newborn infants during a rapid recovery from severe respiratory and circulatory failure. METHODS AND RESULTS: From prolonged ECG recordings, we evaluated heart rate variability in the time domain (mean, relative change, and coefficient of variation of RR intervals), in the frequency domain (using power spectra of the time series of RR intervals), and using a neural network. Qualitatively, RR interval plots showed little heart rate variability during severe illness but became "noisier" during recovery. Quantitatively, recovery was marked by twofold to threefold increases in time-domain parameters, by eightfold increases in frequency-domain parameters, and by more than 20-fold increases in a neural network measure. Time-domain and frequency-domain measures were correlated, but not strongly. Heart rate variability reached stable levels by 4 to 5 days. Heart rate did not change dramatically. CONCLUSION: Recovery from severe neonatal illness is accompanied by large and rapid increases in heart rate variability, but not by large changes in heart rate. This increase can be effectively assessed in the time domain, in the frequency domain, and by using a neural network.