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Biomedical subjects

K J Sullivan

Publications and source records attributed to K J Sullivan.

At least 19 recordsLinked to original sources
PubMed2001

Low exhaled nitric oxide and a polymorphism in the NOS I gene is associated with acute chest syndrome.

Abnormalities of nitric oxide metabolism have been implicated in the pathogenesis of acute chest syndrome in subjects with sickle cell anemia. It is not known whether exhaled nitric oxide levels (FE(NO)) are abnormal in children with a history of the acute chest syndrome (ACS). We compared FE(NO), plasma nitric oxide metabolites (NO(x)), serum arginine and citrulline levels, and the number of AAT repeats in intron 20 of NOS I in subjects with sickle cell disease (SCD) and a history of at least one episode of ACS (ACS(+), n = 13), subjects with SCD and no prior history of ACS (ACS(-), n = 7), and healthy children (HC, n = 6). Mean +/- SD FE(NO) (ppb) was lower in ACS(+) than in ACS(-) and HC: (10.4 +/- 4.3 versus 23.4 +/- 6.1 p = 0.002] and 30.4 +/- 15.8 [p = 0.0001], respectively). Plasma NO(x) (microM) were similar in all three groups (37.3 +/- 19.4, 33.0 +/- 13.2, 44.7 +/- 7.8, respectively). Arginine and citrulline levels (microM) did not differ between ACS(+) and ACS(-) groups. Spirometric data revealed a mildly diminished FEV(1) and FVC in ACS(+) that was statistically different from HC but not ACS(-): (FEV(1) as % of predicted for ACS(+), ACS(-), and HC; 83 +/- 17 versus 87 +/- 16 versus 102 +/- 16, respectively, p < 0.05 between ACS(+) and HC). The level of FE(NO) was significantly associated with the sum of AAT repeats in intron 20 of NOS I gene alleles. The correlation coefficient (r) was 0.62 (p < 0.005). We conclude that FE(NO) levels are significantly reduced in subjects who have a history of ACS and that the FE(NO) levels are significantly correlated with the number of NOS I AAT repeats. FE(NO) is a sensitive marker and may be a predictor of ACS prone children.

Acute Disease↗
PubMed2001

Noninvasive monitoring in the pediatric intensive care unit.

The best ICU monitors are physicians and nurses, who integrate all of the physiologic parameters of patients with the known pathophysiology of the disease process. Over-reliance on raw electronic data, with their inherent errors, jeopardizes the safe and efficient care of patients. Data must be interpreted in the context of the history, repetitive physical examinations, response to therapy, and a background of experience. New modalities and the application of artificial intelligence may facilitate the interpretation of data, but the role of the bedside medical practitioner remains as the heart of pediatric critical care.

Blood Gas Monitoring, Transcutaneous↗
PubMed2001

Activity-dependent factors affecting poststroke functional outcomes.

Over the last several years, there has been increasing recognition of the potential for central nervous system (CNS) recovery after brain damage. One commonality across the recovery and brain plasticity literature is that practice induces plastic, dynamic changes in the CNS. However, more than simply repetition, it is the manipulation of specific practice variables that appears to drive these dynamic processes in the CNS. The experimental manipulations used in the studies on neuroplasticity largely derive from the concept that in the undamaged or healthy brain neuronal connections and cortical maps are continuously remodeled by experience and by the performance of specific, intensive, and complex movements used to solve motor problems and attain goals. Intervention designed to promote recovery rather than compensation after stroke would then manipulate these same practice variables that have consistently promoted behavioral recovery and neuroplasticity in laboratory settings. Three current intervention strategies that incorporate these practice variables are reviewed. Preliminary results provide evidence that manipulation of task intensity and specificity and the sensorimotor experience of the task training are the necessary ingredients for maximizing the tremendous potential for recovery in patients with stroke.

Journal Article↗
PubMed2000

Bedside placement of transpyloric feeding tubes in the pediatric intensive care unit using gastric insufflation.

OBJECTIVE: To test the effectiveness of gastric insufflation as an adjunct to placement of feeding tubes in the small bowel. DESIGN: Prospective, randomized, controlled study. SETTING: Pediatric intensive care unit in a tertiary children's hospital. PATIENTS: A total of 50 children requiring enteral nutrition via a nasoenteral feeding tube in the small bowel. INTERVENTIONS: An unweighted nasoenteral feeding tube attached to a three-way stopcock and a 60 mL syringe was inserted through the nares into the stomach. After 10 mL/kg of air was injected, the tube was advanced a distance estimated to position the tip of the tube proximal to the pylorus. An additional 10 mL/kg of air was then injected, and the tube was advanced a distance needed to place the tube in the fourth part of the duodenum. In the control group, feeding tubes were inserted through the nares and into the stomach. The tube was then advanced a distance estimated to place the tube in the fourth part of the duodenum. No air was injected in the control group. MEASUREMENTS AND MAIN RESULTS: When gastric insufflation was used, 23 of 25 feeding tubes were successfully placed in the small bowel on the first attempt compared with 11 of 25 in the control group (p = .001). All feeding tubes were successfully placed after two attempts in the gastric insufflation group compared with 18 of 25 in the control group (p < .001). The time between the first attempt at placement of a transpyloric feeding tube and the initiation of feeding was significantly shorter in the study group than in the control group. There were no complications in either group. CONCLUSION: Gastric insufflation allows rapid placement of feeding tubes into the small bowel with fewer attempts compared with a standard insertion technique in children.

Child, Preschool↗
PubMed1999

Motor learning after unilateral brain damage.

Forty adults, post-stroke from anterior circulation unilateral cerebrovascular accident (approximately 2 years post onset) and 40 age-matched controls (M = 57 years) practiced a rapid, spatially and temporally constrained programmed action under one of two augmented feedback practice conditions. Participants in the stroke group used the upper limb ipsilateral to the lesion. After an extended practice period (198 trials), acquisition, retention, and reacquisition performance was assessed for accuracy and consistency and compared over trials, between groups and feedback conditions. Both stroke and control groups demonstrated significant improvement in accuracy and consistency over practice with relative persistence of these changes during retention. There were no differences between groups (stroke vs control) in performance patterns across trials for acquisition, retention, or reacquisition phases. In addition, there were no differential effects of the two augmented feedback conditions on performance and no interactions of feedback condition with group. However, independent of feedback condition, the stroke group performed with more error than did the control group during all experimental phases (i.e., acquisition, retention, reacquisition). These results suggest that unilateral stroke-related damage in the sensorimotor areas primarily effects the processes underlying the control and execution of motor skills but not the learning of those skills. Implications of these findings for physical rehabilitation are discussed.

Adult↗
PubMed1999

Nitric oxide successfully used to treat acute chest syndrome of sickle cell disease in a young adolescent.

OBJECTIVES: To report a case of acute chest syndrome (ACS) of sickle cell disease treated successfully with nitric oxide and to review the physiologic effects of nitric oxide and its potential ability to improve outcome in ACS. DESIGN: Descriptive case report. SETTING: Eighteen-bed pediatric intensive care unit in a university children's hospital. PATIENT: A 15-yr-old black male with sickle cell disease, bilateral pulmonary infiltrates, refractory hypoxemia, and unstable hemodynamics. INTERVENTION: In addition to exchange transfusion, invasive hemodynamic monitoring, and aggressive ventilatory support, inhaled nitric oxide was administered in the gas mixture in a concentration of 20 ppm for 72 hrs. MEASUREMENTS AND MAIN RESULTS: Cardiac output, pulmonary arterial pressure, pulmonary artery occlusion pressure, systemic vascular resistance, pulmonary vascular resistance, shunt fraction, and alveolar-arterial oxygen gradient were compared with and without inhaled nitric oxide. Marked reductions in pulmonary arterial pressure and pulmonary vascular resistance were noted. Cardiac output improved, and shunt fraction and alveolar-arterial oxygen gradient were markedly reduced. The patient required decreased ventilator and hemodynamic support and rapidly made a complete recovery. CONCLUSIONS: Nitric oxide may be beneficial for patients with ACS because of its ability to ameliorate pulmonary hypertension and ventilation/perfusion mismatch. Nitric oxide may confer some protection against polymerization of sickle hemoglobin and exert a reversible antiplatelet effect that may be beneficial in ACS. Further study is necessary to determine the safety and efficacy of inhaled nitric oxide as a treatment for ACS.

Acute Disease↗
PubMed1998

Respiratory work in elastase treated hamsters.

Biomechanical adaptations of the diaphragm in the hamster model of emphysema are similar to those observed in skeletal muscle with exercise training. The aim of this study was to evaluate whether the dynamic pressure-volume (PV) work of breathing in hamsters with elastase-induced emphysema may contribute to these adaptations. PV work in elastase treated animals was compared to healthy controls. The studies were performed in adult hamsters 14-16 months following intratracheal administration of elastase (elastase treated group, ET) or saline (control group, CTL). Airway and esophageal pressures and air flows were measured during spontaneous breathing in anesthetized, supine animals. Pulmonary work (WL) was computed from transpulmonary pressures and airflows. Functional residual capacity (FRC) and total lung capacity (TLC; defined as volume at 25 cmH2O) in ET were increased 2 and 1.8 times, respectively, compared with CTL. Averaged tidal volume (VT) and inspiratory flows were comparable between groups. Total work of breathing (WT) normalized per ml VT was not significantly affected with elastase treatment but the pulmonary elastance work (WE) was significantly less in ET animals than controls (0.88 +/- 0.61 g cm(-2) vs. 1.63 +/- 0.32). Pulmonary resistive work was not significantly different between ET and CTL animals. These results suggest that biomechanical adaptations of the diaphragm observed in ET hamsters are caused by mechanisms other than the changes in dynamic mechanical properties of the lung following elastase treatment.

Animals↗
PubMed1997

The independent pathology laboratory as a reporting source for cutaneous melanoma incidence in Iowa, 1977-1994.

BACKGROUND: Health care changes during the past decade have resulted in a greater proportion of cutaneous melanoma (CM) cases diagnosed in nonhospital settings, increasing the potential for cases to be missed by population-based cancer registries. OBJECTIVE: Our purpose was to assess changes in case-finding sources in Iowa from 1977 to 1994 and to determine the extent of underreporting for the State Health Registry of Iowa, a population-based cancer registry. METHODS: This study examines changing trends in the incidence of CM and compares case-finding sources (hospitals/clinics, hospital pathology laboratories, and independent pathology laboratories). A survey of dermatologists serving Iowans provides estimates of underreporting. RESULTS: During the period 1977 to 1994, invasive CM increased 82%, whereas in situ CM increased 900%. The proportion of CM cases diagnosed in independent pathology laboratories increased to 25% of all cases. A range of 10.4% to 17.1% underreporting was estimated based on the survey of dermatologists. CONCLUSION: To improve the accuracy of surveillance, population-based cancer registries need to make a greater effort accessing pathology reports from nonhospital settings.

Dermatology↗
PubMed1997

Intramuscular atropine sulfate in children: comparison of injection sites.

In children undergoing inhaled induction of anesthesia with halothane who suffer bradycardia, submental glossal injection of atropine may result in more rapid onset of vagolysis than traditional intramuscular sites. We compared the intervals between injection and onset of heart rate acceleration (tHR increases) after intramuscular injection of atropine into the deltoid, vastus lateralis, and glossa in children between 1 mo and 10 yr of age scheduled for elective surgery. The tHR increases was determined by measuring the interval between atropine injection and the time point at which the slope of the heart rate curve initially became positive. To ensure that the drug had taken effect before surgical stimulation, heart rate observation was continued until it increased at least 5% above baseline with evidence of continuing acceleration. Anesthesia was induced in all subjects by mask with nitrous oxide and halothane. After tracheal intubation, constant inspired concentrations of the anesthetics were administered for 3 min. While heart rate was monitored, atropine (0.02 mg/kg) was injected into one of the three sites. Each patient's end-tidal anesthetic concentrations were recorded, and minimum alveolar anesthetic concentrations (MAC) were subsequently calculated and adjusted for age. The tHR increases was recorded and averaged for each group. The study groups did not differ by age, weight, end-tidal anesthetic concentrations, age-adjusted MAC, or heart rate at the time atropine was administered. After submental glossal injection (n = 11), tHR increases increase was fastest (3.0 +/- 1.1 min) and was significantly faster than that found with deltoid injection (n = 16; 4.4 +/- 1.1 min) or vastus lateralis injection (n = 8; 6.4 +/- 2.4 min) (P < 0.05 compared with both). The tHR increases also differed significantly between the deltoid and the vastus lateralis (P < 0.05). We conclude that submental glossal injection of atropine results in a more rapid onset of vagolysis than injection at traditional intramuscular sites.

Anesthesia, Inhalation↗
PubMed1996

Estrogenic triarylethylene acetic acids: effect of structural variation on estrogen receptor affinity and estrogenic potency and efficacy in MCF-7 cells.

Triarylethylenecarboxylic acids exemplified by (E,Z)-2-{4-[1-(p-hydroxyphenyl)-2-phenyl]-1-butenyl}phenoxyacetic acid (8) are a new class of estrogen receptor (ER) ligands capable of tissue selective estrogen agonist and antagonist effects. We report the syntheses of 8 and of analogues incorporating structural features known or anticipated to facilitate ER affinity in triarylethylenes. These studies revealed that the p-hydroxyphenyl moiety, ethylenic bond, and ether oxygen of 8 were all critical for high ER affinity. Although a 1,1-bisphenolic analogue bearing the p-(oxyacetic acid) moiety on its 2-phenyl ring, 12, had low ER affinity, it exhibited estrogenic potency approaching that of 8 in MCF-7 cells. Unlike 8 which was a partial agonist with weak antagonist potency, 12 was a full agonist. A similar profile of potency/efficacy in MCF-7 cells was seen in 9, an ethylenic bond saturated analogue of 8. Growth-promoting effects of 8, 9, and 12 were fully antagonized by the antiestrogen tamoxifen, suggesting that such effects were mediated solely via ER. Thus, our studies in MCF-7 cells have confirmed the estrogenicity of 8 and have enabled identification of two analogues with favorable estrogenic potency and full estrogen efficacy. On this basis, these three (triarylethylene)acetic acids have been selected for more intensive animal studies of their extrareproductive tract estrogenic effects.

Animals↗
PubMed1996

Prism: a new approach to radiotherapy planning software.

PURPOSE: We describe the capabilities and performance of Prism, an innovative new radiotherapy planning system with unusual features and design. The design and implementation strategies are intended to assure high quality and clinical acceptability. The features include Artificial Intelligence tools and special support for multileaf collimator (MLC) systems. The design provides unusual flexibility of operation and ease of expansion. METHODS AND MATERIALS: We have implemented Prism, a three-dimensional (3D) radiotherapy treatment-planning system on standard commercial workstations with the widely available X window system. The design and implementation use ideas taken from recent software engineering research, for example, the use of behavioral entity-relationship modeling and the "Mediator Method" instead of ad-hoc programming. The Prism system includes the usual features of a 3D planning system, including Beam's Eye View and the ability to simulate any treatment geometry possible with any standard radiotherapy accelerator. It includes a rule-based expert system for automated generation of the planning target volume as defined in ICRU Report 50. In addition, it provides special support for planning treatments with a multileaf collimator (MLC). We also implemented a Radiotherapy Treatment Planning Tools Foundation for Prism, so that we are able to use software tools form other institutions without any source code modification. RESULTS: The Prism system has been in clinical operation at the University of Washington since July 1994 and has been installed at several other clinics. The system is run simultaneously by several users, each with their own workstation operating from a common networked database and software. In addition to the dosimetrists, the system is used by radiation oncologists to define tumor and target volumes and by radiation therapists to select treatment setups to load into a computer controlled accelerator. CONCLUSIONS: Experience with the installation and operation has shown the design to be effective as both a clinical and research tool. Integration of software tools has eased the development and significantly enhanced the clinical usability of the system. The design has been shown to be a sound basis for further innovation in radiation treatment planning software and for research in the treatment planning process.

Computer Communication Networks↗
PubMed1993

Correlations between flow resistance and geometry in a model of the human nose.

The relationship between the pressure losses within the nasal airways and nasal geometry were studied in a 3:1 scale model. The geometry of the model was based on magnetic resonance images of the skull of a healthy male subject. Pressure measurements, flow visualization, and hot-wire anemometry studies were performed at flow rates that, in vivo, corresponded to flows of between 0.05 and 1.50 l/s. The influence of nasal congestion and the collapse of the external nares were examined by using modeling clay to simulate local constrictions in the cross section. A dimensionless analysis of the pressure losses within three sections of the airway revealed the influence of various anatomic dimensions on nasal resistance. The region of the exterior nose behaves as a contraction-expansion nozzle in which the pressure losses are a function of the smallest cross-sectional area. Losses in the interior nose resemble those associated with channel flow. The nasopharynx is modeled as a sharp bend in a circular duct. Good correspondence was found between the predicted and actual pressure losses in the model under conditions that stimulated local obstructions and congestion.

Adult↗
PubMed1991

A new method to measure nasal impedance in spontaneously breathing adults.

As an alternative to standard rhinomanometric methods, we applied forced oscillations at the mouth in five normal subjects and determined their nasal impedance with a novel method involving flow subtraction. Pressure oscillations of constant amplitude were applied at the mouth of a subject both when the nostrils were open and when they were closed with a noseclip. The airflows measured under the two conditions were subtracted to yield the oscillating nasal airflow at the imposed pressure. The resultant pressure-flow relation defined the nasal impedance of the subject. For frequencies between 3 and 15 Hz, the transnasal pressure-flow relation was well described by a linear lumped parameter model consisting of a resistive and inertial element. Nasal resistance obtained with flow subtraction did not differ significantly from control measurements obtained while the subjects performed the Valsalva maneuver. In contrast, nasal inertance obtained with flow subtraction was approximately twice that obtained with the Valsalva method. The difference between inertances may reflect structural changes in nasopharyngeal dimensions that occur with the Valsalva maneuver. We conclude that the mechanical impedance of the nasal passage may be determined during spontaneous breathing from the response to imposed forced oscillations at the mouth. The noninvasive nature of this method suggests that it may be simpler to implement than traditional rhinomanometric methods.

Adult↗
PubMed1991

Steady and oscillatory transnasal pressure-flow relationships in healthy adults.

The influence of flow characteristics and gas physical properties on nasal resistance (NR) is difficult to ascertain with traditional rhinomanometric methods because the respiratory airflows used in these methods are largely uncontrolled. As an alternative, we used a novel method of rhinomanometry in which an externally generated flow is passed through the nasal passage via a mouthpiece. The transnasal pressure-flow relationships for both quasi-steady and oscillating flows and with different gases were obtained in five healthy adults with this method. For quasi-steady nasal flows the dimensionless pressure losses were largely independent of physical properties of the gas and a function of the Reynolds number (Re) of the flow. Values of NR for quasi-steady flows were largely independent of flow direction for Re up to roughly 3,000 in all five subjects and for Re up to roughly 19,000 in two of the five subjects. Airway collapse occurred in two subjects at Re greater than 3,000, suggesting that the nonrigid segments of the nasal passage contribute to the intersubject variations in NR at high flow rates. Pressure losses associated with oscillating flows measured at frequencies between 1 and 16 Hz were similar to steady flow losses provided that Re was less than roughly 3,000. For Re greater than 3,000 the oscillating flow resistances were affected by the phasic redistribution of flow into compliant segments of the nasal passage. These results indicate that, for flow rates and harmonic frequencies associated with breathing at rest, the nasal passage behaves as a rigid rough-walled pipe in which pressure losses are largely determined by forces relating to viscous friction and convective accelerations.

Adult↗
PubMed1991

A forced perturbation method of assessing pulmonary mechanical function in intubated infants.

Short pulses in airway pressure were used to assess the pulmonary mechanical function of nine infants suffering acute respiratory distress syndrome or bronchopulmonary dysplasia. All patients were intubated, spontaneously breathing, and mechanically ventilated at the time they were examined. The endotracheal tube was disconnected from the ventilator and connected to a mechanical oscillator that produced brief pulses in airway pressure at a rate of two pulses/s. These pulses were applied to the infants airway for 20-30 s, at which time the infant was replaced on the ventilator. The mean airway pressure during the procedure was maintained at the level of the positive and expiratory pressure that was set on the ventilator. Two classes of patients were identified from the pulse response primarily by the presence or absence of a local resonance in the impedance spectra. Similar results were obtained in five other patients who were examined with zero mean airway pressure, suggesting that the pulse response is little influenced by changes in mean lung volume or total lung compliance. Patient classification appeared related to the duration of ventilation therapy and the transition from one class to another was consistent with the development of high peripheral airway resistance and significant volume shunting in the central airways. These results suggest that brief pulses in airway pressure can be used to detect changes in the pulmonary mechanical function of preterm infants that result from long-term ventilation therapy.

Airway Resistance↗
PubMed1989

Evaluation of lung mechanics in rabbits using short duration flow pulses.

An alternative method of evaluating pulmonary mechanical function that uses short duration flow pulses was applied in five adult rabbits with high frequency flow interruption (HFFI) at 4 cycles per second. Variations in the total pressure across the respiratory system were partitioned into separate lungs and chest wall components, and the mechanical impedance of each component was evaluated in the range of 4 to 40 Hz using cross and power spectral analysis and spectral averaging. The resistances, R, of the respiratory system, lungs, and chest wall were 23.5 (2.3 SD), 18.6 (2.8), and 4.9 (1.5) cm H2O.L-1.s, respectively. These values were similar to R obtained by the conventional method at ordinary rates of ventilation, with the exception of chest wall resistance, which was approximately 50% smaller than R obtained by the conventional method. The compliances of the respiratory system, lungs and chest wall were 1.40 (0.19), 2.88 (0.94), and 2.85 (0.86) ml.cm H2O-1, respectively. In all cases, compliance values obtained by pulse analysis were roughly 70% of the values obtained by the conventional method. The smaller compliance values obtained with the pulse method may reflect the multicompartment behavior of the lungs and chest wall at the high frequencies found in the pulse spectra. We conclude that the response of the respiratory system to short duration flow pulses may be used to evaluate pulmonary mechanical function. The brief duration of the flow pulse suggests that this method may be well suited to evaluate lung function in uncooperative subjects, particularly newborns and premature infants.

Airway Resistance↗
PubMed1988

Gas exchange during high frequency flow-interruption in rabbits before and after bronchoalveolar lavage.

The performance of a high frequency flow-interrupter (HFFI) type neonatal ventilator was evaluated on nine adult rabbits (control) and on five adult rabbits after bronchoalveolar lavage (BAL). Tidal volumes and airway pressures were measured during conventional ventilation and during HFFI at rates of 4, 6, 8, 10, and 12 cycles/s. Tidal volumes were adjusted to maintain PaCO2 between 35 and 42 mm Hg in control rabbits and 35-55 mm Hg in BAL rabbits; a positive end-expiratory pressure of 4 cm H2O was applied to BAL rabbits to reduce atelectasis and improve gas exchange. The normalized tidal volume required to maintain PaCO2 within the specified range during HFFI varied between 2.02 ml/kg (0.30 SD) and 2.55 (0.41) in control rabbits and between 2.65 (0.57) and 2.97 (0.51) in BAL rabbits. In neither group did the normalized tidal volume vary systematically with the rate of ventilation (p less than 0.05). Mean airway pressures were lower during HFFI than during conventional ventilation in control rabbits but comparable in the BAL group. Peak inflation pressures were greater during HFFI than conventional ventilation in control rabbits but similar in the BAL group. End-expiratory lung volume was not affected by ventilation rate during HFFI in control rabbits. We conclude 1) that HFFI can maintain gas exchange in rabbits suffering from acute respiratory distress with airway pressures that are comparable to those measured during conventional ventilation and 2) the capacity of HFFI to ventilate the lungs with significantly lower airway pressures than conventional ventilation depends, in part, on the condition of the lungs.

Animals↗