Search tips
Search criteria

Results 1-9 (9)

Clipboard (0)

Select a Filter Below

Year of Publication
Document Types
1.  Noninvasive Autoregulation Monitoring in a Swine Model of Pediatric Cardiac Arrest 
Anesthesia and Analgesia  2012;114(4):825-836.
Cerebrovascular autoregulation after resuscitation has not been well studied in an experimental model of pediatric cardiac arrest. Furthermore, developing noninvasive methods of monitoring autoregulation using near-infrared spectroscopy (NIRS) would be clinically useful in guiding neuroprotective hemodynamic management after pediatric cardiac arrest. We tested the hypotheses that the lower limit of autoregulation (LLA) would shift to a higher arterial blood pressure between 1 and 2 days of recovery after cardiac arrest and that the LLA would be detected by NIRS-derived indices of autoregulation in a swine model of pediatric cardiac arrest. We also tested the hypothesis that autoregulation with hypertension would be impaired after cardiac arrest.
Data on LLA were obtained from neonatal piglets that had undergone hypoxic-asphyxic cardiac arrest and recovery for 1 day (n=8) or 2 days (n=8), or that had undergone sham surgery with 2 days of recovery (n=8). Autoregulation with hypertension was examined in a separate cohort of piglets that underwent hypoxic-asphyxic cardiac arrest (n=5) or sham surgery (n=5) with 2 days of recovery. After the recovery period, piglets were reanesthetized, and autoregulation was monitored by standard laser-Doppler flowmetry and autoregulation indices derived from NIRS (the cerebral oximetry [COx] and hemoglobin volume [HVx] indices). The LLA was determined by decreasing blood pressure through inflation of a balloon catheter in the inferior vena cava. Autoregulation during hypertension was evaluated by inflation of an aortic balloon catheter.
The LLAs were similar between sham-operated piglets and piglets that recovered for 1 or 2 days after arrest. The NIRS-derived indices accurately detected the LLA determined by laser-Doppler flowmetry. The area under the curve of the receiver operator characteristic curve for cerebral oximetry index was 0.91 at 1 day and 0.92 at 2 days after arrest. The area under the curve for hemoglobin volume index was 0.92 and 0.89 at the respective time points. During induced hypertension, the static rate of autoregulation, defined as the percent change in cerebrovascular resistance divided by the percent change in cerebral perfusion pressure, was not different between postarrest and sham-operated piglets. At 2 days recovery from arrest, piglets exhibited neurobehavioral deficits and histologic neuronal injury.
In a swine model of pediatric hypoxic-asphyxic cardiac arrest with confirmed brain damage, the LLA did not differ 1 and 2 days after resuscitation. The NIRS-derived indices accurately detected the LLA compared to laser-Doppler flow measurements at those time points. Autoregulation remained functional during hypertension.
PMCID: PMC3310318  PMID: 22314692
2.  Cost-effective therapeutic hypothermia treatment device for hypoxic ischemic encephalopathy 
Despite recent advances in neonatal care and monitoring, asphyxia globally accounts for 23% of the 4 million annual deaths of newborns, and leads to hypoxic-ischemic encephalopathy (HIE). Occurring in five of 1000 live-born infants globally and even more in developing countries, HIE is a serious problem that causes death in 25%–50% of affected neonates and neurological disability to at least 25% of survivors. In order to prevent the damage caused by HIE, our invention provides an effective whole-body cooling of the neonates by utilizing evaporation and an endothermic reaction. Our device is composed of basic electronics, clay pots, sand, and urea-based instant cold pack powder. A larger clay pot, lined with nearly 5 cm of sand, contains a smaller pot, where the neonate will be placed for therapeutic treatment. When the sand is mixed with instant cold pack urea powder and wetted with water, the device can extract heat from inside to outside and maintain the inner pot at 17°C for more than 24 hours with monitoring by LED lights and thermistors. Using a piglet model, we confirmed that our device fits the specific parameters of therapeutic hypothermia, lowering the body temperature to 33.5°C with a 1°C margin of error. After the therapeutic hypothermia treatment, warming is regulated by adjusting the amount of water added and the location of baby inside the device. Our invention uniquely limits the amount of electricity required to power and operate the device compared with current expensive and high-tech devices available in the United States. Our device costs a maximum of 40 dollars and is simple enough to be used in neonatal intensive care units in developing countries.
PMCID: PMC3540914  PMID: 23319871
therapeutic hypothermia; evaporative cooling; hypoxic ischemic encephalopathy; birth asphyxia; neuroprotection
3.  Cerebral Blood Flow and Cerebrovascular Autoregulation in a Swine Model of Pediatric Cardiac Arrest and Hypothermia 
Critical care medicine  2011;39(10):2337-2345.
Knowledge remains limited regarding cerebral blood flow autoregulation after cardiac arrest and during post-resuscitation hypothermia. We determined the relationship of cerebral blood flow to cerebral perfusion pressure in a swine model of pediatric hypoxic-asphyxic cardiac arrest during normothermia and hypothermia and tested novel measures of autoregulation derived from near-infrared spectroscopy.
Prospective, balanced animal study.
Basic physiology laboratory at an academic institution.
Eighty-four neonatal swine.
Piglets underwent hypoxic-asphyhxic cardiac arrest or sham surgery and recovered for 2 hours with normothermia followed by 4 hours of either moderate hypothermia or normothermia. In half of the groups, blood pressure was slowly decreased through inflation of a balloon catheter in the inferior vena cava to identify the lower limit of cerebral autoregulation at 6 hours post-resuscitation. In the remaining groups, blood pressure was gradually increased by inflation of a balloon catheter in the aorta to determine the autoregulatory response to hypertension. Measures of autoregulation obtained from standard laser-Doppler flowmetry and indices derived from near-infrared spectroscopy were compared.
Measurements and Main Results
Laser-Doppler flux was lower in post-arrest animals compared to sham-operated controls during the 2-hour normothermic period after resuscitation. During the subsequent 4-hour recovery, hypothermia decreased laser-Doppler flux in both the sham surgery and post-arrest groups. Autoregulation was intact during hypertension in all groups. With arterial hypotension, post-arrest, hypothermic piglets had a significant decrease in the perfusion pressure lower limit of autoregulation compared to post-arrest, normothermic piglets. The near-infrared spectroscopy-derived measures of autoregulation accurately detected loss of autoregulation during hypotension.
In a pediatric model of cardiac arrest and resuscitation, delayed induction of hypothermia decreased cerebral perfusion and decreased the lower limit of autoregulation. Metrics derived from non-invasive near-infrared spectroscopy accurately identified the lower limit of autoregulation during normothermia and hypothermia in piglets resuscitated from arrest.
PMCID: PMC3178742  PMID: 21705904
pediatrics; heart arrest; cerebrovascular circulation; ischemia; blood pressure; hypothermia
4.  CPAF: A Chlamydial Protease in Search of an Authentic Substrate 
PLoS Pathogens  2012;8(8):e1002842.
Bacteria in the genus Chlamydia are major human pathogens that cause an intracellular infection. A chlamydial protease, CPAF, has been proposed as an important virulence factor that cleaves or degrades at least 16 host proteins, thereby altering multiple cellular processes. We examined 11 published CPAF substrates and found that there was no detectable proteolysis when CPAF activity was inhibited during cell processing. We show that the reported proteolysis of these putative CPAF substrates was due to enzymatic activity in cell lysates rather than in intact cells. Nevertheless, Chlamydia-infected cells displayed Chlamydia-host interactions, such as Golgi reorganization, apoptosis resistance, and host cytoskeletal remodeling, that have been attributed to CPAF-dependent proteolysis of host proteins. Our findings suggest that other mechanisms may be responsible for these Chlamydia-host interactions, and raise concerns about all published CPAF substrates and the proposed roles of CPAF in chlamydial pathogenesis.
Author Summary
Chlamydia are bacteria that invade eukaryotic host cells and live within a membrane-bound compartment called the chlamydial inclusion. Growth and survival of these important human and animal pathogens depends on extensive interactions with the host cell, which allow chlamydiae to acquire critical nutrients and to avoid host anti-microbial defenses. Chlamydiae are proposed to cause many of these host-pathogen interactions through the cleavage or degradation of host proteins by the chlamydial protease CPAF, which is secreted into the host cytoplasm. Here, we raise questions about the proposed roles of this virulence factor during infection, as well as its published substrates. We found that there was no detectable cleavage or degradation of 11 previously reported CPAF substrates in Chlamydia-infected cells and that CPAF-mediated proteolysis of these host proteins occurs during cell harvest and lysis. However, we still observed host-pathogen interactions previously attributed to CPAF proteolysis of these proteins, suggesting that Chlamydia is likely to cause these effects on the host cell through other mechanisms. Our findings call for a re-evaluation of all published CPAF substrates as well as the proposed roles of this protease in chlamydial pathogenesis.
PMCID: PMC3410858  PMID: 22876181
5.  Current state of the art in laparoscopic colorectal surgery for cancer: Update on the multi-centric international trials 
Laparoscopic colectomy is now widely applied to cases of malignancy, supported by early data from several large randomized controlled trials. Long-term follow-up is now available from those trials, supporting equivalency of cancer-free and overall survival for open and laparoscopic resections. This promising data has inspired further exploration of other applications of laparoscopic techniques, including use of single incision laparoscopy. This article reviews recent reports of long-term data for colorectal cancer resection from four randomized, prospective international trials.
PMCID: PMC3444362  PMID: 22846394
Laparoscopy; Colorectal cancer; Cost; Classic; Color
6.  Radiographic and Endoscopic Diagnosis and Treatment of Enterocutaneous Fistulas 
The management of enterocutaneous fistulas continues to be a challenging postoperative complication. Understanding the anatomy of the fistula optimizes its evaluation and management. Diagnostic radiology has always played an important role in this task. The use of plain radiography with contrasted studies and fistulograms is well documented in the earliest investigations of fistulas and they continue to be helpful techniques. The imaging techniques have evolved rapidly over the past 15 years with the introduction of cross-sectional imaging, ultrasound and endoscopy. The purpose of this chapter is to review both the diagnostic and therapeutic roles of fistulograms, small bowel follow-through, computed tomography, magnetic resonance imaging, ultrasound, and endoscopy in the setting of acquired enterocutaneous fistulas.
PMCID: PMC2967314  PMID: 21886464
Enterocutaneous fistula; fistulogram; small bowel follow-through; computed tomography; magnetic resonance imaging
7.  Continuous Measurement of Autoregulation by Spontaneous Fluctuations in Cerebral Perfusion Pressure Comparison of 3 Methods 
Background and Purpose
Clinical application of continuous autoregulation monitoring would benefit from a comparison of curves generated by online monitoring with standard autoregulation curves in animal models. We characterized the accuracy of 3 continuous monitors of autoregulation in a piglet model of hypotension.
Piglets 5 to10 days old with intracranial pressure (ICP) at naïve or elevated (20 mm Hg) levels had gradual arterial hypotension induced by a balloon catheter in the inferior vena cava. Elevated ICP was maintained by a continuous infusion of artificial cerebrospinal fluid. Three indices of autoregulation were simultaneously and continuously calculated. A moving, linear Pearson's coefficient between spontaneous slow waves of cerebral perfusion pressure and slow waves of laser-Doppler flux or cortical oxygenation rendered the laser-Doppler index and cerebral-oximetry index, respectively. Similar correlation between slow waves of arterial blood pressure and ICP rendered the pressure-reactivity index. The lower limit of autoregulation was determined directly for each animal by plotting laser-Doppler cortical red blood cell flux as a function of cerebral perfusion pressure. Receiver-operator characteristics were determined for the 3 indices.
The areas under the receiver-operator characteristics curves for discriminating the individual lower limit of autoregulation at low and high ICP were 0.89 and 0.85 for the laser-Doppler index, 0.89 and 0.84 for the cerebral-oximetry index, and 0.79 and 0.79 for the pressure-reactivity index. The pressure-reactivity index performed equally well at low and high ICPs.
Continuous monitoring of autoregulation by spontaneous slow waves of cerebral perfusion pressure can accurately detect loss of autoregulation due to hypotension in piglets by all 3 modalities.
PMCID: PMC2566962  PMID: 18669896
autoregulation; cerebral blood flow; hypotension; neonates; oxygenation; piglets
8.  Neurocognitive Monitoring and Care During Pediatric Cardiopulmonary Bypass—Current and Future Directions 
Current Cardiology Reviews  2008;4(2):123-139.
Neurologic injury in patients with congenital heart disease remains an important source of morbidity and mortality. Advances in surgical repair and perioperative management have resulted in longer life expectancies for these patients. Current practice and research must focus on identifying treatable risk factors for neurocognitive dysfunction, advancing methods for perioperative neuromonitoring, and refining treatment and care of the congenital heart patient with potential neurologic injury. Techniques for neuromonitoring and future directions will be discussed.
PMCID: PMC2779352  PMID: 19936287
9.  Continuous Time-Domain Analysis of Cerebrovascular Autoregulation Using Near-Infrared Spectroscopy 
Background and Purpose
Assessment of autoregulation in the time domain is a promising monitoring method for actively optimizating cerebral perfusion pressure (CPP) in critically ill patients. The ability to detect loss of autoregulatory vasoreactivity to spontaneous fluctuations in CPP was tested with a new time-domain method that used near-infrared spectroscopic measurements of tissue oxyhemoglobin saturation in an infant animal model.
Piglets were made progressively hypotensive over 4 to 5 hours by inflation of a balloon catheter in the inferior vena cava, and the breakpoint of autoregulation was determined using laser-Doppler flowmetry. The cerebral oximetry index (COx) was determined as a moving linear correlation coefficient between CPP and INVOS cerebral oximeter waveforms during 300-second periods. A laser-Doppler derived time-domain analysis of spontaneous autoregulation with the same parameters (LDx) was also determined.
An increase in the correlation coefficient between cerebral oximetry values and dynamic CPP fluctuations, indicative of a pressure-passive relationship, occurred when CPP was below the steady state autoregulatory breakpoint. This COx had 92% sensitivity (73% to 99%) and 63% specificity (48% to 76%) for detecting loss of autoregulation attributable to hypotension when COx was above a threshold of 0.36. The area under the receiver-operator characteristics curve for the COx was 0.89. COx correlated with LDx when values were sorted and averaged according to the CPP at which they were obtained (r=0.67).
The COx is sensitive for loss of autoregulation attributable to hypotension and is a promising monitoring tool for determining optimal CPP for patients with acute brain injury.
PMCID: PMC2377358  PMID: 17761921
autoregulation; cerebral blood flow; hypotension; neonate; oxygenation; piglet

Results 1-9 (9)