Division of Critical Care Medicine Research Section Miami Children's Hospital, Miami, FL 33155, USA. Division of Critical Care Medicine (CCM) in Miami Children's Hospital (MCH) has a fellowship program, involving research in various aspects of pulmonary critical care. Our Fellowship program requires participation of the Fellows in planning, performance, analysis and publications in a Peer Reviewed Journals, as the first author. The Division's Faculty, including the Attending Physicians, a Ph.D. Physiologist, and a Pharm. D. Pharmacologist, provide mentorship and assistance in planning, execution, analyses and publication of the research data. The faculty provides yearly educational and training courses in biostatistics, experimental design, extracorporeal life support systems and ventilation strategies. The Fellows conduct weekly seminars and journal clubs and are encouraged to participate in National Critical Care Related Conventions. Since 1995, we have developed a number of in vivo and in vitro methods for experimental critical care research, including: 1) Animal models of respiratory support in rabbits, and lamb models of extracorporeal life support systems. 2) Developmental aspects of Hyperoxia and weaning from Oxygen Therapy in a neonatal rat’s model. 3) Genomics of the developing brain, in neonatal rat models. 4) An adult rat model to study pathophysiology and pharmacotherapy during pulmonary critical care conditions (hypercapnia, hypoxia and hyperoxia), sepsis, hypothermia and hemorrhagic hypotension. 5) In vitro studies designed to investigate various mechanical aspects of experimental models of ventilator support, and inflammatory response. 6) Prospective and retrospective clinical studies involving critically ill neonatal and pediatric patients, compared with healthy children. 7) Clinical studies within PICU in MCH and with other institutions (collaborative, multicentral studies). 2 PUBLICATION: Peer Review Journals (Bolded Names: CCM Investigators) Wong HR, Cvijanovich N, Allen GL, Lin R, Anas N, Meyer K, Freishtat RJ, Monaco M, Odoms K, Sakthivel B, Shanley TP; Genomics of Pediatric SIRS/Septic Shock Investigators. Genomic expression profiling across the pediatric systemic inflammatory response syndrome, sepsis, and septic shock spectrum. Crit Care Med. 2009 May;37(5):1558-66. Koppada R, Norozian FM, Torbati D, Kalomiris S, Ramachandran C, Totapally BR. Physiologic effects of a novel immune stimulator drug, (1,4)-α-D-glucan, in rats. Basic Clin Pharmacol Toxicol, 2009 Mar 10. [Epub ahead of print]. Velazquez E, Kimura D, Torbati D, Ramachandran C, Totapally BR. Effect of (1,4)-α-D-glucose, an immune stimulatory agent during endotoxemia in juvenile rats. Basic Clin Pharmacol Toxicol, In Press, 2009. Shaik SS, Soltan TD, Chaturvedi G, Totapally B.R., et al. Low-intensity sheer stress increases endothelial ELR+CXC chemokine production via a PAKP38β Mark-NF-κB pathway. J Biol Chem. 2009 Feb 27;284(9):5945-55. Epub 2008 Dec 31.. Valcourt K, Norozian F, Lee H, Raszynski A, Torbati D, and B.R. Totapally. Drug use density in critically ill children and newborns: analysis of various methodologies. Pediat Crit Care Med. In Press, 2009. Torbati D, Totapally BR, Raszynski A, Osborne J, van Zyl L, Kalomiris S, Wolfsdorf J. Age and sex differences in brain gene expression in the neonatal rats. Neuropediatric. 39:219-225, 2008. Kimura D, Totapally B.R., Raszynski A, Ramachandran C, and D. Torbati. The effects of CO2 on cytokine concentrations in endotoxin-stimulated human whole blood. Crit Care Med. 36:2823-2827, 2008. Ali S, Totapally B.R., Raszinski A. Strong ion gap, anion gap, and base excess in critically ill neonates and infants during ECMO. Internat Pediatrics 23: 34-40, 2008. Meyappan R.T, Raszynski A, J. Bohorrquez, B.R. Totapally, B.P. Pulin, F.M. Norozian, P.B. Koul, K. Valcourt, D. Torbati. Carbon dioxide clearance during expiratory phase intratracheal pulmonary ventilation in rabbits. ASAIO J. 53: 163167, 2007. Koul P.B., Minarik M., Totapally B.R. Lactic acidosis in children with acute exacerbation of severe asthma. Eur J Emerg Med 14:56-58, 2007. 3 Torbati D, G.H. Tan, S. Smith, K.S. Frazier, J. Gelvez, H. Fakioglu, and B.R. Totapally. Multiple-organ effect of normobaric hyperoxia in neonatal rats. J Crit Care; 21:85-94, 2006. Gim H. Tan, B.R. Totapally, D. Torbati, J. Wolfsdorf. End-of-life decisions and palliative care in a children’s hospital. J Palliative Med; 9:332-342, 2006. Hon K.L., Olsen H., Totapally B. R., Leung TF. Air versus ground transportation of artificially ventilated neonates: comparative differences in selected cardiopulmonary parameters/ Pediatr Emerg Care; 22:107-112, 2006. Thornton A, Choy HY, Branch III E, Honeywell M. The Clinical Use of Tipranavir in HIV Infection. Pharmacy and Therapeutics 31: 709-715, 2006. Koul PB, Sussmane JB. Metabolic hyperglycemic emergencies with acute pancreatitis in a child with known insulin-dependent diabetes mellitus. Eur J Emerg Med. 12:309-311, 2005. Fakioglu H, B.R. Totapally, D. Torbati, A. Raszynski, J.B. Sussmane, J. Wolfsdorf. Hypoxic respiratory failure in term newborns: Clinical indicators for inhaled nitric oxide and extracorporeal membrane oxygenation therapy. J Crit Care; 20:288-293, 2005. Hon KE, Olsen H, Totapally B, Leung T. Hyperventilation at referring hospitals is common before transport in intubated children with neurologic disease. Pediatr Emerg Care. 21(10):662-666, 2005. Koul PB, Sussmane JB, Cunill-De Sautu B, Minarik M. Atrial fibrillation associated with alcohol ingestion in adolescence: holidy heart in pediatrics. Pediatr Emerg Care, 21:38-39, 2005. Totapally, B.R., J.B. Sussmane, D. Torbati, J. Gelvez, H. Fakioglu, Y. Mao, J. Olarte, and J. Wolfsdorf. Cardiovascular stability during arterio-venous extracorporeal therapy: a randomized controlled study in lambs with acute lung injury. Crit Care Forum, 8:R496-R503, 2004. Gelvez, J, H. Fakioglu, JL Olarte, A. Soliz, B.R. Totapally, and D. Torbati. Effect of aerosolized milrinone during drug-induced pulmonary hypertension in lambs. Pharmacol Res, 50:87-91, 2004. Fakioglu H, D. Torbati, J. Gelvez, M.T. Glover and J. Wolfsdorf. Effect of aminophiline treatment during endotoxemia in rats. Pharmacol Res, 49:45-50, 2004. Torbati D. Carbon Dioxide: a “waste product” with potential therapeutic utilities in critical care. Crit Care Med, 31:2705-2707; 2003. 4 Dave K. R., R. Prado, R. Busto, A.P. Raval, W.G. Bradley, D. Torbati, and M.I. PerezPinzon. Hyperbaric oxygen therapy protects against mitochondrial dysfunction and delays onset of motor neuron disease in Wobbler mice. Neuroscience, 120:113120, 2003 Olarte J., J. Gelvez, H. Fakioglu, D. Torbati, K.S. Frazier, B. R. Totapally and A. Raszynski. Tracheobronchial damage during conventional mechanical ventilation and intratracheal pulmonary ventilation in rabbits. Crit Care Med, 31:916-923, 2003 Totapally RB, H. Fakioglu, D. Torbati, J. Wolfsdorf. Esophageal capnometry during hemorrhagic shock and after resuscitation in rats. Crit Care, 7:79-84, 2003 Glover ML, JB Sussmane. Assessing pediatric residents’ mathematical skills for prescribing medication: A need for improved training. Acad Med, 77:1007-1010, 2002. Totapally, B.R., C. Demerci, G. Zureikat and B. Nolan: Tidal breathing flow-volume loops in infancy: the effect of albuterol. Crit Care 6:160-165, 2002. Tan G.H. and J.B. Sussmane: Images in clinical medicine. Massive airembolism in a neonate with pulmonary hypoplasia. New Eng J Med, 346:751, 2002. Glover ML, Machado C, Totapally B. The Use of Magnesium Sulfate via continuous intravenous infusion for the treatment of refractory wheezing.J. Crit Care, 17:255258, 2002. Bolivar, J., K. Hultquist, A. Raszynski, D. Torbati, N. Sheri, and J. Wolfsdorf: Intratracheal pulmonary ventilation versus conventional mechanical ventilation: airway pressures at low and high flows and frequencies. ASAIO J., 2001, 47:215-219. Sussmane J.B., M. deSoto, D. Torbati. Plasma colloid osmotic pressure in healthy infants. Crit Care Forum, 2001: 5:261-264. Olarte J.L., Glover M, and B.R. Totapally: The use of alteplase for the resolution of an intravesical clot in a neonate receiving extracorporeal membrane oxygenation. ASAIO J, 2001, 47:565-568. Camacho, M.T., B.R. Totapally, D. Torbati, and J. Wolfsdorf: Pulmonary and extrapulmonary effects of increased colloid osmotic pressure during endotoxemia in rats. Chest. 2001, 120:1655-1662. Sussmane, J. B., R.B. Totapally, K. Haultquist, D. Torbati, and J. Wolfsdorf: Effects of arterio-venous extracorporeal therapy on hemodynamic stability, ventilation, and oxygenation in normal lambs. Crit Care Med. 29:1972-1978, 2001. 5 Torbati D., M.T. Camacho, A. Raszynski, J.B. Sussmane, B.R. Totapally, K. Hultquist, and J. Wolfsdorf: Effect of hypothermia on ventilation and gas-exchange in anesthetized, spontaneously breathing, rats: theoretical implications for a safe mechanical ventilation. Intensive Care Med. 26:585-591, 2000. Ramirez, J., B.R. Totapally, E. Hon, D. Torbati, M.J. Mangino, K.A. Hultquist, and J. Wolfsdorf: Oxygen carrying capacity during prolonged hypercapnia in ventilated dogs. Crit. Care Med. 28: 1918-1923, 2000 Camacho M.T., B. R. Totapally, K. Hultquist, g. Nelson, D. Eawaz, J. Sussmane, and J. Wolfsdorf: Insensible water loss during extracorporeal life support: an in vitro study. ASAIO J., 46:620-624, 2000. Hon, E., K.A. Hultquist, T. Loescher, A. Raszynski, D. Torbati, C. Tabares, and J. Wolfsdorf: Intratracheal pulmonary ventilation in a rabbit lung injury model: Continuous airway pressure monitoring and gas exchange efficacy. Crit. Care Med. 28:2480-2485, 2000. Totapally, B.R., J. Sussmane, K. Hultquist, D. Sapp, N. Andreolakis, and J. Wolfsdorf: Variability in systemic arterial blood pressure during closed- and open-bridge extracorporeal life support: An in vitro evaluation. Crit. Care Med. 28:2076-2080, 2000. Glover, M.L. Cole, E. and J. Wolfsdorf: Vancomycin dosage requirements among pediatric intensive care unit patients. J. Crit. Care 15:1-4, 2000. Totapally, B.R., A. Raszynski, J. Sussmane, K. Hultquist, N. Andreoulakis, and J. Wolfsdorf: Nitric oxide and nitrogen dioxide concentrations during in vitro high frequency ventilation. J. Crit. Care 14:141-149, 1999. Torbati, D., B.R. Totapally, M.T. Camacho, and J. Wolfsdorf: Experimental critical care in ventilated rats: effect of hypercapnia on arterial oxygen carrying capacity. J. Crit. Care 14:191-197, 1999. Glover, M., Maria T. Camacho, and J. Wolfsdorf: The use of alteplase in a newborn receiving extracorporeal membrane oxygenation. Ann. Pharmacotherapy. 3:416:418, 1999. Torbati, D., J. Ramirez, E. Hon, M.T. Camacho, J.B. Sussmane, A. Raszynski, and J. Wolfsdorf: Experimental critical care in rats: Gender differences in anesthesia, ventilation and gas-exchange. Crit. Care Med. 27:1878-1884, 1999. Totapally, BR., and W.T. Walsh. Pneumococal bacteremia in childhood. A 6year experience in a community hospital. Chest, 133(5):1207-1214, 1998. 6 Torbati, D., M.J. Mangino, E. Garcia, M. Estrada, B. Totapally, and J. Wolfsdorf. Acute hypercapnia increases the O2-carrying capacity of the blood in ventilated dogs. Crit. Care Med. 26:1863-1867, 1998. Totapally BR, Nolan B, Zureikat G, Inoue S. An unusual case of methemoglobinemia in infancy. Am J Emerg Med. 16:723-724, 1998. Deepak, A, D.F. Church, D. Torbati and WA Pryor. Oxidative Stress Following traumatic brain injury in rats. Surg Neurol 47:575-582, 1997. Soler, M, A. Raszynski, R.J. Kandrotas, J.B. Sussmane, R. Aznavorian and J. Wolfsdorf. Fewer interventions in the immediate post-extubation management of pediatric intensive care unit patients: safety and cost containment. J Clin Care 12:173-176, 1997. Mangino M.J., J.E. Mangino, B. Kotadia, and M Sielczak. Effects of the 5lipoxygenase inhibitor A-64077 on intestinal hypothermic organ preservation injury. J Pharmacol Exp Therap 281:950-956, 1997. Mangino J.E., Kotadia B., M.J. Mangino. Characterization of hypothermic intestinal ischemia-reperfusion injury in dogs: Effects of glycine 1. Transplantation 62(2): 173-178, 1996. Torbati D., G.A. Peyman, H., Wafapoor, S.B. Shaibani. Khoobehi B. Experimental retinopathy by hyperbaric oxygenation. Undersea Hyperbaric Med, 22(1): 31-39, 1995. Soler M, Raszynski A, Wolfsdorf J. Neurogenic pulmonary edema associated with pneumococcal meningitis. Clin Pediatr (Phila). 1995 Aug; 34(8):442445. Torbati D., G.A. Peyman, J.A. Rodriguez, G.C. Navarro. Modulation of sensitivity to hyperbaric oxygen by CO2 in newborn rats. Undersea and Hyperbaric Med 22(3): 209-218, 1995. 7 PUBLICATIONS (Non Peer Review Journals) (Bolded Names: CCM Investigators) Johansson B.E., Meyer K. Influenza: A Review for Clinician –part 1. Internat Pediatr 23:203-208, 2008. Bhalala U.S., Totapally B.R. Acute bronchiolitis. Internat Pediatr 23:209-215, 2008. Torbati D. Oxidative stress in neonatal and pediatric diseases. Internat Pediatr, 23: 23:151-161, 2008. Lee H. Preparing for the National conversion of CFC propelled inhalers to HFA propelled inhalers. Internat Pediatr 23:163-164, 2008. Lee H. Increasing number of medications used in children are being associated with neuropsychiatric events. Internat Pediatr 23:96, 2008. Totapally B.R., Raszynski A. Pulse oximetry in pediatric practice. Internat Pediatr 23:88-94, 2008. Meyer K., Totapally B.R. Procedural analgesia and sedation for the general pediatric practice. Internat Pediatr 23:70-73, 2008. Lee H., Totapally B.R. Hypertensive crises in pediatric practice. Internat Pediatr 22:214-223, 2007. Meyer K. Perspectives for the pediatrician: Creating a culture of safety. Internat Pediatr 22:121-123, 2007. Torbati D. Biostatistics: a search for “real difference” versus “by chance alone”. Internat Pediatr; 22:124-136, 2007. Totapally B.R., Lee H, Naqvi S, Meyer K, Raszynski A. Status epilepticus in pediatric practice. Internat Pediatr; 22:154-163, 2007. Totapally R.B., A. Raszynski. Understanding the anion gap. Internat Pediatr; 22:8692, 2007. Totapally R.B., A. Raszynski. New dietary guidelines: my pyramid. Internat Pediatr, 22:32-35, 2007. Meyer K. Evidence-based medicine: benefits, limitations and implementation strategies. Internat Pediatr, 21:239-243, 2006. Totapally B.R., A. Raszynski. Probiotics in pediatric practice. Internat Pediatr, 21:228-236, 2006. 8 Torbati D, A.F. Soliz. Neonatal oxygen therapy: Theory Practice and Controversy. Internat Pediatr, 21:175-182, 2006. Totapally B.R., A. Raszynski. Stridor in Children. Internat Pediatr 21:100-111, 2006. Sussmane J.F. Plasmapheresis. In: ECMO Extracorporeal cardiopulmonary support in critical care. 3rd Edition, Van Meurs k, Lally k.P, Peek G, and Zwischenberger JB (Eds). Pp. 561-575, 2006. Totapally B.R., Raszynski A. Hyponatremia in pediatric practice. International Pediatr 21(1):37-50, 2006. Torbati D. and K. Meyer. From genetics to genomics and beyond: impact on clinical pediatricians. Internat Pediatr 20:212-223, 2005. Totapally B.R. and D. Torbati. Neonatal Jaundice. Internat Pediatr 20:47-54, 2005. Totapally, BR. Severe sepsis and septic shock in children: pathophysiology and management-Part I. International Pediatr. 20(3):162-172, 2005. Totapally, BR. Severe sepsis and septic shock in children: pathophysiology and management-Part II. International Pediatr. 20(4):237-248, 2005. Totapally B.R. Fever, fever phobia and hyperthermia: What Pediatricians need to know. Internat Pediat 20:95-19, 2005. Meyer GK, DeLaMora P. Last minute pediatrics: A concise review for the speciality boards. McGraw-Hill, New York, London, Sydney, Toronto, 2004. Raszynski, A: Aviation physiology and interhospital transport of infants and children. Internat. Pediatrics, 14: 2, 1999. Totapally, B.R., and A. Raszynski: Nitric oxide in health and disease. Internat. Pediatrics, 14:140-145, 1999. Soler, M. Hon, E, and K. Hultquist: Reduction in intracranial hemorrhage in neonates during extracorporeal membrane oxygenation may be possible by elevation of the patient’s head [Letter] ASAIO J. 44:327, 1998. Jain, K.K., and D. Torbati. Oxygen Toxicity. In: Textbook of Hyperbaric Medicine. K.K. Jain (ed.), Second Edition. (Hogrefe & Huber Publishers, Seattle). Chapter 6, pp. 63-78, 1996. 9 Torbati, D. Effects of hypoxia and hyperoxia on CNS. In: Central Nervous System Trauma: Research Techniques. Chapter 2; Mechanisms of CNS injury S.T. Ohnishi & T. Ohnishi (eds.), CRC. Press Inc., Boca Raton FL., pp. 7-57, 1995. Wolfsdorf J, Raszynski A, Sussmane J. Ethical Dilemmas of Extracorporeal Membrane Oxygenation for the Newborn. Internat Pediatr. 1995; 10(3). Torbati, D. Gunshot wounds to the brain. In: Central Nervous System Trauma: Research Techniques. T. S. Ohnishi & T. Ohnishi (eds.), Chapter 40; CRC Press Inc., Boca Raton FL., pp. 523-541, 1995. 10 Articles Under Preparation: MacCarrick MJ, Velazquez E, Kimura D, Totapally BR, Raszynski A, Torbati D. Modulation by hypercapnia of hyperoxic lung injury in neonatal rats. Norozian FM, Kimura D, Totapally BR, Meyer K, Torbati D. Systemic inflammatory response to exogenous hypercapnia in endotoxemic rats. Koul PB, Meyappan RT, Norozian FM, Raszynski A, Valcourt K, Torbati D, and B.R. Totapally. Resucitation end-point following hemorrhagic hypovolemia in rabbits: systolic pressure versus pulse pressure variability and base deficit. 11 Presentations in National / International Meetings (Abstracts) Skaletsky S, Raszynski A, Totapally B. Validation of a Modified Pediatric Early Warning System Score. Pediatric Academic Societies Annual Meeting, Baltimore 2009. Patten W, Raszynski A, Totapally B.R., Sayed Naqvi. Refractory status epilepticus: Treatment related complications. Society of Critical Care Medicine, 2009. Patten W, Geltner M, Sussmane J. Rescue veno-arterial extracorporeal membrane oxygenation in a pediatric patient with neurogenic cardiac arrest. Keystone Symposia, 2009. Geltner M, Morgan L, Scheflow Allison, Amjad I, Sussmane J. Decubiti prevention on ECMO: A clinical case study. Keystone Symposia, 2009. Machado JC, Raszynski A, Totapally BR. Children with special health care needs (CSHCN):Resource utilization and outcomes in a tertiary-care pediatric intensive care unit. Society of Critical Care Medicine, 2009. Totapally BR, Norozian F, Torbati D, Meyer K, Raszynski A. Inflammatory response to therapeutic hypercapnia (TH) in the lung of endotoxemic rats. Society of Pediatric Research, 2009, Baltimore MD. Leoncio M, Norozian F, Torbati D, Totapally BR, Meyer K, Raszynski A. Therapeutic hypercapnia (TH) induced morphologic changes in the lung of endotoxemic rats. American Thoracic Society, 2009, San Diego CA. Lee H, Norozian F, Valcourt K, Raszynski A, Totapally BR. Vancomycin use density: Discrepancy between defined and prescribed daily dose in children. Society of Critical Care Medicine, 2008. Machado JC, Bagdure DN, Lee HY, Raszynski A, Totapally BR. Renal dysfunction during vancomycin therapy in critically ill children. Society of Critical Care Medicine, 2008. Torbati D, Totapally B.R., and Raszynski A. Effect of exogenous hypercapnia on lung’s pro- and anti-inflammatory cytokines during development of pulmonary oxygen toxicity in neonatal rats. Experimental Biology 2008, San Diego CA. Choy H, Norozian F, Valcourt K, Raszynski A, Totapally BR. Vancomycin Use Density: discrepancy between defined and prescribed daily doses in children. Society of Critical Care Medicine, 2007, Orlando, FL. Crit Care Med; 34(Suppl):A153, 2006. 12 Velezquez E, Nair R, McCarrick M, Ramachandran C, Totapally BR, Torbati D. Immunomodulatory effect of (1,4)-α-D-glucan in endotoxemic juvenile rats. American Thoracic Society, 2007, San Francisco CA. Torbati D, Totapally BR, Raszynski A. Short-term hyperoxia stimulates T-cell receptor (TCR) Vß 8.3b gene expression in the brain of neonatal rats. Pediatric Academic Society, 2007, Toronto Canada. MacCarrick M, Velezquez E, Torbati D, Totapally BR, Raszynski A. Effects of exogenous hypercapnia on pulmonary oxygen toxicity in neonatal rats. Society of Critical Care Medicine, 2007, Orlando, FL. Crit Care Med, 34(Suppl):A4, 2006. Kimura D, Totapally BR, Raszynski A., Ramachandran C, N. Raveendran, Torbati D. Hypocapnia and hypercapnia-induced immunomodulation in endotoxinstimulated human blood. Society of Critical Care Medicine, 2007, Orlando, FL. Crit Care Med; 34(Suppl):A44, 2006. Torbati D, Totapally BR, Osborne J, van Zil L, Kalomiris S, Raszynski A. Brain differential gene expression following 72 hour of graded hyperoxia in rats. European Societies for Pediatric Research, October 2006, Barcelona, Spain. Torbati D, Totapally BR, Raszynski A, Kalomiris S, Wolfsdorf J.. Brain differential gene expression in neonatal rats: age- and gender differences. Presented in European Society for Pediatric Research, Siena, Italy. Pediatr Res 58:419, 2005. Torbati D, Totapally BR, Raszynski A, Gil S, Bertrand S, Osborne J, Kalomiris S, Wolfsdorf J.. Brain gene expression following prenatal global hypoxiaischemia in neonatal rats. Soc Neurosci, 2005. Ramachandran C, Torbati D, Nair RPK, Norozian FM, Totapally BR, Kalomiris S, Melnick SJ. Effect of (1,4)-α-D-glucan on blood cellular profile, inflammatory cytokines and hemodynamic variables following surgical stress in rats. FASEB J, 19(5): 2005. Koul PB, Meyappan RT, Valcourt K, Norozian FM, Totapally BR, Torbati D. Systolic and pulse pressure variability during hemorrhagic hypovolemia and resuscitation in rabbits. Soc Crit Care Med, 2005. Meyappan RT, Raszynski A, Koul PB, Valcourt K, Norozian FM, Totapally BR, Torbati D. Carbon dioxide clearance during expiratory phase intratracheal pulmonary ventilation in rabbits. Soc Crit Care Med, 2005. Meyappan RT, Norozian FM, Koul P, Magnarelli FD, Totapally BR, Torbati D. Carbon dioxide removal during bi-level ventilation and dual frequency ventilation (combined bi-level and high frequency oscillatory ventilation) in normal rabbits. 2004 Pediat Acad Soc 13 Meyappan RT, Totapally BR, Magnarelli F, Torbati D. Carbon dioxide clearance during bi-level ventilation compared with combined bi-level and oscillatory ventilation (Duel Frequency Ventilation) in a test lung model. Crit Care Med, 31(Suppl):151, 2003. Torbati D, G. Tan, J. Gelvez, Totapally BR, Olarte J, Wolfsdorf J. Intestinal and renal effects of oxygen therapy in neonatal rats. Crit Care Med, 31(Suppl): A149, 2003. Olarte J, Torbati D, Totapally BR, Raszynski A. Combination of high frequency oscillatory ventilation and bi-level pressure ventilation (dual frequency ventilation) improves bulk minute ventilation in a test lung. Crit Care Med, 31(Suppl): A89, 2003. Sussmane JB, Totapally BR. Alveolar-arterial gradient during weaning from Extracorporeal Membrane Oxygenation. Crit Care Med, 31(Suppl): A94, 2003. Totapally BR, Sussmane J. “Hidden” Metabolic Acid-base Disturbances in Critically Ill Neonates and Infants on ECMO. Crit Care Med, 30(Suppl): A150, 2003. Sussmane JB, Totapally BR. Dexemedetomidine as a Bridge to Extubation in Children. Crit Care Med, 30 (Suppl): A-157, 2003. Parungao RJ, J.L. Olarte, B.R. Totapally, A. Raszynski. The effect of heliumoxygen gas mixture on delivered FiO2 and tidal volume during high frequency oscillatory ventilation. Crit Care Med, 30 (Suppl): A-85, 2003. Parungao RJ, B.R. Totapally, J Sussmane, N. Timmer. Alveolar-arterial oxygen gradient prior to decannulation predicts ventilator days. Crit Care Med, 30 (Suppl): A94, 2003. Ali SA, Timmer N, Totapally BR, Sussmane J. Continuous Hemofiltration During Extracorporeal Membrane Oxygenation in Neonates. Crit Care Med 30 (Suppl): A-152, 2003. Fregeolle T.C., Brezina K, Rising R, D. Torbati, and F.H. Dube. Gene expression in liver of rats fed with low and high fat diets for 120 days and treated with lipator or pravacol. Experimental Biology, April 2002, New Orleans, LA. Tan G.H., Totapally B.R., Torbati D. and J. Wolfsdorf. End-of-Life decisions, withdrawal versus withholding of life-sustaining therapy in children’s hospital. Society of Critical Care Medicine. January 2002, San Diego, CA. Tan G.H., Totapally B.R., and D. Torbati. The use of opioid analgesics and sedatives in the terminally ill children: Does end-of-life discussion changes the usage? Society of Critical Care Medicine. January 2002, San Diego, CA. Fakioglu H, Gelvez J, Olarte JL, Torbati D, Camacho M.T., Glover M.L., and J. Wolfsdorf. Effects of aminophylline on gas-exchange and multiple organ edema in a 14 rat model of endotoxemia. Society of Critical Care Medicine, January 2002, San Diego, CA. Olarte J., J. Gelvez, H. Fakioglu, D. Torbati, Frazier K.S., Totapally B.R., and A. Raszynski. Comparison of tracheobronchial damage during intratracheal pulmonary ventilation and conventional mechanical ventilation in rabbits. Recepient of an Educational Research Award. 31th International Educational and Scientific Symposium of Society of Critical Care Medicine. January 2002, San Diego, CA. Olarte J, Raszynski A, Totapally B. Dead space monitoring by single breath CO2 analysis during intratracheal pulmonary ventilation. 31st International Educational and Scientific symposium of Society of Critical Care Medicine, Crit Care Med 29:A-114, 2002. Totapally, B.R., J.B. Sussmane, J. Gelvez, H. Fakioglu, Yong M. Mao, J. Olarte, and D. Torbati. Arterio-venous extracorporeal oxygenation in a lung-injured lamb model. 30th International Educational and Scientific Symposium of Society of Critical Care Medicine. February 2001, San Francisco, CA. Camacho, MT, D. Torbati, B.R. Totapally and J. Wolfsdorf. Does diuretic effect of Fruosemide, combined with albumin treatment, ameliorate endotoxemiainduced multiple organ edema in endotoxemic rats? 30th International Educational and Scientific Symposium of Society of Critical Care Medicine. February 2001, San Francisco, CA. Gelvez, J, A. Soliz, H. Fakioglu, Y.M. Mao, JL Olarte, B.R. Totapally, and D. Torbati. Nebulized milrinone during thromboxane-induced pulmonary hypertension. 30th International Educational and Scientific Symposium of Society of Critical Care Medicine. February 2001, San Francisco, CA. Fakioglu H, Totapally B, Gelvez J, Raszynski A. Response to inhaled nitric oxide in term, out born hypoxemic newborns referred for ECMO therapy. Society of Critical Care Medicine, Crit Care Med 28:A-88, 2001. Vazzalwar R., Totapally B., Raszynski A. Course and outcome of children with systemic lupus erythematosis in pediatric intensive care unit. Society of Critical Care Medicine, Crit Care Med 28(Suppl):A-95, 2001. Gelvez J, Olarte J, Totapally B, Raszynski A. Tidal volume delivery in pressure control ventilation depends on the proximal airway pressure-time relationship. Society of Critical Care Medicine, Crit Care Med 12(Suppl)A189, 2001. 15 Dave K.R., R. Prado, M.A. Perez-Pinzon, I Saul, D. Torbati, and R. Busto. Hyperbaric strategies for the treatment of global cerebral ischemia in rats. J Cereb Blood Flow and Metab 21: (Suppl-1), S23, 2001. Bramlett H.M., K.R. Dave, R. Prado, M.A. Perez-Pinzon, D. Torbati, O.F. Alonso and R. Busto. Hyperbaric oxygen treatment provides histopathologic protection following fluid percussion brain injury and secondary hypoxia. J Cereb Blood Flow and Metab 21: (Suppl-1), S190, 2001. Olarte J.L., B. Totapally, D. Torbati and A. Raszynski. Auto-PEEP, alveolar and carinal pressures during tracheal gas insufflation with direct and reverse thruster flow catheters in a test lung model. Chest 2001 Annual Meeting. November 2001, Philadelphia, PA. Torbati D, Y. Mao, MT Camacho and J. Wolfsdorf. Growth rate during hyperoxia and weaning from oxygen therapy in neonatal rats. Biology 2001 Annual Scientific Meeting; Orlando FL; FASEB J 15:A596, 2001. Torbati D, KS Frazier, J. Wolfsdorf. Cerebral histopathology after hyperoxia and weaning from oxygen therapy in neonatal rats. Annual Scientific Meeting of the Society for Neuroscienc; November 2001, San Diego, CA. Camacho MT, BR Totapally, D. Torbati, J Wolfsdorf. Effect of albumin treatment on gas exchange efficiency and organ edema in endotoxemic rats. 29th Educational & Scientific Symposium of the Society of Critical Care Medicine. February 2000, San Diego, CA Totapally BR, D. Torbati, K Hultquist, MT Camacho, J Wolfsdorf. Esophageal arterial PCO2 gradient during hemorrhagic shock in rats. 29th Educational & Scientific Symposium of the Society of Critical Care Medicine. February 2000, San Diego CA. Torbati D, BR Totapally, A Alamo, H Fakioglu, J Gelvez, and J wolfsdorf. Hematological effects of prolonged hyperoxia in newborn rats. American Federation for Medical Research. February 2000, New Orleans, LA. Brezina K, A. Alamo, R. Rising, R. Warren and D. Torbati. Metabolic changes associated with the treatment of hypercholesterolemia in rats: Drug vs dietary intervention. Experimental Biology 1999. Alamo A, R. Rising, K. Brezina, S. Smith, R. Warren and D. Torbati. Comparison of mannual and automated determinations of blood cellular populations in rats. Experimental Biology, 1999. 16 Torbati D, B.R. Totapally, K. Hultquist, J.B. Sussmane, A. Razynski and J. Wolfsdorf. Arterial oxygenation in ventilated rats during permissive hypercapnia. ALA/ATS Internat. Conf. 1999. Bolivar J., K. Hultquist, e. Hon, A. Raszynski, J. Sussmane, N. Shery, D. Torbati. Carinal and proximal pressures during intratracheal pulmonary ventilation in an artificial lung and in rabbits. Crit Care Med 26 (Suppl):288, 1998. Torbati D., M. Camacho, K. Hultquist, J. Sussmane, A. Raszynski and J. Wolfsdorf. Ventilation and gas-exchange responses to hypothermia and pentobarbital anesthesia in female rats. Crit. Care Med. 26:A-119, 1998. Torbati D., K. Hultquist, A. Raszynski, M. J. Mangino, M. T. Camacho, E. Garcia, J. B. Sussmane, and J. Wolfsdorf. Increased arterial oxygenation by exogenously-induced arterial hypercapnia in the rat. Crit. Care Med. Suppl. 25 (1): A-100, 1997. Torbati D., J. Ramirez, E. Hon, M.T. Camacho, J. Bolivar, E. Garcia and J. Wolfsdorf. Ventilatory and blood gas responses to hypoxia, hyperoxia, and hypercapnia in male and female rats. The FASEB J., 11 (3): A345, 1997. Mangino M., D. Torbati, E. Garcia, M. Estrada, and J. Wolfsdorf. Exogenously-induced hypercapnia signigicantly increases hemoglobin concentration and oxygen content in dogs. The FASEB L., 11(3): A346,1997. Torbati D., K. Hultquist, A. Raszynski, M. Mangino, J. Sussmane, and J. Wolfsdorf. Exogenous hypercapnia generates a sustained increase in the PaO2 in paralyzed and ventilated rats. Am. Rev. Respir. Crit Care Med., Suppl (4): A905, 1997. Torbati, D., M.J. Mangino, and J. Wolfsdorf. Pulmonary and intestinal effects of hyperoxia in newborn rats. FASEB J. 10 (3): A355, 1996. Torbati, D., M. Mangino, Y. Mao, and J. Wolfsdorf. Retardation of brain growth by heperoxia in newborn rats. Neurosci. Absts. Vol. 21 (part 1): 557, 1995. Torbati, D., M.J. Mangino, and J. Wolfsdorf. Hyperoxia as a factor in the etiology of necrotizing enterocolitis in newborn rats. Undersea and Hyperbaric Med. Vol. 22 (Suppl) : 75, 1995. 17 RESEARCH GRANTS 1996: Ventilatory response to O2/CO2 during sexual development in rats. Awarded to Dan Torbati, Ph.D. by Miami Children's Hospital Foundation. ($ 28,700). 1998: Isolation and characterization of airway antioxidant enzymes in a rat model of pulmonary critical care. Awarded to Dan Torbati, Ph.D. by Miami Children's Foundation ($,16,000). 1998: Arterio-venous extracorporeal oxygenation versous conventional mechanical ventilation in lambs. Awarded to Balagangadhar R. Totapally, M.D. by Miami Children's Hospital Foundation. ($18,800). 1999: Intestinal effects of hyperoxia in newborn rats. Awarded to Dan Torbati, Ph.D. by Miami Children's Hospital Foundation. ($8,450). 1999: Comparison of tracheobronchial damage during intratracheal pulmonary ventilation and conventional mechanical ventilation. Awarded to Andre Raszynski, M.D. by Miami Children's Hospital Foundation. ($17,500). 1999: Arterio-venous extracorporeal oxygenation versous Veno-venous extracorporeal oxygenation in lung-injured lambs. Awarded to Jeffrey B. Sussmane, M.D. ($17,000). 1999: Continuous intramucosal PCO2 measurements during hemorrhagic shock in a rat model. Awarded by Miami Children's Hospital Foundation to Balagangadhar R. Totapally, M.D. ($10,500). 1999: The hemodynamic and respiratory effects of aminophylline in septic rats. Awarded by Miami Children's Hospital Foundation to Mark Glover, Pharm. D. ($8,000). 2000: Effect of aerosolized milrinone during acute pulmonary hypertension. Awarded to Dan Torbati, Ph.D. by Neonatology Association of South FL. ($12,000). 18 2001: Multiple organ edema and apoptosis during and after oxygen therapy in neonatal rats. Awarded to Dan Torbati, Ph.D. by Miami Children's Hospital Foundation. ($16,420) 2002: Does combination of Bi-level conventional mechanical ventilation and high frequency ventilation improve CO2 clearance. Awarded to Balagangadhar Totapally, M.D. by Miami Children’s Hospital Foundation. ($14,650). 2002: Can expiratory phase intratracheal pulmonary ventilation (ITPV) prevent tracheobronchial injury induced by continuous ITPV? Awarded to Andre Raszynski, M.D. by Miami Children’s Hospital Foundation. ($24,475). 2002: Efficiency of CO2 removal and cardio-respiratory stability in a lung-injured rabbit during arterio-venous extracorporeal oxygenation with pediatric membrane. Awarded to Jeffrey B. Sussmane, M.D. by Miami Children’s Foundation. ($13,340). 2003: Functional genomic of the brain following neonatal, hypoxic-ischemic encephalopathy in rats: Long-term behavioral outcome and neuroprotective strategies. Awarded to Dan Torbati, Ph.D. by Miami Children’s Hospital Research Institute. ($119,000). 2004: Oximetric pulse wave variability as a predictor of fluid responsiveness in critically ill children. Awarded to Bala R. Totapally, M.D.by Miami Children's Hospital Foundation ($25,000). 2005: Effect of therapeutic hypercapnia on mortality and morbidity in septic mice. Awarded to Keith Meyer, M.D., by Miami Children’s Hospital Foundation. ($20,000). 2006: Effect of therapeutic hypercapnia on pro- and anti-inflammatory cytokines in septic rats. Awarded to Keith Meyer , M.D. by Robert Bellamy Research Fund. 19 ($10,000). 2007: Immunomodulatory effects of hypocapnia and hypercapnia on human blood in vitro. Awarded to Bala R. Totapally, M.D.by Wachovia Critical Care Fund. ($17,000). 2008: Performance of a prototype miniature capnometer probe in conventionally ventilated rabbits. A joint NIH awarded grant for CCM-MCH investigators (Totapally B.R., Torbati D, & Raszynski A) with Physical Optic Corporation (POC; Zeltser G, M.D.). (CCM: $87,000). 2009 Multimodal Neuromonitoring and Neuroprotection in Critically Ill Children. A joint Department of Defence (DOD) awarded grant to Department of neurology and Critical Care Medicine of Miami Children’s Hospital. CCM P.I.: Dr. Bala R. Totapally (Total Research Grant: $1.5 millions; Co-investigators see “Clinical Studies” below). 20 CLINICAL STUDIES: MULTI-CENTRAL AND/OR DIVISIONAL Title: “Multimodal Neuromonitoring and Neuroprotection in Critically Ill Children” P.I: Sub-PI Balagangadhar R. Totapally, M.D. Prasanna Jayakar, PhD Amed Soliz, MD Andre Raszynski, MD Sayed Naqvi, MD Israel Alfonso, MD Wei-Chiang Lin, PhD Tara Stewart, PhD Title: “Genomic Analysis of Pediatric Systemic Inflammatory Response Syndrome (SIRS)” P.I.: Sub-P.I.: George Keith Meyer, M.D. Andre Raszynski, M.D. Balagangadhar Totapally, M.D. Dr. Jeffery Sussmane Sponsor: NIH through Cincinnati Children’s Hospital Medical Center Title: “A Multicenter, Randomized, Masked, Placebo-Controlled Trial to Assess the Safety and Efficacy of Lucinactant in Acute Hypoxemic Respiratory Failure in Children Up To Two Years of Age.” P.I.: Sub-P.I.: George Keith Meyer, M.D. Andre Raszynski, M.D. Balagangadhar Totapally, M.D. Jeffery Sussmane, M.D. Sponsor: Discovery Laboratories. Title: “Critical Pertussis in U.S. Children: Severe Morbidity, Sequelae, and Mortality: A Prospective Cohort Study.” P.I.: Sub-P.I.: Balagangadhar Totapally, M.D. Michael Leoncio, M.D. Sponsor: NICHD through Arkansas Children’s Hospital Title: P.I.: Sub-P.I.: “Genetic epidemiology of Life-Threatening Influenza Infection in Children and Young Adults.” George Keith Meyer, M.D. Andre Raszynski, M.D. Balagangadhar Totapally, M.D. Pablo M. Laufer, M.D. Jeffery Sussmane, M.D. 21 Sponsor: Title: American Health Insurance Plans Foundation (AHIP) under Auspice of Center for Disease Control (CFDC) through Boston Children’s Hospital “Effects of Hypercapnia on NF-KB and downstream cytokine production in ex-vivo human blood” P.I.: Sub-P.I.: William Patten, M.D. Dai Kimura, M.D. Balagangadhar Totapally, M.D. Dan Torbati, Ph.D. Sponsor: MCH/PICU Title: “Needs for and Utilization of Health Care Services of Children with Special Care Needs in Tertiary-Care Pediatric Intensive Care Unit.” P.I.: Sub-P.I.: Jacqueline C. Machado, M.D. Balagangadhar Totapally, M.D. Sponsor: MCH/PICU Title: P.I.: Sub-P.I.: Sponsor: Title: “Delta Gap and duration needed for treatment in children with diabetic ketoacidosis.” Dai Kimura, M.D. Balagangadhar Totapally, M.D. MCH/PICU “International Society for Thrombosis and Haemostasis Scoring System for Disseminated Intravascular Coagulation as a predictor of Thrombotic bleeding complication in newborns undergoing Extracorporeal Membrane Oxygenation.” P.I.: Sub-P.I.: Jeffery Sussmane, M.D. Sergio Bustos, M.D. Marla Geltner, CCP, RN, BA Wilma Sanchez, BS, MT Sponsor: MCH/PICU Title: “Twenty Years of ECMO Experience at Miami Children’s Hospital” P.I.: Sub-P.I.: Jeffery Sussmane, M.D. Marla Geltner CCP, RN, BA Sponsor: MCH/PICU 22 “Comparison of Activated Clotting for Pediatric ECMO Patients” Title: P.I.: Sub-P.I.: Sponsor: Jeffery Sussmane, M.D. Sergio Bustos, M.D. Marla Geltner, CCP, RN, BA Wilma Sanchez, BS, MT MCH/PICU “A Retrospective chart Review and a DMAIC Six Sigma Performance Improvement Tool development of Patients on Apheresis in Miami Children’s Hospital from 1996 through 2008.” Title: P.I.: Sub-P.I.: Jeffery Sussmane, M.D. Marla Geltner, RN, CCP Milton Sanchez, MBA Sponsor: MCH/PICU “Parental Bereavement after child death” Title: P.I.: JoAnne Youngblut, Ph.D., RN, FAAN. (Professor of Nursing in FIU College of Nursing and Health). Sub-PI: Bala R. Totapally, M.D., MCH-PICU. Sponsor An NIH Funded Study. “Evaluation of safety and effectiveness of the rapid intravascular start system vs conventional catheters. Title: P.I.: Debra Delfavero, RN (MCH-PICU) Sub-PI: BalaR. Totapally, M.D. (MCH-PICU).