Biomedical subjects
James Doherty
Publications and source records attributed to James Doherty.
Traumatic rupture of the gallbladder.
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The effect of antipyretic therapy upon outcomes in critically ill patients: a randomized, prospective study.
BACKGROUND: Despite the large body of evidence suggesting a beneficial role of fever in the host response, antipyretic therapy is commonly employed for febrile critically ill patients. Our objective was to evaluate the impact of antipyretic therapy strategies on the outcomes of critically ill patients. METHODS: Patients admitted to the Trauma Intensive Care Unit over a nine-month period were eligible for inclusion, except those with traumatic brain injury. Patients were randomized on day three of the ICU stay into aggressive or permissive groups. The aggressive group received acetaminophen 650 mg every 6 h for temperature of >38.5 degrees C and a cooling blanket was added for temperature of >39.5 degrees C. The permissive group received no treatment for temperature of >38.5 degrees C, but instead had treatment initiated at temperature of >40 degrees C, at which time acetaminophen and cooling blankets were used until temperature was <40 degrees C. Patient demographics, daily temperatures, systemic inflammatory response syndrome (SIRS) scores, multiple organ dysfunction syndrome (MODS) scores, and infections and complications were recorded. RESULTS: Between December, 2002 and September, 2003, 572 patients were screened, of whom 82 met criteria for enrollment. Forty-four patients were randomized to the aggressive group and 38 patients were randomized to the permissive group for a total of 961 and 751 ICU days, respectively. There were 131 infections in the aggressive group and 85 infections in the permissive group (4 +/- 6 vs. 3 +/- 2 infections per patient, p = 0.26). There were seven deaths in the aggressive group and only one death in the permissive group (p = 0.06, Fisher Exact Test). The study was stopped after the first interim analysis due to the mortality difference, related to the issues of waiver of consent and the mandate for minimal risk. CONCLUSIONS: Aggressively treating fever in critically ill patients may lead to a higher mortality rate.
Functional interactions between cannabinoid and metabotropic glutamate receptors in the central nervous system.
The recent appreciation that two G-protein-coupled receptors, metabotropic glutamate and cannabinoid, are trans-synaptically linked by a small lipid messenger has profound implications, both for control of synaptic transmission and for novel therapeutic strategies. There is much evidence for this assertion and on the significance of this dual receptor cooperation for modulation of synaptic transmission in the central nervous system.
Elevated immunoreactive endothelin-1 levels in newborn rabbit lungs after meconium aspiration.
OBJECTIVE: Our prime objective was to study the production of big endothelin-1 (Big ET-1) and its conversion to ET-1 in the lungs of newborn rabbits exposed to meconium. Our second objective was to study the effect of captopril on endothelin expression. DESIGN: Prospective, comparative study. SETTING: Research laboratory of the Michael Reese Hospital and the University of Illinois, Chicago. SUBJECTS: Two-wk-old rabbit pups. INTERVENTIONS: Rabbit pups were instilled with meconium or saline into the lungs. Another group, pretreated with captopril, was also instilled with either meconium or saline. MEASUREMENTS AND MAIN RESULTS: After meconium or saline instillation, lung lavage was performed. Big ET-1 and ET-1 were measured in lung lavage fluid by using a commercially available enzyme-linked immunosorbent assay kits in all groups. Also, lungs were studied by histochemistry analysis for a morphologic evaluation of meconium-induced damage. In the lavage fluid of saline-instilled pups, ET-1 remained low and no increase in Big ET-1 levels was observed. In meconium-instilled animals, bioactive ET-1 levels were significantly higher, with a peak at 8 hrs after instillation. The conversion ratio of Big ET-1 to ET-1 in the meconium group increased from 2.19 at the initial period to 7.19 at 8 hrs after meconium instillation. CONCLUSIONS: Our conclusion is that aspiration of meconium causes lung injury in the newborn and that this injury is associated with a significant increase in ET peptide production in the lungs. We also showed that ET production is inhibited by pretreatment of rabbits with captopril before meconium-induced injury. ET-1 and its conversion from ET-1 in response to meconium may play important roles in increasing pulmonary vascular resistance and lung cell death, even in the absence of hypoxia. In general, we conclude, that ET-1 levels are significantly elevated in meconium-instilled rabbits compared with saline-instilled ones, and both can be significantly inhibited by pretreatment with captopril. Whether ET-1 contributes directly to the pathophysiology of or is simply a marker of meconium aspiration syndrome remains speculative.
The roles of metabotropic glutamate receptors in seizures and epilepsy.
Epilepsy is a disorder that afflicts more than 50 million people worldwide. Current antiepileptic drugs (AEDs), although effective in controlling seizures for the majority of individuals, remain far from ideal as therapeutics. There is a need for new drugs that act at different molecular targets than currently available AEDs and for new therapies designed to block the process of epileptogenesis. Because of their central role in modulating numerous physiological processes in the central nervous system, metabotropic glutamate receptors (mGluRs) have been implicated in the pathophysiology of a variety of neurological conditions including epilepsy. mGluRs represent attractive new targets for therapeutic control of seizures and interruption of the epileptogenic process. We review the involvement of mGluRs in the induction and expression of epileptic seizures, their potential roles in the process of epileptogenesis, and their altered expression and function in the epileptic human brain.