Chemotherapy for pain: reversing inflammatory and neuropathic pain with the anticancer agent mithramycin A.

The persistence of inflammatory and neuropathic pain is poorly understood. We investigated a novel therapeutic paradigm by targeting gene networks that sustain or reverse persistent pain states. Our prior observations found that Sp1-like transcription factors drive the expression of TRPV1, a pain receptor, that is blocked in vitro by mithramycin A (MTM), an inhibitor of Sp1-like factors.

Information Asymmetry in Hospitals: Evidence of the Lack of Cost Awareness in Clinicians.

Background: Information asymmetries and the agency relationship are two defining features of the healthcare system. These market failures are often used as a rationale for government intervention. Many countries have government financing and provision of healthcare in order to correct for this, while health technology agencies also exist to improve efficiency.

Transcription factor Sp4 is required for hyperalgesic state persistence.

Understanding how painful hypersensitive states develop and persist beyond the initial hours to days is critically important in the effort to devise strategies to prevent and/or reverse chronic painful states. Changes in nociceptor transcription can alter the abundance of nociceptive signaling elements, resulting in longer-term change in nociceptor phenotype. As a result, sensitized nociceptive signaling can be further amplified and nocifensive behaviors sustained for weeks to months.

Increased Cytokines at High Altitude: Lack of Effect of Ibuprofen on Acute Mountain Sickness, Physiological Variables, or Cytokine Levels.

Unlabelled: Lundeberg, Jenny, John R. Feiner, Andrew Schober, Jeffrey W. Sall, Helge Eilers, and Philip E.

[Nephroprotection--anaesthetic management of renal transplantation].

Kidney transplantation is a standard surgical procedure. Improvements of immunosuppressive therapy, donor management and surgical technique reduced perioperative complications and improved graft survival. In this review the authors discuss the anaesthetic management of kidney transplantation and nephroprotective strategies: reduction of ischemia-reperfusion injury, maintenance of optimal graft perfusion, avoidance of nephrotoxic agents and effective immunosuppression.

Intraoperative care of the transplant patient.

Patients undergoing abdominal organ transplantation have extensive comorbidities that can affect many organ systems including the cardiovascular system. Intraoperative anesthesia care can be very challenging and requires thorough understanding of the disease specific physiology as well as knowledge of the comorbidities and the surgical procedure. There is no approach to intraoperative anesthesia care that will work equally well for every center but standardization of protocols for each transplant center will improve patient care and safety and ultimately contributes to superior outcomes.

Accuracy of carboxyhemoglobin detection by pulse CO-oximetry during hypoxemia.

Background: Carbon monoxide poisoning is a significant problem in most countries, and a reliable method of quick diagnosis would greatly improve patient care. Until the recent introduction of a multiwavelength "pulse CO-oximeter" (Masimo Rainbow SET(®) Radical-7), obtaining carboxyhemoglobin (COHb) levels in blood required blood sampling and laboratory analysis. In this study, we sought to determine whether hypoxemia, which can accompany carbon monoxide poisoning, interferes with the accurate detection of COHb.

N-glycosylation determines ionic permeability and desensitization of the TRPV1 capsaicin receptor.

The balance of glycosylation and deglycosylation of ion channels can markedly influence their function and regulation. However, the functional importance of glycosylation of the TRPV1 receptor, a key sensor of pain-sensing nerves, is not well understood, and whether TRPV1 is glycosylated in neurons is unclear. We report that TRPV1 is N-glycosylated and that N-glycosylation is a major determinant of capsaicin-evoked desensitization and ionic permeability.

Transcription factors Sp1 and Sp4 regulate TRPV1 gene expression in rat sensory neurons.

Background: The capsaicin receptor, transient receptor potential vanilloid type -1 (TRPV1) directs complex roles in signal transduction including the detection of noxious stimuli arising from cellular injury and inflammation. Under pathophysiologic conditions, TRPV1 mRNA and receptor protein expression are elevated in dorsal root ganglion (DRG) neurons for weeks to months and is associated with hyperalgesia. Building on our previous isolation of a promoter system for the rat TRPV1 gene, we investigated the proximal TRPV1 P2-promoter by first identifying candidate Sp1-like transcription factors bound in vivo to the P2-promoter using chromatin immunoprecipitation (ChIP) assay.

Emergent orthotopic liver transplantation for hemorrhage from a giant cavernous hepatic hemangioma: case report and review.

Introduction: Cavernous hemangiomas represent the most common benign primary hepatic neoplasm, often being incidentally detected. Although the majority of hepatic hemangiomas remain asymptomatic, symptomatic hepatic hemangiomas can present with abdominal pain, hemorrhage, biliary compression, or a consumptive coagulopathy. The optimal surgical management of symptomatic hepatic hemangiomas remains controversial, with resection, enucleation, and both deceased donor and living donor liver transplantation having been reported.

TRPV1 splice variants: structure and function.

The capsaicin receptor (TRPV1) is a non-selective cation channel predominantly expressed in specialized sensory neurons that detect painful stimuli. Although its many functional roles continue to be revealed, it has been confirmed to play a critical role in the perception of peripheral inflammatory hyperalgesia and pain. TRPV1 not only is sensitized and/or activated under a wide range of conditions including inflammation and nerve injury but also undergoes changes in expressed levels in response to these same pathologic conditions.

Pungent general anesthetics activate transient receptor potential-A1 to produce hyperalgesia and neurogenic bronchoconstriction.

Background: Volatile anesthetics such as isoflurane and halothane have been in clinical use for many years and represent the group of drugs most commonly used to maintain general anesthesia. However, despite their widespread use, the molecular mechanisms by which these drugs exert their effects are not completely understood. Recently, a seemingly paradoxical effect of general anesthetics has been identified: the activation of peripheral nociceptors by irritant anesthetics.

The effect of ketamine and nitrous oxide on the human pupillary light reflex during general anesthesia.

The neurotransmitters and receptor types involved in the afferent arm of the human pupillary light reflex are unknown. We hypothesized that the pupillary light reflex is mediated in part by NMDA receptors and that it would be depressed by the NMDA antagonists, nitrous oxide and ketamine. To study this question, sixteen patients received general anesthesia with desflurane, fentanyl, and muscular relaxation with rocuronium.

Increasing the duration of isoflurane anesthesia decreases the minimum alveolar anesthetic concentration in 7-day-old but not in 60-day-old rats.

Background: While studying neurotoxicity in rats, we observed that the anesthetic minimum alveolar anesthetic concentration (MAC) of isoflurane decreases with increasing duration of anesthesia in 7-day-old but not in 60-day-old rats. After 15 min of anesthesia in 7-day-old rats, MAC was 3.5% compared with 1.

The rat vanilloid receptor splice variant VR.5'sv blocks TRPV1 activation.

The capsaicin receptor (VR1, TRPV1) is a ligand-gated ion channel predominantly expressed in peripheral nociceptors and activated by multiple noxious stimuli including products of inflammation. A 5'-splice variant (VR.5'sv) of TRPV1 has been previously isolated and found to be insensitive to noxious stimuli.

Central venous pressure monitoring during living right donor hepatectomy.

Low central venous pressure (CVP) has been advocated during liver resection to reduce blood loss and transfusion requirements. As a consequence, CVP catheter placement has been considered essential for hepatic surgery, including living donor hepatectomies. We retrospectively analyzed whether intraoperative management without CVP monitoring influenced fluid administration, blood loss, and patient outcome.

Isolation of an mRNA binding protein homologue that is expressed in nociceptors.

The peripheral detection of painful stimuli requires the activation of small-diameter primary afferent neurons known as nociceptors. We have exploited two features of nociceptor biology, expression of the high affinity receptor for nerve growth factor (TrkA) and sensitivity to capsaicin, to isolate novel proteins using a differential display cloning scheme. A resulting approximately 4.

Clinically important drug interactions with intravenous anaesthetics in older patients.

There is a continuously growing population of older surgical patients who require an increasing number of anaesthetics and sedation. Pharmacokinetic and pharmacodynamic changes associated with increasing age are often not appreciated enough. Dose requirements for midazolam, a benzodiazepine commonly used for outpatient procedures, have been demonstrated in prospective studies to decrease with increasing age.