John Maa

Substance P mediates inflammatory oedema in acute pancreatitis via activation of the neurokinin-1 receptor in rats and mice.

Pancreatic oedema occurs early in the development of acute pancreatitis, and the overall extent of fluid loss correlates with disease severity. The tachykinin substance P (SP) is released from sensory nerves, binds to the neurokinin‐1 receptor (NK1‐R) on endothelial cells and induces plasma extravasation, oedema, and neutrophil infiltration, a process termed neurogenic inflammation. We sought to determine the importance of neurogenic mechanisms in acute pancreatitis. Pancreatic plasma extravasation was measured using the intravascular tracers Evans blue and Monastral blue after administration of specific NK1‐R agonists/antagonists in rats and NK1‐R(+/+)/(−/−) mice. The effects of NK1‐R genetic deletion/antagonism on pancreatic plasma extravasation, amylase, myeloperoxidase (MPO), and histology in cerulein‐induced pancreatitis were characterized. In rats, both SP and the NK1‐R selective agonist [Sar9 Met(O2)11]SP stimulated pancreatic plasma extravasation, and this response was blocked by the NK1‐R antagonist CP 96,345. Selective agonists of the NK‐2 or NK‐3 receptors had no effect. In rats, cerulein stimulated pancreatic plasma extravasation and serum amylase. These responses were blocked by the NK1‐R antagonist CP 96,345. In wildtype mice, SP induced plasma extravasation while SP had no effect in NK1‐R knockout mice. In NK1‐R knockout mice, the effects of cerulein on pancreatic plasma extravasation and hyperamylasemia were reduced by 60%, and pancreatic MPO by 75%, as compared to wildtype animals. Neurogenic mechanisms of inflammation are important in the development of inflammatory oedema in acute interstitial pancreatitis.

The Impact of Smoking on Surgical Outcomes

t m t w c c s d p b t b c v a u a i Smoking substantially increases a patient’s risk of surgical complications. Despite this, almost half of all surgeons do not routinely counsel their patients to stop smoking before an operation. Studies show that although up to 75% of smokers who undergo surgery would like to quit, only about 5% will stop smoking permanently around the time of elective surgery. The intent of this article is to raise surgeon awareness of the deleterious impact of smoking on surgical outcomes and emphasize the unique opportunity in the teachable moment of surgery to enable patients to succeed in their efforts to quit smoking.

Transient Receptor Potential Vanilloid (trpv-1) Promotes Neurogenic Inflammation in the Pancreas Via Activation of the Neurokinin-1 Receptor (nk-1r)

Objectives: The transient receptor potential vanilloid 1 (TRPV-1) is an ion channel found on primary sensory afferent neurons. Activation of TRPV-1 leads to the release of the proinflammatory neuropeptide substance P (SP). SP then binds to the neurokinin-1 receptor (NK1-R) on endothelial cells and promotes extravasation of plasma and proteins into the interstitial tissue and neutrophil infiltration, a process called neurogenic inflammation. We tested 2 hypotheses: (1) activation of TRPV-1 in the pancreas leads to interstitial edema and neutrophil infiltration and (2) TRPV-1-induced plasma extravasation is mediated by the release of SP and activation of the NK1-R in the rat. Methods: We measured extravasation of the intravascular tracer Evans blue as an index of plasma extravasation and quantified pancreas tissue myeloperoxidase activity (MPO) as a marker of neutrophil infiltration. The severity of inflammation following intravenous infusion of the secretagogue cerulein (10 μg/kg/h × 4 hours) was assessed using a histologic scoring system. Results: Intravenous injection of the TRPV-1 agonist capsaicin induced a dose-dependent increase in Evans blue accumulation in the rat pancreas (P < 0.05 vs. vehicle control). This effect was blocked by pretreatment with the TRPV-1 antagonist capsazepine (1.8 mg/kg), or the NK1-R antagonist CP 96,345 (1 mg/kg). Capsazepine also reduced cerulein-induced Evans blue, MPO, and histologic severity of inflammation in the pancreas but had no effect on serum amylase. Conclusion: Activation of TRPV-1 induces SP-mediated plasma extravasation in the rat pancreas via activation of the NK1-R. TRPV-1 mediates neurogenic inflammation in cerulein-induced pancreatitis in the rat.

Substance P inhibits pancreatic exocrine secretion via a neural mechanism

We investigated the effects of the sensory neuropeptide substance P (SP) on amylase and fluid secretion in the isolated vascularly perfused rat pancreas. SP inhibited CCK-induced amylase release and secretin-induced juice flow via the pancreatic duct in a dose-related fashion. Threshold inhibition occurred following addition of 10(-10) M SP to the perfusate, and maximal inhibition was seen with 10(-8) M SP. The effects of SP were partially blocked by both the neurokinin-1 (NK1) and neurokinin-2 (NK2) receptor antagonists. Atropine and TTX blocked SP-induced effects on both amylase secretion (26 and 63% blockade, respectively) and pancreatic juice flow (21 and 79% blockade, respectively). Excitation of pancreatic sensory nerves using capsaicin (in the absence of SP) inhibited both amylase and pancreatic juice flow via activation of the NK1 receptor. We conclude that SP inhibits exocrine secretion via an indirect neural mechanism.We investigated the effects of the sensory neuropeptide substance P (SP) on amylase and fluid secretion in the isolated vascularly perfused rat pancreas. SP inhibited CCK-induced amylase release and secretin-induced juice flow via the pancreatic duct in a dose-related fashion. Threshold inhibition occurred following addition of 10-10 M SP to the perfusate, and maximal inhibition was seen with 10-8 M SP. The effects of SP were partially blocked by both the neurokinin-1 (NK1) and neurokinin-2 (NK2) receptor antagonists. Atropine and TTX blocked SP-induced effects on both amylase secretion (26 and 63% blockade, respectively) and pancreatic juice flow (21 and 79% blockade, respectively). Excitation of pancreatic sensory nerves using capsaicin (in the absence of SP) inhibited both amylase and pancreatic juice flow via activation of the NK1 receptor. We conclude that SP inhibits exocrine secretion via an indirect neural mechanism.

The impact of smoking on neurosurgical outcomes

Cigarette smoking is a common health risk behavior among the general adult population, and is the leading preventable cause of morbidity and mortality in the US. The surgical literature shows that active tobacco smoking is a major risk factor for perioperative morbidity and complications, and that preoperative smoking cessation is an effective measure to lower these risks associated with active smoking. However, few studies have examined the effects of smoking and perioperative complications following neurosurgical procedures. The goal of this review was to highlight the scientific data that do exist regarding the impact of smoking on neurosurgical outcomes, to promote awareness of the need for further work in the specific neurosurgical context, and to suggest ways that neurosurgeons can promote smoking cessation in their patients and lead efforts nationally to emphasize the importance of preoperative smoking cessation. This review indicates that there is limited but good evidence that smoking is associated with higher rates of perioperative complications following neurosurgical intervention. Specific research is needed to understand the effects of smoking and perioperative complications. Neurosurgeons should encourage preoperative smoking cessation as part of their clinical practice to mitigate perioperative morbidity associated with active smoking.

Resident Work Hour Restrictions and the Future of Medical Student Surgical Education

e read with great interest the article by Dr Curet in he November 2008 JACS reviewing the impact of the ccreditation Council for Graduate Medical Education ACGME) resident work hour restrictions. Another imortant area of further research is the effect of the 80-hour ork week on medical student surgical education and inerest in surgical careers, both of which may have been dversely affected by the decreased availability of house taff to serve as educators and role models. In some instiutions, resident and medical student interactions have een further curtailed by the need to restrict afternoon ork rounds to achieve compliance with work hour reguations. Of concern is the finding that medical student erceptions of a surgeon’s lifestyle have improved after inroduction of the 80 hours workweek, but this has not ecessarily lead to an increase in interest in a surgical areer. A small number of studies have examined the impact of he 80 hours workweek on the medical student experience cross specialties. These survey studies have focused priarily on the quantity and quality of resident teaching, ith mixed conclusions. Of three studies examining the quantity of teaching, one howed decreased accessibility to resident teaching, anther showed no significant change, and a third demontrated a small improvement in resident availability. Anther observed impact of the hour restriction was that edical students reported spending more time on nonducational duties, leaving less time for independent earning. The results for the quality of resident teaching are qually inconclusive. Three studies found no change in kill of teaching, and one showed a significantly negative mpact on resident teaching quality. One study revealed a mall increase in residents’ interest in teaching, but without ny effect on the quality of instruction. Another element f the resident-student interaction that has been adversely

Helping Smokers Quit Around the Time of Surgery

Elective surgery offers a powerful opportunity for physicians to help smokers quit, yet 25% to 30% of patients smoke perioperatively, and approximately 10 million patients who smoke undergo surgical procedures annually.1- 2 Approximately 42% of all surgeons and 70% of anesthesiologists do not routinely counsel patients to stop smoking before an operation or do not refer them to appropriate cessation services.3

Emerging Trends in the Outsourcing of Medical and Surgical Care

As total health care expenditures are expected to constitute an increasing portion of the US gross domestic product during the coming years, the US health care system is anticipating a historic spike in the need for care. Outsourcing medical and surgical care to other nations has expanded rapidly, and several ethical, legal, and financial considerations require careful evaluation. Ultimately, the balance between cost savings, quality, and patient satisfaction will be the key determinant in the future of medical outsourcing.

Holospinal epidural abscess.

Holospinal epidural abscess (HEA) is an extremely rare condition in which spinal epidural abscesses extend from the cervical to the sacral spine. We report two patients who presented with myelopathy secondary to HEA. Both patients underwent urgent surgical decompression and abscess drainage, and had significant improvement in neurological function. We discuss the surgical management strategies and briefly review the literature regarding HEA.

Cholecystectomy in the presence of a large patent foramen ovale: laparoscopic or open?

An obese patient with cholelithiasis and acute cholecystitis was scheduled for an emergency laparoscopic cholecystectomy. On preoperative workup, a 5-year-old echocardiogram showed a large patent foramen ovale (PFO) with a right-to-left shunt that was open at rest. Noting both the benefits of laparoscopic surgery and the substantial incidence of PFO in the general population (10% to 30%), the attending and consulting surgeons reasoned that the benefits of laparoscopy greatly exceeded an immeasurably small risk of paradoxical emboli.