Ketamine Inhibits Presynaptic and Postsynaptic Nicotinic Excitation of Identified Cardiac Parasympathetic Neurons in Nucleus Ambiguus

Background: Ketamine increases both blood pressure and heart rate, effects commonly thought of as sympathoexcitatory. The authors investigated possible central nervous system actions of ketamine to inhibit cardiac parasympathetic neurons in the brainstem by inhibiting multiple nicotinic excitatory mechanisms.

Methods: The authors used a novel in vitro approach to study the effect of ketamine on identified cardiac parasympathetic preganglionic neurons in rat brainstem slices. The cardiac parasympathetic neurons in the nucleus ambiguus were retrogradely prelabeled with the fluorescent tracer by placing rhodamine into the pericardial sac. Dye-labeled neurons were visually identified for patch clamp recording. The effects of ketamine were tested on nicotine-evoked ligand-gated currents and spontaneous glutamatergic miniature synaptic currents (mini) in cardiac parasympathetic preganglionic neurons.

Results: Ketamine (10 [mu]m) inhibited (1) the nicotine (1 [mu]m)-evoked presynaptic facilitation of glutamate release (mini frequency, 18 +/- 7% of control; n = 9), and (2) the direct postsynaptic ligand-gated current (27 +/- 8% of control; n = 9), but ketamine did not alter the amplitude of postsynaptic miniature non-N-methyl-d-aspartate currents. [alpha] Bungarotoxin, an antagonist of [alpha]7 containing nicotinic presynaptic receptors, blocked ketamine actions on mini frequency (n = 10) but not mini amplitude.     

Copolymers of substituted styrenes with vinylidene cyanide or methylvinylidene cyanide. 13C NMR studies of their microstructures

Various copolymers of vinylidene cyanide ( 1a ) and methylvinylidene cyanide ( 1b ) with substituted styrenes ( 2a–g ) were synthesized by radical copolymerization, and their microstructures were studied by ¹³C NMR spectroscopy. The copolymers of vinylidene cyanide with substituted styrenes have a perfectly alternating structure, but the copolymers of methylvinylidene cyanide are rich in alternating structure and might contain a minor part of poly(substituted styrene) as blocks or as homopolymers. A distinction between the two possibilities was not possible.     

Genomic analyses lead to novel secondary metabolites. Part 3. ECO-0501, a novel antibacterial of a new class

Genomic analyses of Amycolatopsis orientalis ATCC 43491 strain, deposited as a vancomycin producer, revealed the presence of genetic loci for the production of at least 10 secondary metabolites other than vancomycin. One of these gene clusters, which contained a type I polyketide synthase, was predicted to direct the synthesis of novel class of compound, a glycosidic polyketide ECO-0501 (1). Screening of culture extracts for a compound with the predicted physicochemical properties of the product from this locus, led to the isolation of the 13-O-glucuronide of 13-hydroxy-2,12,14,16,22-pentamethyl-28-(N-methyl-guanidino)-octacosa-2,4,6,8,10,14,20,24-octaenoic acid (2-hydroxy-5-oxo-cyclopent-1-enyl)-amide (ECO-0501, 1). The structure, confirmed by spectral analyses including MS, and ID and 2D NMR experiments, were in accord with that predicted by genomic analyses. ECO-0501 possessed strong antibacterial activity against a series of Gram-positive pathogens including several strains of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE). ECO-0501 was chemically modified by esterification (1a-1c), N-acetylation (1d) and hydrogenation (1e) in order to explore structure activity relationships (SAR).     

Procalcitonin as a prognosis and diagnosis aid in post-operative cardiac surgery

Procalcitonin (PCT), has been identified as a reliable marker of bacterial infection in critically ill patients. After cardiac surgery, infectious and non infectious inflammatory processes can cause a significant increase in PCT production. At present, literature data seem to confirm that repeated measurements of PCT are a better marker than other parameters, both as prognosis and diagnosis aid. Normal PCT levels are less than 0.1 ng/ml. PCT levels < 2ng/ml can be observed after extracorporeal circulation in case of systemic inflammatory response, in the absente of any post operative complication. However, bacterial infection with organ dysfunction should be suspected when PCT levels are higher 5 ng/ml.     

A randomized controlled trial of 0.5% ferric hyaluronate gel (Intergel) in the prevention of adhesions following abdominal surgery

INTRODUCTION: Intestinal adhesion following abdominal surgery is a significant sequela to abdominal surgery. Intergel is a hyaluronate-based gel that reduces the incidence of postoperative adhesions when added to the peritoneal cavity before closure in gynecologic surgery. This is a randomized controlled trial evaluating the efficacy and safety of Intergel in colorectal resections. Although the study aimed to recruit 200 patients based on power analysis, recruitment was suspended because of the high morbidity in the treatment group. METHODS: A total of 32 patients were randomized to either Intergel treatment (treatment group) or no treatment (control group) following open abdominal surgery. Primary endpoints included the incidence of adhesive obstruction, the need for subsequent adhesiolysis, and the incidence of wound and anastomotic complications. A secondary endpoint involved quality-of-life assessment. RESULTS: Seventeen patients were randomized to the treatment group and 15 to the control group. All patients, except 1 in the treatment group, underwent resection and anastomosis of the colon or rectum for benign or malignant disease. A significant difference was observed in the number of patients with postoperative morbidities between the 2 groups (65% treatment group versus 27% control group, P = 0.031). There was a high rate of anastomotic dehiscence (5 treatment group versus 1 control group, P = 0.178) and prolonged postoperative ileus (10 treatment group versus 2 control group, P = 0.011) observed in treatment group. One case of peritonitis occurred in the treatment group in the presence of an intact anastomosis. Wound complications were more common in treatment group but failed to reach statistical significance. CONCLUSION: The use of Intergel in abdominal surgery where the gastrointestinal tract is opened leads to unacceptably high rates of postoperative complications.     

Leiomyosarcoma of the inferior vena cava: experience in 22 cases

From 1979 to 2004, 22 patients were seen with leiomyosarcomas of the inferior vena cava (IVC). Twenty were treated surgically. Involvement of the IVC included the infrarenal segment in 3 cases, the suprarenal and/or retrohepatic segment in 13, and the suprahepatic segment in 4. Nineteen patients underwent wide tumor resection followed by ligation of the IVC in 5 cases, replacement with a PTFE prosthesis in 13, and cavoplasty in 1. An intracardiac tumor extension was resected during hypothermic circulatory arrest in 1 patient. Vascular exclusion of the liver was used in 5 cases and simple clamping of the IVC in 13 cases. There were 1 intraoperative death due to cardiac failure and 3 postoperative deaths due to multiple organ failure, liver failure, and duodenal fistula after treatment of a bleeding ulcer. Fifteen of the 16 surviving patients underwent adjuvant chemotherapy associated with radiation therapy in 4 cases. One patient was lost from follow-up at 10 months. Four patients including one with metastasis are still alive with a mean follow-up of 18.3 months. Eleven patients died after a mean follow-up period of 43.7 months due to local recurrence and/or distant metastasis in 9 cases and complications of chemotherapy in 2. The 3- and 5-year mean actuarial survival rates in patients who underwent resection were 52.0% and 34.8%, respectively. Leiomyosarcoma of the IVC is a serious disease. Although surgical resection combined with chemotherapy is usually not curative, it can achieve reasonably long-term survival. We recommend aggressive operative management using the latest vascular surgery and oncology techniques.     

Impact of adult-to-adult living donor liver transplantation on access to transplantation and patients' survival: an 8-year single-center experience.

While the number of candidates for liver transplantation has increased in the recent years, the pool of cadaveric donor organs has remained constant and the waiting time progressively increases. These facts led us to start a program of adult-to-adult living-donor liver transplantation in 1998. The aim of this study was to compare the outcome of all patients put on the waiting list since 1998. Between January 1, 1998, and January 1, 2005, 505 patients were put on the waiting list in our center, and living donor liver transplantation was considered in 57 cases (11.3%). At the time of evaluation (April 1, 2006), liver transplantation was performed in 377 patients (46 living donor liver transplantations), and 89 patients died on waiting list. On an intention-to-treat basis, the 1-year survival rate from the time of listing was 87.5% in the "living donor" group vs. 76.2% in the "cadaveric donor" group (P < 0.05), whereas the 1-year survival after liver transplantation was similar (92.3% vs. 86.9%). Our living donor liver transplantation program was able to improve the access to liver transplantation by reducing waiting time and the number of deaths on waiting list, despite the fact that these patients were more critically ill (liver failure and/or liver cancer).