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Acute stroke care requires rapid assessment and intervention. Replacing traditional sequential algorithms in stroke care with parallel processing using telestroke consultation could be useful in the management of acute stroke patients. The purpose of this study was to assess the feasibility of a nurse-driven acute stroke protocol using a parallel processing model.This is a prospective, nonrandomized, feasibility study of a quality improvement initiative. Stroke team members had a 1-month training phase, and then the protocol was implemented for 6 months and data were collected on a "run-sheet." The primary outcome of this study was to determine if a nurse-driven acute stroke protocol is feasible and assists in decreasing door to needle (intravenous tissue plasminogen activator [IV-tPA]) times.Of the 153 stroke patients seen during the protocol implementation phase, 57 were designated as "level 1" (symptom onset4.5 hours) strokes requiring acute stroke management. Among these strokes, 78% were nurse-driven, and 75% of the telestroke encounters were also nurse-driven. The average door to computerized tomography time was significantly reduced in nurse-driven codes (38.9 minutes versus 24.4 minutes; P .04).The use of a nurse-driven protocol is feasible and effective. When used in conjunction with a telestroke specialist, it may be of value in improving patient outcomes by decreasing the time for door to decision for IV-tPA.

The present report describes our efforts to convert an existing LXR agonist into an LXR antagonist using a structure-based approach. A series of benzenesulfonamides was synthesized based on structural modification of a known LXR agonist and was determined to be potent dual liver X receptor (LXR α/β) ligands. Herein we report the identification of compound 54 as the first reported LXR antagonist that is suitable for pharmacological in vivo evaluation in rodents.

α-Hydroxyketones undergo MnO2-mediated oxidation, followed by in situ trapping with 2-pyridylamidrazone, to give 3-pyridyl-5-substituted 1,2,4-triazines in a one-pot procedure, which avoids the need to isolate the reactive α-ketoaldehyde intermediates. By modifying this procedure to allow condensation prior to oxidation, the corresponding 6-substituted 1,2,4-triazines were obtained. The preparation of a novel unsymmetrical 2,2′-bipyridine using one of the pyridyl 1,2,4-triazines prepared herein is also described.

Summary Purpose: This is a phase II study to assess the role of induction chemotherapy in the management of stage IIIA non-small-cell lung cancer (NSCLC). We are now reporting the long-term follow-up of the Toronto phase II trial. Methods: Sixty five patients with mediastinoscopy proven stage IIIA NSCLC received two cycles of preoperative MVP or VLB/P followed by thoracotomy followed by two further courses of chemotherapy. Results: The overall response rate was 67.7% with three complete and 41 partial responders. Forty seven patients went on to thoracotomy with 35 complete resections. Pathologically 4.6% of patients had no tumour remaining. There were three postop deaths as well as five chemotherapy related deaths. Of the 35 patients completely resected 19 have recurred including eight in brain. The median survival for the entire 65 patients is 18.6 months with a 1 year survival of 66%, 5 year survival of 29% and a 10 year survival of 22%. Conclusions: The long-term survival of induction chemotherapy is maintained. The high incidence of brain recurrences warrants assessment of the role of prophylactic cranial radiation. The role of surgery for stage IIIA NSCLC following induction chemotherapy awaits further study.

A novel isonitrile derivative was synthesized and used in an Ugi four component coupling reaction to explore aryl group substitution effects on inhibition of the coagulation cascade serine protease factor Xa.

Factor Xa, a critical serine protease in the blood coagulation cascade, has become a target for inhibition as a strategy for the invention of novel anti-thrombotic agents. Here we describe the development of phenylglycine containing benzamidine carboxamides as novel, potent and selective inhibitors of factor Xa.

Pyridone derivatives, especially with 6-aryl substituents, have been shown to be useful P2-P3 peptidomimetic scaffolds for the design of potent inhibitors of ICE.

The total synthesis of an analogue of FK506, in which the substituted cyclohexyl residue at C28 has been replaced by a phenyl group, is described. This synthesis demonstrates (i) the successful application of new methodology for the introduction of the masked tricarbonyl grouping (C8-C10), and (ii) new synthetic routes to the (C10-C19) and (C22-C26) regions.

The asymmetric synthesis of a fragment corresponding to the C 1 -C 8 region of the immunosuppressant dicodermolide is reported. A trihydroxylactone of defined absolute stereochemistry is also prepared. This compound is a potential reductive ozonolysis product of discodermolide and may aid the determination of the absolute stereochemistry of the natural product.

The 5-year survival rates for patients undergoing a potentially curative surgical resection for pre-operatively identified stage 3A N2 non-small cell lung cancer (NSCLC) vary from 2–13%. In an attempt to improve the curative potential of surgery, 39 patients with mediastinoscopy stage 3A unresectable N2 NSCLC received induction chemotherapy with 2 cycles of mitomycin-C, vindesine and cisplatin (MVP). Responding patients underwent thoracotomy for resection and 2 further courses of MVP. The overall response rate was 64% ( 25 39 ) with 3 complete and 22 partial responses. 22 patients were resected which included a radical mediastinal node dissection. 18 resections were complete and 4 were incomplete. Pathologically 3 patients (7.7%) had no tumor remaining. There were 2 post-op deaths secondary to a BP fistula. In addition to GI and neurologic side effects, toxicity of chemotherapy included mitomycin pulmonary toxicity in 2 patients and 4 septic deaths. 28 patients have died, 20 with recurrent or progressive disease. Of the 18 patients completely resected, 8 have recurred with a median time to recurrence of 20.6 months. Sites of recurrence include 2 loco-regional, 5 distant (2 in brain) and 1 both. Median survival of the entire 39 patients is 18.6 months with a 3-year survival of 26%. The median survival for those patients completely resected is 29.7 months with a 3-year survival of 40%. These findings suggest that MVP is an effective but toxic chemotherapeutic regimen for limited NSCLC, and although the median survival appears to be prolonged, the role of induction chemotherapy followed by surgery in stage IIIA N2 NSCLC requires a Phase III randomized trial comparing it to other treatment modalities.

Mice immunized with an aromatic-dependent ( aro − ) S. dublin strain CS101 by either the intraperitoneal (i.p.) or oral route, were protected against oral challenge with a virulent S. dublin strain CS90, the degree of protection being the greatest when mice had received 3 immunizing doses at weekly intervals. Mice immunized with an aromatic-dependent ( aro − ) S. typhimurium strain CS332 by the i.p. or oral routes were protected against challenge with virulent S. dublin strain CS90 at 1 or 2 weeks but not at 3 or 4 weeks post-immunization. Mice immunized with 1 dose of aro − S. dublin strain CS101 by the i.p. route developed low levels of lipopolysaccharide (LPS) and flagellin-specific antibody but no delayed-type hypersensitivity (DTH) whereas those immunized with 2 or 3 doses developed significantly higher antibody titres and DTH. In contrast, mice immunized by the oral route developed neither significant antibody response nor DTH. The aro − S. dublin strain CS101 could not be detected beyond day 28 post-inoculation in visceral organs including liver, spleen, mesentery, small intestine, caecum or large intestine of mice inoculated by the i.p. route or in mice inoculated by the oral route with the exception of day 42 post-inoculation. Challenge of mice previously immunized with 3 doses of the aro − S. dublin strain CS101 by the i.p. or oral route with virulent S. dublin strain CS90 resulted in their rapid clearance from the above visceral organs. Calves immunized with the aro − S. dublin strain CS101 by either the intramuscular (i.m.) or oral routes were significantly protected against oral challenge with virulent S. dublin strain CS90. In contrast to the observations in mice, somatic (O) and flagellar (H) antibody titres of calves immunized by either route were negligible as were anti-LPS antibody titres. However, flagellin-specific antibody titres were higher in calves immunized by the i.m. than the oral route. These results indicate that the protection observed in immunized mice or calves against oral challenge with virulent S. dublin was unlikely to have been mediated by humoral salmonella-specific immune mechanism(s).

Emission spectra and ionization are compared in premixed flames of CH 4 burning in commercial F 2 (0.4% O 2 ) with those burning in purified F 2 . Oxygen impurity is reduced to below 0.02% in the purified F 2 by reaction with SbF 5 . No appreciable differences exist between the spectra of flames burning in commercial and purified F 2 ; both are dominated by bands of CHF and CH. CH emission is thus an intrinsic property of F 2 -hydrocarbon combustion. In contrast, ionization (as measured by a Langmuir probe) is reduced to an undetectable level in flames with purified F 2 and is roughly proportional to O 2 concentration in flames with unpurified F 2 . Ionization is thus not an inherent property of F 2 -hydrocarbon combustion.