Enantioselective synthesis of atropisomeric indoles via iron-catalysed oxidative cross-coupling.

Heterobiaryl compounds that exhibit axial chirality are of increasing value and interest across several fields, but direct oxidative methods for their enantioselective synthesis remain elusive. Here we disclose that an iron catalyst in the presence of a chiral PyBOX ligand and an oxidant enables direct coupling between naphthols and indoles to yield atropisomeric heterobiaryl compounds with high levels of enantioselectivity. The reaction exhibits remarkable chemoselectivity and exclusively yields cross-coupled products without competing homocoupling. Mechanistic investigations enable us to postulate that an indole radical is generated in the reaction but that this is probably an off-cycle event, and that the reaction proceeds through formation of a chiral Fe-bound naphthoxy radical that is trapped by a nucleophilic indole. We envision that this simple, cheap and sustainable catalytic manifold will facilitate access to a range of heterobiaryl compounds and enable their application across the fields of materials science, medicinal chemistry and catalysis.

Hemodynamic and pulmonary fluid status in the trauma patient: are we slipping?

Recent reports point to problems in the clinical assessment of the cardiopulmonary system in hemodynamically unstable patients, especially with the decreasing usage of pulmonary artery catheters. Our purpose was to evaluate the hypothesis that clinical judgment alone is inadequate for a reliable estimate of cardiopulmonary status in critically ill patients. Physician assessments (high, normal, or low) of cardiac index (CI) and thoracic fluid content (TFC) were made in 68 acute trauma cases and compared to the results obtained with impedance cardiography (ICG). Physician assessment using clinical judgment alone was correct only 42 per cent and 57 per cent, respectively, for CI and TFC. There was very little difference in heart rate (HR), blood pressure (BP), Glasgow Coma Score (GCS), and the number of injured systems between the incorrect and correct assessments of CI. However, the mean Injury Severity Score (ISS) was markedly higher for the incorrect than the correct CI values (18.8 +/- 9.3 vs 14.2 +/- 9.8, P = 0.0589). Thus, there is a need for an objective measurement of CI and TFC especially in the more severely injured patient. The inaccuracy of the clinical exam strongly suggests the need for a supplemental measurement, which the new and improved ICG monitor could provide.

The effect of repeated tuberculin skin testing of cattle on immune responses and disease following experimental infection with Mycobacterium bovis.

The comparative intradermal skin test, in which a delayed type hypersensitivity (DTH) response to purified protein derivative of tuberculin (PPD) from Mycobacterium bovis and M. avium is assessed and compared, may be used repeatedly on non-infected animals on farms where bovine tuberculosis (TB) has occurred. A skin test is known to affect subsequent skin tests in infected animals. The reported study was to determine whether repeated skin testing prior to infection with M. bovis might affect the development of the comparative skin test and IFNgamma response subsequent to exposure to virulent M. bovis. The comparative intradermal skin test was applied to one group of six calves five times at 8-week intervals. These and six control calves were subsequently inoculated intratracheally with a dose of M. bovis that produced mild disease. The development of the DTH reaction, IFNgamma, IL-10 and proliferative responses were compared in the two groups of animals. No differences in IFNgamma, IL-10 and proliferative responses were seen between the two groups of calves prior to challenge. After infection with M. bovis no differences in the development of the DTH and IFNgamma responses to PPD were noted as a consequence of the repeated skin testing prior to challenge. No differences between the groups were evident when ESAT-6 was used as antigen and IFNgamma was assayed, although two animals that responded to PPD did not respond with ESAT-6. However, there did appear to be subtle effects of repeated skin testing on the immune response post-challenge that did not affect the diagnostic tests. After challenge control animals showed greater proliferative responses than animals given repeated skin tests prior to challenge, indicating that the procedure did have consequences for immune responses following infection. In both groups a marked reduction in the intensity of the skin test and in the number of animals that would be recognized as reactors was evident when animals were tested 15 weeks post-infection compared to their responses 8 weeks earlier that could have consequences for diagnosis of TB. An antibody response was not evident as a result of repeat skin testing prior to infection but was seen in both groups of calves following skin testing performed 7 weeks after infection.

Talar fractures: three case studies.

Three case studies of fractures are presented that demonstrate the potential morbidity that these injuries can cause as well as the acceptable outcomes if treated appropriately. Two of the cases are talar fracture dislocations; the third is an osteochondral fracture of the talus. The importance of early treatment with open reduction and internal fixation is demonstrated. Success following surgical intervention in a nonhealed osteochondral fracture of the talus is also demonstrated.

Clopidogrel for prevention of major cardiac events after coronary stent implantation: 30-day and 6-month results in patients with smaller stents.

OBJECTIVES: We developed this study to assess the procedural outcome, complications, and clinical follow-up in patients treated with different antiplatelet regimens after intracoronary stent implantation with small stents. Three hundred sixty-one consecutive patients, in whom at least one 3.0-mm intracoronary stent was implanted, were studied. METHODS: The study was a prospective, observational registry of unselected consecutive patients treated in our institution. Patients who underwent stent implantation between December 1997 and July 1998 were treated with aspirin and ticlopidine; those who received stents between August 1998 and February 1999 were treated with aspirin and clopidogrel. RESULTS: In the group treated with ticlopidine, there were 190 patients who had 253 lesions treated with 274 stents. Mean age was 59.1 years, 72% were male, 31% had unstable angina, 64% had 1 stent, 36% had >1 stent, and 23% had multivessel intervention. In the group treated with clopidogrel, there were 171 patients who had 226 lesions treated with 245 stents. Mean age was 60.4 years, 79% were male, 26% had unstable angina, 70% had 1 stent, 30% had >1 stent, and 26% had multivessel intervention. Complications at 30 days in the ticlopidine group were death in 1 (0.5%), stent occlusion in 3 (1. 6%; all reopened with repeat angioplasty), non-Q-wave myocardial infarction in 2 (1%), and urgent revascularization in 4 (2%). Complications at 30 days in the clopidogrel group were noncardiac death in 1 (1.2%), cardiac death in 1 (1.2%), stent occlusion in 0, non-Q-wave myocardial infarction in 3 (1.8%), and urgent revascularization in 0. Follow-up was available in 100% of patients in both groups (mean 253 +/- 75 days in the ticlopidine group, 198 +/- 53 days in the clopidogrel group). Complications at >30 days in the ticlopidine group were death in 1 and clinical restenosis in 11 (5.8%); 1 additional patient had an admission with unstable angina to the local hospital. Hence, recurrent angina as a consequence of target lesion restenosis occurred in 5.8%. Complications at >30 days in the clopidogrel group were death in 0 and clinical restenosis in 8 (4.7%); 2 additional patients were admitted with unstable angina to the local hospital, and 1 patient had a myocardial infarction 164 days after stent implantation. Hence, recurrent angina as a consequence of target lesion restenosis occurred in 4.7%. There were no significant differences in complications between the 2 groups. CONCLUSIONS: Our observations suggest that clopidogrel can be used instead of ticlopidine in patients treated with stents with a diameter of

Pediatric all-terrain vehicle trauma: a 5-year statewide experience.

BACKGROUND/PURPOSE: This is a retrospective review of the pediatric all-terrain vehicle trauma victims who presented to the five major trauma centers serving the state of West Virginia during the 5-year period from January 1991 to December 1995. The purpose of this research is to characterize the nature of the injuries and the individuals injured to better appreciate the magnitude of the problem of ATV-related injuries in the pediatric population. METHODS: This study is a retrospective review of these 218 consecutive pediatric patients from trauma registry data and their medical records. RESULTS: Two hundred eighteen patients between the ages of 2 years and 16 years presented during the study period. Boys outnumbered girls three to one. The average Injury Severity Score (ISS) was 8.76, the average Glasgow Coma Score (GCS) was 14.4, and the average Trauma Score (TS) was 15.2. The most common injuries were orthopedic followed by head and facial injuries. The majority of the children did not wear helmets, and their injuries resulted in an average hospital length of stay of 4.3 days. Thirty-eight percent of the children required surgery. There were a total of four deaths for a mortality rate of 1.8%. The estimated total hospitalization cost for the 218 patients was $1,918,400.00. CONCLUSIONS: All-terrain vehicle-related trauma remains an ongoing safety concern facing society today. Every physician who cares for children should address this important issue when talking to children and parents about safety issues and injury prevention.

Comparative in vitro activity of doxycycline and oxytetracycline against porcine respiratory pathogens.

Minimum inhibitory concentrations of doxycycline and oxytetracycline were determined against 55 Pasteurella multocida strains, 59 Actinobacillus pleuropneumoniae strains and 26 Mycoplasma hyopneumoniae strains isolated from the respiratory tract of pigs. An additional set of 76 P multocida strains isolated from pneumonic pigs was tested for their minimum inhibitory concentrations of doxycycline. The P multocida and A pleuropneumoniae strains were isolated in France and the minimum inhibitory concentrations were determined by an agar dilution method. The M hyopneumoniae strains were isolated in the United Kingdom and minimum inhibitory concentrations were determined by a serial broth dilution method. All the strains tested were susceptible to doxycycline whereas 15 per cent of the P multocida strains and 22 per cent of the A pleuropneumoniae strains were resistant to oxytetracycline. Doxycycline concentrations inhibiting 90 per cent of strains were 1 microgram/ml for P multocida and 2 micrograms/ml for A pleuropneumoniae. The ratio of the minimum inhibitory concentrations of doxycycline and oxytetracycline ranged between 1/1 and 1/4 for the oxytetracycline-susceptible strains and between 1/16 and 1/64 for the oxytetracycline-resistant strains. All the M hyopneumoniae strains were susceptible to doxycycline and oxytetracycline, the concentrations inhibiting 90 per cent of strains being 1 microgram/ml and 2 micrograms/ml, respectively. These data confirm that doxycycline has a higher in vitro activity against pig respiratory pathogens than oxytetracycline.

A survey of Eimeria species in commercially-reared chickens in France during 1994.

In a survey of chicken coccidia in France during 1994, samples of litter were collected from 41 farms. On 31 of these farms, eimerian oocysts were abundant enough to allow monitoring of their numbers in the litter. Peak total oocyst counts on these farms ranged from 16,200 to 1,254,000/g of litter, but no coccidiosis was observed. The chickens reared without anticoccidial agents in their food (poulets biologiques) produced higher and earlier peak oocyst counts in litter than the chickens given medicated food (poulets labels). The oocysts in litter samples from 22 farms (13 poulet biologique, five poulet label, two standard broiler, one breeder and one layer) of the original 41 were identified. Six of the seven eimerian species known to parasitize chickens were found, using combinations of five methods (oocyst morphology, intestinal lesions, enzyme electrophoresis, growth in embryonating eggs and prepatent time). Multispecific infections predominated (95% of 22 farms), up to six species occurring together. Of farms where oocysts were detected, the percentages with each species were: Eimeria acervulina (100%), E. mitis (82%), E. tenella (77%), E. maxima (73%), E. praecox (45%) and E. brunetti (27%). These appear to be the first definite records of E. mitis and E. praecox for France. Although E. necatrix was not found in this survey, it had recently been detected by other workers in France, so that all seven chicken Eimeria species were known to be contemporaneous.

Listeria innocua isolated from a case of ovine meningoencephalitis.

This paper reports a naturally occurring case of meningoencephalitis associated with Listeria innocua in a Polled-Dorset ewe. The ewe was one of a housed group of twenty-five, fed ad lib. on wrapped baled silage. L. innocua was isolated after one week from cold enrichment culture of brain and pituitary tissue. Its identity was confirmed by conventional biochemical tests, API Listeria (BioMerieux UK Ltd), the absence of hly and prfA genes using PCR assay and sequencing two variable regions of 16S rDNA. Histological examination demonstrated lesions of vasculitis and perivascular cuffing in the midbrain which were consistent with listeriosis although limited in distribution and severity.

Pathogenicity of porcine intestinal spirochetes in gnotobiotic pigs.

Twelve intestinal spirochete strains of porcine origin were characterized on the basis of their phenotypic properties, by multilocus enzyme electrophoresis, and by pathogenicity testing in gnotobiotic pigs. The spirochetes used included two strains of Serpulina hyodysenteriae (B204 and P18A), two strains of Serpulina innocens (B256 and 4/71), one strain from the proposed new genus and species "Anguillina coli" (P43/6/78), and seven non-S. hyodysenteriae strains recently isolated from United Kingdom pig herds with a history of nonspecific diarrhea and typhlocolitis. By multilocus enzyme electrophoresis, five of these were identified as S. innocens, one was identified as an unspecified Serpulina sp., and one was identified as "A. coli." S. hyodysenteriae B204 and P18A, "A. coli" P43/6/78 and 2/7, and three (22/7, P280/1, and 14/5) of the five S. innocens field isolates induced mucoid feces and typhlocolitis in gnotobiotic pigs. None of the other spirochetes produced clinical signs or large intestinal pathology in this model. The "A. coli" strains induced a more watery diarrhea, with lesions present more proximally in the large intestine, than did the other pathogenic spirochetes. S. innocens 22/7 was also tested for pathogenicity in hysterotomy-derived pigs that had previously been artificially colonized with a spirochete-free intestinal flora and shown to be susceptible to swine dysentery. Despite effective colonization, strain 22/7 did not produce any disease, nor was there any exacerbation of large intestinal pathology or clinical signs when pigs with an experimentally induced existing colitis caused by Yersinia pseudotuberculosis were superinfected with strain 22/7. Certain non-S. hyodysenteriae spirochetes are therefore capable of inducing disease in gnotobiotic pigs, but their role as primary or opportunistic pathogens in conventional pigs remains equivocal.

Hypoxemia after blunt chest injury: right-to-left intracardiac shunt managed non-operatively.

A case of patent foramen ovale with right-to-left intracardiac shunt after blunt chest injury is presented. The association of pulmonary contusion, pulmonary hypertension, and patent foramen ovale in a previously healthy subject is discussed. In such a case reduction of the afterload on the right ventricle is the suggested modality of treatment for hypoxemia due to the right-to-left shunt.

Nurses' performance of inhalation technique with metered-dose inhaler plus spacer device.

OBJECTIVE: To determine if nurses could correctly use a metered-dose inhaler plus spacer (MDI-spacer) device after a brief description and demonstration of proper use by a clinical pharmacist. DESIGN: Pretest, educational intervention, posttest. SETTING: University hospital. PARTICIPANTS: Twenty-three nurses. INTERVENTIONS: Nurses were asked to use the MDI-spacer (Aerochamber) and were scored using a nine-point checklist (pretest). Educational intervention by the clinical pharmacist consisted of a five-minute discussion and correct demonstration of the device. Nurses were then asked to use the device again (posttest). MAIN OUTCOME MEASURES: Pre- and posttest scores. RESULTS: Total scores were improved after the educational intervention (66 percent pretest vs. 88 percent posttest, p = 0.0001). In an item analysis, four of the nine steps had improved significantly. CONCLUSIONS: A brief discussion and demonstration of correct use of MDI-spacers is effective in improving nurses' skill in using the device.

Isolation of Actinobacillus seminis from rams in the United Kingdom.

Actinobacillus seminis was isolated from the semen of five rams on four farms. Four of the rams had abnormal semen and three were also infertile. The isolates of A seminis showed similar phenotypic profiles and electrophoretic protein patterns to the type strain of A seminis but were distinct from Histophilus ovis previously isolated from rams with epididymitis in Scotland. The infection appeared to be subclinical but two of the five rams had palpable abnormalities of their testes. Three rams were treated with antibiotics but the infection persisted. No gross lesions were found in the genitalia of two of three rams examined post mortem but one had necrotic abscesses in the testes and epididymis. A seminis was isolated from the seminal vesicles and epididymis of one ram without gross lesions but not from the genitalia of the other two. On one farm the infection in a recently purchased ram led to the detection of another case as a result of the bacteriological screening of 11 stock rams not in contact with the initial case. These five subclinical cases, which included a supposedly healthy stock ram, suggest that A seminis infection may be widespread and should be considered in cases of infertility.

Protein recovery from the all-agarose ProSieve gel system.

Electrophoresis in polyacrylamide gels is one of the most powerful tools used for the analysis of proteins. However, this technique is not widely used for protein purification for a variety of reasons such as the following: less than quantitative recoveries; involved, time-consuming methodologies; and impurities in the protein preparations from gel-polymerization by-products that can modify the proteins and interfere with subsequent experiments. As an alternative, we have developed a simple and quantitative recovery procedure for proteins separated by electrophoresis in the all-agarose ProSieve gel system. Using this procedure, greater than 90% of each protein examined was recovered, and these proteins were unaffected by the recovery procedure.

A three-year study of Salmonella dublin infection in a closed dairy herd.

Over a period of three years, Salmonella dublin was isolated occasionally from the faeces of nine adult cattle in a closed dairy herd. The organism was also isolated from 12 of the samples collected after parturition; isolations were made from newborn calves on 11 occasions, from a vaginal swab once and from a milk sample once. Nine of the isolations from the calves were made from swabs obtained within 24 hours of birth. Throughout the investigation isolations were made from heifers, steers and older calves and 11 infected animals were detected. S. dublin was widespread in the farm environment and it was concluded that environmental contamination was an important source of infection for animals of all ages, some of which may have become latent carriers. The family history of one cow, seven of whose offspring were infected with S dublin, suggested the possibility of vertical transmission. Without reliable tests to detect latent carriers, it is suggested that control of this infection must be based on improved hygiene and the use of vaccination to improve the immunity of the herd.