Metals and Organohalogen Contaminants in Bald Eagles (Haliaeetus leucocephalus) from Ontario, 1991-2008.

We examined the degree of exposure of lead (Pb), mercury (Hg), and several organohalogen contaminants and its potential impact on survival of bald eagles in Ontario from 1991 to 2008. Overall, results for 43 dead or dying bald eagles collected in the province indicate that 23% (10/43) of birds died of Pb poisoning and 9% (4/43) died of suspected Hg poisoning. Pb poisoning was diagnosed based on exceedances of toxicity thresholds in liver and kidney and supported by clinical observations, necropsy results, and histology findings when available. Evidence for Hg poisoning in eagles was limited; however, Hg concentrations exceeded the toxicity threshold in kidney. Pb concentrations ranged widely in liver and kidney. Total Hg concentrations were relatively higher in kidney compared with liver and were significantly correlated with selenium (Se) concentrations in both tissues. Concentrations of p,p'-DDE and sum PCBs in livers of 12 bald eagles collected from 2001 to 2004 were likely below concentrations associated with adverse effects. Hepatic concentrations of total polybrominated diphenyl ethers were generally higher in birds collected from southern Ontario compared with northern Ontario. Potential impacts of exposure to these flame retardants and others are not known. Elevated metal exposure appears to influence survivorship and may affect the recovery of bald eagles in the province, particularly in southern Ontario and along the Great Lakes where a disproportionate number of poisoned eagles were collected. Increased efforts are needed to identify sources of exposure and develop measures to reduce metal exposure in this top predator.

Relationships among mercury, selenium, and neurochemical parameters in common loons (Gavia immer) and bald eagles (Haliaeetus leucocephalus).

Fish-eating birds can be exposed to levels of dietary methylmercury (MeHg) known or suspected to adversely affect normal behavior and reproduction, but little is known regarding Hg's subtle effects on the avian brain. In the current study, we explored relationships among Hg, Se, and neurochemical receptors and enzymes in two fish-eating birds--common loons (Gavia immer) and bald eagles (Haliaeetus leucocephalus). In liver, both species demonstrated a wide range of total Hg (THg) concentrations, substantial demethylation of MeHg, and a co-accumulation of Hg and Se. In liver, there were molar excesses of Se over Hg up to about 50-60 microg/g THg, above which there was an approximate 1:1 molar ratio of Hg:Se in both species. However, in brain, bald eagles displayed a greater apparent ability to demethylate MeHg than common loons. There were molar excesses of Se over Hg in brains of bald eagles across the full range of THg concentrations, whereas common loons often had extreme molar excesses of Hg in their brains, with a higher proportion of THg remaining as MeHg compared with eagles. There were significant positive correlations between brain THg and muscarinic cholinergic receptor concentrations in both species studied; whereas significant negative correlations were observed between N-methyl-D-aspartic acid (NMDA) receptor levels and brain Hg concentration. There were no significant correlations between brain Se and neurochemical receptors or enzymes (cholinesterase and monoamine oxidase) in either species. Our findings suggest that there are significant differences between common loons and bald eagles with respect to cerebral metabolism and toxicodynamics of MeHg and Se. These interspecies differences may influence relative susceptibility to MeHg toxicity; however, neurochemical responses to Hg in both species were similar.

Re-establishment of neurochemical coding of preganglionic neurons innervating transplanted targets.

We investigated the effect on neurochemical phenotype of changing the targets innervated by sympathetic preganglionic neurons. In neonatal rats, the adrenal gland was transplanted into the neck, to replace the postganglionic neurons of the superior cervical ganglion. Transplanted adrenal glands survived, and contained noradrenergic and adrenergic chromaffin cells, and adrenal ganglion cells. Retrograde tracing from the transplants showed that they were innervated by preganglionic neurons that would normally have supplied postganglionic neurons of the superior cervical ganglion. The neurochemical phenotypes of preganglionic axons innervating transplanted chromaffin cells were compared with those innervating the normal adrenal medulla or superior cervical ganglion neurons. As in the normal adrenal gland, preganglionic nerve fibres apposing transplanted chromaffin cells were cholinergic. The peptide and calcium-binding protein content of preganglionic fibres was similar in normal and transplanted adrenal glands. In both cases, cholinergic fibres immunoreactive for enkephalin targeted adrenergic chromaffin cells, whilst cholinergic fibres with co-localised calretinin-immunoreactivity innervated noradrenergic chromaffin cells and adrenal ganglion cells. In contrast to the innervation of normal adrenal glands, these axons lacked immunoreactivity to nitric oxide synthase. In a set of control experiments, the superior cervical ganglion was subjected to preganglionic denervation in rat pups the same age as those that received adrenal transplants, and the ganglion was allowed to be re-innervated over the same time course as the adrenal transplants were studied. When the superior cervical ganglion was re-innervated by preganglionic nerve fibres, we observed that all aspects of chemical coding were restored, including cholinergic markers, nitric oxide synthase, enkephalin, calcitonin gene-related peptide and calcium binding proteins in predicted combinations, although the density of nerve fibres was always lower in re-innervated ganglia. These data show that the neurochemical phenotypes expressed by preganglionic neurons re-innervating adrenal chromaffin cells are selective and similar to those seen in the normal adrenal gland. Two explanations are advanced: either that contact of preganglionic axons with novel target cells has induced a switch in their neurochemical phenotypes, or that there has been target-selective reinnervation by pre-existing fibres of appropriate phenotype. Regardless of which of these alternatives is correct, the restoration of normal preganglionic codes to the superior cervical ganglion following denervation supports the idea that the target tissue influences the neurochemistry of innervating preganglionic neurons.

Therapy of nosocomial pneumonia.

HAP remains a major cause of morbidity and mortality among hospitalized patients. Although early appropriate therapy results in improved outcomes, the cause of HAP frequently is not known at the time antimicrobial therapy is initiated. Most cases of HAP result from microaspiration of oropharyngeal secretions previously colonized with pathogenic bacteria, and the spectrum of potential pathogens is broad. Taking several factors into account can narrow this spectrum, including severity of illness, length of stay before the onset of pneumonia, and presence of risk factors for specific pathogens. When therapy has been initiated, follow-up of microbial studies and careful monitoring of the patient's course is important. The clinical improvement, even when therapy is appropriate, frequently takes days; therapy should not be changed for the first 2 to 3 days unless frank deterioration is noted. Patients who fail to respond or experience clinical deterioration should be re-examined carefully, and thought should be given to the possibility of other noninfectious processes.

Treatment of hospital-acquired penumonia.

Hospital-acquired pneumonia (HAP) remains a significant cause of morbidity and attributable mortality, especially among patients undergoing mechanical ventilation. The clinical approach to this disorder continues to evolve. Although our understanding of the epidemiology, risk factors, and pathogenesis of this disorder are expanding, consensus on diagnostic, therapeutic, and preventive strategies is lacking. Although outcome is significantly improved by the rapid introduction of appropriate antimicrobial therapy, presently available diagnostic tests rarely are able to identify a specific pathogen when antimicrobial choices are made. Thus, most therapy is by necessity empirical. The American Thoracic Society (ATS) published guidelines for the empiric treatment of HAP in 1996, this article reviews the recommendations of these guidelines and, if new information is available, updates these recommendations.

Hygiene at winter bird feeders in a southwestern Ontario city.

To further understand the source of the epidemic of salmonellosis in some species of birds using bird feeders in southern Ontario in the winter of 1997-1998, 124 bird feeder stations were examined for their state of hygiene and for Salmonella on 5 occasions during the winter of 1999 in a city of 100,000 people in southwestern Ontario. No Salmonella were isolated from feed contaminated with feces recovered from the feeders. Squirrel-proof feeders were significantly less contaminated with feces than were other feeder types (hopper, platform, silo), which did not differ significantly in their hygiene scores. Contamination of squirrel-proof feeders increased significantly through the course of the study, but other feeder types showed no significant change. Hygiene was poorer if feeders were maintained equally by both male and female household members, particularly as they grew older, but no age or gender effect was observed if only one person was largely responsible for maintaining the feeders. We concluded that winter bird feeder stations in a southern Ontario city were not contaminated with Salmonella but that bird feeder stations could be designed better to reduce fecal contamination of feed.

Practice guidelines for the management of patients with blastomycosis. Infectious Diseases Society of America.

Guidelines for the treatment of blastomycosis are presented; these guidelines are the consensus opinion of an expert panel representing the National Institute of Allergy and Infectious Diseases Mycoses Study Group and the Infectious Diseases Society of America. The clinical spectrum of blastomycosis is varied, including asymptomatic infection, acute or chronic pneumonia, and extrapulmonary disease. Most patients with blastomycosis will require therapy. Spontaneous cures may occur in some immunocompetent individuals with acute pulmonary blastomycosis. Thus, in a case of disease limited to the lungs, cure may have occurred before the diagnosis is made and without treatment; such a patient should be followed up closely for evidence of disease progression or dissemination. In contrast, all patients who are immunocompromised, have progressive pulmonary disease, or have extrapulmonary disease must be treated. Treatment options include amphotericin B, ketoconazole, itraconazole, and fluconazole. Amphotericin B is the treatment of choice for patients who are immunocompromised, have life-threatening or central nervous system (CNS) disease, or for whom azole treatment has failed. In addition, amphotericin B is the only drug approved for treating blastomycosis in pregnant women. The azoles are an equally effective and less toxic alternative to amphotericin B for treating immunocompetent patients with mild to moderate pulmonary or extrapulmonary disease, excluding CNS disease. Although there are no comparative trials, itraconazole appears more efficacious than either ketoconazole or fluconazole. Thus, itraconazole is the initial treatment of choice for nonlife-threatening non-CNS blastomycosis.

Antimicrobial effects of lidocaine in bronchoalveolar lavage fluid.

The antimicrobial activity of lidocaine in bronchoalveolar lavage fluid (BAL(f)) was investigated. Clinical respiratory isolates were added to BAL(f) suspensions containing lidocaine and to normal saline. The growth of two of four isolates of Streptococcus pneumoniae was significantly reduced in the presence of lidocaine-BAL(f) compared with controls in saline. Growth of Moraxella catarrhalis isolates was reduced in normal saline when compared with BAL(f) containing lidocaine. There was no effect upon the growth of Haemophilus influenzae, Pseudomonas aeruginosa and Candida albicans isolates. The recovery of isolates of S. pneumoniae may be reduced below the critical threshold of 10(5) cfu/mL during bronchoscopy when using lidocaine as a local anaesthetic.

Drug-resistant pathogens in community- and hospital-acquired pneumonia.

Antimicrobial resistance has been a problem since the early days of the antibiotic era, but in recent years, this resistance has increased in the hospital and is being recognized more in the community setting. Respiratory pathogens such as S. pneumoniae and H. influenzae, for example, have developed resistance to traditional antimicrobial therapy, often over a very short period of time. This increase in resistance patterns requires physicians to closely monitor antimicrobial resistance in their community and to appreciate that some antimicrobial resistance mechanisms may result in resistance for a complete class of antibiotics or different classes of antibiotics with similar mechanisms of action.

The role of antimicrobial therapy in acute exacerbations of chronic bronchitis.

Acute exacerbations of chronic bronchitis (AECB) result in increased morbidity and mortality. The role of bacteria in AECB, the importance of antimicrobial therapy, and the choice of antimicrobial agents have been debated for decades. Fortunately, within the past few years, a number of studies and one consensus statement have been reported that have increased the understanding of the role of bacteria in AECB and suggest approaches in selecting antimicrobial therapy. This article will review these studies and present an empiric approach in treating AECB based upon the patient's presenting findings, related risk factors, and potential antimicrobial resistance patterns that may be encountered.

Commentary on the 1993 American Thoracic Society guidelines for the treatment of community-acquired pneumonia.

Early treatment of community-acquired pneumonia (CAP) is associated with improved outcome. Since extensive diagnostic testing identifies an etiologic agent in only half of the cases and usually requires several hours or even days for results, CAP is most often initially treated empirically. In 1993, the American Thoracic Society (ATS) established guidelines to assist primary care physicians in antibiotic selection for the initial empiric treatment of CAP in immunocompetent adults. Since publication of the guidelines, the incidence of certain bacteria has been redefined, antimicrobial resistance patterns have changed, risk factors for stratifying need for hospitalization have been further defined, and newer antibiotics have been introduced. These changes necessitate a reevaluation of the 1993 ATS guidelines. This article proposes a modification of the ATS guidelines. This modification continues to classify patients into groups, based on specific risk factors, to which a limited number of likely pathogens are identified and for which antibiotic treatment regimens are developed. The modification differs from the original ATS guidelines because of the changes in risk factors. Patient groups are still broadly divided into outpatient and inpatient care, but earlier risk factors of age and coexisting illness have been refined. Risk factors suggested herein as considerations to guide treatment include the presence of cardiopulmonary disease, history of smoking, severity of illness, risk of drug-resistant Streptococcus pneumoniae and Pseudomonas aeruginosa, and need for ICU admission.

All-D peptides recognized by an anti-carbohydrate antibody identified from a positional scanning library.

Monoclonal antibodies recognize antigens with high affinity and specificity, but the structural basis for molecular mimicry remains unclear. It is often assumed that cross-reactive antigens share some structural similarity that is specifically recognized by a monoclonal antibody. Recent studies using combinatorial libraries, which are composed of millions of sequences, have examined antibody cross-reactivity in a manner entirely different from traditional epitope mapping approaches. Here, peptide libraries were screened against an anti-carbohydrate monoclonal antibody for the identification of peptide mimics. Positional scanning libraries composed of all-l or all-d hexapeptides were screened for inhibition of monoclonal antibody HGAC 39.G3 binding to an antigen displaying N-acetyl-d-glucosamine (GlcNAc) residues on a polyrhamnose backbone. Inhibitory activity by mixtures from the all-d hexapeptide library was greater than the activity from the all-l libraries. The most active d-amino acid residues defined in each of the six positions of the library were selected to prepare 27 different individual hexapeptides. The sequence Ac-yryygl-NH2 was specifically recognized by mAb HGAC 39.G3 with a relative affinity of 300 nM when measured in a competitive binding assay. The contributions to overall specificity of the residues of the all-d peptide (Ac-yryygl-NH2) in binding to mAb HGAC 39.G3 were examined with a series of truncation, l and d-amino acid substitution, and retro analogs. Dimeric forms of the all-d peptide were recognized with tenfold to 100-fold greater affinities relative to the monomer. The all-d peptide was found to inhibit mAb HGAC 39.G3 binding to an anti-idiotype antibody with approximately 1000-fold greater affinity than GlcNAc. As demonstrated here, the study of immune recognition using combinatorial chemistry may offer new insights into the molecular basis of cross-reactivity.

Hospital-acquired pneumonia: epidemiology, etiology, and treatment.

Despite improvements in diagnosis, treatment, and prevention, hospital-acquired pneumonia (HAP) remains the number one cause of nosocomial mortality. This article reviews the current knowledge regarding the incidence, epidemiology, and causes of HAP, with the appreciation that the available information is incomplete and that controversies are common, and thus the authors provide a rational approach to the initial management of HAP in immunocompetent adults. A discussion of therapy and what to do with patients who do not respond to the empiric therapy are included. The American Thoracic Society (ATS) statement on HAP has served as a foundation for this review but has been supplemented by newer literature that was not available when the ATS statement was developed.

Hospital-acquired pneumonia: recent advances in diagnosis, microbiology and treatment.

Nosocomial or hospital-acquired pneumonia occurs frequently, despite preventative measures and advances in diagnostic procedures and treatment of this severe infection. This article will highlight the recent literature with emphasis on significant publications and advances in the area of pneumonia pathogenesis, microbiology, diagnosis, and response to antimicrobial therapy.

Drug-resistant Streptococcus pneumoniae.

Streptococcus pneumoniae remains a major cause of infection in both children and adults, annually resulting in significant morbidity and mortality. The past two decades have seen an alarming worldwide increase in the incidence of drug-resistant S. pneumoniae (DRSP). DRSP is now common throughout the United States, and physicians are questioning how best to approach this epidemic. With the introduction of a number of newer antimicrobial agents, the potential for improved preventive measures, and a better understanding of DRSP, the approach to the management of DRSP infections may change greatly in the next few years. In this article we will review the development of DRSP, identify populations at increased risk of exposure to DRSP, address what approaches might be used to limit its spread, and suggest initial empirical therapy when treating patients with pneumonia due to DRSP.

Nosocomial pneumonia guidelines: an international perspective.

Hospital-acquired pneumonia is a serious illness with substantial morbidity and mortality. Management of this illness is challenging for the physician and a number of diverse issues must be considered when initiating therapy. Guidelines for the treatment of hospital-acquired pneumonia have been developed in Canada and the United States. A questionnaire sent to infectious disease physicians or clinical microbiologists in 29 countries showed that Australia, Sweden, and France had national guidelines in addition to Canada and the United States, while Hong Kong and France had single hospital-based guidelines. These guidelines are reviewed and some of the controversial issues relating to nosocomial pneumonia are discussed.