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G D Campbell

Publications and source records attributed to G D Campbell.

At least 19 recordsLinked to original sources
PubMed2003

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.

Adrenal Glands↗
PubMed2001

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.

Anti-Bacterial Agents↗
PubMed2000

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.

Amphotericin B↗
PubMed2000

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.

Anti-Bacterial Agents↗
PubMed2000

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.

Anti-Bacterial Agents↗
PubMed2000

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.

Animals↗
PubMed1999

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.

Adolescent↗
PubMed1999

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.

Acute Disease↗
PubMed1999

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.

Adult↗
PubMed1998

Health of tree swallows (Tachycineta bicolor) nesting in pesticide-sprayed apple orchards in Ontario, Canada. I. Immunological parameters.

The degree of pesticide exposure and its effects on the immune system and its development were determined in 16-d-old tree swallow (Tachycineta bicolor) chicks from 4 sprayed apple orchards and three nonsprayed sites in southern Ontario, Canada, during 1994-1995. Persistent contaminant residues were measured in tree swallow eggs and in each chick hepatic ethoxyresorufin O-deethylase (EROD) activity; body, immune organ, and liver masses; lymphocyte blastogenesis response; respiratory burst and phagocytic responses; hemarological evaluation; and histological development of thymus, bursa of fabricius, and spleen were determined. Chemicals sprayed on apple orchards were mainly ethylene bisdithiocarbamate and myclobutanil fungicides and organophosphorus, carbamate, and synthetic pyrethroid insecticides. During the period between oviposition of the first egg in each nest to d 16 after hatching, individual nests in orchards were exposed to between 4 and 11 individual chemical applications and up to 3 mixtures of pesticide sprays. Concentrations of pesticides, polychlorinated biphenyls (PCBs), and lead and arsenic residues in tree swallow eggs and liver were low and not variable among sites except p,p'-DDE, which was as high as 2.29 microg/g wet weight in eggs. EROD activity was not different among sites. Organochlorine and trace metal residues and EROD activity were not correlated with any immune parameter. In sprayed birds, we found a significantly increased blastogenic response to pokeweed mitogen (12.5 microg/ml). However, nests were initiated over a period of several weeks and we also found changes in other tree swallow immune parameters that were related to the date of chick collection. Hematological parameters, bursal and thymic masses, phagocytic response, and thymic development were all correlated with the day the chicks were 16 d of age. After accounting for the collection date of birds from each nest, we found cell proliferation in the cortex and delayed thymic involution correlated positively with increasing spray exposure. We also found that birds in sprayed orchards were slightly anemic compared to birds from nonsprayed sites, and there were smaller bursal masses and an increase in relative heterophil concentrations in the sprayed orchard birds. The local inflammation may have been caused by trematode parasite infections, although pesticide exposure also correlated positively with these parameters. This is the first study of the immunology and effects of current pesticide exposures in wild passerines; therefore it is difficult to predict the long-term consequences of the apparent stimulated immune systems in sprayed birds. However, some environmental contaminants that overtly stimulate the immune system in mammals have induced hypersensitivity and/or autoimmunity. Therefore we speculate that these effects are possible in tree swallows.

Animals↗
PubMed1998

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.

Amino Acid Sequence↗
PubMed1998

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.

Acinetobacter↗
PubMed1998

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.

Adolescent↗
PubMed1998

Characterization of antigen-antibody interactions using single substitution analogs and mixture-based synthetic combinatorial libraries.

In an effort to use monoclonal antibodies (mAbs) as selective probes for early detection of breast cancer, the specificities of a number of antipeptide mAbs have been studied at the individual amino acid level using single substitution peptide analogs and peptide combinatorial libraries. In this study, the mapping results are presented for mAb172-12A4, which was raised against the haptenic peptide LGSGAFGTIYKG(C), corresponding to residues 138-149 of the oncogene v-erbB. This peptide is homologous with a region in epidermal growth factor receptor (EGFR) and human oncogene c-erbB-2, and contains the ATP binding motif that is common among protein kinases. The substitution profile of this interaction correlated well with the results from the screening of hexa- and decapeptide positional scanning libraries. Based on the results of this mAb's specificity for the antigenic determinant (-AFGTIYK-), proteins that have sequence homology were found from a database search of human sequences. Thirty-two unique peptide sequences, a majority of which was from protein kinases, were synthesized and tested for recognition by mAb 172-12A4. Eleven peptides had activities that differed from the original peptide by less than an order of magnitude, and the activities for 29 of the 32 (90%) could be accurately predicted based on the individual substitution analog results. While both epitope mapping approaches address the amino acid level of mAb specificity, positional scanning libraries offer an advantage of identifying the positional importance of each antigenic determinant residue without any prior knowledge of the mAb's specificity. The fine specificity mapping of peptide-specific mAbs using the synthetic tools illustrated here will be useful for the development of immunodiagnostics that detect cancer-related proteins in clinical samples.

Amino Acid Substitution↗