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Biomedical subjects

B Herndon

Publications and source records attributed to B Herndon.

14 recordsLinked to original sources

Bronchiolitis obliterans induced by intratracheal papaverine: a novel animal model.

Constrictive bronchiolitis obliterans (CBO), a highly fatal syndrome seen following toxicant exposure and lung transplantation, is in need of mechanistic study. This report creates an animal model of toxicant induced CBO, validates its pathology and suggests a physiologic mechanism for its origin. Papaverine, the alkaloid in Sauropus plants and responsible for human toxicant-induced CBO, was used to create the rat model. A mini-osmotic pump delivered papaverine intratracheally for up to 28 days (0.25 microL/hr, totaling 6.4 mg). Bronchoalveolar lavage (BAL) was measured. Lung tissue was evaluated for signs of CBO (H&E and Trichrome staining). Cytokines deregulated in human CBO were also measured (TGF-beta and eNOS). Peribronchial inflammation, extensive denudation and destruction of bronchial mucosa, as well as increased peribronchial collagen (all classic signs of CBO) were observed as early as 7 days in papaverine treated animals, with more extensive damage after 28 days. Significant elevations of TGF-beta and eNOS were seen in lung homogenates. Our toxicant induced model of CBO via a novel delivery method of intratracheal papaverine accurately reproduces pathology and cytokine profiles of human CBO. Papaverine has potential for producing CBO by multiple routes. This model introduces a vehicle for both understanding and development of innovative treatment for CBO.

Animals↗

Osteomyelitis: etiology, diagnosis, treatment and outcome in a public versus a private institution.

BACKGROUND: Although bone infections are difficult to diagnose and manage, primary health care providers often give comprehensive care to patients with few referrals. To evaluate how trends in care impact upon management of bone infections, we performed a retrospective review of medical records of 198 osteomyelitis patients. PATIENTS AND METHODS: 130 patients were hospitalized at a private institution and 68 were hospitalized at a public (teaching) institution. Outcomes measured were bone salvage or loss in relation to predisposing co-morbidities and infectious disease (ID) physician involvement in the patient care. RESULTS: Co-morbidities predominating at the public and private hospitals, respectively, were presence of metal implants (20% and 37%) and diabetes (32% and 31%). The most common pathogens at the public and private hospitals, respectively, were methicillin-susceptible Staphylococcus aureus (MSSA, 16 and 32%) and methicillin-resistant S. aureus (MRSA, 3% and 31%). ID specialists treated longer with i.v. antibiotics (42 and 43.5 median treatment days) than non-ID specialists (14 and 7 median treatment days). When ID specialists were involved in case management, a trend to bone salvage was seen at the public hospital (p < 0.09). CONCLUSION: Osteomyelitis patient outcome varies less by hospital setting than by case management.

Clinical Competence↗

Cost-effective post-exposure prevention of poison ivy dermatitis.

BACKGROUND: Poison ivy (toxicodendron) dermatitis is the most common allergic contact dermatitis in the USA. No studies have shown an effect of washing after a short period of time for the prevention of binding of urushiol to the skin. Objective To evaluate the efficacy of three different modes of postcontact prevention using a surfactant (Dial ultra dishwashing soap), an oil-removing compound (Goop), and chemical inactivation (a commercial product Tecnu). METHODS: A consented, unsponsored, volunteer experimental study on medical students from the University of Missouri School of Medicine, Kansas City. Each subject served as his/her own control, comparing four 2.5-cm exposed squares on the inner aspect of the forearm, three of which were treated and one untreated. RESULTS: Comparisons between the different agents were nonsignificant with P > 0.05. Each treatment, however, was significantly improved over the untreated control. CONCLUSIONS: Our study showed 70%, 61.8%, and 56. 4% protection with Tecnu, Goop, and Dial, respectively, when compared to the positive control, or to the possible maximum response, with a cost per ounce (in a local drug and automotive store) of $1.25, $0.07, and $0.07, respectively, for a decrease in protection that is nonsignificant.

Adult↗

Beta-blocker use in patients with acute myocardial infarction treated by hospitalists.

It is well recognized that the administration of beta blockers to patients after myocardial infarction improves survival. This retrospective cohort and prospective study sought to define the usage of a large hospitalist group and enhance this usage by education and the utilization of a uniform discharge summary. All patients with a discharge diagnosis of acute myocardial infarction were included for analysis. The use of beta blockers by the hospitalist group was initially collected retrospectively and compared with two large cohorts. The data were presented to the hospitalist group. Prospective data collection then commenced. Retrospective analysis of the use of beta blockers showed a rate of 68% as compared with 21% and 34% in two large cohorts (P < .0001). After data were reviewed and conference occurred, prospective use of beta blockers increased to 90% (P < .0005). Patients with myocardial infarction were extremely likely to be treated with beta blockers by this hospitalist group. Review of previous usage and review of contraindications along with the use of a uniform discharge summary resulted in a significant increase in the use of these life-saving drugs.

Adrenergic beta-Antagonists↗

Survival benefits of pulmonary cellular activation in AIDS patients with Pneumocystis infection.

Pneumocystis carinii pneumonia (PCP) is the most common life-threatening, opportunistic infection in patients with acquired immunodeficiency syndrome. Between 1984 and 1987, patients infected with human immunodeficiency virus (HIV) received bronchoalveolar lavages to confirm PCP diagnosis. Unstained slides containing bronchoalveolar cells from 20 of these patients were stored. Eight years after the last diagnostic bronchoalveolar lavage, blinded investigators immunohistochemically analyzed the unstained bronchoalveolar cells for the presence of proliferating cells and pneumocystic cysts. A significant association was found between the percentage of activated macrophages and patient survival after diagnostic bronchoalveolar lavage. On chart review, patients with higher CD4/CD8 ratios had significantly greater alveolar macrophage activation. The correlation of life span and pulmonary cellular activation in these cases (most predating retroviral therapy) suggests the importance of pulmonary cellular function to immunity and survival in patients infected with HIV.

AIDS-Related Opportunistic Infections↗

Does pulmonary airway inflammation relate to intercellular adhesion molecule (ICAM-1) in bronchoalveolar lavage specimens? A pilot study.

BACKGROUND: The objective of this study was to assess the value of intercellular adhesion molecule-1 (ICAM-1) levels in bronchoalveolar lavage (BAL) specimens. METHODS: BALs from 44 unselected patients undergoing routine diagnostic bronchoscopy with bronchoalveolar lavage were studied. Cell-free supernatants of the BAL specimens were frozen at -70 degrees C until tested. BAL ICAM-1 concentration was measured using enzyme immunoassay and degree of patient illness assessed by modified APACHE II scores. RESULTS: ICAM-1 in BAL fluid was positively correlated to the patient illness score (modified APACHE II) at a p value of 0.026. No such association was found between ICAM-1 levels and cigarette use or infection with pneumocystis carinii, although a few individuals in the smoker's group with pulmonary infection had 10-fold elevations of BAL ICAM-1. CONCLUSIONS: BAL ICAM-1 may relate to the pulmonary pathogenic process as supported by the association between modified APACHE II scores and ICAM-1 values. Specific pulmonary-related diagnosis and BAL ICAM-1 did not produce significant relationships in this study.

APACHE↗

Contribution of the host to test results in assays of Staphylococcus epidermidis.

From two human populations (one pediatric and one adult), clinically diagnosed with Staphylococcus epidermidis (S. epidermidis) sepsis of similar severity, bacteria were isolated from pre-antibiotic blood samples and evaluated for virulence. The LD50 of the bacteria in a mouse model was performed, with evaluation of animals dying acutely following intravenous S. epidermidis administration. More simple assays of virulence were also performed, including bacterial adherence to a fibrin clot and carbohydrate specific lectin binding. The eight pediatric-host S. epidermidis isolates required a significantly larger dose to produce lethality in dosed animals (LD50) when compared to the 20 adult-host S. epidermidis isolates. The fibrin clot assay, a test that has corroborated bacterial virulence in endocarditis models, did not differentiate the groups: all but one of the 28 isolates were well above the adherence seen with the ATCC control, suggesting endocarditis-producing potential. Glycocalyx (slime) from eight of the more virulent isolates showed reactivity with a glucose-specific biotinylated lectin which was lacking in other isolates. Necropsy of mice dying at 12 hr showed S. epidermidis strain differences in specific organ effects. Overall, this study demonstrates the utility of the LD50 to provide a highly sensitive quantification of bacterial virulence. Necropsy of test animals dying acutely has showed an apparent organ tropism of some of these isolates which are usually considered harmless commensals.

Adult↗

Bacterial characterization in Staphylococcus epidermidis septicemia.

An analysis of the in vitro characteristics of Staphylococcus epidermidis strains isolated from patients with true S. epidermidis septicemia was undertaken. From a potential population of 921 cultures from adult patients with coagulase-negative bacteremia, highly defined selective criteria limited the population to 20 patients with S. epidermidis sepsis, from whose blood cultures the study organisms were isolated. Another population of 11 S. epidermidis blood isolates, clinically determined to be contaminants, were tested as a control group. In vitro assays performed on all isolates included slime quantification, hydrophobicity, surface hexoses, and capsule presence. Murine spleen phagocytosis of intravenously administered isolates was measured in vivo. The assayed quantity of cell-associated bacterial hexose sugars positively correlated with organism virulence to the host (p = 0.02). This bacterial population was also low in slime but varied as to the presence of capsule and ease of phagocytosis. Permanent catheter-bearing patients' bacteria were somewhat more hydrophobic (p = 0.07). We conclude that in vitro assays can differentiate bacteremic cultures from contaminants and that the characteristic that best relates to host toxicity in these S. epidermidis isolates was bacterial cell surface-associated carbohydrate.

Adult↗

Pulmonary effects of ischemic limb reperfusion: evidence for a role for oxygen-derived radicals.

OBJECTIVE: To evaluate the lung as a reperfusion target after limb ischemia-reperfusion, and to measure specifically the oxygen radical response to this reperfusion. DESIGN: Paired simple randomized, with continuous interval data in dependent variable and both continuous and nominal independent variables. SUBJECTS AND INTERVENTION: Sprague-Dawley male rats (n = 195) were anesthetized and both hind limbs occluded for 3.75 hr, the overnight LD50. Alveolar lavage was performed on the animals 1 hr after reperfusion or on survivors 20 hr after reperfusion. Groups were either undosed or pretreated with alpha-tocopherol as an antioxidant (50 mg/kg.day) 2 days before ischemia. MEASUREMENTS AND MAIN RESULTS: Luminol-enhanced chemiluminescence was measured in both phorbol myristate acetate-stimulated and unstimulated macrophages. Nanomoles of superoxide radicals per 10(6) alveolar cells/min were also measured using a cytochrome c reduction assay. A significant (p less than .01, Student's t-test), time-dependent increase in response of cells from ischemic-reperfused rats was seen. Pretreatment with antioxidant had no effect at 1 hr, but significant differences were seen in the 20-hr survivors. CONCLUSIONS: These studies show that alveolar lavage cells, 95% macrophages, reflect the reperfusion of ischemic-reperfused hind limbs by a significant increase in oxygen radical activity, an effect partly suppressed in antioxidant-dosed survivors.

Animals↗

Clindamycin effect on glycocalyx production in experimental viridans streptococcal endocarditis.

Abundant glycocalyx production by viridans streptococci in the rabbit model of endocarditis has been associated with delayed antimicrobial sterilization. Enzymatic digestion of the glycocalyx with dextranase enhances antibiotic activity. The effect of clindamycin (30 mg/kg, subcutaneous, three times daily) was studied in rabbits with experimental aortic valve endocarditis caused by high glycocalyx-producing viridans streptococci. Animals receiving clindamycin had smaller vegetations that were sterilized more quickly than did controls or animals receiving penicillin or dextranase alone (P less than .001). Penicillin plus dextranase treatment allowed greater bacterial killing than penicillin alone and did not differ significantly from clindamycin treatment. Electron micrographs revealed markedly less cell-adherent glycocalyx on organisms grown in vitro treated with clindamycin versus penicillin and controls. It is hypothesized that clindamycin inhibits glycocalyx production in vivo, allowing better antimicrobial penetration in the infected cardiac vegetation.

Animals↗

Hemodynamic and respiratory effects of thyrotropin-releasing hormone and epinephrine in anaphylactic shock.

Thyrotropin-releasing hormone (TRH) has been shown to increase mean arterial pressure during anaphylactic shock. The hemodynamic mechanism of action and the effect of TRH on the respiratory system during anaphylactic shock are not known. A rabbit model of anaphylaxis was used to determine the effect of TRH, epinephrine (EPI), and normal saline (NS) on various cardiovascular and respiratory parameters during anaphylactic shock. Anaphylactic shock was induced by antigen challenge in 31 sensitized animals. After a 25% decrease in mean arterial pressure, they were randomly treated with TRH (2 mg/kg), EPI (0.005 mg/kg), or NS (10 mL/kg). Blood was drawn at baseline and at the end of the experiment for laboratory analysis. Cardiac and respiratory parameters were monitored continuously and measured at baseline, at onset of shock (time zero), and at time intervals for 30 minutes. Animals were treated with repeated doses during the first 15 minutes as needed to maintain mean arterial pressure above shock level. Five of ten TRH-, five of 11 EPI-, and six of ten NS-treated animals survived. The TRH-treated group required fewer doses than the other groups and had increased heart rate, mean arterial pressure, peripheral vascular resistance, respiratory rate, and minute ventilation as well as decreased stroke volume index and lung compliance compared with the NS-treated group. EPI treatment resulted in increased minute ventilation and decreased pulmonary airway resistance compared with NS treatment. The EPI group also had a higher postsurvival epinephrine level than the other groups. No difference in right atrial pressure, cardiac index, acid-base status, pO2, A- a gradient, lung weight, lactate, or norepinephrine levels was found.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗

Quantitative assay of glycocalyx produced by viridans group streptococci that cause endocarditis.

A quantitative method to determine glycocalyx production by strains of viridans group streptococci from patients with endocarditis is presented. There is good correlation between this new tryptophan quantitative assay and qualitative assays employing polysaccharide stains (ruthenium red, periodic acid-Schiff, and Cellufluor) or the Molisch test. The quantification of the glycocalyx production in glucose substrate in vitro by viridans group streptococci correlates with the size of cardiac vegetation and ease of antimicrobial sterilization in experimental endocarditis. The relationship of in vitro quantification of glycocalyx to maintenance of infection, morbidity of infection, and antimicrobial treatment is discussed.

Animals↗

Pharmacodynamic effects of dopamine stratified by race.

The purpose of this investigation was to evaluate the effects of dopamine on heart rate (HR), systolic blood pressure (SBP), aldosterone, plasma renin activity (PRA), bradykinin, prolactin, corticotropin (ACTH), urinary output (UO), and urinary sodium (UNa) stratified by race. Sixteen healthy age- and weight-matched Caucasian and African American male subjects participated in this single-blind, three-phase study. The three phases included the following treatments and assessments: (i) 90-minute infusion of D(5)W 100 mL/h and control piggyback (control period); (ii) 90-minute infusion D(5)W 100 mL/h and 3 microg/kg/min dopamine (dopamine phase); (iii) assessments repeated 24 hours after dopamine administration (washout period). Plasma was analyzed for dopamine concentrations. Dopamine significantly increased HR and SBP across the study population. In addition, UO and UNa increased, prolactin was reversibly depressed, bradykinin and ACTH were unchanged, and aldosterone significantly rebounded on washout. With regard to race differences, SBP significantly increased in African Americans compared with Caucasians, and UNa significantly increased in Caucasians compared with African Americans. In summary, 3 microg/kg/min dopamine produced significant renal, hormonal, and hemodynamic changes in healthy men. Selected effects varied by race.

Acute Kidney Injury↗