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Biomedical subjects

C W Hanson

Publications and source records attributed to C W Hanson.

At least 19 recordsLinked to original sources

Causes of hypercarbia with oxygen therapy in patients with chronic obstructive pulmonary disease.

OBJECTIVES: To compare data derived from a computer model of the pulmonary circulation with data from a case series of patients with chronic obstructive pulmonary disease (COPD). To evaluate the specific factors contributing to CO2 retention due to oxygen therapy in patients with acute exacerbations of COPD. DESIGN: Data from a computer model of the pulmonary circulation were compared with a previous case series. PATIENTS: Patient data were derived from previous case series. INTERVENTIONS: Simulated application of oxygen therapy. MEASUREMENTS AND MAIN RESULTS: The computer model of the pulmonary circulation generates data comparable with those data from a series of patients with COPD treated with supplemental oxygen and permits identification of the causes for hypercarbia. Therapy with supplemental oxygen alters hypoxic pulmonary vasoconstriction and modulates the Haldane effect, resulting in changes in physiologic deadspace. CONCLUSION: Changes in physiologic deadspace are sufficient to account for the hypercarbia developed by patients with acute exacerbations of COPD when treated with supplemental oxygen.

Blood Pressure

Role of hypoxic pulmonary vasoconstriction in pulmonary gas exchange and blood flow distribution. 1. Physiologic concepts.

The regulation of the distribution of ventilation/perfusion ratios by hypoxic pulmonary vasoconstriction contributes to both the efficiency of gas exchange and to pulmonary hemodynamics. In this review, the first of two part series, are summarized the physiologic principles on which the analysis of ventilation/perfusion ratios and of pressure-flow relationships are based. A new combined analysis is introduced that permits the important contributions of hypoxic pulmonary vasoconstriction to overall gas exchange to be demonstrated in the circumstances of clinical complexity.

Humans

Role of hypoxic pulmonary vasoconstriction in pulmonary gas exchange and blood flow distribution. 2. Pathophysiology.

In this review, the second of a two part series, the analytic techniques introduced in the first part are applied to a broad range of pulmonary pathophysiologic conditions. The contributions of hypoxic pulmonary vasoconstriction to both homeostasis and pathophysiology are quantitated for atelectasis, pneumonia, sepsis, pulmonary embolism, chronic obstructive pulmonary disease and adult respiratory distress syndrome. For each disease state the influence of principle variables, including inspired oxygen concentration, cardiac output and severity of pathology are explored and the actions of selected drugs including inhaled nitric oxide and infused vasodilators are illustrated. It is concluded that hypoxic pulmonary vasoconstriction is often a critical determinant of hypoxemia and/or pulmonary hypertension. Furthermore this analysis demonstrates the value of computer simulation to reveal which of the many variables are most responsible for pathophysiologic results.

Humans

Localized hypothermia influences assessment of recovery from vecuronium neuromuscular blockade.

The purpose of this study was to determine the extent to which localized hypothermia of a monitored extremity alters the assessment of recovery from vecuronium-induced neuromuscular blockade. Bilateral integrated evoked electromyographic (IEMG) responses were measured in the ulner distribution of 14 anaesthetized patients who had differing upper extremity temperatures as measured at the adductor pollicis to determine whether localized hypothermia alters the clinical assessment of spontaneous recovery from vecuronium-induced neuromuscular blockade. All patients received general anaesthesia with thiopentone, N2O/O2 and opioid; 11/14 patients received isoflurane for blood pressure control. Bilateral adductor pollicis, oesophageal and ambient temperatures, and IEMG evoked response (t1) expressed as percent unparalyzed control were recorded during the anaesthetic. The difference in evoked response between the warmer and the colder upper extremity was calculated at 25%, 50% and 75% spontaneous recovery from neuromuscular blockade in the warm extremity. Differences in temperature between extremities ranged from 0.2-11 degrees C. The difference in IEMG-evoked response between extremities was proportional to the difference in temperature, and there was a direct correlation (r = 0.78) between IEMG response and extremity temperature; IEMG response was absent when extremity temperature was less than 25 degrees C. We concluded that localized hypothermia in the monitored extremity decreases the IEMG-evoked response to vecuronium neuromuscular blockade; the greater the temperature decrease, the less the evoked response.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Pharmacology of neuromuscular blocking agents in the intensive care unit.

In critically ill patients, organ function, blood flow, and caregiving personnel change constantly. The risks inherent in paralyzing a patient, such as those of positioning (nerve injuries, stasis injuries) and ventilator disconnection are compounded by the duration of paralysis in the ICU. When used with attention to the pharmacologic properties, patient organ function, and cost, however, muscle relaxants are a useful adjunct to ICU management.

Blood-Brain Barrier

Urgent paralysis and intubation of trauma patients: is it safe?

Physicians, fearful of an increase in the incidence of intubation mishaps (IMs) and pulmonary complications (PUCs), have been reluctant to use paralysis and intubation (PI) outside the OR. This study examines the correlations between PI, IM, and PUC. Since 1987, we have used PI when complex injury or combative behavior warranted. From January through December 1989, 851 patients meeting major trauma triage guidelines were evaluated. The medical records of 231 patients (27%) who underwent PI within 8 hours of admission were reviewed; 27 patients were eliminated because of incomplete records. The indications for PI were emergency surgery (131), airway control (30), combativeness (24), and hyperventilation (19). The location was the OR (121), ED (82), other (1). Presence or absence of IM was documented in 198 of 204 charts: Twenty-four IMs (12%) occurred--14 multiple attempts, seven aspirations, three esophageal intubations. Frequency of IM was not statistically related to PI location (Fisher's exact test), AIS, or ISS. In 194 of 204 patients who survived at least 24 hours, there were 15 PUCs (8%): eight pneumonia, five persistent infiltrates, two severe atelectases. No deaths were related to IM or PUC. There was no statistical relationship between IM and PUC (Fisher's exact test). However, patients with PUCs had a significantly higher AIS-chest score (2.9 +/- 1.7 vs. 0.9 +/- 1.5) (p < 0.0005, Student's t test) and ISS (27.3 +/- 9.6 vs. 14.5 +/- 10.8) (p < 0.0005, Student's t test). In our hands, PI is associated with low morbidity, no mortality, and can be safely used to facilitate injury management or to control combative behavior.

Dangerous Behavior

In vitro and in vivo evaluation of tiacumicins B and C against Clostridium difficile.

Tiacumicins B and C are members of a novel group of 18-membered macrolide antibiotics with in vitro activity against Clostridium difficile. The MICs against 15 strains of C. difficile were 0.12 to 0.25 microgram/ml for tiacumicin B, 0.25 to 1 microgram/ml for tiacumicin C, and 0.5 to 1 microgram/ml for vancomycin. The resistance frequency for both compounds against C. difficile was less than 2.8 x 10(-8) at four and eight times the MIC. The in vivo activities of the tiacumicins against two strains of C. difficile were compared with that of vancomycin in a hamster model of antibiotic-associated colitis. Oral therapy with 0.2, 1, or 5 mg of tiacumicin B or C per kg of body weight protected 100% of clindamycin-treated hamsters exposed to C. difficile ATCC 9689. Oral treatment with identical doses of vancomycin produced a prolonged, dose-dependent survival of hamsters, but it did not prevent the development of fatal colitis at doses of up to 5 mg/kg. When clindamycin-treated animals were exposed to another strain of C. difficile, both tiacumicin B and vancomycin were protective at 5 mg/kg, but not at lower doses. Tiacumicin C was not tested in vivo against the second strain of C. difficile. No tiacumicin B or C was detected in the sera of hamsters treated with single oral doses of 25 mg/kg, while antibiotic levels in the ceca of these hamsters reached 248 micrograms/ml and 285 mg/ml for tiacumicins B and C, respectively. The tiacumicins demonstrated in vitro and in vivo potencies against C. difficile and achieved high concentrations in the cecum, but not the serum, of hamsters after oral administration.

Aminoglycosides

In vitro and in vivo activities of clarithromycin against Mycobacterium avium.

There is no effective therapy to treat Mycobacterium avium complex infection in patients with acquired immune deficiency syndrome. Clarithromycin (A-56268; TE-031) is a new macrolide which is twofold more active than erythromycin against most aerobic bacteria. In addition, higher levels in serum and tissue are achieved with clarithromycin than with erythromycin. In this study, clarithromycin, erythromycin, difloxacin, temafloxacin, ciprofloxacin, rifampin, amikacin, and ethambutol were tested in vitro and in vivo against the M. avium complex. The MICs for 90% of strains tested were 4 micrograms/ml for clarithromycin, 64 micrograms/ml for erythromycin, 32 micrograms/ml for difloxacin, 8 micrograms/ml for temafloxacin, 4 micrograms/ml for ciprofloxacin, 4 micrograms/ml for rifampin, 32 micrograms/ml for amikacin, and 32 micrograms/ml for ethambutol. Beige mice were infected intravenously with 10(7) CFU of M. avium ATCC 25291. Treatment was started on day 6 after infection and was administered twice a day at 8-h intervals for 9 days. Clarithromycin was the most effective compound in these tests and was effective in reducing the viable bacterial counts in the spleen when it was administered subcutaneously or orally at a dose of 25 mg/kg. Amikacin was the only other compound which showed activity in vivo. The peak concentration in serum at which clarithromycin was active was approximately 1.0 microgram/ml.

Animals

Pacidamycins, a novel series of antibiotics with anti-Pseudomonas aeruginosa activity. III. Microbiologic profile.

Pacidamycins are nucleosidyl-peptide antibiotics which have activity only against Pseudomonas aeruginosa. Their MICs for other organisms such as Enterobacteriaceae, Staphylococcus aureus, most Streptococci and other Pseudomonas species are greater than 100 micrograms/ml. These compounds had no activity against erythromycin-susceptible Streptococci. The MICs for Streptococcus pyogenes with constitutive- and inducible-type of macrolide-lincosamide-streptogramin resistance were 12.5 and 25 micrograms/ml, respectively. The MICs against P. aeruginosa ranged from 8 to 64 micrograms/ml. The activity of these compounds was 1 to 2-fold less in serum than broth. Time-kill curves were performed using 4 and 8 times the MIC of pacidamycin 1. It was bactericidal against P. aeruginosa (3 log10 decrease in 4 to 6 hours). At 24 hours, resistant mutants were found in the cultures. The MICs of piperacillin and gentamicin for these mutants were the same as for the parent strain. The frequency of resistance to these compounds was less than 3.5 x 10(-6). The resistant mutants were stable after 10 transfers in antibiotic-free medium. The pacidamycins were inactive against P. aeruginosa in mouse protection test. After a single subcutaneous injection of 25 mg/kg of pacidamycin 1, the Cmax was approximately 50 micrograms/ml and the serum half-life was 0.5 hour.

Animals

Coumamidines, new broad spectrum antibiotics of the cinodine type. III. Microbiologic activity of coumamidine gamma 1.

The coumamidines are novel antibiotics with activity against a wide spectrum of aerobic Gram-positive and Gram-negative bacteria. All microbiological studies were performed on coumamidine gamma 1. The MIC90s (micrograms/ml) of coumamidine are as follows: Staphylococcus aureus 1.0, Streptococcus pyogenes 8, Enterobacteriaceae 2.0, Pseudomonas aeruginosa 8, Campylobacter jejuni and Campylobacter coli 1, Legionella pneumophila 8, Haemophilus influenzae 0.5, Neisseria gonorrhoeae 0.5. Coumamidine had MICs ranging from 8 to greater 0.5, Neisseria gonorrhoeae 0.5. Coumamidine had MICs ranging from 8 to greater than 64 for most anaerobes, except some Peptostreptococcus strains. The aminoglycoside super-sensitive strain, P. aeruginosa BMH 10, was also super-sensitive to coumamidine (MIC 0.2 micrograms/ml). Coumamidine was rapidly bactericidal for S. aureus. The viable bacterial count in logarithmic phase cultures was reduced to less than 10 cfu within 2 hours after exposure to 4 times the MIC (3.12 micrograms/ml) of coumamidine. The frequency of resistance development was less than 1 X 10(-9) for Escherichia coli and S. aureus when selected at 4 and 8 times the MIC. The Cmax in mouse serum after a single subcutaneous dose of 25 mg/kg of coumamidine was 4.5 micrograms/ml and t1/2 was 1 hour. Coumamidine is stable in serum. In mouse protection tests against S. aureus NCTC 10649 the ED50 was less than 0.6 mg/kg/day when it was administered subcutaneously at 1 and 5 hours after infection. Coumamidine was not absorbed after oral administration. The antibacterial spectrum, bactericidal activity, stability in serum and low frequency of resistance make this an interesting new class of antibiotics.

Aminoglycosides

Phenelfamycins, a novel complex of elfamycin-type antibiotics. III. Activity in vitro and in a hamster colitis model.

Phenelfamycins A, B, C, E, F and unphenelfamycin make up a recently isolated group of elfamycin-type antibiotics. All of the phenelfamycins were active against Gram-positive anaerobes, including Clostridium difficile. Phenelfamycin A was also active in vitro against Neisseria gonorrhoeae and Streptococci. Phenelfamycin A was found to be effective in prolonging the survival of hamsters in an animal model of C. difficile enterocolitis. After oral administration of phenelfamycin A to hamsters, antibiotic was detected in the caecal contents but not in the blood.

Aminoglycosides

Susceptibility of Campylobacter pylori to macrolides and fluoroquinolones.

The in-vitro activities of several 14-, 15- and 16-membered macrolides and fluoroquinolones against Campylobacter pylori were determined. In general, 14-membered macrolides, such as clarithromycin and flurithromycin, were more active than the 15-membered macrolide, azithromycin, which was more active than 16-membered macrolides, such as miocamycin and rokitamycin. Fluoroquinolones, except ciprofloxacin and A-61827, were less active than macrolides. Clarithromycin was the most active of the new compounds against C. pylori and was as active as ampicillin. MICs of all compounds at pH 5.5 were increased when compared to MICs determined at pH 7.3. All compounds had MBCs which were the same as or within one two-fold dilution of their MICs. Frequencies of spontaneous resistance development by C. pylori NCTC 11637 at four and eight times the MIC of the compounds were low and ranged from less than 1 x 10(-9) to 1 x 10(-7).

4-Quinolones

A-61827 (A-60969), a new fluoronaphthyridine with activity against both aerobic and anaerobic bacteria.

A-61827 (A-60969 is the hydrochloric salt of A-61827) is a new aryl-fluoronaphthyridine which is active against aerobic and anaerobic bacteria. The MICs of A-61827 for 90% of strains (MIC90) of staphylococci and streptococci were less than or equal to 1 microgram/ml and were generally 1 to 4 twofold dilutions less than those of ciprofloxacin for these bacteria. The MIC90S of A-61827 for members of the family Enterobacteriaceae and Pseudomonas aeruginosa were also less than or equal to 1 microgram/ml. Ciprofloxacin was 1 to 3 twofold dilutions more active than A-61827 against these gram-negative bacteria. Neisseria gonorrhoeae, Campylobacter jejuni, and Haemophilus influenzae were susceptible to less than 0.06 microgram of A-61827 per ml. The MIC90 of A-61827 for Legionella pneumophila was 0.25 microgram/ml. A-61827 was as potent or 1 to 2 twofold dilutions more potent than ciprofloxacin against these organisms. The MIC90 of A-61827 for all anaerobic bacteria was less than or equal to 4 micrograms/ml compared with less than or equal to 32 micrograms/ml for ciprofloxacin. In mouse protection tests, A-61827 was as active as ciprofloxacin against Escherichia coli, P. aeruginosa, and Salmonella typhimurium and 5 to 10 times more active than ciprofloxacin against Staphylococcus aureus and Streptococcus pyogenes. A-61827 was as active as ciprofloxacin against P. aeruginosa in a mouse pyelonephritis model and more active than ciprofloxacin and metronidazole in a mouse Bacteroides fragilis abscess model. After oral administration of 100 mg/kg to mice, the peak concentrations of A-61827 and ciprofloxacin in serum were 2.3 and 2.4 micrograms/ml and the half-lives in serum were 3.9 and 1.2 h, respectively.

Abscess