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Biomedical subjects

R L Danner

Publications and source records attributed to R L Danner.

61 records · Page 4Linked to original sources

Cardiovascular performance with E. coli challenges in a canine model of human sepsis.

We investigated cardiovascular dysfunction by injecting lethal and nonlethal bacterial challenges into conscious dogs. E. coli bacteria of varying numbers were placed in a peritoneal clot. Cardiovascular function was studied with simultaneous radionuclide scans and thermodilution cardiac outputs. In surviving animals, the number of bacteria in the clot increased as the corresponding systolic cardiac function decreased (P = 0.01). Cardiac function was measured by left ventricular (LV) ejection fraction (EF) and LV function curves [LV stroke work index (LVSWI) vs. end-diastolic volume index (EDVI), and peak systolic pressure vs. end-systolic volume index]. Furthermore, the diastolic volume-pressure relationship of survivors shifted progressively to the right [i.e., increasing EDVI (P less than 0.02) with minimal change (P = NS) in LV filling pressure]. This increase in LV size was associated with maintenance of measures of cardiac performance [stroke volume index (SVI) and stroke work index (SWI)] at similar levels. Death occurred only in the group with the highest bacterial dose. Compared with survivors receiving the same number of bacteria, nonsurvivors had a decrease in (P less than 0.05) LV size, a leftward shift (P less than 0.01) in LV diastolic volume-pressure relationship, and a decrease in both LVSWI and SVI (possibly related to volume and/or LV functional status). Data from survivors suggest that increasing the number of bacteria produces changes in myocardial compliance and contractility. These changes increase LV size (preload), a major determinant of cardiac performance that possibly enhances survival.

Animals↗

Inhibition of endotoxin-induced priming of human neutrophils by lipid X and 3-Aza-lipid X.

Lipid X, a precursor of lipid A (the toxic moiety of endotoxin), has been shown to protect animals from the lethal effects of endotoxin challenge. We investigated the mechanism of action of lipid X and 3-aza-lipid X, a diamino-analogue, in vitro, using the ability of lipopolysaccharide (LPS) to prime neutrophils for an enhanced release of toxic oxygen radicals. Lipid X and 3-aza-lipid X inhibited LPS-induced neutrophil priming in a concentration-dependent manner. At high concentrations, 3-aza-lipid X was a partial agonist of priming. Lipid X was found to inhibit LPS-induced priming by directly interacting with the neutrophil in contrast to polymyxin B, which neutralized LPS by binding to it. Increasing concentrations of lipid X shifted the LPS dose response curve of neutrophils rightward but did not prevent maximum priming at higher LPS concentrations, a finding consistent with competitive inhibition. These results suggest that lipid X, a compound structurally related to lipid A, may block neutrophil priming by competing with LPS for cellular binding sites. Lipid X appears to have a novel mechanism of inhibiting LPS effect and may have efficacy in the treatment of gram-negative sepsis.

Dose-Response Relationship, Drug↗

Hypotension with ventricular pacing: an atria vasodepressor reflex in human beings.

Hypotension with ventricular pacing has generally been attributed to loss of atrial transport, but it has been suggested that atrial vasodepressor reflexes may play a role. To study this, constant rate atrial and ventricular pacing was performed in 20 supine patients 24 to 36 hours after surgical coronary artery bypass or aortic valve replacement. The pulmonary capillary wedge tracing was examined for the presence or absence of cannon A waves during ventricular pacing in each patient. Thirteen patients had cannon A waves (group I) and seven did not (group II). Ten of the 13 patients with cannon A waves had ventriculoatrial conduction compared with only 2 of 7 patients without cannon A waves. There was a nonsignificant trend toward an association between cannon A waves and ventriculoatrial conduction (p = 0.1). Stroke volume index decreased in both groups when patients were changed from atrial to ventricular pacing. In the patients with cannon A waves, stroke volume index decreased from 31.2 to 26.3 cc/min per m2 (p less than 0.001) and from 31.2 to 25.0 cc/min per m2 (p less than 0.001) in those without cannon A waves (group I versus group II, p = NS). However, mean systemic blood pressure decreased only in patients with cannon A waves (99.4 to 85.9 mm Hg [p less than 0.001] versus 101.8 to 100.9 mm Hg [p = NS]) in those without cannon A waves (group I versus group II, p less than 0.001). Hypotension in patients with cannon A waves was caused by inhibition of the normal reflex increase in systemic vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Cryptosporidiosis in homosexual men.

Between April 1982 and June 1983, cryptosporidiosis was diagnosed in six homosexual men. Four patients with the acquired immunodeficiency syndrome had lymphopenia, cutaneous anergy, and profoundly impaired cellular immunity; their cryptosporidiosis was severe, unremitting, and refractory to all therapy. Two patients without other opportunistic infections or Kaposi's sarcoma had moderately impaired cellular immunity but not lymphopenia or anergy; their enteric illness was self-limited. Cryptosporidium recently had been recognized as a human pathogen that is transmitted through fecal-oral contamination. The severity of human cryptosporidiosis appears to be determined primarily by immunocompetence of the patient. These six homosexual men, with different degrees of immunologic impairment, had two clinically divergent forms of cryptosporidiosis. Their cases raise questions about human transmission of Cryptosporidium and the prognostic significance of this disease in patients who are at high risk for developing the acquired immunodeficiency syndrome.

Acquired Immunodeficiency Syndrome↗

Testosterone secretion in the rat in response to chorionic gonadotrophin: alterations with age.

It has been reported by others that both prevailing blood concentrations of testosterone and Leydig cell response to gonadotrophin (up to 1 h after injection) are reduced in the aged male rat. Although resting levels of plasma testosterone in our aged (24-26 months old) Sprague-Dawley rat are also depressed compared with young (3-4 months) or mature (12 months) animals of the same strain, subcutaneous injection with human chorionic gonadotrophin for 3 days restores secretory function, producing testosterone levels indistinguishable from those of similarly stimulated younger rats. In short term experiments, old rats did show a diminished testesterone secretory response to human chorionic gonadotrophin 1 h after a single intravenous injection, consistent with previous reports, but restoration of normal stimulated levels was observed by 2 h, and persisted up to 24 h. These findings differ from the demonstrated intrinsic testicular hyporesponsiveness to gonadotrophin of aged men, and probably represented a state of chronic understimulation of the aged rat Leydig cells, due to low prevailing levels of LH.

Aging↗

Rapid measurement of an index of testosterone binding to serum binding globulin using ion exchange columns.

DEAE cellulose "mini" columns at pH 7.4 retain testosterone (T) bound to testosterone binding globulin (TeBG), which can be eluted at pH 2. Small 1:2 diluted serum or plasma samples are incubated with a tracer dose of tritiated T in pH 7.4 Tris buffer at 37 C then chilled and placed on columns at 4 C. Free and albumin bound T are washed off columns with pH 7.4 Tris buffer and columns are eluted with pH 2 Tris into vials for scintillation counting. After a simple mathematical correction for the small residual fraction of albumin bound T eluted at pH 2, we obtain a measure of TeBG binding of T which is highly correlated (r = .945) with that determined by dialysis. The method is quick, reproducible and applicable to serum or plasma volumes of 50 to 200 microliter. A single operator can process 100 samples in approximately 4 h.

Adult↗

Update on spinal epidural abscess: 35 cases and review of the literature.

Thirty-five cases of spinal epidural abscess were evaluated retrospectively and compared with 153 cases reported in the literature. As in other series, Staphylococcus aureus was the major pathogen. Patients with acute abscesses had fever, leukocytosis, and purulence at surgery. Patients with chronic abscesses had less fever and leukocytosis, more granulation tissue at surgery, and a greater delay in diagnosis but retained the potential for rapid neurologic deterioration. In contrast to other studies, abscesses in both the lumbar and anterior spinal compartments and patients with specific sources of infection occurred with greater frequency. Myelography was the diagnostic method of choice. Only four of nine patients had diagnostic computed tomography. Earlier diagnosis and treatment led to a significant improvement in outcome. Both steroid administration and greater neurologic impairment adversely affected outcome. Neurologic improvement following surgery was dependent on the duration of the deficit. A combination of antibiotics and surgical drainage remains the treatment of choice.

Abscess↗