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Biomedical subjects

D L Dunn

Publications and source records attributed to D L Dunn.

266 records · Page 15Linked to original sources
PubMed1982

Immunotherapy of gram-negative bacterial sepsis: enhanced survival in a guinea pig model by use of rabbit antiserum to Escherichia coli J5.

A rough mutant of Escherichia coli (J5), which expresses a core lipopolysaccharide antigen common to gram-negative organisms on its cell surface, was used to immunize rabbits. Passively transferred anti-E. coli J5 rabbit antiserum (anti-J5 RS), normal rabbit serum (NRS), and saline were compared in a guinea pig model of intravenous gram-negative sepsis, with E. coli 0111:B4 and Pseudomonas aeruginosa as challenge organisms. Physiologic monitoring demonstrated a consistent pattern associated with gram-negative sepsis in this model: hypothermia, hypotension, bradycardia, a fall in white blood cell count and platelet count, and persistence of challenge organisms within the circulation. Pretreatment with anti-J5 RS prevented hypothermia and the fall in platelet count while augmenting bacterial clearance. Survival was markedly enhanced by anti-J5 RS, but not by NRS or saline. Concomitant heparin pretreatment was thought to be a significant factor in demonstrating the protective effect in this model. Parallel in vitro cross-reactivity measured by an enzyme-linked immunosorbent assay and an opsonization assay demonstrated that anti-J5 RS extensively cross-reacted with a variety of gram-negative bacilli. Demonstration of enhanced opsonization by anti-J5 RS of gram-negative organisms was thus well correlated with enhanced systemic clearance of bacteria and improved survival subsequent to intravenous bacterial challenge.

Animals↗
PubMed1982

Fibrin in peritonitis. III. The mechanism of bacterial trapping by polymerizing fibrin.

We have previously shown that fibrin can act to contain microorganisms and prevent early septic death in experimental peritonitis. However, this trapping eventuates in abscess formation. Fibrinogen, the precursor molecule of fibrin, is known to possess binding structures for some pathogenic organisms. We compared the extent of incorporation of various aerobic and anaerobic bacteria as well as polystyrene latex microspheres into fibrin clots. Similar numbers of organisms and microspheres were incorporated into either noncontracted or contracted fibrin clots. Detailed comparisons of the binding of Escherichia coli or Staphylococcus aureus to human fibrinogen were then made. The addition of 111:B4 lipopolysaccharide did not inhibit incorporation of E. coli 0111:B4 into either type of fibrin clot. With initial inoculum sizes of 10(6) to 10(8) colony-forming units (CFU)/ml, S. aureus was better incorporated into contracted fibrin clots (P less than 0.01) than was E. coli, possible evidence for an easily saturable receptor mechanism. We concluded that microorganisms are incorporated into the polymerizing fibrin matrix in the same fashion as are inert particles of similar size, irrespective of external chemical structure. Adherence of bacteria to fibrinogen or polymerizing fibrin did not appear to represent a specific bacterial virulence factor, more likely representing an effective host defense mechanism of broad specificity.

Abscess↗
PubMed1981

Analysis of pilocarpine and isopilocarpine in ophthalmic solutions by normal-phase high-performance liquid chromatography.

A normal-phase high-performance liquid chromatographic separation for pilocarpine and isopilocarpine was developed which is suitable for the routine analysis of ophthalmic preparations. The method utilizes a column packed with 5-micron silica with a mobile phase of hexane-2% ammonium hydroxide in 2-propanol (70:30). Peak detection is by UV at 220 nm. It is suggested that a partition separation mechanism is involved rather than adsorption. A separation factor (alpha) of 1.17 was obtained with a relative separation (Rs) of 2.13. Column lifetimes were typically 6-8 months with daily use. Several standard pilocarpine-isopilocarpine mixtures and five commercially available ophthalmic solutions from different manufacturers were analyzed. The method was specific for pilocarpine and isopilocarpine in the presence of each other and pilocarpine acid and is a significant improvement over the nonspecific colorimetric methods of analysis.

Chromatography, High Pressure Liquid↗
PubMed1981

Analysis of pilocarpine and isopilocarpine in ophthalmic solutions by UV spectrophotometry-polarimetry.

An improved analytical method was developed that simultaneously quantitates pilocarpine and isopilocarpine in the presence of each other and pilocarpic acid. Pilocarpine and isopilocarpine are first separated from any pilocarpic acid present in the sample by eluting with water-washed chloroform through a column packed with acid-washed diatomaceous earth. The concentrations of pilocarpine and isopilocarpine then are determined by a combination of UV spectrophotometric and polarimetric measurements. UV absorbance is measured at the absorption maximum (215 nm), and optical rotation is measured at the 254-nm line of mercury. Standard curve and standard recovery data are presented. The method is applicable to several commercially available ophthalmic solutions of pilocarpine and is compared to both the USP colorimetric method and a high-performance liquid chromatographic method.

Magnetic Resonance Spectroscopy↗
PubMed1979

Synthesis and biological activity of 8-oxadihydropteridines.

A series of 6-substituted and 6,7-disubstituted pyrimido[4,5-b][1,4]oxazines (8-oxadihydropteridines) was synthesized through the condensation of an alpha-halo ketone and 2,5-diamino-4,6-pyrimidinediol. The resulting 8-oxadihydropteridines were assayed as potential antifolates in a dihydrofolate reductase enzyme system. The 2-amino-4-hydroxyoxa-dihydropteridines were found to possess greater biological activity than the corresponding 2,4-diamino compounds. The pteroic acid homeostere 2-amino-4-hydroxy-6-phenethyl-8-oxadihydropteridine was the most potent of the compounds tested.

Enterococcus faecalis↗
PubMed1976

Racemic diastereoisomers of 1-amino-2-hydroxycyclopentanecarboxylic acid.

The synthesis and characterization of the two diastereoisomeric forms of 1-amino-2-hydroxycyclopentanecarboxylic acid have been accomplished. A previously reported synthesis produced a racemic mixture of the threonine analog trans-2-hydroxy-1-aminocyclopentanecarboxylic acid (trans with respect to the hydroxy and carboxyl group). The alternate allothreonine analog was produced by conversion of cyclopentene oxide to trans-2-methoxycyclopentanol, followed by oxidation to 2-methoxycyclopentanone and conversion to a hydantoin. Fractional crystallization of the hydantoin sample, followed by hydrolysis, produced cis-2-hydroxy-1-aminocyclopentanecarboxylic acid (cis with respect to the hydroxy and carboxyl group) in high purity. Neither of the isomeric forms significantly inhibited the growth of the bacterial strains examined nor were they effective in inhibiting Jensen sarcoma cells in tissue culture.

Amino Acids↗
PubMedDate not supplied

Human immunodeficiency virus infection in patients with solid-organ transplants: report of five cases and review.

Five recipients of solid-organ transplants who were infected with human immunodeficiency virus (HIV) were studied at the University of Minnesota, and our data were compared with data from 83 reported cases of HIV-infected recipients of solid organs from other centers. Sixty-six of the 88 patients were seronegative for HIV before transplantation and received organs or transfusions of blood from individuals who were seropositive for HIV. Seven patients (four recipients of kidney transplants and three recipients of liver transplants) received transplants after routine screening for HIV. Twenty-five (28%) of the 88 patients developed AIDS, and 20 (80%) of these 25 patients died of AIDS-related complications a mean of 37 months after transplantation. Another nine patients (10%) had other HIV-related diseases. The mean time of progression to AIDS was 27.5 months among all patients with AIDS. For patients who were seronegative for HIV at the time of transplantation, the mean time of progression to AIDS was 32 months, whereas patients seropositive before transplantation developed AIDS within 17 months. Shortly after transplantation, eleven (17%) of the patients who were initially seronegative experienced a febrile syndrome attributed to HIV. Ten patients, including eight recipients of kidney transplants and two recipients of liver transplants, maintained normal allograft function despite low-dose immunosuppressive therapy.

Adult↗
PubMedDate not supplied

The role of anaerobic bacteria in intraabdominal infections.

The exact role the anaerobic enteric flora plays in the pathogenesis and persistence of intraabdominal infections due to perforation of a hollow viscus is still unclear. Four lines of evidence have been evaluated. (1) Careful cultures of intraabdominal infections almost always yield anaerobic bacteria, but only relatively few species are predictably found, compared with the hundreds of species populating the colon. (2) Experimental models have demonstrated that the pathogenetic roles of aerobes and anaerobes differ from one another during the establishment of mixed intraabdominal sepsis. Facultative organisms induce more systemic toxicity, and anaerobes predispose to abscess formation. Evidence is inconclusive whether true synergy between aerobes and anaerobes exists in such models. (3) Studies of oral prophylactic antibiotics strongly support the important role of the anaerobic component of colonic contents in the pathogenesis of postoperative infections. (4) Studies using therapeutic antibiotics generally favor coverage for both aerobic and anaerobic components of the contaminating enteric contents. Properly performed clinical studies directed at this latter point, however, are disappointingly few.

Animals↗