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Biomedical subjects

G R Hodges

Publications and source records attributed to G R Hodges.

At least 19 recordsLinked to original sources

How should xanthine oxidase-generated superoxide yields be measured?

The rate of formation of superoxide measured by its reduction of tetranitromethane (TNM) and by its reduction of ferric cytochrome c (Fe(III) cc) are in excellent agreement when the superoxide is generated from a simple chemical precursor. In contrast, the rate of formation of superoxide generated in the reaction of xanthine oxidase with acetaldehyde is much higher (up to a factor of 6) when measured with TNM and compared with Fe(III) cc. It is shown that Fe(III) cc measures superoxide that has diffused from the enzyme, and that TNM probably scavenges all the dioxygen that is reduced by one electron by the enzyme. The TNM traps enzyme-bound superoxide in competition with the second-electron transfer and proton transfer, which normally yield hydrogen peroxide. The proton transfer is probably rate determining, k(p) </= 3.8x10(3)s(-1).

Acetaldehyde↗

A novel procedure for generating both nitric oxide and superoxide in situ from chemical sources at any chosen mole ratio. First application: tyrosine oxidation and a comparison with preformed peroxynitrite.

The first method for generating (*)NO and O(2)(*)(-) at any known, constant ratio has been developed. Spermine NONOate and di(4-carboxybenzyl)hyponitrite decay with first-order kinetics and exactly equal rate constants (half-lives of 80 min) at 37 degrees C and pH 7.5 to give 200 and 40 mol % (*)NO and O(2)(*)(-), respectively. Tyrosine oxidation to dityrosine and 3-nitrotyrosine (the major and minor products under the conditions used in these experiments) has been studied (mainly in the presence of CO(2)) using various different ratios of the rates of formation of (*)NO and O(2)(*)(-). The (*)NO/O(2)(*)(-) = 1.0 product profiles are very similar to those of the products derived from equal amounts of (*)NO and O(2)(*)(-) generated at a (*)NO/O(2)(*)(-) ratio of 1.0 from SIN-1 but are very different from those derived from preformed peroxynitrite. All the experimental results can be explained in terms of free radical chemistry. The product profiles at all the (*)NO/O(2)(*)(-) ratios could be satisfactorily simulated provided an important group of reactions which lead to the consumption of dityrosine was included.

Molsidomine↗

Superoxide, amine buffers and tetranitromethane: a novel free radical chain reaction.

The amine buffer Tris slowly reduces tetranitromethane (TNM) to the nitroform anion in a non-accelerating reaction. The amine buffers HEPES and MOPS also (slowly) react with TNM but the dialkylaminoalkyl radicals formed from these two buffers undergo further reactions resulting in a rapid, accelerating, free radical chain process whereby the amine is oxidized and TNM reduced. The chemical functionality in any reaction component, not necessarily the buffer, required for this radical chain mechanism is >N-CH<. In the presence of such groups, the quantification of superoxide by TNM is impossible.

Amines↗

Mycobacterium kansasii infection in a patient with AIDS.

We have presented the case of a 45-year-old HIV-positive man who had a 2-week history of shortness of breath and fever and who was found to have pneumonia due to an acid-fast bacillus. Despite treatment with isoniazid, rifampin, ethambutol, and clofazimine, he died of the infection. Culture results obtained after his death showed the organism to be Mycobacterium kansasii. Mycobacterial infections are common in patients with AIDS, but are usually due to M tuberculosis or M avium complex. Of the 35 patients with AIDS and M kansasii infection mentioned in the literature, only eight of these were described; and of the four patients (including our patient) who received therapy considered appropriate for this infection, only two survived.

Acquired Immunodeficiency Syndrome↗

Mild nephrotoxicity associated with vancomycin use.

Nephrotoxicity related to vancomycin hydrochloride therapy has been reported at overall rates of 7% to 16% and as high as 35% when combined with an aminoglycoside antibiotic. We conducted a prospective study in older men. A group that received vancomycin was compared with a control group to determine the incidence of nephrotoxicity secondary to vancomycin therapy alone and in combination with aminoglycosides, to identify possible risk factors associated with nephrotoxicity, and to determine the incidence of other adverse effects associated with vancomycin use. Nephrotoxicity occurred in 11 (17%) of 66 patients receiving vancomycin and in 3 (5%) of 57 controls overall. Stepwise logistic-regression analysis failed to identify underlying illnesses or concurrent risks that may have contributed to the development of nephrotoxicity associated with vancomycin. Adverse effects, including phlebitis (14%), neutropenia (1%), rash (0%), and red neck syndrome (0%), occurred at rates similar to previous reports.

Aged↗

Coagulase-negative staphylococci.

Coagulase-negative staphylococci, long considered to be harmless commensals or contaminants, have emerged as major pathogens as medical technology has advanced. They are a major cause of intravenous-catheter-associated bacteremia, endocarditis, otitis media, and infection of joint prostheses, vascular grafts, cardiac pacemakers, cerebrospinal fluid shunts, postoperative wounds, the urinary tract, and the eye. Therapy includes removal of infected foreign bodies and administration of appropriate antimicrobial agents.

Anti-Bacterial Agents↗

Effect of Fluosol DA 20% on antibody response to type 3 pneumococcal polysaccharide in rats.

Exchange transfusion with the oxygen-carrying resuscitation fluid, Fluosol DA 20% (FDA), interferes with the efficacy of penicillin therapy of pneumococcal infection in rats. Because this effect could not be attributed to an interaction between FDA and penicillin, the effect of FDA on the ability of rats to mount an antibody response to type 3 pneumococcal polysaccharide was tested. FDA (25 ml) was administered by isovolumetric exchange transfusion. Rats were immunized intravenously with 0.2 microgram of type 3 pneumococcal polysaccharide 3 days before, 1 day before, 1 day after, or 3 days after transfusion with FDA. IgM and IgG antibody responses were determined by ELISA 0, 3, 7, 10, 14, 21, and 28 days after immunization. When rats were immunized 3 days before or 1 day before transfusion with FDA, antibody levels were increased above control levels and remained relatively high through Day 28. When the animals were immunized 1 day after transfusion, antibody levels were approximately the same as in the control group. When the rats were immunized 3 days after transfusion, antibody levels were suppressed. These data suggest that FDA does not inhibit the humoral immune response when administered after or within 1 day before immunization, but does inhibit the response when immunization is given 3 days after transfusion.

Animals↗

Haemophilus paraphrophilus brain abscess.

The clinical course of a patient with brain abscess due to Haemophilus paraphrophilus is described. The organism was recovered in pure culture from purulent material collected at surgery. The role of this organism as a human pathogen is reviewed.

Brain Abscess↗

Nosocomial Hemophilus influenzae type C meningitis in an adult.

Hemophilus influenzae type C meningitis developed in a 68-yr-old man with a cerebrospinal fluid leak which occurred after craniotomy for an olfactory groove meningioma. Hemophilus influenzae is an uncommon cause of meningitis in adults, and most reported cases have been due to type B or nontypeable strains.

Aged↗

Bordetella bronchiseptica bronchitis.

The clinical course of a patient with bronchitis caused by Bordetella bronchiseptica is described. The organism was recovered on one occasion from a protected catheter brush specimen obtained at bronchoscopy and on two occasions from expectorated sputum specimens. The infection was eradicated with antimicrobial therapy.

Bordetella↗

Spurious elevation of automated leukocyte counts induced by Fluosol DA 20%.

During studies with Fluosol DA 20% (FDA) in rats, an artifactual leukocytosis was observed when an impedance type electronic cell counter was used. The effect was found to be directly related to the duration of the interval between addition of an erythrocyte lysing fluid and counting, observed up to 11 d after transfusion with FDA, blood cell associated, reproducible in vitro, FDA concentration dependent, temperature dependent, and present when human blood was used instead of rat blood. Microscopically, the effect appears to be the result of agglutination of lysed erythrocyte membranes due to the interaction of erythrocytes, the emulsion component of FDA, and the quaternary ammonium salt component of the lysing fluid. These data suggest that FDA causes subtle changes in erythrocytes and raises the possibility that other cells may be similarly affected.

Animals↗

Effect of exchange transfusion with Fluosol DA 20% on splenic distribution and immunocompetence of rat lymphocytes.

T- and B-splenic lymphocyte frequency, immune response 4 days after immunization with sheep red blood cells (SRBC), and proliferative response to concanavalin A (Con A) were determined 1, 3, and 5 days after exchange transfusion with Fluosol DA 20% (FDA) in adult, male Sprague-Dawley rats vs sham transfused rats. T-cell, T-helper, T-suppressor, and B-lymphocyte were reduced 1 day after transfusion (P less than or equal to 0.001). T- and B-lymphocyte frequencies were still reduced at day 3 (P = 0.0372). By day 5, there were no significant reductions in T-cell, T-helper, T-suppressor, and B-cell frequencies in the FDA-transfused rats. The frequency of cells with cytoplasmic IgG was reduced (P less than or equal to 0.025) in cells harvested from spleens of FDA-transfused rats and tested fresh. Proliferative response of splenic lymphocytes to Con A was unaffected by transfusion with FDA (P greater than or equal to 0.078). Splenic hemolytic plaques in response to SRBC were unaffected if rats were transfused 3 days after immunization with SRBC and 1 day prior to study (P = 0.941), enhanced if rats were transfused 1 day after SRBC immunization and 3 days prior to study (P = 0.0015), and suppressed if rats were transfused 1 day before SRBC immunization and 5 days before study (P less than 0.0001). Transfusion with FDA causes transient decreases in identifiable T and B lymphocytes, depresses cytoplasmic IgG-positive B cells, does not affect proliferative response to Con A, does not affect an ongoing specific immune response, enhances an early specific immune response, and inhibits the induction of a specific immune response.

Animals↗

Comparison of two testing methods to determine hepatitis B surface antibody response to hepatitis B vaccine among health-care workers.

Because of variations in reported seroconversion rates and to compare enzyme-linked immunoassay (EIA) and radioimmunoassay (RIA) methods to assess hepatitis B vaccine response, hepatitis B surface antibody (anti-HBs) was tested in 116 of 174 high-risk hospital employees enrolled in a hepatitis B vaccine program. All individuals were vaccinated with three injections of Heptavax-B, 1.0 ml containing 20 micrograms of HBsAg intramuscularly in the deltoid. The same lot of appropriately stored vaccine was used. Of the 41 individuals tested within zero to six months postvaccination, 35 (85%) and 38 (93%) were positive by EIA and RIA, respectively. Of the 75 individuals tested 7-24 months postvaccination, 61 (81%) and 71 (95%) were positive by EIA and RIA, respectively. Results of EIA tests performed at two laboratories were similar. Of 109 individuals positive by RIA, 13 did not have protective antibody levels. In contrast, of 96 individuals positive by EIA, only one did not have a protective antibody level. RIA may be a more sensitive test for anti-HBs, but a positive EIA result correlates better with protective antibody levels.

Adult↗

Peptostreptococcal vertebral osteomyelitis.

The clinical course of a patient with vertebral osteomyelitis caused by Peptostreptococcus micros is described. The organism was isolated on two occasions from lumbar vertebral biopsies and was visualized in histologic sections of one of the biopsies. The patient had no apparent infections at other body sites. The infection was eradicated after 6 weeks of intravenous clindamycin therapy.

Aged↗

Perforated granulomatous colitis caused by Histoplasma capsulatum.

A 57-year-old man who presented with an acute abdomen and clinically was thought to have perforated colonic diverticulitis, was found to have transmural granulomatous inflammation and perforation of colon that was caused by Histoplasma capsulatum. Although involvement of any part of the gastrointestinal tract may occur with disseminated histoplasmosis, the complication of intestinal perforation requiring emergency surgery (particularly in the colon) is extremely rare and warrants this case report with discussion of the various clinicopathologic features of gastrointestinal histoplasmosis and the occurrence of primary intestinal histoplasmosis.

Colon↗

Legionnaires' disease associated with rash and renal failure.

Legionnaires' disease is recognized as a multisystemic illness. Afflicted patients may have pulmonary, gastrointestinal tract, and central nervous system complications. However, dermal involvement is not well documented and renal insufficiency is uncommon and usually of mild severity. We report two consecutive cases of proven Legionella infection that were unusual in that a macular rash and profound renal failure requiring hemodialysis were noted. Skin biopsy specimens of the rash and autopsy findings suggest that these atypical features may have been mediated by the Legionella infection. Although it is not entirely clear from these two cases, we suggest that the skin and renal involvement may have been mediated by either a "toxin" elaborated by the organism, an immunologic response of the host to the organism, or some other unidentified mechanism.

Acute Kidney Injury↗