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Biomedical subjects

J J Marr

Publications and source records attributed to J J Marr.

At least 91 records · Page 5Linked to original sources

Antileishmanial effect of allopurinol. II. Relationship of adenine metabolism in Leishmania species to the action of allopurinol.

Allopurinol was shown to be effective in vitro against Leishmania mexicana and Leishmania donovani as well as against Leishmania braziliensis. The major metabolic derivative of allopurinol in humans, oxipurinol, also is antileishmanial for L. donovani. The antileishmanial effect of allopurinol and oxipurinol can be specifically reversed by adenine, and its metabolic precursors and derivatives, but by no other purines or their derivative. It is proposed that the adenylosuccinate synthetase or the adenine phosphoribosyltransferase may be sites of action for these agents.

Adenine↗

Profound neutropenia caused by oxacillin.

An instance of profound neutropenia secondary to oxacillin which resolved rapidly on withdrawal of the drug was reported. It was accompanied by eosinophilia. Although the bone marrow findings were indicative of destruction of granulocytes in the periphery, antibody could not be demonstrated.

Adult↗

Phosphofructokinase of Leishmania donovani and Leishmania braziliensis and its role in glycolysis.

It was shown in an investigation of the phosphofructokinases of Leishmania donovani and Leishmania braziliensis that both enzymes are similar to that of Crithidia fasciculata. Although the enzymes are allosteric with respect to their substrates and require AMP for activation, there is no influence by other heterotropic modifiers. The Mg2+-ATP chelate activates these enzymes in a first order process and they can be inhibited by free ATP. The inhibition is reversed by the activator, AMP, in a competitive manner. The requirement for the nucleotide in L. donovani can be eliminated by decreasing the pH. The data indicate that phosphofructokinase, a pivotal enzyme in glycolysis for most organisms, probably does not play an important role in glycolysis in Leishmania.

Adenosine Monophosphate↗

Detection of pneumococci in respiratory secretions: clinical evaluation of gentamicin blood agar.

The use of sheep blood agar containing 5 microng of gentamicin per ml has been suggested as a means of selectively isolating Streptococcus pneumoniae from respiratory secretions. We have tested this method, in parallel with standard methods, on 844 respiratory specimens in a clinical laboratory and have confirmed that the yield of pneumococci can be increased approximately 40% by using agar containing gentamicin. However, since the antibiotic suppresses the growth of staphylococci, group A streptococci, and gram-negative bacilli, gentamicin agar cannot be used as a replacement for the standard method. The requirement for duplicate plating raises the cost per additional pneumococcal isolate to prohibitive amounts. Although the method is useful in studies designed to isolate only pneumococci, it cannot be recommended for the routine clinical laboratory. An unanticipated observation from our study is that the yield of pneumococci in respiratory secretions can be increased 10-fold simply by screening sputum for the presence of leukocytes using the Gram stain. This is in agreement with results reported from other laboratories.

Agar↗

Regulation of aerobic fermentation in protozoans. VI Comparative biochemistry of pathogenic and nonpathogenic protozoans.

We have investigated the oxidation of carbohydrate by several protozoan organisms. The oxidation is incomplete and results in a mixture of organic acid and carbon dioxide. The phosphofructokinase and pyruvate kinase, enzymes normally under strict metabolic regulation, are not subject to the normal feedback inhibition or activation mechanisms found in other cells. Moreover, our investigations and those of others support the hypothesis that a primary pathway for glucose metabolism is to phosphoenolpyruvic acid and then to oxalacetic acid with subsequent reduction to succinic acid.

Aerobiosis↗

A rapid radiometric method for determining the sensitivity of clinical isolates of Mycobacterium tuberculosis to several chemotherapeutic agents.

Current methods of performing antibiotic susceptibility tests on M. tuberculosis require 4 to 6 weeks for completion and in some cases have a poor correlation with clinical results. We have developed a rapid radiometric method of sensitivity testing which utilizes the incorporation of 3H-uracil into ribonucleic acid (RNA) as a measure of mycobacterial growth. The radiometric method is sensitive and reproducible and the results are completed in 48 hours. An excellent correlation was found between the radiometric method of sensitivity testing and the traditional agar plate technique when the two were compared with respect to isoniazid, streptomycin, and rifampicin sensitivities. There was no correlation between the two methods when ethambutol was tested. These results have confirmed our previous experiments on the usefulness of the radiometric method for the rapid determination of antibiotic susceptibilities of mycobacteria.

Ethambutol↗

Positive FTA-ABS tests in subjects with corticosteroid-induced uveitis.

Of 17 subjects who developed severe anterior nongranulomatous uveitis during or immediatelyy after testing with topical corticosteroid preparations, 14 (82%) had a positive fluorescent-treponemal-antibody absorption (FTA-ABS) test. No association was found between corticosteroid-induced uveitis and any specific HL-A locus.

Adrenal Cortex Hormones↗

Variation in the susceptibility of strains of Staphylococcus aureus to oxacillin, cephalothin, and gentamicin.

Three cases of staphylococcal bacteremia caused by organisms that were inhibited by low concentrations of oxacillin, but were resistant to the killing effects of oxacillin, stimulated us to screen 60 clinical isolates of Staphylococcus aureus for their susceptibility to oxacillin, cephalothin, and gentamicin. All 60 strains were inhibited by low concentrations of the antibiotics. The antibiotics were bactericidal against 27 of the 60 strains and only bacteriostatic against the other 33 after 24 h of incubation. However, after 48 h of incubation, the antibiotics were also bactericidal against the latter group.

Adolescent↗

Anaerobic infections in surgery: clinical review.

Anaerobic bacteria are being recognized with increasing frequency as important micro-organisms in surgical infections. Clostridium, Bacteriodes, Fusobacterium, and Peptostreptococcus are the clinically prominent pathological anaerobes. All are commensals and, consequently, most anaerobic infections are endogenous in origin. In the colon, anaerobes are 1,000 times more prevalent than aerobes. This has important implications regarding the management of gastrointestinal tract operations and the treatment of infections originating from the bowel. Typical anaerobic infections include gas gangrene, brain abscess, oral infections, putrid lung abscesses, intra-abdominal abscesses, and wound infections following gynecologic and bowel surgery, perirectal abscesses, postabortal infections, and septic thrombophlebitis. Infections with anaerobic organisms must be suspected when there is feculent odor and/or gas production following gynecologic or bowel surgery, when there are organisms on gram staining but no growth on aerobic cultures, or when septicemia is associated with repeatedly negative blood cultures. Debridement and drainage constitute the main stay of treatment. All anaerobes are sensitive to chloramphenicol and clindamycin and all but Bacteroides fragils are sensitive to penicillin. Identification of anaerobes requires proper specimen sampling, immediate culturing on prereduced media, and careful gram staining of clinical material. The frequency of anaerobic organisms in surgical infections generally is not recognized by many surgeons; their importance needs to be stressed in the future.

Abscess↗

Decreasing reliability of acid-fast smear techniques for detection of tuberculosis.

The ability of any screening test to correctly identify diseased patients is directly related to the prevalence of the disease in question. The continuing use of smears for the detection of acid-fast bacilli when the prevalence of tuberculosis is declining will produce increasing numbers of false-positive results. To determine the usefulness of smear techniques, we carried out a retrospective study of approximately 10 000 consecutive smears and cultures. Positive smears were classified as true- or false-positive on the basis of whether the corresponding cultures grew mycobacteria. The overall incidence of false-positive smears was 0.7%; however, the ratio of the number of false-positive to total positive smear was about 0.5. Thus, for each true-positive result, one false-positive result was obtained. Patients in the true-positive group had clinical and radiological evidence to support the diagnosis of tuberculosis, while those in the false-positive group had new findings of the disease. These data suggest that the smear is a poor screening technique in a population where the prevalence of tuberculosis is low.

Bacteriological Techniques↗

Bacterial studies of Clindamycin-associated colitis. A preliminary report.

The cause of pseudomembraneous colitis is not known but has been attributed to an alteration in the microbial flora of the colon. To test this hypothesis, a blind, prospective study was undertaken in which fecal samples were cultured quantitatively for aerobic and anaerobic organisms. The patients from which these samples were taken were all receiving clindamycin and had diarrhea secondary to the use of the drug. We were able to show definite differences in the colonic microflora which correlated with the presence of pseudomembranes on biopsy. Those patients who had diarrhea and pseudomembranous colitis showed a striking decrease, both quantitatively and qualitatively, in the number of anaerobes present. Those patients who had diarrhea but no pseudomembranes had large numbers of anaerobes which qualitatively approximated normal fecal cultures but quantitatively were fewer in number. A third group of patients, which had resolving pseudomembranous colitis, and were no longer symptomatic, had large numbers of anaerobic organisms which approximated those found in normal fecal cultures. There were no differences among the three groups with regard to facultative anaerobic microflora. Thus, the presence of pseudomembranous colitis correlated directly with a striking quantitative and qualitative decrease in the anaerobic microflora of the colon. The symptom of diarrhea alone appeared to have no meaning with regard to changes in the bacterial flora. Resolution of pseudomembranous colitis was associated with a return of the anaerobic microflora.

Bacteroides↗

A mechanism for decreased resistance to infection by gram-negative organisms during acute alcoholic intoxication.

The propensity of alcoholics to develop infections with gram-negative bacteria is well known. However, the known effects of ethanol on host-defense mechanisms do not explain this tendency satisfactorily. Since the principal defense mechanism against gram-negative bacteria is their destruction by complement in the presence of specific antibody, we investigated the effect of acute ethanol intoxication on serum complement concentrations and correlated these with serum bactericidal activity against a gram-negative organism. Serial measurements of total hemolytic complement (CH5O) and C'3, ethanol concentration, and serum bactericidal capacity were performed on the serum of 7 dogs infused with a 10 per cent ethanol solution. All animals showed a substantial decrease in total hemolytic complement activity which was inversely related to the increase in serum ethanol concentration. A decrease in serum bactericidal activity correlated with the decrease in CH50. Control animals showed no variation in either CH50 or serum bactericidal activity. Immunoprecipitation studies, using antibody to dog C'3, indicated that serum concentrations of this protein were not altered by infusing the animals with ethanol. Incubation of serum in vitro with both ethanol and acetaldehyde had no effect on CH50. We conclude that the effect of ethanol on serum complement is an in vivo phenomenon probably relating to decrease in the synthesis of one or more of the components of complement other than C'3, although the formation of an anticomplementary substance cannot be excluded. These findings are presented as a possible explanation for the development of infections with gram-negative bacteria in ethanol-intoxicated subjects.

Acetaldehyde↗

Antileishmanial effect of allopurinol.

Allopurinol (4-hydroxypyrazolo[3,4-d]pyrimidine) has been shown to inhibit the growth of Leishmania braziliensis in vitro at concentrations which are attainable in human tissues and body fluids. This compound is believed to act by interdicting the de novo synthesis of pyrimidines, probably through the formation of allopurinol ribotide. Its lack of toxicity makes it a potential candidate for animal experimentation and it may serve as a prototype for other agents with similar mechanisms of action.

Allopurinol↗