Biomedical subjects
Publications and source records attributed to G F Webster.
Bacillary angiomatosis is a recently recognized bacterial infectious disease that is seen mainly in patients with the acquired immunodeficiency syndrome. Including this publication, 45 patients have been described in the medical literature. In this report we describe examples of the clinical presentations of bacillary angiomatosis and review therapeutic strategies.
Reflex sympathetic dystrophy is a poorly understood syndrome of posttraumatic pain and sympathetic nervous aberration. We have observed previously unreported cutaneous manifestations of reflex sympathetic dystrophy. Seven patients with reflex sympathetic dystrophy were referred to our institution because of skin disorders. Three had recurrent ulcerating papules, and two had reticulate hyperpigmentation. Xerosis was common, and cutaneous atrophy was infrequent. Cutaneous ulceration and reticulate hyperpigmentation are previously unappreciated aspects of reflex sympathetic dystrophy. Further investigation regarding neural influences on the skin is warranted.
Three patients with severe, treatment-resistant cutaneous sarcoidosis were treated with low-dose oral methotrexate on a weekly basis. Facial granulomas and ulcerations responded best. A response was apparent after several weeks of treatment, but 6 to 9 months were required to reach maximal effect.
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Low-dose oral methotrexate therapy was associated with the onset of anemia, leukopenia, and thrombocytopenia in two patients with psoriasis. Both patients survived, but required prolonged hospitalization. No precipitating factor other than methotrexate could be identified.
Unusual cutaneous vascular neoplasms distinct from Kaposi's sarcoma were observed in five patients with the acquired immunodeficiency syndrome (AIDS) or human immunodeficiency virus (HIV)-1 infection. The cutaneous lesions were solitary or multiple papules and nodules. In some patients the lesions also affected internal organs. Histologically the neoplasms were composed of proliferating blood vessels and cells with epithelioid features. Immunoperoxidase studies of one lesion showed that the cells expressed both factor VIII antigen, a maker for endothelial cells, and alpha 1-anti-chymotrypsin, a marker for histiocytes. In some patients the lesions gradually disappeared but in two they were the cause of death, in one case from disseminated intravascular coagulation and in the other from laryngeal obstruction by the tumour.
Aerobic diphtheroids from human skin (commonly referred to as lipophilic diphtheroids), pathogenic bacteria of the JK group, and classic species of the genus Corynebacterium were studied for their cellular fatty acids and mycolates, composition of their cell wall peptidoglycans, nutritional requirements, biochemical reactions, and antibiotic sensitivities. Lipophilic diphtheroids and JK strains were catalase positive and contained corynemycolic acid and meso-diaminopimelic acid in their cell walls, a characteristic shared with all corynebacteria. The lipophilic diphtheroid and JK strains were found to have a strict nutritional requirement for lipid and a similar composition of cellular fatty acid, mycolic acid, and peptidoglycan; they differed only in the multiple antibiotic resistance of the JK strains. Results of the biochemical reactions were inconclusive and did not permit grouping of lipophilic diphtheroids or JK with any of the reference strains. The reference strains did not require lipid and contained cellular fatty acids that were clearly distinct from those of the JK strains or lipophilic diphtheroids. These results suggest that JK bacteria are Corynebacterium spp. and may represent resident lipophilic diphtheroids that have acquired antibiotic resistance.
In order to determine which structures in Propionibacterium acnes are most antigenic to severe acne patients, we studied the specificity of anti-P. acnes antibodies in serum from 15 nodulocystic acne patients and 5 normals. Complement fixation titers to P. acnes cell wall fractions were determined using guinea pig serum as a complement source. The mean titers of patients and normals to whole cells were 39.6 and 3 (p less than 0.1); to crude cell wall, 138 and 8 (p less than 0.01); and to protein and nucleic acid-free cell wall, 225 and 9.33 (p less than 0.001), respectively. The mean precipitin titer to P. acnes cytosol was 12.7 for patients and 0 for normals. Immunoelectrophoresis of cytosol from 8 P. acnes strains were developed with each of the 15 patient sera. A single broadly migrating anionic antigen was detected. The antigen was also present in P. acnes culture supernatants. Sephadex G-100 chromatography of cytosol revealed a single peak of antigenic reactivity at Mr = 100,000. Three patients' sera revealed a second weakly reacting antigen in the cytosol preparation. Twentyfold concentration of immunoglobulin from patient sera failed to reveal any other antigenic reactivities. The antigen was found to be resistant to nuclease, pronase, and lysozyme treatment; was precipitable with 70% ethanol; and was destroyed by sodium m-periodate--findings that are consistent with a carbohydrate structure.
The cutaneous distribution of lipophilic diphtheroids was determined in normal human volunteers. The organisms were found to be plentiful in moist regions (scalp, nares, axilla, groin, and toe web) and scarce in dry and purely oily regions. The lipid requirement, cellular fatty acids, mycolic acid and cell wall diaminopimelic acid content of these lipophilic diphtheroids was compared to those of strains of Corynebacterium bovis, C. xerosis, C. diphtheriae, and C. minutissimum. Only lipophilic diphtheroids and C. bovis strains were found to have a strict lipid requirement. Lipophilic diphtheroids were found to have meso-diaminopimelic acid and corynemycolic acid in their cell walls, consistent with membership in the genus Corynebacterium. Lipophilic diphtheroids were also found to comprise a homogeneous group which was distinct from the speciated strains on the basis of cellular fatty acids and mycolic acids.
Propionibacterium acnes, the target of inflammation in acne, was tested for its sensitivity to the bactericidal and degradative functions of human polymorphonuclear leukocytes (PMN), monocytes, and their fractions. P. acnes strains were not killed by PMN under any conditions and were variably killed by monocytes in the presence of serum from acne patients. Control strains of Staphylococcus aureus and Micrococcus lysodeicticus were susceptible to both PMN and monocyte killing. P. acnes strains were also not killed by lysozyme, chymotrypsin, H2O2, human serum, PMN granule lysate, and PMN and monocyte cell lysates. The organism was sensitive to the bactericidal activity of myeloperoxidase in acid pH. In addition, P. acnes was shown to be relatively resistant to the degradative action of PMN and monocyte lysates, whereas M. lysodeicticus, S. aureus, and Staphylococcus epidermidis were all degraded to various degrees. The moieties that were liberated from P. acnes by PMN enzymes were predominantly low in molecular weight (1,000 to 25,000) and were consistent with cell wall fragments.
Dapsone at doses of 0.5 to 5.0 micrograms/ml was found to produce a dose-dependent inhibition of opsonized zymosan-induced human polymorphonuclear leukocyte (PMN) chemiluminescence (CL) in vitro. Simultaneous exposure of PMN to dapsone and zymosan was as effective in reducing CL as preincubation of PMN with dapsone. Preincubation of PMN with dapsone followed by washing, resulted in the loss of dapsone-mediated CL inhibition, indicating that dapsone did not permanently alter the CL-generating mechanism and that the drug had to be present to inhibit CL. Dapsone did not absorb light at the wavelength of CL and was not toxic to PMN at concentrations tested. Sodium azide, an inhibitor of myeloperoxidase-mediated CL inhibited PMN CL to the same degree as dapsone. When incubated together with PMN, dapsone and azide did not produce an additive inhibition of CL. These data suggest that inhibition of myeloperoxidase may be the mechanism by which dapsone inhibits PMN CL.
The minimal inhibitory concentration (MIC) of Propionibacterium acnes in seventy-five acne patients receiving long-term antibiotic therapy demonstrated the emergence of resistant strains. The mean MIC in thirty-three patients receiving long-term tetracycline was four to five times higher than that found in control groups of acne patients not receiving antibiotic therapy and controls free of acne. The average MIC for erythromycin was more than 100 times higher in those receiving long-term antibiotic therapy. In a second group of sixty-two patients, the clinical course and number of P. acnes were correlated with the presence of "resistant strains" defined as P. acnes with a tenfold increase in MIC to tetracycline or erythromycin. Patients with resistant strains had higher counts of P. acnes and clinically were not doing as well as those with sensitive strains.
The trichloroacetic acid (TCA) extractable molecules in Propionibacterium acnes cell wall were tested for the ability to activate the alternative pathway of complement in human serum treated with ethyleneglycol-bis (beta-aminoethyl ether) N,N-tetracetic acid (EGTA). The extracted molecules failed to consume hemolytic activity against antibody-coated sheep erythrocytes but gave a dose-dependent consumption of rabbit erythrocyte (RE) lytic activity. Similarly, the extract produced significant cleavage of Factor B, but failed to cleave C3, as detected by immunoelectrophoresis. Adsorption of the extracted material to sheep erythrocytes did not render the cells susceptible to lysis via the alternative pathway. Sephadex G-25 chromatography yielded several fractions which were able to consume RE lytic activity from EGTA-treated serum. These fractions were analyzed and found to contain glucose, mannose, and galactose. No teichoic acid or protein was detected. The alternative pathway activator in P. acnes is thus a nonteichoic acid cell wall carbohydrate which, in its extractable form is capable of activating only alternative pathway reactants prior to C3.
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Propionibacterium acnes is the cause of inflammation in acne vulgaris and has been shown to produce potent neutrophil chemoattractants. Different strain of P. acnes that were sensitive or resistant to ampicillin, erythromycin, minocycline, and tetracycline were grown in the presence of subminimal inhibitory concentrations of the drugs, and their culture supernatants were assayed for neutrophil chemotactic activity. The presence of subminimal inhibitory concentrations of ampicillin failed to affect chemotactic factor production by any of the strains. Subminimal inhibitory concentrations of tetracycline, minocycline, and erythromycin all produced decreased neutrophil chemotactic activity in P. acnes culture supernatants. This inhibition of chemotactic activity was most pronounced in strains of P. acnes which were susceptible to the drugs. The addition of antibiotics at appropriate concentrations to control supernatants failed to affect neutrophil migration. The results indicate that subminimal inhibitory concentrations of antibiotics are capable of reducing the inflammatory capacity of P. acnes.