Update on mycobacterial issues for the acquired immune deficiency syndrome era.

Patients with immunosuppression are especially susceptible to Mycobacterium tuberculosis and Mycobacterium avium-intracellularae, (also known as Mycobacterium avium Complex). Mycobacterium tuberculosis is the causative agent of pulmonary and extrapulmonary manifestations of tuberculosis, whereas the M. avium-intracellularae group has become recognized as a significant pathogen. Treatment problems center on multiresistant bacteria and poor patient compliance with prolonged treatment regimens. Lengthy multidrug treatment plans and special precautions against nosocomial transmission of these pathogens to patients and health care workers are necessary to limit the spread of these pathogens.

Hydration of the stratum corneum.

Synopsis Topically applied water, occlusion and topically applied glycerol were used to investigate and characterize some of the changes which occur in the hydrated stratum corneum. The effects of these treatments were monitored using non-invasive techniques under controlled conditions. The Servomed Evaporimeter was used to determine natural water flux from the skin surface before and after treatment. The performance of the Evaporimeter in this type of study had previously been improved by attaching a paper baffle to the detector. This eliminated the variance in output caused by atmospheric movement. Experiments were carried out at temperatures below the threshold of thermal sweating and emotional sweating was minimized. Skin surface topography was characterized by means of a new type of profilometer. The instrument's design allowed a diamond stylus to traverse the living skin surface without significantly altering its structure. Changes in skin surface roughness were further elucidated using scanning electron microscopy and macrophotography. In vivo penetration of glycerol was assessed by chemical analysis of stratum corneum layers of treated skin. Samples were obtained by sequential stripping of the stratum corneum using adhesive tape. Topically applied water produced only a transient benefit because of rapid evaporation. More prolonged hydration was achieved by suppressing transepidermal water loss with polyethylene film. This occlusive hyperhydration was characterized by a significant reduction in profile roughness and by a smoother macroscopic appearance. Glycerol achieved the same effects by reducing the magnitude of the natural water flux from the skin surface and by reducing the rate of evaporation of water from applied aqueous glycerol solution or cosmetic product. Both effects were seen as the result of lowered water activity in the proximity of glycerol. Smoothing effects of glycerol on the skin surface, and improved appearance, persisted for at least 24 h. This persistence was explained by evidence for diffusion of glycerol into the stratum corneum where it formed a reservoir. Hydration of the skin is known to affect its barrier function and thereby exert a profound effect on penetration of both lipophilic and hydrophilic molecules. Clinically, this effect may be achieved using liberal applications of occlusive petroleum jelly and ointments. The results presented in this paper suggest that the use of humectants could achieve useful hydration using cosmetically acceptable materials.

Tuberculin test conversion during repeated skin testing, associated with sensitivity to nontuberculous mycobacteria.

To determine whether repeating the tuberculin test after a brief interval might result in tuberculin conversion, we tested 213 healthy volunteers twice, 1 month apart, with 5 TU of tuberculin purified protein derivative (PPD). Three nontuberculous mycobacterial antigens (PPD-G, PPD-Y, and PPD-B) were also applied with the first tuberculin test. By widely used criteria, 14 volunteers (6.6 per cent) converted their tuberculin tests from negative to positive on the second testing. Whereas 13 of 103 subjects (12.6 per cent) with nontuberculous antigen sensitivity converted their tuberculin test to positive, only one of 110 subjects (0.9 per cent) with no known prior mycobacterial sensitivity converted to positive (P less than 0.005; x2 = 10.05). When retested with 5 TU of tuberculin PPD 6.5 months after the second test, nine of 13 converters reverted to negative. We conclude that tuberculin conversion may occur when the skin test is repeated at 1 month, and that boosting of cross-reacting mycobacterial sensitivity might have caused a portion of the conversions in this population of young, healthy midwestern volunteers. Sensitivity to Mycobacterium tuberculosis might also be boosted by tuberculin testing. Because the prevalence of sensitization by tuberculous and nontuberculous mycobacteria can be expected to vary in different populations, the significance of tuberculin conversion will also vary with the population being tested.

Trichosporon cholangitis associated with hyperbilirubinemia, and findings suggesting primary sclerosing cholangitis on endoscopic retrograde cholangiopancreatography.

Usually, ascending cholangitis is a bacterial process. However, in the debilitated or immunocompromised patient, mycotic cholangitis must be placed in the differential diagnosis. We report a patient with cryptogenic cirrhosis whose presenting problem in his terminal hospitalization was spontaneous bacterial peritonitis, for which he was treated with broad-spectrum antibiotics. Endoscopic retrograde cholangiopancreatogram was performed during the hospital course to explain his profound hyperbilirubinemia. The findings were grossly consistent with primary sclerosing cholangitis or cholangiocarcinoma. The patient subsequently continued to deteriorate, and died with hepatic and renal failure. At autopsy, he was found to have choledocholithiasis, marked biliary duct proliferation, and ascending cholangitis, with Trichosporon demonstrated histologically to be invading the bile ducts. To our knowledge, this is the first reported case of Trichosporon cholangitis.

The dansyl chloride technique for stratum corneum renewal as an indicator of changes in epidermal mitotic activity following topical treatment.

Using a hypomitotic agent, triamcinolone acetonide, and a hypermitotic agent, retinyl propionate, we investigated the relationship between epidermal mitotic activity and stratum corneum renewal time of topically treated skin as determined by the dansyl chloride staining technique. Treatment with the base cream resulted in a reduction in renewal time compared with an untreated control site. The predicted increase in renewal time with the hypomitotic agent and reduction with the hypermitotic agent was only observed when daily treatment was commenced 2 weeks prior to and continued after dansyl chloride staining and not when treatment was started after staining. These results indicate that in order to use cell renewal methods to demonstrate changes in mitotic activity brought about by topical treatments, it is necessary to pre-treat the skin with the test material to establish full epidermal equilibrium at the changed mitotic state before labelling with dansyl chloride. Meaningful claims for effects on cell renewal of specific cosmetic ingredients should only be made after comparison with a base cream treated site, both having been allowed to equilibrate, rather than on the basis of comparison with untreated skin.

Sunscreens with low sun protection factor inhibit ultraviolet B and A photoaging in the skin of the hairless albino mouse.

We examined the chronic effect of long daily suberythemal, fluorescent solar-stimulated radiation (FSSR; ultraviolet B (UVB)+A(UVA)) and UVA alone on female Skh-1 hairless albino mouse skin. Mice were dorsally irradiated 8 h every weekday for 16 weeks with FSSR or UVA, or 32 weeks with UVA alone. Various topical, low concentration, UVB and/or UVA sunscreens were applied before irradiation. Damage was assessed by skin-fold thickness, histology and biochemically by changes in the proportion of type III collagen. All FSSR-exposed mice showed increased skin thickening, elastic fibre hyperplasia, collagen damage and an increased proportion of type III collagen. Application of the UVB sunscreen (2.00%) resulted in marked protection for all nonbiochemical endpoints. There was no obvious advantage of adding 0.75% UVA sunscreen to the UVB sunscreen, but adding 2.00% UVA sunscreen reduced biochemical changes and connective tissue damage. Sixteen weeks of UVA irradiation caused skin thickening and laxity but the histology and biochemistry were indistinguishable from the controls. The mice irradiated with UVA for 32 weeks showed slight elastic fibre hyperplasia and collagen damage histologically, and increased skin thickening and laxity; these changes were unmodified by the 0.75% UVA sunscreen. These mice showed a significant increase in the proportion of type III collagen against which the UVA sunscreen offered protection. Our data suggest that UVA may be important in photoaging and that the use of low sun protection factor UVB+ UVA sunscreens on a day-to-day basis may offer some protection from solar photoaging.

The role of adenoviruses in the pertussis syndrome.

To define the role of adenoviruses in the pertussis syndrome, a study was done of a group of 134 children with clinical pertussis and a healthy control population of similar age, race, sex, and socioeconomic status. Adenovirus infections occurred in 30 (22.4%) of 134 patients with the pertussis syndrome and 5 (4.9%) of 101 control subjects (p smaller than 0.001). B. pertussis was recovered from 46 (34.3%) patients, and from 18 (39.1%) of these patients adenoviruses were also isolated. Although adenovirus infections also occurred in patients with the pertussis syndrome with negative cultures for B. pertussis, the rate, 12 of 88 patients (13.6%), was significantly lower (p smaller than 0.001). The clinical course was similar irrespective of the results of bacterial or viral cultures. These data substantiate the frequent association of adenoviruses with the pertussis syndrome, It would appear that adenoviruses do not usually have an independent role in the pathogenesis of the pertussis syndrome since we found them so commonly to be one agent in a mixed infection.

Purified duck embryo rabies vaccine. An accelerated schedule for preexposure immunization against rabies.

Seroconversion and adverse reaction rates were studied in 92 persons given four or five doses in a two-week period of duck embryo rabies vaccine (DEV) or duck embryo rabies vaccine purified by ultracentrifugation (P-DEV). Mouse-neutralizing antibodies developed in 78 of 92 (84.8%) persons in these accelerated schedules. There were no significant differences in the frequency of antibody conversion or in geometric mean titers of antibody between persons given either vaccine. However, local and systemic adverse reactions were substantially less common with P-DEV. These data suggest that four of five doses of DEV or P-DEV given in a two-week course can be used for preexposure prophylaxis in situations where the more drawn-out regimens would result in continuation of a high-risk of rabies exposure. The antibody response of persons given this more accelerated regimen must be determined.