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Biomedical subjects

R B Johnson

Publications and source records attributed to R B Johnson.

At least 91 records · Page 5Linked to original sources

A controlled trial of a single dose of azithromycin for the treatment of chlamydial urethritis and cervicitis. The Azithromycin for Chlamydial Infections Study Group.

BACKGROUND: Currently, there is no single-dose therapy that is effective in the treatment of urethral or endocervical infections with Chlamydia trachomatis. Azithromycin is a new azalide antibiotic that has substantial activity against C. trachomatis, is concentrated intracellularly, and has a long half-life in serum and tissue. METHODS: We conducted a trial in which 299 female patients and 158 male patients with uncomplicated genital infection and a positive C. trachomatis antigen test were randomly assigned to receive either azithromycin (1 g once orally) or doxycycline (100 mg orally twice daily for seven days). Only patients subsequently determined to have a culture positive for C. trachomatis at base line were included in the evaluation of efficacy. RESULTS: Among the patients who could be evaluated, 5 of the 141 patients (4 percent) treated with azithromycin did not respond to treatment, as compared with 3 of the 125 patients (2 percent) treated with doxycycline (difference between groups, 2 percent; 95 percent confidence interval, 0 to 6 percent). Of the patients evaluated 21 to 35 days after treatment, none of 112 treated with azithromycin and 1 of 102 treated with doxycycline had a positive culture. The rates of bacteriologic cure were similar for the 98 female patients (97 percent) and the 43 male patients (95 percent) treated with azithromycin. Seventeen percent of the patients who received azithromycin and 20 percent of those treated with doxycycline had mild-to-moderate drug-related side effects, mainly gastrointestinal symptoms. CONCLUSIONS: A single 1-g dose of azithromycin is as effective for the treatment of uncomplicated genital chlamydial infections as a standard seven-day course of doxycycline.

Adolescent↗

Long-term, low-level microwave irradiation of rats.

Our goal was to investigate effects of long-term exposure to pulsed microwave radiation. The major emphasis was to expose a large sample of experimental animals throughout their lifetimes and to monitor them for effects on general health and longevity. An exposure facility was developed that enabled 200 rats to be maintained under specific-pathogen-free (SPF) conditions while housed individually in circularly-polarized waveguides. The exposure facility consisted of two rooms, each containing 50 active waveguides and 50 waveguides for sham (control) exposures. The experimental rats were exposed to 2,450-MHz pulsed microwaves at 800 pps with a 10-microseconds pulse width. The pulsed microwaves were square-wave modulated at 8-Hz. Whole body calorimetry, thermographic analysis, and power-meter analysis indicated that microwaves delivered at 0.144 W to each exposure waveguide resulted in an average specific absorption rate (SAR) that ranged from 0.4 W/kg for a 200-g rat to 0.15 W/kg for an 800-g rat. Two hundred male, Sprague-Dawley rats were assigned in equal numbers to radiation-exposure and sham-exposure conditions. Exposure began at 8 weeks of age and continued daily, 21.5 h/day, for 25 months. Animals were bled at regular intervals and blood samples were analyzed for serum chemistries, hematological values, protein electrophoretic patterns, thyroxine, and plasma corticosterone levels. In addition to daily measures of body mass, food and water consumption by all animals, O2 consumption and CO2 production were periodically measured in a sub-sample (N = 18) of each group. Activity was assessed in an open-field apparatus at regular intervals throughout the study. After 13 months, 10 rats from each group were euthanatized to test for immunological competence and to permit whole-body analysis, as well as gross and histopathological examinations. At the end of 25 months, the survivors (11 sham-exposed and 12 radiation-exposed rats) were euthanatized for similar analyses. The other 157 animals were examined histopathologically when they died spontaneously or were terminated in extremis.

Animals↗

A re-evaluation of the distribution of the elastic meshwork within the periodontal ligament of the mouse.

The elastic properties of the periodontal ligament have been attributed, in part, to oxytalan fibers, as no other types of elastic fibers are described there. It has been difficult to study the periodontal elastic meshwork by standard microscopic techniques because it is partially obscured by the adjacent periodontal ligament collagen fibers. Our study employed methods which either completely or partially removed mandibular molar periodontal ligament collagen fibers, exposing a previously undescribed periodontal elastic meshwork. The periodontal elastic meshwork was composed of many elastin lamellae containing both peripheral microfibrils of regular arrangement and central microfibrils of irregular arrangement, which could only be demonstrated in oxidized tissues. Peripheral, regularly arranged bundles of microfibrils resembled oxytalan fibers, which were often adherent to the border of the elastin lamella. Elastin lamellae containing irregular microfibrils resembled elaunin fibers. These fibers probably enclosed either blood vessels, nerves or collagen fiber bundles. Peripheral microfibrils attached elaunin to cementum, alveolar bone, blood vessels, and principal periodontal collagen fibers. Thus, the periodontal elastic meshwork is composed of both oxytalan and elaunin fibers. Microfibrils attach elaunin fibers to the adjacent non-elastic tissue and also form bundles which traverse the periodontal ligament space and are probably the oxytalan fibers demonstrable by light microscopic techniques. This meshwork of oxytalan and elaunin fibers probably contributes to tooth support and maintenance of periodontal homeostasis by dissipating chewing forces and maintaining patency of periodontal blood vessels.

Animals↗

Morphological characteristics of the depository surface of alveolar bone of diabetic mice.

Sharpey's fibers support teeth by attachment of periodontal ligament fibers to alveolar bone. The effects of diabetes mellitus on this support mechanism have not been described and were the subject of this study. Male Swiss mice were rendered diabetic by streptozotocin. Mandibles were removed 9 weeks after injections, the mineralizing front of the depository surface of the interdental septum was exposed by fracture through the periodontal ligament, rendered anorganic, and examined by scanning electron microscopy. No significant reduction in alveolar crest height was evident in diabetic as compared to control animals; however, significant changes in the a) mineralization patterns of bone depository surfaces and Sharpey's fibers, and b) number of Sharpey's fibers inserting into alveolar bone were evident in diabetics. Unmineralized fissures, characteristic of Sharpey's fibers of control, were nearly obliterated by mineralized tissue in diabetic animals. The mineralizing front of the middle and apical thirds of the diabetic alveolar wall was covered by numerous large calcified globules resembling enlarged calcospherites, which were not evident over the cervical third or control tissues. The mean Sharpey fiber density was greater in controls than in diabetics (p less than 0.001); however, there was no significant difference between their mean diameters. These observations suggest that, in early diabetes, Sharpey's fibers and depository surfaces of the middle and apical thirds of the interdental septum have morphologic evidence of aging, which precedes significant reduction in alveolar crest height. These changes may weaken the attachment of periodontal ligament fibers to bone and reduce resistance of the periodontium to intrusive forces.

Alveolar Bone Loss↗

Concentrations of azithromycin in human tonsillar tissue.

Patients scheduled to undergo tonsillectomy were administered 500 mg oral azithromycin as two 250 mg capsules given 12 h apart. Between 9 h and one week after the second dose, tonsil samples were taken during surgery and assayed for azithromycin. Mean concentrations in tonsillar tissue, 12 and 24 h after the second of the two 250 mg doses given 12 h apart, were 4.5 and 3.9 micrograms/g, respectively. Concurrent mean serum concentrations were approximately 0.03 and 0.01 micrograms/g, respectively. The mean concentration in tonsillar tissue 7.5 days after the last dose was 0.93 micrograms/g. The apparent half-life of drug in the tissue was 76 h. The ratio of mean concentration in tissue to that in serum was greater than 150-fold for all time intervals. The presence of high azithromycin concentrations in tonsillar tissue suggests that a once-daily regimen over five days or less may be effective in treating tonsillo-pharyngitis.

Administration, Oral↗

The role of azalide antibiotics in the treatment of Chlamydia.

Chlamydia trachomatis causes an estimated 4 million infections each year in the United States. Sequelae in women include infertility and ectopic pregnancy. Doxycycline, the current standard therapy, must be taken twice daily for at least 7 days. Patient compliance is often poor, leading to recurrent disease. Azithromycin, a new antibiotic of the azalide class, achieves high and sustained intracellular levels and demonstrates excellent in vitro activity against C. trachomatis. Reported herein are the results of three comparative clinical trials, which demonstrate that single-dose oral therapy with azithromycin is as effective as a standard 7-day twice-daily course of doxycycline in the treatment of uncomplicated genital infections caused by C. trachomatis.

Azithromycin↗

Evidence of phenotypic dichotomy within an individual Pasteurella multocida type strain and among some haemorrhagic septicaemia-causing field isolates.

Haemorrhagic septicaemia-causing strains of Pasteurella multocida were identified by a disease-specific ELISA. Some strains, however, were of the same serotype as those which cause haemorrhagic septicaemia (HS) but were negative when tested in the disease specific ELISA. The suspect false negative isolates were passaged in mice and retested in the HS ELISA with the same result. Immunoelectron microscopy was used to examine further these suspect HS-causing strains. Monoclonal antibodies and protein A-gold showed that the suspect negative organisms were a mixture of phenotypes with less than 10 per cent, and usually less than 2 per cent, of the population expressing HS-associated epitopes. The degree of staining on the organisms expressing the HS-epitopes was of the same intensity as the positive control organism. Expression of the HS-associated epitopes is presumably too low to allow detection in the current HS ELISA.

Animals↗

Haemorrhagic septicaemia: correlation of vaccinal antibody responses in mice with protection against Pasteurella multocida strain M1404.

This study examined the protection induced by oil adjuvant vaccine and broth bacterin in mice. Protective immunity was induced by both oil adjuvant and bacterin vaccination procedures. Oil adjuvant vaccination induced a 10(5)-fold increase for lethal challenge over control mice, while secondary vaccination induced a further 10-fold increase in resistance to lethal challenge. Broth bacterin induced a slightly weaker protective response with 10(4)- and 10(5)-fold increases in resistance to lethal challenge following primary and secondary vaccination, respectively. There was a significant relationship between IgG antibody levels and resistance to challenge (P = 0.026). Protection lasted for at least 20 weeks after a primary oil adjuvant vaccination. There was also a strong and significant relationship between IgG antibody levels and the passive protection afforded by serum transfer in each experiment within this study and the overall correlation was highly significant (P = 0.00001). There appeared to be a relationship between protection and the antibody response to major protein bands with the apparent molecular mass Mr. 94,000; 80,000; 67,000; 35,000 and 32,000 as well as to the bands in the region of the lipopolysaccharide components of P. multocida (approximately Mr, 14-15,000). Whether protection resulted from recognition of specific antigens or was a result of both antibody levels and antibody specificity remains to be defined.

Adjuvants, Immunologic↗

Measuring the reliability of a computer-aided systematic observation instrument.

The inter- and intraobserver reliabilities of data collected by observers trained in the use of the coach analysis instrument (CAI) are reported. The CAI is part of the computerized coaching analysis system (CCAS). The CAI collects data related to the learning environment created by the coach in a team/sport practice situation. Both inter- and intraobserver reliabilities are reported for each of the instrument's seven dimensions as well as for the overall instrument. The reliability measures reported are total percent agreement (T) and Cohen's kappa (K). The results indicated that, although the overall coaching analysis instrument reached a T value of 90.8%, it failed to meet the 80% level for the K measure (K = 78.5%). A dimension by dimension examination of the data was undertaken to determine the reasons for these results and it was revealed that the problem was associated with three specific dimensions of the instrument.

Algorithms↗

Electrophoretic profiles of Pasteurella multocida isolates from animals with hemorrhagic septicemia.

We determined that the protein profiles of 14 isolates from animals with hemorrhagic septicemia were relatively homogeneous and could be placed in 2 distinct groups on the basis of their country of origin. Such differences correlated with the serotypic properties of the individual isolates; hemorrhagic septicemia isolates of Asian and North American origin (Carter B) had a major protein band with an apparent molecular mass of 32 kDa, whereas those of African origins (Carter E) had a major protein band with an apparent molecular mass of 37 kDa. The possession of a major 32-kDa protein band appeared to be unique to Carter B isolates, suggesting that electrophoresis may be a useful nonserologic technique for the identification of organisms of this serotype. Other major bands with apparent molecular masses of 27, 45, and 47 kDa were shared by all strains, regardless of their serotype. The lipopolysaccharides were of low molecular mass and relatively uniform from 1 isolate to the next.

Africa↗

Effect of altered occlusal function on transseptal ligament and new bone thicknesses in the periodontium of the rat.

Alteration of tooth function is assumed to change stress/strain on the adjacent alveolar bone and its mucoperiosteum, producing changes in morphology similar to those described for other load-bearing bones. The present study suggested that crestal alveolar bone and its mucoperiosteum respond differently to stress/strain than load-bearing bones in other locations, possibly due to differences in the mechanism of bone loading by muscles and teeth. Occlusal hypofunction was initiated by extraction of agonist teeth; the contralateral teeth were placed in hyperfunction by the surgery. Untreated animals were also studied. 3H-proline was injected, animals were killed 1-5 weeks later, and the thicknesses of new bone and transseptal ligament were measured. After 5 weeks of altered function, total thickness (new bone + transseptal ligament) was similar in untreated and in hypofunctional and hyperfunctional situations; however, a new ratio between transseptal ligament and new bone thicknesses was established. Occlusal force was negatively correlated with new bone and positively correlated with transseptal ligament thickness; both thicknesses were statistically correlated in each functional situation (P less than 0.001). Hyperfunction resulted in increased transseptal ligament thickness, but decreased new bone thickness as compared to untreated controls (P less than 0.001). In contrast, hypofunction resulted in an increased new bone thickness, but a decreased transseptal ligament thickness (P less than 0.001). Tissue responses assure appropriate support for the teeth in each functional situation.

Alveolar Process↗

Distribution of 3H-proline within transseptal fibers of the rat following release of orthodontic forces.

Maxillary right first molar teeth of rats were tipped mesially with an orthodontic appliance for 2 weeks (experimental group), 3H-proline was injected, and orthodontic forces were removed 6 hr later (time 0). The contralateral molar teeth of treated (internal control group) and age- and weight-matched untreated animals (external control group) were also studied. Diastemata were created between the molar teeth by the orthodontic appliance, and transseptal fibers between first and second (P less than 0.001) and second and third molars (P less than 0.005) were significantly lengthened as compared to external and internal controls at time 0. Diastemata between molar teeth were closed 5 days after removal of orthodontic force. Transseptal fibers adjacent to the source of the orthodontic force (mesial region) had the highest mean number of 3H-proline-labeled proteins at time 0 and at all times following removal of the force (P less than 0.001), and had the highest rate of labeled protein removal (P less than 0.001). Half-lives for removal of 3H-proline-labeled transseptal fiber proteins were significantly greater in mesial and distal regions and significantly less in middle regions of experimentals than in corresponding regions of external controls (P less than 0.001). These data suggest the following: 1) transseptal fibers adjust their length by rapid remodeling in regions experiencing a tensile force; 2) collagenous protein turnover within the middle third of the transseptal fibers is more rapid subsequent to release of orthodontic force than during normal physiologic drift, suggesting that this region adapts rapidly to changes in adjacent tooth position and that these fibers do not play a significant role in relapse of orthodontically relocated teeth; and 3) significant differences in turnover rates of 3H-proline-labeled transseptal ligament proteins of external and internal control quadrants suggest that tooth movement produces both local and systemic effects on collagenous protein metabolism.

Animals↗

Effects of tooth function on adjacent alveolar bone and Sharpey's fibers of the rat periodontium.

There is little information about the effects of short-term non-hypo-, and hyperfunction of teeth on the 1) mineralization patterns of intrinsic and extrinsic (Sharpey's) fibers and 2) mean number and diameter of Sharpey's fibers of adjacent alveolar bone. The mineral density of intrinsic and Sharpey's fibers and the size and number of Sharpey's fibers could indicate the relative strength of the attachment of a tooth to bone in various functional situations. In the present study, non- and hypofunctional situations were created by selective extraction of right molar teeth of the rat; the contralateral teeth were placed in hyperfunction by the surgery. In non- and hypofunctionals, intrinsic and Sharpey's fibers of the crestal third of the alveolus were less densely mineralized than in hyperfunctionals or untreated controls. Mean Sharpey's fiber diameters were significantly greater and their mean number/unit area significantly less in non- than in hypo- or hyperfunctionals or untreated controls (P less than 0.001). Mean Sharpey's fiber diameters in hyperfunctionals were significantly less than in untreated controls (P less than 0.05). Hypofunction ameliorated the effects of nonfunction on mean diameter and number of Sharpey's fibers, but had little effect on the density of mineralization of either the intrinsic or Sharpey's fibers of the alveolus, suggesting that their mineralization may be controlled by factors other than occlusal forces from the adjacent teeth. Thus changes in the stress/strain environment within the periodontium, coincident to altered occlusal function of the adjacent teeth, rapidly affects the morphology of intrinsic and Sharpey's fibers of alveolar bone and ensures that adequate tooth support is maintained in the new functional situation.

Alveolar Process↗