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Biomedical subjects

R B Johnson

Publications and source records attributed to R B Johnson.

At least 19 recordsLinked to original sources

The effects of smokeless tobacco extract on bone nodule formation and mineralization by chick osteoblasts in vitro.

Short-term exposure to smokeless tobacco extracts (STE) reportedly inhibits osteoblast metabolism. The objective of this study was to determine the effects of serial dilutions of a water-soluble extract of smokeless tobacco on osteoblast proliferation and their potential to form and mineralize bone nodules. STE significantly stimulated cell proliferation when diluted 10(2)-10(4) times; 10(3) and 10(4) dilutions produced the greatest effect. 10(2)-10(4) STE dilutions significantly increased alkaline phosphatase activity at day 7 but 10(6) STE dilutions significantly decreased it. 10(3) and 10(4) dilutions significantly increased bone nodule formation, but inhibited their mineralization. In contrast, 10(5) and 10(6) dilutions significantly decreased bone nodule formation, but increased their mineralization. Stimulation of in vitro bone nodule formation by STE was similar to that produced by 10(-7) M insulin-like growth factor 1 (IGF-1) in vivo. Heat and acid treatment of STE significantly reduced its beneficial effect on cell proliferation, suggesting that a peptide within STE may be responsible for enhancement of osteogenic cell proliferation. Thus, STE may contain a peptide capable of significantly stimulating osteoblast proliferation, differentiation and metabolism, similar to the effects of IGF-1. This peptide could have potential therapeutic benefits.

Analysis of Variance

Effectiveness of ethylene oxide for sterilization of dental handpieces.

Ethylene oxide gas has been utilized as an alternative method for sterilization of dental handpieces, as it is less corrosive than steam. However, its effectiveness for sterilization of the internal components of dental handpieces has not been established. The objective of this study was to compare the effectiveness of ethylene oxide and steam for sterilization of dental handpieces. Unused handpieces and handpieces which had been exposed to clinical dental procedures ('clinical') were contaminated with Streptococcus mutans, exposed to steam or ethylene oxide, and flushed with sterile saline. Washings were plated on mitis-salivarius agar, and colonies identified and counted. No viable colonies could be established from washings from 'clinical' or 'unused' handpieces exposed to steam. However, viable colonies could be established from 'clinical' handpieces exposed to ethylene oxide. This data suggests that a substance entrapped within 'clinical' handpieces (possibly the biofilm) may protect bacteria from ethylene oxide gas, preventing adequate sterilization.

Biofilms

Gingival interleukin-6 concentration following phase I therapy.

There is little information available on the effects of periodontal therapy on tissue levels of interleukin-6 (IL-6). This study compares IL-6 concentrations in gingiva and gingival crevicular fluid (GCF) from patients requiring surgical procedures following Phase I periodontal therapy. Sites requiring surgery due to "unresolved" intrabony pockets were compared to sites not requiring surgery ("resolved") in each patient. Resolved sites had minimal histologic evidence of chronic inflammation and IL-6 accumulation; unresolved sites contained a substantial number of chronic inflammatory cells and IL-6 was widely distributed. IL-6 levels in GCF were significantly greater at resolved than at unresolved gingival sites (P < 0.001); however, IL-6 tissue levels were significantly greater at unresolved than in resolved gingival sites (P < 0.01). These results suggest that IL-6 levels were elevated in gingival connective tissue adjacent to intrabony pockets which had not been resolved following Phase I therapy. Thus, intrabony pocket resolution may be affected by accumulation of IL-6 in the adjacent gingival connective tissue, which may result from increased rates of synthesis or reduced rates of release from gingiva into the GCF.

Adult

Pilot study of azithromycin for treatment of primary and secondary syphilis.

Azithromycin has in vitro activity against Treponema pallidum and is effective against experimental syphilis in rabbits. We undertook an open, noncomparative pilot study of oral azithromycin (500 mg once daily for 10 days) to treat 16 patients with primary or secondary syphilis who were seronegative for human immunodeficiency virus. Cure was documented for 11 of 13 patients observed > or = 3 months; three patients were lost to follow-up. The serological response of one patient with secondary syphilis was indeterminate, and one patient with primary syphilis had either relapse or reinfection. Four patients had mild gastrointestinal side effects, and another patient had an episode of nausea and vomiting; all side effects occurred in the first 3 days and resolved spontaneously as treatment continued. Azithromycin shows promise as an alternative agent for treatment of early syphilis; controlled trials and assessment of other dosage regimens are indicated.

Administration, Oral

Public hospitals and managed care.

Managed health care is used increasingly in the public and private sectors to control rising health-care costs and to assure quality of care. While current proposals for health-care reform promote even wider application of managed care as a component in cost control, the formal use of managed care by public hospitals has not been fully explored. This article identifies possible reasons for providing managed care within a public-hospital system, explores the implications of managed care for public hospitals and their patients, and addresses some of the barriers to implementing managed care in a traditional public-hospital setting.

Cost Control

Comparative metabolism of 3H-glucosamine by fibroblast populations exposed to cyclosporine.

Cyclosporine and nifedipine therapy produces gingival overgrowth in many patients. Neither the mechanism underlying this undesirable side effect nor the possibility of synergism between these drugs is known, although many renal transplant patients receive both drugs. This study compared the rates of 3H-glucosamine utilization by three groups of fibroblasts: untreated gingival fibroblasts, fibroblasts from gingival overgrowth tissue of a patient receiving both cyclosporine and nifedipine, and normal gingival fibroblasts exposed to cyclosporine-A in vitro. Significant differences in the rates of deposition of 3H-glucosamine into the extracellular matrix by each group of gingival fibroblasts were demonstrated, suggesting that increased rates of deposition of proteoglycans into the gingival extracellular matrix by fibroblasts should be further investigated as a biologic mechanism for gingival overgrowth.

Adult

In vitro changes in platelet function and metabolism following increasing doses of ultraviolet-B irradiation.

Ultraviolet-B (UV-B) irradiation of platelet concentrates (PCs) may prevent the development of posttransfusion HLA alloimmunization. This study evaluated the effect of increasing doses of UV-B radiation on stored PCs. Pooled PCs were irradiated at UV-B doses of 600, 2400 or 10,000 mJ per cm2 and stored up to 96 hours under standard blood bank conditions. Compared to nonirradiated room-temperature and 37 degrees C controls, the irradiated units showed no significant changes in platelet count, white cell count, discharge of lactate dehydrogenase, release of beta-thromboglobulin, metabolism of ATP, ADP, ammonia, glutamine, glutamate, hypoxanthine, pCO2, or pO2 at any time of storage following any of the three UV-B doses. However, after a dose of 10,000 mJ per cm2, there were significant decreases in in vitro assays of platelet function-specifically, osmotic recovery and morphology score. Some metabolic systems were also affected by the 10,000 mJ per cm2 radiation dose, as shown by a decline in pH and bicarbonate and an increase in glucose consumption and lactate production (p < 0.05). The changes in these latter assays appeared only after 96 hours of postirradiation storage. Such changes were not seen in either the room-temperature or 37 degrees C control groups. Thus, heat generated during irradiation, per se, did not appear responsible for the observed in vitro changes in platelet function and metabolism. On the basis of the assays analyzed, it is concluded that UV-B irradiation of PCs at doses up to 10,000 mJ per cm2 does not induce significant metabolic or functional derangements following short-term storage (24-48 hours).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate

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