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Biomedical subjects

L G Johnson

Publications and source records attributed to L G Johnson.

At least 73 records · Page 4Linked to original sources

Hearing thresholds with outer and inner hair cell loss.

Hearing impairment and related cochlear histopathologic changes were evaluated in experimental animals after treatment with aminoglycoside antibiotics or exposure to intense sound. In the course of treatment with kanamycin, neomycin, or dihydrostreptomycin, permanent hearing loss in monkeys and guinea pigs occurred first at the high frequencies and progressed toward the lows. Exposure to different octave bands of noise at 120 dB SPL in monkeys and chinchillas produced permanent hearing loss at frequencies related to the spectral characteristics of the octave band. In most instances loss of outer hair cells was substantially greater than that of inner hair cells. In fact, the pattern and location of missing outer hair cells on the basilar membrane were most often correlated with threshold shifts of 50 dB or less. Generally inner hair cell loss was observed when the threshold shift was greater than 50 dB. Our data support the place principle and the inference that the outer hair cells are essential for hearing from threshold to about 50 dB SL. The inner hair cells, if functioning normally, apparently take over above that level. Although there is little doubt that such a generalization will, in the long term, be found to have been greatly oversimplified, there is every reason to believe that a combination of behavioral and morphologic procedures, as used in this study, will play an important part in elucidating the differences in functional significance of the two types of hair cells.

Animals↗

Cardiovascular manifestations of ankylosing spondylitis.

The incidence of cardiovascular lesions in 97 patients with ankylosing spondylitis (AS) was found to be 14%; 8 patients had isolated aortic insufficiency (AI), 3 had isolated heart block, 2 had combined AI and heart block, and 1 had mitral insufficiency. In comparison with control groups of 81 patients with rheumatoid arthritis and 99 random hospital patients there was no increased incidence of isolated heart block in patients with AS. Clinical and postmortem findings indicated that the cardiovascular lesions of some patients with AS may antedate articular disease and may regress spontaneously. In addition, the unusual occurrence of AI in two patients with psoriatic spondylitis and in one with AS and regional enteritis is documented.

Aortic Valve Insufficiency↗

Evaluation of indomethacin by a controlled, cross-over technique in 30 patients with ankylosing spondylitis.

A clinical evaluation of indomethacin employing a controlled, cross-over technique with an inert placebo was undertaken in 30 patients with ankylosing spondylitis. Patients were studied for the frequency and dose relationship of side effects and for the subjective response of morning stiffness, chronic spinal pain, acute exacerbations of pain and peripheral arthralgia. Objective evaluation assessed measured change in movements of the cervical and lumbar spines, in chest expansion and in the range of movement of involved peripheral joints.Evaluation of the results indicated that a significant number of patients experienced side effects in the form of headache and dizziness while receiving indomethacin in doses above 150 mg. per day. Many other side effects reported by the patients were not found to occur at a statistically significant level. The significance of pulmonary infections encountered in three patients was reviewed. Relief of chronic spinal pain and peripheral arthralgia occurred in 14 and 16 patients, respectively (p < 0.05). Relief of morning stiffness and acute exacerbations of pain, and increase in the range of movement of any of the segments of the spine or the involved peripheral joints were not significant (p > 0.05). Based on the results of this study, it is suggested that the role of indomethacin in the management of ankylosing spondylitis be re-evaluated and that the daily therapeutic dose of this drug which has been heretofore recommended be decreased.

Alkaline Phosphatase↗

Ankylosing spondylitis: a late re-evaluation of 92 cases.

Ninety-two patients who satisfied the criteria proposed by Kellgren for the diagnosis of ankylosing spondylitis were re-evaluated by clinical, radiological and laboratory parameters after an average length of illness of 18.7 years. The following associated clinical lesions were studied: aortic insufficiency 8%, heart block 3%, iritis 11%, and other associated lesions. Long-term effects of x-ray therapy were evaluated by comparing irradiated and non-irradiated patients; no significant difference was noted in the clinical course of these two treatment groups. On serum protein electrophoresis no characteristic dysproteinemia was demonstrated; in no instance was there a marked hypergammaglobulinemia. Test results for rheumatoid factor, antinuclear factor and antithyroglobulin were all within the range expected for a normal population. In addition to bilateral sacroiliitis, several other characteristic radiological lesions, such as anterior spondylitis, were present in a high percentage of cases. It is suggested that the diagnostic criteria proposed by Kellgren, although useful, should be enlarged and refined.

Humans↗

(R) and (S) RS 56532: mixed 5-HT3 and 5-HT4 receptor ligands with opposing enantiomeric selectivity.

The pharmacological properties of the (R) and (S) enantiomers of RS 56532 have been studied in vitro and in vivo. In radioligand binding studies at 5-HT4 receptors in guinea-pig striatum, (S) RS 56532 exhibited a higher affinity than (R) RS 56532 (-log Ki = 7.6 and 6.5, respectively). (S) RS 56532 acted as a potent agonist at 5-HT4 receptors mediating relaxation of rat oesophageal muscularis mucosae (-log EC50 = 7.9) while (R) RS 56532 acted as a weaker agonist at this receptor (-log EC50 < 6.0). These data suggest that at 5-HT4 receptors, the enantiomeric selectivity of RS 56532 was (S) > (R). In binding studies at 5-HT3 receptors in rat cortex, (R) RS 56532, conversely, exhibited a higher affinity than (R) RS 56532 (-log Ki = 9.1 and 8.0, respectively). At 5-HT3 receptors in guinea-pig isolated ileum, (R) RS 56532 exhibited an affinity (-log KB) of 7.9, whereas (S) RS 56532 (1 nM-1 microM) was inactive. No agonism was observed at ileal 5-HT3 receptors with either enantiomers. These data suggest that at 5-HT3 receptors in rat and guinea-pig, both enantiomers acted as antagonists, with (R) > (S) RS 56532. At the non-5-HT3, high affinity '(R) zacopride' site, (R) RS 56532 exhibited a higher affinity than (S) RS 56532 (-log Ki = 6.1 and 4.9). This site was insensitive to potent 5-HT3 antagonists such as (R) YM 060 or ondansetron. However, it was recognized with relatively high affinity (-log Ki = 7.5) by the (R), but not (S) enantiomer, of RS 42358 (-log Ki = 4.7). Since (S) RS 42358 is a high affinity 5-HT3 receptor antagonist, these data further highlight the dissimilarity between the 5-HT3 receptor and the '(R) zacopride' site. The '(R) zacopride' site also appeared to be pharmacologically distinct from the 5-HT4 receptor, since 5-HT4 ligands such as renzapride, SDZ 205,557 or RS 23597-190 exhibited low affinities. The enantiomeric selectivity of (R) and (S) RS 56532 in vivo was consistent with findings in vitro. At 5-HT4 receptors mediating tachycardia in the pig, 5-HT induced a dose-dependent tachycardia (ED50 = 3 micrograms kg-1, i.v.; maximum response = 90-100 beats min-1). (S) RS 56532 increased heart rate by 88 min-1 with a potency of (ED50) of 3 micrograms kg-1, i.v.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗