The intra-rater reliability of measured thoracic spine mobility in chronic rotator cuff pathology.

OBJECTIVES: The relationship between thoracic spine dysfunction and painful shoulder pathologies is poorly understood. This study sought to determine the intra-rater reliability of a protocol aimed at assessing the active mobility of the thoracic spine in individuals with chronic rotator cuff pathology. METHODS: Ten individuals (6 men and 4 women) with chronic rotator cuff pathology were recruited and screened according to strict criteria. Voluntary active thoracic spine motion was recorded in two planes using a multidimensional motion analysis system. Each assessment was undertaken on two occasions, two days apart. RESULTS: The dominant upper-limb was affected in the majority of cases. There were no statistically significant differences between sessions during measurement of thoracic extension (p = 0.93), lateral flexion towards the affected side (p = 0.09), and lateral flexion away from the affected side (p = 0.38). Intraclass correlation coefficients for each of the thoracic spine movements ranged from 0.968 to 0.995. No significant difference was observed between thoracic lateral flexion between sides. CONCLUSIONS: Excellent intra-rater reliability of the test protocol was observed among individuals with chronic rotator cuff pathology. Future studies assessing impairment among these disorders should interpret results in light of these reliability measurements.

The expression of dystrophin-associated glycoproteins during skeletal muscle degeneration and regeneration. An immunofluorescence study.

The distribution and expression of dystrophin and three of the dystrophin-associated glycoproteins (DAG), alpha-dystroglycan (156 kDa DAG), beta-dystroglycan (43 kDa DAG) and adhalin (50 kDa DAG) in rat skeletal muscle were studied during a controlled cycle of degeneration and regeneration induced by the injection of a snake venom. Cryosections of muscle at various stages of degeneration and regeneration were labeled using monoclonal antibodies to the three glycoproteins and examined at fixed time points after venom injection. Adhalin and alpha-dystroglycan remained present at the sarcolemma throughout the entire cycle of degeneration and regeneration. beta-Dystroglycan, on the other hand, was lost from the sarcolemma by 12 hours and reappeared 2 days after venom injection when new muscle fibers were being formed. Dystrophin was not lost from the sarcolemma until 24 hours after venom injection and did not reappear at the membrane until 4 days. It is suggested that dystrophin and the glycoprotein complex are synthesized separately, both temporally and spatially, and only become associated at the plasma membrane during the later stages of regeneration. The expression of beta-dystroglycan in the regenerating muscle fibers was first seen at sites of newly forming plasma membrane that were closely associated with the old basal lamina tube. The basal lamina may therefore have a regulatory or modulatory role in the expression of the DAG.

Synthesis and analgetic activity of some 5-aryl-2azabicyclo[3.2.1]octanes.

A series of 5-aryl-2-azabicyclo[3.2.1]octanes II has been synthesized and evaluated for analgetic agonist-antagonist activity. These compounds can be regarded as five-membered, conformationally more rigid analogues of the potent agonist-antagonist (-)-5-(3-hydroxyphenyl)-2-methylmorphan (I). Several of these compounds have demonstrated marked analgesic potency comparable to morphine in the mouse writhing assay. Structure-activity correlations, generated by varying N-substitution and O-acetylation of the phenolic function, seem to indicate that optimum activity is associated with an arylethyl side chain attached to the basic nitrogen. Among the most interesting compounds in this series are the phenethyl analogue 31 and its O-acetate 39; the former shows the profile of a well-balanced analgetic-antagonist virtually devoid of physical dependence liability as demonstrated in the rat infusion test.

Synthesis and analgesic activity of some 5-(4-hydroxyphenyl)-2-azabicyclo[3.2.1]octanes.

A representative series of 5-(4-hydroxyphenyl)-2-azabicyclo[3.2.1]octanes was synthesized and evaluated in vitro, as well as in vivo, as potential analgetic agents. In general, moderate to good activity (19 twice as active as morphine) was observed in the phenylquinone writhing assay (PQW), while only marginal activity was detected by the tail-flick method. Compounds 19 and 18, being the most active in the PQW model, also demonstrated weak binding affinity for the opiate receptors labeled by [3H]naloxone in rat brain homogenates.

Tricyclics with analgesic and antidepressant activity. 1. [[(Alkylamino)ethyl]thio]dibenz[b,f]oxepins and 10,11-dihydro derivatives.

A series of [[(alkylamino)ethyl]thio]dibenz[b,f]oxepins (I) and their 10,11-dihydro derivatives (II) was synthesized and subjected to broad analgesic/CNS screening. Several analogues of both types, carrying small N-substituents and frequently a nuclear fluorine function, have been found to possess potent analgesic activity in the phenylquinone writhing assay (PQW) and the tail-flick test in mice. Many of these compounds also exhibited significant activity in antagonizing tetrabenazine-induced ptosis, as exemplified by 10b, 16b, and 18b. Results from the mouse jumping test indicated low physical dependence potential for these compounds, and further evidence for a nonnarcotic profile was provided by the absence of significant naloxone interactions with the tail-flick response. Compound 10b did not produce tolerance in mice following chronic administration in the PQW screen.

Carboxyarylindoles as nonsteroidal antiinflammatory agents.

An extensive series of carboxyarylindoles has been evaluated for antiinflammatory activity in the carrageenin paw edema assay. The requirements for optimal antiinflammatory activity in this series are relatively specific: a central pyrrole nucleus with (a) a 3-carboxy-4-hydroxyphenyl moiety substituted directly on the nitrogen, (b) a 2-phenyl group (R2) with a substituent of low electronegativity, (c) absence of a substituent in the 3 position (R3), and (d) a system fused across the 4,5 positions (X), which is lipophilic, quasiplanar, and does not interact sterically with the N-phenyl group. One derivative, 3-(3-carboxy-4-hydroxyphenyl)-2-phenyl-4,5-dihydro-3H-benz[e]indole (42), has been selected for further study.

Tricyclics with analgesic and antidepressant activity. 2. [[(Alkylamino)ethyl]thio]dibenzo[b,f]thiepins and 10,11-dihydro derivatives.

A series of [[(alkylamino)ethyl]thio]dibenz[b,f]thiepins (III) and their 10,11-dihydro derivatives (IV) was synthesized and subjected to broad analgesic/CNS screening. Preliminary results indicated a combination of analgesic/antidepressant profiles, similar to that observed for the [[(alkylamino)ethyl]thio]dibenz[b,f]oxepins (I) and their corresponding dihydro derivatives (II). The most active congener from the present series, 10b, shows an antinociceptive potency in the pentazocine range as assessed by phenyl-p-quinone-induced writhing (PQW) and tail flick in mice. It is also more than twice as active as imipramine in preventing tetrabenazine-induced ptosis (TBZ), a test widely recognized to be of predictive value for clinically efficacious antidepressants.

Novel tetracyclic spiropiperidines. 1. 3-Aryl-1,3-dihydrospiro[benzo[c]thiophene-1,4'-piperidines] as potential antidepressants.

A series of 3-aryl-1,3-dihydrospiro[benzo[c]thiophene-1,4'-piperidine] derivatives was synthesized and evaluated pharmacologically for potential psychotropic activity. Potent antidepressant-like activity was noted throughout the series, as assessed by tetrabenazine (TBZ) ptosis prevention in mice and potentiation of 5-hydroxytryptophan (5-HTP) induced behavioral effects in rats. A possible therapeutic advantage of the title compounds appears to be the overall low anticholinergic potential in comparison with the classic tricyclic antidepressants. Several congeners with nuclear halogen substitution also exhibited CNS stimulant properties, as evidenced by their ability to induce a dopamine agonist-like stereotypy and to increase the spontaneous motor activity in mice.

Fendosal (HP 129): a potent anti-inflammatory and analgesic compound.

Fendosal (HP 129) is one of a series of potent non-steroidal anti-inflammatory agents. Fendosal was compared with aspirin in several anti-inflammatory and analgesic bioassay procedures. Results indicate that fendosal has an anti-inflammatory activity 1.4 times greater than does aspirin in carrageenan-induced rat paw edema. Fendosal is 6.9 to 9.5 times more active than aspirin in the prophylactic and therapeutic adjuvant-induced polyarthritis models of chronic inflammation. The analgesic activity of fendosal is considered to be superior to that of aspirin, with the advantage of a prolonged duration of action. The gastric-irritating properties of fendosal are very low in comparison with those of aspirin. Fendosal has a much wider separation of effective and gastric-irritating doses than does aspirin.