Improved diagnostic criteria for digital flexor tendon sheath pathology using contrast tenography.

BACKGROUND: Pathology of the digital flexor tendon sheath is a significant cause of lameness in the horse. Imaging is important to identify lesions and inform on prognosis prior to tenoscopic surgery. OBJECTIVES: To use a large population to evaluate 1) the sensitivity and specificity of digital flexor tendon sheath (DFTS) contrast radiographs in diagnosing manica flexoria (MF) tears, deep digital flexor tendon (DDFT) tears and constriction of the palmar/plantar annular ligament (PAL) using novel criteria; 2) predisposition to pathology in signalment and limb affected. STUDY DESIGN: Multicentre retrospective cohort study. METHODS: The medical records of 206 horses with lameness localised to the DFTS, contrast radiographs and subsequent tenoscopic surgery were reviewed. Breed and limb predispositions were evaluated for pathology of the DDFT, MF and PAL constriction. Contrast radiographs of the DFTS were reviewed by four masked operators and for each pathology the sensitivity, specificity and interobserver variability were calculated. RESULTS: Contrast tenography was a sensitive test for MF tears (92% confidence interval [CI] 88.4-94.4%; specificity 56%, CI 51.1-61.1%) and specific for diagnosing DDFT tears (73%, CI 68.6-76.8%; sensitivity 54%, CI 47.8-60.2%) but had a lower sensitivity (71%, CI 65.1-75.9% ) and specificity (45%, CI 39.1-52.0%) for PAL constriction. It had good to substantial interobserver agreement for MF and DDFT tears (Krippendorff's alpha 0.68 and 0.46 respectively). Ponies (57%) and cobs (58%) were significantly more likely to be affected with MF tears (other breeds 20-39%, P = 0.003) and Thoroughbreds (50%), warmbloods (45%) and draught breeds (48%) were more likely to have DDFT tears (other breeds 22-34%, P = 0.01). MF tears and PAL constriction were overrepresented in the hindlimbs compared to DDFT tears in forelimbs. MAIN LIMITATIONS: No standardisation of contrast radiographs was possible. The subjectivity of diagnosis of PAL constriction may also have led to bias. Radiographs were read as JPEGS reducing ability to manipulate images. CONCLUSIONS: Contrast radiography of the DFTS is accurate in the pre-operative diagnosis of DFTS pathologies. Different pathologies are overrepresented in certain breeds and limbs.

Effects of daily melatonin injections on activity rhythms of rats in constant light.

Although from pinealectomy studies the pineal body does not appear to participate in the generation of circadian rhythms of mammals, daily injections of the pineal hormone melatonin entrain free-running locomotor activity rhythms of rats in constant darkness. The aim of the present study was to determine whether rats whose circadian activity and drinking rhythms were disrupted in constant light (LL) could be synchronized by daily melatonin administration. Rats were subjected to a regime of gradually increasing photoperiod until they were maintained in LL. Rats whose rhythms became disrupted or showed intact free-running rhythms were injected daily with either melatonin (1 mg/kg) or vehicle (ethanol-saline) solution. Daily melatonin injections either synchronized or partly synchronized disrupted circadian patterns of activity. In contrast to previous findings from experiments conducted in constant darkness, melatonin did not entrain but only partly synchronized intact free-running rhythms. Results are interpreted in terms of melatonin acting on the coupling or phase relationships between oscillators generating circadian locomotor activity rhythms.

Synchronization of mammalian circadian rhythms by melatonin.

While pinealectomy (Px) has little effect on mammalian circadian rhythms, daily injections of the pineal hormone melatonin in rats have profound effects. These can be classified according to their effects under three categories of desynchronization: external desynchronization, internal desynchronization and phase-shift of the zeitgeber (Aschoff, 1969). Externally desynchronized rats, free-running in constant darkness (DD), can be entrained to a 24-hour regime of melatonin injection. Entrainment depends upon the suprachiasmatic nuclei (SCN) since lesions to the SCN prevent it. Although no animal model for internal desynchronization exists, rats whose circadian rhythms are disrupted or arrhythmic in constant light (LL) are synchronized by daily melatonin injection, and the rate and direction of responses to phase-shift of the zeitgeber can be altered with daily melatonin administration. These and other results suggest melatonin may be useful therapeutically for such human desynchronizations as jet-lag and shiftwork, and preliminary data using human subjects are presented.

Dose-dependent entrainment of rat circadian rhythms by daily injection of melatonin.

Previous work in our laboratory has shown that daily injection of large doses of the pineal hormone melatonin entrains the free-running locomotor rhythms of rats held in constant darkness and synchronizes the disrupted patterns of rats maintained in constant bright light. The present experiments determined the dose-response characteristics of entrainment to daily melatonin injections and made preliminary biochemical estimates of blood melatonin levels and half-lives after two critical doses of the hormone. The data indicated that the median effective dose for melatonin as an entraining agent in free-running rats was 5.45 +/- 1.33 micrograms/kg, considerably lower than doses previously employed and lower than doses employed in reproductive and metabolic studies in rats and hamsters. The data further indicated that the response to melatonin was quantal; rats either entrained to melatonin or they did not. No "partial entrainment" was evident, nor were there differences in phase angle, activity, or period among all effective doses. Biochemical estimates of blood melatonin after either 1 mg/kg or 1 microgram/kg of melatonin indicated that all effective doses resulted in supraphysiological levels of blood melatonin, although doses of 1 microgram/kg resulted in blood levels that were within one order of magnitude of normal nighttime values. Together, the data suggest that the rat circadian system is sensitive to the pineal hormone melatonin at or below doses required to effect rodent reproduction. Whether this sensitivity reflects a role for the pineal gland in rat circadian organization, however, still remains to be determined.

Entrainment of rat circadian rhythms by daily injection of melatonin depends upon the hypothalamic suprachiasmatic nuclei.

Although pinealectomy has little effect on the generation of circadian rhythmicity by mammals, daily injections of the pineal hormone melatonin entrain free-running rats [30]. The present study was designed to determine if known components of mammalian circadian organization were necessary for melatonin entrainment. Rats received either lesions to the suprachiasmatic nuclei (SCN), sham-lesions or neurotoxic lesions to brain catecholamines or serotonin. They were then allowed to free-run in constant dim red light (DD) before each received daily injections of either 1 mg/kg melatonin or ethanol:saline vehicle for 90 days. They were allowed to free-run for 30 days afterwards. Rats which received sham-lesions or neurotoxic lesions entrained to melatonin injections but not to vehicle. Rats which received complete SCN lesions were unaffected by melatonin or vehicle. These data suggest that the behavioral effects of melatonin, like those on reproduction in seasonally breeding mammals, depend upon an intact circadian system and the SCN.