DAP12 deficiency in liver allografts results in enhanced donor DC migration, augmented effector T cell responses and abrogation of transplant tolerance.

Liver interstitial dendritic cells (DC) have been implicated in immune regulation and tolerance induction. We found that the transmembrane immuno-adaptor DNAX-activating protein of 12 kDa (DAP12) negatively regulated conventional liver myeloid (m) DC maturation and their in vivo migratory and T cell allostimulatory ability. Livers were transplanted from C57BL/6(H2(b) ) (B6) WT or DAP12(-/-) mice into WT C3H (H2(k) ) recipients. Donor mDC (H2-K(b+) CD11c(+) ) were quantified in spleens by flow cytometry. Anti-donor T cell reactivity was evaluated by ex vivo carboxyfluorescein diacetate succinimidyl ester-mixed leukocyte reaction and delayed-type hypersensitivity responses, while T effector and regulatory T cells were determined by flow analysis. A threefold to fourfold increase in donor-derived DC was detected in spleens of DAP12(-/-) liver recipients compared with those given WT grafts. Moreover, pro-inflammatory cytokine gene expression in the graft, interferon gamma (IFNγ) production by graft-infiltrating CD8(+) T cells and systemic levels of IFNγ were all elevated significantly in DAP12(-/-) liver recipients. DAP12(-/-) grafts also exhibited reduced incidences of CD4(+) Foxp3(+) cells and enhanced CD8(+) T cell IFNγ secretion in response to donor antigen challenge. Unlike WT grafts, DAP12(-/-) livers failed to induce tolerance and were rejected acutely. Thus, DAP12 expression in liver grafts regulates donor mDC migration to host lymphoid tissue, alloreactive T cell responses and transplant tolerance.

Ex vivo application of carbon monoxide in UW solution prevents transplant-induced renal ischemia/reperfusion injury in pigs.

I/R injury is a major deleterious factor of successful kidney transplantation (KTx). Carbon monoxide (CO) is an endogenous gaseous regulatory molecule, and exogenously delivered CO in low concentrations provides potent cytoprotection. This study evaluated efficacies of CO exposure to excised kidney grafts to inhibit I/R injury in the pig KTx model. Porcine kidneys were stored for 48 h in control UW or UW supplemented with CO (CO-UW) and autotransplanted in a 14-day follow-up study. In the control UW group, animal survival was 80% (4/5) with peak serum creatinine levels of 12.0 +/- 5.1 mg/dL. CO-UW showed potent protection, and peak creatinine levels were reduced to 6.9 +/- 1.4 mg/dL with 100% (5/5) survival without any noticeable adverse event or abnormal COHb value. Control grafts at 14 days showed significant tubular damages, focal fibrotic changes and numerous infiltrates. The CO-UW group showed significantly less severe histopathological changes with less TGF-beta and p-Smad3 expression. Grafts in CO-UW also showed significantly lower early mRNA levels for proinflammatory cytokines and less lipid peroxidation. CO in UW provides significant protection against renal I/R injury in the porcine KTx model. Ex vivo exposure of kidney grafts to CO during cold storage may therefore be a safe strategy to reduce I/R injury.

Clinical and electrodiagnostic findings in copper deficiency myeloneuropathy.

INTRODUCTION: Copper deficiency is an increasingly recognised cause of neurological impairment. This retrospective review highlights clinical and electrodiagnostic findings in patients diagnosed at our institution with copper deficiency. METHODS: Clinical, radiographic and electrodiagnostic findings were reviewed in patients with evidence of copper deficiency. Patients with other potential causes of myelopathy or neuropathy were excluded. RESULTS: The predominant clinical feature in all six patients was a sensory ataxia, resulting in marked gait unsteadiness. Nerve conduction studies and needle EMG were performed in all patients and revealed a mild to moderate distal, axonal, sensorimotor peripheral neuropathy. Median and tibial somatosensory evoked potentials were abnormal in all five patients in which it was performed, showing impaired conduction in central or proximal peripheral somatosensory pathways. CONCLUSIONS: This pattern of electrodiagnostic findings suggests that impairment in somatosensory pathways demonstrated by somatosensory evoked potential testing is the main cause of the sensory ataxia in patients with copper deficiency.

Emersion and Terrestrial Locomotion of the Northern Snakehead (Channa argus) on Multiple Substrates.

Most fishes known for terrestrial locomotion are small and/or elongate. Northern snakeheads (Channa argus) are large, air-breathing piscivores anecdotally known for terrestrial behaviors. Our goals were to determine their environmental motivations for emersion, describe their terrestrial kinematics for fish 3.0-70.0 cm and compare kinematics among four substrates. For emersion experiments, C. argus was individually placed into aquatic containers with ramps extending through the surface of the water, and exposed to 15 ecologically-relevant environmental conditions. For kinematic experiments, fish were filmed moving on moist bench liner, grass, artificial turf, and a flat or tilted rubber boat deck. Videos were digitized for analysis in MATLAB and electromyography was used to measure muscular activity. Only the low pH (4.8), high salinity (30 ppt), and high dCO2 (10% seltzer solution) treatments elicited emersion responses. While extreme, these conditions do occur in some of their native Asian swamps. Northern snakeheads >4.5 cm used a unique form of axial-appendage-based terrestrial locomotion involving cyclic oscillations of the axial body, paired with near-simultaneous movements of both pectoral fins. Individuals ≤3.5 cm used tail-flip jumps to travel on land. Northern snakeheads also moved more quickly on complex, three-dimensional substrates (e.g., grass) than on smooth substrates (e.g., bench liner), and when moving downslope. Release of snakeheads onto land by humans or accidentally by predators may be more common than voluntary emersion, but because northern snakeheads can respire air, it may be necessary to factor in the ability to spread overland into the management of this invasive species.

Emersión y locomoción terrestre de la cabeza de serpiente del norte (Channa argus) en múltiples sustratos (Emersion and terrestrial locomotion of the northern snakehead (Channa argus) on multiple substrates) La mayoría de los peces conocidos por locomoción terrestre son pequeños y/o alargados. Las cabezas de serpiente del norte (Channa argus) son grandes pesces piscívoros que respiran aire, anecdóticamente conocidos por sus comportamientos terrestres. Nuestros objetivos fueron determinar sus motivaciones ambientales para la emersión, describir su cinemática terrestre para peces de 3, 0 a 70, 0 cm y comparar la cinemática entre cuatro sustratos. Para los experimentos de emersión, C. argus se colocó individualmente en contenedores acuáticos con rampas que se extienden a través de la superficie del agua y fueron expuesto a quince condiciones ambientales ecológicamente pertinentes. Para los experimentos cinemáticos, los peces se filmaron moviéndose sobre un revestimiento de banco húmedo, césped, césped artificial y una cubierta de bote de goma plana o inclinada. Los videos se digitalizaron para su análisis en MATLAB y se usó electromiografía para medir la actividad muscular. Solo los tratamientos de bajo pH (4, 8), alta salinidad (30 partes por mil) y alto dCO2 (solución de agua de Seltz 10%) provocaron respuestas de emersión. Aunque son extremas, estas condiciones si ocurren en algunos de sus pantanos asiáticos nativos. Las cabezas de serpiente del norte >4, 5 cm usaron una forma única de locomoción terrestre basada en movimientos apéndiculares-axiales que involucra oscilaciones cíclicas del cuerpo axial, junto con movimientos casi simultáneos de ambas aletas pectorales. Los individuos de ≤3, 5 cm usaron saltos de cola para moverse en tierra. Las cabezas de serpiente del norte también se movían más rápidamente en sustratos tridimensionales complejos (ej., césped) que en sustratos lisos (ej., revestimiento de banco), y al moverse cuesta abajo. La liberación de cabezas de serpiente en la tierra por humanos o accidentalmente por depredadores puede ser más común que la emersión voluntaria, pero debido a que las cabezas de serpiente del norte pueden respirar aire, puede ser necesario tener en cuenta la capacidad de propagarse por tierra en el manejo de esta especie invasora. Translated to Spanish by YE Jimenez (yordano_jimenez@brown.edu).

Niacin skin test response in dyslexia.

The niacin skin test reflects a flush and oedema owing to the production of prostaglandin D2 from arachidonic acid. A diminished response may indicate abnormalities in the phospholipid metabolism, which has been shown in schizophrenia. There is evidence that dyslexia might also involve phospholipid abnormalities, therefore we examined the skin response in 51 dyslexics and 45 controls. Four concentrations of aqueous methyl nicotinate were applied topically to the forearm. Flushing was rated using a seven-point scale at 3 min intervals over 21 min. Repeated measures ANOVA for the four concentrations across all seven time-points showed no significant effect of subject group, but when analyses were confined to the first 9 min, flushing was reduced in dyslexics. Significant group differences were also found for the lowest niacin concentration (0.0001M) across six out of seven time-points. The results indicate a slightly reduced and delayed response to niacin in dyslexia.

Antioxidant supplementation decreases oxidative DNA damage in human lymphocytes.

The association between high intake of fruit and vegetables and low incidence of certain cancers is well established. Dietary antioxidants present in these foods are thought to decrease free radical attack on DNA and hence to protect against mutations that cause cancer, but this causal mechanism remains conjectural. We have adopted a molecular epidemiological approach to this question, based on a modified alkaline single-cell gel electrophoresis assay ("comet assay") which specifically detects oxidation of pyrimidines in the DNA of human lymphocytes. In a survey of men 50-59 years of age living in the northeast of Scotland, smokers initially showed significantly more base damage than nonsmokers. Correlations between oxidative base damage and plasma concentrations of various antioxidants were generally negative but not statistically significant. Supplementation of the diet for 20 weeks with vitamin C (100 mg/day), vitamin E (280 mg/day), and beta-carotene (25 mg/day) resulted in a highly significant (P < 0.002) decrease in endogenous oxidative base damage in the lymphocyte DNA of both smokers and nonsmokers. In addition, lymphocytes of antioxidant-supplemented subjects showed an increased resistance to oxidative damage when challenged in vitro with H2O2. These findings strongly support the hypothesis that fruit and vegetables exert a cancer-protective effect via a decrease in oxidative damage to DNA.

Psychogenic seizures: ictal characteristics and diagnostic pitfalls.

We analyzed ictal features of psychogenic seizures using video-EEG recordings in 47 patients and reviewed the medical records to determine if patients received antiepileptic drug therapy and whether they were treated pharmacologically for status epilepticus. Unresponsive behavior in the absence of motor manifestations was the single most common ictal presentation. Motor characteristics previously considered to distinguish psychogenic seizures (out-of-phase limb movements, side-to-side head movements, pelvic thrusting) were infrequent. Most patients (74%) received anticonvulsants, and six were treated as status epilepticus. Slow, subtle writhing or in-phase limb movements were most likely to be mistaken for status epilepticus. Physicians, assuming that the spells constituted a neurologic emergency, omitted the neurologic examination and chart review and proceeded with aggressive pharmacotherapy based merely on observation.

Toward earlier diagnosis of amyotrophic lateral sclerosis: revised criteria. rhCNTF ALS Study Group.

We modified the World Federation of Neurology (WFN) diagnostic criteria for ALS to facilitate early diagnosis and used these criteria for enrollment of ALS patients in a clinical trial. The criteria developed required lower motor neuron (LMN) involvement in at least two limbs and upper motor neuron involvement in at least one region (bulbar, cervical, or lumbosacral). The EMG finding of fibrillation potentials was required for evidence of LMN involvement. Electrodiagnostic studies, neuroimaging, and laboratory studies were also used to exclude disorders that might mimic ALS. Using these criteria, the diagnosis of ALS was made at a mean time of 9.7 months from onset of symptoms, which compares favorably with the 12-month period cited in the literature. Using clinical assessment at completion of the trial, the diagnosis of ALS was believed to be accurate in those patients entered in the trial. However, pathologic confirmation of the diagnosis of ALS was not obtained. Based on our preliminary experience, we propose that these ALS diagnostic criteria will facilitate early diagnosis of ALS. Future studies should prospectively compare these criteria with the WFN criteria currently in use.

Placebo-controlled trial of gabapentin in patients with amyotrophic lateral sclerosis. WALS Study Group. Western Amyotrophic Lateral Sclerosis Study Group.

We designed a phase II trial to evaluate the efficacy of gabapentin in slowing the rate of decline in muscle strength of patients with amyotrophic lateral sclerosis (ALS) and to assess safety and tolerability. Gabapentin (800 mg) or placebo was administered t.i.d. in a randomized, double-blinded, placebo-controlled, trial for 6 months. We enrolled 152 patients at eight sites in the United States. The primary outcome measure was the slope of the arm megascore, the average maximum voluntary isometric strength from eight arm muscles standardized against a reference ALS population. A secondary outcome measure was forced vital capacity. Slopes of arm megascores for patients on gabapentin were compared with slopes of those taking placebo using a two-way ANOVA. We observed a nonstatistically significant trend (p = 0.057-0.08) toward slower decline of arm strength in patients taking gabapentin compared with those taking placebo (mean difference 24%, median 37%). We observed no treatment effect on forced vital capacity. Gabapentin was well tolerated by patients with ALS. These results suggest that further studies of gabapentin in ALS are warranted.

Impact on the care of the emergency department chest pain patient from the chest pain evaluation registry (CHEPER) study.

This study examines the question of whether chest pain observation units increase the proportion of chest pain patients with an extended evaluation for cardiac ischemia ("rule out myocardial infarction [MI] evaluation"), decrease the number of missed MIs, and decrease costs. This is a multiple site registry study of 8 established chest pain observation units (complying with the American College Emergency Physician's Observation Section's standards) compared with previous studies on chest pain evaluation without the use of observation (5 studies, 12,405 patients). A total of 23,407 of 444,189 emergency department patients (5.3%) had the chief complaint of chest pain during the study period. In the chest pain observation units, 153 of 2,229 patients (6.9%) with acute MI were identified. Most of the observation chest pain patients (76%) were discharged home without hospital admission. Compared to previous studies, a higher proportion of patients underwent a "rule out MI evaluation" (67%, 95% confidence interval [CI] 66%, 68% vs 57%, 95% CI 56%, 58%; p <0.001) equal to 2,250 additional patients completely evaluated ($1,219,500 additional costs). A lower proportion of MIs were missed (0.4%, 95% CI 0.3%, 0.5% vs 4.5%, 95% CI 4.0% to 5.5%; p <0.001) as estimated by return visits within 72 hours. Compared to previous studies, final hospital admission rate was lower (47%, 95% CI 46%, 48% vs 57%, 95% CI 56%, 58%; p <0.001), equal to 2,314 hospital admissions avoided in the study population ($4,093,466 saved costs). Calculated true costs overall were lower by $2,873,966 at the study hospitals. Thus, chest pain observation units increased the proportion of chest pain patients thoroughly evaluated with improved quality of care and lower costs.

Could oxidative stress be a factor in neurodevelopmental disorders?

There is evidence of co-morbidity in the neurodevelopmental disorders and they display depletion of polyunsaturated fatty acids (PUFAs) in their plasma and red cell membranes. This suggests an abnormal fatty acid metabolism, which may affect cell signalling and synthesis of eicosanoids. This common feature in the neurodevelopmental disorders may be genetic in origin: however, oxidative stress may also contribute to decreased PUFAs found in these disorders.

Fatty acid metabolism in neurodevelopmental disorder: a new perspective on associations between attention-deficit/hyperactivity disorder, dyslexia, dyspraxia and the autistic spectrum.

There is increasing evidence that abnormalities of fatty acid and membrane phospholipid metabolism play a part in a wide range of neurodevelopmental and psychiatric disorders. This proposal is discussed here in relation to attention-deficit/hyperactivity disorder (ADHD), dyslexia, developmental coordination disorder (dyspraxia) and the autistic spectrum. These are among the most common neurodevelopmental disorders of childhood, with significant implications for society as well as for those directly affected. However, controversy still surrounds both the identification and management of these conditions, and while their aetiology is recognized as being complex and multifactorial, little progress has yet been made in elucidating predisposing factors at the biological level. An overview is provided here of the contents of this Special Issue, which contains a selection of reports from a unique multidisciplinary workshop involving both researchers and clinicians. Its purpose was to explore the possibility that ADHD, dyslexia, dyspraxia and autism fall within a phospholipid spectrum of disorders. This proposal could explain the high degree of co-morbidity between these conditions, their aggregation within families and relation to other psychiatric disorders, and a range of associated features that are already well known at a clinical level. The existing evidence for fatty acid abnormalities in these disorders is summarized, and new approaches are outlined that have the potential to improve both the identification and the management of these and related neurodevelopmental and psychiatric conditions.

Omega-3 and omega-6 fatty acid concentrations in red blood cell membranes relate to schizotypal traits in healthy adults.

Reduced omega-3 and omega-6 fatty acids in red blood cell (RBC) membranes are often found in patients with schizophrenia. Here we investigated whether membrane concentrations of these fatty acids might vary as a function of schizotypal traits in non-psychotic individuals. Twenty-five healthy adults completed the O-LIFE schizotypal trait inventory and fatty acid composition of their venous blood samples was analysed via gas-liquid chromatography. Correlations between schizotypy measures and RBC fatty acids were examined and comparisons made between groups high and low on fatty acid measures and schizotypy scores. The omega-6 fatty acids arachidonic, adrenic and docosapentaenoic acid were directly related to positive schizotypal trait measures, as were most omega-3 fatty acids, but none were related to a negative, withdrawn form of schizotypy. Our findings of high RBC concentrations of omega-3 and omega-6 fatty acids in healthy adults with positive schizotypal traits clearly contrast with the low levels often found in schizophrenia, but are quite consistent with evidence that omega-3 fatty acids (notably EPA) can be useful in the treatment of schizophrenic illness.

Neuropathies associated with diabetes.

Diabetic neuropathy is the most frequent complication of diabetes and the leading cause of polyneuropathy in the Western world. A distal symmetric predominantly sensory polyneuropathy is the most common of the diverse neuropathies that occur secondary to diabetes. Pain is often the most bothersome and difficult to treat symptom of diabetic neuropathy. Autonomic neuropathy is a frequent feature of diabetic neuropathy and the source of many significant problems including postural hypotension, gastroparesis, diarrhea, constipation, neurogenic bladder, and male impotence. Physicians need to be familiar with the multiple, less common forms of diabetic neuropathy, as these often mimic other medical or neurologic conditions. The cause of diabetic neuropathy is not determined, but abundant evidence suggests that both metabolic and ischemic nerve injury are likely factors. These should not be considered mutually exclusive causes of diabetic neuropathy as both factors likely operate to different degrees to produce the clinical spectrum of neuropathies that are seen in diabetes. Although no effective treatment exists to cure diabetic neuropathy, improvement is possible with glycemic control and symptomatic therapy.

Views of older people on cataract surgery options: an assessment of preferences by conjoint analysis.

BACKGROUND: Key issues in the quality of care for people with cataracts in the UK include hospital waiting lists, complication rates from surgery, and the use of junior surgeons. The main objective of this study was to investigate the relative importance that older people attach to these factors when given theoretical choices over options for cataract surgery. METHOD: A systematic sample of 194 individuals aged 60-84 years on a general practice register in Nottingham were invited to take part in an interview based survey. Respondents ranked 11 "cataract surgery packages" containing different waiting list lengths, complication risks, and surgeon grades. Conjoint analysis was performed to determine the relative importance of these factors for individuals and for the group as a whole. RESULTS: Of the 194 subjects invited to participate, 146 (72%) completed the interview. For the group as a whole the "averaged importance" of the factors was: complication risk 45.8%; waiting time 41.1%, surgeon grade 13.1%. Analysis of importance scores for individuals showed that some were particularly concerned about complication risk while others were more concerned about waiting times. There was a strong negative correlation between importance scores for these factors (Spearman's rho -0.78, p<0.001). CONCLUSIONS: Most respondents thought that either risk of damage to sight and/or waiting time were important, while surgeon grade was relatively unimportant. The findings show that some potential cataract patients prefer a greater risk of complication combined with a short wait than a low complication rate and a longer wait.

A brief quality-of-life measure for ALS clinical trials based on a subset of items from the sickness impact profile. The Syntex-Synergen ALS/CNTF Study Group.

We previously demonstrated a significant relationship (P<0.0001) between maximum voluntary isometric contraction (MVC) plus pulmonary function scores (the Tufts Quantitative Neuromuscular Exam Combination Megascore (TQNE CM)), and the Sickness Impact Profile (SIP) in a cohort of 524 ALS patients. Because the 136-item SIP questionnaire can be difficult to administer in this population, we examined SIP subscales and clinically derived item sets in relation to the TQNE CM in an effort to define a briefer measure of quality of life for use in clinical trials. Two 'Mini-SIP' indices performed as well as the overall SIP in reflecting the impact of muscle weakness on ALS patients' quality of life: a combination of two SIP subscales ('SIP-33'), and a 19-item set of questions independently chosen by a panel of ALS specialists ('SIP/ALS-19'). Either index potentially could be useful in ALS clinical trials. The SIP/ALS-19 is currently being used in a National ALS data base, providing an opportunity to evaluate its utility prospectively against other QOL measures in ALS patients.

Does dexamethasone suppress the Mazzotti reaction in patients with onchocerciasis?

The Mazzotti reaction is a frequent complication in patients with onchocerciasis being treated with diethylcarbamazine (DEC); and more severe manifestations of this reaction may be unacceptable in many patients. It has recently been demonstrated that prednisone modifies the severity of this reaction and reduces the microfilaricidal activity of DEC. A clinical trial was performed at the National Leprosy Training Center in Wau, Sudan, to evaluate the clinical and histologic effect of the use of corticosteroids in patients receiving DEC. Administration of a low dose of dexamethasone (3 mg/day), begun after onset of the Mazzotti reaction, modifies the progression of the Mazzotti reaction without interfering with the microfilaricidal efficacy of DEC. Pretreatment with low-dose dexamethasone--prior to beginning DEC therapy--prevents the development of the Mazzotti reaction and greatly reduces the microfilaricidal activity. Administration of diphenhydramine, after onset of the Mazzotti reaction, has no effect on the course and intensity of the Mazzotti reaction nor on microfilaricidal activity. We recommend that low-dose corticosteroids be administered in conjunction with DEC--after onset of the Mazzotti reaction--and that they be tapered rapidly.

Are physicians' ratings of pain affected by patients' physical attractiveness?

The degree to which physical attractiveness and nonverbal expressions of pain influence physicians' perceptions of pain was investigated. Photographs of eight female university students were represented in four experimental conditions created by the manipulation of cosmetics, hairstyles, and facial expressions: (a) attractive-no pain, (b) attractive-pain, (c) unattractive-no pain, and (d) unattractive-pain. Each photograph was accompanied by a brief description of the patient's pain problem that was standard across conditions. Medical residents (N = 60) viewed the photographs and rated each patient's pain, distress, negative affective experience, health, personality, blame for the situation, and the physician's own solicitude for the patient. The results showed that physicians' ratings of pain were influenced both by attractiveness of patients and by nonverbal expressions of pain. Unattractive patients, and patients who were expressing pain, were perceived as experiencing more pain, distress, and negative affective experiences than attractive patients and patients who were not expressing pain. Unattractive patients also received higher ratings of solicitude on the doctor's part and lower ratings of health than attractive patients. Physician's assessments of pain appear to be influenced by the physical attractiveness of the patient.

Plasma concentrations of carotenoids and antioxidant vitamins in Scottish males: influences of smoking.

OBJECTIVE: To quantify the major carotenoids in plasma of Scottish males and establish which were affected by habitual smoking. DESIGN: Concentrations of carotenoids, vitamin C and vitamin E (alpha and gamma-tocopherol) were determined in plasma samples from 50 fasted male smokers and 50 age-matched males who had never smoked (aged 50-59 years). RESULTS: Significantly less alpha-carotene, beta-carotene and beta-cryptoxanthin and vitamin C in plasma of smokers than in never-smokers whereas concentrations of lycopene, lutein/zeaxanthin, phytofluene and vitamin E were similar between the groups. CONCLUSION: Whether lower carotenoid and vitamin C concentrations in smokers than never-smokers reflect different dietary patterns or increased metabolic turnover is unclear but smokers may benefit from increased carotenoid and vitamin C intakes.

Fetlock joint kinematics differ with age in Thoroughbred [was thoroughbred] racehorses.

Fetlock joint kinematics during galloping in 2-, 3-, 4-, and 5-year-old Thoroughbreds in race training were quantified to determine if differences due to age could account for the observation that 2-year old Thoroughbred racehorses incur a high number of injuries to the bones and soft tissues in the distal forelimbs during training and at the outset of racing. Twelve Thoroughbred racehorses were videotaped in the sagittal plane at 250 frames/s during their daily galloping workout on a 7/8 mile sand-surface training track. Four galloping strides were recorded for each horse and subsequently digitized to determine fetlock joint angles of the leading forelimb during the limb support period of a stride. Four kinematic variables were measured from each stride's angular profile: angle of fetlock joint dorsi-flexion at mid-stance, negative angular velocity, positive angular velocity and time from hoof impact to mid-stance phase of limb support. The 2-year old Thoroughbreds had significantly quicker rates of dorsi-flexion of their fetlock joints than 3- (p=0.01), 4- (p=0.01), and 5-year old (p<0.01) Thoroughbreds following impact of the leading forelimb during moderate galloping (avg. 14 m/s). Higher rates of dorsi-flexion in young Thoroughbreds may reflect immaturity (lack of stiffness) of the suspensory apparatus tissues.