The impact of age on vitamin D receptor expression, vitamin D metabolism and cytokine production in ex vivo Rhodococcus equi infection of equine alveolar macrophages.

Rhodococcus equi (R. equi), a pneumonia-causing intracellular bacterium, results in significant morbidity and mortality in young foals, while healthy adult horses rarely develop disease. Survival and replication within alveolar macrophages (AMφ) are the hallmarks of R. equi's pathogenicity. The vitamin D receptor (VDR) and its ligand, the active vitamin D metabolite 1,25(OH)2D, are important in immune responses to intracellular bacteria. The vitamin D/VDR pathway regulates the downstream production of cytokines in infected human AMφ. The immunomodulatory role of the vitamin D/VDR pathway in equine leukocytes is unknown. The objective of the current study was to determine the impact of R. equi infection and age on synthesis of 1,25(OH)2D, VDR expression, and cytokine production in an ex vivo model of R. equi infection in equine AMφ. AMφ were collected from ten healthy foals at 2-, 4- and 8-weeks old and from nine healthy adult horses once via bronchoalveolar lavage. AMφ were mock infected (CONTROL) or infected with a virulent laboratory strain of R. equi for 7 days (INFECTED). VDR expression was determined via RT-qPCR from cell lysates. 1,25(OH)2D and cytokines were measured in cell supernatant by immunoassays. VDR expression was impacted by age (P = 0.001) with higher expression in AMφ from 8-week-old foals than from 2-week-old foals and adults. There was no significant effect of infection in foal AMφ, but in adults, relative VDR expression was significantly lower in INFECTED AMφ compared to CONTROL AMφ (P = 0.002). There was no effect of age or infection on 1,25(OH)2D concentration (P > 0.37). Mean TNFα production was significantly higher from INFECTED compared to CONTROL AMφ from 4- and 8-week-old foals and adults (P < 0.005). Mean IFNγ production was significantly higher from AMφ from foals at 8-weeks-old compared to 2-weeks-old (P = 0.013) and higher from INFECTED AMφ than from CONTROL AMφ in foals at 4-weeks-old and in adults (P < 0.027). The proportion of samples producing IL-1ß and IL-10 was also significantly higher from INFECTED compared to CONTROL AMφ isolated from 4-week-old foals (P < 0.008). Similarly, in adult samples, IL-17 was produced from a greater proportion of INFECTED compared to CONTROL samples (P = 0.031). These data document age-associated changes in VDR expression and cytokine production in equine AMφ in response to R. equi infection. This preliminary investigation supports the need for further research to fully elucidate if the vitamin D pathway has an immunomodulatory role in the horse.

Age-related changes in vitamin D metabolism and vitamin D receptor expression in equine alveolar macrophages: A preliminary study.

The vitamin D receptor (VDR)-vitamin D axis modulates pulmonary immunity in people but its role in equine immunity is unknown. Bacterial pneumonia causes high morbidity/mortality in foals and alveolar macrophages (AMφ) are important for pulmonary defenses. Age-related variations in vitamin D-mediated function of AMφ might contribute to the foal's susceptibility to pneumonia. Our aim was to assess the impact of age on equine vitamin D metabolism and VDR expression in AMφ. AMφ and plasma was collected from healthy foals (2, 4 and 8 weeks old) and adult horses (once). AMφ VDR expression was determined via RT-qPCR and plasma vitamin D metabolites quantified via immunoassays. Data were analyzed with linear mixed models. Inactive-vitamin D metabolite concentrations were lowest in foals at 2 weeks and lower at 2 and 4 weeks compared to adults (P < 0.001). Active-vitamin D metabolite concentrations were higher in foals than adults (P < 0.05). VDR expression was detected in AMφ in all animals and was highest in 2-week-old foals. Vitamin D metabolism and AMφ VDR expression are impacted by age in horses. This may have immunological consequences in foals given the key role that the VDR-vitamin D axis has in pulmonary immunity in other species.

Effects of pituitary pars intermedia dysfunction and Prascend (pergolide tablets) treatment on endocrine and immune function in horses.

It remains unclear how pituitary pars intermedia dysfunction (PPID) and pergolide treatment (Prascend [pergolide tablets]) affect endocrine and immune function in horses. To evaluate these effects, blood was collected regularly from 28 university-owned horses (10 Non-PPID, 9 PPID control [PC], and 9 PPID treatment [PT]) over approximately 15 mo. Pergolide treatment was initiated after Day 0 collections. Analyses included ACTH, insulin, total cortisol, free cortisol, complete blood counts, plasma myeloperoxidase, and cytokine/receptor gene expression in basal whole blood and in vitro stimulations (PMA/ionomycin, heat-inactivated Rhodococcus equi, and heat-inactivated Escherichia coli) of whole blood and peripheral blood mononuclear cells (PBMCs). The results were analyzed using a linear mixed model (SAS 9.4) with significance set at P < 0.05. Significant group (P = 0.0014) and group-by-time (P = 0.0004) effects were observed in resting ACTH such that PT horses differed from Non-PPID horses only at Day 0. PT horses had significantly lower changes in ACTH responses to thyrotropin-releasing hormone stimulation tests than PC horses at non-fall time points only, mid-late February 2018 (P = 0.016) and early April 2018 (P = 0.0172). When PT and PC horses did not differ, they were combined before comparison to Non-PPID horses. No significant group or group-by-time effects were seen in resting insulin, total cortisol, or free cortisol; however, significant time effects were observed in these measures. PPID horses had lower absolute lymphocyte (P = 0.028) and red blood cell (P = 0.0203) counts than Non-PPID horses. In unstimulated whole blood, PPID horses had increased IL-8 expression compared with Non-PPID horses (P = 0.0102). In addition, PPID horses had decreased interferon γ production from PBMCs after stimulation with R. equi (P = 0.0063) and E. coli (P = 0.0057) and showed increased transforming growth factor ß expression after E. coli stimulation (P = 0.0399). The main limitations of this study were a limited sample size and an inability to truly randomize the PPID horses into treatment groups. Resting ACTH is likely the best choice for determining successful responses to pergolide. Neither PPID nor pergolide appears to influence insulin, total cortisol, and free cortisol. As measured, systemic immune function was altered in PPID horses, and it is likely that these horses are indeed at increased risk of opportunistic infection. Despite reducing ACTH, pergolide treatment did not appear to influence immune function.

Identification of macrolide- and rifampicin-resistant Rhodococcus equi in environmental samples from equine breeding farms in central Kentucky during 2018.

Rhodococcus equi causes severe pneumonia in foals and is most often recognized in people as an opportunistic pathogen. Longitudinal studies examining antimicrobial-resistant R. equi from environmental samples are lacking. We hypothesized that antimicrobial-resistant R. equi would be detectable in the ground (pasture soil or stall bedding) and air at breeding farms with previous documentation of foals infected with resistant isolates, and that concentrations of resistant isolates would increase over time during the foaling season. In this prospective cohort study, ground and air samples were collected from stalls and paddocks in January, March, May and July of 2018 at 10 horse-breeding farms with history of foal pneumonia attributed to macrolide- or Rifampicin-resistant R. equi. Environmental samples were cultured in the presence and absence of macrolides and Rifampicin to select for resistant organisms. Data were analyzed with linear mixed-effects and Hurdle models. Concentrations of total R. equi in bedding or air of stalls were significantly (P < 0.05) higher in January than other months. The proportion of resistant R. equi in soil samples from paddocks was significantly (P < 0.05) higher than stall bedding during all months. For each month, air samples from paddocks had a significantly (P < 0.05) higher proportion of resistant isolates than those from stalls. Fifty-five percent of resistant soil isolates and 34% of resistant air isolates were considered virulent by identification of the vapA gene. Concentrations of resistant R. equi isolates did not increase over time during the foaling season. Antimicrobial-resistant R. equi can persist in the environment at farms with a history of pneumonia caused by resistant R. equi infections, and exposure to resistant isolates in paddocks and stalls appears stable during the foaling season. Resistant isolates in the environment not only pose a risk for disease but also can serve as a repository for dissemination of resistance genes.

Pharmacokinetics of the anticonvulsant levetiracetam in neonatal foals.

BACKGROUND: Seizures are a common manifestation of neurological disease in the neonatal foal and are an important cause of morbidity and mortality in this population. Current antiepileptic options are effective, but often have undesirable adverse effects, short duration of action and high cost. Levetiracetam has an ideal safety and pharmacokinetic profile in multiple species, including the adult horse, and may be a safe and cost-effective alternative anticonvulsant in neonatal foals. Due to differences in drug disposition and clearance dosages in neonates, dosing recommendations in other species or adult horses cannot be extrapolated to foals. OBJECTIVE: To establish the pharmacokinetic profile of single-dose i.v. and intragastric administration of levetiracetam in healthy neonatal foals. STUDY DESIGN: Randomised crossover experimental study. METHODS: Levetiracetam was administered as a single dose to six healthy foals (ages 1-10 days) at a dose of 32 mg/kg bwt i.v. or intragastrically. Plasma levetiracetam concentrations were measured using a validated HPLC protocol. RESULTS: After i.v. administration to healthy foals, levetiracetam had a mean (±s.d.) elimination half-life of 7.76 ± 0.51 h, a mean systemic clearance of 61.67 ± 10.96 (mL/h/kg) and a mean apparent volume of distribution at steady state of 0.670 ± 0.124 (L/kg). Following intragastric administration, levetiracetam had a peak concentration of 38.34 ± 7.42 mg/L and time to achieve peak concentration was 0.875 (0.5-1.5) h. Mean bioavailability for IG administration was excellent (103.04 ± 14.51%). No significant differences in pharmacokinetic variables between routes and order of administration were observed. MAIN LIMITATIONS: Small sample size and single-dose administration. CONCLUSIONS: Levetiracetam has excellent intragastric bioavailability in foals and is predicted to maintain plasma concentrations at or above the proposed target concentration with twice daily i.v. or oral administration. Once-daily administration may be possible in some foals based on the therapeutic range recommended in other species.

Bioavailability and tolerability of nebulised dexamethasone sodium phosphate in adult horses.

BACKGROUND: Nebulisation of the injectable dexamethasone sodium phosphate (DSP) would offer an inexpensive way of delivering a potent corticosteroid directly to the lungs of horses with asthma. However, this approach would be advantageous only if systemic absorption is minimal and if the preservatives present in the formulation do not induce airway inflammation. OBJECTIVE: To investigate the bioavailability of nebulised DSP and determine whether it induces airway inflammation or hypothalamic-pituitary-adrenal (HPA) axis suppression in healthy adult horses. STUDY DESIGN: Randomised crossover experiment. METHODS: Dexamethasone sodium phosphate was administered to six healthy adult horses at a dose of 5 mg q. 24 h for 5 days via nebulised, or intravenous (i.v.) routes. Plasma dexamethasone concentrations were measured by UPLC/MS-MS to calculate bioavailability. Cytological examination of bronchoalveolar fluid was performed at baseline and after the last dose of DSP. A validated chemiluminescent immunoassay was used to measure basal serum cortisol concentrations. RESULTS: After nebulisation to adult horses, dexamethasone had a mean (±s.d.) maximum plasma concentration of 0.774 ± 0.215 ng/mL and systemic bioavailability of 4.3 ± 1.2%. Regardless of route of administration, there was a significant decrease in the percentage of neutrophils in bronchoalveolar lavage fluid over time. During i.v. administration, basal serum cortisol concentration decreased significantly from baseline to Day 3 and remained low on Day 5. In contrast, basal serum cortisol concentration did not change significantly during administration via nebulisation. MAIN LIMITATIONS: Small sample size and short period of drug administration. CONCLUSIONS: Dexamethasone sodium phosphate administered via nebulisation had minimal systemic bioavailability and did not induce lower airway inflammation or HPA axis suppression in healthy horses.

Steroids, steroid precursors, and neuroactive steroids in critically ill equine neonates.

Hypothalamic-pituitary-adrenal axis (HPAA) dysfunction has been associated with sepsis and mortality in foals. Most studies have focused on cortisol, while other steroids have not been investigated. The objectives of this study were to characterise the adrenal steroid and steroid precursor response to disease and to determine their association with the HPAA response to illness, disease severity, and mortality in hospitalised foals. All foals (n=326) were classified by two scoring systems into three categories: based on the sepsis score (septic, sick non-septic [SNS] and healthy) and the foal survival score (Group 1: 3-18%; Group 2: 38-62%; Group 3: 82-97% likelihood of survival). Blood concentrations of adrenocorticotropic hormone (ACTH) and steroids were determined by immunoassays. ACTH-cortisol imbalance (ACI) was defined as a high ACTH/cortisol ratio. Septic foals had higher ACTH, cortisol, progesterone, 17α-OH-progesterone, pregnenolone, and androstenedione concentrations as well as higher ACTH/cortisol, ACTH/progesterone, ACTH/aldosterone, and ACTH/DHEAS ratios than SNS and healthy foals (P<0.01). Foals with DHEAS of 0.4-5.4ng/mL were more likely to have ACI (OR=2.5). Foals in Group 1 had higher ACTH, aldosterone, progesterone, and cortisol concentrations as well as ACTH/cortisol, ACTH/progesterone, and ACTH/DHEAS ratios than foals in Groups 2 and 3 (P<0.01). High progesterone concentrations were associated with non-survival and the cutoff value below which survival could be predicted was 23.5ng/mL, with 75% sensitivity and 72% specificity. In addition to cortisol, the response to the stress of illness in foals is characterised by the release of multiple adrenal steroids. DHEAS and progesterone were good predictors of HPAA dysfunction and outcome in hospitalised foals.

Effect of Age, Season, Body Condition, and Endocrine Status on Serum Free Cortisol Fraction and Insulin Concentration in Horses.

BACKGROUND: Increased free cortisol fraction is associated with insulin dysregulation (ID) in people with Metabolic Syndrome and Cushing's Disease. Free cortisol has not been investigated in equine endocrine disorders. HYPOTHESES: (1) In healthy horses, sex, age, body condition score (BCS), and season impact free cortisol; (2) free cortisol is increased in horses with Pituitary Pars Intermedia Dysfunction (PPID) or Equine Metabolic Syndrome (EMS). ANIMALS: Fifty-seven healthy horses; 40 horses and ponies with PPID (n = 20) or EMS (n = 20). METHODS: Prospective study. Serum collected seasonally from healthy animals and archived serum from PPID and EMS animals was analyzed for insulin, total and free cortisol concentrations, and free cortisol fraction (FCF). Linear mixed models were used to determine effects of age, sex, season, and BCS on hormones in controls. Hormone measurements were compared between disease groups and age- and season-matched controls with t-tests. EMS and hyperinsulinemic PPID animals were combined in an ID (hyperinsulinemia) group. RESULTS: Free cortisol concentrations were increased in overweight/obese controls (0.3 ± 0.1 µg/dL) compared to lean controls (0.2 ± 0.1 µg/dL; P = .017). Mean FCF was significantly higher in animals with PPID (8.8 ± 5.8 µg/dL, P = .005) or ID (8.8 ± 10.2 µg/dL, P = .039) than controls (5.0 ± 0.9 µg/dL), but total cortisol concentrations were similar (P ≥ .350) (PPID: 4.2 ± 4.3 µg/dL; ID: 5.0 ± 4.5 µg/dL; controls: 4.6 ± 1.7 and 5.1 ± 2.1 µg/dL). CONCLUSIONS AND CLINICAL IMPORTANCE: Increased FCF is associated with obesity in healthy horses and with ID (hyperinsulinemia) in horses and ponies with endocrine disease. Decreased plasma cortisol-binding capacity could be a component of these endocrine disorders in horses.

Adverse reactions in horses that underwent general anesthesia and cervical myelography.

BACKGROUND: The study was prompted by a perceived high prevalence of myelographic complications varying in severity and type, and attributed to the contrast material or the procedure. HYPOTHESES: 1. Any adverse reaction (AAR) is associated with a change in CSF volume induced either by removal of CSF or addition of contrast material. 2. AAR occurs more frequently in horses with higher premyelography neurologic grade. 3. Nonspecific hyperthermia is attenuated by anti-inflammatory and osmotic agents. ANIMALS: Horses (n = 278) that underwent myelography between 2000 and 2012 at 5 institutions: A (87), B (68), C (65), D (46), and E (12). METHODS: Multi-institutional, retrospective, observational cross-sectional study. RESULTS: AAR were observed in 95/278 (34%) horses, were associated with longer general anesthesia time (P = .04) and higher contrast-medium volume (P = .04); euthanasia because of AAR was performed in 5/278 (2%) horses. Adverse neurologic reactions were the most common type of complication observed occurring in 15/278 (5%) and 42/235 (18%) of horses in the intra- and postmyelography periods. A relationship between AAR and premyelography neurologic grade was not identified (P = .31). Nonspecific hyperthermia was observed in 25/235 (11%) horses; no relationship was observed with administration of anti-inflammatory drugs and osmotic agents (P = .30). CONCLUSIONS AND CLINICAL IMPORTANCE: The category of AAR occurred in one-third of the horses generally was mild and self-limiting. These reactions were associated with increased contrast-medium volume and longer anesthesia time; but, no specific procedural recommendations could be made because of small odds ratios (OR) of <2 for each 1 mL increase in contrast material and for each 1 minute of additional anesthesia time.

Effect of N-butylscopolammonium bromide on equine ileal smooth muscle activity in an ex vivo model.

REASONS FOR PERFORMING STUDY: N-butylscopolammonium bromide (NBB) is an anticholinergic agent used to treat spasmodic colic in horses. Intestinal smooth muscle spasm also occurs in horses with intraluminal intestinal obstructions, such as ileal impactions. The antispasmodic effects of NBB may be useful in managing ileal impactions, but the effects of NBB on equine ileal smooth muscle are unknown. OBJECTIVES: To investigate the effects of NBB on spontaneous and induced contraction of the equine ileum in an ex vivo model. STUDY DESIGN: Ex vivo biomechanical study assessing contractile properties in isolate equine ileal smooth muscle with and without exposure to NBB. METHODS: Ileal tissue was collected from 6 healthy horses after euthanasia, and isolated circular and longitudinal smooth muscle strips were connected to isometric force transducers in organ baths. After equilibration, the effect of NBB (1 nmol/l to 100 µmol/l) on spontaneous and carbachol-induced contraction was determined and compared with responses in control tissue. RESULTS: At ≥30 µmol/l, NBB inhibited spontaneous contractions in all muscle strips that exhibited spontaneous activity. N-butylscopolammonium bromide pre-treatment inhibited carbachol-induced contraction in circular (NBB-treated half maximal effective concentration [EC50] 0.530 × 10(-8) mol/l vs. control EC50 41.57 × 10(-8) mol/l) and longitudinal muscle strips (NBB-treated EC50 0.243 × 10(-8) mol/l vs. control EC50 90.84 × 10(-8) mol/l). Abolition of carbachol-induced contraction with NBB was observed at lower concentrations in circular than longitudinal muscle strips. Pretreatment with NBB significantly inhibited carbachol-induced contractions; NBB-treated tissue required greater carbachol concentrations to produce sustained contractions than control muscle strips. Histamine-evoked contraction was not affected by NBB. CONCLUSIONS: N-butylscopolammonium bromide inhibits spontaneous and cholinergically mediated contraction in equine ileal smooth muscle strips ex vivo. Thus, NBB might reduce intestinal spasm in equine ileal impactions and could be useful for medical management of these cases, although further study is needed to confirm these effects in vivo.

Medical management of sand enteropathy in 62 horses.

REASONS FOR PERFORMING STUDY: Medical management of sand enteropathy is common in equine practice, but the clinical features and outcomes associated with medically managed sand enteropathy are not well described. OBJECTIVES: To review clinical features, therapeutic approaches and outcomes associated with primary medical management of sand enteropathy in the mature horse. METHODS: Medical record databases at 3 equine referral hospitals from January 2000 to April 2010 were reviewed for cases of sand enteropathy diagnosed via abdominal radiographs in mature horses that were initially managed medically. Data were collected and descriptive analyses compiled. Uni- and multivariate logistic regression was used to evaluate factors potentially associated with treatment failure. RESULTS: The medical records of 62 horses were analysed; 90% of horses survived to discharge and 50% of horses that had repeat abdominal radiographs taken demonstrated improvement in the degree of sand accumulation after treatment. Nine horses underwent exploratory laparotomy during hospitalisation, and colonic sand impaction was found in all 9, with a concurrent gastrointestinal lesion identified in 7. Four horses were subjected to euthanasia during or after surgery because of disease severity or complications. Need for exploratory laparotomy was the factor most strongly associated with nonsurvival. CONCLUSIONS: These data suggest that medical management can result in clinical and radiographic resolution of uncomplicated sand enteropathy in mature horses, and is associated with a good prognosis. Horses with sand enteropathy that exhibit persistent colic signs despite medical management are likely to have a concurrent gastrointestinal lesion, so prompt exploratory laparotomy should be considered in such cases. POTENTIAL RELEVANCE: Uncomplicated sand enteropathy can be managed medically in mature horses, and serial abdominal radiography can be used to monitor sand clearance. Surgery to evaluate for and correct concurrent gastrointestinal lesions should be recommended without delay in horses showing persistent colic signs.

Serum free cortisol fraction in healthy and septic neonatal foals.

BACKGROUND: Relative cortisol insufficiency occurs in septic foals and impacts survival. Serum free (biologically available) cortisol concentration might be a better indicator of physiologic cortisol status than serum total cortisol concentration in foals. HYPOTHESES: In septic foals, (1) low free cortisol concentration correlates with disease severity and survival and (2) predicts disease severity and outcome better than total cortisol concentration. ANIMALS: Fifty-one septic foals; 11 healthy foals; 6 healthy horses. METHODS: In this prospective clinical study, foals meeting criteria for sepsis at admission were enrolled. University-owned animals served as healthy controls. Basal and cosyntropin-stimulated total cortisol concentration and percent free cortisol (% free cortisol) were determined by chemiluminescent immunoassay and ultrafiltration/ligand-binding methods, respectively. Group data were compared by ANOVA, Mann-Whitney U-tests, and receiver operator characteristic curves. Significance was set at P < .05. RESULTS: Basal % free cortisol was highest in healthy foals at birth (58 ± 8% mean ± SD), and was higher (P ≤ .004) in healthy foals of all ages (33 ± 6 to 58 ± 8%) than in adult horses (7 ± 3%). Cosyntropin-stimulated total and free cortisol concentrations were lower (P ≤ .03) in foals with shock (total = 6.2 ± 8.1 µg/dL; free = 3.5 ± 4.8 µg/dL versus total = 10.8 ± 6.0 µg/dL; free = 6.9 ± 3.3 µg/dL in foals without shock) and in nonsurvivors (total = 3.8 ± 6.9 µg/dL; free = 1.9 ± 3.9 µg/dL versus total = 9.1 ± 7.7 µg/dL; free = 5.5 ± 4.4 µg/dL in survivors). Free cortisol was no better than total cortisol at predicting disease severity or outcome in septic foals. CONCLUSIONS AND CLINICAL IMPORTANCE: Serum free cortisol is impacted by age and illness in the horse. There is no advantage to measuring free over total cortisol in septic foals.

Molecular identification of prey in the stomach contents of Harp Seals (Pagophilus groenlandicus) using species-specific oligonucleotides.

All methods of diet analysis in marine mammals, including hard part analysis (HPA), have biases affecting the accuracy of prey-species identification and frequency in the estimated diet due to differential consumption, digestion and retention. Using PCR amplification of specific prey DNA with species-specific primers, we developed a DNA-based method that complements HPA and provides an alternative means to detect prey from stomach contents of Harp Seals (Pagophilus groenlandicus). The target size that could be reliably amplified was determined using a digestion time-series of Atlantic Cod (Gadus morhua) tissue in simulated seal stomachs. Various target lengths were trialed using general teleost primers; amplicons of approximately 800 bp or less were consistently obtained. Prey species-specific PCR primers for Atlantic Cod, Arctic Cod (Boreogadus saida) and Capelin (Mallotus villosus) were designed and tested with DNA from the stomach contents of 31 Harp Seals. Amplicons were obtained for all three species-specific primer sets. Amplification results compared with HPA revealed: (i) Atlantic Cod hard parts were found in five stomachs where no Atlantic Cod DNA amplified, suggesting that Atlantic Cod may be over-represented in the estimated diet, (ii) amplification of Arctic Cod DNA occurred for 17 stomachs, including all 12 stomachs with, and five stomachs without, Arctic Cod hard parts, and (iii) Capelin DNA amplified for four of five stomachs with Capelin hard parts and for one stomach without Capelin hard parts. We conclude that PCR amplification of specific prey DNA provides a viable means to complement Harp Seal diet analysis by HPA, but suggest that valuable information for quantitative diet analysis rests in a quantitative PCR approach.

Hypothalamic-pituitary-adrenal axis dysfunction in hospitalized neonatal foals.

BACKGROUND: Transient hypothalamic-pituitary-adrenal (HPA) axis dysfunction occurs frequently in critically ill humans and impacts survival. The prevalence and impact of HPA axis dysfunction in critically ill neonatal foals are not well characterized. HYPOTHESES: (1) HPA axis dysfunction occurs in hospitalized neonatal foals, and is characterized by inappropriately low basal serum cortisol concentration or inadequate cortisol response to exogenous adrenocorticotropic hormone (ACTH); (2) hospitalized foals with HPA axis dysfunction have more severe disease and are less likely to survive than hospitalized foals with normal HPA axis function. ANIMALS: Seventy-two hospitalized foals and 23 healthy age-matched foals. METHODS: Basal ACTH and cortisol concentrations were measured and a paired low-dose (10 microg)/high-dose (100 microg) cosyntropin stimulation test was performed at admission in hospitalized foals. HPA axis dysfunction was defined as (1) an inappropriately low basal cortisol concentration or (2) an inadequate increase in cortisol concentration (delta cortisol) after administration of cosyntropin, with cut-off values for appropriate basal and delta cortisol concentrations determined from results obtained in healthy age-matched foals. RESULTS: Forty-six percent of hospitalized foals had an inappropriately low basal cortisol concentration and 52% had an inadequate delta cortisol concentration after administration of the 100 microg dose of cosyntropin. An inadequate delta cortisol response to the high (100 microg) dose of cosyntropin was significantly correlated with shock and multiple organ dysfunction syndrome in hospitalized foals, and with decreased survival in a subgroup of septic foals. CONCLUSIONS AND CLINICAL IMPORTANCE: HPA axis dysfunction occurs frequently in hospitalized neonatal foals, and negatively impacts disease severity and survival.

Hypothalamic-pituitary-adrenal axis assessment in healthy term neonatal foals utilizing a paired low dose/high dose ACTH stimulation test.

BACKGROUND: Hypothalamic-pituitary-adrenal (HPA) axis function is dynamic in the neonatal foal. The paired low dose/high dose cosyntropin (ACTH) stimulation test allows comprehensive HPA axis assessment, but has not been evaluated in neonatal foals. HYPOTHESIS: Foal age will significantly affect cortisol responses to a paired 10 and 100 microg dose cosyntropin stimulation test in healthy neonatal foals. ANIMALS: Twenty healthy neonatal foals. METHODS: HPA axis function was assessed in 12 foals at birth and at 12-24, 36-48 hours, and 5-7 days of age. At each age, basal cortisol and ACTH concentrations were measured and cortisol responses to 10 and 100 microg cosyntropin were assessed with a paired ACTH stimulation test protocol. Eight additional 36-48-hour-old foals received saline instead of 10 microg cosyntropin in the same-paired ACTH stimulation test design. RESULTS: At birth, foals had significantly higher basal cortisol and ACTH concentrations and higher basal ACTH : cortisol ratios compared with foals in all other age groups. A significant cortisol response to both the 10 and 100 microg doses of cosyntropin was observed in all foals. The magnitude of the cortisol response to both doses of cosyntropin was significantly different across age groups, with the most marked responses in younger foals. There was no effect of the paired ACTH stimulation test design itself on cortisol responses. CONCLUSIONS AND CLINICAL IMPORTANCE: A paired 10 and 100 microg cosyntropin stimulation test can be used to evaluate HPA axis function in neonatal foals. Consideration of foal age is important in interpretation of HPA axis assessment.

Evaluation and promotion of the clinician-educator: the faculty viewpoint.

Changes in healthcare management and reimbursement have contributed to alterations in the traditional culture of academic medical centers and the roles and responsibilities of their physician faculty, including clinician-educators. Questions concerning the appropriate evaluation methodology and criteria for promotion of such clinical faculty have been raised. In our survey of a large university-based physical medicine and rehabilitation department, only minimal differences were related to age, gender, and academic rank, and these are discussed.

The relation of shoulder pain and range-of-motion problems to functional limitations, disability, and perceived health of men with spinal cord injury: a multifaceted longitudinal study.

OBJECTIVES: To determine if shoulder pain and range-of-motion (ROM) problems can be predicted by demographic, injury-related, body weight, and radiographic data over 3 years and to determine the relationships among these shoulder problems and functional limitations, disability, and perceived health. DESIGN: A longitudinal, 2-panel study in which data were collected at 2 points in time, 3 years apart. SETTING: The community. PARTICIPANTS: Eighty-nine adult men with traumatic spinal cord injury (SCI) in the Houston-Galveston, TX, area. MAIN OUTCOME MEASURES: The acromioclavicular (AC) and the glenohumeral (GH) joints were x-rayed on plain film in standard anteroposterior position. Functional limitations were determined with the FIM instrument; disability was measured with the Craig Handicap Assessment and Reporting Technique (CHART). RESULTS: Thirty percent had shoulder pain and 22% had shoulder ROM problems. Men with shoulder pain had lived longer with SCI, were more likely to report shoulder ROM problems, had lower CHART mobility scores, and were more likely to rate their health as fair than those without shoulder pain. Shoulder ROM problems were more common among men who were older, had AC joint narrowing, had lower FIM scores, and reported poorer health. CONCLUSION: Shoulder pain and ROM problems were relatively prevalent. Demographic, injury-related, and radiographic variables were identified that were predictive of these problems over a period of at least 3 years. The shoulder problems were related to functional limitations, disability, and perceived health.