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 mg)/high-dose (100 mg) 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 mg dose of cosyntropin. An inadequate delta cortisol response to the high (100 mg) 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.

Summary There are important interactions between prostatic tumours and bone. This study was designed to examine whether prostatic tissue can express bone inductive factors, in particular, the Bone Morphogenetic Proteins (BMPs). The polymerase chain reaction (PCR) has been used to screen Prostate cancer is the third most common malignancy in men in England and Wales (OPCS-Cancer Statistics, 1985). Of the 9,000 patients that present every year, approximately 50% are already suffering from metastatic disease, one of the major causes of their mortality (Whitmore, 1984 Thompson, 1990).An important group of bone-inducing factors are the bone morphogenetic proteins which have the capacity to induce new bone formation when implanted ectopically into experimental animals (Urist, 1965). Seven BMPs have so far been identified and, with the exception of BMP-1, they are all members of the TGF-P superfamily (Celeste et al., 1990; Wozney et al., 1988;Wozney, 1989). To date there has been no examination of BMP gene expression in prostatic tissue.The aims of this study were 2-fold. Firstly, to establish whether prostatic tissue and prostatic cell lines expressed the genes for BMPs. Secondly, to examine the pattern of BMP expression in patients with benign prostatic hyperplasia, and metastatic and non-metastatic prostatic adenocarcinoma in order to determine whether any differences in expression were related to the tumorigenic and metastatic phenotype of the prostatic cancer. The expression of BMPs one to six has been determined by mRNA phenotyping (Brenner et al., 1989) utilising specifically designed oligonucleotide primers selected for non-homologous regions of the BMPs. Materials and methods PatientsForty-one patients were studied. The study was approved by the ethics committee and informed consent was obtained from each patient prior to entering the study. Nineteen men had histologically proven prostatic adenocarcinoma, 11 of whom had skeletal metastases as shown by a positive technetium 99-m bone scan. Twelve patients had known benign prostatic hyperplasia (BPH) and 10 others had ocular melanomas and were used as controls, since ocular melanomas rarely metastasise to the bony skeleton and such metastases are a very late phenomenon. None of the 10 ocular melanoma patients had bony metastases. Prostatic tissue samples were obtained from transurethral resection specimens or by transrectal needle core biopsy, and ocular melanoma samples were obtained following enucleation. The nature of each sample was confirmed by standard histological examination, and graded using the Gleason scoring system (Gleason et al., 1974). Samples were snap frozen in liquid nitrogen immediately after removal and stored at -70°C prior to RNA extraction. Cell linesTwo well characterised mycoplasma-free human prostate cell lines, PC-3 (Kaighn et al., 1979) and DU145 (Stone et al., 1978), were used. Cells were grown in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal calf serum (FCS), glutamine, penicillin and streptomycin. The...

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Summary A 21‐year‐old Thoroughbred gelding was examined for intermittent fever, lethargy, inappetance and weight loss. Initial diagnostic evaluation revealed pancytopenia (anaemia, thrombocytopenia and neutropenia), hyperfibrinogenaemia and multifocal pulmonary nodules. Bacterial and fungal culture and viral isolation on transtracheal aspirate samples were negative, consistent with either pulmonary neoplasia, idiopathic granulomatous pneumonia or equine multinodular pulmonary fibrosis (EMPF). Bone marrow evaluation was consistent with pancytopenia due to a combination of peripheral consumption/destruction and suppression/destruction of progenitor cells at the level of the marrow. Pancytopenia resolved and clinical signs improved transiently with immunosuppressive corticosteroid therapy, but the horse deteriorated rapidly one month after presentation and was subjected to euthanasia. Necropsy findings were consistent with EMPF, and equine herpesvirus‐5 (EHV‐5) DNA was found in both the lung and bone marrow. The specific role of EHV‐5 in the development of the pulmonary pathology in EMPF and the pancytopenia in this horse is unclear, but an aberrant host immune/inflammatory response to EHV‐5 infection may be important.

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 mg 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 mg cosyntropin were assessed with a paired ACTH stimulation test protocol. Eight additional 36-48-hour-old foals received saline instead of 10 mg 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 mg 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 mg 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.

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.

SYNOPSIS The adrenal cortices produce a variety of steroid hormones (corticosteroids) that play vital roles in a number of physiologic processes, including: electrolyte and fluid balance; cardiovascular homeostasis; carbohydrate, protein and lipid metabolism; immune and inflammatory responses; and sexual development and reproductive function. While permanent adrenocortical insufficiency is rare in all species, emerging evidence in both human and equine medicine suggests that transient, reversible adrenocortical dysfunction resulting in cortisol insufficiency frequently develops during critical illness. This syndrome is termed relative adrenal insufficiency (RAI) or critical illness-related corticosteroid insufficiency (CIRCI), and can contribute substantially to morbidity and mortality associated with the primary disease. Thus, this review will primarily cover the mechanisms, diagnosis and clinical consequences of adrenocortical insufficiency, with particular focus on our current understanding of RAI/CIRCI in horses and 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 o .05.Results: Basal % free cortisol was highest in healthy foals at birth (58AE8% meanAESD), and was higher (P .004) in healthy foals of all ages (33AE6 to 58AE8%) than in adult horses (7AE3%). Cosyntropin-stimulated total and free cortisol concentrations were lower (P .03) in foals with shock (total 5 6.2AE8.1 mg/dL; free 5 3.5AE4.8 mg/dL versus total 5 10.8AE6.0 mg/dL; free 5 6.9AE3.3 mg/dL in foals without shock) and in nonsurvivors (total 5 3.8AE6.9 mg/dL; free 5 1.9AE3.9 mg/dL versus total 5 9.1AE7.7 mg/dL; free 5 5.5AE4.4 mg/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.