Key Factors Affecting Reproductive Success of Thoroughbred Mares and Stallions on a Commercial Stud Farm.

To evaluate factors contributing to fertility of thoroughbred mares, data from 3743 oestrous periods of 2385 mares were collected on a large thoroughbred farm in Ireland. Fourteen stallions (mean age 8.3 years; range 4-15 years) had bred 2385 mares (mean age 9.4 years; range 3-24 years). Maiden mares accounted for 12%, mares with a foal at foot for 64%, and barren, slipped or rested mares for 24% of the total. The mean pregnancy rate per cycle was 67.8% (68.6% in year 1 and 66.9% in year 2). Backward stepwise multivariable logistic regression analysis was utilized to develop two models to evaluate mare factors, including mare age, reproductive status, month of foaling, dystocia, month of cover, foal heat, cycle number, treatments, walk-in status and stallion factors including stallion identity, stallion age, shuttle status, time elapsed between covers and high stallion usage on the per cycle pregnancy rate and pregnancy loss. Old age (p < 0.001) and cover within 20 days post-partum (p < 0.003) were associated with lowered pregnancy rates. High mare age (p < 0.05) and barren, slipped or rested reproductive status (p = 0.05) increased the likelihood of pregnancy loss. Uterine inflammation or infection, if appropriately treated, did not affect fertility. Only high usage of stallions (used more than 21 times in previous week) was associated with lowered (p = 0.009) pregnancy rates. However, shuttle stallions were more likely to have increased (p = 0.035) pregnancy survival, perhaps reflecting a bias in stallion selection. In conclusion, mare age exerted the greatest influence on fertility; nonetheless, thoroughbreds can be effectively managed to achieve high reproductive performance in a commercial setting.

Interovulatory intervals in mares receiving deslorelin implants in Ireland (2009 to 2010).

Deslorelin acetate implants, recently licensed in Ireland and the UK for ovulation induction in mares, have been associated with prolonged interovulatory intervals in USA studies, leading to the practice of removing implants postovulation. Trial data in Australia indicate a less pronounced effect on interovulatory intervals, suggesting possible geographical variation. Objectives of the current study were to assess the effect of deslorelin implants, with and without removal on oestrous cycle length in Irish- and UK-based Thoroughbred broodmares. Data were collected retrospectively from 88 oestrous cycles. A statistically significant difference (P=0.02) was found between interovulatory intervals in mares in which the deslorelin implant was not removed, compared with administration and removal of the implant or the use of human chorionic gonadotrophin. The results suggest that implant removal when possible is advisable. The delay in subsequent ovulations was less marked than that reported in some studies from the USA. This information is useful in deciding when to schedule subsequent breeding for mares which received a deslorelin implant during the previous oestrous period and provides evidence to counter-concerns that mares treated with deslorelin implants may experience a long delay in return to oestrus if the implant is not removed.

Study of the short- and long-term outcomes of 65 horses with peritonitis.

The records of 65 horses with peritonitis examined at two UK referral centres over a period of 12 years were reviewed. Peritonitis was defined in terms of the horse's peritoneal fluid containing more than 5 x 10(9) nucleated cells/l. Horses that had developed peritonitis after abdominal surgery or a rupture of the gastrointestinal tract were excluded. Of the 65 horses, 56 (86 per cent) survived to be discharged. Follow-up information was obtained from practice records and telephone calls to the owners for 38 of the horses. Of these, 32 (84 per cent) had survived for at least 12 months and were considered to be long-term survivors; the others six were euthanased within 12 months. Thirteen (34 per cent) of the horses discharged had experienced complications that could have been sequelae to peritonitis and eight of the 13 were euthanased. The cause of the peritonitis was identified in 15 cases; survival rates were lowest in horses with peritonitis secondary to urinary tract involvement or intra-abdominal masses. Of the other 50 cases, 47 (94 per cent) survived to discharge, but two were euthanased owing to recurrent colic.

Prognostic value of troponin T in hemodialysis patients is independent of comorbidity.

BACKGROUND: Patients on long-term hemodialysis have a high mortality. Various clinical and biochemical markers are of prognostic value. Cardiac troponin T (cTnT) is a sensitive and specific marker for myocardial damage. Asymptomatic dialysis patients have a high prevalence of cTnT concentrations above the diagnostic threshold for myocardial damage. There is controversy over whether this represents a false positive cTnT or an underlying pathology with a poor outcome. It is not known whether cTnT reflects comorbidity in these patients. METHODS: A cohort of 73 long-term hospital hemodialysis patients had cTnT estimated once prior to a mid-week dialysis. Samples were analyzed using the second-generation cTnT assay from Boehringer Mannheim on an Elecsys 1010 analyzer. The standard diagnostic threshold for myocardial damage of 0.1 ng/mL was used. A commonly employed measure of comorbidity (Khan) was applied at the time cTnT was measured. Patients were followed for 15 months. Mortality was used as the clinical end point. Kaplan-Meier survival analysis was employed and differences between groups were assessed using the Cox-Mantel log-rank test. RESULTS: Of the 73 patients, 20 were positive for cTnT and 53 were negative, at the cut-off of 0.1 ng/mL. At fifteen months, 65% of the positive patients were dead, whereas only 15% of the negative patients were dead. Survival analysis confirmed that this difference was statistically significant (P < 0.00001), and that the effect of cTnT on survival was independent of comorbidity. CONCLUSIONS: There is a high prevalence of positive cTnT in stable hemodialysis patients. A single estimation of cTnT in this group has significant prognostic value, independent of comorbidity.

Evaluation of clinical guidelines for the management of end-stage renal disease in europe: the EU BIOMED 1 study.

BACKGROUND: There are wide national and international variations in the management of patients with end-stage renal disease (ESRD). The aim of this study was to develop, harmonize, implement, and evaluate consensus-based clinical guidelines for the management of renal anaemia and renal bone disease in patients with ESRD, and for the prevention and management of cytomegalovirus disease in renal transplant recipients across six renal centres in Europe. METHODS: The trial was a prospective, multicentre, randomized balanced incomplete block design. Nephrologists from the six European renal units were randomized to develop and implement guidelines for two out of the three conditions and to act as a control for the third condition. Data were collected pre- (1 year) and post- (9 months) intervention on aspects of patient monitoring, management, and outcome. RESULTS: Eight hundred and twenty-nine dialysis patients from the six European dialysis centres were included in the study. Multivariate analysis (adjusting for case-mix and secular trends) showed a significant increase in the number of monitoring events in the guideline group compared with control group (6%, 95% CI, 1-11%). There was no concomitant increase in either appropriate management or the number of favourable patient outcomes. CONCLUSIONS: In the first European collaboration on renal guidelines, the introduction of the guidelines improved the monitoring of the patients, but did not improve patient management or outcome. This study suggests the potential for creating clinical guidelines with the aim of standardizing treatment protocols across international boundaries, and improving the quality of the medical care provided.

Limb amputation on renal replacement therapy.

Ten (10) diabetic and 7 non-diabetic patients on renal replacement therapy have undergone limb amputation in the authors' unit in the 1988 to 1996 period. The article examines the course of illness and survival patterns in this distinct and increasing sub-set in the amputee population. Rehabilitation and survival were significantly better in the diabetic group and it is recommended that it would be helpful for both prognosis and analysis if the sub-set of amputees on treatment for chronic renal failure is further divided into diabetic and non-diabetic sub-sets.

Comparing outcomes in renal replacement therapy: how should we correct for case mix?

The need to evaluate the effectiveness of clinical practice to justify expensive therapy in the face of financial constraints in all areas of health care delivery makes it necessary to identify groups of patients who are likely to benefit most from treatment. Various risk stratification methods have been used for analyzing survival probabilities for patients receiving renal replacement therapy. Complicated risk stratification methods produce large numbers of risk groups of small sizes, which makes comparison between individual centers difficult. We compared three simple methods of risk stratification, that divided patients into low-, medium-, and high-risk groups, in a cohort of 1,407 patients who commenced renal replacement therapy in five European countries during a 7-year period. Method 1 considered age (>55 years) and diabetes alone; method 2 used a higher age limit (>70 years) and comorbid illnesses, including those other than diabetes; and method 3 used only the number of comorbidities (none, 1, or > or =2) for stratification. Kaplan-Meier survival curves were constructed for comparison between risk groups and Cox's regression model used to assess strength of relationship with mortality. Although patient survival was significantly different between the low-, medium-, and high-risk groups using all three methods, Cox's regression analysis showed that method 2 provided the greatest discrimination between risk groups. In predicting mortality, method 2 (based on comorbidities and age) showed the highest sensitivity and specificity (84% and 80%, respectively) compared with method 1 (80% and 74%) and method 3 (64% and 82%). Validation of this approach in other populations in a prospective study is required before this method, which takes into account the influences of both age and comorbidity for risk stratification, can be used for comparing survival data and for presenting results of renal replacement therapy.

Treatment of severe acute vascular rejection in a renal allograft with mycophenolate mofetil and high dose steroids.

A case of a highly sensitised haemodialysis patient who developed severe vascular rejection in her third renal allograft is presented. This severe rejection episode responded to mycophenolate mofetil (MMF) and high dose steroids.

Acquired perforating dermatosis in a British dialysis population.

A perforating disorder of the skin developing in association with chronic renal failure and often also diabetes, acquired perforating dermatosis (APD), affects up to 10% of patients receiving maintenance haemodialysis in North America. The prevalence of this condition in British dialysis patients has not yet been ascertained. We have undertaken a skin survey of our dialysis population (n = 80) to determine the prevalence and clinical presentation of APD, with subsequent assessment of disease management and outcome. Of 72 patients who participated in the survey, eight were found to have APD, seven of whom were also diabetic. Skin lesions had developed pre-dialysis in two patients, on commencement of dialysis in one, and after 1-3 years on dialysis in the remaining five. Patients typically presented with pruritic dome-shaped papules with central crusts arising on the trunk and extensor limb surfaces. Histological examination of biopsy specimens revealed two types of lesion, typified by either narrow or broad ulcer craters, each showing perforation of both collagen and elastic fibres. Topical/intradermal steroid or topical retinoid were effective therapies in certain of our patients. Clinical clearance was achieved after 3-12 months of treatment in five patients with improvement in the remaining two patients who received treatment. Of the four patients who were alive at 2-year review, three remained clear, while one patient continued to develop new lesions. We report an 11% prevalence of APD in our dialysis population, suggesting the disorder to be as prevalent in patients with chronic renal failure in Britain as in North America. An association of the disorder with long-standing diabetes was confirmed.

Peripheral microcirculatory blood flow in haemodialysis patients treated with erythropoietin.

BACKGROUND: Haemodialysis patients have abnormal blood vessels, and increased morbidity from vascular causes, effects which may potentially be enhanced by erythropoietin (EPO) therapy. METHODS: Microcirculatory blood flow was assessed using a laser-Doppler flowmeter in a group of 19 haemodialysis patients before and during treatment with recombinant human (EPO). RESULTS: Haemodialysis patients had significantly impaired microcirculatory blood flow under both basal (25 degrees C) and hyperaemic (44 degrees C) conditions by comparison with 19 normal controls (baseline flow, median and range: patients 1.54 (0.28-2.54) volts, controls 3.39 (0.94-5.23) volts, p < 0.001 Mann Whitney U Test; hyperaemic flow, patients 2.69 (1.08-3.82) volts, controls 3.81 (1.32-8.00) volts, p < 0.001). There was no significant influence on microcirculatory blood flow of patient age, duration of haemodialysis, short-term EPO therapy (subcutaneous or intravenous), therapy with a calcium-channel blocker/vasodilator (nifedipine), or radiological evidence of vascular calcification. CONCLUSIONS: Haemodialysis patients have an abnormal peripheral microvasculature, which may be relevant to their increased risk of ischaemic tissue damage and poor wound healing.

Survival on renal replacement therapy in Europe: is there a 'centre effect'?

OBJECTIVE: Survival is the ultimate outcome measure in renal replacement therapy (RRT) and may be used to compare performance among centres. Such comparison, however, is meaningless if the influences of comorbidity, age and early deaths are not considered. We therefore studied survival rates on RRT in seven centres in Europe after taking into account the influence of age, early deaths, primary renal diagnoses, and comorbidity. DESIGN: A retrospective survival analysis was carried out on 1407 patients who commenced RRT in seven centres across five European countries during a 7-year period. Patients were stratified into low-, medium- and high-risk groups based mainly on comorbidity and to a lesser extent on age at commencement of RRT. Kaplan-Meier survival and Cox's proportional hazards model were used to compare survival. RESULTS: Before risk stratification overall 2-year survival across the seven centres ranged from 60.2 to 85.3% (69.3-89.9%) after excluding early deaths) masking a range of survivals of 27.4% for the high-risk group with the worst survival to 100% in the low-risk group with the best survival. After excluding early deaths 2-year survival in the low risk groups (n=622) was greater than 90% in all centres. Multivariate analysis showed that the mortality risk increased four fold from low- to medium- and a further 1.6-fold from medium- to high-risk group. However, despite this adjustment for comorbidity and age there still remained a significant difference in survival among some centres, i.e. a 'centre effect' which ranked the centres. CONCLUSION: Risk stratification diminishes the variance in survival between centres but a centre effect remains despite adjusting for age and comorbidity. Multicentre prospective studies are urgently required to identify the reasons for this apparent centre effect.

The effect of cefodizime on phagocyte function in non-patient volunteers and patients with chronic renal failure. In vitro and ex vivo studies.

Cefodizime has previously been shown to possess a number of immunomodulating properties in vivo and in vitro using several different test systems. Since most in vitro studies have been performed with cells from normal individuals, we first investigated whether cells from chronic renal failure patients would respond in vitro to cefodizime in the same way as healthy subjects. Subsequently, we investigated the effect of cefodizime (10 g over 10 days in 2-g doses) on phagocyte function ex vivo in an open study of 26 chronic renal failure patients and 16 healthy subjects. Polymorphonuclear leukocytes were tested for their ability to polarize in response to cefodizime and/or f-met-leu-phe peptide. Polymorphonuclear leukocytes and monocytes were tested for their ability to produce chemiluminescence on stimulation with either phagocytic (zymosan) or soluble phorbol myristate acetate stimuli. Phagocyte and lymphocyte membrane receptor expression was compared after exposure to cefodizime. Exposure to cefodizime in vitro causes a significant increase in polarization of polymorphonuclear leukocytes from both normal individuals and renal failure patients (both P < 0.001). It also caused increased chemotaxis and chemokinesis in a modified Boyden chamber assay. Cefodizime did not affect lucigenin-enhanced chemiluminescence and there were only minor effects on cell membrane antigen levels. In the ex vivo study there was a significant increase in polymorphonuclear leukocyte polarization (P < 0.001) attributable to cefodizime, but other investigations showed no significant differences. The results suggest that cefodizime may act as a mild priming agent for some functions, particularly chemotaxis.

Erythropoietin response and route of administration.

The effect of route of erythropoietin (EPO) administration was assessed in sixteen hemodialysis patients who completed a randomised crossover study of thrice weekly subcutaneous (SC) and intravenous (IV) erythropoietin with an EPO-free washout period separating the two phases of treatment. Route of EPO administration had no significant effect on absolute reticulocyte counts, and change in hemoglobin (Hb) during the first six weeks of therapy, at a constant EPO dose (120 iu/kg/week). Similarly, there was no significant difference in EPO dose requirement between the two routes, both during and after correction of anemia, and after maintenance of target Hb (10-12 g/dl) for an eight-week period (end of maintenance period dose; median [range]; SC EPO: 120 [30-367] iu/kg/week, IV EPO: 124.5 [37-377] iu/kg/week). Following EPO withdrawal, Hb fell at a rate of 0.38 (0.14-0.69) g/dl/week. Route of EPO administration did not influence the incidence of thrombotic and hypertensive side effects, or increases in dialysis heparin requirement and albumin, and decreases in ferritin, alpha-1-antitrypsin and ceruloplasmin during the study period. In conclusion, thrice weekly SC and IV EPO are comparable in terms of efficacy and safety.

Calcium acetate versus calcium carbonate as phosphate-binding agents in chronic haemodialysis.

Hyperphosphataemia plays a key role in the pathogenesis of renal osteodystrophy, and phosphate-binding agents are required in many chronic dialysis patients. Aluminium hydroxide and calcium carbonate are well-established phosphate binders, but their use is associated with toxicity or poor efficacy. Calcium acetate is known to be a potent phosphate binder, and has recently been used successfully in chronic dialysis patients. In this randomized cross-over trial in 31 chronic haemodialysis patients, equimolar doses of calcium acetate and calcium carbonate were administered for 6 weeks each. Compliance was estimated from tablet counts, and biochemical parameters were measured at the end of each treatment period. Of the 31 patients 23 completed both treatment arms; of the remainder, three withdrew due to adverse symptoms, hypercalcaemia necessitated treatment withdrawal in two, and three died. Non-compliance was significantly higher with acetate (18.3% tablets not taken) than with carbonate (8.7%). Serum phosphate was significantly lower after treatment with acetate (1.51 mmol/l) than with carbonate (1.80), as was the Ca x PO4 product (3.59 vs 4.18 respectively) and PTH (17.8 vs 25.4 pmol/l respectively). Serum calcium was significantly higher after acetate therapy (2.40 vs 2.32 mmol/l). No significant difference was found for sodium, potassium, bicarbonate, urea, creatinine, and haemoglobin. This study confirms that the treatment of hyperphosphataemia is more effective with calcium acetate than with calcium carbonate. For the first time an associated beneficial effect on secondary hyperparathyroidism has also been demonstrated. Patient tolerability of calcium acetate was considerably poorer, probably due in part to tablet formulation and bulkiness, as well as possible direct gastrointestinal effects of the acetate salt.

Effect of erythropoietin therapy and withdrawal on blood coagulation and fibrinolysis in hemodialysis patients.

Erythropoietin (EPO) therapy in hemodialysis patients may be associated with an enhanced risk of vascular access and extracorporeal thrombosis. Assessment of blood coagulation and fibrinolysis was performed monthly on a group of 21 hemodialysis patients treated with EPO, and on four iron-deficient hemodialysis patients treated with iron dextran infusions alone. Seventeen of the EPO treated patients were also monitored after withdrawal of EPO to allow hemoglobin to fall to pre-EPO levels, and 16 of these patients during a second subsequent phase of EPO therapy with EPO administered using the alternative route (subcutaneous/intravenous) from the first phase of treatment. Ten untreated hemodialysis patients with intrinsically high hemoglobins were studied as controls. EPO was associated with significant increases in the endothelial product Factor VIII von Willebrand factor antigen (FVIIIvWFAg), and plasma fibrinogen, to levels comparable to those observed in the untreated control patients. Both FVIIIvWFAg and fibrinogen remained significantly elevated when EPO was withdrawn. Whole blood platelet aggregation (spontaneous, collagen, and ADP-induced) also increased following EPO, collagen and ADP-induced aggregation, increasing further when EPO was withdrawn. Transient but significant changes occurred in plasma measures of thrombin-antithrombin III complex, prostacyclin stimulating factor, and protein C during the first EPO treatment phase, and also thrombin-antithrombin III complex during the second treatment phase, all favoring a tendency to thrombosis. D-dimer increased significantly following EPO withdrawal. Erythrocyte deformability, and granulocyte aggregation did not change. There was no effect of route of EPO administration (subcutaneous or intravenous) or EPO dose on any of these parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Oxygen free radicals and platelet and granulocyte aggregability in renal transplant patients.

Oxygen free radical reaction products (plasma malondialdehyde), the free radical scavengers plasma thiol and red cell superoxide dismutase (SOD), and whole blood platelet and granulocyte aggregation were measured in 23 renal transplant patients and 23 age-matched controls. Malondialdehyde-like material (MDA) was significantly increased in transplant patients compared with controls (transplants MDA [median, range], 7.7 [5.3-11.5] nmol/ml; controls MDA, 6.3 [5.4-8.7] nmol/ml; P < 0.001). The patients also had increased red cell superoxide dismutase (transplants SOD, 128.1 [89.4-93.8] U/0.5 ml red cells; controls SOD, 95.9 [62.0-132.6] U/0.5 ml red cells; P < 0.001) and reduced plasma thiol (transplants thiol, 428 [266-496] mumol/L; controls thiol, 445 [358-501] mumol/L; P < 0.05). These factors were not influenced by immunosuppressive therapy, duration of transplantation, or creatinine concentration. Transplant patients had significantly higher levels of collagen-induced and spontaneous whole blood platelet aggregation compared with controls (collagen: transplants, 72 [4-93%]; controls 43 [6-94]%; P < 0.001; spontaneous: transplants 46 [11-93]%; controls 37 [10-75]%; P < 0.05). Spontaneous platelet aggregation, however, was significantly correlated with creatinine concentration (r = 0.525, P < 0.02, Spearman's correlation), and was raised only in those patients with a degree of renal impairment. Granulocyte aggregation was increased in patients receiving cyclosporine (CsA [n = 15], 57 [36-66]%; no cyclosporine [n = 8], 45 [37-62]%; controls [n = 23]; 39 [31-61]%; P = 0.004). Renal transplant patients are subject to oxidative cell damage, and may be at increased risk of vascular thrombosis. Possible contributory factors include an immunological reaction to the graft and/or the effects of immunosuppressive therapy.

Influence of coexisting disease on survival on renal-replacement therapy.

Survival of patients on renal-replacement therapy (RRT) is no longer improving. Increasingly, such patients are older and have co-morbid conditions affecting organs other than the kidney. In a retrospective study, we calculated actuarial survival of 375 patients starting RRT during a 6 1/2 year period at renal units in Aberdeen and Dundee, UK, after stratification of patients into three risk groups (low, medium, and high) based predominantly on co-morbidity and to a lesser extent on age. 2-year survival differed significantly between low, medium, and high risk groups both before (86%, 60%, and 35%, respectively; p < 0.002 for all comparisons) and after (90%, 70%, 46%; p < 0.004 for all comparisons) excluding early deaths (within 90 days of starting RRT). Overall survival was 61% in Aberdeen and 68% in Dundee (p = 0.04), but 73% and 74%, respectively, when deaths in the first 90 days were excluded (p = 0.73). We conclude that RRT is a highly successful treatment (86% 2-year survival) for patients aged under 70 with no co-morbid conditions (low-risk group); that coexisting non-renal disease has an important influence on survival of patients on RRT; and that risk stratification and analysis of data including and excluding early deaths should allow more valid comparison of data from different centres.