A four-kallikrein panel for the prediction of repeat prostate biopsy: data from the European Randomized Study of Prostate Cancer screening in Rotterdam, Netherlands.

BACKGROUND: Most men with elevated levels of prostate-specific antigen (PSA) do not have prostate cancer, leading to a large number of unnecessary biopsies. A statistical model based on a panel of four kallikreins has been shown to predict the outcome of a first prostate biopsy. In this study, we apply the model to an independent data set of men with previous negative biopsy but persistently elevated PSA. METHODS: The study cohort consisted of 925 men with a previous negative prostate biopsy and elevated PSA (>or=3 ng ml(-1)), with 110 prostate cancers detected (12%). A previously published statistical model was applied, with recalibration to reflect the lower positive biopsy rates on rebiopsy. RESULTS: The full-kallikrein panel had higher discriminative accuracy than PSA and DRE alone, with area under the curve (AUC) improving from 0.58 (95% confidence interval (CI): 0.52, 0.64) to 0.68 (95% CI: 0.62, 0.74), P<0.001, and high-grade cancer (Gleason >or=7) at biopsy with AUC improving from 0.76 (95% CI: 0.64, 0.89) to 0.87 (95% CI: 0.81, 0.94), P=0.003). Application of the panel to 1000 men with persistently elevated PSA after initial negative biopsy, at a 15% risk threshold would reduce the number of biopsies by 712; would miss (or delay) the diagnosis of 53 cancers, of which only 3 would be Gleason 7 and the rest Gleason 6 or less. CONCLUSIONS: Our data constitute an external validation of a previously published model. The four-kallikrein panel predicts the result of repeat prostate biopsy in men with elevated PSA while dramatically decreasing unnecessary biopsies.

Asymmetries of saccadic eye movements in oriented-line-target search.

Visual search for a line-element target differing sufficiently in orientation from a background of line elements can be performed rapidly, effortlessly, and without eye movements. There is, however, a response asymmetry: detection is better with an oblique target element in vertical or horizontal background elements than when these orientation are interchanged. If the underlying visual mechanisms also provide an input to the oculomotor system, then a similar asymmetry should be observed in eye-movement behaviour. To test this hypothesis, an experiment was undertaken in which eye movements were recorded while subjects searched for a line-element target in background of line elements; orientations were chosen from the range 0 degree, 30 degrees, 60 degrees, and 90 degrees to the vertical. Data from three subjects showed that (1) latencies for the initial saccade, (2) angular errors in initial-saccade direction, and (3) manual response times depended similarly on the combination of target- and background-element orientations, performance being better for 30 degrees or 60 degrees targets in 0 degree or 90 degrees backgrounds than vice-versa. The early orientation-selective mechanisms responsible for the rapid detection of oriented-line targets are probably the same as those providing signals for saccadic eye movements.

Foaling-management practices associated with the occurrence of enterocolitis attributed to Clostridium perfringens infection in the equine neonate.

Enterocolitis associated with Clostridium perfringens (C. perfringens) infection in neonatal foals is often severe and has been associated with a high case-mortality risk. We designed a premises-based survey to evaluate the associations of regional foaling practices, premises environmental management, periparturient foal and brood-mare management, and periparturient brood-mare ration with the occurrence of neonatal enterocolitis attributed to C. perfringens infection. Potential risk factors individually associated with enterocolitis were breed type, housing type at foaling and in the first three days of life, ground/floor surface type at foaling and in the first three days of life, brood-mare ration before and after foaling, and the presence of livestock other than horses on the premises in the past. From the multivariable-logistic regression models, six variables were significantly associated with an increased risk of the outcome of interest (p<0.05): foals of the stock horse type, housing in a stall or drylot in the first three days of life, other livestock present on the premises in the past, foal born on dirt, sand or gravel surface, and low amounts of grass hay and grain fed post-partum. Low grain amounts fed pre-partum represented a decreased risk of the outcome of interest.

Survey of the large animal diplomates of the American College of Veterinary Internal Medicine regarding percutaneous lung biopsy in the horse.

A survey designed to obtain information on the indications, contraindications, complications, and methodology of percutaneous lung biopsy in the horse was sent to large animal diplomates of the American College of Veterinary Internal Medicine. Sixty-five of 190 diplomates returned the survey (response rate: 34%) and 59 of these 65 respondents (91%) indicated that they worked with horses. Forty-four diplomates had performed a percutaneous lung biopsy in 1 or more horses (i.e. 75% of those diplomates working with horses and 68% of total respondents). Clinical and radiologic diagnoses that prompted diplomates to perform percutaneous lung biopsy in the horse included a pulmonary miliary pattern (93%), suspicion of pulmonary infiltrative disease (91%), suspicion of pulmonary neoplasia (91%), suspicion of chronic obstructive pulmonary disease (COPD) (20%), and suspicion of exercise-induced pulmonary hemorrhage (EIPH) (7%). Only one of the respondents reported the use of percutaneous lung biopsy in the diagnostic workup if pneumonia was suspected, but 11% of respondents reported that suspicion of pulmonary abscessation would prompt them to perform a percutaneous lung biopsy. In contrast, a variable percentage of respondents felt there were contraindications to performance of this technique, which included neonatal septicemia (68%), pulmonary abscessation (65%), pleuropneumonia (55%) and pneumonia (42%), EIPH (41%), and COPD (26%). No respondent indicated that suspicion of neoplasia was a contraindication to percutaneous biopsy. Most common complications observed by respondents were epistaxis (68% of respondents), putative pulmonary hemorrhage (52%), tachypnea (39%), and respiratory distress (32%). Ten of 44 respondents (23%) had not seen any complications with percutaneous lung biopsy. Forty-two of 44 respondents (96%) warned owners about possible complications before performing percutaneous lung biopsy. All respondents to this question reported that they would perform percutaneous lung biopsies in horses in the future, but 4 of 41 would use the procedure only as a last resort.

Subcutaneous emphysema in a neonatal foal.

A 16-hour-old foal was examined because of subcutaneous emphysema, which began developing 3 hours after a routine delivery. Physical examination did not reveal soft-tissue or musculoskeletal trauma, and there were no skin injuries to explain the subcutaneous accumulation of air. Results of CBC and serum biochemical analysis were within reference limits, and findings on endoscopy of the pharyngeal area, trachea, and esophagus were within normal limits other than observation of dorsal pharyngeal compression. A pulmonary bulla, pneumomediastinum, and pneumothorax were detected on thoracic radiography. Because of the apparent association of the subcutaneous emphysema and thoracic abnormalities, a diagnosis of primary subcutaneous emphysema was made. A tracheostomy tube was placed to facilitate ventilation and to provide an exit point for the trapped air. Supportive care was provided. The foal's condition resolved over the subsequent 8 days.

Enterocolitis associated with Clostridium perfringens infection in neonatal foals: 54 cases (1988-1997).

OBJECTIVE: To identify clinical signs, physical examination findings, results of diagnostic tests, treatments administered, and clinical outcome of neonatal foals with enterocolitis associated with Clostridium perfringens infection. DESIGN: Retrospective study. ANIMALS: 54 neonatal foals. RESULTS: Most foals had acute onset of obtunded mentation, colic, or diarrhea and developed leukopenia, neutropenia, an abnormally high number of band neutrophils, toxic WBC, and hypoproteinemia within 24 hours after admission, despite high serum IgG concentrations (> 800 mg/dl). Abdominocentesis and abdominal radiography of some foals revealed exudative peritonitis and gaseous distention of the small and large intestine, respectively. Cytologic examination of feces revealed spores or gram-positive rods in 8 of 10 foals. The most common genotypes of C perfringens isolates were type A and C, alone or in combination. Treatment did not alter mortality rate for most foals that had a positive culture for C perfringens type C. Of 54 foals, 29 (54%) that had C perfringens-associated enterocolitis died. Foals that had a culture that yielded C perfringens had higher sepsis scores, IgG concentrations, and mortality rates, compared with the overall hospital population of neonatal foals. CLINICAL IMPLICATIONS: Foals less than 7 days old that have enterocolitis associated with C perfringens infections, especially type C, have a guarded prognosis. Cytologic examination of feces to determine spore counts and detect rods may be a means for early identification of C perfringens infections. Polymerase chain reaction assays to determine genotype are important for designing preventive treatment regimens.

Putative uremic encephalopathy in horses: five cases (1978-1998).

OBJECTIVE: To determine historical, physical examination, clinicopathologic, and postmortem findings in horses with putative uremic encephalopathy. Design-Retrospective study. Animals-5 horses with renal failure and neurologic disease not attributable to abnormalities in any other organ system. PROCEDURE: Medical records from 1978 to 1998 were examined for horses with renal disease and neurologic signs not attributable to primary neurologic, hepatic, or other diseases. Signalment, history, physical examination findings, clinicopathologic data, renal ultrasonographic findings, and postmortem data were reviewed. RESULTS: Of 332 horses with renal disease, 5 met selection criteria. Historical findings, physical examination findings, clinicopathologic data, ultrasonographic data, and postmortem findings were consistent with chronic renal failure. Swollen astrocytes were detected in all 4 horses examined at necropsy. CONCLUSIONS AND CLINICAL RELEVANCE: A single criterion was not determined to be pathognomonic for uremic encephalopathy in horses. Uremic encephalopathy should be considered as a differential diagnosis in horses with evidence of chronic renal failure and encephalopathic neurologic sign not attributable to other causes. Astrocyte swelling, which was common to all 4 horses examined at necropsy, may serve as a microscopic indicator of uremic encephalopathy in horses.

Outbreak of Salmonella infantis infection in a large animal veterinary teaching hospital.

During the past 11 years, there have been numerous reports of outbreaks of salmonellosis involving horses in veterinary teaching hospitals. Some of these outbreaks have been associated with Salmonella serotypes not commonly associated with infection of horses. Salmonella infantis is among the more common Salmonella serotypes isolated from human beings, and is an important pathogen in the broiler chicken industry. However, it was not commonly isolated from horses or cattle on a national basis between 1993 and 1995. In this report, we describe an outbreak of S infantis infection among large animals, primarily horses, in a veterinary teaching hospital and the control measures that were implemented. Factors that appeared to be key in control of this outbreak in this hospital included providing biosecurity training sessions for hospital personnel, adopting a standard operating procedure manual for biosecurity procedures, installing additional handwashing sinks throughout the facility, painting the interior of the facility with a nontoxic readily cleanable paint, replacing the dirt flooring in 4 stalls with concrete flooring, and removing noncleanable surfaces such as rubber stall mats, wooden hay storage bins, and open grain bins. Our experience with this outbreak suggests that although it is virtually impossible to eliminate Salmonella organisms from the environment, minimizing contamination is possible. Prevention of nosocomial infection must be approached in a multifaceted manner and care must be taken to search out covert sources of contamination, especially if standard intervention procedures do not prevent spread of the disease.

ESA developments in life support technology: achievements and future priorities.

Following an enthusiastic start in 1985, ESA's life support technology development programme was re-assessed in the mid- to late-1990s to reflect the strong reduction in European manned space ambitions which occurred at that time. Further development was essentially restricted to activities that could constitute ISS upgrades or enhancements, or support ISS utilisation/operations, together with a single, limited, activity (MELISSA) aimed at bioregenerative life support, in the continuing hope that there might be "life after Station". The paper describes the current status of these activities and summarises the main priorities for future development that were identified at the April 1999 Workshop on Advanced Life Support.

The monitoring of gaseous contaminants in spacecraft cabin atmospheres.

The accumulation of toxic or otherwise harmful trace gases in a spacecraft cabin is a very serious concern in terms of the health and safety of the crew. Although methods exist for controlling the evolution of such contaminants, techniques for monitoring the success of these methods, on board and in near- real-time, are still under development. One such technique, based on the use of FTIR interferometry, is being developed in Europe. A prototype instrument has been assembled, making extensive use of 'off-the-shelf' hardware and software, and tested for its ability to detect and quantify--within a maximum period of 1 minute and in the presence of water vapour and carbon dioxide 21 of the most frequently detected contaminants on past Shuttle and Spacelab flights. Results have confirmed that such contaminants can be detected and measured with an acceptable degree of precision.

Water recovery in space.

In the absence of recycling, water represents over 90% of the life-support consumables for a manned spacecraft. In addition, over 90% of the waste water generated can be classified as moderately or slightly contaminated (e.g. shower water, condensate from the air-conditioning system, etc.). The ability to recover potable water from moderately contaminated waste water hence enables significant savings to be made in resupply costs. A development model of such a water-recovery system, based on membrane technology has been produced and tested using "real waste water" based on used shower water Results indicate some 95% recovery of potable water meeting ESA standards, with total elimination of microbial contaminants such as bacteria, spores and viruses.

Accelerated vaccination schedule provides protective levels of antibody and complete herd immunity to equine influenza.

REASONS FOR PERFORMING STUDY: During the 2007 Australian equine influenza (EI) outbreak, an accelerated primary course 14 day intervaccination schedule was proposed, but not widely implemented. Expert opinion was divided as to the efficacy of such a schedule given the lack of published data. This study determined the level and duration of humoral immunity following administration of a recombinant canarypox-vectored vaccine (ALVAC-EIV) with a primary intervaccination interval of 14 days and booster at 105 days. OBJECTIVES: To examine whether protective levels of immunity of adequate duration were achieved following a primary course reduced from a minimum interval of 28 to 14 days. Antibody responses to 2 H3N8 American lineage virus strains (including A/equine/Sydney/6085/2007) were assessed and compared to previous challenge studies using ALVAC-EIV at conventional intervaccination intervals. METHODS: Fourteen Thoroughbred horses and 2 ponies from a rural racehorse training property in Victoria, Australia, were vaccinated with ALVAC-EIV on Days 0, 14 and 105. Serial blood samples were collected over the next 32 weeks and tested with haemagglutination inhibition and single radial haemolysis (SRH) in full assays to evaluate the serological response. RESULTS: All horses and ponies responded to the accelerated ALVAC-EIV vaccination schedule. Mean SRH antibodies remained above those consistent with clinical protection for the duration of the study period. All vaccinates demonstrated high SRH antibodies 14 days following V2, thereby achieving 100% herd immunity to homologous viral challenge. CONCLUSIONS: An accelerated vaccination schedule conferred long-lasting protective antibody levels despite a >50% reduction in the recommended V1-V2 interval. POTENTIAL RELEVANCE: High levels of rapidly acquired herd immunity are critical in containing an outbreak of such a highly contagious pathogen as EIV. In a strategic vaccination programme, it is important that horses remain protected for sufficient time to allow control programmes to succeed. An accelerated 14 day primary course intervaccination interval and booster at 105 days achieves both of these objectives.

Effects of hyperimmune equine plasma on clinical and cellular responses in a low-dose endotoxaemia model in horses.

Endotoxaemia is a major cause of equine morbidity, and plasma from horses immunised against Escherichia coli is used in its treatment. The aim of this study was to determine the effects of hyperimmune plasma on the clinical and leukocyte responses, including production and activity of TNFα, in an in vivo endotoxin challenge model. Pre-treatment with hyperimmune equine plasma had no significant effect on peak total plasma TNFα concentration (occurring 90min after the administration of 30ng/kg LPS). However, the bioavailable (unbound) TNFα measured by bioassay was significantly reduced in plasma-treated horses (1044.44±193.93pg/ml at 90min) compared to saline treated controls (1373.92±107.63pg/ml; P=0.05). Therefore, although pre-treatment with hyperimmune equine plasma did not significantly modify the clinical signs of endotoxaemia in this model, there was some evidence of reduced TNF bioactivity, which may be due to factors in the plasma which bind and reduce the activity of this cytokine.

Serum cardiac troponin I concentrations in horses with cardiac disease.

OBJECTIVES: To measure the cardiac troponin I (cTnI) concentration in horses and determine whether it could be used in the diagnosis of myocardial disease, as well as determining the association between cTnI and survival. DESIGN: Prospective, observational study. PROCEDURE: Physical examination, echocardiography, telemetric electrocardiography and postmortem were used to diagnose cardiac disease. Diagnoses were grouped as myocardial disease, structural heart disease or lone arrhythmia. Blood samples were collected at admission for cTnI analysis and the results were compared with those for 18 healthy horses. RESULTS: In total, 49 horses were admitted with cardiac disease. Elevated cTnI concentration (>0.03 ng/mL) was observed in a greater proportion of horses with myocardial disease (7/7), compared with healthy horses (0/18; P < 0.0001), horses with structural heart disease (7/25; P = 0.001), and horses with a lone arrhythmia (2/17; P = 0.0001). The median cTnI concentration for horses with myocardial disease was 17.5 ng/mL (range 0.78-49.87 ng/mL), which was higher than in the healthy horses (0.01 ng/mL, range 0.01-0.03 ng/mL; P < 0.0001). Of the 49 horses with cardiac disease, the median cTnI concentration for non-survivors (0.28 ng/mL, range 0.01-49.87 ng/mL) was higher than for survivors (0.01 ng/mL, range 0.01-30.31 ng/mL; P = 0.0035). However, the proportion of surviving horses with an elevated cTnI (10/39, 26%) was not significantly different from the proportion of non-surviving horses with an elevated cTnI (6/10, 60%; P = 0.060). CONCLUSIONS: cTnI is elevated in horses with myocardial disease and elevated to a lesser degree in some horses with structural heart disease or lone arrhythmias. The association between cTnI concentration and survival was not clear.

Activin A as a novel biomarker of equine inflammatory abdominal disease: preliminary findings.

This study evaluated the inflammatory mediator activin A in horses with acute abdominal disease and compared this putative novel biomarker with serum amyloid A (SAA). Thirty-three adult horses referred for evaluation of acute abdominal disease were grouped into three lesion categories, non-strangulating, strangulating or inflammatory. Eleven healthy adult horses served as controls. Serum activin-A was significantly increased in animals with inflammatory or strangulating lesions compared with controls. Horses with non-strangulating, strangulating or inflammatory lesions had significantly elevated SAA concentrations. Activin A, along with other biomarkers, may be useful in monitoring inflammation in cases of acute abdominal disease in horses. Further validation is warranted to determine the utility of this biomarker in evaluating the effectiveness of novel anti-inflammatory treatments for equine colic and endotoxaemia.

Acute myeloid leukaemia (M6B: pure acute erythroid leukaemia) in a Thoroughbred foal.

A 10-week-old Thoroughbred filly was referred for anaemia of 4 weeks' duration. Haematology revealed severe anaemia and panleucopenia. Cytological examination of bone marrow smears revealed a myeloid to erythroid ratio <0.02:1 (reference range 0.5-2.4:1.0) and an abundance of erythroid precursor cells. The erythroid cell population included rubriblasts, prorubricytes and rubricytes, with only scant numbers of metarubricytes present. There were numerous mitotic erythroid cells, some of which were atypical and megaloblastic. These cytomorphological changes are consistent with pure acute erythroid leukaemia. No treatment was instituted and the filly died three days after presentation. This case illustrates the need to consider both haematology and bone marrow findings to establish a diagnosis of pure erythroid leukaemia. To our knowledge, there is no documented case of acute myeloproliferative disease in horses involving cells of erythroid lineage, but this condition should be considered a differential diagnosis for horses presenting with anaemia.

Evaluation of the equine respiratory system using physical examination and endoscopy.

Defining respiratory disease is not always easy in the horse because auscultation with accurate interpretation of lung sounds can be difficult. However, performing a thorough physical examination, including rebreathing auscultation and percussion of the thorax and sinuses, is very useful in elucidating the problem. Endoscopic examination of the upper respiratory system is also critical for definitively diagnosing certain conditions.

Lymphoproliferative and myeloproliferative disorders.

Nomenclature regarding neoplasia of the hematopoietic and lymphoid tissues in the horse is confusing. This article will clarify terminology, and discuss the individual lymphoproliferative and myeloproliferative disorders recognized in the horse. Diagnostic techniques that are useful in cases in which hematopoietic or lymphoid tissue neoplasia are suspected include histochemical staining profiles, bone marrow aspiration, and bone marrow biopsy.

Abdominal neoplasia (excluding urogenital tract).

Neoplasia of the equine gastrointestinal tract and abdominal organs occurs predominantly in geriatric horses, although lymphoma and hepatocellular carcinoma and a few other neoplasms can be found in young horses. This article discusses diagnostics that can be used in weight-loss situations, suspicious of neoplasia, as well as tumors themselves including clinical signs, diagnostic tools, histopathologic appearance, and management.