Hematologic reference intervals in Cynomolgus (Macaca fascicularis) monkeys.

BACKGROUND: Reference intervals are important aids for interpreting clinical pathology laboratory data especially in Cynomolgus monkey (Macaca fascicularis), the non-human primate species most widely used in biomedical research. The purpose of this study was to establish hematologic reference intervals for Cynomolgus according to the International Federation of Clinical Chemistry and Clinical and Laboratory Standards Institute guidelines using the databank at a primatology center. METHODS: Blood specimens from 272 healthy Cynomolgus imported from Mauritius, the Philippines and Vietnam, were analyzed. Reference intervals were established by nonparametric method. Effects of sex, age, body weight, and breeding origin were investigated. RESULTS: Hemoglobin, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration decreased slightly and mean corpuscular volume increased slightly with age. Lower red blood cell concentration, hemoglobin, and hematocrit were observed in monkeys from the Philippines. CONCLUSIONS: These hematology reference intervals, established according to international recommendations, can be used in settings using similar animals and analyzers.

[Quality management in intensive care medicine]. / Qualitätsmanagement in der Intensivmedizin.

Treatment of critical ill patients in the intensive care unit is tantamount to well-designed risk or quality management. Several tools of quality management and quality assurance have been developed in intensive care medicine. In addition to external quality assurance by benchmarking with regard to the intensive care medicine, peer review procedures have been established for external quality assurance in recent years. In the process of peer review of an intensive care unit (ICU), external physicians and nurses visit the ICU, evaluate on-site proceedings, and discuss with the managing team of the ICU possibilities for optimization. Furthermore, internal quality management in the ICU is possible based on the 10 quality indicators of the German Interdisciplinary Society for Intensive Care Medicine (DIVI, "Deutschen Interdisziplinären Vereinigung für Intensiv- und Notfallmedizin"). Thereby every ICU has numerous possibilities to improve their quality management system.

Comparison of measurements of canine plasma glucose, creatinine, urea, total proteins, alanine aminotransferase, and alkaline phosphatase obtained with the APOLOWAKO and Vitros 250 analyzers.

The APOLOWAKO is an entirely automatic benchtop biochemistry analyzer that uses stabilized liquid reagents. It was tested for canine blood and plasma glucose, creatinine, urea, total proteins, alanine aminotransferase, and alkaline phosphatase. The APOLOWAKO gave very similar results for whole blood and the corresponding plasma (n=32). Within-laboratory imprecision was below 2.2% and 5.8% for substrates and enzymes, respectively. Comparison of results with whole blood by APOLOWAKO and with the corresponding plasma by Vitros 250 (n=139) showed very good correlations. Passing-Bablok's regression slopes ranged from 0.83 to 1.12 and intercepts were close to zero, except for ALP where the results obtained by APOLOWAKO were approximately 1.5 times higher than by Vitros. The APOLOWAKO system can be a reliable instrument in veterinary practices where larger systems are not available but it should be further validated and reference intervals should be determined.

A multicentric retrospective study of serum/plasma urea and creatinine concentrations in dogs using univariate and multivariate decision rules to evaluate diagnostic efficiency.

BACKGROUND: Urea and creatinine are the most frequently used indirect markers in plasma and serum of glomerular filtration rate in dogs. Both have been shown to lack sensitivity but their diagnostic efficiency for the diagnosis of kidney disease has been minimally investigated. OBJECTIVE: The purpose of this retrospective study was to investigate the influence of possible factors of variation on both analytes and to determine whether specific decision rules should be drawn up for subpopulations of dogs. METHODS: The results of urea and creatinine measurements, breed, sex, age, and health status (healthy, renal disease, or nonrenal disease) of 3822 dogs were collected from the archives of 5 veterinary clinics. Data were analyzed with univariate and multivariate decision rules with and without adjustment. RESULTS: There were significant effects and interactions of almost all of the sources of variation. Slight improvements in diagnostic efficiency were obtained by adjusting the decision rules to these sources of variations. Univariate decision rules gave approximately the same diagnostic efficiency for urea and creatinine concentrations, with sensitivity and specificity in the range of 70% and 90%, respectively, using the upper limit of the reference interval as the threshold value. Multivariate decision rules provided only minor improvements in diagnostic efficiency. CONCLUSION: Simultaneous measurement of both urea and creatinine is of limited diagnostic value over the analysis of a single variable. Creatinine is the preferred analyte as it is affected by fewer extrarenal factors of variation.

Barrier function of the gut and multiple organ dysfunction after cardiac surgery.

We studied the influence of sequential involvement of the gastrointestinal (GI) tract on the development of multiple organ dysfunction (MOD) after cardiopulmonary bypass (CPB). One hundred and forty-six patients undergoing elective cardiac surgery were included in this prospective observational study. Standardized oral inert-sugar tests (sucrose, lactulose, mannitol, sucralose) were performed before and after CPB in different patients. Enzyme-linked immunosorbent assay of plasma levels of endotoxin core antibodies (EndoCAb) were performed peri-operatively. The functional mucosal surface was calculated from the amount of mannitol absorbed from the GI tract. Lower urine concentrations of absorbed mannitol were observed pre-operatively in patients developing MOD. In binary logistic regression this was an independent parameter. Decreased plasma concentrations of EndoCAb after surgery were seen in every patient, but were more significant in patients developing MOD. A reduced pre-operative functional mucosal surface may predict the early occurrence of MOD after surgery.

Establishment of the European College of Veterinary Clinical Pathology (ECVCP) and the current status of veterinary clinical pathology in Europe.

After 5 years of development, the European College of Veterinary Clinical Pathology (ECVCP) was formally recognized and approved on July 4, 2007 by the European Board of Veterinary Specialisation (EBVS), the European regulatory body that oversees specialization in veterinary medicine and which has approved 23 colleges. The objectives, committees, basis for membership, constitution, bylaws, information brochure and certifying examination of the ECVCP have remained unchanged during this time except as directed by EBVS. The ECVCP declared full functionality based on the following criteria: 1) a critical mass of 65 members: 15 original diplomates approved by the EBVS to establish the ECVCP, 37 de facto diplomates, 7 diplomates certified by examination, and 5 elected honorary members; 2) the development and certification of training programs, laboratories, and qualified supervisors for residents; currently there are 18 resident training programs in Europe; 3) administration of 3 annual board-certifying examinations thus far, with an overall pass rate of 70%; 4) European consensus criteria for assessing the continuing education of specialists every 5 years; 5) organization of 8 annual scientific congresses and a joint journal (with the American Society for Veterinary Clinical Pathology) for communication of scientific research and information; the College also maintains a website, a joint listserv, and a newsletter; 6) collaboration in training and continuing education with relevant colleges in medicine and pathology; 7) development and strict adherence to a constitution and bylaws compliant with the EBVS; and 8) demonstration of compelling rationale, supporting data, and the support of members and other colleges for independence as a specialty college. Formal EBVS recognition of ECVCP as the regulatory body for the science and practice of veterinary clinical pathology in Europe will facilitate growth and development of the discipline and compliance of academic, commercial diagnostic, and industry laboratories in veterinary clinical pathology. Future needs are in developing sponsorship for resident positions, increasing employment opportunities, increasing compliance with laboratory, training, and continuing education standards, and advancing relevant science and technology.

Stability of selected hematology variables in canine blood kept at room temperature in EDTA for 24 and 48 hours.

BACKGROUND: Most hematologic analyses are performed within a short time of blood sampling, but samples collected at the end of a week may have to be stored for up to 2 days. The stability of hematologic constituents is poorly documented. OBJECTIVE: The objective of this study was to compare the results of RBC, WBC and platelet counts, hemoglobin (Hgb) concentration, and MCV before and after storage of canine blood at room temperature for 24 and 48 hours. METHODS: One hundred fifty-two K3-EDTA canine blood specimens from 2 veterinary hospitals were analyzed within 4 hours of collection, then 24 and 48 hours later with a Coulter T540 hematology analyzer. Results were compared by Passing-Bablock agreement, difference plots, and according to their classification as normal or abnormal based on reference intervals. RESULTS: RBC count and Hgb concentration were stable for the duration of the study. Differences in WBC and platelet counts varied with the specimen, independently of the initial value. MCV increased consistently over the 2 days. However, only a few results were misclassified. CONCLUSION: Whole blood specimens stored for up to 2 days at room temperature are suitable for cell counts and Hgb measurement. However, potential variations have to be known to avoid misinterpretations, especially near the decision limits.

Passive containment and reverse remodeling by a novel textile cardiac support device.

BACKGROUND: Progressive remodeling and dilation of cardiac chambers is responsible in part for myocardial dysfunction in chronic heart failure. Preclinical studies with suitable animal models indicate that a passive cardiac constraint device can promote reverse remodeling, with improvement in cardiac function. We hypothesize that such a device could provide benefit for stable heart failure patients in New York Heart Association (NYHA) class II and III. METHODS AND RESULTS: From April 1999 to March 2000, 27 patients received Acorn's Cardiac Support Device (CSD) during an initial safety/feasibility study. In 11 patients, the only surgical measure was CSD placement. Most patients suffered from idiopathic cardiomyopathy; 4 were in NYHA class II, one was in class II/III, and 6 were in class III. All were stable on intensive medical treatment. The CSD, a textile polyester device, was fitted snugly around the heart during surgery. All patients survived surgery and recovered smoothly. Three months after surgery, 56% of patients were in NYHA class I, 33% were in class II, and 11% were in class II/III. Echocardiography showed an improvement in left ventricular ejection fraction from an average of 22% to 28% and 33% at 3 and 6 months, respectively. Simultaneously, the left ventricular end-diastolic dimension decreased from 74 mm to 68 mm and 65 mm, respectively. Mitral valve regurgitation (on a scale of 0 to 4+) decreased from 1.3 to 0.7 by 3 months. Quality-of-life indices correlated with the apparent reversal of ventricular remodeling. Preoperative cardiac medications remained virtually unchanged after implant. CONCLUSIONS: In the short- and intermediate-term, CSD implantation seems to ameliorate symptoms and improve cardiac and functional performance in heart failure patients. Worldwide randomized trials are currently underway.

Comparison of measurements of canine plasma creatinine, glucose, proteins, urea, alanine aminotransferase, and alkaline phosphatase obtained with Spotchem SP 4430 and Vitros 250 analyzers.

The suitability of the Spotchem 4430 benchtop biochemistry analyzer for canine blood samples was tested for creatinine, glucose, proteins, urea, alkaline phosphatases and alanine aminotransferase. Results obtained from whole blood and corresponding heparin plasma were identical except for proteins which were higher in plasma (n=10). Between series imprecision (n=10) was <5% for substrates and <10% for enzymes. Comparison of results from 100 Li-heparin samples with those measured with a Vitros 250 analyzer showed good correlation (r>0.93). The slopes of the Passing-Bablock's regression ranged from 0.90 to 1.20 and intercepts were low. The mean biases were low, except for creatinine for which the results obtained by Spotchem (Jaffe reaction) were about 20 micromol/L higher than with the Vitros (enzymatic reaction). The results of this study show that the Spotchem analyzer is suitable for use in canine whole blood or plasma when small numbers of tests are to be performed and large analyzers are not available.

[Quality assurance concepts in intensive care medicine]. / Qualitätssicherungskonzepte in der Intensivmedizin.

Intensive care medicine (ICM) is characterized by a high degree of complexity and requires intense communication and collaboration on interdisciplinary and multiprofessional levels. In order to achieve good quality of care in this environment and to prevent errors, a proactive quality and error management as well as a structured quality assurance system are essential. Since the early 1990s, German intensive care societies have developed concepts for quality management and assurance in ICM. In 2006, intensive care networks were founded in different states to support the implementation of evidence-based knowledge into clinical routine and to improve medical outcome, efficacy, and efficiency in ICM. Current instruments and concepts of quality assurance in German ICM include core intensive care data from the data registry DIVI REVERSI, quality indicators, peer review in intensive care, IQM peer review, and various certification processes. The first version of German ICM quality indicators was published in 2010 by an interdisciplinary and interprofessional expert commission. Key figures, indicators, and national benchmarks are intended to describe the quality of structures, processes, and outcomes in intensive care. Many of the quality assurance tools have proved to be useful in clinical practice, but nationwide implementation still can be improved.

Feasibility and influence of hTEE monitoring on postoperative management in cardiac surgery patients.

Monoplane hemodynamic TEE (hTEE) monitoring (ImaCor(®) ClariTEE(®)) might be a useful alternative to continuously evaluate cardiovascular function and we aimed to investigate the feasibility and influence of hTEE monitoring on postoperative management in cardiac surgery patients. After IRB approval we reviewed the electronic data of cardiac surgery patients admitted to our intensive care between 01/01/2012 and 30/06/2013 in a case-controlled matched-pairs design. Patients were eligible for the study when they presented a sustained hemodynamic instability postoperatively with the clinical need of an extended hemodynamic monitoring: (a) hTEE (hTEE group, n = 18), or (b) transpulmonary thermodilution (control group, n = 18). hTEE was performed by ICU residents after receiving an approximately 6-h hTEE training session. For hTEE guided hemodynamic optimization an institutional algorithm was used. The hTEE probe was blindly inserted at the first attempt in all patients and image quality was at least judged to be adequate. The frequency of hemodynamic examinations was higher (ten complete hTEE examinations every 2.6 h) in contrast to the control group (one examination every 8 h). hTEE findings, including five unexpected right heart failure and one pericardial tamponade, led to a change of current therapy in 89% of patients. The cumulative dose of epinephrine was significantly reduced (p = 0.034) and levosimendan administration was significantly increased (p = 0.047) in the hTEE group. hTEE was non-inferior to the control group in guiding norepinephrine treatment (p = 0.038). hTEE monitoring performed by ICU residents was feasible and beneficially influenced the postoperative management of cardiac surgery patients.

Urine gamma-glutamyl transferase in rat kidney toxicology: nephropathy by repeated injections of mercuric chloride. Effects of sodium selenite.

Groups of 5 male and 4 female Cobs CD rats weighing 250--350 g were injected intraperitoneally, daily for 15 days, with 5 mumol HgCl2/kg, 5 mumol Na2SeO3/kg, or (5 mumol HgCl2 + 5 mumol Na2SeO3)/kg in a 10 ml/kg vol. of saline. Control animals were injected with saline only. Injection of saline or sodium selenite produced neither modification of diuresis, nor of urine elimination of sodium, potassium, chloride, phosphates, urea, creatinine and gamma-glutamyl transferase (GGT). Injection of mercuric chloride induced a massive increase of urine GGT, diuresis and phosphaturia and a decrease of kaliuria and natriuria. Those effects reflect a kidney tubular lesion which seems to be more severe in males than in females. Injection of mixed sodium selenite and mercuric chloride or separate injection of both compounds had similar effects. In both sexes, urine GGT elimination was delayed and about 2 times lower than with HgCl2 alone. In females, the other urine parameters were almost normal whereas in males, diuresis and phosphaturia were slightly increased and kaliuria decreased. The observation of urine GGT elimination attests, in vivo, that sodium selenite decreases tubular toxicity of mercuric chloride and resulting kidney function disturbances.

Ethionine and methionine distribution and toxicity in the rat kidney.

Autoradiographic studies demonstrated that in the rat kidney radioactivity was localized mainly in the medulla in animals injected with [14C]ethionine, whereas it was distributed homogeneously throughout the whole parenchyma in rats given [14C]methionine. This difference of distribution was consistent with a difference in renal toxicity: a single i.p. dose (1 g/kg) of ethionine induced a slight but persistent (6 days) damage to kidney tubule cells evidenced by an increase of urinary GGT and slight disturbance of renal function, such damage was not observed with methionine.

Comparison of sodium and stannous fluoride nephrotoxicity.

Single i.p. injections of 0.5 mmol F-/kg and repeated i.p. injections of 0.25 mmol F-/kg as NaF or SnF2 to male rats showed that both compounds produced early lesions of kidney tubule demonstrated by an intense increase of urine gamma-glutamyl transferase (GGT). Disturbance of kidney function with an increase of diuresis and phosphaturia and a decrease of natriuria and kaliuria were more marked in SnF2-treated animals as was the decrease of urine GGT after a few days. These results indicate that tin nephrotoxicity adds to that of fluoride and antagonizes tubule regeneration.

Acute kidney toxicity of sodium fluoride in the rat.

Single i.p injection of 0, 0.05, 0.10, 0.25, 0.50 and 1.00 mmol NaF/kg to male rats induced a dose-related increase of urine gamma-glutamyl transferase (GGT) elimination on the first day for all doses higher or equal to 0.25 mmol NaF/kg. Kidney damage began between 2--4 h following the injection and lasted only 12 h for the 0.50 mmol NaF/kg dose. There was an increase of diuresis and of phosphaturia even at lower doses.

Acute kidney disturbances by lead acetate in the rat.

Four groups of 5 male and 5 female rats were dosed i.p. with 0, 0.05, 0.15 and 0.30 mmol Pb2+/kg as neutral acetate. A minimal kidney damage shown by an increased urinary GGt was only observed in males at the highest dose. In all animals and for all doses natriuria was significantly decreased on the first day (from the 4th hour). Such disturbances evoke mild tubular disturbances but glomerular disturbances may also be involved.

Protection against mercuric chloride nephrotoxicity by cold exposure in rats.

The influence of cold exposure (+ 1 degree C for 24 h) was studied in rats dosed i.p. with 0, 2.5 or 5.0 mumol HgCl2/kg. Cold exposure of controls caused an increased diuresis and solute elimination, except sodium, with almost no variations in urine alkaline phosphatase (ALP) and gammaglutamyl transferase (GGT). Proximal tubule brush border damage was demonstrated by a marked increase in ALP and GGT in HgCl2-dose animals at room temperature. Cold exposure protected against this kidney damage.

The effects of fluoride on animals and plants in the south Safi zone.

Fluoride pollution caused by the factories processing natural phosphates 10 km south of Safi affects animals and plants. Fluoride concentrations are 4-10 times higher in contaminated plants than in plants from the non-polluted areas. Fluoride levels of 700 ppm, 280 ppm, 75 ppm, 25 ppm, and 1.6 ppm were found in grass, forage, straw, barley caryopses and drinking water, respectively. The ingestion of polluted plants and the inhalation of fluoride (as gases and dusts) induce a high daily intake in animals which show important signs and lesions of dental fluorosis. Serious toxicity signs were also observed in plants.

Plasma potassium measurement with a new reagent carrier (Reflotron): comparison with ion-selective electrode results.

Potassium concentrations were measured in the plasma of 336 animals with a new reagent carrier (Reflotron; Boehringer Mannheim) K+ and with an ion-specific electrode system: results were highly correlated (r = 0.991; y = 0.993 x + 0.02) and day-to-day coefficient of variation of the new reagent measurements was lower than 2.5 per cent. This system offers a good alternative to the ion-selective electrode system for plasma potassium measurement in veterinary practice.

Plasma erythropoietin concentrations in dogs and cats: reference values and changes with anaemia and/or chronic renal failure.

Reference ranges of plasma erythropoietin concentration measured by immunoassay in 67 healthy cats and 40 healthy dogs were 1.9 to 22.9 mU ml-1 and 1.3 to 13.4 mU ml-1 respectively. Very significant increases of plasma erythropoietin concentration were observed in 22 cats and 32 dogs with anaemia without chronic renal failure (CRF), but 35 cats and 37 dogs with CRF had normal or moderately reduced erythropoietin concentrations. In cats there was almost no overlap of erythropoietin between the groups but in dogs there was a significant overlap. The measurement of plasma erythropoietin is therefore probably more useful in the diagnosis of anaemia in cats than in dogs, either with or without CRF.