[Urinary specific gravity--comparative measurements using reagent strips and refractometer in 340 morning urine samples]

The specific gravity of urine (SG) indicates the number and weight of solute particles in urine; its measurement is helpful in interpreting proteinuria detected by dipstick tests and in monitoring adequate hydration in patients with nephrolithiasis. Four methods for measuring SG or osmolality of urine are currently available (depression of the freezing-point, urometry, refractometry, cation exchange on a reagent strip). Using a recently developed reagent strip, we have measured SG in morning urines of 340 non-selected outpatients and compared the results with SG measurements by refractometry of the same urines. In 86.2% of all urines, a good positive correlation between SG measured by reagent strip and refractometry was noted (r = 0.913, p = 0.0001). In 13.8% of the urines, however, the SG measured by reagent strip deviated by more than +/- 5 from the value obtained by refractometry; in 90% of these urines, glucosuria (reagent strip values too low or too high), proteinuria (values too high), or bacteriuria/leukocyturia (values too low or too high) could be found. In alkaline urine (pH > 7.0), SG values obtained by reagent strip have to be corrected by +5.

PS-GANS: A Patient-Specific, Gravity Assisted Navigation System for Acetabular Cup Placement

In this paper we propose a new system that allows reliable acetabular cup placement when the THA is operated in lateral approach. Conceptually it combines the accuracy of computer-generated patient-specific morphology information with an easy-to-use mechanical guide, which effectively uses natural gravity as the angular reference. The former is achieved by using a statistical shape model-based 2D-3D reconstruction technique that can generate a scaled, patient-specific 3D shape model of the pelvis from a single conventional anteroposterior (AP) pelvic X-ray radiograph. The reconstructed 3D shape model facilitates a reliable and accurate co-registration of the mechanical guide with the patient’s anatomy in the operating theater. We validated the accuracy of our system by conducting experiments on placing seven cups to four pelvises with different morphologies. Taking the measurements from an image-free navigation system as the ground truth, our system showed an average accuracy of 2.1 ±0.7 o for inclination and an average accuracy of 1.2 ±1.4 o for anteversion.

Recombinant major urinary proteins of the mouse in specific IgE and IgG testing

Background: Recombinant allergens are preferred over natural allergen extracts in measuring antibodies. We tested the use of recombinant variants of the major mouse allergen Mus m 1 in detection of mouse-specific antibodies in sera of laboratory animal workers and children. Methods: Six recombinant major urinary proteins (MUPs) were produced and antibody-binding capacity was compared to natural Mus m 1 and to mouse urine extract. In a specific subset, cross-reactivity of MUP with Mus m 1 and between the different recombinant MUPs was determined. Results: For IgE antibodies, MUP8 showed high cross-reactivity with Mus m 1. MUP8-specific IgE was found in 55% of the mouse urine IgE-positive sera. Specific IgG and IgG4 antibodies against natural Mus m 1 correlated strongly with antibodies against recombinant MUP8 and were cross-reactive. IgG4 levels against MUP8 and mouse urine extract correlated, but detection of mouse urine-specific IgG4 in the absence of MUP-specific IgG4 was not uncommon. Cross-reactivity of IgG antibodies between MUP8 and Mus m 1 as well as between the different MUPs was high and inhibition varied between 54 and 99%. Conclusion: The mouse allergen Mus m 1 can be replaced in antibody testing by recombinant MUP8. Other MUPs, except MUP4, are interchangeable with MUP8. However, mouse urine extract showed better detection of both mouse-specific IgE and IgG4 levels. Other components in the mouse urine, like mouse albumin and other yet unidentified components, also induce IgE and IgG(4) antibodies.

Empty sella syndrome, hyperadrenocorticism and megaoesophagus in a dachshund

A five-year-old, entire, male dachshund was presented with a five day history of hypersalivation and regurgitation as well as polyuria and polydipsia for several months. Chest radiographs demonstrated megaoesophagus and aspiration pneumonia. Furthermore, hyperadrenocorticism was demonstrated by means of elevations in levels of serum alkaline phosphatase and cholesterol, decreased urinary specific gravity, increased response to adrenocorticotropic hormone stimulation, insufficient suppression of the post-dexamethasone plasma cortisol levels, an increased endogenous adrenocorticotropic hormone concentration and bilaterally enlarged adrenal glands on abdominal ultrasound. The dog became severely dyspnoeic and was euthanased after magnetic resonance imaging was performed. The magnetic resonance imaging and necropsy revealed the sellar region mainly filled with fluid, with only small tissue remnants, a condition defined as empty sella syndrome in human medicine. To the author's knowledge, this is the first dog described with empty sella syndrome and only the second dog described with hyperadrenocorticism secondary to ectopic adrenocorticotropic hormone production. However, the association between empty sella syndrome and hyperadrenocorticism may be no more than incidental.

UPLC-MS-based urine metabolomics reveals indole-3-lactic acid and phenyllactic acid as conserved biomarkers for alcohol-induced liver disease in the Ppara-null mouse model

Since the development and prognosis of alcohol-induced liver disease (ALD) vary significantly with genetic background, identification of a genetic background-independent noninvasive ALD biomarker would significantly improve screening and diagnosis. This study explored the effect of genetic background on the ALD-associated urinary metabolome using the Ppara-null mouse model on two different backgrounds, C57BL/6 (B6) and 129/SvJ (129S), along with their wild-type counterparts. Reversed-phase gradient UPLC-ESI-QTOF-MS analysis revealed that urinary excretion of a number of metabolites, such as ethylsulfate, 4-hydroxyphenylacetic acid, 4-hydroxyphenylacetic acid sulfate, adipic acid, pimelic acid, xanthurenic acid, and taurine, were background-dependent. Elevation of ethyl-β-d-glucuronide and N-acetylglycine was found to be a common signature of the metabolomic response to alcohol exposure in wild-type as well as in Ppara-null mice of both strains. However, increased excretion of indole-3-lactic acid and phenyllactic acid was found to be a conserved feature exclusively associated with the alcohol-treated Ppara-null mouse on both backgrounds that develop liver pathologies similar to the early stages of human ALD. These markers reflected the biochemical events associated with early stages of ALD pathogenesis. The results suggest that indole-3-lactic acid and phenyllactic acid are potential candidates for conserved and pathology-specific high-throughput noninvasive biomarkers for early stages of ALD.

Role of DNA methylation in the tissue-specific expression of the CYP17A1 gene for steroidogenesis in rodents

The CYP17A1 gene is the qualitative regulator of steroidogenesis. Depending on the presence or absence of CYP17 activities mineralocorticoids, glucocorticoids or adrenal androgens are produced. The expression of the CYP17A1 gene is tissue as well as species-specific. In contrast to humans, adrenals of rodents do not express the CYP17A1 gene and have therefore no P450c17 enzyme for cortisol production, but produce corticosterone. DNA methylation is involved in the tissue-specific silencing of the CYP17A1 gene in human placental JEG-3 cells. We investigated the role of DNA methylation for the tissue-specific expression of the CYP17A1 gene in rodents. Rats treated with the methyltransferase inhibitor 5-aza-deoxycytidine excreted the cortisol metabolite tetrahydrocortisol in their urine suggesting that treatment induced CYP17 expression and 17alpha-hydroxylase activity through demethylation. Accordingly, bisulfite modification experiments identified a methylated CpG island in the CYP17 promoter in DNA extracted from rat adrenals but not from testes. Both methyltransferase and histone deacetylase inhibitors induced the expression of the CYP17A1 gene in mouse adrenocortical Y1 cells which normally do not express CYP17, indicating that the expression of the mouse CYP17A1 gene is epigenetically controlled. The role of DNA methylation for CYP17 expression was further underlined by the finding that a reporter construct driven by the mouse -1041 bp CYP17 promoter was active in Y1 cells, thus excluding the lack of essential transcription factors for CYP17 expression in these adrenal cells.

Earth gravity field recovery using GPS, GLONASS, and SLR satellites

The time variable Earth’s gravity field provides the information about mass transport within the system Earth, i.e., the relationship of mass transport between atmosphere, oceans, and land hydrology. We recover the low-degree parameters of the time variable gravity field using microwave observations from GPS and GLONASS satellites and from SLR data to five geodetic satellites, namely LAGEOS-1/2, Starlette, Stella, and AJISAI. GPS satellites are particularly sensitive to specific coefficients of the Earth's gravity field, because of the deep 2:1 orbital resonance with Earth rotation (two revolutions of the GPS satellites per sidereal day). The resonant coefficients cause, among other, a “secular” drift (actually periodic variations of very long periods) of the semi-major axes of up to 5.3 m/day of GPS satellites. We processed 10 years of GPS and GLONASS data using the standard orbit models from the Center of Orbit Determination in Europe (CODE) with a simultaneous estimation of the Earth gravity field coefficients and other parameters, e.g., satellite orbit parameters, station coordinates, Earth rotation parameters, troposphere delays, etc. The weekly GNSS gravity solutions up to degree and order 4/4 are compared to the weekly SLR gravity field solutions. The SLR-derived geopotential coefficients are compared to monthly GRACE and CHAMP results.

Protein profiling of organic stone matrix and urine from dogs with urolithiasis

Two-thirds of the organic matrix in urinary stones consists of proteins. Their relationship to calculogenesis remains controversial with regard to their effect as inhibitors or promoters during stone formation. The purpose of the present study was to determine the differences in peptide and protein pattern between the urine of stone formers (n = 23) and control dogs (n = 12), as well as between organic matrix of different urinary stones (struvite n = 11, calcium oxalate n = 8, uric acid n = 4) using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Specific differences in protein and peptide profiles were found in the organic matrix of different mineral compositions. Characteristic differences were also found in urinary peptide and protein pattern especially in molecular masses below 20 kDa between affected and healthy dogs. Based on the obtained molecular masses they were in some cases tentatively identified as proteins that are known to be involved in stone formation in humans. The study shows that in dogs, specific-urinary peptides and proteins might be associated with urolithiasis. It indicates the importance to further characterize those proteins for possible diagnostic purposes in prognosis and therapy

Protein profiling of urine from dogs with renal disease using ProteinChip analysis

Measurement of total urinary proteins in individuals that tested positive by urinary dipstick is a typical method for assessing the presence of potentially serious renal disorders. In the absence of such overt proteinuria, however, measurement of specific urinary proteins may be useful in the diagnosis of nephropathies and may provide greater insight into the pathogenesis. The urine of 28 dogs (16 with renal disease and 12 healthy) was evaluated to determine whether specific low-molecular-weight proteins or the pattern of protein excretion could also be used as a marker of tubular dysfunction in dogs. Specific proteins were assessed by immunological methods, whereas protein profiles were determined by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (MS). In particular, changes in the excretion of retinol-binding protein (RBP) and Tamm-Horsfall protein (THP) appear to be of clinical relevance in the diagnosis of canine kidney diseases. The pattern of urinary protein and peptides revealed specific changes in abundance in dogs with renal disease at molecular masses (kD) of 11.58, 12.41, 12.60, 14.58, 20.95 (RBP), 27.85, and 65.69 (albumin). In conclusion, comparable proteins as in humans might be used as urinary markers for proximal (RBP) and distal (THP) tubular dysfunction in dogs. Surface-enhanced laser desorption/ionization time-of-flight MS is a promising tool for the study of kidney physiology and pathophysiology and might aid in the discovery of new biomarkers of renal disease.

Detection and quantification of leptospires in urine of dogs: a maintenance host for the zoonotic disease leptospirosis.

Leptospirosis is a global zoonotic disease. Pathogenic Leptospira species, the causative agent of leptospirosis, colonize the renal tubules of chronically infected maintenance hosts such as dogs, rats and cattle. Maintenance hosts typically remain clinically asymptomatic and shed leptospires into the environment via urine. In contrast, accidental hosts such as humans can suffer severe acute forms of the disease. Infection results from direct contact with infected urine or indirectly, through contaminated water sources. In this study, a quantitative real-time PCR specific for lipL32 was designed to detect the urinary shedding of leptospires from dogs. The sensitivity and specificity of the assay was evaluated using both a panel of pathogenic Leptospira species and clinical microbial isolates, and samples of urine collected from experimentally infected rats and non-infected controls. The lower limit of detection was approximately 3 genome equivalents per reaction. The assay was applied to canine urine samples collected from local dog sanctuaries and the University Veterinary Hospital (UVH) at University College Dublin. Of 525 canine urine samples assayed, 37 were positive, indicating a prevalence of urinary shedding of leptospires of 7.05%. These results highlight the need to provide effective canine vaccination strategies and raise public health awareness.

New anthropometry-based age- and sex-specific reference values for urinary 24-hour creatinine excretion based on the adult Swiss population.

BACKGROUND Urinary creatinine excretion is used as a marker of completeness of timed urine collections, which are a keystone of several metabolic evaluations in clinical investigations and epidemiological surveys. The current reference values for 24-hour urinary creatinine excretion rely on observations performed in the 1960s and 1970s in relatively small and mostly selected groups, and may thus poorly fit to the present-day general European population. The aim of this study was to establish and validate anthropometry-based age- and sex-specific reference values of the 24-hour urinary creatinine excretion on adult populations with preserved renal function. METHODS We used data from two independent Swiss cross-sectional population-based studies with standardised 24-hour urinary collection and measured anthropometric variables. Only data from adults of European descent, with estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73 m(2) and reported completeness of the urinary collection were retained. A linear regression model was developed to predict centiles of the 24-hour urinary creatinine excretion in 1,137 participants from the Swiss Survey on Salt and validated in 994 participants from the Swiss Kidney Project on Genes in Hypertension. RESULTS The mean urinary creatinine excretion was 193 ± 41 μmol/kg/24 hours in men and 151 ± 38 μmol/kg/24 hours in women in the Swiss Survey on Salt. The values were inversely correlated with age and body mass index (BMI). Based on current reference values (177 to 221 μmol/kg/24 hours in men and 133 to 177 μmol/kg/24 hours in women), 56% of the urinary collections in the whole population and 67% in people >60 years old would have been considered as inaccurate. A linear regression model with sex, BMI and age as predictor variables was found to provide the best prediction of the observed values and showed a good fit when applied to the validation population. CONCLUSIONS We propose a validated prediction equation for 24-hour urinary creatinine excretion in the general European population, based on readily available variables such as age, sex and BMI, and a few derived normograms to ease its clinical application. This should help healthcare providers to interpret the completeness of a 24-hour urine collection in daily clinical practice and in epidemiological population studies.

The impact of common versus separate estimation of orbit parameters on GRACE gravity field solutions

Gravity field parameters are usually determined from observations of the GRACE satellite mission together with arc-specific parameters in a generalized orbit determination process. When separating the estimation of gravity field parameters from the determination of the satellites’ orbits, correlations between orbit parameters and gravity field coefficients are ignored and the latter parameters are biased towards the a priori force model. We are thus confronted with a kind of hidden regularization. To decipher the underlying mechanisms, the Celestial Mechanics Approach is complemented by tools to modify the impact of the pseudo-stochastic arc-specific parameters on the normal equations level and to efficiently generate ensembles of solutions. By introducing a time variable a priori model and solving for hourly pseudo-stochastic accelerations, a significant reduction of noisy striping in the monthly solutions can be achieved. Setting up more frequent pseudo-stochastic parameters results in a further reduction of the noise, but also in a notable damping of the observed geophysical signals. To quantify the effect of the a priori model on the monthly solutions, the process of fixing the orbit parameters is replaced by an equivalent introduction of special pseudo-observations, i.e., by explicit regularization. The contribution of the thereby introduced a priori information is determined by a contribution analysis. The presented mechanism is valid universally. It may be used to separate any subset of parameters by pseudo-observations of a special design and to quantify the damage imposed on the solution.

Gestation-specific reference intervals for comprehensive spot urinary steroid hormone metabolite analysis in normal singleton pregnancy and 6 weeks postpartum

BACKGROUND: Normal pregnancy depends on pronounced adaptations in steroid hormone concentrations. Although in recent years, the understanding of these hormones in pregnancy has improved, the interpretation is hampered by insufficient reference values. Our aim was to establish gestation-specific reference intervals for spot urinary steroid hormone levels in normal singleton pregnancies and 6 weeks postpartum. METHODS: Cross-sectional multicentre observational study. Women recruited between 2008 and 2013 at 3 University Hospitals in Switzerland (Bern), Scotland (Glasgow) and Austria (Graz). Spot urine was collected from healthy women undergoing a normal pregnancy (age, 16-45 years; mean, 31 years) attending routine antenatal clinics at gestation weeks 11, 20, and 28 and approximately 6 weeks postpartum. Urine steroid hormone levels were analysed using gas-chromatography mass spectrometry. Creatinine was also measured by routine analysis and used for normalisation. RESULTS: From the results, a reference interval was calculated for each hormone metabolite at each trimester and 6 weeks postpartum. Changes in these concentrations between trimesters and postpartum were also observed for several steroid hormones and followed changes proposed for index steroid hormones. CONCLUSIONS: Normal gestation-specific reference values for spot urinary steroid hormones throughout pregnancy and early postpartum are now available to facilitate clinical management and research approaches to steroid hormone metabolism in pregnancy and the early postpartum period.