[Laboratory tests for kidney disease]. / Labordiagnostik zum Nachweis einer Nierenerkrankung.

Kidney diseases are among the most frequently reported diseases with a poor prognosis that are diagnosed too late. According to current Kidney Disease Improving Global Outcomes (KDIGO) guidelines, diagnosis and risk stratification are mainly based on functional markers (creatinine and cystatin C), which are used to determine the estimated glomerular filtration rate (eGFR) and the analysis of urinary albumin excretion as a marker of kidney damage. These methods have limitations that can complicate the interpretation of the results and can lead to a delay of the diagnosis as well as to a misinterpretation of the prognosis. Therefore, new damage markers are required that sensitively and specifically detect kidney damage and enable targeted treatment. Urinalysis complements the laboratory diagnostic spectrum of diseases of the kidneys and urinary tract. It is mainly used for screening and provides important information on localization (renal/postrenal) and differentiation of kidney diseases (glomerular/tubulointerstitial).

Doubling immunochemistry laboratory testing efficiency with the cobas e 801 module while maintaining consistency in analytical performance.

OBJECTIVES: The new immunochemistry cobas e 801 module (Roche Diagnostics) was developed to meet increasing demands on routine laboratories to further improve testing efficiency, while maintaining high quality and reliable data. DESIGN AND METHODS: During a non-interventional multicenter evaluation study, the overall performance, functionality and reliability of the new module was investigated under routine-like conditions. It was tested as a dedicated immunochemistry system at four sites and as a consolidator combined with clinical chemistry at three sites. RESULTS: We report on testing efficiency and analytical performance of the new module. Evaluation of sample workloads with site-specific routine request patterns demonstrated increased speed and almost doubled throughput (maximal 300 tests per h), thus revealing that one cobas e 801 module can replace two cobas e 602 modules while saving up to 44% floor space. Result stability was demonstrated by QC analysis per assay throughout the study. Precision testing over 21 days yielded excellent results within and between labs, and, method comparison performed versus the cobas e 602 module routine results showed high consistency of results for all assays under study. In a practicability assessment related to performance and handling, 99% of graded features met (44%) or even exceeded (55%) laboratory expectations, with enhanced reagent management and loading during operation being highlighted. CONCLUSION: By nearly doubling immunochemistry testing efficiency on the same footprint as a cobas e 602 module, the new module has a great potential to further consolidate and enhance laboratory testing while maintaining high quality analytical performance with Roche platforms.

Particle characterisation and cytokine expression in failed small-diameter metal-on-metal total hip arthroplasties.

The peri-prosthetic tissue response to wear debris is complex and influenced by various factors including the size, area and number of particles. We hypothesised that the 'biologically active area' of all metal wear particles may predict the type of peri-prosthetic tissue response. Peri-prosthetic tissue was sampled from 21 patients undergoing revision of a small diameter metal-on-metal (MoM) total hip arthroplasty (THA) for aseptic loosening. An enzymatic protocol was used for tissue digestion and scanning electron microscope was used to characterise particles. Equivalent circle diameters and particle areas were calculated. Histomorphometric analyses were performed on all tissue specimens. Aspirates of synovial fluid were collected for analysis of the cytokine profile analysis, and compared with a control group of patients undergoing primary THA (n = 11) and revision of a failed ceramic-on-polyethylene arthroplasty (n = 6). The overall distribution of the size and area of the particles in both lymphocyte and non-lymphocyte-dominated responses were similar; however, the subgroup with lymphocyte-dominated peri-prosthetic tissue responses had a significantly larger total number of particles. 14 cytokines (interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17, interferon (IFN)-γ, and IFN-gamma-inducible protein 10), chemokines (macrophage inflammatory protein (MIP)-1α and MIP-1ß), and growth factors (granulocyte macrophage colony stimulating factor (GM-CSF) and platelet derived growth factor) were detected at significantly higher levels in patients with metal wear debris compared with the control group. Significantly higher levels for IL-1ß, IL-5, IL-10 and GM-CSF were found in the subgroup of tissues from failed MoM THAs with a lymphocyte-dominated peri-prosthetic response compared with those without this response. These results suggest that the 'biologically active area' predicts the type of peri-prosthetic tissue response. The cytokines IL-1ß, IL-5, IL-10, and GM-CSF are associated with lymphocyte-dominated tissue responses from failed small-diameter MoM THA.

Impact of proton pump inhibitor use on magnesium homoeostasis: a cross-sectional study in a tertiary emergency department.

BACKGROUND: To date, the use of proton pump inhibitors (PPIs) has been associated with a low risk of hypomagnesaemia and associated adverse outcomes. We hypothesised that a better risk estimate could be derived from a large cohort of outpatients admitted to a tertiary emergency department (ED). METHODS: A cross-sectional study was performed in 5118 patients who had measurements of serum magnesium taken on admission to a large tertiary care ED between January 2009 and December 2010. Hypomagnesaemia was defined as a serum magnesium concentration < 0.75 mmol/l. Demographical data, serum electrolyte values, data on medication, comorbidities and outcome with regard to length of hospital stay and mortality were analysed. RESULTS: Serum magnesium was normally distributed where upon 1246 patients (24%) were hypomagnesaemic. These patients had a higher prevalence of out-of-hospital PPI use and diuretic use when compared with patients with magnesium levels > 0.75 mmol/l (both p < 0.0001). In multivariable regression analyses adjusted for PPIs, diuretics, renal function and the Charlson comorbidity index score, the association between use of PPIs and risk for hypomagnesaemia remained significant (OR = 2.1; 95% CI: 1.54-2.85). While mortality was not directly related to low magnesium levels (p = 0.67), the length of hospitalisation was prolonged in these patients even after adjustment for underlying comorbid conditions (p < 0.0001). CONCLUSION: Use of PPIs predisposes patients to hypomagnesaemia and such to prolonged hospitalisation irrespective of the underlying morbidity, posing a critical concern.

Treatment of severe, nonfulminant acute hepatitis B with lamivudine vs placebo: a prospective randomized double-blinded multicentre trial.

Acute hepatitis B virus (aHBV) infection can lead to fulminant liver failure, which likely is prevented by early lamivudine therapy. Even nonfulminant but severe acute hepatitis B can lead to significant morbidity and impaired quality of life. Therefore, lamivudine was evaluated in patients with severe aHBV in a placebo-controlled trial. Patients with severe aHBV infection (ALT >10× ULN, bilirubin >85 µm, prothrombin time >50%) were prospectively treated with lamivudine 100 mg/day or with placebo within 8 days after the diagnosis. The primary end point was time to bilirubin <34.2 µm. Secondary end points were time to clear HBsAg and HBV-DNA, development of anti-HBs and normalization of ALT. Eighteen cases were randomized to lamivudine, 17 to placebo. 94% of patients were hospitalized. No individual progressed to hepatic failure; all but one patient achieved the primary end point. Due to smaller than expected patient numbers, all study end points did not become statistically significant between treatment arms. Median time end points [in days] were bilirubin <34.2 µm (26.5 vs 32), ALT normalization (35 vs 48) and HBsAg clearance (48 vs 67) referring to earlier recovery under lamivudine, in contrast to loss of HBV-DNA (62 vs 54) and development of anti-HBs (119 vs 109). In all but two patients (one in every group), HBsAg clearance was reached in the study. Adverse events occurred more frequently during lamivudine therapy, but did not reach statistical significance. Lamivudine may ameliorate severe aHBV infection, but limited patient numbers prevented definite conclusions.

Phenotypic and genetic variation in leptin as determinants of weight regain.

AIMS: Over 75% of obese subjects fail to maintain their weight following weight loss interventions. We aimed to identify phenotypic and genetic markers associated with weight maintenance/regain following a dietary intervention. SUBJECTS AND METHODS: In the 2-year Dietary Intervention Randomized Controlled Trial, we assessed potential predictors for weight changes during the 'weight loss phase' (0-6 months) and the 'weight maintenance/regain phase' (7-24 months). Genetic variation between study participants was studied using single-nucleotide polymorphisms in the leptin gene (LEP). RESULTS: Mean weight reduction was -5.5% after 6 months, with a mean weight regain of 1.2% of baseline weight during the subsequent 7-24 months. In a multivariate regression model, higher baseline high-molecular-weight adiponectin was the only biomarker predictor of greater success in 0- to 6-month weight loss (ß = -0.222, P-value = 0.044). In a multivariate regression model adjusted for 6-month changes in weight and various biomarkers, 6-month plasma leptin reduction exhibited the strongest positive association with 6-month weight loss (ß = 0.505, P-value < 0.001). Conversely, 6-month plasma leptin reduction independently predicted weight regain during the following 18 months (ß = -0.131, P-value < 0.013). Weight regain was higher among participants who had a greater (top tertiles) 6-month decrease in both weight and leptin (+3.4% (95% confidence interval 2.1-4.8)) as compared with those in the lowest combined tertiles (+0.2% (95% confidence interval -1.1 to 1.4)); P-value < 0.001. Weight regain was further significantly and independently associated with genetic variations in LEP (P = 0.006 for both rs4731426 and rs2071045). Adding genetic data to the phenotypic multivariate model increased its predictive value for weight regain by 34%. CONCLUSION: Although greater reduction in leptin concentrations during the initial phase of a dietary intervention is associated with greater weight loss in the short term, plasma leptin reduction, combined with the degree of initial weight loss and with genetic variations in the LEP gene, constitutes a significant predictor of subsequent long-term weight regain.

Multicenter evaluation of the first automated Elecsys sFlt-1 and PlGF assays in normal pregnancies and preeclampsia.

OBJECTIVES: Performance evaluation of Elecsys sFlt-1 and PlGF assays. DESIGN AND METHODS: Within-, between-run, total imprecision, functional sensitivity, inter-laboratory comparison, method comparison and lot-to-lot reproducibility were evaluated. RESULTS: Within- and between-run CVs were below 4% for sFlt-1 >60 and PlGF > 20 pg/mL. Total imprecision CVs were below 4.3%. Functional sensitivity was < 5 pg/mL. Inter-laboratory CVs were <5%. Elecsys correlated well with Quantikine VEGF-R1 (r=0.960) and PlGF (r=0.968). Lot-to-lot comparisons yielded highly correlated results (r>0.999). In healthy pregnancies, the median levels of sFlt-1 remained constant in first (1107 pg/mL) and second trimesters (1437 pg/mL) but increased in the third trimester (2395 pg/mL), while median PlGF levels increased in the first (30 pg/mL) and second trimesters (279 pg/mL) and peaked at 29 to 32 weeks (626 pg/mL) and decreased thereafter (340 pg/mL). The sFlt-1/PlGF ratio is highest in the first trimester (median: 28) but remained constant in the second (median: 4.7) and third trimesters (median: 5.1). In PE/HELPP samples matched for gestational age the sFlt-1 levels were significantly higher (6894-34,624 pg/mL), whereas PlGF levels were lower (9.2-80 pg/mL) and the median sFlt-1/PlGF ratio is much higher (461; range: 121-2614) than in apparently healthy pregnancies (3.6; range: 0.3-105). CONCLUSION: The new Roche Elecsys sFlt-1 and PlGF immunoassay showed excellent precision and reliability. There was a clear difference in the Elecsys sFlt-1/PlGF ratio between samples obtained from women with apparently normal pregnancy at the time of blood collection and those diagnosed with PE/HELLP at the same age of gestation.

Body weight and oral contraceptives are the most important modulators of serum CRP levels.

BACKGROUND: C-reactive protein (CRP) levels are modulated by endogenous and exogenous factors independently of inflammation. The present study investigated the impact of oral contraceptives, endogenous oestrogens, age, gender, smoking, body mass index (BMI) and lipid levels on CRP concentrations in a healthy collective. METHODS: Highly sensitive CRP, total cholesterol, HDL-cholesterol and LDL-cholesterol levels were measured in 850 blood donors (438 M, 412 F); 227 women in this group used oral contraceptive formulations (OC). Additionally, serum samples from 58 women undergoing in vitro fertilization cycles (IVF) were tested for CRP. Results. The 97.5th percentile of CRP levels of the blood donors was 4.91 mg/L in men, 7.52 mg/L in OC non-users and 11.95 mg/L in OC users. Overweight gives a 2-fold increase of median CRP levels in men and women. The combination of overweight and OC use in women resulted in 6-fold median CRP levels. Age, smoking and lipid levels were influencing factors of lower significance. In IVF patients the elevated oestradiol levels had no influence on CRP concentrations in multivariance analysis. CONCLUSION: The diagnostic and predictive value of CRP levels is most affected by BMI and oral contraceptive use, which suggests the need for further investigations into the role of CRP modulating factors in monitoring infectious diseases.

Glycoprotein IIb/IIIa inhibitor-induced thrombocytopenia: diagnosis and treatment.

Thrombocyte glycoprotein IIb/IIIa inhibitors prevent fibrinogen binding and thereby thrombocyte aggregation. The inhibition of thrombocyte activation at the damaged coronary plaque is the target of the new therapeutic strategies in treating acute coronary syndrome. This reduces the ischemic complications associated with the non-STelevation myocardial infarction (NSTEMI) and percutaneous coronary intervention (PCI). Thrombocytopenia is a known complication of glycoprotein (GP) IIb/IIIa inhibitors. Although, in general, GP IIb/IIIa inhibitor-induced thrombocytopenia is a harmless side effect which responds readily to thrombocyte transfusion, it can occasionally be a very serious complication associated with serious bleeding. In addition patients developing thrombocytopenia have unfavorable outcome (e.g., death, myocardial infarction, bypass surgery or additional PCI) in comparison to patients without thrombocytopenia. Advanced age (> 65 years), low BMI and a low initial thrombocyte count (<180,000/microl) are independent risk factors of thrombocytopenia. The risk of bleeding is higher with this form of thrombocytopenia not only due to the low thrombocyte count but also to the impaired function of the remaining thrombocytes. It is important to closely monitor platelet count during GP IIb/IIIa antagonist treatment. Platelet count monitoring two, six, twelve and 24 hour after starting the treatment reveals most cases of acute thrombocytopenia. Side effects can be avoided by the early discontinuation of the GP IIb/IIIa antagonist treatment. This article reviews the diagnosis and treatment of glycoprotein IIb/IIIa inhibitor-induced thrombocytopenia and summarizes the differential diagnosis from heparin-induced thrombocytopenia and laboratory-related pseudothrombocytopenia.

[The "incorrect" laboratory result. II: Common misinterpretations of laboratory results]. / Der "fehlerhafte" Laborbefund. Teil 2: Häufige Ursachen von Fehlinterpretationen labormedizinischer Befunde.

In the second part of our review the most frequent misinterpretations of laboratory results in the daily clinical practise are discussed. Special attention has been given to frequent misinterpretations in the analysis of electrolytes, enzymes and hormones in plasma/serum (pseudohyperkalemia, macroenzymes, macroprolactinemia). Misinterpretations of the testing of blood gases, serum glucose, lipid concentrations, and calcium are described in greater detail. In addition, potential errors in the urinanalysis and the importance of adequate sampling of blood specimens for coagulation testing are described. The hematological results can be misinterpreted in the presence of EDTA-induced pseudothrombocytenia and of irregular immunoglobulines. Immunological methods themselves can lead to misinterpretations of the laboratory result, e. g. caused by the high dose hook effect and interferences in the presence of rheumatoid factor or HAMA. Finally clinical relevant errors in the therapeutic drug monitoring are discussed which are associated with the limited specificity of the antibodies in the commonly used immunological tests.

[The incorrect laboratory result. Part 1: Pre- and postanalytical phase]. / Der "fehlerhafte" Laborbefund Teil 1: Fehlerquellen der prä- und postanalytischen Phase.

Laboratory results play a key role in the diagnostic procedure, the decision of treatment and the follow up of diseases. A high validity of the laboratory result is an important precondition for the efficacy in clinical medicine. Analytical standards have been developed under strong quality control criteria, however, there are no sufficiently defined standards for the pre- and postanalytical phase in laboratory diagnostics. Thus, most of laboratory errors are caused by pre- and postanalytical mistakes. The competent knowledge of possible sources for laboratory errors is a critical precondition for their avoidance. Diagnostic sensitivity and specificity play an important role for the choice of a laboratory test, whereas the predictive value should be considered for the medical relevance of the test result. In addition, many interference factors, which may influence the results of the laboratory tests have to be considered as age, sex, race, lifestyle, drugs, pregnancy, specimen collection, quality and handling as well as special factors, which may influence the complex of immunological and molecular diagnostics.

Human renal fibroblasts derived from normal and fibrotic kidneys show differences in increase of extracellular matrix synthesis and cell proliferation upon angiotensin II exposure.

Angiotensin II (Ang II) as a vasoactive hormone may be involved in progressive renal interstitial fibrosis. We investigated the influence of Ang II on cell proliferation and synthesis of extracellular matrix (collagen I, III and fibronectin) in human renal fibroblasts derived from normal (TK 173 cell line) and fibrotic (TK 188 cell line) kidneys which possess both Ang II type l and type 2 (AT1 and AT2) receptors. Incubation of the cells with Ang II increased the cell proliferation and the synthesis of extracellular matrix significantly in both cell lines. However, proliferation and extracellular matrix synthesis showed a greater increase in the cells derived from the fibrotic kidney. The Ang II mediated effect on cell proliferation and extracellular matrix synthesis was diminished in the presence of the AT1 receptor blocker losartan in both cell lines. No inhibition was observed using the AT2 receptor blocker PD123319. Ang II induced cell proliferation could be completely inhibited by incubation with human TGF-beta1 antibody. Incubation with Ang II did not affect TGF beta 1 production but in untreated cells TGF-beta 1 content was higher in the cells derived from the fibrotic kidney. This might be the reason for the more sensitive reaction on exposure to Ang II.

Polarized function of thick ascending limbs of Henle cells in osmoregulation.

BACKGROUND: Organic osmolytes are necessary for osmoregulation in mammalian kidney. Since renal epithelial cells in many cases possess specific mechanisms both for uptake and osmotically regulated release, we investigated their localization in polarized cells. METHODS: An immortalized epithelial cell line derived from the thick ascending limb of Henle's loop (TALH) was used to examine the transport characteristics of the apical and basolateral plasma membranes for osmotic regulation of organic osmolytes. Cells were cultured on filters in a two-compartment chamber. RESULTS: In culture under hypertonic conditions the TALH cells accumulated in the following balance: sorbitoverline> betaine = myo-inositoverline> glycerophosphoryl choline (GPC). When extracellular osmolarity was decreased, then sorbitol was released on the apical side, whereas betaine and myo-inositol efflux occurred on the basolateral side. GPC release showed no preference of either side. Taurine did not seem to be necessary for osmoregulation under these conditions. Osmotically regulated myo-inositol and betaine uptake was located on the apical side, and choline uptake took place on both sides equally. CONCLUSION: These results show that in renal epithelial cells, both osmotically induced release and the uptake of organic osmolytes are divided between the apical and the basolateral sides. This might be important for volume regulation.

Evidence for a sorbitol transport system in immortalized human renal interstitial cells.

Sorbitol plays a major role in the maintenance of cell volume and functional integrity of several renal cells. Sorbitol synthesis takes place in inner collecting duct cells, whereas sorbitol dehydrogenase activity, which catalyzes the degradation of sorbitol to fructose, could mainly be detected in renal inner medullary interstitial cells. Therefore, we supposed that interstitial cells would require a sorbitol transport into the cells. However, such a transport system has not yet been described. Therefore, we have characterized the uptake of sorbitol in immortalized interstitial TK-173 cells, which were derived from human renal fibroblasts. Comparable to fresh isolated renal fibroblasts of the rat, immortalized TK-173 cells have a high sorbitol dehydrogenase activity. In this report, a temperature-dependent sorbitol uptake with saturation kinetics could be detected in immortalized TK-173 cells. The transport is characterized by a high velocity (Vmax 84 mmol/l x h) and an apparent Km of 10 mmol/l. The sorbitol uptake is independent of membrane potential, sodium, and chloride. Altogether, the physiological characteristics of this sorbitol transport are different from those of the osmotically regulated sorbitol efflux from epithelial cells. These results provide evidence that TK-173 cells derived from renal fibroblasts have a specific sorbitol transport. Furthermore, these data suggest a cooperation between epithelial and interstitial cells concerning osmoregulation.

Volume regulation of thick ascending limb of Henle cells: significance of organic osmolytes.

The thick ascending loop of Henle (TALH) is exposed to high osmotic stress, which is particularly due to high sodium and chloride reabsorption and very low water permeability of the luminal membrane. Therefore, the volume regulation of TALH cells, derived from the TALH loop of rabbit kidneys, was analyzed. The volume was determined by impedance measurements. TALH cells, which were adapted to different osmolarities (300 and 600 mosm/l), showed no significant differences in their cell volume. Therefore, a complete volume regulation could be supposed. An increase in extracellular osmolarity from 300 to 600 mosm/l (osmolarity adjusted by addition of 150 mM NaCl) immediately led to a reduction in the cell volume by 37 +/- 6% (n = 6). A regulatory volume increase (RVI) was not observed within 10 min but after 24 h. Conversely, a sudden cell swelling by 44 +/- 5% (n = 4) was detected within 20 s following an extracellular hypoosmotic challenge (from 600 to 300 mosm/l). The subsequent volume regulatory decrease (RVD) required a period of 7 days. Specific inhibitors of important ion transporters had no effect on volume regulation. Thus, changes in the ion conductivity do not seem to influence the processes of RVI and RVD. Conversely, the intracellular content of the organic osmolytes, sorbitol, inositol, betaine, and glycerophosphorylcholine, changed in the course of RVI and RVD. These results provide evidence that TALH cells are capable of maintaining their volume despite large extracellular osmotic changes. RVI and RVD are mainly regulated by changes in the intracellular content of organic osmolytes within 1 and 7 days.

Immunocytological determination of lymphocytes and monocytes/macrophages in urinary sediments of renal allograft recipients.

BACKGROUND: Urinary studies using Papanicolaou staining following kidney transplantation led to the conjecture that acute allograft rejection might be accompanied by an increased lymphocyturia. However, it is difficult to distinguish lymphoid cells from other urinary cells using conventional stains. METHODS: Staining of urinary lymphocytes using FITC-labelled antibodies is complicated by a high unspecific fluorescence that limits the evaluation. Therefore, we developed a method to stain urinary lymphocytes using enzyme-linked antibodies. The cells were cytocentrifuged onto microscope slides and were fixed. RESULTS: By means of a combined evaluation of Papanicolaou and immunocytochemical staining, CD3-positive pan T cells, CD4-positive T-helper cells, CD8-positive cytotoxic/suppressor cells, and CD14-positive monocytes/macrophages of urinary sediments were determined in 41 kidney graft recipients following renal transplantation. During periods of normal graft function, neither positive lymphocytes nor positive monocytes/macrophages were found in the urinary sediments. However, in the course of acute allograft rejection a significant increase in positive lymphocytes and positive monocytes/macrophages could be observed. Interestingly, in cases of acute allograft rejection the distribution of urinary lymphocytes and monocytes was comparable to the distribution of infiltrating immunocompetent cells in renal allograft biopsies. CONCLUSION: The present study demonstrates that immunocytochemical staining via enzyme-conjugated antibodies is a reliable method to visualize T lymphocytes and monocytes/macrophages in the urinary sediment, and that this technique may be of special diagnostic value in the diagnosis of acute allograft rejection.

Soluble CD-4 and CD-8 as markers of immunological activation in renal transplant recipients.

BACKGROUND: T lymphocytes are activated following kidney transplantation in cases of acute graft rejection and viral infections. In plasma, elevated levels of T-cell markers can be measured in soluble form. The reason for this shedding is still not entirely understood. METHODS: Plasma concentrations of soluble CD-4 and CD-8 (sCD-4, sCD-8) were determined in 78 patients following kidney transplantation by commercially available enzyme-linked immunosorbent assay (ELISA) test kits. RESULTS: The concentrations of both soluble T-cell markers increased significantly in the course of acute allograft rejections and cytomegalovirus (CMV) infections. Frequently, the parameters increased shortly before clinical diagnosis and decreased under successful therapy. Additionally, sCD-8 showed significant higher plasma concentrations in cases of CMV infection as compared with acute allograft rejections. Accordingly, the sCD-4/sCD-8 ratio increased in cases of acute allograft rejection and decreased during CMV infections. Cyclosporin A nephrotoxicity caused no significant changes in the sCD-4 and sCD-8 levels in plasma. CONCLUSION: The present study demonstrates that sCD-4 and sCD-8 are markers of immunological activation and may enable a further differentiation of T-cell activation if serial measurements are performed. However, further prospective investigations are necessary to elucidate the diagnostic potential of sCD-4 and sCD-8 for monitoring acute rejection and viral infection in kidney graft recipients.

[Unusual diagnosis in recurrent arthritis, erythema nodosum and arrhythmia]. / Ungewöhnliche Diagnose bei rezidivierender Arthritis, Erythema nodosum und Herzrhythmusstörungen.

HISTORY AND ADMISSION FINDINGS: A 42-year-old woman, with recurrent arthritis of the large joints and erythema nodosum for 7 years, was admitted because of recent onset of bouts of rapid heart rate. A 2/6 systolic murmur at Erb's point was the only contributory finding on physical examination. INVESTIGATIONS: The transaminases and gamma-GT were elevated, as were total cholesterol, LDL fraction, IgM, total protein, gamma-globulin and IgM. Antimitochondrial antibodies, especially anti-M2, were positive, while rheumatoid factor and C-reactive protein were negative. ANA, ANCA and antibodies against double-strand DNA were not demonstrated. ENA screening was negative. Abdominal computed tomography showed discrete intrahepatic cholestasis. Liver biopsy revealed chronic destructive cholangitis, i.e. the early stage of primary biliary cirrhosis. TREATMENT AND COURSE: On treatment with ursodeoxycholic acid (10 mg/kg daily) the patient has remained free of symptoms for 3 years and laboratory tests no longer showed evidence of impaired liver function. CONCLUSION: Primary biliary cirrhosis should be included in the differential diagnosis of recurrent arthritis and erythema nodosum, as early treatment with ursodeoxycholic acid can favourably influence its course.

Night vision goggle (NVG) visual acuity under ideal conditions with various adjustment procedures.

Night operations involve diverse mission areas and require an increased reliance on the use of night vision devices, such as night vision goggles (NVG's). Any reduction in goggle or visual performance which goes undetected can have a serious effect on flight safety and operational capability. Under controlled lighting conditions, a crewmember should be able to obtain the best possible goggle performance, and to determine if the goggle is functioning properly. These data represent a sample of 218 current USAF aircrew members representing all crew positions in both rotary and fixed-wing aircraft. Three measurements of goggle performance, expressed as NVG visual acuity, were obtained. The first measure, obtained after crewmembers adjusted the goggles with their usual adjustment methods, showed that they routinely obtain less than optimal acuity levels; i.e., averaging between 20/50 and 20/55. The second measure, taken when the NVG Resolution Chart was provided to augment their "usual" method of adjustment, showed improved performance; i.e., averaging 20/45. The third measure, taken following participation in an NVG Adjustment Procedures class, showed the greatest improvement, averaging between 20/35 and 20/40. In summary, it is reasonable to conclude that aircrew members who are able to obtain the best possible performance for their NVG's under controlled preflight conditions will obtain the best possible goggle performance under the widely varying flight conditions.