Labormedizinisches Zentrum Dr. Risch

Bern, Switzerland

Labormedizinisches Zentrum Dr. Risch

Bern, Switzerland
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Nydegger U.E.,Labormedizinisches Zentrum Dr. Risch
LaboratoriumsMedizin | Year: 2017

With big data algorithms and artificial intelligence (AI) at stake the optimal assembly of the most appropriate lab assays selected to diagnose, treat and follow up patients suffering from well-delineated disease may get lost. The physician ordering a lab test, instead of asking for a good composition of screening tests is tempted to order a large number of assays, including genome sequencing hoping to find the diagnostic evidence for his/her patient at once. Four major specialities of medical laboratory assays, i.e. clinical chemistry, hematology, immunology and microbiology are embraced by genome sequencing techniques and have attained the degree of robotics, facilitating assays to such a degree, that the prescriber is free of concern as to how costly/complicated an investigation might become. Diagnostics with autoimmune diseases is not an exemption and autoantibody screening using multiplex assays or therapeutic drug monitoring to adjust treatments of inflammatory/autoimmune diseases is bound to become more and more informative even more so as the pharmacodynamics of modern pharmaceutical agents are explored. As the most appropriate therapeutical agents to monitor in the lab, biological response modifiers, immunosuppressants and monoclonal antibodies are at the forefront and we need to explore their efficacy and side effect profiles not only using phase III clinical studies but also by using postmarketing surveillance. Behind the profiles provided by big data and artificial intelligence, the therapeutically-induced regained immune balance can thus be traced to the single best lab assay. The next decade promises a series of new assays, e.g. inflammasome profiles, lymphocyte markers by fluorescence activated cell sorters as well as single cell secretome analysis. © 2017 Walter de Gruyter GmbH, Berlin/Boston 2017 Bei aller Technikaffinität für die richtige Diagnose bleiben vom Arzt erhobene Anamnese und klinischen Befunde wichtige Pfeiler zur Einleitung der Behandlung einer Krankheit. Dazu kommt aber heute unabdingbar die Computer-Unterstützung-anfänglich mit der Anhäufung von grossen Datenmengen nicht nur aus dem medizinischen Labor sondern aus Bildgebung, Histopathologie, und Ergebnissen aus Gen-und FACS-Analysen peripherer Blutzellen. Das reichliche Angebot von Laboranalysen ist derzeit so verlockend gross, dass der Auftrag-gebende Arzt der Versuchung oft nicht widerstehen kann, eine exzessive Anzahl Marker-Analysen aus einem Tropfen Blut zu verlangen. Die generierten Datenmengen bergen jedoch die Gefahr, dass das Bestellmuster von Analysen vom Leidensmuster des Patienten abweichen wird. Hier setzt die künstliche Intelligenz (AI: Artificial intelligence) den Griffel an: dem geduldigen Computer werden Anamnese-und Untersuchungs-relevante Daten eingespeist und der Algorhythmus berechnet Wahrscheinlichkeiten mit integrierten Grundannahmen, in welche Richtung die Laboranalysen der klinischen Diagnostik und Therapie hilfreich sein würden. Die vorliegende Arbeit versucht diese Entscheidungswege für Arzt und Patient am Beispiel der Autoimmun-Krankheiten zu konkretisieren. In einem solchen Fach wie auch in der Krebsbehandlung mit der Immune Checkpoint-Identifizierung entsteht dank der derzeit unaufhörlichen Entwicklung monoklonaler Antikörper für Diagnostik und Therapie eine zusätzliche Ebene mit grossen Datenmengen-ohne Bioinformatik ist die moderne Medizin undenkbar geworden.

Krisai P.,University of Basel | Aeschbacher S.,University of Basel | Schoen T.,University of Basel | Bossard M.,University of Basel | And 9 more authors.
Hypertension | Year: 2015

Hypertension and diabetes mellitus are highly correlated, but the underlying mechanisms are only partly understood. Therefore, the aim of our study was to investigate the relationships between plasma levels of glucagon-like peptide-1, a key factor in the regulation of glucose homeostasis, and various blood pressure indices. Healthy adults aged 25 to 41 years were enrolled in a population-based study. Established cardiovascular disease, diabetes mellitus, or a body mass index >35 kg/m were exclusion criteria. Fasting plasma glucagon-like peptide-1 levels as determined with a novel high-sensitive assay and ambulatory blood pressure data were available in 1479 participants not using antihypertensive treatment. Median age of our population was 38 years. Mean systolic and diastolic blood pressure across increasing glucagon-like peptide-1 quartiles were 120.6, 122.8, 123.2, and 124.9 mm Hg and 77.1, 78.7, 78.9, and 79.9 mm Hg, respectively. We found a linear relationship of glucagon-like peptide-1 with 24-hour ambulatory blood pressure after multivariable adjustment (β per 1 log-unit increase 2.01; 95% confidence interval, 1.02-3.00; P<0.0001 for systolic and 1.22; 0.47-1.97; P=0.002 for diastolic blood pressure). In separate analyses, glucagon-like peptide-1 was significantly related to both awake (β per 1 log-unit increase 2.05; 1.02-3.09; P=0.0001 for systolic and 1.15; 0.35-1.96; P=0.005 for diastolic blood pressure) and asleep blood pressure (β per 1 log-unit increase 1.34; 0.26-2.42; P=0.01 for systolic and 1.05; 0.26-1.84; P=0.009 for diastolic blood pressure). In conclusion, plasma levels of glucagon-like peptide-1 are significantly associated with both systolic and diastolic blood pressure levels. © 2014 American Heart Association, Inc.

Sakem B.,Labormedizinisches Zentrum Dr. Risch | Nock C.,Private Medical Office | Stanga Z.,University of Bern | Medina P.,Labormedizinisches Zentrum Dr. Risch | And 5 more authors.
BMC Medicine | Year: 2013

Background: Vitamin D and the components of humoral immunity play important roles in human health. Older people have lower 25-hydroxyvitamin D (25(OH)D) serum levels than younger adults. We aimed to determine the levels of 25(OH)D serum concentrations in healthy senior citizens and to study their relationship to the levels of components of humoral immunity.Methods: A total of 1,470 healthy Swiss men and women, 60 years or older, were recruited for this study. A total of 179 subjects dropped out of the study because of elevated serum concentrations of C-reactive protein. Fasting blood sera were analyzed for 25(OH)D with the high-performance liquid chromatography (HPLC) and for parathyroid hormone (PTH), immunoglobulins and complement C4 and C3 concentrations with immunoassays. The percentage of participants in each of the four 25(OH)D deficiency groups - severely deficient (<10 ng/ml), deficient (10 to 20), insufficient (21 to 29 ng/ml) and normal (>=30 ng/ml) - were statistically compared. The relationship of the major components of the humoral system and age with 25(OH)D levels was also assessed.Results: About 66% of the subjects had insufficient levels of 25(OH)D. Normal levels of 25(OH)D were found in 26.1% of the subjects of which 21% were males and 30.5% were females (total study population). Severely deficient levels of 25(OH)D were found in 7.98% of the total study population. Low levels of 25(OH)D were positively associated with IgG2 (P = 0.01) and with C4 (P = 0.02), yet were inversely related to levels of IgG1 and IgA (P < 0.05) and C3 (P = 0.01). Serum levels of total IgA, IgG, IgG2 and IgG4 peaked together with 25(OH)D during late summer.Conclusions: Approximately two-thirds of the healthy, older Swiss population presented with Vitamin D insufficiency. The incremental shift in IgA and C3 levels might not necessarily reflect a deranged humoral immune defense; however, given the high prevalence of vitamin D deficiency, the importance of this condition in humoral immunity will be worth looking at more closely. This study supports the role of vitamin D in the competent immune system. © 2013 Sakem et al.; licensee BioMed Central Ltd.

Risch M.,Labormedizinisches zentrum Dr. Risch
Swiss medical weekly : official journal of the Swiss Society of Infectious Diseases, the Swiss Society of Internal Medicine, the Swiss Society of Pneumology | Year: 2010

A completely new approach to diagnose microbial agents at least one day earlier based on mass spectrometric analysis becomes possible in the microbiology laboratory: MALDI TOF: matrix-assisted laser desorption/ionisation time-of-flight. Comparison between results of the new procedure with those obtained by conventional testing is mandatory. 204 clinical isolates grown on agar plates were analysed both, by the MALDI TOF Bruker microflex apparatus and by conventional identification using the VITEK II and API systems, both from bioMérieux. Of the identified isolates, 72 were gram-positive and 130 gram-negative; 2 were yeasts (candida). Concordance was seen with 61/72 (85%) of the Gram-positive bacteria and with 115/130 (88%) of the Gram-negative bacteria. In 27 samples (13.2%), a discrepancy of the species and/or genus was obvious. The discrepancy appeared with 16 gram-negative (12.2%) and with 11 gram-positive germs (15.3%, n.s.). In the latter group, 6 samples showed discordance with Streptococcus pneumoniae (MALDI) and Streptococcus mitis/oralis (conventional identification) constellation. Among gram-negative samples, most differences occurred on the species level only, e.g. Enterobacter cloacae versus Enterobacter kobei. In 5 cases, discordance was major and appeared on the genus level: Enterobacter/Raoultella, Streptococcus/Gemella, Pseumdomonas/Burkholderia, Microbacter/Sphingomonas and Candida/Cryptococcus. The most outstanding difference was Microbacterium arborescens (MALDI TOF) and Sphingomonas paucimobilis (conventional). Molecular biological identification of two Streptococcus mitis group bacteria confirmed the erroneous diagnosis by MALDI TOF of Streptococcus pneumoniae. Good comparability between MALDI TOF analysis and conventional identification procedures (86.8%) but special caution is needed when identifying streptococcal species.

Nydegger U.E.,Labormedizinisches Zentrum Dr. Risch | Luginbuhl M.,University of Bern | Risch M.,Central Laboratory
Transfusion and Apheresis Science | Year: 2015

In this review the different mechanisms of aging and frailty such as DNA defects due to impaired DNA repair, inflammatory processes, disturbances of oxidative phosphorylation are discussed together with mechanisms of cell repair. Components of blood plasma, such as the growth-differentiation protein GDF11, were shown to enhance neurogenesis and to improve the vasculature in the animal cortex and to rejuvenate muscle tissue. Advances in laboratory assays allow to identify plasma proteins that may affect tissue regeneration. This new knowledge from animal research might affect transfusion practice in geriatric patients in the future. Provided it can be translated and confirmed in human research, blood products might no longer be considered only as oxygen carriers or drugs to improve hemostasis.In the present time blood transfusion (RBCs, plasma or platelets) should be directed by differentiated guidelines considering not only cut-off values of hemoglobin, platelet count or coagulation but also old age-specific biologic variation, comorbidities and the clinical context e.g. of bleeding. © 2015 Elsevier Ltd.

Nydegger U.E.,Labormedizinisches Zentrum Dr. Risch | Fierz W.,Labormedizinisches Zentrum Dr. Risch | Risch L.,Labormedizinisches Zentrum Dr. Risch
Transfusion and Apheresis Science | Year: 2012

The case of Immunoglobulin A (IgA) in transfusion medicine is unsettled: on one hand IgA is an important component of adaptive immunity and its deficiency may cause disease, on the other its presence in blood products might induce, in rare instances, allergy-like symptoms if not anaphylaxis. The practice with i.v. immunoglobulins currently changes as up to 10% concentrated preparations are given at fast rates hence even trace amounts of IgA contained in these IgG preparations can cause unexpected (side-) effects. Fortunately, the spectrum of sensitive IgA assays, along with anti-IgA screening assays now permits laboratories to narrow down IgA-dependent transfusion reactions to the real cases, in which IgA was the decisive trigger of anaphylaxis, proven or not by the presence of anti-IgA of the IgG or even IgE class. Tolerance to allogenic IgA has recently been reported. The known association of HLA with IgA deficiency (IgAD) has now been completed with an association to the nonsynonymous variant in IFHI1, allowing physicians to more precisely spot recipients at risk for an IgA-dependent transfusion reaction. Our review, along with our own experience here in Switzerland, allows us to conclude that IgA is a beneficial antibody rather than an allergen to be placed at the end of the list of non-infectious transfusion complications such as TRALI, febrile non-hemolytic reactions, purpura or volume overload. © 2011 Elsevier Ltd.

Ciardo D.E.,University of Zürich | Burger S.,University of Zürich | Payer M.,NeuroZentrum Hirslanden | Lee C.,Labormedizinisches Zentrum Dr. Risch | McCallum N.,University of Zürich
Journal of Clinical Microbiology | Year: 2010

A cefoxitin-susceptible Staphylococcus aureus strain was identified by the Cepheid GeneXpert as methicillin-resistant S. aureus (MRSA). This strain was highly unstable and rapidly lost SCCmec upon subculturing in vitro, indicating that unstable MRSA is best detected by gene amplification-based methods. Copyright © 2010, American Society for Microbiology. All Rights Reserved.

Risch L.,Labormedizinisches Zentrum Dr. Risch | Hess B.,Innere Medizin and Nephrologie Hypertonie
Therapeutische Umschau | Year: 2013

When it comes to interpret parameters of electrolyte balance and kidney function, it is important to keep pathophysiology and the theory on reference intervals in mind. Hyponatremia is most often caused by excess water. A low sodium concentration in urine should prompt a clinical evaluation of volume status. In case of suspected acute kidney failure, fractionated sodium excretion and fractionated urea excretion are able to provide insights on prerenal or renal origin of the disorder. Disruption in potassium homoeostasis can occur due to changes in supply or renal elimination as well as due to changes in the potassium balance between the extra- and intracellular compartments. The transtubular potassium gradient can help in the differential diagnosis of hyperkalemia. Evaluation of kidney function should begin with determination of serum creatinine, accompanied by an estimate of the glomerular filtration rate, as calculated by the CKD-EPI equation. As a consequence of non-renal determinants of serum creatinine, this equation has been shown to overestimate true GFR in elderly and hospitalized patients. This can result in overdosing of renally-cleared drugs. Clearance determinations can be of use in this context. © 2013 Verlag Hans Huber, Hogrefe AG, Bern.

Sakem B.,Labormedizinisches Zentrum Dr. Risch | Michel R.,Labormedizinisches Zentrum Dr. Risch | Nydegger U.E.,Labormedizinisches Zentrum Dr. Risch | Radjenovic D.,Labormedizinisches Zentrum Dr. Risch | And 3 more authors.
Infection | Year: 2011

Background: The prevalence of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infection in a Swiss cohort among individuals consulting for screening or symptomatic reasons is not very well known. Methods: Between January 2009 and January 2010, diagnostic samples referred to us to test for either CT or NG or both were simultaneously analysed for both infections. Testing was performed using the commercial m2000sp and m2000rt devices from Abbott Diagnostics involving automated DNA extraction and semi-quantitative real-time polymerase chain reaction (PCR), respectively. Results: A total of 9,245 individuals (8,009 female, 1,236 male) were tested. CT alone was found in 318 (3.97%) samples from female patients and NG infections were found in 5 (0.06%) of the female samples. Six (0.08%) women had both CT and NG infections. The numbers for males were 72 (5.83%) for CT alone, 18 (1.14%) for NG alone and 8 (0.65%) for coincident infections. Among women, a selective testing approach in which only the presence of CT was investigated missed six NG cases (0.07% prevalence, 54.55% of all NG-positive women) and the request to test only for NG missed two CT cases (0.02% prevalence, 0.62% of all CT-positive women). For the male samples, one NG case (0.08% prevalence, 3.85% of all NG-positive men) was missed when only CT was requested and three CT cases (0.24% prevalence, 3.75% of all CT-positive men) were overlooked when only NG testing was requested. Conclusion: A sizeable number (12) of CT and NG cases is missed by physician-referred testing for only one of the two pathogens. © 2011 Springer-Verlag.

Schneider S.C.,University of Bern | Tinguely R.,University of Bern | Droz S.,University of Bern | Hilty M.,University of Bern | And 3 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2015

Antibiotic resistance in Ureaplasma urealyticum/Ureaplasma parvum and Mycoplasma hominis is an issue of increasing importance. However, data regarding the susceptibility and, more importantly, the clonality of these organisms are limited. We analyzed 140 genital samples obtained in Bern, Switzerland, in 2014. Identification and antimicrobial susceptibility tests were performed by using the Mycoplasma IST 2 kit and sequencing of 16S rRNA genes. MICs for ciprofloxacin and azithromycin were obtained in broth microdilution assays. Clonality was analyzed with PCR-based subtyping and multilocus sequence typing (MLST), whereas quinolone resistance and macrolide resistance were studied by sequencing gyrA, gyrB, parC, and parE genes, as well as 23S rRNA genes and genes encoding L4/L22 ribosomal proteins. A total of 103 samples were confirmed as positive for U. urealyticum/U. parvum, whereas 21 were positive for both U. urealyticum/U. parvum and M. hominis. According to the IST 2 kit, the rates of nonsusceptibility were highest for ciprofloxacin (19.4%) and ofloxacin (9.7%), whereas low rates were observed for clarithromycin (4.9%), erythromycin (1.9%), and azithromycin (1%). However, inconsistent results between microdilution and IST 2 kit assays were recorded. Various sequence types (STs) observed previously in China (ST1, ST2, ST4, ST9, ST22, and ST47), as well as eight novel lineages, were detected. Only some quinolone-resistant isolates had amino acid substitutions in ParC (Ser83Leu in U. parvum of serovar 6) and ParE (Val417Thr in U. parvum of serovar 1 and the novel Thr417Val substitution in U. urealyticum). Isolates with mutations in 23S rRNA or substitutions in L4/L22 were not detected. This is the first study analyzing the susceptibility of U. urealyticum/U. parvum isolates in Switzerland and the clonality outside China. Resistance rates were low compared to those in other countries. We hypothesize that some hyperepidemic STs spread worldwide via sexual intercourse. Large combined microbiological and clinical studies should address this important issue. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

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