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Biomedical subjects

Walter Fierz

Publications and source records attributed to Walter Fierz.

10 recordsLinked to original sources
PubMed2004

Diagnostic significance of intrathecally produced herpes simplex and varizella-zoster virus-specific antibodies in central nervous system infections.

BACKGROUND AND OBJECTIVES: The optimal strategy for the diagnosis of herpes simplex virus (HSV) and varizella-zoster virus (VZV) disease of the central nervous system is the detection of viral DNA by polymerase chain reaction assay (PCR) in cerebrospinal fluid (CSF) and the examination of intrathecal production of specific antibodies. However, in acute neurological disease caused by either HSV or VZV, dual intrathecal synthesis of HSV-1, 2- as well as VZV-specific antibodies may be detectable and thus can hamper accurate aetiological diagnosis. This paper illustrates such equivocal findings in two case reports, investigates their frequency and discusses the possible reasons. METHODS: Consecutive CSF/serum pairs of two patients with central nervous system (CNS) disease were tested by HSV-1-, HSV-2-, and VZV-specific PCR and by different serological assays for detection of neurotropic viruses and bacteria. Additionally, the results of microbiological investigations of 1'155 CSF/serum samples were retrospectively analyzed for coincident intrathecal antibody synthesis against HSV-1, 2 and VZV. RESULTS: Although only HSV-1 and VZV-specific DNA was detectable in the CSF of two patients with encephalitis and chronic meningitis, respectively, increasing intrathecal antibody production against both virus species could be demonstrated. Retrospective analysis of 1155 CSF/serum pairs revealed 55 (4.8%) pairs with evidence for intrathecally produced antibodies against either HSV-1, 2 (30/55) or VZV (14/55). Eleven of these 55 (20%) pairs showed intrathecal antibody-production against both virus species. CONCLUSIONS: Patients with CNS infection with HSV and VZV can be diagnosed by detecting intrathecally produced virus-specific antibodies, in addition to virus-specific PCR. However, in an appreciable proportion of patients a correct diagnosis is hampered by coincidentally detected antibodies in CSF against both virus species. Possible reasons for these equivocal findings are given.

Adult↗
PubMed2004

Challenge of personalized health care: to what extent is medicine already individualized and what are the future trends?

Personalized medicine: is it hype or revolution? In any case, there is not only real demand for it, but it also has a history. As it is, the personal aspects of health care have been partly neglected in the current era of evidence-based, scientific medicine. We now know that a 'one fits all' type of treatment has its limits. Medicine needs to be (re-)personalized. The time is right: the post-genomic era provides the necessary molecular tools, but does it provide for the risks involved? Privacy, protection of minorities, and prevention of discrimination are at stake. Regulations are required. The health-care process needs redesigning to render personalized medicine effective. Information and communication management is challenged to handle the wealth of personal information and link to global medical knowledge. But the goal is magnificent: personal health planning, early diagnosis, the right drug for the right patient, and predictable side effects.

Biomedical Technology↗
PubMed2004

Prevalence of human T-cell leukemia virus types I and II in Switzerland.

The retroviruses human immunodeficiency virus (HIV)-1/2 and human T-cell leukemia virus (HTLV)-I/II share modes of transmission, suggesting that efforts to monitor the current HIV-1 epidemic in Switzerland should be complemented by assessment of HTLV-I/II prevalence. This study presents an updated evaluation of HTLV-I/II infection among groups within the Swiss population polarized towards either low or increased risk of infection. Archived serum and peripheral blood mononuclear cell (PBMC) samples were examined for evidence of HTLV-I/II infection by enzyme-linked immunosorbant assay (ELISA), type-specific Western blot, type-specific polymerase chain reaction (PCR), DNA sequence analysis, and virus culture. Among blood donations obtained from low-risk Swiss donors, we report a complete lack of HTLV-II infection and the occurrence of HTLV-I infection limited to a prevalence of 0.079 per 100,000 (1/1,266,466). Among high-risk HIV-positive persons and HIV-negative persons at increased risk of HIV-infection, we report a focus of HTLV-I and HTLV-II infection at prevalence rates of 62 per 100,000 (1/1,620) and 309 per 100,000 (5/1,620), respectively. The finding of low HTLV-I/II prevalence among Swiss blood donors and containment of HTLV-I/II infection within known risk-groups does not support initiation of HTLV-I/II screening for Swiss blood, tissue, and organ donations.

Blood Donors↗
PubMed2004

Statin-induced immunomodulatory effects on human T cells in vivo.

Statins are widely used for treatment of hypercholesterolemia. Recent experimental studies revealed that these drugs also exert anti-inflammatory effects. The aim of this study was to assess immunomodulatory effects of statins in humans in vivo. Twenty-seven healthy volunteers were analyzed for serum cytokines and acute phase proteins, HLA-DR and CD38 expression on T cells and superantigen-mediated T cell activation ex vivo before and after 14 days of statin treatment. First, simvastatin 40 mg was compared to atorvastatin 20 mg. Second, two different doses of simvastatin (20 and 40 mg) were tested. Atorvastatin treatment led to a significant down-regulation of HLA-DR and the CD38 activation marker on peripheral T cells, whereas simvastatin up-regulated both of these molecules. In contrast, superantigen-mediated T cell activation was inhibited by simvastatin and enhanced by atorvastatin. No significant effect of statin treatment on inflammatory serum markers was detected. Thus, immunomodulatory effects of statins on human T cells are first demonstrated in vivo and are differentially induced by two different statins: atorvastatin led to a major histocompatibility class II (MHC II) antigens down-regulation and may therefore be investigated for treatment of chronic transplant rejection; simvastatin inhibited superantigen-mediated T cell activation, which might explain reduced mortality of simvastatin-treated patients with staphylococcal bacteremia.

ADP-ribosyl Cyclase↗
PubMed2004

Interpretation of erythropoietin levels in patients with various degrees of renal insufficiency and anemia.

BACKGROUND: Chronic renal failure leads to hyporegenerative anemia due to erythropoietin deficiency. The creatinine clearance and hemoglobin levels, at which anemia treatment with recombinant erythropoietin should be started, are unclear. Interpretation of serum erythropoietin levels in the context of renal insufficiency remains controversial and was addressed in this study. METHODS: Three hundred and ninety-five patients were randomly chosen out of over 5000 consecutive patients investigated by coronary angiography at a single center between 1997 and 2001. Laboratory values and clinical information were prospectively collected in a central registry. Serum samples were frozen before angiography and now used to measure serum erythropoietin levels and evaluate the relationship between erythropoietin and hemoglobin levels in the context of various degrees of renal insufficiency. RESULTS: The patients with the lowest renal function (creatinine clearance <20 mL/min) had significantly lower hemoglobin levels than the group with normal renal function. However, erythropoietin levels were identical indicating a lower set point for erythropoietin regulation. Above a creatinine clearance of 40 mL/min a significant inverse correlation between erythropoietin and hemoglobin levels was observed and described with the formula erythropoietin [U/L]= 2.5 x (140 - hemoglobin [g/L]) or alternatively Deltaerythropoietin (U/L) =-2.5 xDeltahemoglobin (g/L). Below 40 mL/min no significant correlation was found. CONCLUSION: A cut-off level for an altered set point of erythropoietin regulation was determined at 40 mL/min creatinine clearance. Above this cut-off hemoglobin negatively regulates erythropoietin. Below the cut-off erythropoietin levels remain stable. Pathophysiologic concepts for this finding and clinical implications in patients with moderate renal failure are discussed.

Adult↗
PubMed2004

Basic problems of serological laboratory diagnosis.

Serological laboratory diagnosis of infectious diseases is inflicted with several kinds of basic problems. One difficulty relates to the fact that the serological diagnosis of infectious diseases is double indirect: The first indirect aim in diagnosing an infectious disease is to identify the microbial agent that caused the disease. The second indirect aim is to identify this infectious agent by measuring the patient's immune response to the potential agent. Thus, the serological test is neither measuring directly disease nor the cause of the disease, but the patient's immune system. The latter poses another type of problem, because each person's immune system is unique. The immune response to an infectious agent is usually of polyclonal nature, and the exact physicochemical properties of antibodies are unique for each clone of antibody. The clonal makeup and composition and, therefore, the way an individual's immune system sees an infectious agent, depends not only on the genetic background of the person but also on the individual experience from former encounters with various infectious agents. In consequence, the reaction of a patient's serum in an analytical system is not precisely predictable. Also, the antigenic makeup of an infectious agent is not always foreseeable. Antigenic variations leading to different serotypes is a quite common phenomenon. Altogether, these biological problems lead to complexities in selecting the appropriate tests and strategies for testing, in interpreting the results, and in standardizing serological test systems. For that reason, a close collaboration of the laboratory with the clinic is mandatory to avoid erroneous conclusions from serological test results, which might lead to wrong decisions in patient care.

Antibody Affinity↗
PubMed2003

Subclinical disease activity in systemic lupus erythematosus: immunoinflammatory markers do not normalize in clinical remission.

OBJECTIVE: To correlate various laboratory measures in systemic lupus erythematosus (SLE) with the British Isles Lupus Assessment Group (BILAG) disease activity index, to search for organ-specific laboratory patterns and to compare with a control population. METHODS: A cohort of 57 Caucasian outpatients fulfilling the American College of Rheumatology criteria for SLE and a control population of 17 patients admitted for coronarography were examined. Disease activity was assessed with BILAG index. Plasma samples were investigated for sCD44, interleukin 6 (IL-6), IL-10, IL-12, tumor necrosis factor-a (TNF-a), soluble TNF receptor-55 (sTNFR-55), sTNFR-75, IL-1-receptor antagonist, soluble intercellular adhesion molecule (sICAM), soluble vascular cell adhesion molecule (sVCAM), E-selectin, and neopterin as well as for C3, C4, dsDNA, and other conventional indicators. RESULTS: Thirty-nine patients had inactive disease (total BILAG score < or = 5), 18 patients had active SLE. Surprisingly, except for C-reactive protein (p < 0.001), no statistically significant difference of the laboratory indicators was found between patients with active and those with inactive SLE. However, there was a significant difference between SLE patients and controls for sTNFR-75 (p < 0.008). We found significant correlations between laboratory markers and some BILAG organ system scores, such as between IL-1ra and the musculoskeletal score (p < 0.003) and between sTNFR-55/sTNFR-75 and renal BILAG (p < 0.001, p < 0.004, respectively). Significant nonparametric correlations were revealed between C3 and C4 (p < 0.0001), and between sTNFR-75 and dsDNA, neopterin, sVCAM, sICAM and sTNFR-55 concentrations (p < 0.0001 for all), and between sTNFR-75 and IL-1ra (p < 0.006). CONCLUSION: Patients with SLE in clinical remission show ongoing systemic immunoinflammatory activity measured with a variety of cytokines, adhesion molecules, and other inflammatory markers. This indicates that laboratory measures may provide qualitatively different additional information to validated disease activity indexes such as the BILAG. Different laboratory markers correlate with disease activity in different organ systems. This suggests differences in pathogenic mechanisms in SLE depending on the organ system involved.

Adult↗
PubMed2002

Prevalence of asymptomatic celiac disease in adolescents of eastern Switzerland.

BACKGROUND: The prevalence of symptomatic CD in Switzerland is thought to be 1 in 1,000 inhabitants. As in other countries, oligo- and asymptomatic CD is being diagnosed with increasing frequency in all age groups. AIM: To assess the prevalence of asymptomatic CD in adolescents in eastern Switzerland. METHOD: Between September 1999 and July 2000 total serum IgA titres, anti-endomysium IgA (EMA) titres and anti-human tissue transglutaminase IgA (hTTG) titres were measured in the serum of healthy 11- to 18-year-old Swiss lower and upper secondary school students. RESULTS: Of the 1,450 students (871 f = 60.1%, CI 95%) tested, 11 (10 f) had elevated levels of both EMA and TTG. The diagnosis of CD was confirmed in eight of these students by mucosal jejunal morphology (Marsh III); one exhibited normal histology. Two of the 11 students refused to undergo mucosal biopsy. None of the students, however, had symptoms suggestive of CD, nor were they stunted or underweight, and none of them had family members with known CD. All of the eight students with enteropathy went on a glutenfree diet and felt subjectively better than on a normal diet. Of the remaining students, 38 (2.6%) had family members with known CD. None of those with the relevant family history had elevated EMA or TTG levels. CONCLUSION: Asymptomatic CD is common. It occurs in 1 in 132 (0.75%) Swiss adolescents. The absence of subjectively recognisable symptoms suggestive of family history or other risk factors makes it difficult to diagnose this type of CD.

Adolescent↗
PubMed2002

Information management driven by diagnostic patient data: right information for the right patient.

Existing and future diagnostic technologies are providing a huge amount of data about the patient, which are to be sensibly managed by the treating physician. More than that, the sheer complexity of the interrelation between these data are calling for a radically new approach in the handling of medical data and information. The physician--representing the pivot between the diagnostic knowledge about the patient's condition and the globally available medical information--is to be supported in his decision-making by automated systems that provide the appropriate information in a timeframe and with a degree of detail that is adjusted to the actual needs of the decision process. To find the right drug for the right patient the doctor needs the right information for the right patient. In this article, requirements for a future Medical Data Web are discussed and possible routes to solutions are indicated.

Forecasting↗