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Biomedical subjects

H Schmitz

Publications and source records attributed to H Schmitz.

At least 19 recordsLinked to original sources

Quality assurance for the diagnostics of viral diseases to enhance the emergency preparedness in Europe.

The threat posed by emerging and re-emerging communicable diseases and, more recently, by the intentional release of infectious agents in a susceptible population, has been receiving considerable attention at the national and international levels. Public health efforts to strengthen disease detection, surveillance and control have been intensified. However, clinicians and clinical microbiology laboratories play an important role in the early detection of disease, the identification of the putative agent, and notification of the appropriate authorities. To be effective in this role, laboratories must be specially prepared to handle viral agents safely, and need, among other things, the appropriate rapid and sensitive diagnostic tests. In 1998 the European Network for Diagnostics of 'Imported' Viral Diseases (ENIVD) was established. ENIVD presently comprises, as permanent members, 44 expert laboratories in 21 European Union (EU) member states and 4 non-EU countries and is one of the networks on infectious diseases funded by the European Commission. ENIVD fulfils many of the important tasks required for the surveillance and control of imported, rare and emerging viral infections such as the exchange of expertise and the organisation of external quality assurance (EQA) programmes, both of which are needed to improve diagnostics. Here, we summarise the data generated by recent EQA activities focussed on the diagnostics of infections with hantavirus, dengue virus, filovirus, Lassa virus, orthopox virus and the SARS-coronavirus (SARS-CoV). These were carried out between 1999 and 2004 and involved 93 laboratories from 41 countries, including laboratories from additional countries outside of Europe. Particularly the EU-candidate countries and Eastern neighbouring countries will be invited to join the network in the near future. A public website is available at http://www.enivd.de.

Bioterrorism↗

[Performance and costs of outpatient clinics of university hospitals for medical care, teaching, research activities].

BACKGROUND: Outpatient clinics of university hospitals (Hochschulambulanzen) play a significant role in the German health care system. Universities have in contrast to other hospitals the right to implement an outpatient clinic, but the health care services they can render are restricted to clinical research and teaching activities. The university outpatient clinic study evaluates the intensity of medical care, teaching, research activities, and the related costs. METHOD AND DATABASE: 6 university hospitals with 51 outpatient departments in Germany were included. The prospective documentation of consultations was restricted to 800 visits per department. A total of 26,312 consultations with approximately 40,000 diagnoses and 150,000 services were documented. Furthermore, data concerning costs, teaching activities and research facilities were documented. RESULTS: Clinical treatment without any correlation to research or teaching activities amounted to about 81 % of the working time in the outpatient department (research 11 %; teaching 8 %). The primary task of the university outpatient clinics takes up less than 20 % of the working time. The physicians documented that the disease of every fourth visit was in accordance with their main field of research. 6.9 % of the visits were asked to take part in clinical trials, of these 1.25 % were included for the first time, 3.7 % were already included. 6.5 % of the visits were addressed to participate in specific teaching activities. The average total costs per case added up to 149 Euro. No outpatient clinic could cover the total per case costs with the lump sum payments. On the average 31 % of these costs were covered by lump sum payments (without cases concerning research and teaching). CONCLUSION: Treatment in outpatient departments of university clinics is far beyond research and teaching activities required by law. However, the ability of outpatient departments of universities to provide excellent outpatient services should have a more dominant role in the health care system. Therefore access to care should be deregulated for the patients and reimbursement schemes should be adjusted to adjust for the present losses.

Biomedical Research↗

Nature as a model for technical sensors.

Nature has developed a stunning diversity of sensory systems. Humans and many animals mainly rely on visual information. In addition, they may use acoustic, olfactory, and tactile cues for object detection and spatial orientation. Beyond these sensory systems a large variety of highly specialized sensors have evolved. For instance, some buprestid beetles use infrared organs for the detection of forest fires. The infrared sensors of boid and crotalid snakes are used for prey detection at night. For object detection and spatial orientation many species of nocturnal fish employ active electrolocation. This review describes certain aspects of the detection and processing of infrared and electrosensory information. We show that the study of natural exotic sensory systems can lead to discoveries that are useful for the construction of technical sensors and artificial control systems. Comparative studies of animal sensory systems have the power to uncover at least a small fraction of the gigantic untapped reservoir of natural solutions for perceptive problems.

Animals↗

[Relevance of coronaviruses. The SARS example].

The emergence of the new SARS coronavirus has shown dramatically the high relevance of human coronavirus infections. This overview presents data of both epidemiological and clinical studies of this new virus infection. Moreover, details of research on the pathogenesis, diagnostics, and therapy are given. The recent infections in December 2003 clearly document that SARS will be a major topic also in 2004.

Communicable Disease Control↗

Qualitative effect of fenofibrate and quantitative effect of atorvastatin on LDL profile in combined hyperlipidemia with dense LDL.

INTRODUCTION: The association of elevated plasma triglyceride concentrations, decreased HDL-cholesterol, and dense LDL (dLDL) is referred to as the atherogenic lipoprotein phenotype. dLDL particularly plays a role in the metabolic syndrome and type 2 diabetes and may be one of the factors responsible for the increased risk for coronary artery disease in these patients. The effect of fenofibrate and atorvastatin on the LDL subfraction profile in patients with combined hyperlipidemia and a preponderance of dLDL was studied in a sequential design. METHODS: Six male patients with combined hyperlipidemia and dLDL received 160 mg/die supra-bioavailable fenofibrate. After a washout phase of 8 weeks all patients received 10 mg/die atorvastatin for another 8 weeks. At baseline, after fenofibrate, and after atorvastatin treatment LDL subfractions were analyzed by equilibrium density gradient ultracentrifugation. RESULTS: Treatment with atorvastatin and fenofibrate reduced serum cholesterol by 30 % and 21 % (p = 0.046) (p-values for differences between treatment groups), triglycerides by 32 % and 45 %, LDL cholesterol by 28 % and 16 %, and increased HDL cholesterol by 3 % and 6 %, respectively. Atorvastatin and fenofibrate treatment resulted in the following changes of apoB and LDL subfractions: LDL-1 (1.019 - 1.031 kg/L) - 31 % and + 15 % (p = 0.028); LDL-2 (1.031 - 1.034 kg/L) - 14 % and + 57 % (p = 0.028); LDL-3 (1.034 - 1.037 kg/L) - 20 % and + 30 % (p = 0.028); LDL-4 (1.037 - 1.040 kg/L) - 25 % and - 6 %; LDL-5 (1.040 - 1.044 kg/L) - 29 % and - 38 %; and LDL-6 (1.044 - 1.063 kg/L) - 39 % and - 55 % (p = 0.028). As a consequence, fenofibrate reduced LDL density significantly (p = 0.028 versus atorvastatin). CONCLUSIONS: Atorvastatin decreased all LDL-subfractions to a similar extent (quantitative effect) whereas fenofibrate reduced predominantly dLDL and changed the LDL profile towards medium dense LDL-particles (qualitative effect). Since medium dense LDL have a higher affinity to the LDL-receptor fenofibrate may have a higher antiatherogenic potential than assessed by the reduction of total LDL-cholesterol and triglycerides alone.

Adult↗

Mechanisms of diarrhea in the interleukin-2-deficient mouse model of colonic inflammation.

Colitis in interleukin-2-deficient (IL-2(-/-)) mice resembles ulcerative colitis in humans. We studied epithelial transport and barrier function in IL-2(-/-) mice and used this model to characterize mechanisms of diarrhea during intestinal inflammation. (22)Na(+) and (36)Cl(-) fluxes were measured in proximal colon. Net Na(+) flux was reduced from 4.0 +/- 0.5 to 0.8 +/- 0.5 micromol.h(-1).cm(-2), which was paralleled by diminished mRNA and protein expression of the Na(+)/H(+) exchanger NHE3. Net Cl(-) flux was also decreased from 2.2 +/- 1.6 to -2.7 +/- 0.6 micromol.h(-1).cm(-2), indicating impaired Na(+)-Cl(-) absorption. In distal colon, aldosterone-induced electrogenic Na(+) absorption was 6.1 +/- 0.9 micromol.h(-1).cm(-2) in controls and was abolished in IL-2(-/-) mice. Concomitantly, mRNA expression of beta- and gamma-subunits of the epithelial sodium channel (ENaC) was reduced. Epithelial barrier was studied in proximal colon by impedance technique and mannitol fluxes. In contrast to ulcerative colitis, epithelial resistance was increased and mannitol fluxes were decreased in IL-2(-/-) mice. This was in accord with the findings of reduced ion transport as well as increased expression of tight junction proteins occludin and claudin-1, -2, -3, and -5. In conclusion, the IL-2(-/-) mucosa exhibits impaired electroneutral Na(+)-Cl(-) absorption and electrogenic Na(+) transport due to reduced mRNA and protein expression of NHE3 and ENaC beta- and gamma-subunit mRNA. This represents a model of early intestinal inflammation with absorptive dysfunction due to impaired transport protein expression/function while epithelial barrier is still intact. Therefore, this model is ideal to study regulation of transporter expression independent of barrier defects.

Animals↗

Electrophysiological characterization of the multipolar thermoreceptors in the "fire-beetle" Merimna atrata and comparison with the infrared sensilla of Melanophila acuminata (both Coleoptera, Buprestidae).

A thermosensitive multipolar neuron innervates each of the four abdominal receptors of the Australian buprestid beetle Merimna atrata. The neuron is spontaneously active within a broad range of body temperatures (tested between 10 degrees C and 40 degrees C). We heated the receptors with a red diode laser (lambda=0.66 microm) at intensities ranging from 5.3 mW cm(-2) up to 1.3 W cm(-2). In general, warming caused an increase of receptor activity. Peak discharge frequencies were reached 100-300 ms after onset of irradiation. After peak frequencies were reached, distinct adaptation took place within seconds. A linear increase in irradiation intensity caused an exponential increase in peak frequencies. Lowest threshold was found to be at 40 mW cm(-2) where latencies were 47 ms. At the highest intensity tested (1.3 W cm(-2)), peak frequencies increased up to about 300 Hz and latencies decreased to 24 ms. Considering the pyrophilous behaviour of Merimna and the morphological data from previous studies, our results support the hypothesis that the abdominal receptors are infrared receptors. We also recorded the responses of the photomechanic infrared sensilla of Melanophila acuminata under the same experimental conditions. These results show that the photomechanic sensillum of Melanophila has a higher sensitivity, and that the latencies are considerably shorter.

Animals↗

The proteins of the Hepatitis C virus: their features and interactions with intracellular protein phosphorylation.

Chronic infection with Hepatitis C virus (HCV) often results in cirrhosis and enhances the probability of developing hepatocellular carcinoma (HCC). The underlying mechanisms that lead to malignant transformation of infected cells, however, remain unclear. Observations made with isolated HCV antigens and/or with HCV subgenomic replicon systems demonstrated that the products encoded in the HCV genome interfere with and disturb intracellular signal transduction, often by phosphorylation of cellular proteins. Moreover, some of the HCV-encoded proteins seem to serve as substrates for host cell protein kinases. These phosphorylations affect the biological functions of the antigens. In many cases it could be demonstrated that only short stretches of the linear sequence of the viral or cellular proteins are involved and play a crucial role for these phosphorylation events. The identification of these small polypeptide elements and the subsequent development of strategies to inhibit protein-protein interactions involving them may be the first step towards reducing the chronicity and/or of the carcinogenicity of the virus. This review summarizes current knowledge of intracellular phosphorylation processes that are affected by HCV.

Carcinoma, Hepatocellular↗

[Tendinitis of the long head of biceps tendon associated with lesions of the "biceps reflection pulley"].

UNLABELLED: In some patients with persistent pain around the Long Head of Biceps Tendon (LHB), lesions of the "biceps reflection pulley", associated with biceps tendinitis, can be found. The aim of this study is to describe the anatomy of the reflection pulley and the arthroscopic appearance of the pulley lesion. Therapeutic options will be discussed. METHOD: The results of a former histo-anatomic study done by the authors in 13 cadaver shoulders are compared with the intra-operative findings in patients with persistent tendinitis of the LHB together with a lesion of the reflection pulley and signs of LHB instability. Intra-operative findings from patients with either posttraumatic anterior instability or calcific tendinitis served as control. RESULTS: The superior glenohumeral ligament (SGHL) together with the coraco-humeral ligament (CHL) and fibers from the subscapularis and supraspinatus tendons form a stabilizing reflection pulley for the LHB in the rotator cuff interval. Arthroscopy shows an association between a lesion of this pulley and persistent LHB-tendinitis. Pulley lesions can occur as isolated ligamentous pathology or together with a partial detachment of rotator cuff tendons. CONCLUSION: In patients with therapy-resistant pain around the LHB, lesions of the reflection pulley need to be excluded beside more common causes of biceps problems. Arthroscopy is a reliable tool to assess these lesions. Therapy should address the definite pathology.

Adult↗

A Belgian traveler who acquired yellow fever in the Gambia.

A 47-year-old Belgian woman acquired yellow fever during a 1-week vacation in The Gambia; she had never been vaccinated against yellow fever. She died of massive gastrointestinal bleeding 7 days after the onset of the first symptoms. This dramatic case demonstrates that it is important for persons to be vaccinated against yellow fever before they travel to countries where yellow fever is endemic, even if the country, like The Gambia, does not require travelers to be vaccinated.

Belgium↗

Arthroscopic treatment of septic joints: prognostic factors.

From 1987 to 1993, 88 patients (average age 48 years, range 3 months to 83 years) with septic arthritis were treated at the orthopaedic clinic König Ludwig Haus of the University of Würzburg by arthroscopic means consisting of joint debridement and application of suction drains, combined with appropriate antibiotics and early functional treatment. The series consisted of 78 knees, 8 shoulders and 3 ankles. At the first visit to our clinic, patients typically presented with fever, leucocytosis, elevated sedimentation rate and localized findings in almost every joint involved (generalized tenderness, swelling, effusion, painful and limited range of motion). All the patients were taken to the operating room on an emergency basis. Broad-spectrum antibiotics were given before the initial culture was evaluated, and its sensitivity was determined. Recovery from arthritis by elimination of joint effusion and disappearance of the inflammatory syndrome occurred in all the joints except for 3 (1 knee joint and 2 shoulders). The number of arthroscopic procedures needed to become free from infection depended on the one hand on the time between onset of symptoms and arthroscopic surgery and on the other on the kind of microorganism discovered. At the average follow-up evaluation after 2.5 years (range 6 months to 5 years), the functional results were excellent or good in 61% of the patients, satisfactory in 20% and poor in 19% from our series. This functional outcome depends on the degenerative changes of the joint before infection, patient's age, and the time interval between onset of symptoms and surgical intervention; indirectly, the time lapse between the onset of infection and surgical intervention also had an influence on the intraoperative macroscopic appearance.

Adolescent↗

Cross-reactivity in flavivirus serology: new implications of an old finding?

To investigate the influence of pre-existing antibodies against tick-borne encephalitis (TBE) or yellow fever (YF) viruses on dengue virus antibody test results, we examined sera from vaccinees and from individuals with previous TBE virus infection. Distinct IgG antibody cross-reactivity was found in about 15.1% in the YF-vaccinated group and in about 9.5% in the TBE-vaccinated group. Altogether 15 out of a total of 80 samples tested (18.8%) had detectable dengue virus IgG antibody titres. The serum samples from patients with acute TBE virus infection not only had the highest anti-TBE virus antibodies but were also highly cross-reactive against dengue virus antigens. The high cross-reactivity rate of YF and TBE antibody-positive sera in dengue virus antibody assays should be taken into account in the interpretation of laboratory tests for the diagnosis of flavivirus infections and when undertaking seroepidemiological surveys.

Antibodies, Viral↗

Calibration results obtained with Liulin-4 type dosimeters.

The Mobile Radiation Exposure Control System's (Liulin-4 type) main purpose is to monitor simultaneously the doses and fluxes at 4 independent places. It can also be used for personnel dosimetry. The system consists of 4 battery-operated 256-channel dosimeters-spectrometers. We describe results obtained during the calibrations of the spectrometers at the Cyclotron facilities of the University of Louvain, Belgium and of the National Institute of Radiological Sciences-STA, Chiba, Japan with protons of energies up to 70 MeV. The angular sensitivities of the devices are studied and compared with Monte-Carlo predictions. We also present the results obtained at the HIMAC accelerator with 500 MeV/u Fe ions and at the CERN high energy radiation reference fields. Records made during airplane flights are shown and compared with the predictions of the CARI-6 model.

Aerospace Medicine↗

Identification of CCK-B/gastrin receptor splice variants in human peripheral blood mononuclear cells.

There is increasing evidence for a direct interaction of the enteric nervous and immune system. Receptors for neuropeptides such as VIP, somatostatin, and substance P have been characterised in human immuno-haematopoietic cells but little is known about the functional significance and expression of receptors for cholecystokinin (CCK) on cells of the immune system. There are only few studies that describe the expression of CCK receptors on human leukaemia-derived cell lines but the receptor structure and function in normal leukocytes have not been clearly established. We therefore sought to determine CCK receptor expression, structure, and function in nontransformed human peripheral blood mononuclear cells.Full-length cDNA clones encoding the human CCK-A and CCK-B/gastrin receptor are expressed in peripheral blood mononuclear cells from healthy volunteers without haematopoietic malignancy. In addition to wild-type CCK-B/gastrin receptor cDNAs, we isolated a splice variant with an in frame insertion of 69 amino acids within its putative third intracellular receptor loop. Dideoxy sequence analysis revealed that the cDNA of this splice variant comprises exons 1-4 but retains intron 4 (207 bp) in the absence of mutations within the splice donor sites. Transient expression of this splice variant in COS-7 cells reveals wild-type affinity for CCK-8, Gastrin-17, and antagonist L-365,260. Affinity for glycine-extended gastrin-17 was not increased when compared to the wild-type CCK-B/gastrin receptor. In vitro, gastrin decreased 3H-thymidine labelling in phytohaemagglutinin-pretreated mononuclear cells at a half-maximally effective concentration of 1.5 nM. We also isolated a cDNA encoding another splice variant of the CCK-B/gastrin receptor with a 158 bp deletion of the entire exon 4 sequence. We conclude that wild-type transcripts of both CCK receptor subtypes and splice variants of the CCK-B/gastrin receptor are expressed in nontransformed human mononuclear cells and that gastrin exhibits antiproliferative effects.

Alternative Splicing↗

Permeability of human HT-29/B6 colonic epithelium as a function of apoptosis.

1. The barrier function of colonic epithelia is challenged by apoptotic loss of enterocytes. In monolayers of human colonic HT-29/B6 cells, apoptosis induced by camptothecin was assessed by poly-(ADP-ribose)-polymerase (PARP) cleavage, histone ELISA and DNA-specific fluorochrome staining (with 4',6'-diamidino-2'-phenylindoladihydrochloride (DAPI)). Epithelial barrier function was studied in Ussing chambers by measuring transepithelial conductivity and unidirectional tracer fluxes. The ion permeability associated with single cell apoptoses was investigated with the conductance scanning technique. 2. The spontaneous rate of apoptotic cells was 3.5 +/- 0.3 % with an overall epithelial conductivity of 3.2 +/- 0.1 mS cm(-2). Camptothecin induced a time- and dose-dependent increase of apoptosis and permeability. With 20 microg ml(-1) of camptothecin for 48 h, apoptosis increased 4.1-fold to 14.3 +/- 1.5 % and the conductivity doubled to 6.4 +/- 1.0 mS cm(-2). 3. While 3H-mannitol flux increased 3.8-fold and 3H-lactulose flux increased 2.6-fold, the flux of 3H-polyethylene glycol 4000 remained unchanged. Hence, the higher permeability was limited to molecules < 4000 Da. 4. The local epithelial conductivity was higher at the sites of apoptosis than in non-apoptotic areas. With camptothecin the leaks associated with apoptosis became more numerous and more conductive, while in non-apoptotic areas the conductivity remained at control level. Hence, the camptothecin-induced increase in epithelial conductivity reflected the opening of apoptotic leaks and thus the results described, for the first time, epithelial permeability as a function of apoptosis only. 5. The conductivity of apoptotic leaks contributed 5.5 % to the epithelial conductivity of controls and 60 % to the conductivity of monolayers treated with 20 microg ml(-1) of camptothecin. Thus apoptosis increased the contribution of paracellular pathways to the overall epithelial permeability. Under control conditions the paracellular conductivity (G(para)) was smaller than the transcellular (G(trans)), but with 12 % apoptosis, G(para) exceeded G(trans). By definition, the epithelium became 'leaky'.

Apoptosis↗

Lassa fever encephalopathy: Lassa virus in cerebrospinal fluid but not in serum.

The pathogenesis of neurologic complications of Lassa fever is poorly understood. A Nigerian patient had fever, disorientation, seizures, and blood-brain barrier dysfunction, and Lassa virus was found in cerebrospinal fluid (CSF) but not in serum. The concentration of Lassa virus RNA in CSF corresponded to 1 x 10(3) pfu/mL, as determined by a quantitative real-time polymerase chain reaction assay. To characterize the Lassa virus in CSF, the 3.5-kb S RNA was sequenced. In the S RNA coding sequences, the CSF strain differed between 20% and 24.6% from all known prototype strains. These data suggest that Lassa virus or specific Lassa virus strains can persist in the central nervous system and thus contribute to neuropathogenesis. Lassa virus infection should be considered in West African patients or in travelers returning from this area who present only with fever and neurologic signs.

Amino Acid Sequence↗

First outbreak of callitrichid hepatitis in Germany: genetic characterization of the causative lymphocytic choriomeningitis virus strains.

Callitrichid hepatitis (CH) is a highly fatal, rodent-borne zoonosis of New World primates (family Callitrichidae) caused by lymphocytic choriomeningitis virus (LCMV). It is unclear whether virulence in Callitrichidae is associated with specific genetic or phylogenetic markers of the virus as only a partial S RNA sequence of a single CH-associated isolate is known. In a period of 10 months, three pygmy marmosets (Cebuella pygmaea) and one Goeldi's monkey (Callimico goeldii) died from CH in a German zoo. LCMV was most likely transmitted by wild mice. Infection was associated with characteristic histopathological lesions in liver, brain, and lymphoid tissue. Virus sequences from all callitrichids and a captured mouse were > or =99.2% identical. LCMV strains from a pygmy marmoset and the Goeldi's monkey were isolated in cell culture and the 3.4-kb S RNA was completely sequenced. Both strains differed considerably in their genetic and phylogenetic characteristics from known LCMV strains, including the previously described CH-associated strain. These data show that CH is widespread and can be caused by distantly related LCMV strains.

Amino Acid Sequence↗

A novel model for the study of the therapy of flavivirus infections using the Modoc virus.

The murine Flavivirus Modoc replicates well in Vero cells and appears to be as equally sensitive as both yellow fever and dengue fever virus to a selection of antiviral agents. Infection of SCID mice, by either the intracerebral, intraperitoneal, or intranasal route, results in 100% mortality. Immunocompetent mice and hamsters proved to be susceptible to the virus only when inoculated via the intranasal or intracerebral route. Animals ultimately die of (histologically proven) encephalitis with features similar to Flavivirus encephalitis in man. Viral RNA was detected in the brain, spleen, and salivary glands of infected SCID mice and the brain, lung, kidney, and salivary glands of infected hamsters. In SCID mice, the interferon inducer poly IC protected against Modoc virus-induced morbidity and mortality and this protection was associated with a reduction in infectious virus content and viral RNA load. Infected hamsters shed the virus in the urine. This allows daily monitoring of (inhibition of) viral replication, by means of a noninvasive method and in the same animal. The Modoc virus model appears attractive for the study of chemoprophylactic or chemotherapeutic strategies against Flavivirus infections.

Animals↗