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Biomedical subjects

M Kuhn

Publications and source records attributed to M Kuhn.

At least 19 recordsLinked to original sources
PubMed2006

Establishment of an early warning system against bluetongue virus in Switzerland.

Bluetongue (BT) is a vector-borne animal disease of economical importance due to the international trade restrictions likely to be put into place in a country once the infection is discovered. The presence of BT and its vectors in countries adjacent to Switzerland stresses the need of implementing a surveillance system and to raise disease awareness among potential stakeholders. A national survey in Switzerland 2003 indicated freedom of Bluetongue virus (BTV), although a single individual of the main BT vector Culicoides imicola was caught in the canton of Ticino. The survey also demonstrated that potential BT vectors, C. obsoletus and C. pulicaris are locally abundant in Switzerland. Therefore, a new surveillance method based on sentinel herds in high risk areas was implemented in 2004 for the early detection of both an incursion of BT vectors into Switzerland, and potential virus circulation among cattle.

Animals↗
PubMed2005

Automated alignment and pattern recognition of single-molecule force spectroscopy data.

Recently, direct measurements of forces stabilizing single proteins or individual receptor-ligand bonds became possible with ultra-sensitive force probe methods like the atomic force microscope (AFM). In force spectroscopy experiments using AFM, a single molecule or receptor-ligand pair is tethered between the tip of a micromachined cantilever and a supporting surface. While the molecule is stretched, forces are measured by the deflection of the cantilever and plotted against extension, yielding a force spectrum characteristic for each biomolecular system. In order to obtain statistically relevant results, several hundred to thousand single-molecule experiments have to be performed, each resulting in a unique force spectrum. We developed software and algorithms to analyse large numbers of force spectra. Our algorithms include the fitting polymer extension models to force peaks as well as the automatic alignment of spectra. The aligned spectra allowed recognition of patterns of peaks across different spectra. We demonstrate the capabilities of our software by analysing force spectra that were recorded by unfolding single transmembrane proteins such as bacteriorhodopsin and NhaA. Different unfolding pathways were detected by classifying peak patterns. Deviant spectra, e.g. those with no attachment or erratic peaks, can be easily identified. The software is based on the programming language C++, the GNU Scientific Library (GSL), the software WaveMetrics IGOR Pro and available open-source at http://bioinformatics.org/fskit/.

Algorithms↗
PubMed2005

Novel approach for assessing performance of PCR cyclers used for diagnostic testing.

As part of a large international project for validation and standardization of PCR, the influence of thermocyclers on PCR was tested. Six brand-new, Peltier technology-driven 96-well thermocyclers were subjected to a novel and stringent in-tube (not block) physical testing. The temperature was directly monitored in PCR tubes containing 50 microl of distilled water at 13 different block positions. The certified temperature accuracy of the measurement system was +/-0.3 degrees C. Finally, the results of the physical testing were compared to those of an amplification efficiency study running an in-house PCR assay. The cyclers did not perform within the manufacturer's specification. Premature timing, under- and overshooting, and spatial variation of heat transfer were found to be the critical factors. The physical testing allowed us to distinguish accurate from less-accurate (2/6) cyclers. The lack of thermal homogeneities became most evident at the denaturation level during the first 15 s. At the time point zero, the accurate cyclers showed temperature deviations of 0.5 to 1.5 degrees C, whereas less-accurate cyclers failed to reach the set temperature by 13 to 20 degrees C. Consequently, the two less-accurate cyclers could not gain positive PCR results by running an in-house PCR assay. However, by modifying the original temperature protocol by increasing the denaturation temperature and time, the amplification efficiency of these two cyclers could be improved significantly. The results have implication for laboratories using diagnostic PCR testing.

DNA, Bacterial↗
PubMed2004

[The importance of a careful examination of all persons in close contact with newly diagnosed infectious tuberculosis].

The diagnosis of infectious pulmonary tuberculosis was made in a 53-year-old Macedonian man. A careful examination of all persons in close contact with him according to the guidelines of the Swiss respiratory society was performed. Pulmonary tuberculosis was diagnosed in his 22-year-old son, in his 20-year-old daughter and in his 3-year-old granddaughter. Seven persons had isoniazid preventive treatment for latent tuberculosis. These data shows very clearly that a careful examination of all persons in close contact with contagious tuberculosis is very important.

Adult↗
PubMed2004

Pharmacokinetics and pharmacodynamic effects of amiodarone in plasma of ponies after single intravenous administration.

Atrial fibrillation is a well-known heart disease in horses. The common therapy consists of administration of quinidine. More potent antiarrhythmic drugs have become available for human therapy and the use of these as alternatives to quinidine for equine antiarrhythmic therapy is a matter of interest. Amiodarone (AMD) is used in human medicine for treatment of many arrhythmias, including atrial fibrillation. Its disposition in horses has not yet been investigated. The purpose of this study was to measure the effect of single intravenous doses of amiodarone (5 and 7 mg/kg) on the surface electrocardiogram (ECG) of healthy minishetland ponies during the first 2 days after drug administration and to calculate pharmacokinetic parameters with a physiologically based pharmacokinetic model (PBPK) using amiodarone and desethylamiodarone (DAMD) plasma levels that were determined by high-performance liquid chromatography (HPLC). As expected for a K(+)-channel-blocker, the main effect on the measured ECG could be seen on the ventricular complex, as the QT interval and the T wave showed statistically significant alterations. The doses investigated were well tolerated clinically. Results from the pharmacokinetic model were found to compare well with literature data of rats, dogs, and humans. It showed a rapid distribution in the tissue, beginning with the rapidly perfused tissue, like the heart, followed by slowly perfused tissues, and finally an accumulation in fat. The half-life for total elimination was calculated to be 16.3 days with 99% eliminated by 97 days. The model predicts that approximately 96% of amiodarone is eliminated as desethylamiodarone in urine, 2% eliminated as desethylamiodarone in bile, and 2% as other metabolites.

Adrenergic beta-Antagonists↗
PubMed2004

[Diarrhea and weight loss in common variable immunodeficiency].

A 25-year-old male was hospitalized for diarrhea and weight loss. Since childhood he had experienced recurrent episodes of pneumonia and diarrhea. Physical and laboratory findings were compatible with malabsorption. On endoscopy, nodular lymphoid hyperplasia (NLH) of the small intestine was found. Common variable immunodeficiency syndrome (CVID) was suspected and diagnosis was established by demonstrating a significant reduction of plasma gamma-globulin levels. Immediately after starting immunoglobulin treatment diarrhea stopped, and both incidence and severity of pulmonary infections were significantly reduced, while recurrent gastrointestinal infections (notably lambliasis and Campylobacter infections) continued to occur and both bronchiectases and splenomegaly were progressive over years. This case report focuses on CVID as a potential underlying cause of diarrhea. The most important complications of the disease are presented. Therapeutical options are discussed in the light of recently published data.

Adult↗
PubMed2004

A validated PCR-based method to detect Listeria monocytogenes using raw milk as a food model--towards an international standard.

A PCR assay with an internal amplification control was developed for Listeria monocytogenes. The assay has a 99% detection probability of seven cells per reaction. When tested against 38 L. monocytogenes strains and 52 nontarget strains, the PCR assay was 100% inclusive (positive signal from target) and 100% exclusive (no positive signal from nontarget). The assay was then evaluated in a collaborative trial involving 12 European laboratories, where it was tested against an additional 14 target and 14 nontarget strains. In that trial, the inclusivity was 100% and the exclusivity was 99.4%, and both the accordance (repeatability) and the concordance (reproducibility) were 99.4%. The assay was incorporated within a method for the detection of L. monocytogenes in raw milk, which involves 24 h of enrichment in half-Fraser broth followed by 16 h of enrichment in a medium that can be added directly into the PCR. The performance characteristics of the PCR-based method were evaluated in a collaborative trial involving 13 European laboratories. In that trial, a specificity value (percentage of correct identification of blank samples) of 81.8% was obtained; the accordance was 87.9%, and the concordance was 68.1%. The sensitivity (correct identification of milk samples inoculated with 20 to 200 L. monocytogenes cells per 25 ml) was 89.4%, the accordance was 81.2%, and the concordance was 80.7%. This method provides a basis for the application of routine PCR-based analysis to dairy products and other foodstuffs and should be appropriate for international standardization.

Animals↗
PubMed2003

[Unilateral pulmonary edema in a dialysis patient with massive fluid overload and mitral valve insufficiency].

A pulmonary edema is not a rare complication in patients with chronic renal failure. Arterial hypertension and fluid overload play a pathogenetically important role. The diagnosis of an unilateral pulmonary edema is often difficult. The following arguments favour the diagnosis: rapid clinical amelioration and disappearance of the alveolar opacities after diuretic treatment alone within 24-72 hours. We describe the case of a 37-year-old patient on dialysis treatment who showed a pulmonary edema of the right lung, predominantly in the upper lobe. This edema was due to fluid overload and mitral insufficiency. After diuretic treatment alone the patient rapidly recovered and the lung infiltrates on the chest X-ray disappeared within a few days.

Adult↗
PubMed2003

[Brain irradiation and phenytoin: a dangerous liaison?].

Three patients are presented, who developed a severe skin reaction after brain-irradiation and concomitant phenytoin treatment. A fourth patient from the databAse of the Swiss Drug Monitoring Center, showed a Stevens-Johnson-Syndrome after a severe electric shock and phenytoin treatment. Possible pathogenic mechanisms of these life-threatening complications and possible alternatives to the phenytoin treatment in irradiated patients are discussed.

Adenocarcinoma↗
PubMed2003

Impaired vasodilator responses to atrial natriuretic peptide in essential hypertension.

BACKGROUND: Atrial natriuretic peptide (ANP) has vasodilating and diuretic/natriuretic properties, both of which contribute to lower blood pressure. These effects are mediated by binding of ANP to a cell-surface receptor [type A guanylyl cyclase (GC-A)]. It has been demonstrated by studies in monogenetic mouse models that the ANP/GC-A system participates in the maintenance of blood pressure homeostasis. METHODS: In male patients with essential hypertension (EH; n = 36) as the only cardiovascular risk factor and normotensive controls (n = 12), blood flow was measured in the forearm circulation in response to i.a. infusion of synthetic human ANP, acetylcholine, orciprenaline, and sodium nitroprusside by strain-gauge venous plethysmography. In blood samples, cyclic guanosine'5-monophosphate (cGMP) and ANP concentrations were measured at resting conditions and during exogenous ANP infusion. In 200 patients with EH, genomic DNA was screened for an inhibitory deletion mutation of the GC-A gene, which has been recently linked to EH in a Japanese cohort. RESULTS: The vasodilatations in response to ANP and acetylcholine were impaired in the forearm circulation of patients with EH, whereas the responses to orciprenaline and nitroprusside were preserved. Plasma ANP and cGMP concentrations were increased in the patients with EH both at resting conditions and during ANP infusion; the resting plasma cGMP levels correlated significantly with the plasma ANP levels (r = 0.68). A specific deletion mutation of the GC-A gene did not account for the diminished relaxant effects of ANP in our study population. CONCLUSIONS: The vascular ANP/GC-A pathway is altered in patients with EH, in addition to the known defects on the nitric oxide/cGMP pathway. Attenuation of the vasodilative responses to ANP suggests impaired receptor or postreceptor responsiveness of GC-A. It is possible that this dysfunction participates in the pathomechanism of EH.

Atrial Natriuretic Factor↗
PubMed2002

Identification and characterisation of regions in the cellular protein LaXp180 and the Listeria monocytogenes surface protein ActA necessary for the interaction of the two proteins.

The Listeria monocytogenes surface protein ActA is an important virulence factor that plays an essential role in intracellular movement of Listeria cells by inducing actin polymerisation. The ActA protein is known to interact with several mammalian proteins including the phosphoprotein VASP, actin and the Arp2/3 complex. In a search for additional ActA-binding proteins we recently employed the yeast two-hybrid system to search for proteins that interact with ActA, and identified, among others, the mammalian protein LaXp180 as a binding partner. In the present study the interaction of the two proteins was investigated in more detail. A number of variants were tested in the yeast two-hybrid system for their ability to interact. On the basis of these assays, the 14 C-terminal amino acids of LaXp180 were identified as being necessary for the interaction with ActA. The proline-rich repeat (PRR) region of ActA was found to be necessary for the interaction with LaXp180, but upstream or downstream sequences are also required to enhance the specificity of the interaction. The second and third repeats in ActA are especially important, and the minimal sequence of ActA capable of interacting with LaXp180 was a proline- and glutamate-rich stretch of PRR3 fused to part of the N-terminal sequence of ActA. Further analysis using site-specific mutations located in either the C-terminal region of LaXp180 or the proline-rich motif of PRR3 of ActA showed that three positively charged amino acids in LaXp180 and two negatively charged amino acids in ActA are critical for the interaction of the two proteins.

Amino Acid Sequence↗
PubMed2002

[Ambulance transport of patients with respiratory problems: a prospective observational study].

The aim of this study was to prospectively compile and analyze all emergency transports of patients with respiratory problems. The main target variables were frequency of the different reasons for transport and treatments administered during the emergency event. Special emphasis was placed on the use of inhalation therapy. The data of all patients who, in 2000, were transported by the "Realü" emergency medical service of the Chur Rhine Valley (a community with a population of approximately 100,000) due to respiratory problems were prospectively compiled according to predefined criteria. The emergency records and the medical release reports were evaluated. A total of 137 patients were prospectively included for the year 2000, corresponding to 8% of all patients transported by "Realü" (out of a total of 1675 patients). The average age was 66 years (2-98 years). Around one-fifth of the transports involved patients with exacerbations of chronic obstructive pulmonary disease (COPD), pulmonary embolisms, pulmonary infections or cardiac dyspnea. Six patients (5%) were transported by ambulance because of bronchial asthma. Inhalation therapy was administered in only 41% of the cases with obstructive pulmonary disease in which it would have been indicated. In conclusion, our evidence shows that bronchial asthma is the primary diagnosis in only 6% of the patients requiring emergency transport due to respiratory symptoms. In these emergency situations, antiobstructive inhalation therapy was given to a mere 41% of the patients suffering exacerbations of COPD or bronchial asthma. More frequent use of such a simple and effective treatment should be encouraged.

Adolescent↗
PubMed2002

[Suspected neurological side-effects of tick-borne meningoencephalitis vaccination: experiences of the Swiss Adverse Drug Reaction Reporting Center].

The number of patients affected by tick-born encephalitis (TBE) in Switzerland has increased in the last years and an extension of the endemic foci of TBE has been observed. Therefore, active immunization by TBE vaccination has become more important. The possible adverse vaccine reactions have to be known as exactly as possible. The Swiss Drug Monitoring Center SANZ received from 1987 until June 2000 33 spontaneous cases reporting on 39 neurological adverse reactions in a close temporal relationship with a TBE vaccination and a suspected causal relationship. The following adverse reactions were reported most frequently: headache in 36%, neuropathy in 18% and meningeal irritation in 13%. Twelve out of 33 patients were hospitalized due to the adverse reaction. All neurological reactions were reversible. The spontaneous reporting scheme of the SANZ does not allow to calculate the incidence of neurological reactions after TBE vaccination. In general, adverse neurological reactions after TBE vaccination seem to be rare. According to the experiences of SANZ all reported neurological reactions were reversible.

Adolescent↗
PubMed2002

Progressive cardiac hypertrophy and dysfunction in atrial natriuretic peptide receptor (GC-A) deficient mice.

OBJECTIVE: To investigate how permanent inhibition of guanylyl cyclase A receptor (GC-A) affects cardiac function. METHODS: Hearts of GC-A-/- and corresponding wild type mice (GC-A+/+) were characterised by histological, western blotting, and northern blotting analyses. Cardiac function was evaluated in isolated, working heart preparations. RESULTS: At 4 months of age, GC-A-/- mice had global cardiac hypertrophy (about a 40% increase in cardiac weight) without interstitial fibrosis. Examination of heart function found a significant delay in the time of relaxation; all other parameters of cardiac contractility were similar to those in wild type mice. At 12 months, the hypertrophic changes were much more severe (about a 61% increase in cardiac weight), together with a shift in cardiac gene expression (enhanced concentrations of atrial natriuretic peptide (3.8-fold), B type natriuretic peptide (2-fold), beta myosin heavy chain (1.6-fold) and alpha skeletal actin (1.7-fold) mRNA), increased expression of cytoskeletal tubulin and desmin (by 29.6% and 25.6%, respectively), and pronounced interstitial fibrosis. These changes were associated with significantly impaired cardiac contractility (+dP/dt decreased by about 10%) and relaxation (-dP/dt decreased by 21%), as well as depressed contractile responses to pressure load (all p < 0.05). CONCLUSIONS: Chronic hypertension in GC-A-/- mice is associated with progressive cardiac changes--namely, initially compensated cardiomyocyte hypertrophy, which is complicated by interstitial fibrosis and impaired cardiac contractility at later stages.

Animals↗
PubMed2002

Blood viscosity and platelet function in patients with obstructive sleep apnea syndrome treated with nasal continuous positive airway pressure.

Patients with obstructive sleep apnea syndrome (OSA) have a high incidence of cardiovascular events. We measured whole blood viscosity at high (94.5 s(-1)) and low (0.1 s(-1)) shear rate, hematocrit, fibrinogen, and platelet hemostatic function (PTA-100) at 7-8 p.m. and 7-8 a.m. in 8 controls and 13 patients, once with the established nasal continuous positive airway pressure (NCPAP) treatment and once without. OSA patients had a higher plasma viscosity (1.37+/-0.11 vs. 1.19+/-0.11 mPa.s in the evening, p<0.05) and fibrinogen (2.61+/-0.49 vs. 2.11+/-0.29 g/l, p<0.05) than controls, without diurnal difference, and similar values with or without NCPAP. Whole blood viscosity and hematocrit were similar in controls and patients before and after a night with or without NCPAP. Platelet activity was significantly higher in the morning than in the evening in controls and patients with or without NCPAP. We conclude that blood viscosity and platelet activity are similar in controls and patients with OSA on a long-term treatment with NCPAP, which is not worsened by a single night without NCPAP. The increase of plasma viscosity and fibrinogen in OSA patients as well as the general increase of platelet aggregation in the morning may contribute to the increased incidence of cardiovascular events.

Aged↗