Biomedical subjects

Andreas Müller

Publications and source records attributed to Andreas Müller.

At least 37 records · Page 2Linked to original sources

PubMed2005

Endogenous Ca2+ buffer concentration and Ca2+ microdomains in hippocampal neurons.

Ca2+-binding proteins are ubiquitously expressed throughout the CNS and serve as valuable immunohistochemical markers for certain types of neurons. However, the functional role of most Ca2+-binding proteins has to date remained obscure because their concentration in central neurons is not known. In this study, we investigate the intracellular concentration of the widely expressed Ca2+-binding protein calbindin-D28k in adult hippocampal slices using patch-clamp recordings and immunohistochemistry. First, we show that calbindin-D28k freely exchanges between patch pipette and cytoplasm during whole cell patch-clamp recordings with a time constant of approximately 10 min. Substituting known concentrations of recombinant calbindin-D28k in patch pipettes enabled us to determine the endogenous calbindin-D28k concentration by postrecording immunohistochemistry. Using this calibration procedure, we find that mature granule cells (doublecortin-) contain approximately 40 microm, and newborn granule cells (doublecortin+) contain 0-20 microm calbindin-D28k. CA3 stratum radiatum interneurons and CA1 pyramidal cells enclose approximately 47 and approximately 45 microm calbindin-D28k, respectively. Numerical simulations showed that 40 microm calbindin-D28k is capable of tuning Ca2+ microdomains associated with action potentials at the mouth of single or clustered Ca2+ channels: calbindin-D28k reduces the increment in free Ca2+ at a distance of 100 and 200 nm by 20 and 35%, respectively, and strongly accelerates the collapse of the Ca2+ gradient after cessation of Ca2+ influx. These data suggest that calbindin-D28k equips hippocampal neurons with approximately 160 microm mobile, high-affinity Ca2+-binding sites (kappa(S) approximately 200) that slow and reduce global Ca2+ signals while they enhance the spatiotemporal fidelity of submicroscopic Ca2+ signals.

Aging↗

PubMed2005

Acute heart failure: clinical presentation, one-year mortality and prognostic factors.

AIMS: Acute heart failure (HF) is a common but ill-defined clinical entity. We describe patients hospitalised with acute HF in regard of clinical presentation, mortality, and risk factors for an unfavourable outcome. METHODS AND RESULTS: We conducted a prospective study including 312 consecutive patients from two European centers hospitalised with acute HF, defined as new onset or worsening of symptoms and signs of HF within 7 days. The mean age was 73 years and 56% were men. Twenty-eight percent had de-novo acute HF and 72% a decompensation of chronic HF. Coronary heart disease (CHD) was the most frequent underlying heart disease, elevated blood pressure >150 mmHg and acute ischemia being the most important triggers. Four percent of the patients had cardiogenic shock, 13% presented with pulmonary edema. LV-EF was <35%, 35-50% and >50% in 35%, 32% and 33% of the patients, respectively. ICU-treatment was necessary in 39% of the patients. Thirty-day mortality (11%) was increased in the presence of shock or elevated troponin T levels. Twelve-month all-cause mortality (29%) increased in the presence of shock, left ventricular dysfunction, renal insufficiency, CHD, and age. CONCLUSIONS: This prospective study shows that despite modern treatment, morbidity and mortality of patients hospitalised with acute HF remain high.

Acute Disease↗

PubMed2005

Performance of community-based glaucoma screening using Frequency Doubling Technology and Heidelberg Retinal Tomography.

PURPOSE: To assess the performance of a community-based glaucoma screening algorithm in the general population. METHODS: A total of 659 individuals aged 50-90 years were screened for glaucoma. Presenting visual acuity, family history of glaucoma, FDT perimetry, and HRT tests were assessed. Additional samples of participants served as control groups. Participants identified as glaucoma positive received a full ophthalmic examination. Based on this exam a consensus diagnosis was made which served as the gold standard. RESULTS: The optimal screening strategy combining visual acuity and family history with FDT and HRT had sensitivities, specificities, positive predictive values and negative predictive values of 96.8%, 89.7%, 31.9%, and 99.8% respectively for detecting glaucoma. CONCLUSIONS: By combining assessments of presenting visual acuity and family history of glaucoma with Frequency Doubling Technology perimetry and Heidelberg Retina Tomography, we devised a community glaucoma-screening algorithm that showed a high sensitivity and specificity for detecting glaucoma in the general population.

Aged↗

PubMed2005

Detection of polyomavirus BK and JC in children with kidney diseases and renal transplant recipients.

BACKGROUND: Reactivation of polyomavirus is a known reason for severe renal dysfunction in adult renal transplant recipients. Testing for polyomavirus DNA in plasma has been described as a sensitive and specific method to discover viral nephropathy in adult patients. We were now interested in polyomavirus status in a pediatric patient setting. METHODS: Plasma and urine samples were obtained from 80 children including 38 children after renal transplantation (group 1), 7 children with different kidney diseases receiving immunosuppressive treatment (group 2) and 35 children with different kidney diseases not receiving immunosuppressive treatment (group 3). A nested polymerase chain reaction method was used for amplification of polyomavirus DNA fragments. Differentiation between JC and BK virus was done by digestion with restriction endonucleases. RESULTS: Polyomavirus DNA was detected in the urine sample of 19 of 38 (50%) renal transplant recipients (group 1), of 1 of 7 (14%) patients from group 2 and in none of the 35 patients of group 3. Plasma samples from 3 (8%) of group 1 patients and from 1 child each of group 2 (14%) and group 3 (3%) were tested positive for polyomavirus DNA. CONCLUSION: Urinary polyomavirus excretion seems to be more frequent in pediatric patients with kidney diseases receiving immunosuppressive treatment and after renal transplantation than in children with various kidney diseases without immunosuppressive treatment.

Adolescent↗

PubMed2005

Extravasation injury in the perioperative setting.

Extravasation is an unintentional injection or leakage of fluid in the perivascular or subcutaneous space. Extravasation injury results from a combination of factors, including solution cytotoxicity, osmolality, vasoconstrictor properties, infusion pressure, regional anatomical peculiarities, and other patient factors. We reviewed the hospital files of patients who had sustained a significant extravasation injury in the perioperative setting at two German hospitals. These cases highlight the risk of devastating consequences from extravasation injury. Vasoactive drugs and hyperosmolar and concentrated electrolyte solutions are the predominant vesicants in the perioperative setting. Prompt and appropriate intervention is important for avoiding or minimizing extensive tissue injury.

Adult↗

PubMed2004

Infrared depletion spectra of 2-aminopyridine2-pyridone, a Watson-Crick mimic of adenine.uracil.

The 2-aminopyridine2-pyridone (2AP2PY) dimer is linked by N-H...O=C and N-H...N hydrogen bonds, providing a model for the Watson-Crick hydrogen bond configuration of the adenine.thymine and adenine.uracil nucleobase pairs. Mass-specific infrared spectra of 2AP2PY and its seven N-H deuterated isotopomers have been measured between 2550 and 3650 cm(-1) by IR laser depletion combined with UV two-color resonant two-photon ionization. The 2PY amide N-H stretch is a very intense band spread over the range 2700-3000 cm(-1) due to large anharmonic couplings. It is shifted to lower frequency by 710 cm(-1) or approximately 20% upon H bonding to 2AP. On the 2AP moiety, the "bound" amino N-H stretch gives rise to a sharp band at 3140 cm(-1), which is downshifted by 354 cm(-1) or approximately 10% upon H bonding to 2PY. The amino group "free" N-H stretch and the H-N-H bend overtone are sharp bands at approximately 3530 cm(-1) and 3320 cm(-1). Ab initio structures and harmonic vibrations were calculated at the Hartree-Fock level and with the PW91 and B3LYP density functionals. The PW91/6-311++G(d,p) method provides excellent predictions for the frequencies and IR intensities of all the isotopomers.

Adenine↗

PubMed2004

Quantitation of microsporidia in cultured cells by flow cytometry.

BACKGROUND: Microsporidia are obligate intracellular protozoan parasites that emerged as major opportunistic pathogens in humans since the onset of the AIDS pandemic. In the present study, we investigated whether FCM is a useful method for the quantitation of intracellular microsporidian spores in cultured cells. METHODS: Microsporidia (Encephalitozoon cuniculi) were grown in cell cultures and various cell-lines were coincubated with microsporidian spores at different multiplicities of infection, as well as for different periods of time. After permeabilization of the cells, intracellular spores were stained with a polyclonal anti-E. cuniculi serum and a FITC-labeled secondary antibody. Stained cells were analyzed on a flow cytometer and results were compared with those of fluorescence microscopy. RESULTS: Noninfected cells showed a lower fluorescence, while the relative fluorescence observed for infected cells was significantly higher. The cell population with the more intense fluorescence, representing cells with internalized microsporidian spores, increased with the multiplicity of infection as well as over time. Results of FCM and fluorescence microscopy were in excellent agreement for all experiments. CONCLUSIONS: We have developed a flow cytometric assay to detect and quantify cells with intracellular microsporidian spores. This method is easy to use, highly reproducible, and should be useful for future research.

Animals↗

PubMed2004

Ross-Konno procedure in neonates: report of three patients.

The Ross-Konno procedure, applied to neonates with severe left ventricular outflow tract (LVOT) obstruction, offers a satisfactory solution in fully releasing the LVOT gradient, and in replacing the aortic valve with a pulmonary autograft with an excellent growth potential. We reported on three recent neonatal cases.

Aortic Valve↗

PubMed2004

Potential cardiovascular risk factors in chronic kidney disease: AGEs, total homocysteine and metabolites, and the C-reactive protein.

BACKGROUND: Total homocysteine (tHcy) and advanced glycation end-products (AGEs) are implicated in the pathogenesis of vascular damage. This study aimed to investigate whether elevated serum levels of the AGEs pentosidine, N(epsilon)-carboxymethyllysine (CML) and imidazolone; tHcy, cystathionine, methylmalonic acid (MMA), and 2-methylcitric acid (2-MCA), as well as C-reactive protein (CRP), are related to a higher risk for cardiovascular events. METHODS: A total of 232 patients with chronic kidney diseases (mean age 57.6 +/- 13.1 years, 82 female and 150 male); 99 with chronic renal failure (CRF), 84 maintenance hemodialysis patients and 49 renal transplant recipients were followed for 2 years. The relationship between the parameters of interest, conventional risk factors and elevated levels of CRP with cardiovascular events was tested in all subjects by the Cox proportional hazards model. RESULTS: Mean serum levels of AGEs, tHcy, and of the metabolites were found to be significantly increased in all three groups compared to the healthy subjects (P < 0.01, respectively). Fifty-three cardiovascular events occurred during follow-up; a total of 40 patients died. Final multivariate analysis showed diabetes (RR 2.06, 95% CI 1.17-3.60, P= 0.013), end-stage renal disease (ESRD) (RR 4.88, 95% CI 2.40-9.89, P < 0.001) and elevated CRP levels (RR 2.00, 95% CI 1.11-3.60, P= 0.021) as independent risk factors for cardiovascular events. CONCLUSION: Data from a group consisting of patients with CRF, patients undergoing maintenance hemodialysis treatment, and renal transplant recipients provide evidence that conventional risk factors such as the presence of diabetes, ESRD, as well as elevated levels of the considered risk factor CRP, seem to play a more important role for cardiovascular outcome in patients with chronic kidney disease than elevated levels of AGEs, tHcy, and related metabolites. The evidence suggests that routine CRP measurement can be recommended in cases of chronic renal insufficiency.

Aged↗

PubMed2004

Sudden sensorineural hearing loss during oral anticoagulant therapy.

This study investigated the role of sudden sensorineural hearing loss (SSNHL) as a symptom in oral anticoagulant therapy with vitamin K antagonists (Phenprocoumon; Marcumar, Falithrom). Vascular compromise of the cochlea due to thrombosis, embolus, reduced blood flow or vasospasm is one of the four possible pathways that can lead to SSNHL. Oral anticoagulant therapy should prevent thrombosis; if it does not the question arises as to whether the anticoagulation is working, or the wrong hypothesis of vascular compromise has been made. Patients with SSNHL during oral anticoagulant therapy who were admitted to the ENT Department of the University Hospital in Jena from 1998 to 2001 were included. The pure-tone audiograms and the prothrombin time (PT) values before and after the event of the SSNHL were evaluated. The study found 10 patients with SSNHL during oral anticoagulant therapy. Although the audiograms showed some improvement in the majority of cases, three cases showed almost no improvement in hearing. On admission, half of the patients showed a PT-value higher than 30 per cent and in nine cases a PT-value >30 per cent could be demonstrated at least once during testing. It was not possible to demonstrate a relationship between the SSNHL and oral anticoagulation. Vascular compromise cannot be excluded as a cause for sudden hearing loss in patients undergoing oral anticoagulant therapy. It is possible that oral anticoagulants influence the viscosity of the plasma leading to interference with the microcirculation in the inner ear. Further research into this area is currently being conducted.

Aged↗

PubMed2003

Analysis of TP53 and PTEN in gliomatosis cerebri.

Gliomatosis cerebri (GC) is a rare glial neoplasm with extensive diffuse brain infiltration but relative preservation of the underlying architecture. Previous molecular studies, mostly analyzing biopsy samples, have suggested an astrocytic origin of GC, but a larger collective of autopsy tissue has not been investigated so far. Furthermore, whether the widespread neoplastic infiltration is based on a monoclonal process is still a matter of debate. In the present study, we screened paraffin-embedded brain tissue from different areas of 18 cases (8 autopsy cases and 10 biopsies) for alterations in the TP53 and PTEN genes. Nuclear accumulation of p53 protein was detected in 9 cases (50%). Somatic TP53 mutations occurred in two autopsy cases (11% of all cases). In the first case, a C-->T transition in codon 273 (Arg-->Cys) was detected in all tumor samples. In the second case, in tumor samples from one hemisphere, nuclear accumulation of p53 was caused by a G-->A transition in codon 244 (Gly-->Asp). In the present series, no mutations within the coding region of PTEN were found. Pten expression was observed in two autopsy cases (25%) and seven biopsy samples (70%). These data suggest that TP53 is affected in some cases, but other yet-unidentified genetic alterations might contribute to tumorigenesis in GC. Furthermore, although GC might be a monoclonal process, the presence of different tumor clones cannot be ruled out.

Adolescent↗

PubMed2003

Method for high-accuracy reflectance measurements in the 2.5-microm region.

Reflectance measurement with spectroradiometers in the solar wavelength region (0.4-2.5 microm) are frequently conducted in the laboratory or in the field to characterize surface materials of artificial and natural targets. The spectral surface reflectance is calculated as the ratio of the signals obtained over the target surface and a reference panel, yielding a relative reflectance value. If the reflectance of the reference panel is known, the absolute target reflectance can be computed. This standard measurement technique assumes that the signal at the radiometer is due completely to reflected target and reference radiation. However, for field measurements in the 2.4-2.5-microm region with the Sun as the illumination source, the emitted thermal radiation is not a negligible part of the signal even at ambient temperatures, because the atmospheric transmittance, and thus the solar illumination level, is small in the atmospheric absorption regions. A new method is proposed that calculates reflectance values in the 2.4-2.5-microm region while it accounts for the reference panel reflectance and the emitted radiation. This technique needs instruments with noise-equivalent radiances of 2 orders of magnitude below currently commercially available instruments and requires measurement of the surface temperatures of target and reference. If the reference panel reflectance and temperature effects are neglected, the standard method yields reflectance errors up to 0.08 and 0.15 units for 7- and 2-nm bandwidth instruments, respectively. For the new method the corresponding errors can be reduced to approximately 0.01 units for the surface temperature range of 20-35 degrees C.

Journal Article↗

PubMed2003

Detection of HHV-8 sequences and antigens in a MALT lymphoma associated with Sjögren's syndrome.

We describe the case of a bilateral parotid mucosa-associated lymphoid tissue (MALT) lymphoma associated with 2 years history of Sjögren's syndrome (SS), which was linked to human herpes virus 8 (HHV-8) infection. Using polymerase chain reaction (PCR) assay HHV-8 sequences were detectable in the lymphoma tissue of both sides. Serologic testing of the patient revealed HHV-8 antibodies in enzyme-linked immunosorbent assay (ELISA) and immunofluorescence assay (IFA). Immunohistologic staining with two antibodies against open reading frame (ORF) 26 and v-cyclin homologues of HHV-8 revealed positive staining of the salivary acinic cells whereas the lymphoma cells were negative. The potential influence of HHV-8 infection for MALT lymphoma development in this case and possible parallels to gastric MALT lymphoma are discussed.

Antigens, Viral↗

PubMed2003

Are advanced glycation end products cardiovascular risk factors in patients with CRF?

BACKGROUND: Chronic renal failure (CRF) is characterized by enhanced formation and accumulation of advanced glycation end products (AGEs), which are involved in the pathogenesis of vascular damage. Their role as risk factors for cardiovascular complications is still unknown. This study aims to investigate whether elevated serum levels of the AGEs pentosidine, N(epsilon)-carboxymethyllysine (CML), and the 3-deoxyglucosone-derived imidazolone involve a greater risk for cardiovascular events (CVEs) and left ventricular hypertrophy (LVH). METHODS: Patients with CRF (n = 99), on maintenance hemodialysis (HD) therapy (n = 84), and renal transplant recipients (RTRs; n = 50) were included. Pentosidine was measured by high-performance liquid chromatography, and CML and imidazolone, by enzyme-linked immunosorbent assays. Statistical analyses were performed using Mann-Whitney U test, logistic regression analysis, and Cox proportional hazards model. RESULTS: At baseline in all investigated groups, patients with a history of CVEs or LVH showed greater mean serum AGE levels. By retrospective data analysis, significant odds ratios for increases in CML and imidazolone levels were calculated for LVH in HD patients, as well as for increases in CML levels for CVEs in RTRs, respectively. By prospective data analysis, serum AGE levels could not be evaluated as independent risk factors for CVEs in all investigated groups. CONCLUSION: From these preliminary results, serum AGE levels could not be identified as independent risk factors for CVEs or LVH in patients with CRF. Prospective studies are needed to answer this question.

Adult↗

PubMed2003

[Successful treatment of a periocular lymphoma with radiotherapy].

BACKGROUND: MALT (mucosa associated lymphoma tissues) reveal specific histological specifications, such as cells like B-lymphocytes with circular structure, B-lymphocytes in the epithelium and a region of larger B-lymphocytes, from the centre to the epithelium. The difference between local and systemic infiltration of tissue is important, and hence MALT must be diagnosed via an interdisciplinary approach. PATIENT: A 45-year old female patient presented initially to our institution in December 1997. She complained of swelling and redness of her upper eyelid which had developed during the last 9 months. Additionally, her visual acuity in the involved eye had decreased steadily over the last 6 months. Ophthalmological examination revealed a swollen right upper eyelid associated with bilateral salmon-coloured conjunctival lesions of the inferior fornices. Additionally, there was a serous detachment of the neurosensory retina in the peripapillary area of the right eye. Systemic work-up including biopsy of the ocular lesions revealed the presence of a localised B-cell lymphoma of the MALT type. Initial treatment with topical and systemic steroids resulted only in a temporary improvement of signs and symptoms. Another treatment trial with steroids was unsuccessful and radiotherapy was therefore performed. Radiotherapy resulted in a complete remission and no signs of recurrent disease during a follow-up period of 4 years. CONCLUSIONS: In patients with isolated MALT lymphomas of the periocular regions radiation may be a successful treatment modality. Side effects as observed in former radiation procedures can be avoided by state-of-the-art treatment modalities. Treatment with steroids may be associated with merely temporary improvement of signs and symptoms. In these patients an interdisciplinary approach utilizing ophthalmology, internal medicine, pathology and radiology is imperative.

Biopsy↗

PubMed2003

[Optical coherence tomography versus ultrasound biomicroscopy of conjunctival and eyelid lesions].

BACKGROUND: The value of ultrasound biomicroscopy in the diagnosis of conjunctival and eyelid lesions is still unknown. METHOD: For the examination of conjunctival and eyelid lesions, we used an anterior segment OCT (4optics, Lübeck) and an ultrasound biomicroscope (Humphrey, Zeiss, Oberkochen) with high frequency transducer (30 MHz). Included in this study were all patients with conjunctival and eyelid lesions, which were consecutively operated on between December 2002 and January 2003. Histological examination of the excised tissue was performed. RESULTS: 38 tumours of 35 patients, aged 8 - 93 years, were examined. 13 tumours were conjunctival lesions and 25 tumours were eyelid lesions. Histological examination displayed the presence of a pterygium (8/38), a seborrhoic keratosis (7/38), a cyst of the eyelid (5/38), a basal cell carcinoma of the eyelid (4/38), a compound naevus of the conjunctiva (4/38), a chalazion (3/38), a primary acquired melanosis (1/38), an actinic keratosis (1/38), a naevus (1/38), a cavernous haemangioma (1/38), a melanoma in situ (1/38), a foreign body (1/38), and an epidermoid cyst (1/38). Using both ultrasound biomicroscopy and optical coherence tomography (OCT) we were able to demonstrate a cystic tumour in the five patients (13 %) with a cyst of the eyelid. With OCT and with ultrasoundbiomicroscopy in all patients with pterygium a slit was found and in patients with compound naevus very small cystic structures were seen, but with OCT the imaging was more reliable. In patients with solid tumours the definite diagnosis could not be differentiated by ultrasound biomicroscopy or OCT alone. Using OCT, assessment of the margins of the tumours (particularly in depth) was impossible or uncertain. CONCLUSION: Compared to ultrasound biomicroscopy OCT is able to show very small cystic structures more distinctly. For assessing the margins of the tumour ultrasound biomicroscopy is the better tool.

Adolescent↗

PubMed2003

A linkage map of an F2 hybrid population of Antirrhinum majus and A. molle.

To increase the utility of Antirrhinum for genetic and evolutionary studies, we constructed a molecular linkage map for an interspecific hybrid A. majus x A. molle. An F(2) population (n = 92) was genotyped at a minimum of 243 individual loci. Although distorted transmission ratios were observed at marker loci throughout the genome, a mapping strategy based on a fixed framework of codominant markers allowed the loci to be placed into eight robust linkage groups consistent with the haploid chromosome number of Antirrhinum. The mapped loci included 164 protein-coding genes and a similar number of unknown sequences mapped as AFLP, RFLP, ISTR, and ISSR markers. Inclusion of sequences from mutant loci allowed provisional alignment of classical and molecular linkage groups. The total map length was 613 cM with an average interval of 2.5 cM, but most of the loci were aggregated into clusters reducing the effective distance between markers. Potential causes of transmission ratio distortion and its effects on map construction were investigated. This first molecular linkage map for Antirrhinum should facilitate further mapping of mutations, major QTL, and other coding sequences in this model genus.

Antirrhinum↗

PubMed2003

Analysis of the transcobalamin II 776C>G (259P>R) single nucleotide polymorphism by denaturing HPLC in healthy elderly: associations with cobalamin, homocysteine and holo-transcobalamin II.

A relatively new method for the detection of single nucleotide polymorphisms is the use of denaturing high-performance liquid chromatography (DHPLC). DHPLC was used to analyse the transcobalamin II 776C>G polymorphism in DNA from 159 healthy elderly. Furthermore, cobalamin, folate, homocysteine and holo-transcobalamin II (holo-TC II) were measured. The allele frequency of the G-allele was 17% with n = 55 harbouring the CC genotype, n = 77 being heterozygous and n = 27 showing the GG genotype. Holo-TC II concentrations were significantly decreased in patients harbouring the GG genotype. There was no effect on cobalamin, methylmalonyl-CoA, folate or homocysteine concentrations. A new G>A variant at nucleotide position 810 in the TC II gene was detected by an altered peak pattern in the DHPLC and further elucidated by direct sequencing. The TC II G810A variant is a silent mutation without replacement of the corresponding amino acid (alanine) at position 270 in the TC II protein and was only found as a heterozygous genotype in a single patient. The new variant would have been undetected by other methods used for single nucleotide polymorphism detection, e.g., restriction fragment length polymorphism analysis. The results suggest that the common TC II 776C>G polymorphism has no major influence on vitamin B12 metabolism.

Aged↗