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T Neuhaus

Publications and source records attributed to T Neuhaus.

At least 19 recordsLinked to original sources
PubMed2006

Free-energy calculations with multiple Gaussian modified ensembles.

We present a Monte Carlo algorithm, which samples free energies of complex systems. Less probable configurations are populated with the help of a multitude of additional Gaussian weights and parallel tempering is used for efficient Monte Carlo moves within phase space. The algorithm is easily parallelized and can be applied to a wide class of problems. We discuss algorithmic performance for the case of low-temperature phase separation in two-dimensional and three-dimensional Ising models, where we determine the magnetic interface tension. Multiple Gaussian modified ensemble simulations, unlike multicanonical ensemble simulations do not require a priori knowledge of the free energy and are of similar efficiency as multicanonical ensemble and Wang-Landau simulations.

Journal Article↗
PubMed2004

Reliability of non-invasively acquired human genomic DNA as a substrate for real-time PCR-assisted analysis of genetic polymorphisms.

Molecular epidemiological studies require high numbers of participants. The combination of an non-invasive access to human DNA with a rapid genotyping analysis, e.g. by use of LightCycler assisted real-time polymerase chain reaction (PCR), can be helpful in conducting such trials. The aim of our study was to define, for the first time, the use of LightCycler technology in analysis of non-invasively derived DNA. DNA extracted from blood, mouthwash and buccal cytobrush samples from 100 volunteers was analyzed for the genotypes of cytochrome P450 CYP1B1, and glutathione S-transferases GSTT1, GSTM1 and GSTP1. The median amounts of DNA isolated from blood, mouthwash and buccal cytobrush samples were 95, 11 and 8 microg, respectively. While genotyping for CYP1B1 codon 432 polymorphism and GSTP1 codon 105 polymorphism resulted in a complete correspondence for all three modes of sampling, the identification of individuals with null-genotype for GSTT1 or GSTM1 failed in some cases due to atypical courses of the corresponding melting curves, leading to high false-positive rates in the group of non-invasively derived samples. Thus, the results presented here call for caution in using LightCycler assisted real-time PCR in non-invasively collected samples, at least when appropriate control strategies are not implemented.

Adult↗
PubMed2003

Fatal pulmonary scedosporiosis.

We report on a case of scedosporiosis in a 72-year-old German woman. Her disease started with a purulent ulceration of unknown course at her left foot. Soon after onset of oral antibacterial therapy she needed in-hospital treatment because of an acute pneumonia. The infection progressed despite the application of different antibiotics. Microscopic examination of tracheal fluid revealed fungal hyphae and therefore treatment with itraconazole was initiated. However, the patient developed renal failure, required mechanical ventilation and finally died in treatment-resistant septic shock. Post-mortem Scedosporium apiospermum was cultured from lung tissue taken during autopsy. This is the fourth case of human infection caused by Scedosporium species diagnosed in our laboratory during the last 4 years.

Aged↗
PubMed2002

[Recurrent spontaneous hemorrhage in a patient with light chain immunocytoma].

The 48-year-old female patient was sent to our clinic for further evaluation of a spontaneous decrease of prothrombin- and prolongation of the bleeding-time. She presented in good conditions with an enlargement of cervical lymphnodes and the history of a monoclonal plasmacyte dyscrasia. The laboratory results revealed a pronounced decrease of prothrombin-time, a prolonged activated partial thromboplastin-time, a decrease of factor VII and X activity and a light chain paraprotein. The histological examination of the bone marrow led to the diagnosis of an immunocytoma and a medullar amyloidosis. For the aim of influencing the coagulopathy the patient was treated with chemotherapy. However, she developed severe bleedings. Further haemostaseological tests presented an amyloidosis-associated decrease of factor VII and X, an acquired von Willebrands disease, an acquired thrombozytopathy and a lupus-like anticoagulans. Under substitution of factor VIII-von Willebrand-factor-complex and chemotherapeutic treatment a stabilisation over several years was achieved till the patient died due to an amyloid-associated acute pancreatitis.

Amyloidosis↗
PubMed2002

[Local and systemic symptoms after snake bite by a diamondback rattlesnake (Crotalus atrox)].

The incidence of snake bites grows more and more. The effects of the snake poison depend on the snake species. They can be cardio-, neuro-, myo-, tissue-, and/or cytotoxic, as well as hemorrhagically. In most cases a symptomatically therapy together with close controls of the labor parameters and a good monitoring is enough. Antivenom-therapy should be reserved for cases with strong indication.

Adult↗
PubMed2001

[An uncommon cause of severe soft tissue bleeding during phenprocoumon treatment].

HISTORY AND ADMISSION FINDINGS: A 66-year-old patient presented to our clinic with extensive left arm and left flank haematomas, anaemia, a prolonged activated partial thromboplastin time (aPTT), and reduced factor IX activity 6 weeks after prosthetic mechanical aortic valve implantation. INVESTIGATION: Treatment with both vitamin K and a single injection of factor IX concentrate led to normalization of the activated partial thromboplastin time and factor IX activity, which remained constant for several days. No acquired factor IX inhibitor was detectable. Analysis of exon 2 of the factor IX gene revealed a C-->T mutation in codon 10 of the propeptide region, resulting in the substitution of alanine by valine. Echocardiography revealed a significant paravalvular leak. TREATMENT AND COURSE: The substitution of valine for alanine in the factor IX propeptide leads to an impaired affinity of factor IX to the vitamin K-carboxylase complex. In this situation, treatment with coumarin derivatives can profoundly reduce factor IX activity and result in severe bleeding episodes. This patient was re-exposed to warfarin under close hematological monitoring. After 4 days factor IX activity had decreased to 15%, which was associated with an increase of the aPTT and a mild decrease of the prothrombin time. Due to rapid progression of the paravalvular leak and almost impossible long-term orale anticoagulation with coumarin derivatives, we recommended replacement of the prosthetic mechanical valve with a biological device. CONCLUSION: The development of severe bleeding in the context of initiating warfarin therapy raises the suspicion of a factor IX propeptide mutation. The initial screening test is the activated partial thromboplastin time, which is elevated in the presence of the mutation. If concomitantly diminished factor IX activity is found the factor IX propeptide mutation should be excluded. Use of lifelong coumarin derivatives is contraindicated in patients with this mutation. However, a general screening of the activated partial thromboplastin time after coumarin initiation is not justified by cost/benefit analysis.

Aged↗
PubMed2001

The effect of dexamethasone on respirator-dependent very-low-birth-weight infants is best predicted by chest X-ray.

BACKGROUND: Chronic lung disease (CLD) in premature infants shows a variable clinical course with different radiological manifestations. OBJECTIVE: To evaluate the correlation between parameters of trans-membrane permeability [albumin/secretory component (SC)] and oxidative stress [malondialdehyde (MDA)/SC] in tracheal aspirate fluid (TAF) and radiological findings with the effect of a 5-day course of dexamethasone (0.5 mg/kg per day). MATERIALS AND METHODS: Fifty ventilator-dependent premature infants with birth weights < 1,500 g (gestational ages 23-31 weeks) and radiological signs of early chronic lung disease (CLD) were treated with dexamethasone at day of life 5-27 (median 10 days) because of respiratory deterioration. TAF was collected serially. Chest X-rays taken before and 8-10 days after dexamethasone were scored for changes of opacification, consolidation and hyperinflation/emphysema, and classified into three groups. RESULTS: Twenty-four infants had a positive response to dexamethasone, defined as a reduction of the ventilation index FiO2 x mean airway pressure > 40% at day 5, compared to pretreatment values. About 80% of the responders showed homogeneous lung opacification on chest X-ray, reflecting leaky lung syndrome. In contrast, seven of eight infants with predominantly emphysema on radiology were non-responders; 80% of infants with a mixed radiological picture characterized by predominance of consolidations alternating with regions of emphysema were also non-responders. Ratios of albumin/SC and MDA/SC in TAF decreased significantly within 3 days after the onset of dexamethasone. However, MDA/SC was persistently higher in non-responders compared to responders. Opaque lungs were largely improved by dexamethasone, in contrast to streaky or patchy consolidations and emphysema. In a logistic regression model, radiographic classification was the most important factor influencing the response to dexamethasone with a positive predictive value of 86%, followed by albumin/SC ratio. CONCLUSIONS: The optimum timing of dexamethasone treatment may be determined by the stage of developing CLD and radiological findings rather than by the age of the premature infant.

Albumins↗
PubMed2001

Defining severe community-acquired pneumonia.

Based on the recognition of the main pathophysiologic features of pneumonia and currently available data on prognosis and clinical severity assessment, key points for a definition of severe pneumonia are as follows: 1. Independent predictors of pneumonia severity are factors reflecting acute respiratory failure and severe sepsis or septic shock. 2. In view of the dependence of the development of acute respiratory failure on pulmonary comorbidities, radiographic extension may prove to be an additional independent predictor of severe respiratory compromise. 3. Vital sign abnormalities other than acute respiratory failure and severe hypotension may be independent predictors of severity, particularly in patients presenting in early and asymptomatic stages of severe sepsis. 4. Several pathogens have been shown to have adverse prognostic potential. Because the cause is unknown at the initial evaluation, however, pathogens cannot form part of the criteria for the initial severity assessment. 5. Because pneumonia is a dynamic process, any assessment of severity takes place at an arbitrary point of disease evolution. It would be desirable to define a set of parameters reflecting initial severity as well as a state of increased risk for early deterioration toward severe pneumonia. 6. Severity stratification within the population of patients with severe pneumonia may open the prospect of identifying patients who may have the greatest benefit from intensive care.

Age Factors↗
PubMed2000

Identification of syntenin and other TNF-inducible genes in human umbilical arterial endothelial cells by suppression subtractive hybridization.

Endothelial cells play an important regulatory role in inflammatory responses by upregulating various proinflammatory gene products including cytokines and adhesion molecules. A highly potent mediator of this process is tumor necrosis factor-alpha (TNF). In the present study, the suppression subtractive hybridization (SSH) method was employed to identify rarely transcribed TNF-inducible genes in human umbilical arterial endothelial cells. Following mRNA isolation of non-stimulated and TNF-stimulated cells, cDNAs of both populations were prepared and subtracted by suppression PCR. Sequencing of the enriched cDNAs identified 12 genes differentially expressed including vascular cell adhesion molecule-1, monocyte chemoattractant protein-1, interleukin-8 and IkappaBalpha, an inhibitor of the transcription factor nuclear factor-kappaB. Interestingly, also syntenin, a PDZ motif-containing protein which binds to the cytoplasmic domain of syndecans, was identified by SSH. Time course studies using RT-PCR analysis confirmed that all genes were differentially expressed and rapidly induced by TNF. Our data reveal that SSH is a powerful technique of high sensitivity for the detection of differential gene expression in primary arterial endothelial cells.

Carrier Proteins↗
PubMed2000

Rapid analysis of alpha1-antitrypsin PiZ genotype by a real-time PCR approach.

alpha1-Antitrypsin (AAT) deficiency is a common inherited cause of emphysema and cirrhotic liver disease. Current laboratory diagnosis of Pi (proteinase inhibitor) status by protein analysis depends on the availability of blood samples and has a limited accuracy. Single-strand conformational polymorphism (SSCP) analysis and direct DNA sequencing can be performed from blood cells or from tissue samples, but it is a time-consuming procedure not suitable for screening purposes. We used a Light-Cycler assisted PCR approach to identify the PiZ mutation and to determine hetero- and homozygous carrier status from whole blood and from paraffin-embedded archival tissue specimens. The results were compared to those obtained by standard PCR amplification followed by SSCP and direct DNA sequencing. Light-Cycler assisted PCR identified heterozygous PiZ mutations in 16 samples, a homozygous PiZ status in three cases, and wild-type PiM in five control samples. In all cases the results were confirmed by SSCP and direct DNA sequencing. Light-Cycler assisted PCR has a high detection rate for the PiZ mutation. It can be performed from blood or from fixed archival tissues, requires only small amounts of DNA, and allows a rapid diagnosis on a high output level.

DNA↗
PubMed2000

Tumour necrosis factor-alpha gene expression and production in human umbilical arterial endothelial cells.

Endothelial cells act as an interface between the blood and tissues, and are known to be involved in inflammatory processes. These cells are responsive to and produce different cytokines. Tumour necrosis factor-alpha (TNF-alpha) not only is one of the most important inflammatory peptides, but also can be induced by lipopolysaccharide (LPS). The focus of the present study was on TNF-alpha gene expression and production in human umbilical arterial endothelial cells (HUAEC), including the kinetics of this process. Interleukin-1alpha (IL-1alpha), LPS and TNF-alpha, which are all known to be elevated in septic shock, were used as stimulators at concentrations commonly found in patients with sepsis. Through the use of reverse transcriptase/PCR, immunohistochemical reactions and ELISA techniques, we showed that, in HUAEC, all three stimuli were able to induce gene expression and production of TNF-alpha. Furthermore, this induction by IL-1alpha, LPS and TNF-alpha occurred in a time- and concentration-dependent manner in these cells. TNF-alpha expression and production was induced by all three agents at concentrations commonly found in patients with sepsis. TNF-alpha mRNA was observed within 30 min regardless of the stimulus used, but the levels peaked at different times. Since it is well established that TNF-alpha is able to induce the synthesis of IL-1alpha in endothelial cells and, as shown in the present study, TNF-alpha and IL-1alpha are themselves able to induce the synthesis of TNF-alpha in endothelial cells, an autocrine potentiation of cytokine release in sepsis can be proposed. This situation could lead to a locally acting 'vicious cycle' which, when considered in addition to the known ability of TNF-alpha to induce apoptosis, could mean that various organs will be damaged, a condition associated with sepsis. Thus these results provide further evidence for the important role played by the endothelium in inflammation.

Blotting, Southern↗
PubMed1999

[Cushing syndrome with occult ectopic ACTH production].

A 19-year old patient was admitted to our hospital with the typical stigmata of a prolonged Cushing's syndrome. He presented first at another hospital with elevated ACTH values and the diagnosis of pituitary Cushing's syndrome was made. A partial hypophysectomy was performed, but neither this nor a therapy with ketokonazole could influence the cortisol levels. Because of this background the diagnosis of ectopic ACTH-production was established. Since we were not able to locate a source of ACTH, we recommended a bilateral adrenalectomy, after which the symptoms of Cushing's syndrome disappeared within a few months. About one year after the operation a CT-scan demonstrated an intrapulmonary mass, which was removed surgically. There were neither signs of local infiltration nor of lymphogenic metastasis. The histological and immunhistochemical diagnosis was typical of bronchial carcinoid with ACTH-production. The follow up so far did not reveal a recurrence.

ACTH Syndrome, Ectopic↗
PubMed1999

Renal chloride channel, CLCN5, mutations in Dent's disease.

Dent's disease is an X-linked renal tubular disorder characterized by low-molecular-weight proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis, and renal failure. Patients with Dent's disease may also suffer from rickets and other features of the renal Fanconi Syndrome. Patients may have mutations in the X-linked renal chloride channel gene, CLCN5, which encodes a 746-amino-acid protein with 12-13 transmembrane domains. We have investigated the 11 coding exons of CLCN5 for mutations in eight unrelated patients with Dent's disease. Leukocyte DNA was used for the polymerase chain reaction amplification of CLCN5 and the products analyzed for single-stranded conformational polymorphisms (SSCPs). Abnormal SSCPs were sequenced and revealed eight mutations. These consisted of three nonsense mutations (Arg34Stop, Arg648Stop, Arg704Stop), four deletions involving codons 40, 86, 157, and 241, and one acceptor splice consensus sequence mutation tgcag --> tgaag. The mutations were confirmed either by restriction endonuclease or sequence-specific oligonucleotide hybridization analysis. In addition, an analysis of 110 alleles from 74 unrelated normal individuals demonstrated that the DNA sequence changes were not common polymorphisms. All of the mutations predict truncated chloride channels that are likely to result in a functional loss. Thus, our findings expand the spectrum of CLCN5 mutations associated with Dent's disease and the results will help to elucidate further the functional domains of this novel chloride channel.

Amino Acid Sequence↗
PubMed1998

Effect of plasma from patients with idiopathic nephrotic syndrome on proteoglycan synthesis by human and rat glomerular cells.

In vivo and in vitro findings have shown that plasma of patients with idiopathic nephrotic syndrome (INS) contain factors that increase glomerular permeability to proteins. The effects of these factors on proteoglycan synthesis by glomerular cells are unknown. To investigate the effect of plasma from patients with INS (n = 23) and other glomerulopathies (n = 12) on the amount of proteoglycans synthesized by cultured rat mesangial cells and human glomerular epithelial cells, glomerular cells were cultured for 24 h with plasma from patients or control subjects, and incorporation of Na2(35)SO4 in chondroitin dermatan sulfate and heparan sulfate was assessed using a cationic nylon membrane. The mean ratio of glycosaminoglycan produced by rat mesangial cells when in contact with plasma (5%) from INS patients to the amount produced when in contact with control plasma was 0.70+/-0.06. The mean ratio of heparan sulfate was 0.58+/-0.08. The decrease of heparan sulfate production was present in the cellular and in the extracellular fraction. It was observed when the cells were in contact with plasma from patients in relapse but not when in remission. No decrease of heparan sulfate production was observed with four of the five patients with membranous glomerulonephritis (ratio of 1.27+/-0.03), IgA nephropathy (n = 5, ratio of 1.27+/-0.03), and membranoproliferative glomerulonephritis (n = 2, ratio of 1.39+/-0.34). When human glomerular epithelial cells were exposed to 5% plasma from INS patients in relapse (n = 9), the mean ratio of heparan sulfate was 0.62+/-0.06 in the cellular fraction and 0.72+/-0.08 in the medium. When in contact with plasma from patients in remission, no difference of glycosaminoglycan production was observed. A factor present in plasma from patients with INS during initial episodes or relapses is able to decrease the proteoglycan production of glomerular cells.

Animals↗
PubMed1997

Influence of nutrition on urinary oxalate and calcium in preterm and term infants.

Few data for normal urinary oxalate (Ox) and calcium (Ca) excretion related both to gestational age and nutritional factors have been reported in preterm or term infants. We therefore determined the molar Ox and Ca to creatinine (Cr) ratios in spot urines from 64 preterm and 37 term infants aged 1-60 days, either fed formula or human milk (HM). Only vitamin D was supplemented; renal or metabolic diseases were excluded. Urinary Ox/Cr ratio was higher in preterm than in term infants, both when formula fed (1st month 253 vs. 180 mmol/mol and 2nd month 306 vs. 212 mmol/mol; P<0.05) or HM fed (206 vs. 169 mmol/ mol and 283* vs. 232 mmol/mol; *P<0.05). Ox/Cr was also higher in formula- than HM-fed preterm infants. The ratio increased during the first 2 months of life irrespective of nutrition. Urinary Ca/Cr ratio was comparable in all groups during the 1st month of life, except for a lower (P < 0.05) value in term infants fed HM (0.10 mol/mol). It increased in all groups during the 2nd month of life, being highest in HM-fed preterm infants (1.86 mol/mol). In conclusion, urinary Ox and Ca excretion is influenced by both gestational age and nutrient intake in preterm and term infants.

Breast Feeding↗
PubMed1997

A vertical (pseudodominant) pattern of inheritance in the autosomal recessive disease primary hyperoxaluria type 1: lack of relationship between genotype, enzymic phenotype, and disease severity.

Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disease caused by a deficiency of alanine:glyoxylate aminotransferase (encoded by the AGXT gene). Primary hyperoxaluria type 1 is characterized by the elevated urinary excretion of oxalate and glycolate, and the deposition of insoluble calcium oxalate in the renal parenchyma and urinary tract. In the present study, we investigated an unusual family containing four affected individuals in two different generations. Based on our genetic, enzymic, metabolic, and clinical analyses, we have come to the following conclusions. First, although the pattern of inheritance of PH1 is usually horizontal (ie, all patients in the same generation), as expected for an autosomal recessive disease, it can sometimes show a vertical (pseudodominant) pattern of inheritance (ie, patients in more than one generation) due to the segregation within a family of three, rather than two, mutant AGXT alleles. Second, affected members of such a family can manifest very different clinical phenotypes both within and between generations. Although the clinical differences between generations might be at least partly due to differences in AGXT genotype, differences can equally occur within the same generation in individuals who possess the same AGXT genotype. Finally, individuals with PH1 at the level of the AGXT genotype might remain asymptomatic and undiagnosed for many years. The consequences of these findings for the clinical management and genetic counseling of families with PH1 are profound and wide-ranging.

Adolescent↗