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Biomedical subjects

M Lindner

Publications and source records attributed to M Lindner.

At least 19 recordsLinked to original sources
PubMed2006

Clinical course of collagenous colitis over a period of 10 years.

AIM: The aim of this study was to evaluate the long-term outcome of patients with collagenous colitis 10 years after the diagnosis. PATIENTS AND METHODS: In 1989/1990, 65 patients were diagnosed to have collagenous colitis. Initially and after an interval of ten years these patients were asked to complete a questionnaire including onset and duration of diarrhea, stool frequency and consistency, other gastrointestinal symptoms including weight loss, drug history, treatment response and concomitant diseases. RESULTS: Questionnaires from 47 patients (72.3 %) (female 40; mean age 68 years, range 41 - 95 years) were available for analysis. After a follow-up of ten years, 11 patients (23.4 %) had persistent diarrhea with no change of frequency and consistency compared to baseline. Four patients (8.5 %) showed a reduction of diarrhea frequency of at least 50 %. Diarrhea was resolved in 23 patients (48.9 %) during the follow-up period. Of those, 20 patients received anti-inflammatory treatment. After a complete resolution of diarrhea during the long-term follow-up, 9 patients (19.2 %) showed recurrence of diarrheal symptoms. None of the patients developed any malignancies of the GI-tract. CONCLUSION: The long-term outcome of CC is benign with a resolution of diarrhea in up to 50 % of patients receiving anti-inflammatory treatment. About 30 % of patients may experience persistent diarrhea even 10 years after diagnosis. Our data confirm that CC is a chronic disorder with a variable course of symptoms during a long-term follow-up.

Adult↗
PubMed2006

Expression of chemokine receptors on peripheral blood mononuclear cells of patients with immune-mediated neuropathies treated with intravenous immunoglobulins.

Intravenous immunoglobulin (IVIg) is an efficacious treatment for immune-mediated neuropathies like Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating neuropathy (CIDP), and multifocal motor neuropathy (MMN). In the pathogenesis of immune-mediated neuropathies chemokines and their receptors play a crucial role. Using flow cytometry we examined whether IVIg modulates chemokine expression repertoires of T cells and monocytes. The expression of inflammatory chemokine receptors CCR1, CCR2, CCR4, CCR5, CCR6 and CXCR3 was investigated on circulating T-cell subsets, and CCR1, CCR2 and CCR5 on circulating monocytes before and after IVIg treatment in patients with immune-mediated neuropathies (MMN, n = 7; GBS, n = 1; CIDP, n = 2). Furthermore, the homing potential of T cells was analyzed by the expression of CCR7, a chemokine receptor known to be utilized by mature T cells to recirculate into secondary lymphoid organs. In contrast to studies in chronic heart failure, no differences in expression patterns before and after IVIg treatment of any of the investigated chemokine receptors were found. Furthermore, the proportion of CD45RO-positive CD4+ or CD8+ T-cell subsets was not changed by IVIg treatment. Thus, we concluded that modulation of the expression of chemokine receptors on circulating leukocytes by IVIg is not a mode of action in immune-mediated neuropathies.

Adult↗
PubMed2005

Hypereosinophilic syndrome associated with acute necrotizing myocarditis and cardiomyopathy.

We report the rare case of a 55-year-old female with massive eosinophilic myocarditis and severe, however reversible, impairment of left ventricular function. The patient presented with reduced physical condition, progressive dyspnea on exertion and peripheral edema. The white blood count revealed a leukocytosis and markedly elevated peripheral blood eosinophilics (48.8%). An endomyocardial biopsy demonstrated massive myocardial infiltration with eosinophilic granulocytes and necrosis. The symptoms and laboratory parameters indicate the presence of a hypereosinophilic syndrome. The differential diagnosis of a Churg-Strauss syndrome is discussed. Medical heart failure treatment according to international guidelines and an immunosuppressive treatment with prednisolone (Decortin H) 1.5 mg/kgBW) were initiated. This therapy led to a dramatic reduction of the eosinophilic granulocyte count and normalization of the peripheral blood count, which correlated with a significant improvement of clinical symptoms. Consistently, an increase of left-ventricular function was observed. Upon successive dose reduction to a maintenance dosage of 10 mg prednisolone, the patient's clinical status and peripheral blood count remained stable.

Acute Disease↗
PubMed2004

Neonatal screening for glutaryl-CoA dehydrogenase deficiency.

Acute encephalopathic crisis in glutaryl-CoA dehydrogenase deficiency results in an unfavourable disease course and poor outcome, dominated by dystonia, feeding problems, seizures and secondary complications, and quite often leading to early death. The prerequisite for the prevention of irreversible brain damage in this disease is the detection of affected patients and initiation of treatment before the manifestation of such crisis. Apart from macrocephaly there are no signs or symptoms characteristic for this disease in presymptomatic children and, thus, they are usually missed. In some countries, implementation of extended neonatal screening programmes using electrospray ionization tandem mass spectrometry (ESI-MS/MS) allows detection of affected newborns and start of therapy before onset of neurological complications. This article summarizes recent strategies, pitfalls and shortcomings of a mass screening for glutaryl-CoA dehydrogenase deficiency using ESI-MS/MS. Furthermore, an alternative strategy, namely DNA-based neonatal screening for the Oji-Cree variant of this disease, is demonstrated. An optimization of diagnostic as well as therapeutic procedures must be achieved before GCDH deficiency unequivocally fulfills the criteria of a reliable and successful newborn screening programme.

Amino Acid Metabolism, Inborn Errors↗
PubMed2004

Emergency treatment in glutaryl-CoA dehydrogenase deficiency.

The history of glutaryl-CoA dehydrogenase deficiency is determined by acute encephalopathic crises that are precipitated by common febrile diseases, vaccinations or surgical interventions during infancy and early childhood. Such crises result in an irreversible destruction of the basal ganglia (in particular of the putamina), and consequently dystonia, dyskinesia and choreoathetosis. Secondary complications include feeding and speech problems, failure to thrive, recurrent aspiration, immobilization, severe motor deficits and early death. It is generally accepted that maintenance treatment based on dietary lysine or protein restriction and supplementation with carnitine (and riboflavin) is insufficient to prevent acute crises during intercurrent illnesses or conditions that enhance catabolic state. Consequently, outpatient and inpatient emergency therapies have been implemented. The present review describes a recommended approach to emergency therapy for this disease.

Amino Acid Metabolism, Inborn Errors↗
PubMed2003

Tetrahydrobiopterin sensitivity in German patients with mild phenylalanine hydroxylase deficiency.

We report the results of tetrahydrobiopterin (BH4) loading tests in 10 German patients with mild phenylketonuria. A significant decline of phenylalanine values after application of BH4 was observed in all but one patients. Molecular genetic analyses revealed a range of different PAH gene mutations. Re-testing of one patient previously reported as non-responsive to BH4 loading showed a moderate response with a higher dose of BH4. Nevertheless, there appear to be kinetic differences in phenylalanine hydroxylation in patients with the same genotype. Non-responsiveness to 20 mg/kg BH4 was observed only in a single patient who was compound heterozygous for the novel mutation R176P (c.527G>C) and the common null-mutation P281L. In summary, our data are in line with recent reports indicating that BH4 sensitivity is a normal feature of most mild forms of PAH deficiency but may be influenced by other factors.

Administration, Oral↗
PubMed2002

Emergency management of inherited metabolic diseases.

Inherited metabolic diseases with acute severe manifestations can be divided into five categories: (1) disorders of the intoxication type, (2) disorders with reduced fasting tolerance, (3) disorders with disturbed energy metabolism, (4) disorders of neurotransmission and (5) disorders in which no specific emergency treatment is available. Diagnostic emergency laboratory evaluation should cover all differential diagnoses that are therapeutically relevant and should always include ammonia, glucose, lactate and acid-base status as well as testing the urine for ketones. These are indispensable for planning and conducting the first steps of metabolic emergency treatment and should be available within 30 min. According to the clinical situation and biochemical derangement, special metabolic investigations must be initiated in parallel. These include acylcarnitine profiling with tandem mass spectrometry (in plasma or dried blood spots) and analysis of amino acids in plasma and of organic acids in urine. The results of all laboratory investigations relevant to the diagnosis of metabolic disorders for which specific emergency therapy exists should be available within 24 h. There is general agreement with regard to some therapeutic strategies that are clearly explained by pathophysiology: in disorders with endogenous intoxication, anabolism must be promoted and specific detoxification measures initiated. In disorders with reduced fasting tolerance, administration of glucose at the rate of hepatic glucose production forms the basis of treatment. Correction of acidosis is a major goal in disorders with disturbed mitochondrial energy metabolism, while glucose supply may have to be limited. Many current therapeutic strategies are based on case reports and personal experiences at different metabolic centres. The aim of devising the 'best' management is often hampered by the lack of objective evidence of efficacy.

Emergency Medical Services↗
PubMed2002

Calcium sparks in human ventricular cardiomyocytes from patients with terminal heart failure.

Cardiomyocytes from terminally failing hearts display significant abnormalities in e-c-coupling, contractility and intracellular Ca(2+) handling. This study is the first to demonstrate the influence of end-stage heart failure on specific properties of Ca(2+) sparks in human ventricular cardiomyocytes. We investigated the frequency and characteristics of spontaneously arising Ca(2+) sparks in single isolated human myocytes from terminally failing (HF) and non-failing (NF) control myocardium by using the Ca(2+) indicator Fluo-3. The Ca(2+) sparks were recorded by line-scan images along the longitudinal axis of the myocytes at a frequency of 250Hz. After loading the sarcoplasmic reticulum (SR) with Ca(2+) by repetitive field stimulation (10 pulses at 1Hz) the frequency of the Ca(2+) sparks immediately after stimulation (t = 0s) was reduced significantly in HF compared to NF (4.15 +/- 0.42 for NF vs. 2.81 +/- 0.20 for HF sparks s(-1), P = 0.05). This difference was present constantly in line-scan recordings up to 15s duration (t = 15s: 2.75 +/- 0.65 for NF vs. 1.36 +/- 0.34 for HF sparks s(-1), P = 0.05). The relative amplitude (F/F(0)) of Ca(2+) sparks was also significantly lower in HF cardiomyocytes (1.33 +/- 0.015 NF vs. 1.19 +/- 0.003 HF, t = 0s) and during subsequent recordings of 15s. Significant differences between HF and NF were also present in calculations of specific spark properties. The time to peak was estimated at 25.75 +/-0.88ms in HF and 18.68 +/- 0.45ms in NF cardiomyocytes (P = 0.05). Half-time of decay was 66.48 +/- 1.89ms (HF) vs. 44.15 +/- 1.65ms (NF, P < 0.05), and the full width at half-maximum (FWHM) was 3.99 +/- 0.06 microm (HF) vs. 3.5 +/- 0.07 microm (NF, P < 0.05). These data support the hypothesis that even in the absence of cardiac disease, Ca(2+) sparks from human cardiomyocytes differ from previous results of animal studies with respect to the time-to-peak, half-time of decay and FWHM. The role of elevated external Ca(2+) in HF was studied by recording Ca(2+) sparks in HF cardiomyocytes with 10mmol external Ca(2+) concentration. Under these conditions, the average spark amplitude was increased from 1.19 +/- 0.003 (F/F(0), 2mmol Ca(2+)) to 1.26 +/- 0.01 (F/F(0), 10mmol Ca(2+)). We conclude that human heart failure causes distinct changes in Ca(2+) spark frequency and characteristics comparable to results established in animal models of heart failure. A reduced Ca(2+) load of the SR alone is unlikely to account for the observed differences between HF and NF and additional alterations in intracellular Ca(2+) release mechanisms must be postulated.

Calcium↗
PubMed2002

[Choristoma of the diaphragm. Case report of a rare tumor and approach through lateral thoracotomy].

Tumors of the diaphragm are rare and caused by there special localisation difficult to diagnose. We describe the case of a 31 year old man with a choristoma of the left diaphragmal crux where the localisation and genesis could only be cleared through lateral thoracotomy. Nor the CT guided puncture or the laparoscopy-although sufficient samples for the pathology could be gained-allowed the right diagnose. The importance of good diagnostic approach to select the right operative procedure-in this case the anterolateral thoracotomy-is described.

Adult↗
PubMed2001

Tetrahydrobiopterin responsiveness in phenylketonuria differs between patients with the same genotype.

Recently, BH(4)-responsive phenylalanine hydroxylase (PAH) deficiency was reported in patients with specific mutations in the PAH gene, and it was suggested that BH(4) responsiveness may be determined by the respective genotypes. We now report on three patients with PAH deficiency and the same genotype but different responses to standardized BH(4) loading. Our results suggest that BH(4) responsiveness in PAH deficiency is at least partly independent from PAH genotype.

Amino Acid Substitution↗
PubMed2001

Molecular and functional characterisation of mild MCAD deficiency.

We report a novel mild variant of medium-chain acyl-CoA dehydrogenase deficiency (MCADD) diagnosed in four infants who, in neonatal screening, showed abnormal acylcarnitine profiles indicative of MCADD. Three patients showed completely normal urinary organic acids and phenylpropionic acid loading tests were normal in all four patients. Enzyme studies showed residual MCAD activities between "classical" MCADD and heterozygotes. ACADM gene analysis revealed compound heterozygosity for the common mutation K329E and a novel mutation, Y67H, in two cases, and homozygosity for mutation G267R and the novel mutation S245L, respectively, in two children of consanguineous parents. As in other metabolic disorders, the distinction between "normal" and "disease" in MCAD deficiency is blurring into a spectrum of enzyme deficiency states caused by different mutations in the ACADM gene potentially influenced by factors affecting intracellular protein processing.

Acyl-CoA Dehydrogenase↗
PubMed2001

Characteristics of calcium sparks in cardiomyocytes derived from embryonic stem cells.

In embryonic stem (ES) cell-derived cardiomyocytes, spontaneous Ca(2+) sparks representing Ca(2+) release through ryanodine receptor (RyR) channels were characterized and correlated to the expression of RyRs as well as the Ca(2+) load of the sarcoplasmic reticulum (SR). In very early developmental stage (VEDS) cardiac precursor cells, global intracellular Ca(2+) concentration ([Ca(2+)](i)) fluctuations occurred, whereas Ca(2+) sparks and contractions were absent. In early developmental stages (EDS), contractions as well as Ca(2+) sparks were obvious. During the further differentiation to late developmental stage (LDS) cardiomyocytes, a marked increase in the frequency of global [Ca(2+)](i) transients, the amplitude and the frequency of Ca(2+) sparks, as well as the expression of RyRs and the volume of RyR-positive SR, was observed. Furthermore, the caffeine-releasable SR Ca(2+) load was elevated in LDS compared with EDS cardiomyocytes. A high-Ca(2+) solution raised spark frequency as well as amplitude in EDS cardiomyocytes to the levels of LDS cardiomyocytes. The characteristics of Ca(2+) sparks occurring in cardiomyocytes differentiated from ES cells may be governed by the Ca(2+) load of the SR and/or the density of RyRs.

Animals↗
PubMed2000

Synchrotron beam test with a photon-counting pixel detector.

Synchrotron beam measurements were performed with a single-photon-counting pixel detector to investigate the influence of threshold settings on charge sharing. Improvement of image homogeneity by adjusting the threshold of each pixel individually was demonstrated. With a flat-field correction, the homogeneity could be improved. A measurement of the point spread function is reported.

Journal Article↗
PubMed2000

Leptogenesis with dirac neutrinos

We describe a "neutrinogenesis" mechanism whereby, in the presence of right-handed neutrinos with sufficiently small pure Dirac masses, (B+L)-violating sphaleron processes create the baryon asymmetry of the Universe, even when B = L = 0 initially. It is shown that the resulting neutrino mass constraints are easily fulfilled by the neutrino masses suggested by current experiments. We present a simple toy model which uses this mechanism to produce the observed baryon asymmetry of the Universe.

Journal Article↗
PubMed2000

Mutation analysis in glycogen storage disease type 1 non-a.

We report molecular and clinical findings in 13 patients with rare types of glycogen storage disease 1 (GSD1 non-a). Analysis of G6PT encoding a microsomal transporter protein has revealed mutations on both chromosomes in each case, four of which are novel. Diagnosis has been confirmed in three patients suspected of having GSD1 non-a without enzymatic studies involving liver biopsy, thus emphasising the advantage of G6PT mutation analysis for all GSD1 non-a patients.

Adolescent↗