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Biomedical subjects

M Wehner

Publications and source records attributed to M Wehner.

17 recordsLinked to original sources

[Streptococcal Toxic Shock-like Syndrome associated with detectable autoantibodies].

We report on the severe course of a Streptococcal Toxic Shocklike Syndrome (STSLS). The initial diagnosis as well as the causal therapeutic approaches were complicated and prolongated definitely by the serological detection of auto-antibodies. Besides the presentation of clinical and paraclinical findings the report responds to relevant differential diagnoses and the corresponding strategies of therapeutic intervention.

Adult↗

Identification and ablation of atypical atrial flutter. Entrainment pacing combined with electroanatomic mapping.

Differentiation between typical and atypical atrial flutter solely based upon surface ECG pattern may be limited. However, successful ablation of atrial flutter depends on the exact identification of the responsible re-entrant circuit and its critical isthmus. Between August 2001 and June 2003, we performed conventional entrainment pacing within the cavotricuspid isthmus in 71 patients with sustained atrial flutter. In patients with positive entrainment we considered the arrhythmia as typical flutter and treated them with conventional ablation of the cavotricuspid isthmus. As a consequence of negative entrainment we performed 3D-electroanatomic activation mapping (CARTO trade mark ). Conventional ablation of the right atrial isthmus was successful in all patients (n = 54) with positive entrainment. We performed electroanatomic mapping in the remaining 17 patients (14 male; age 60.9 +/- 16 years) resulting in the identification of 6 cases with typical and 11 cases with atypical flutter. Therefore, entrainment pacing was able to predict the true presence of typical atrial flutter in 91.5%. Atypical flutter was right sided in 4 patients and left sided in 7 cases. Electrically silent ("low voltage") areas probably demonstrating atrial myopathy were identified in all cases with left sided and in 2 patients with right sided flutter. In these patients targets for ablation lines were located between silent areas and anatomic barriers (inferior pulmonary veins, mitral respectively tricuspid annulus, or vena cava inferior). In 1 patient, the investigation was stopped due to variable ECG pattern and atrial cycle lengths. In the remaining cases, ablation was acutely successful. One patient, after surgical closure of a ventricular septal defect, demonstrated a dual-loop intra-atrial reentry tachycardia dependent on two different isthmuses. This arrhythmia required ablation of those distinct isthmuses to be interrupted. After a mean follow-up of 8.8 +/- 3.4 months, there was one patient with a recurrence of left-sided atrial flutter. Another patient developed permanent atrial fibrillation shortly after the procedure. Mean duration time of the procedure was 235.6 +/- 56.4 min (right atrium: 196 +/- 17.3 min; left atrium: 267.2 +/- 59.5 min), and average fluoroscopy time was 21.8 +/- 11.7 min (right atrium: 9.5 +/- 6 min; left atrium: 28.9 +/- 7 min). There was no incidence of serious complications associated with these procedures. In conclusion, conventional pacing in the cavotricuspid isthmus combined with electroanatomic mapping was an effective method to differentiate between typical and atypical atrial flutter. Electroanatomic mapping was a powerful tool both for identification of different atrial re-entrant circuits including their critical isthmuses as well as for effective application of individual ablation line strategies.

Adolescent↗

Calcium release from sarcoplasmic reticulum is facilitated in human myotubes derived from carriers of the ryanodine receptor type 1 mutations Ile2182Phe and Gly2375Ala.

Malignant hyperthermia (MH) is caused by increased calcium release from sarcoplasmic reticulum, triggered by volatile anesthetics or depolarizing muscle relaxants. Numerous mutations associated with MH have been detected in the skeletal muscle type ryanodine receptor gene (RyR1), but so far facilitated calcium release has only been demonstrated for a few of them. This is a prerequisite for confirming the causative role of an RyR1 mutation for MH. Calcium release from sarcoplasmic reticulum induced by 4-chloro-m-cresol (4CmC), caffeine, and halothane was determined in human myotubes by calcium imaging. The RyR1 Ile2182Phe mutation and the RyR1 Gly2375Ala mutation have been identified in individuals susceptible to MH. In myotubes of individuals carrying the RyR1 Ile2182Phe or the RyR1 Gly2375Ala mutation, the EC(50) for caffeine and halothane was reduced; in the Ile2182Phe myotubes, the EC(50) for 4CmC was also reduced, all consistent with facilitated calcium release from the sarcoplasmic reticulum. From these data we conclude that both mutations are pathogenic for MH.

Adult↗

Increased sensitivity to 4-chloro-m-cresol and caffeine in primary myotubes from malignant hyperthermia susceptible individuals carrying the ryanodine receptor 1 Thr2206Met (C6617T) mutation.

Malignant hyperthermia (MH) is an autosomal-dominant disorder of skeletal muscle, triggered by volatile anaesthetics and depolarizing muscle relaxants. The causative defect lies in the control of Ca(2+) release from the sarcoplasmic reticulum in skeletal muscle. Numerous mutations have been detected in the ryanodine receptor 1 (RyR1) gene, but so far an MH-causative role has only been confirmed for 16 human RyR1 mutations. In this report we show that myotubes derived from individuals carrying the RyR1 Thr2206Met (C6617T) mutation have an abnormal response of the intracellular calcium concentration to 4-chloro-m-cresol and to caffeine. Satellite cells were obtained from muscle biopsies of patients referred for diagnosing MH. The intracellular calcium concentration in response to 4-chloro-m-cresol and to caffeine was investigated by fluorescence calcium imaging. In myotubes the half-maximal activation concentration (EC(50)) for 4-chloro-m-cresol was reduced from 203 micro m (wild type) to 98 micro m (Thr2206Met), and for caffeine from 3.8 mm to 1.8 mm. From the reduction of EC(50) we conclude that the RyR1 Thr2206Met mutation is pathogenic for MH.

Amino Acid Substitution↗

[Clonidine vs. Midazolam for premedication - comparison of the anxiolytic effect by using the STAI-test].

OBJECTIVE: Many investigations described a positive effect of clonidine for premedication (reduction of perioperative stress response, analgetic effect, anaesthetic-saving effect, prophylaxis of postoperative shivering). The most important objective in premedication is undisputed anxiolysis. The anxiolytic effect of clonidine is differently discussed. Therefore we investigated the anxiolytic effect of clonidine in comparison to midazolam. METHODS: 50 patients (ASA 1 - 3) were included in the present doubleblinded, prospective study. These patients got an oral premedication with 1 mg flunitrazepam in the evening before surgery and 5 microg/kg(-1) clonidine or 100 microg/kg(-1) midazolam 60 - 90 minutes before surgery. By using Spielbergers State-Trait Anxiety Inventory (STAI-G X1) we registered the degree of state-anxiety before and after premedication. RESULTS: Both clonidine as well as midazolam showed a significant reduction of the state-anxiety over time (p < 0,001). Between the groups there were no differences in the STAI-scores at any time (p > 0,05). The degree of reduction in the state-anxiety were comparable between the groups. CONCLUSION: In addition to the higher up listed effects clonidine showed a anxiolytic effect, which is comparable to midazolam. Therefore clonidine is an interesting alternative to benzodiazepines, which are commonly used drugs for premedication.

Adrenergic alpha-Agonists↗

Incidence of tracheo-oesophageal fistulas after primary voice rehabilitation with the Provox or the Eska-Herrmann voice prosthesis.

Salivary leakage can be a major symptom of valve failure or incorrect positioning of indwelling voice rehabilitation valves in a tracheo-oesophageal fistula. Usually, removal of the valve for a short time leads to shrinking of the fistula or a simple valve replacement procedure resolves the problem. If the fistula, however, does not close spontaneously, symptoms persist and the fistula may have to be closed surgically. In a retrospective study, data of 103 patients who underwent laryngectomy and primary voice rehabilitation between 1989 and 1998 with either the Provox or the Eska-Herrmann prosthesis were compared with regard to surgical fistula closure requirement. A total of 55 patients underwent laryngectomy and primary voice rehabilitation with the Eska-Herrmann and 48 with the Provox prosthesis. Initial tumour treatment also included post-operative radiotherapy for all patients in the study. In total, surgical fistula closure had to be performed in three patients, all of whom had been treated with the Provox prosthesis. The time span between initial voice rehabilitation and surgical closure of the fistula was 5 months, 21 months and 24 months in all three patients respectively. None of the fistulas developed in relation to recurring tumour disease. The Provox prosthesis seem to have a higher risk of developing fistulas necessitating surgical intervention, even years after initial tumour therapy, than the Eska-Herrman prosthesis. These complications may be due to the larger tracheo-oesophageal fistula necessary to fit the larger diameter of the Provox prosthesis.

Adult↗

[Microbiological contamination of intraoperatively collected erythrocyte concentrate in mechanical autotransfusion in tumor surgery].

Intraoperative autotransfusion is an effective method of the autologous haemotherapy. Gamma irradiation of the salvaged erythrocyte concentrates leads to inactivation of malignant cells and allows retransfusion in oncologic surgery. The risk of microbiological contamination of the autologous blood product has not been systematically studied in this field of surgery. During the evaluation of intraoperative autotransfusion in oncologic surgery at the University Hospital of Leipzig, the salvaged blood of 46 patients who underwent tumour surgery (urology, gynaecology and neurosurgery) was processed to a washed erythrocyte concentrate with a Cell Saver 5 or a Haemolite 2 (Haemonetics). Specimens for microbiological studies were taken from the area of surgery, the reservoir bottle of the autotransfusion system and the salvaged erythrocyte concentrates. The investigation with plate cultures and the identification of microorganisms were performed according to standard procedures of microbiological diagnosis. The ethics committee of the University Hospital of Leipzig approved the study protocol. We found a microbiological contamination in 10 of 46 salvaged erythrocyte concentrates (22%), above all the growth of saprophytes (Streptococcus, Staphylococcus and Neisseria species). We also identified bacteria which have their habitats in the intestinal tract (E. coli and Enterococcus). The highest rate of microbial contaminated erythrocyte concentrates was found in urologic oncosurgery (37%). In neurosurgery (laminectomy and craniotomy including tumour extirpation), there was no bacterial growth in the salvaged erythrocyte concentrate. Intraoperative autotransfusion should be avoided during surgery touching the urinary tract, e.g. prostatectomy and cystectomy. In neurosurgery, it seems to be safe as far as microbiological contamination is concerned. To assess the real risk of microbiological contamination of the salvaged erythrocytes, more investigations are necessary to determine not only the extent and nature of contamination but also the clinical effects.

Adult↗

A chiral sensor for arginine and lysine

[structure: see text] We provide access to a new class of C1- or C2-symmetrical host molecules 1 and 2 based on a spirobisindane skeleton. Whereas 1 is selective for short, rigid diamines, 2 prefers longer alpha,omega-dications. Of all the amino acid methyl esters, only those of lysine and arginine with the correct distance between their cationic groups form strong 1:1 complexes in DMSO with 2. NMR titrations reveal high association constants as well as discrimination between the enantiomers of lysine and arginine.

Journal Article↗

Expression of acute and late-stage inflammatory antigens, c-fms, CSF-1, and human monocytic serine esterase 1, in tumor-associated macrophages of renal cell carcinomas.

PURPOSE: Tumor cells influence the differentiation of infiltrating macrophages. In the present study, the differentiation of macrophages in renal cell carcinomas was investigated with special regard to their possible role in tumor growth and spread. METHODS: Macrophages were characterized by means of immunohistochemistry of the Ki-M1P, 25F9, MRP8, MRP14, and MRP8/14 antigens and by means of in situ hybridization of CSF-1, its c-fms-coded corresponding receptor, and human monocytic serine esterase-1 (HMSE-1) mRNA. Macrophage subgroups were quantified within central tumor tissue, the corresponding tumor host interface, and tumor-free tissue and correlated with tumor necrosis, fibrosis, and tumor stage and grade. RESULTS: Macrophage density was much higher within tumor tissue and the tumor/host interface than in tumor-free tissue. Well-differentiated carcinomas showed a lower degree of macrophage density than less-differentiated carcinomas. Tumor-associated macrophages could be divided into an active inflammatory type (MRP14+, MRP8/14+) and into a late-phase inflammatory type (25F9+, MRP8+). Necrosis was seen in less-differentiated carcinomas and associated with a significantly increased density of MRP14+ macrophages, which, however, did not correlate with the extent of necrosis. The density of 25F9+ macrophages was correlated with an extensive connective tissue formation and an advanced tumor stage. c-fms, CSF-1, and HMSE-1 mRNA expression did not discriminate between the macrophage subgroups. CONCLUSIONS: Tumor-associated macrophages of the late-stage inflammatory type potentially support the spread of renal cell cancer. CSF-1 derived from tumor cells and macrophages acts as a monocyte attractant and induces macrophage differentiation able to modulate the extracellular matrix rather than to exert cytotoxicity.

Antigens, CD↗

[Practical aspects of mechanical autotransfusion in tumor surgery in a decentralized clinic].

The surveys of Hansen et al. demonstrated the safe inactivation of tumor cells in salvaged blood by g-irradiation. This method opens up the possibility of extending the intraoperative autotransfusion to tumour surgery. A prospective survey at the University Hospital of Leipzig demonstrated the practicability of intraoperative autotransfusion with gamma-irradiation of salvaged blood at a hospital with a decentralized structure. A clinically-relevant reduction of quality of the blood product by gamma-irradiation with 50 Gray or by transport was not observed. Adherence to fixed working regulations ensures that gamma-irradiation is conducted correctly and the salvaged erythrocyte concentrate is available in an acceptable period of time.

Blood↗

Human cDNA encoding the muscle isoform of the phosphorylase kinase gamma subunit (PHKG1).

Muscle glycogenosis caused by phosphorylase kinase (Phk) deficiency may lead to exercise intolerance, weakness and musculatur atrophy. The gene encoding the muscle isoform of the Phk gamma subunit (gamma M) is one of the candidate genes in which mutations responsible for this condition should be sought. Here, we report the cDNA sequence and the predicted primary structure of the human gamma M subunit.

Amino Acid Sequence↗

Human muscle glycogenosis due to phosphorylase kinase deficiency associated with a nonsense mutation in the muscle isoform of the alpha subunit.

Heritable phosphorylase kinase (Phk) deficiency is responsible for several forms of glycogen storage disease in humans and animals that differ in mode of inheritance and tissue-specificity. Mutations affecting different subunits and isoforms of Phk are expected to contribute to this heterogeneity. In the present study, we have investigated a case of muscle-specific, adult-onset Phk deficiency. The coding sequences of three candidate genes were analyzed by RT-PCR and sequencing: the muscle isoform of the alpha subunit (alpha M), a muscle-specifically expressed exon of the beta subunit, and the muscle isoform of the gamma subunit. Whereas the latter two sequences were found to be normal, we identified a nonsense mutation in alpha M. The condition of this patient therefore is a human homolog of the X-linked muscle Phk deficiency of I-strain mice. To our knowledge, this is the first description of a human Phk deficiency mutation.

Amino Acid Sequence↗

[Diagnostic possibilities using contrast echocardiography].

The contrast echocardiography is based on the occurrence of micro-bubbles in the blood which are stable for a short time and which are passed on the blood stream. These micro-bubbles reflected the ultrasound waves and are represented as contrast echos in the cavities of the heart and the large vessels. They are produced by a bolus injection of saline, glucose, dye (ujoviridin) or the patients' own blood into a peripheral vein or a cavity of the heart. This procedure enables intracardiac insufficiency to be recognized. While the peripheral venous injection is sufficient for differentiating a right-to-left shunt at atrial, ventricular or vascular level, the diagnosis of a left-to-right shunt or of a valvular insufficiency must be made by an injection within a cardiac catheterization. Our results with parasternal and suprasternal transducer position are demonstrated.

Adolescent↗

[Echocardiographic investigation of the left ventricular outflow tract in healthy children (author's transl)].

The width of the left ventricular outflow tract was measured in the echocardiograms at the beginning and the end of the systole in 80 healthy children ranging from 3 to 16 years. The values were referred to the body surface area and the heart volume which was estimated by mean of X-ray. The regression lines as well as the confidence levels of 95 per cent are marked. It becomes obvious that the dispersion of the data related to the heart volume is less than that related to the body surface area. The width of the left ventricular outflow tract with reference to the heart volume and the body surface area resp. shows in relation to the heart volume and the body surface area resp. an exponential behaviour, i.e. in the growing heart the outflow tract decreases in relation to the two parameters. The narrowing of the outflow tract from start to end of the systole is about one third.

Adolescent↗