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Biomedical subjects

D Müller

Publications and source records attributed to D Müller.

At least 181 records · Page 10Linked to original sources

Extreme microcephaly, severe growth and mental retardation, flexion contractures, and ichthyotic skin in two brothers: a new syndrome or mild form of Neu-Laxova syndrome?

Two brothers with congenital microcephaly, growth and mental retardation, flexion contractures, dorsal edema of hands and feet, and ichthyotic skin changes are described. Mild manifestations of Neu-Laxova syndrome have to be considered but long survival and only mild intrauterine growth retardation not described in this syndrome may be evidence of a different condition.

Contracture↗

Influence of anodal electrode position on transvenous defibrillation efficacy in humans: a prospective randomized comparison.

Nonthoracotomy lead systems for implantable cardioverter defibrillators (ICDs) have reduced operative mortality and morbidity as compared to epicardial lead systems but are usually associated with higher defibrillation thresholds (DFTs). The purpose of this prospective randomized trial was to investigate if the second defibrillation electrode in the left subclavian vein can increase defibrillation efficacy and decrease DFT as compared to the superior vena cava (SVC) position in nonthoracotomy lead systems for ICDs. Seventeen patients (mean age: 49.9 +/- 11.3 years, mean ejection fraction: 46.1% +/- 15.8%) were implanted with an investigational unipolar electrode (Medtronic 13001) used as the defibrillation anode. DFT testing was started in the SVC (n = 10, group A) or the left subclavian vein (n = 7, group B), and repeated in the alternative position starting at the DFT of the initial position. Fifteen patients were eligible for analysis (group A: n = 9, group B: n = 6). With the electrode in the SVC, ventricular fibrillation could be successfully terminated in 9 out of 15 patients (60%). In the left subclavian vein the success rate was 100% (P < 0.01). Mean DFT in the SVC was 13.0 +/- 5.2 J and in the left subclavian vein 10.2 +/- 4.9 J. DFTs in the left subclavian vein were either lower (group A: n = 5/9, group B: n = 5/6) or equal to the results in the SVC position (P < 0.001). Thus, the left subclavian vein appears to be a superior alternative for positioning of the defibrillation anode as compared to the SVC for nonthoracotomy lead systems using two separate leads.

Defibrillators, Implantable↗

The combined transvenous implantation of cardioverter defibrillators and permanent pacemakers.

We developed criteria for implantation and programming of permanent endocardial pacemakers in patients with a nonthoracotomy ICD system. These criteria were prospectively used in 10 patients who recieved an ICD prior to (n = 5) or following (n = 5) implantation of a dual chamber (n = 6) or ventricular (n = 4) pacemaker with a unipolar (n = 4) or bipolar (n = 6) lead configuration. All patients were tested for interactions or malfunctions. Undersensing of ventricular fibrillation by the atrial sense amplifier and inadequate atrial pacing occurred in one patient with a unipolar dual chamber system programmed to AAIR but didn't impair ICD sensing. Transient or permanent loss of capture or sensing of the pacemaker was not observed after ICD shocks with the output programmed to double pulse width and voltage of stimulation threshold and the sensitivity to 50% of the detected R wave. One episode of transient reprogramming occurred without clinical consequences. One unipolar ventricular pacemaker lead had to be exchanged against a bipolar lead because of oversensing of the pacing artifact by the ICD. There was no failure of an ICD to detect ventricular arrhythmias due to inadequate pacemaker activity. During a follow-up period of 21 +/- 11 months, a total of 78 ventricular arrhythmias were effectively treated in six patients. Thus, a combined use of transvenous ICD and pacemaker is possible despite the close vicinity of pacing and defibrillations leads. Optimized programming different to the common settings is required. As interactions occurred only in unipolar pacemaker leads bipolar systems should be used in these patients.

Aged↗

Ductuloendocrine cell proliferation in the pancreas of two young dogs with diabetes mellitus.

Two cases of diabetes mellitus in juvenile dogs (a 3-4 month-old Golden Retriever and a 2-month-old Labrador Retriever) are described here in terms of their clinical, histologic, and immunohistologic findings. Only very few insulin-positive cells were demonstrated immunohistochemically in one dog. In the second dog, the alterations of the pancreas consisted of hydropic vacuolar degeneration of B cells in the islets of Langerhans. In both cases, hyperplasia of the vacuolated cells was prominent. These cells formed tubular structures and were immunohistochemically positive for cytokeratin and proliferating cell antigen (MIB-1). Furthermore, within these vacuolated areas, some cells were positive to varying degrees for insulin, glucagon, somatostatin, and pancreatic polypeptide. Apoptotic cells could be seen in the exocrine pancreas, in vacuolated areas, and occasionally in the islets of both dogs. We interpret these alterations as ductuloendocrine cell proliferation, probably as an idiopathic compensatory response.

Age Factors↗

Evidence for production and functional activity of nitric oxide in seminiferous tubules and blood vessels of the human testis.

Previous studies have demonstrated that nitric oxide (NO) influences Leydig cell function. Here we provide evidence for NO production and activity in seminiferous tubules and blood vessels of the human testis. By immunohistochemistry, the soluble guanylyl cyclase (sGC), the intracellular NO receptor, and the second messenger, cyclic guanosine monophosphate (cGMP), were detected in myofibroblasts of the peritubular lamina propria in Sertoli cells, as well as in endothelial and smooth muscle cells of testicular blood vessels. Performed with isolated tubules and blood vessels, the biological activity of sGC could be proved by cGMP generation in response to treatments with the NO donor, sodium nitroprusside. The endothelial and neuronal subtypes of NO synthase (NOS) were localized immunohistochemically to the same cell types that express sGC and cGMP. In isolated tubules and vessels, the presence of endothelial NOS and neuronal NOS was confirmed by immunoblotting, and NOS activity was demonstrated by decreased cGMP production upon incubation with the NOS inhibitor L-nitro arginine methylester. These findings show that peritubular cells, Sertoli cells, and testicular blood vessels may be sites of NO production and activity, possibly involved in relaxation of seminiferous tubules and blood vessels to modulate sperm transport and testicular blood flow, respectively.

Adult↗

[Nasal CPAP therapy of obstructive sleep apnea syndrome with expiratory pressure reduction: a prospective randomized study of acceptance of treatment during therapy initiation].

It is often difficult to achieve adequate acceptance of nasal continuous positive airway pressure (CPAP) therapy by patients with OSA. Many patients find it particularly inconvenient to expire against the treatment pressure. With this in mind, we have attempted to improve acceptance of CPAP therapy by using a bilevel system that reduces the treatment pressure during expiration. 52 patients were randomized either to initial treatment with CPAP therapy followed by bilevel treatment, or to treatment in reversed order. During bilevel therapy the ratio of inspiratory to expiratory pressure was fixed at 1:0.6. After each treatment the patients were interviewed on the basis of visual analogue scales to establish their subjective evaluation of such parameters as general well-being, quality of sleep, comparison of the respective treatment pressures, and possible preference for one of the two systems for long-term treatment. The minimal effective inspiratory treatment pressure during bilevel therapy (IPAP) and the minimal effective CPAP pressure were closely correlated (r = 0.89). There was no difference between the apnoea hypopnoea indices during CPAP therapy as compared with bilevel therapy. Most patients (57%) felt the treatment pressure with the bilevel system to be lower (p = 0.048). There were no differences in patients' well-being early in the morning, or in their assessment of sleep quality. The majority of patients (52%) preferred bilevel therapy for long term treatment, while 38% preferred CPAP therapy (n.s.). In a subgroup of 13 patients with a treatment pressure of > or = 10 mbar during CPAP therapy 10 patients (77%) gave preference to the bilevel system (n.s.). In a considerable number of patients the acceptance of treatment can be improved by using a bilevel system for initiation of nasal positive pressure therapy.

Adult↗

Myc: a single gene controls both proliferation and apoptosis in mammalian cells.

c-myc was discovered as the cellular homologue of the transduced oncogene of several avian retroviruses. The gene encodes a transcription factor, which forms a heteromeric protein complex with a partner protein termed Max. In mammalian cells, Myc is a central regulator of cell proliferation and links external signals to the cell cycle machinery. Myc also induces cells to undergo apoptosis, unless specific signals provided either by cytokines or by oncogenes block the apoptotic pathway. Recent progress sheds light both on the factors regulating the function and expression of Myc and on the downstream targets in the cell cycle. Together, these findings suggest the existence of a novel signal transduction pathway regulating both apoptosis and proliferation.

Animals↗

[Complications of nasal CPAP therapy. Consequences for general practice].

BACKGROUND: The prevalence of the obstructive sleep apnea syndrome is about 5% in the entire population. The amount of treatment-indications grows for this particular sleep-related breathing disorder due to the increasing usage of diagnostic screening tests. In most cases, the positive-pressure ventilation, PPV (nCPAP, nBiPAP) is considered as a highly effective form of treatment, in comparison to other treating methods. The residential polysomnographic supervised adjustment of the treatment is optimally applied to most of the patients. Due to the increasing number of the treated patients, the reports about the appearance of short-termed side effects during the adjustment of the PPV become more frequent. PATIENTS AND RESULTS: We report on 9 patients who showed complications during the initial stage of treatment. The most common one, during the nCPAP-therapy, was the increase of central apneas. Because of this complication, a rapid optimization of the respiratory pressure or a change to a nBiPAP-therapy was necessary in 5 of the patients. 2 of the patients showed cardiac arrhythmias, some of which were severe. One patient produced a remarkable central hypoventilation during the initial phase of a nCPAP-therapy. The nBiPAP-titration combined with right-heart-catheter monitoring could demonstrate in another patient a possible cardiac decompensation through an increased ventilatory pressure. CONCLUSION: The risk of a positive-pressure ventilation is higher in patients with accompanying cardiac, pulmonary, neuropsychiatric and/or otorhinolaryngologic disorders. Considering the various predisposing factors of the patients we suggest an intensive apparative monitoring as well as stuff-supervision during the introduction to a respiratory treatment. If complications appear, a rapid improvement of the ventilatory pressure or a change to another respiratory treatment is indicated.

Aged↗

Characterization of a beta-Asp33 isoform of recombinant hirudin sequence variant 1 by low-energy collision-induced dissociation.

A new low-concentration congener (Ib) of recombinant hirudin sequence variation 1 was structurally characterized as a beta-Asp33 isoform of the parent protein (Ia). alpha-beta Isomerization at the 33-position was expected in view of the previous isolation of a potential precursor (Asp33-Gly34-anhydro-hirudin (Ic)), i.e., a succinimide-type dehydration product liable to undergo facile hydrolysis with ring opening, yielding beta- (along with alpha-) aspartates. In order to identify and locate the modified site in Ib, a sufficiently small peptide ([28-35]-octapeptide IIIb) was prepared by disulfide bond reduction, S-alkylation (pyridylethylation) and twofold enzymatic degradation (Glu-C protease followed by trypsin). When [M + H] + ions of IIIb were analyzed by electrospray ionization tandem mass spectrometry (ESIMS/MS) and low-energy collision-induced dissociation (CID), a singular [bn + H2O]+ ion indicative of beta-Asp in the neighboring 'n + 1' position was observed for n = 5. This located the beta-Asp residue unambiguously in the 6-position of IIIb and thus, as expected, in the 33-position of Ib. The formation of this highly diagnostic [bn + H2O]+ ion, for which precedents had only been reported for CID under high-energy conditions, requires net OH migration from one to another amino acid position. Confirmatory results from 18O-labeling of the suspected migratory oxygen atom (beta-Asp33-CO18OH) together with the low-energy genesis suggest a specific charge-triggered rather than charge-remote mechanism for the formation of the ion. The analogy of this process to the ejection of the C-terminal amino acid similarly involving net OH rearrangement is discussed.

Alkylation↗

The functions of Myc in cell cycle progression and apoptosis.

c-myc has emerged as one of the central regulators of mammalian cell proliferation. The gene encodes a transcription factor of the HLH/leucine zipper family of proteins that activates transcription as part of a heteromeric complex with a protein termed Max. In mammalian fibroblasts, Myc acts as an upstream regulator of cyclin-dependent kinases and functionally antagonises the action of at least one cdk inhibitor, p27. Myc also induces cells to undergo apoptosis, and the relationship between Myc-induced cell cycle entry and apoptosis is discussed.

Animals↗

Effect of adrenalectomy and corticosterone substitution on glucose and glycogen metabolism in rat brain.

In non-nervous tissues, glucocorticoids (GCs) counteract the effects of insulin and stimulate gluconeogenesis. The present study was designed to investigate whether or not adrenalectomy (ADX) and glucocorticoid substitution influence the pathway of both glucose and glycogen metabolism in cerebral parietotemporal cortex and hippocampus, and if so how. The activities of respective key enzymes, such as hexokinase (HK), phosphofructokinase (PFK), pyruvate kinase (PK), glucose-6-phosphatase (G6Pase) and phosphorylase a (PLa), and the concentrations of the intermediates, such as glucose (Glu), glucose-6-phosphate (G6P), fructose-6-phosphate (F6P), fructose-1,6-bisphosphate (F16PP), pyruvate (Pyr), lactate (Lac), glycogen (Glyc) and glucose-1-phosphate (G1P), were measured in the brains of 1-year-old male Wistar rats under controlled conditions 3 days after ADX or sham operation and in a pilot study after ADX and substitution with corticosterone (CST) suspended in sesame oil or after ADX and subcutaneous administration of the vehicle only. An increase in both glycolytic flux and glycogen breakdown and a decrease in gluconeogenesis in cerebral cortex but not in hippocampus were observed after ADX. After substitution with CST in adrenalectomized rats the effect of ADX on enzyme activities was reversed: significant differences from adrenalectomized rats that received vehicle only was shown for PK and G6Pase activities in both areas of the rat brain investigated.

Adrenalectomy↗

Detection of varicella-zoster virus in congenital varicella syndrome: a case report.

BACKGROUND: We studied the possibility of detecting varicella-zoster virus in formalin-fixed tissue samples from a still-born infant with congenital anomalies in order to verify the relationship with maternal varicella. CASE: A girl with hypoplasia of extremities, skin lesions, and microphthalmos was stillborn at 34 weeks' gestation. Her mother had had chickenpox between the 13th and 15th gestational weeks. Varicella-zoster virus DNA could be detected in formalin-fixed tissue samples of lungs, spleen, adrenal glands, bulbus oculi, and placenta by polymerase chain reaction (PCR). The method, with the use of primers from gene 29 encoding the major DNA-binding protein, proved to be highly sensitive. In addition, varicella-zoster virus DNA/antigens were localized in some organs by in situ hybridization/monoclonal antibodies. CONCLUSION: The PCR method should be included in the diagnosis of congenital varicella syndrome. The varicella-zoster virus can be detected in formalin-fixed tissue samples using this technique.

Abnormalities, Multiple↗

Bile ductular proliferation and altered leukotriene elimination in thioacetamide-induced fibrosis of rat liver.

BACKGROUND/AIMS: Liver fibrosis is accompanied by both bile ductular proliferation and inflammation under various conditions. The functional consequences and the interrelationships between these changes are unknown. Altered biliary elimination and retention of cholephilic mediators may be a factor in fibrogenesis. Therefore, the relationship between fibrosis, ductular proliferation and functional changes in biliary elimination was studied. METHODS: Micronodular liver fibrosis was induced by thioacetamide in rats. The relative amount of bile ductular epithelial cells was determined by microscopic morphometry. The functional changes in bile secretion and metabolism of leukotriene C4 were assessed in isolated perfused livers of treated rats. RESULTS: Pretreatment with thioacetamide in vivo resulted in enhanced bile fluid formation in subsequently isolated and perfused livers. Infusion of isoproterenol into the portal vein stimulated bile flow. Both unstimulated and isoproterenol-stimulated bile flows were increased in fibrotic livers and were correlated with liver content of bile ductular epithelia. In contrast, biliary secretion of infused leukotriene C4 was lowered in correlation with that of taurocholate. Enhanced metabolism resulted in a shift of the major fraction in bile from leukotriene C4 to leukotriene D4. CONCLUSIONS: Thioacetamide-induced liver fibrosis is associated with an increased number of functionally intact bile ductules that are responsive to isoproterenol stimulating bile fluid formation. In contrast, biliary secretion of cysteinyl-leukotrienes and taurocholate is inhibited and the relative amount of leukotriene D4 is increased. Bile ductular proliferation as well as retention and altered metabolism of leukotrienes are factors associated with the development of liver fibrosis.

Animals↗

Monooxygenation, cytochrome P4501A1 and P4501A1-mRNA in rat liver slices exposed to beta-naphthoflavone and dexamethasone in vitro.

Precision-cut liver slices (0.5 mm) were incubated at 30 degrees C in a modified William's Medium E for up to 48 hrs. During the incubation, K+ and GSH/GSSG concentrations did not decrease. Cytochrome P450-dependent dealkylation rates of 7-ethoxycoumarin (ECOD), 7-allyloxycoumarin (ACOD) and 7-ethoxyresorufin (EROD) decreased to 1/3, 1/2 or did not change at all, respectively, after a 48 hrs incubation period. Exposure of the slices to 25 microM beta-naphthoflavone (beta NF) resulted in about 3 times higher monooxygenation rates. An exposure to a combination beta NF and dexamethasone (10(-6)M) caused a marked induction (6 times higher rates) after 48 hrs. Simultaneously an increase in P4501A1 content was observed. P4501A1-mRNA expression (measured by RT-PCR) was distinctly increased following beta NF exposure for 6 or 24 hrs. DMSO (0.2%) and dexamethasone alone modified monooxygenation rates, but did not have significant effects on P4501A1 content or, in the case of DMSO, P4501A1 gene expression (for dexamethasone not determined). Liver slices are a useful and simple tool for the detection of a beta NF-like induction within a few hours after preparation of the slices.

Animals↗

Comparison of a unipolar defibrillation system with a dual lead system using an enlarged defibrillation anode.

The unipolar system for transvenous defibrillation, consisting of a single right ventricular lead as the cathode and the device shell as anode, has been shown to combine low defibrillation thresholds (DFTs) and simple implantation techniques. We compared the defibrillation efficacy of this system with the defibrillation efficacy of a dual lead system with a 12-cm long defibrillation anode placed in the left subclavian vein. The data of 38 consecutive patients were retrospectively analyzed. The implantation of an active can system was attempted in 20 patients (group 1), and of the dual lead system in 18 patients (group 2). Both groups had comparable demographic data, cardiac disease, ventricular function, or clinical arrhythmia. The criterion for successful implantation was a DFT of < or = 24 J. This criterion was met in all 18 patients of group 2. The active can system could not be inserted in 3 of the 20 group 1 patients because of a DFT > 24 J. In these patients, the implantation of one (n = 2) or two (n = 1) additional transvenous leads was necessary to achieve a DFT < or = 24 J. The DFTs of the 17 successfully implanted group 1 patients were not significantly different from the 18 patients in group 2 (12.3 +/- 5.7 J vs 10.8 +/- 4.8 J). The defibrillation impedance was similar in both groups (50.1 +/- 6.1 omega vs 48.9 +/- 5.2 omega). In group 1, both operation duration (66.8 +/- 17 min vs 80.8 +/- 11 min; P < 0.05) and fluoroscopy time (3.3 +/- 2.1 min vs 5.7 +/- 2.9 min; P < 0.05) were significantly shorter. Thus, the active can system allows reliable transvenous defibrillation and a marked reduction of operation duration and fluoroscopy time. The dual lead system, with an increased surface area defibrillation anode, seems to be a promising alternative for active can failures.

Defibrillators, Implantable↗