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Biomedical subjects

M Müller

Publications and source records attributed to M Müller.

At least 145 records · Page 8Linked to original sources

Statistical physics of RNA folding.

We discuss the physics of RNA as described by its secondary structure. We examine the static properties of a homogeneous RNA model that includes pairing and base stacking energies as well as entropic costs for internal loops. For large enough loop costs the model exhibits a thermal denaturation transition which we analyze in terms of the radius of gyration. We point out an inconsistency in the standard approach to RNA secondary structure prediction for large molecules. Under an external force a second-order phase transition between a globular and an extended phase takes place. A Harris-type criterion shows that sequence disorder does not affect the correlation length exponent while the other critical exponents are modified in the glass phase. However, at high temperatures, on a coarse-grained level, disordered RNA is well described by a homogeneous model. The characteristics of force-extension curves are discussed as a function of the energy parameters. We show that the force transition is always second order. A reentrance phenomenon relevant for real disordered RNA is predicted.

Journal Article↗

Nucleolar proteins and ultrastructure in bovine in vivo developed, in vitro produced, and parthenogenetic cleavage-stage embryos.

In the present study, ribosomal RNA (rRNA) gene activation, monitored through nucleolus development, was studied by autoradiography following (3)H-uridine incubation, transmission electron microscopy, and immunofluorescence confocal laser scanning microscopy of key nucleolar proteins involved in rRNA transcription (topoisomerase I, upstream binding factor, and RNA polymerase I) and processing (fibrillarin, nucleolin, and nucleophosmin) in in vivo developed, in vitro produced, and parthenogenetic bovine embryos. In general, in vivo developed embryos displayed formation of fibrillo-granular nucleoli during the 4th post-fertilization cell cycle. During the previous stages of development, nucleolus precursor bodies (NPBs) were observed. However, on some occasions the initial steps of nucleolus formation were observed already at the 2- and 4-cell stage in cases where such embryos were collected from superovulated animals together with later embryonic stages presenting nucleolar development and autoradiographic labeling. The in vitro produced embryos displayed very synchronous formation of fibrillo-granular nucleoli and autoradiographic labeling during the 4th cell cycle. In vivo developed and in vitro produced embryos displayed allocation of nucleolar proteins to fibrillar and granular compartments of the developing nucleoli during the 4th cell cycle. The parthenogenetic embryos typically displayed formation of fibrillo- granular nucleoli during the 5th cell cycle and autoradiographic labeling was not observed until the morula stage. Moreover, the 1-, 2-, and 4-cell parthenogenetic embryos practically lacked NPBs. On the other hand, parthenogenetic embryos displayed allocation of nucleoar proteins to nuclear entities during the 4th cell cycle. In conclusion, both in vivo developed and in vitro produced bovine embryos displayed activation of transcription and nucleolar development during the 4th cell cycle. However, in vivo developed embryos flushed together with later developmental stages displayed premature activation of these processes. Parthenogenetic bovine embryos, on the other hand, displayed a delayed activation.

Animals↗

[Surgical standard therapy for cancer of the pancreas].

Approximately 150,000 people worldwide and 40,000 people in Europe die each year of pancreatic cancer,making it one of the five leading causes of cancer-related death and one of the most aggressive human tumors. Resection is still the only option that offers a chance of cure for pancreatic cancer patients. Recent studies have highlighted the correlation between the number of pancreatic resections per year and postoperative mortality. Thus, large centers of pancreatic surgery have mortality rates below 5%, whereas centers with lower caseloads have mortality rates exceeding 10%. Standards have been established for the surgical treatment of pancreatic cancer;however, these are often not based on evidence derived from randomized, controlled studies. Resection for pancreatic cancer is carried out if there are no metastases present and if the tumor is locally resectable; i.e., if there is no complex vessel invasion. However, an isolated infiltration of the portal vein is not considered a contraindication for surgery. At present, there are no evidenced-based data available on palliative (R2) resections,which might be a therapeutic option in centers with low morbidity/mortality. Three randomized controlled trials clearly show that the pylorus-preserving Whipple is equal to the classical Whipple in terms of oncological effectiveness, morbidity, and quality of life. Therefore, the pylorus-preserving Whipple is increasingly considered the standard operation for tumors of the pancreatic head. Based on randomized trials, extended lymph node dissection cannot generally be recommended for pancreatic cancer. Further prospective, randomized, multicenter trials have to be carried out in the upcoming years to find new approaches in the therapy of pancreatic cancer and to establish evidence-based treatment strategies for this disease.

Adenocarcinoma↗

[Catheter ablation of ectopic atrial tachycardia by electrical pulmonary vein disconnection].

We report a 25-year-old female patient with a long history of symptomatic paroxysmal supraventricular tachycardia. Electroanatomic activation mapping demonstrated a focal tachycardia originating in the right upper pulmonary vein, 3 cm distal to the ostium. Due to the recent experiences in the management of focal atrial fibrillation with catheter ablation, direct ablation applied inside the pulmonary vein was avoided. Instead, an electrical disconnection of the pulmonary musculature from the left atrium guided by a circumferential 10-electrode mapping catheter was performed. The patient has since been asymptomatic during follow-up.

Adult↗

Brain lesion size and phase shift as an index of cerebral autoregulation in patients with severe head injury.

BACKGROUND: Whether the phase relationship (phase shift) between cerebral blood flow velocity as assessed by transcranial Doppler ultrasound and blood pressure at 0.1 Hz can be used to assess cerebral autoregulation (CA) in patients with severe traumatic brain injury (TBI). METHODS: In 33 healthy volunteers (mean age, SD; 37+/-17 years, range 17-65) middle cerebral artery (MCA) blood velocity (V) was recorded simultaneously with finger blood pressure (BP) over a period of 10 minutes under normocapnic and hypocapnic conditions to generate normative data. In 27 patients with severe TBI (Glasgow Coma scale score < or =8) serial close in time investigations of cranial computed tomography (CT) scanning and phase shift assessment were performed on days 1, 3, 5, and 8 after trauma. Phase shift in the MCA was compared to brain parenchyma lesion size in the MCA territory on CT scanning. Lesion size was classified into 0, normal; 1, presence of a small lesion (diameter <3 cm); 2, presence of a large lesion (>3 cm). FINDINGS: Compared to normocapnia, hypocapnia significantly increased phase shift at 0.1 Hz from 78+/-28 degrees to 101+/-25 degrees (p < 0.001). In the TBI patients, 115 comparisons between CT findings and CA results were possible. Phase shift detected a pathological CA in 31 instances, which were more frequent in CT lesion type 2 (19/42) than in group 0 (7/44) and group 1 (5/29). INTERPRETATION: When CA is intended to be assessed by use of phase shift, the hyperventilation setting needs its own reference values. In MCA territories containing a traumatic lesion greater than 3 cm in diameter phase shift at 0.1 Hz will detect a high frequency (44%) of a disturbed state of CA.

Adolescent↗

Cytological modifications in zucchini yellow mosaic virus (ZYMV)-infected Styrian pumpkin plants.

The present research demonstrates severe ultrastructural changes induced by zucchini yellow mosaic virus (ZYMV) within the cells of older and younger leaves of Styrian pumpkin plants (Cucurbita pepo L. subsp. pepo var. styriaca GREB.). Cylindrical inclusions (pinwheels), proliferated endoplasmatic reticulum and filamentous viral particles were found throughout the cytoplasm of ZYMV-infected cells and within sieve elements. ZYMV-infection also induced severe modifications in the number and ultrastructure of chloroplasts, whereas mitochondria, nuclei and peroxisomes remained unaffected. A significantly lower number of chloroplasts was observed in all tissues of both ZYMV-infected leaf types when compared to control plants. Statistical quantification revealed that in chloroplasts of ZYMV-infected older and younger leaves the amount of plastoglobuli and starch increased significantly, whereas the amount of thylakoids significantly decreased. The present research gives a more precise insight in ZYMV-induced modifications within single cells and organelles, and provides statistical data of the most affected chloroplasts.

Chloroplasts↗

A new mechanism of model membrane fusion determined from Monte Carlo simulation.

We have carried out extensive Monte Carlo simulations of the fusion of tense apposed bilayers formed by amphiphilic molecules within the framework of a coarse-grained lattice model. The fusion pathway differs from the usual stalk mechanism. Stalks do form between the apposed bilayers, but rather than expand radially to form an axial-symmetric hemifusion diaphragm of the trans leaves of both bilayers, they promote in their vicinity the nucleation of small holes in the bilayers. Two subsequent paths are observed. 1) The stalk encircles a hole in one bilayer creating a diaphragm comprised of both leaves of the other intact bilayer, which ruptures to complete the fusion pore. 2) Before the stalk can encircle a hole in one bilayer, a second hole forms in the other bilayer, and the stalk aligns and encircles them both to complete the fusion pore. Both pathways give rise to mixing between the cis and trans leaves of the bilayer and allow for transient leakage.

Biophysical Phenomena↗

Hyperphosphaturia after kidney transplantation in syngeneic rats: effects on nephrocalcinosis and bone metabolism?

BACKGROUND: Studies on kidney transplantation have thus far mainly dealt with surgical techniques, immunology, and transplant tolerance. Disturbed mineral metabolism after renal denervation has not received much attention. Basic physiological research in short-term experiments has shown that experimental renal denervation in rats leads to parathormone (PTH)-independent hyperphosphaturia (HPU). HPU and other metabolic complications also have been described after clinical kidney transplantation. Furthermore, there is an unexpected increase in the risk of bone fracture. However, these studies have examined an organism pre-damaged with regard to the parathyroid and immunosuppression. Experimental investigations in syngeneic rats were performed to see whether HPU also occurs after transplantation and thus after denervation and which target organs are involved. METHODS: Thirty-six male Lewis rats subjected to laparotomy (n = 12), unilateral nephrectomy (n = 12), or unilateral transplantation and bilateral nephrectomy (n = 12) were observed for 18 weeks. RESULTS: Animals that underwent transplantation had a significant loss of phosphate in the urine not associated with decreased calcium, phosphate, or magnesium in bone. Stability test showed no deterioration, despite a slight increase in the bone parameters of alkaline phosphatase, cyclic AMP, and hydroxyproline with unchanged calciotropic hormones. Nephrocalcinosis was not observed. Parallel to HPU, there was a compensatory reduction in fecal phosphate excretion. CONCLUSIONS: The loss of phosphate after clinical kidney transplantation in the predamaged parathyroid hormone control system as well as immunosuppression and a surprising increase in the incidence of bone fractures may be explained by the denervation-related loss of phosphate. The lack of intestinal counter-regulation could be an important pathomechanism.

Adenosine↗

"Onco-tese": testicular sperm extraction in azoospermic cancer patients before chemotherapy-new guidelines?

OBJECTIVES: To examine the usefulness of pretreatment testicular sperm extraction because some patients have tumor-induced azoospermia. In view of the high cure rates for testicular germ cell tumors and malignant lymphomas, increasing clinical importance is attached to protecting fertility. High-dose cytostatic therapy may be expected to cause long-term infertility. Thus, the standard procedure for fertility protection is cryopreservation of ejaculated spermatozoa before therapy. METHODS: Contralateral testicular biopsies were taken from 14 azoospermic patients with malignant testicular germ cell tumors. In addition, 17 patients with malignant lymphomas underwent unilateral (n = 6) or bilateral (n = 11) testicular biopsy. The tissue specimens were cryopreserved, and the histologic workup was performed at the same time. RESULTS: Of the 14 patients with malignant testicular germ cell tumors, 6 had spermatozoa in their testicular biopsies. Sertoli cell-only syndrome was found in 5 patients, and 3 had maturation arrest without detection of spermatozoa. Successful sperm recovery was possible in 8 of the 17 patients with malignant lymphoma, 4 had Sertoli cell-only syndrome, and 5 had maturation arrest. None of the patients had evidence of secondary wound healing or treatment delay because of the testicular biopsy. CONCLUSIONS: Our results show that testicular sperm extraction is a useful technique for obtaining spermatozoa before cytotoxic therapy in azoospermic cancer patients. This procedure should be considered as an option for fertility preservation in azoospermic cancer patients, because high cumulative cytostatic doses can cause irreversible fertility alterations.

Antineoplastic Agents↗

Target site bacterial killing of cefpirome and fosfomycin in critically ill patients.

We employed an in-vivo pharmacokinetic/in-vitro pharmacodynamic method to simulate bacterial killing in plasma and the interstitium of skeletal muscle tissue after intravenous administration of 2 g of cefpirome and 8 g of fosfomycin alone and in combination to patients with sepsis. Interstitial antimicrobial concentrations were determined by use of in-vivo microdialysis. CFU/ml of Staphylococcus aureus (ATCC 29213) and Pseudomonas aeruginosa (clinical isolate) decreased by approximately 2log(10) for plasma and muscle tissue 6 h after cefpirome and fosfomycin administration compared with the baseline, respectively. The simulation of plasma and tissue pharmacokinetics for the combined administration of these antibiotics resulted in complete eradication of S. aureus within 5 h after drug exposure. No bacterial re-growth occurred in any of the simulations within 6 h. The in-vitro simulation of in-vivo plasma and tissue pharmacokinetics of cefpirome and fosfomycin has shown that both antimicrobial agents kill S. aureus and P. aeruginosa strains effectively after single dose administration. This effect was most pronounced by the combined use of these antimicrobial agents. Therefore, this data corroborates antimicrobial strategies of simultaneous administration of cefpirome and fosfomycin in patients with severe soft tissue infection.

Anti-Bacterial Agents↗

Fixed nucleotide differences on the Y chromosome indicate clear divergence between Equus przewalskii and Equus caballus.

The phylogenetic relationship between Equus przewalskii and E. caballus is often a matter of debate. Although these taxa have different chromosome numbers, they do not form monophyletic clades in a phylogenetic tree based on mtDNA sequences. Here we report sequence variation from five newly identified Y chromosome regions of the horse. Two fixed nucleotide differences on the Y chromosome clearly display Przewalski's horse and domestic horse as sister taxa. At both positions the Przewalski's horse haplotype shows the ancestral state, in common with the members of the zebra/ass lineage. We discuss the factors that may have led to the differences in mtDNA and Y-chromosomal observations.

Animals↗

Gastrointestinal transit and 5-ASA release from a new mesalazine extended-release formulation.

BACKGROUND: Mesalazine (5-aminosalicylic acid, 5-ASA)-containing formulations represent a cornerstone in the treatment of inflammatory bowel diseases. Recently, a new formulation has been developed to provide selective and more homogeneous release of 5-ASA compared to traditional systems. METHODS: In a first study, gastrointestinal transit was followed by gamma-scintigraphy after single-dose application of tablets containing 1200 mg mesalazine to 12 healthy male volunteers. 5-ASA release was verified by the assessment of plasma pharmacokinetics. In a second, 7-day, multiple-dose study, the steady state plasma pharmacokinetics, urinary excretion and safety profile were characterized after twice-daily tablet administration to 12 healthy volunteers. RESULTS: Tablet erosion started after 6.9 +/- 1.1 h in the ascending or transverse colon. Radioactivity spread homogeneously throughout the colon, indicating the sustained release of active 5-ASA. Plasma kinetics indicated an earlier initial absorption of 5-ASA, i.e. during transit of the small intestine and ileum. Mean Cmax values (350.6 +/- 322.6 ng/mL) were observed during location in the ileo-caecal region. The mean relative absorption of 5-ASA was 19.9 +/- 18.2% in the small intestine and ileum and 80.1 +/- 18.2% in the colon. CONCLUSIONS: The administration of the new mesalazine formulation was well tolerated, and 5-ASA was continuously released along the whole colon, a favourable prerequisite for the therapy of distally located inflammatory bowel disease.

Adult↗

Transcapillary insulin transfer in human skeletal muscle.

BACKGROUND: Transcapillary insulin transfer is considered a rate-limiting step in insulin action at supraphysiological insulin concentrations. However, it remains unclear whether this concept also applies for physiological conditions. MATERIALS AND METHODS: In the present study we set out to characterize transcapillary insulin transfer by measuring insulin concentrations in plasma and interstitial space fluid of skeletal muscle during an oral glucose tolerance test and euglycaemic hyperinsulinaemic clamp conditions, respectively. For this purpose we employed in vivo microdialysis of skeletal muscle in conjunction with an ultrasensitive insulin assay in eight healthy lean male volunteers (aged 25 +/- 1 years). RESULTS: Insulin concentrations at baseline were 48 +/- 8 pmol x L(-1) in plasma and 19 +/- 4 pmol x L(-1) in the interstitium (P = 0.002). The mean interstitium to plasma ratio at baseline was 0.48 +/- 0.09 pmol x L(-1). During the oral glucose tolerance test the interstitium to plasma ratio remained unchanged (0.43 +/- 0.12, P = NS vs. baseline), but was significantly reduced during euglycaemic hyperinsulinaemic clamp conditions at steady-state hyperinsulinaemia (0.12 +/- 0.01, P = 0.01 vs. baseline). CONCLUSION: In summary there is a substantial transcapillary insulin gradient in healthy human skeletal muscle under baseline and glucose-stimulated conditions. Our findings support the hypothesis of a saturable transcapillary insulin transport representing a partly rate-limiting step for insulin action.

Adult↗

T-cell activation and the development of an apoptosis-resistant CD45RO+ T-cell population.

Growing experimental evidence supports a broadening role for the caspases; not only do they participate in the process of apoptosis but also in the control of the cell cycle and cellular proliferation. The biological role of the caspases in the process of T-cell activation and proliferation is still not defined. In the present study, we propose a potential role, by demonstrating an association of T-cell receptor-mediated caspase activity with the development of an apoptosis-resistant memory CD45RO+ T-cell population. As previously shown by us, a time-dependent induction of caspase activity, in the absence of apoptosis, can be observed in CD3-stimulated human peripheral blood lymphocytes. We here show that a population of CD45RO+ cells, with activated caspase-3 and with resistance to tributyltin-induced apoptosis, develops after 3 days of stimulation. A concomitant expression of the anti-apoptotic protein Bcl-xL accompanied the caspase activity and the development of the apoptosis-resistant phenotype. Finally, upon co-culturing with dexamethasone (DEX), the CD3-induced caspase-3 activity was blocked. During this condition, the expression of the activation marker HLA-DR as well as the cellular proliferative response was strongly suppressed. The development of memory cells with a CD45RO+ phenotype was also blocked. Our data support the hypothesis that caspase-3 activity, observed in CD3-stimulated cells, may be an important component in the proliferation process and, furthermore, might play a role for the development of memory T cells, and DEX inhibits this process.

Apoptosis↗

[Atrial lead placement in cases of intraoperative atrial fibrillation].

AIM: Evaluating the efficiency of a prescribed concept for atrial lead placement in cases of intraoperative atrial fibrillation (AF). METHODS: Over the period from 11/1998 to 5/2000, we carried out a prospective study on 40 patients with AF. After implantation of the screw electrode into the lateral wall of the atrium, an amplitude of the intracardial ECG of > or = 1.4 mV was arbitrarily defined as tolerable. At amplitudes of < 1.4 mV, atrial overdrive-stimulation occurred at 400 to 800 ppm in order to convert the AF to sinus rhythm (SR). Following successful overdrive-stimulation, the atrial electrode was positioned according to standard values (P-wave > 3 mV, pacing threshold < 0.5 V at 0.5 ms). In the case of unsuccessful intraoperative atrial stimulation, the electrode was repositioned until an amplitude of > or = 1.4 mV was reached. In all cases bipolar atrial screw electrodes (Model 4068, Medtronic Inc., Minneapolis, MN, USA) were implanted. The intraoperative measurements were carried out via the atrial channel of a 5311 PSA (Medtronic Inc., Minneapolis, MN, USA). In follow-up after 6 weeks, the atrial stimulation threshold was measured in [V] at 0.5 ms and the signal amplitude of the P-wave in [mV], or in the case of AF detection with successful mode switch activation. RESULTS: In 31/40 patients (77.5 %) with intraoperative persistent AF, fibrillation amplitudes of 1.4 to 3.1 mV (mean value 1.9 +/- 0.4 mV) were measured. In 9/40 patients (22.5 %) with intraoperative AF, 4 cases of conversion to SR using burst stimulation were documented. Atrial lead placement was performed using standard values. After 6 weeks, 33/40 patients (82.5 %) had SR, while intermittent AF episodes with successful mode switch activation were documented in 21 patients (52.5 %). The P-wave amplitude was 3.63 +/- 0.69 mV (range 1.8 to 4.9 mV), the atrial stimulation threshold was 1.3 +/- 0.4 mV (range 0.4 to 1.9 mV). Atrial lead adjustment due to sensing defects was not required for any patients. CONCLUSION: The results show that all atrial leads implanted in accordance with this concept demonstrate proper sensing at SR as well as under AF, with successful mode switch episodes and acceptable stimulation thresholds.

Aged↗

[Does a Combined Fascial Sling - Burch Colposuspension Display Advantages over a Fascial Sling alone for Treatment of Urinary Stress Incontinence in Females?].

PURPOSE: Despite the development of new surgical techniques, the fascial sling procedure remains an important surgical technique for the treatment of female urinary stress incontinence. An advantage of combining it with an additional Burch colposuspension has been suggested. The objective of our study was to evaluate retrospectively selected patients who had undergone a fascial sling procedure with and without Burch colposuspension. MATERIALS AND METHODS: Of a total of 390 females who underwent an incontinence operation at our department between 1990 and 1999, 56 patients had had a fascial sling plasty. A total of 50 patients (89 %) were followed for a median of 59.5 months. The median age was 60 years. 56 % of the patients displayed recurrent stress incontinence. The previous operations had been performed via a vaginal approach in 42.9 % and an abdominal approach in 57.1 %. The sling procedure used was that of Narik and Palmrich. Of the 50 patients, 14 had an additional Burch colposuspension. RESULTS: The continence rates (no pads) were for patients with a fascial sling procedure alone 63.9 % and for the combination of both operations 64.4 %. An improvement (1-3 pads) was seen in 27.8 % and 21.4 %, respectively. No changes were seen in 5.6 % and 7.1 % and impairment was seen in 2.7 % and 7.1 %, respectively. After a five-year follow-up, the total patient satisfaction rate was 78 %. CONCLUSIONS: The fascial sling is effective operative technique for treating female urinary stress incontinence, especially in severe and type III incontinence and in patients who had undergone previous operations for incontinence. The operation is safe and is the only technique that offers controlled overcorrection in desperate cases. An advantage of adding a Burch colposuspension to the fascial sling procedure was not detected in our patient group.

Adult↗