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Biomedical subjects

M Fuchs

Publications and source records attributed to M Fuchs.

At least 19 recordsLinked to original sources

Second-line chemotherapy with pemetrexed after gemcitabine failure in patients with advanced pancreatic cancer: a multicenter phase II trial.

BACKGROUND: A standard second-line chemotherapy regimen has yet to be defined for patients with gemcitabine (Gem)-refractory advanced pancreatic cancer (PC). PATIENTS AND METHODS: In this multicenter phase II trial, patients with unresectable or metastatic PC who had progressed on single-agent Gem or a Gem-containing regimen received pemetrexed 500 mg/m(2) as a 10-min infusion every 3 weeks until disease progression or occurrence of unacceptable toxicity. The primary end point was the 3-month survival rate. RESULTS: A total of 192 treatment cycles were given to 52 patients. The overall response rate was 3.8% (two partial responses); 10 patients (19.2%) experienced stable disease, nine of them for >12 weeks. At least one CA 19-9 reduction > or =50% occurred in 12 patients (23.1%). The 3-month survival rate was 75% (95% confidence interval 63.2% to 86.8%), the median time to tumor progression was 7 weeks (range 1-62 weeks) and the median overall survival time was 20 weeks (range 1-84 weeks). Grade 3/4 hematological toxic effects included (percent of patients): neutropenia (17.3%), thrombocytopenia (5.8%) and anemia (3.8%). The most frequent non-hematological toxic effects were diarrhea, nausea and stomatitis/pharyngitis (23.1% each). CONCLUSION: Pemetrexed is a safe treatment option with moderate activity in patients with advanced PC after failure of Gem.

Adult↗

[Rare sialadenoma papilliferum in the hard palate: case report and survey of the literature].

Sialadenoma papilliferum is a rare tumour of the salivary glands that usually occurs in the oral cavity. Following the course of the salivary glands of the oral mucosa, the hard and soft palate are the most common locations of this tumor. In the international literature, only a few case reports about this entity can be found. We present a 63-year-old patient with a sialadenoma papilliferum accidentally found during diagnostic procedures for progredient dysphagia. Suffering from infrabifurcal cancer of the oesophagus, the patient had undergone partial oesophagectomy 1 year before. Histological verification was performed with a tumor biopsy at the border of hard and soft palate, on the right side. This case is compared with 39 further cases reported in the literature. The therapy of choice is resection of the tumor. Because of the high frequency of recurrence, in sano resection should be planned.

Adenoma↗

Thermosensitive core-shell particles as model systems for studying the flow behavior of concentrated colloidal dispersions.

We report on a comprehensive investigation of the flow behavior of colloidal thermosensitive core-shell particles at high densities. The particles consist of a solid core of poly(styrene) onto which a network of cross-linked poly(N-isopropylacrylamide) is affixed. Immersed in water the shell of these particles will swell if the temperature is low. Raising the temperature above 32 degrees C leads to a volume transition within this shell which leads to a marked shrinking of the shell. The particles have well-defined core-shell structure and a narrow size distribution. The remaining electrostatic interactions due to a small number of charges affixed to the core particles can be screened by adding 0.05M KCl to the suspensions. Below the lower critical solution temperature at 32 degrees C the particles are purely repulsive. Above this transition, a thermoreversible coagulation takes place. Lowering the temperature again leads to full dissociation of the aggregates formed by this process. The particles crystallize for effective volume fractions between 0.48 and 0.55. The crystallites can be molten by shear in order to reach a fluid sample again. The reduced shear stress measured in this metastable disordered state was found to be a unique function of the shear rate and the effective volume fraction. These reduced flow curves thus obtained can be described quantitatively by the theory of Fuchs and Cates [Phys. Rev. Lett. 89, 248304 (2002)] which is based on the mode-coupling theory of the glass transition.

Journal Article↗

Pathways involved in alanyl-glutamine-induced changes in neutrophil amino- and alpha-keto acid homeostasis or immunocompetence.

We examined the effects of DON [glutamine-analogue and inhibitor of glutamine-requiring enzymes], alanyl-glutamine (regarding its role in neutrophil immunonutrition) and alanyl-glutamine combined with L-NAME, SNAP, DON, beta-alanine and DFMO on neutrophil amino and alpha-keto acid concentrations or important neutrophil immune functions in order to establish whether an inhibitor of *NO-synthase [L-NAME], an *NO donor [SNAP], an analogue of taurine and a taurine transport antagonist [beta-alanine], an inhibitor of ornithine-decarboxylase [DFMO] as well as DON could influence any of the alanyl-glutamine-induced effects. In summary, irrespective of which pharmacological, metabolism-inhibiting or receptor-mediated mechanisms were involved, our results showed that impairment of granulocytic glutamine uptake, modulation of intracellular glutamine metabolisation and/or de novo synthesis as well as a blockade of important glutamine-dependent metabolic processes may led to significant modifications of physiological and immunological functions of the affected cells.

Adult↗

Variable very-high-energy gamma-ray emission from the microquasar LS I +61 303.

Microquasars are binary star systems with relativistic radio-emitting jets. They are potential sources of cosmic rays and can be used to elucidate the physics of relativistic jets. We report the detection of variable gamma-ray emission above 100 gigaelectron volts from the microquasar LS I 61 + 303. Six orbital cycles were recorded. Several detections occur at a similar orbital phase, which suggests that the emission is periodic. The strongest gamma-ray emission is not observed when the two stars are closest to one another, implying a strong orbital modulation of the emission or absorption processes.

Journal Article↗

Biliary lipids, cholesterol and bile synthesis: different adaptive mechanisms to dietary cholesterol in lean and obese subjects.

BACKGROUND: Increased biliary cholesterol secretion together with elevated cholesterol synthesis may predispose obese subjects to cholesterol gallstone formation. AIM: To investigate whether processing of dietary cholesterol is altered in obesity, we enrolled eight lean and seven obese subjects in a double-blind crossover study. METHODS: Cholesterol consumption was 300 mg/day on low and 1300 mg/day on high cholesterol diet. After 3 weeks on either diet, hepatic bile was collected to determine biliary lipid secretion, and bile salt composition by high-performance liquid chromatography and cholesterol saturation index was calculated. Cholesterol synthesis was measured employing mass isotopomer distribution analysis. Bile acid synthesis via neutral and acidic pathway was assessed by serum levels of 7alpha-hydroxy-4-cholesten-3-one and 27-hydroxycholesterol. RESULTS: Cholesterol synthesis was increased in obese compared with lean and feedback inhibited only in obese. On low cholesterol diet, cholesterol secretion was doubled in obese but bile acid composition and synthesis was similar between the two groups. After high cholesterol diet, cholesterol saturation index and bile secretion were unchanged. In contrast to obese, lean increased bile acid synthesis only via the acidic pathway. CONCLUSIONS: Dietary cholesterol appears to preferentially induce bile acid synthesis via the acidic pathway in lean, whereas cholesterol synthesis was inhibited in obese. Thus, stable cholesterol saturation index may be achieved by different mechanisms.

Adult↗

Nitric oxide and polyamine pathway-dependent modulation of neutrophil free amino- and alpha-keto acid profiles or host defense capability.

We have examined the effects of N(omega)-nitro-L-arginine-methylester-hydrochloride [L-NAME; inhibitor of nitric oxide synthase], S-nitroso-N-acetyl-penicillamine [SNAP; nitric oxide donor], alpha-difluoro-methyl-ornithine [DFMO; inhibitor of ornithine decarboxylase] arginine or ornithine as well as the combination of arginine or ornithine with L-NAME, SNAP or DFMO on intracellular free amino- and alpha-keto acid profiles and the immune function markers superoxide anion and hydrogen peroxide generation as well as released myeloperoxidase activity in neutrophils (PMN). Although the underlying mechanisms still remain unclear, we believe from our results that nitric oxide as well as polyamine-dependent pathways are involved in the signal transmission of free radical molecule, beneficial nutritional therapy or maleficient pharmacological stress-induced alterations in PMN nutrient composition. Relevant changes in intragranulocyte free amino- and alpha-keto acid homeostasis and metabolism, especially, may be one of the determinants in PMN nutrition that positively or negatively influences and modulate neutrophil host defence capability and immunocompetence.

Adult↗

[Is there a nonsurgical therapeutic approach to cholangiocellular carcinomas?].

Nonsurgical treatment aims at controlling disease and improving survival and quality of life in patients with nonresectable, recurrent metastatic cholangiocarcinomas. After R0 resection, percutaneous or intraluminal radiotherapy with adjuvant radiochemotherapy may improve survival. Available data, however, are still unsatisfactory, and the efficacy of adjuvant radiochemotherapy after R0 resection remains to be confirmed. Exclusive chemotherapy fails to improve survival postoperatively while, in adequate patients, neoadjuvant chemotherapy can improve R0 resection results. Palliative chemotherapy yielded improved survival and quality of life in only one small prospective randomized trial and cannot be generally recommended at present. Previous biliary stenting for relieving jaundice is mandatory. Beyond established regimens employing 5-fluorouracil/leukovorin and gemcitabine plus platin-based agents, ongoing trials are focussing on topoisomerase-and thyrosine kinase inhibitors. Palliative stenting of malignant bile duct stenoses may eliminate or at least relieve jaundice and pruritus. Single stenting is sufficient for distal bile duct stenoses. In patients with liver metastasis and life expectancy of <6 months, temporary plastic prostheses with 4-6-month patency are sufficient. When the prognosis is for >6 months, self-expanding permanent metal stents, with their significantly longer patency, are superior. In hilar tumors, obstruction of plastic prostheses occurs earlier than in distal bile duct stenoses. Thus, patients with Bismuth II-IV tumors benefit from self-expanding metal stents. These may be inserted by an endoscopic, retrograde approach, percutaneously, or by a combined rendez-vous maneuver. The superiority of bilateral vs unilateral stenting has yet to be proven in Bismuth II-IV tumors. Photodynamic therapy followed by stenting appears to improve survival rates by delaying stent occlusion rather than by regression of the tumoric disease itself.

Antineoplastic Combined Chemotherapy Protocols↗

[Vocal efficiency parameters in children and adolescents: effect of physical development and singing activity].

The influence of physical development and singing activity on vocal efficiency in children and adolescents is well known from clinical experience. There is, however, no comparative study between singing and non-singing children which also considers the influence of age and gender. Therefore, standard values for evaluation in clinical practice are missing. We examined the following parameters in 164 healthy children and adolescents (90 boys, 74 girls; 11-16 years), 86 without singing activity (group A) and 78 members of children's and youth choirs (group B): frequency and dynamic range of voice and its borders with a voice range profile, mean fundamental frequency (normal and loud phonation), maximum voice intensity, and maximum duration of intonation. The statistical analysis was performed using three-way ANOVA. We found significantly higher ranges of frequency and intensity in singing children and adolescents (p<0.0001). The borders of the dynamic range and the upper border of the frequency range were significantly higher in group B (p<0.0001). The boys in group B used a higher mean fundamental frequency during loud phonation. There were no significant differences between groups in maximum voice intensity (p=0.051) but a tendency towards higher values in singing children. As an unexpected result, we found significantly higher values in maximum duration of intonation in group A (p<0.0001) independent of age and gender, which seems to be related to the methods used. Regular training of the singing voice results in positive effects on several voice parameters in children as well as adolescents. Our results can be used for estimating standard values in professional clinical and educational care of young singing voices and non-singing children. For this purpose, voice range profile is particularly suitable.

Adolescent↗

["Iatrogenic acute coronary syndrome"--59 year old patient with adenocarcinoma of ascending colon and stenocardia while receiving adjuvant chemotherapy with 5-fluorouracil].

Fluorouracil-associated cardiotoxic adverse events represent a relevant but underestimated problem in 5-fluorouracil treatment. After right hemicolectomy for adenocarcinoma of the rightsided colonic flexure a 59-year old patient was referred to our hospital for adjuvant chemotherapy according to MOSAIC-protocol with oxaliplatin and 5-fluorouracil. The patient's history was unremarkable for any cardiopulmonary disease and for any cardiovascular risk factors. 24 hours after completing the first cycle the patient was readmitted to our emergency department because of thoracic pain combined with significantly elevated cardiac enzymes and ischaemic changes in ECG. Coronary angiography was performed revealing no coronary artheriosclerosis. Clinical symptoms and pathological ischaemic serum parameters returned to normal range within 12 hours. Diagnosis of 5-FU-induced acute coronary syndrome could be made. Because of the high rate of recurring cardiotoxicity the patient's chemotherapy was modified to an alternative regimen containing raltitrexed instead of 5-fluorouracil. Immediate diagnosis of 5-FU-induced cardiotoxicity and differentiation from preexisting coronary heart disease is still a major problem in daily oncological practice.

Adenocarcinoma↗

A phase III trial of pemetrexed plus gemcitabine versus gemcitabine in patients with unresectable or metastatic pancreatic cancer.

BACKGROUND: This randomized phase III study compared the overall survival (OS) of pemetrexed plus gemcitabine (PG) versus standard gemcitabine (G) in patients with advanced pancreatic cancer. PATIENTS AND METHODS: Patients with unresectable locally advanced or metastatic pancreatic cancer and no prior systemic therapy (including 5-fluorouracil as a radiosensitizer) were randomized to receive either 1,250 mg/m(2) gemcitabine on days 1 and 8 plus pemetrexed 500 mg/m(2) after gemcitabine on day 8 (PG arm) of each 21-day cycle, or gemcitabine 1,000 mg/m(2) on days 1, 8 and 15 of each 28-day cycle (G arm). RESULTS: Five hundred and sixty-five patients with well-balanced baseline characteristics were randomly assigned (283 PG, 282 G). OS was not improved on the PG arm (6.2 months) compared with the G arm (6.3 months) (P=0.8477). Progression-free survival (3.9 versus 3.3 months; P=0.1109) and time to treatment failure (3 versus 2.2 months; P=0.2680) results were similar. Tumor response rate (14.8% versus 7.1%; P=0.004) was significantly better on the PG arm. Grade 3 or 4 neutropenia (45.1% versus 12.8%), thrombocytopenia (17.9% versus 6.2%), anemia (13.9% versus 2.9%), febrile neutropenia (9.9% versus 0.4%; all P <0.001) and fatigue (15% versus 6.6%; P=0.002) were significantly more common on the PG arm. Four treatment-related deaths occurred on the PG arm and none in the G arm. CONCLUSIONS: Pemetrexed plus gemcitabine therapy did not improve OS. Single-agent gemcitabine remains the standard of care for advanced pancreatic cancer.

Adult↗

Alterations in neutrophil (PMN) free intracellular alpha-keto acid profiles and immune functions induced by L-alanyl-L-glutamine, arginine or taurine.

The objective of this study was to determine the dose as well as duration of exposure-dependent effects of L-alanyl-L-glutamine, arginine or taurine on polymorphonuclear neutrophil (PMN) free alpha-keto acid profiles and, in a parallel study, on PMN immune functions. Exogenous L-alanyl-L-glutamine significantly increased PMN alpha-ketoglutarate, pyruvate PMN superoxide anion (O2-) generation, hydrogen peroxide (H2O2) formation and released myeloperoxidase (MPO) activity. Arginine also led to significant increases in alpha-ketoglutarate, pyruvate, MPO release and H2O2 generation. Formation of O2- on the other hand was decreased by arginine. Incubation with taurine resulted in lower intracellular pyruvate and alpha-ketobutyrate levels, decreased O2- and H2O2 formation and a concomitant significantly increased MPO activity. We therefore believe that considerable changes in PMN free-alpha-keto-acid profiles, induced for example by L-alanyl-L-glutamine, arginine or taurine, may be one of the determinants in cell nutrition that considerably modulates the immunological competence of PMN.

Adult↗

Characterization of a naturally occurring recombinant isolate of Grapevine fanleaf virus.

The naturally occurring Grapevine fanleaf virus (GFLV) recombinant isolate A17b was recovered from its grapevine host by sap inoculation and serial passages onto Gomphrena globosa, a pseudo local lesion herbaceous host, and Chenopodium quinoa, a systemic herbaceous host, to characterize some of its biological properties. Sequence analysis of the CP gene, in which a recombinational event was previously detected, demonstrated the genetic stability of recombinant isolate A17b over a 5-year period in its natural host as well as in C. quinoa. Also, recombinant isolate A17b was graft transmissible, as shown by an in vitro heterologous approach, and transmitted by the nematode Xiphinema index as readily as nonrecombinant GFLV isolates. Furthermore, despite a lower pathogenicity on Chenopodium amaranticolor, recombinant isolate A17b had a similar host range and induced similar symptoms in type and severity to nonrecombinant GFLV isolates. Interestingly, the use of infectious chimeric RNA2 transcripts in combination to RNA1 transcripts of GFLV strain F13 suggested no implication of the recombination event in the CP gene of isolate A17b in the reduced pathogenicity on C. amaranticolor. Altogether, recombinant isolate A17b had similar biological properties to GFLV nonrecombinant isolates.

Base Sequence↗

Observation of in-medium modifications of the omega meson.

The photoproduction of omega mesons on nuclei has been investigated using the Crystal Barrel/TAPS experiment at the ELSA tagged photon facility in Bonn. The aim is to study possible in-medium modifications of the omega meson via the reaction gamma + A --> omega + X --> pi(0)gamma + X('). Results obtained for Nb are compared to a reference measurement on a LH2 target. While for recoiling, long-lived mesons (pi(0), eta, and eta;(')), which decay outside of the nucleus, a difference in the line shape for the two data samples is not observed, we find a significant enhancement towards lower masses for omega mesons produced on the Nb target. For momenta less than 500 MeV/c an in-medium omega meson mass of M(medium) = [722(+4)(-4)(stat)+35-5(syst)] MeV/c(2) has been deduced at an estimated average nuclear density of 0.6rho(0).

Journal Article↗

Investigation of gettering effects in CZ-type silicon with SIMS.

Ion implantation is a well-known standard procedure in electronic device technology for precise and controlled introduction of dopants into silicon. However, damage caused by implantation acts as effective gettering zones, collecting unwanted metal impurities. This effect can be applied for "proximity gettering" reducing the concentration of impurities in the active device region. In this study the consequences of high-energy ion implantation into silicon and of subsequent annealing were analysed by means of secondary ion mass spectrometry (SIMS). Depth profiles were recorded of such impurities as copper, oxygen and carbon to obtain information about their gettering behaviour. The differences in impurities gettering behaviour were studied as a function of the implanted ions, P and Si, of the implantation dose and annealing time at T = 900 degrees C. Besides impurities gettering at the mean projected range (Rp) of implanted ions, Rp-effect, defects at around half of the projected ion range, Rp/2-effect, and even in some cases beyond Rp, trans-Rp-effect, have also been found to be effective in gettering of material impurities.

Journal Article↗

Describing static correlation in bond dissociation by Kohn-Sham density functional theory.

We show that density functional theory within the RPA (random phase approximation for the exchange-correlation energy) provides a correct description of bond dissociation in H(2) in a spin-restricted Kohn-Sham formalism, i.e., without artificial symmetry breaking. We present accurate adiabatic connection curves both at equilibrium and beyond the Coulson-Fisher point. The strong curvature at large bond length implies important static (left-right) correlation, justifying modern hybrid functional constructions but also demonstrating their limitations. Although exact at infinite separation and accurate near the equilibrium bond length, the RPA dissociation curve displays unphysical repulsion at larger but finite bond lengths. Going beyond the RPA by including the exact exchange kernel (RPA+X), we find a similar repulsion. We argue that this deficiency is due to the absence of double excitations in adiabatic linear response theory. Further analyzing the H(2) dissociation limit we show that the RPA+X is not size consistent, in contrast to the RPA.

Journal Article↗

Neutral-pion photoproduction off protons in the energy range 0.3 GeV<E(gamma)<3 GeV.

Single pi(0) photoproduction has been studied with the CB-ELSA experiment at Bonn using tagged photon energies between 0.3 and 3.0 GeV. The experimental setup covers a very large solid angle of approximately 98% of 4pi. Differential cross sections dsigma/dOmega have been measured. Complicated structures in the angular distributions indicate a variety of different resonances being produced in the s channel intermediate state gammap-->N(*)(Delta(*))-->ppi(0). A combined analysis including the data presented in this letter along with other data sets reveals contributions from known resonances and evidence for a new resonance N(2070)D15.

Journal Article↗