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Biomedical subjects

Dirk Arnold

Publications and source records attributed to Dirk Arnold.

16 recordsLinked to original sources
PubMed2007

Multicenter phase II trial of chemoradiation with oxaliplatin for rectal cancer.

PURPOSE: To evaluate the activity and safety of preoperative radiotherapy (RT) and concurrent capecitabine and oxaliplatin (XELOX-RT) plus four cycles of adjuvant XELOX in patients with rectal cancer. PATIENTS AND METHODS: One hundred ten patients with T3/T4 or N+ rectal cancer were entered onto the trial in 11 investigator sites and received preoperative RT (50.4 Gy in 28 fractions). Capecitabine was administered concurrently at 1,650 mg/m2 on days 1 to 14 and 22 to 35, and oxaliplatin was administered at 50 mg/m2 on days 1, 8, 22, and 29. Surgery was scheduled 4 to 6 weeks after completion of XELOX-RT. Four cycles of adjuvant XELOX (capecitabine 1,000 mg/m2 bid on days 1 to 14; oxaliplatin 130 mg/m2 on day 1) were administered. The main end points were activity as assessed by the pathologic complete response (pCR) rate and the feasibility of postoperative XELOX chemotherapy. RESULTS: After XELOX-RT, 103 of 104 eligible patients underwent surgery; pCR was achieved in 17 patients (16%), one patient had ypT0N1 disease, and 53 patients showed tumor regression of more than 50% of the tumor mass. R0 resections were achieved in 95% of patients, and sphincter preservation was accomplished in 77%. Full-dose preoperative XELOX-RT was administered in 96%. Grade 3 or 4 diarrhea occurred in 12% of patients. Postoperative complication occurred in 43% of patients. Sixty percent of patients received all four cycles of adjuvant XELOX, with sensory neuropathy (18%) and diarrhea (12%) being the main grade 3 or 4 toxicities. CONCLUSION: Preoperative XELOX-RT plus four cycles of adjuvant XELOX is an active and feasible treatment. This regimen is proposed for phase III evaluation comparing standard fluorouracil-based treatment with XELOX- based multimodality treatment.

Adult↗
PubMed2006

Gefitinib in combination with 5-fluorouracil (5-FU)/folinic acid and irinotecan in patients with 5-FU/oxaliplatin- refractory colorectal cancer: a phase I/II study of the Arbeitsgemeinschaft für Internistische Onkologie (AIO).

BACKGROUND: Gefitinib is an epidermal growth factor receptor tyrosine kinase inhibitor. It potentiates cytotoxic drug activity in human xenografts. This phase I/II dose-finding study evaluated gefitinib in combination with a 5-fluorouracil (5-FU)/folinic acid (FA)/irinotecan (FOLFIRI-AIO) regimen in patients with metastatic colorectal cancer. PATIENTS AND METHODS: Patients received gefitinib 250 mg per day, and escalating doses of FOLFIRI-AIO i.v. (dose level (DL) 1: 1600/ 500/60 mg/m(2); DL2: 1600/500/80 mg/m(2); DL3: 2000/500/ 80 mg/m(2)) weekly x 6. Dose-limiting toxicity (DLT) was determined in patients who completed 1 cycle of therapy. RESULTS: 13 patients were enrolled. 1 out of 6 patients on DL1 exhibited DLT (acute psychosis), and a total of 7 patients received DL2. Of those, 3 patients had DLT during cycle 1 (nausea/vomiting n = 2; diarrhea n = 1, fatigue n = 2). Recruitment was stopped at this DL because of the unfavorable toxicity profile observed during the first and subsequent treatment cycles (out of 7 patients: nausea/vomiting grade 3 n = 2, diarrhea grade 3 n = 2; fatigue n = 3). Only 1 patient showed a partial remission, and 2 patients experienced stabilization of disease. CONCLUSIONS: Dose escalation had to be stopped early because of gastrointestinal toxicity and fatigue. This treatment regimen did not seem advantageous with respect to efficacy in comparison with FOLFIRIAIO alone.

Aged↗
PubMed2006

Treadmill locomotion in normal mice-Step related multi-channel EMG profiles of thigh muscles.

Mouse models are increasingly used in current research on motor disorders. In mice, the myoelectrical activation of thigh muscles during locomotion has not yet, however, been investigated in depth. Especially intramuscular coordination has hardly been clarified. Therefore, the aims of this study were to characterize myoelectrical activity in the vastus lateralis (VL) and the biceps femoris (BF) muscle of the healthy mouse for reference purposes. The VL and the BF muscles of 12 healthy mice performing a total of 1985 steps during treadmill locomotion were investigated with two subcutaneous arrays each incorporating four electrodes. Eight-channel EMG was recorded simultaneously with high-speed videography. The EMG curves of each step were rectified and smoothed by calculating root mean square (RMS) profiles and then time-normalized for comparisons within and between animals. The EMG-activity of both muscles increased during late swing phase. The VL activity rose steeply and peaked during mid-stance phase, while the biceps activity reached a plateau during early stance phase. With increasing gait velocity, stance time decreased. The increase in gait velocity was also associated with greater EMG amplitudes. The results suggest that the BF lifts the lower hind leg during swing phase and stabilizes the leg during stance, while the VL bears the weight of the body during the stance phase.

Journal Article↗
PubMed2006

Calculation of coincidence summing corrections for X-ray peaks and for sum peaks with X-ray contributions.

In this paper, features of the gamma-ray spectra in the presence of important contributions of X-rays to coincidence summing effects are studied. The experimental results concerning the sum peaks with various X-ray combinations as well as the Ge X-ray escape peaks present in the spectrum of a 133Ba point source measured with an n-type detector are in good agreement with the values computed using the GESPECOR software.

Algorithms↗
PubMed2006

Improved determination of plutonium content and isotopic ratios in low activity samples by alpha-particle and underground L X-ray measurement.

The determination of the isotopic ratio of 239Pu and 240Pu by alpha-particle spectrometry is limited due to the small differences in the alpha-particle energies. But taking into account the differences in the L X-ray emission probabilities of the two plutonium isotopes, an additional L X-ray measurement allows the isotopic ratio of 239Pu and 240Pu to be determined. The sensitivity of this method can be improved, as described in this work, by performing the L X-ray measurement in an underground laboratory.

Algorithms↗
PubMed2006

Epidermal growth factor receptor tyrosine kinase inhibitors: present and future role in gastrointestinal cancer treatment: a review.

BACKGROUND: Despite advances in conventional and targeted anticancer therapy, the prognosis remains poor for many patients with solid tumors. Ongoing research into the molecular basis of malignant disease, however, has yielded many novel agents with potential activity, including the epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). DESIGN: This review summarizes current clinical data for EGFR-TKIs as monotherapy or in combination with 5-fluorouracil/leucovorin, irinotecan, or oxaliplatin, focusing on the rapidly developing area of colorectal, gastroesophageal, and pancreatic cancers. RESULTS: EGFR-TKIs have limited but valuable activity as monotherapy in non-small cell lung cancer patients who have received prior anticancer treatment. The potential for application as a single agent in colorectal, gastroesophageal, and pancreatic cancers has yet to be demonstrated conclusively and deserves further investigation, especially as second- or third-line therapy. In combination with oxaliplatin-based regimens and 5-fluorouracil/leucovorin-based regimens, TKIs have shown benefits, suggesting that there may be a synergistic effect with chemotherapy. However, combinations with irinotecan-based regimens have been limited by toxicities. CONCLUSIONS: EGFR-TKIs show benefits when used in combination with chemotherapy, and the favorable toxicity profiles observed suggest that these may be of value in frail or elderly patients.

Antineoplastic Agents↗
PubMed2006

Update on capecitabine in colorectal cancer.

In combination chemotherapy for metastatic colorectal cancer, i.v. 5-fluorouracil (5-FU) can be replaced by oral 5-FU (in the form of capecitabine or another orally available analogue) without negatively affecting overall toxicity and without remarkably reducing the efficacy of treatment in terms of response rate or overall survival. Preclinical evidence of synergy has led to promising early and successfully completed studies combining capecitabine plus oxaliplatin with bevacizumab, cetuximab, and epidermal growth factor receptor tyrosine kinase inhibitors. The use of preoperative capecitabine plus radiation is achieving good rates of pathological complete response in rectal cancer. While capecitabine is generally well tolerated, its potential toxicities need careful management and may require individual dose adaption.

Antimetabolites, Antineoplastic↗
PubMed2005

Evolutionary aspects and muscular properties of the trunk--implications for human low back pain.

Considerations about back pain, its aetiology, pathogenesis and therapy often argue that low back pain is the "price" that humanity has to pay for the upright body posture and the bipedal mode of locomotion. In fact, there are only few species that have evolved an obligate bipedal locomotion (e.g. kangaroos). Surprisingly, there are only minor morphological adaptations in humans clearly connected to the upright body posture (e.g. the habitual lumbar lordosis). The overall organization of the body axis has been evolved in quadrupedal animals and was more or less unchanged suitable for the human bipedal mode of locomotion. Up to now, the assumed uniqueness of human's trunk does not explain the frequency of back problems. Because of minor macroscopic differences between humans and other mammals, and even primates, we started to take a closer look at the paravertebral musculature. A three-dimensional investigation of muscle's fibre type distribution was undertaken on laboratory rats. Serial sections from the caudal thoracic and lumbar regions of the back were analysed, and the fibre type distribution pattern in all paravertebral muscles was described. Comparisons to other species imply more general characters of the fibre type distribution in mammals. Established concepts of human back muscle function were exposed to be valid for quadruped mammals as well. Muscle properties predicted by a biomechanical model based on human's anatomy (Wagner et al., this issue) were confirmed by results of the current study on a small mammal. Therefore, we propose only minor differences from the observed pattern in human back muscles.

Journal Article↗
PubMed2005

Preclinical evaluation of ZD1839 alone or in combination with oxaliplatin in a panel of human tumor cell lines -- implications for clinical use.

BACKGROUND: Preclinical studies have suggested antitumor activity of an epidermal growth factor (EGF)-receptor targeted therapy with selective tyrosine kinase inhibitors alone or in combination with conventional cytostatic drugs. However, in non-small cell lung cancer (NSCLC), addition of ZD1839 (Iressa) to combination chemotherapy did not improve the therapeutic outcome. Thus, further work is necessary to define factors predicting outcome of combination therapy. MATERIALS AND METHODS: In the present study, the activity of ZD1839 alone or in combination with oxaliplatin (Eloxatin) was evaluated in 12 human cancer cell lines including colon, testicular, anaplastic thyroid and epidermoid carcinoma cells. RESULTS: The EGF-receptor protein was overexpressed in line A431 (epidermoid carcinoma) and near the minimum detection limit in all other cell lines. The single agent activity of ZD1839 was highest in cell line A431. In the other cell lines, it was lower and appeared to be independent of EGF-receptor expression levels. The relative antitumor activity (RAA) was low (RAA = 1). Combined exposure to oxaliplatin and ZD1839 (IC30) resulted in significant synergy in 4 out of 6 colorectal cancer (CRC) cell lines and significant antagonism in 4 out of 6 non-colorectal cancer cell lines. Continuous exposure to ZD1839 (IC30) induced a marked G1-phase arrest and dephosphorylation of EGF-receptor in A431, whereas no significant cell cycle perturbation could be detected in the low-expression cell lines. Other factors than cell cycle perturbation seem to determine the mode of drug interaction between oxaliplatin and ZD1839. CONCLUSION: Based on RAA, the single agent activity of ZD1839 in the investigated cell line panel appeared to be low. Combined exposure to ZD1839 and oxaliplatin exerted synergy in colorectal cancer cell lines, warranting further evaluation in this type of cancer. However, based on the observed antagonism in non-colorectal cancer cell lines, combined treatment with ZD1839 and oxaliplatin is not recommended for other types of cancer. Further research is necessary to identify factors which determine the nature of drug interaction in different tumor types including CRC and lung cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

A surface EMG multi-electrode technique for characterizing muscle activation patterns in mice during treadmill locomotion.

In mice a new method for 2x4-channel surface electromyography (EMG) recordings of the vastus lateralis and biceps femoris muscles during locomotion on a treadmill with varying speed is presented. The approach involves high-speed-videography (sampling interval 2.5 ms) in concert with the application of chronically implanted surface EMG multi-electrodes (EMG sampling rate 4000 Hz, frequency range 10-700 Hz). The recordings are started 2 days after surgery and finished 2 weeks after surgery. During the whole investigation period EMG recordings of both muscles have been possible. The monopolar EMG activities recorded by the electrode-arrays and the bipolar EMG signals derived from the monopolar activities permit an evaluation of the extent of myo-electrical activation in larger regions of both muscles and co-ordination between the flexor and extensor muscles. Bipolar EMG signals indicate propagation of activities along the muscle fibers and a slight effect of non-propagating signal components. Thus, the cross talk between these muscles is small and does not influence the evaluation of the EMG results. The resolution of the simultaneously recorded synchronized data allows a precise temporal correlation of kinematic and EMG parameters.

Action Potentials↗
PubMed2002

Continuation of regional chemotherapy of hepatic neoplasms despite occlusion of the hepatic artery-report of four cases.

In clinical practice, regional chemotherapy of the liver applied as 'hepatic arterial infusion' (HAI) is often limited by device dysfunction or hepatic arterial obstruction. We report the case of a patient with mixed hepato/cholangiocellular carcinoma in which HAI with folinic acid (FA) and 5-fluorouracil (5-FU) was continued after thrombotic occlusion of the A. hepatica, resulting in a flow of drugs into the V. portae (via A. lienalis and V. lienalis). By using this 'spleno-portal' access for further chemotherapy with FA/5-FU, long-term control of the patient's disease was achieved. Analyzing our experience with this and three other patients with hepatic arterial thrombosis in which we continued HAI, a total of 33 regional treatment courses were applied, containing 5-FU/FA, mitomycin C, doxorubicin or combinations of these drugs. No unexpected toxicities were observed. In addition, the clinical course of three of those four patients strongly suggests the effectiveness of this approach. Thus, our results indicate that thrombosis of the A. hepatica does not necessarily have to result in an interruption of HAI. Continuation of regional chemotherapy despite hepatic arterial occlusion preserved control of intrahepatic tumor manifestations in patients who previously responded to regular HAI.

Antimetabolites, Antineoplastic↗
PubMedDate not supplied

Application of GESPECOR software for the calculation of coincidence summing effects in special cases.

In this work, coincidence summing correction factors have been measured for 133Ba, 152Eu and 88Y point sources with a 50% relative efficiency p-type detector and a 25% relative efficiency n-type detector in two close-to-detector measurement geometries. The experimental data for 133Ba and 152Eu and the results obtained with the GESPECOR software reveal a complex structure of the conventional dead layer of the p-type detector. The high value of the coincidence summing correction factor for the 511 keV peak of 88Y, in agreement with the values computed by GESPECOR, in this case cautions against the application of the semiempirical method for evaluating coincidence summing effects.

Algorithms↗
PubMedDate not supplied

Extension of the efficiency calibration of germanium detectors using the GESPECOR software.

To avoid losses due to coincidence summing, the efficiency calibration of gamma-spectrometers is often carried out by means of radionuclides emitting only one photon during a single decay. Calibration with this kind of radionuclides has, however the disadvantage that the energy range of the gamma rays (46 keV<E<1115 keV) is limited. Coincidence-summing corrections can be calculated with the Monte Carlo program Germanium Spectrometry Correction for multi gamma radionuclides which emit photons with energies above this range. The efficiency curve as a function of energy can therefore be extended up to 2.7 MeV with uncertainties below 4%.

Journal Article↗
PubMedDate not supplied

Deep underground measurements of 60Co in steel exposed to the Hiroshima atomic bomb explosion.

When using gamma-ray spectrometry performed deep underground, it is possible to measure 60Co activities down to 0.1 mBq in steel samples of some 100 g without any pre-concentration. It is thus still possible to measure 60Co induced by neutrons from the atomic bomb explosion in Hiroshima in pieces of steel collected at distances up to about 1200 m slant range. The results of non-destructive measurements of eight steel samples are compared with the 1986 Dose Re-Evaluation (DS86) model calculations.

Journal Article↗
PubMedDate not supplied

Deep underground gamma spectrometric measurement of 26Al in meteorite samples.

26Al is routinely measured in meteorite samples by accelerator mass spectrometry (AMS). PTB participates in an international intercomparison between laboratories using AMS and gamma-ray spectrometry to improve the quality of such measurements. We performed gamma spectrometric measurements at the underground laboratory UDO using the GESPECOR software to calculate corrections for efficiency transfer, self-attenuation and coincidence summing. Four meteorite samples were measured for more than 30 days each but nevertheless, the uncertainty budgets are dominated by the uncertainties of the count rates.

Journal Article↗