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Biomedical subjects

J Classen

Publications and source records attributed to J Classen.

At least 37 records · Page 2Linked to original sources

Anomalous frequency dependence of the internal friction of vitreous silica

The internal friction Q-1 and the sound velocity deltav/v of vitreous silica were measured at very low temperatures using mechanical double paddle resonators operated at frequencies ranging from 0.33 to 14 kHz. Below approximately 40 mK the internal friction showed an unexpected temperature and frequency dependence, with absolute values of Q-1 clearly exceeding those predicted by the standard tunneling model. Even though the most plausible origin of the observed excess internal friction appears to be the mutual interaction between tunneling states, the results are difficult to reconcile quantitatively with present theories taking into account this interaction.

Journal Article↗

[Interdisciplinary consensus on diagnosis and therapy of testicular tumors. Results of an update conference based on evidence-based medicine. German Testicular Cancer study Group (GTCSG)].

BACKGROUND: An "Interdisciplinary Consensus Statement on the Diagnosis and Therapy of Testicular Tumors" was prepared in 1996 by the "Interdisciplinary Testicular Tumor Working Group" (IAH) with input from representatives from diagnostic and therapeutic disciplines of various working groups of the German Cancer Society (Strahlenther Onkol 1997;173:397-406). In 1998 the IAH met again together with the "Testicular Tumor Working Party" of the Urooncology Working Group (AUO) and formed the "German Testicular Cancer Study Group" (GTCSG). Defined and accepted interdisciplinary standards from the initial meeting were revised based on current scientific developments and clinical results. This cooperating effort increased the quality of the initial recommendations and helped to put the recommendations for diagnosing and treating testicular tumor on a broader scientific basis. METHODS: According to the principles of "evidence-based medicine" (EBM), the Consensus from 1996 was modified, based on the current level of evidence from the published literature. The methodological process and evaluation criteria used were that of the "Cochrane Collaboration". RESULTS: An "Interdisciplinary Update Consensus Statement" summarizes and defines the diagnostic and therapeutic standards according to the current scientific practices in testicular cancer. For 21 separate areas scientifically based decision criteria are suggested. For treatment areas where more than one option exist without a consensus being reached for a preferred strategy, such as in seminoma in clinical Stage I or in non-seminoma Stages CS I or CS IIA/B, all acceptable alternative strategies with their respective advantages and disadvantages are presented. This "Interdisciplinary Update Consensus" was presented at the 24th National Congress of the German Cancer Society on March 21st and subsequently evaluated and approved by the various German scientific medical societies.

Evidence-Based Medicine↗

[Value of radiotherapy in interdisciplinary management of testicular germ cell tumors].

Radiotherapy unequivocally has to be regarded as standard therapy in stage I and IIA/B testicular seminoma. Using low dose abdominal irradiation tumour control rates of 95-98% in stage I disease and 80-95% in stage IIA/B can be achieved. Disease specific survival reaches 100%. Likewise, radiotherapy is treatment of first choice in case of testicular intraepithelial neoplasia (TIN) in a solitary testis or in case of a double-sided TIN yielding safe eradication of the in-situ carcinoma of the testis. Objectives of further clinical research in radiotherapy of testicular malignancies aim at reduction of treatment intensity in order to minimize acute and late side effects of irradiation without compromising tumour control rates.

Carcinoma in Situ↗

Cutaneomotor integration in humans is somatotopically organized at various levels of the nervous system and is task dependent.

Integration of tactile afferent signals with motor commands is crucial for the performance of purposeful movements such as during manipulation of an object in the hand. To study the somatotopic organization of sensorimotor integration we applied electrical peripheral conditioning stimuli to a digit located near (homotopic stimulation) or distant from (heterotopic stimulation) relaxed or isometrically contracted intrinsic hand muscles at variable time intervals prior to transcranial magnetic stimulation (TMS). Cutaneous stimulation has previously been shown to modulate the amplitude of the motor evoked potential (MEP) and to shorten the duration of the silent period (SP) evoked by TMS. In relaxed target muscles the time-dependent modulation of TMS-evoked motor responses by homotopic conditioning stimulation differed from modulation by heterotopic stimulation. Similar differences in the modulation pattern evoked by homotopic and heterotopic conditioning stimulation were observed for two distinct target muscles of the hand (abductor digiti minimi, abductor pollicis brevis muscle). Differences in modulation were maximal when the conditioning stimulation was applied 25-30 ms and 150-200 ms prior to TMS. Comparison of the modulation of the amplitudes of MEPs evoked by transcranial electrical stimulation (TES) and the modulation of those evoked by TMS suggests that differences between homotopic and heterotopic stimulation originate subcortically at 25- to 30-ms and, at least partially, cortically at 150- to 200-ms interstimulus intervals. In isometrically contracted intrinsic hand muscles the degree to which the SP was shortened reflected the location and the timing of the conditioning stimulus. Shortening was maximal when the conditioning stimulus was applied nearest to the contracted target muscle and 20 ms prior to the test stimulus. In contrast to the SP duration, the MEP size in voluntarily contracted target muscles was unaffected by the location of the conditioning stimulus. The somatotopic gradient of SP shortening was abolished when the two target muscles were simultaneously activated isometrically. Together, our findings suggest that somatotopy of input-output relationships is implemented at both a spinal and a cortical level in the human central nervous system and may also depend on the motor task involved.

Adult↗

Motor cortex excitability in patients with focal epilepsy.

We studied the excitability of the motor cortex using, transcranial magnetic stimulation (TMS) in patients with temporal and extratemporal epilepsy. We applied single and paired-pulse TMS to 15 patients with temporal (n = 7), extratemporal (n = 6) and focal epilepsy lateralised to one hemisphere (n = 2). Patients had no antiepileptic drugs in the last 48 h and were seizure free for 4 h prior to testing. We determined the threshold for EMG responses at rest (RMT), the cortically evoked silent period (CSSP) and intracortical inhibition (ICI, intervals of 2-4 ms) and facilitation (ICF, 7-15 ms) and compared the results to those obtained in 17 normal controls. ICI and ICF was reduced in both hemispheres (P < 0.01. ANOVA) compared to the controls. In the hemisphere of seizure origin ('abnormal') there was a reduction of ICF (P < 0.01) and normal ICI, in the 'normal' hemisphere there was a reduced ICI (P < 0.01) and a slight reduction of ICF (P < 0.05). ICF on the 'abnormal' side was reduced (P < 0.05) compared to the 'normal' hemisphere. RMT was increased in two patients, but group comparison of RMT and CSSP showed no significant differences between patients and controls. The results suggest a remote effect of epileptic activity onto the motor cortex leading to an alteration of activity in local inhibitory circuits.

Adolescent↗

Induction of plasticity in the human motor cortex by paired associative stimulation.

Current models of motor cortical plasticity, developed in studies on experimental animals, emphasize the importance of the conjoint activity of somatosensory afferents and intrinsic motor cortical circuits. The hypothesis that an enduring change in excitability in the cortical output circuitry can be induced in the human motor cortex by a paired-stimulation protocol was tested. Low-frequency median nerve stimulation was paired with transcranial magnetic stimulation (TMS) over the optimal cranial site for stimulating the abductor pollicis brevis muscle (APB). This protocol induced an increase in the amplitudes of the motor evoked potentials (MEPs) in the resting APB as well as a prolongation of the silent period measured in the precontracted APB following TMS; amplitudes of MEPs measured in voluntary contraction remained unchanged. Experiments testing the excitability of spinal motoneurons using F-wave studies and electrical stimulation of the brainstem suggested that the site of the plastic changes was within the motor cortex. The increases in resting amplitudes and silent period duration were conditionally dependent on the timing between the afferent and the magnetic stimulation in that they were present when events elicited by afferent and magnetic stimulation were synchronous at the level of the motor cortex. Plasticity induced by paired stimulation evolved rapidly (within 30 min), was persistent (minimum duration 30-60 min) yet reversible, and was topographically specific. This combination of features and the similarity to properties of induced enduring changes in synaptic efficacy, as elucidated in animal studies, leads us to propose that the induced plasticity may represent a signature of associative long-term potentiation of cortical synapses or closely related neuronal mechanisms in the human cortex.

Adult↗

Radiotherapy for stages I and IIA/B testicular seminoma.

Radiotherapy is generally accepted as a standard treatment for early-stage testicular seminoma. Relapse rates of 2% to 5% in clinical stage I and 10% to 20% in stage IIA/B (according to the Royal Marsden classification) can be achieved. Disease-specific survival reaches 100%. With such excellent cure rates, treatment-related side effects gain particular importance. Therefore, a prospective multicenter trial was initiated for radiotherapy of testicular seminoma with limited treatment portals and low total doses of irradiation. In clinical stage I, 483 patients were treated with 26 Gy to the para-aortic region only. In stage IIA, 42 patients and, in stage IIB, 18 patients received irradiation to the para-aortic and high iliac lymph nodes with 30 and 36 Gy, respectively. With a median time to follow-up of 55 months for stage I and 55.5 months for stage IIA/B, there were 18 (3.7%) and 4 (6.7%) cases of relapse in both treatment groups. Disease-specific survival was 99.6% in stage I and 100% in stage IIA/B. Acute toxicity was dominated by moderate gastro-intestinal side effects. No major late toxicity has been observed to date. Limited volume pure para-aortic treatment for stage I and para-aortic/high iliac irradiation for stage IIA/B with 26, 30 and 36 Gy, respectively, yields excellent cure rates with only moderate acute toxicity and is therefore recommended as standard treatment.

Adolescent↗

Differential effects on motorcortical inhibition induced by blockade of GABA uptake in humans.

1. Blockade of uptake carriers of gamma-aminobutyric acid (GABA) has been shown to modulate inhibition in cortical slices of experimental animals, although little is known about this mechanism in vivo and, in particular, in humans. 2. The effects of blockade of GABA uptake were studied using transcranial magnetic stimulation (TMS) in humans. In eight healthy volunteers several measures of cortical excitation and inhibition were obtained before and approximately 2 h after ingestion of 5-15 mg of tiagabine (TGB). 3. After TGB ingestion, the duration of the TMS-induced silent period observable in the electromyogram of the voluntarily contracted target muscle was prolonged. Similarly, paired-pulse inhibition of the motor-evoked potential (MEP), as tested by delivering two magnetic shocks of equal suprathreshold intensities at 160 ms interstimulus interval (ISI), was more pronounced. In apparent contradistinction, paired-pulse inhibition of the MEPs produced by a subthreshold conditioning stimulus delivered 3 ms prior to a suprathreshold stimulus was reduced. Paired-pulse facilitation elicited by the same double-shock protocol at an ISI of 10 ms was increased. 4. The prolongation of the GABAB receptor-mediated component of the inhibitory postsynaptic potential observed with TGB in in vitro studies probably underlies the increase in cortical silent period duration. The reduction of the paired-pulse inhibition at 3 ms, in turn, probably reflects inhibition of GABAA receptor-mediated inhibition via presynaptic GABAB receptors. 5. These data provide in vivo evidence of differential modulation of cortical inhibition by blockade of GABA uptake. Presynaptic GABA autoreceptors may be involved in modulating cortical inhibition in the human motor cortex.

Adult↗

Stimulation of peripheral nerves using a novel magnetic coil.

Magnetic nerve stimulation (MNS) using a novel figure-8 magnetic coil was compared with conventional electric nerve stimulation (ENS) in normal subjects and in patients with disorders of the peripheral nervous system. In contrast to previously tested coils, the virtual cathode of the novel coil was independent of the geometrical or electric conditions of the stimulated tissue. Maximal compound muscle action potentials (CMAPs) were elicited by MNS in all motor nerves tested. The slopes of the recruitment curves of ENS were steeper than those of MNS, indicating a comparatively lower maximal stimulation intensity and a higher intensity resolution of the magnetic stimulator. In four patients with entrapment syndromes at the ulnar groove, motor conduction velocities and amplitudes were similar for MNS and ENS across the affected nerve segment. However, in two patients with chronic inflammatory demyelinating polyneuropathy (CIDP), CMAPs were slightly smaller following MNS. This new technique is a promising step toward the ultimate goal of replacing ENS with MNS.

Adult↗

Task-dependent modulation of inhibitory actions within the primary motor cortex.

In 11 healthy subjects motor-evoked potentials (MEPs) and silent periods (SPs) were measured in the right first dorsal interosseus (FDI) and abductor pollicis brevis muscles (APB): (1) when transcranial magnetic cortex stimulation (TMS) was applied at tonic isometric contraction of 20% of maximum force, (2) when TMS was applied during tactile exploration of a small object in the hand, (3) when TMS was applied during visually guided goal-directed isometric ramp and hold finger flexion movements, and (4) when at tonic isometric contraction peripheral electrical stimulation (PES) of the median nerve was delivered at various intervals between PES and TMS. Of the natural motor tasks, duration of SPs of small hand muscles was longest during tactile exploration (APB 205+/-42 ms; FDI 213+/-47 ms). SP duration at tonic isometric contraction amounted to 172+/-35 ms in APB and 178+/-31 ms in FDI, respectively. SP duration in FDI was shortest when elicited during visually guided isometric finger movements (159+/-15 ms). At tonic isometric contraction, SP was shortened when PES was applied at latencies -30 to +70 ms in conjunction with TMS. The latter effect was most pronounced when PES was applied 20 ms before TMS. PES-induced effects increased with increasing stimulation strength up to a saturation level which appeared at the transition to painful stimulation strengths. Both isolated stimulation of muscle afferents and of low-threshold cutaneous afferents shortened SP duration. However, PES of the contralateral median nerve had no effect on SPs. Amplitudes of MEPs did not change significantly in any condition. Inhibitory control of motor output circuitries seems to be distinctly modulated by peripheral somatosensory and visual afferent information. We conclude that somatosensory information has privileged access to inhibitory interneuronal circuits within the primary motor cortex.

Adult↗

Chemotherapy in the treatment of recurrent glioblastoma multiforme: ifosfamide versus temozolomide.

PURPOSE: Despite the progress made in neurosurgery and radiotherapy, the prognosis of glioblastoma multiforme (GB) is poor, due to the lack of an effective salvage therapy. In vitro analysis revealed activity for ifosfamide and temozolomide. The usefulness of these agents in recurrent disease was investigated. METHODS: Six adult patients with recurrent GB received one to four courses of 1,500 mg/m2 ifosfamide given over 5 days intravenously. Furthermore, temozolomide (100-200 mg/m2) was given orally over 5 days to 14 patients. RESULTS: After ifosfamide treatment, one partial response and two cases of stable disease were observed. The median survival time was 24 weeks (range of 9-52 weeks). Toxicity analysis revealed one paranoid reaction, three grade III leukocytopenia, and one grade I-II nausea, anemia, and hematuria. Temozolomide therapy resulted in three partial responses and four cases of stable disease. The median survival time (Kaplan-Meier) was 21 weeks (range 4-64 weeks). The major toxicities were grade I-II nausea and hematological side effects (one case of grade IV leuko- and thrombocytopenia). CONCLUSIONS: Ifosfamide treatment might be a feasible approach, but it necessitates hospitalization. Temozolomide showed promising results. Due to its oral application, the patient's quality of life (time out of hospital) is favorable. Subgroups with improved survival were observed.

Adult↗

Impressive remission in a patient with locally advanced malignant pleural mesothelioma treated with gemcitabine.

The results of treatment of malignant pleural mesothelioma are quite unsatisfactory regardless of the substance or schedule employed. Although some activity is proved for anthracyclines, platinum compounds and alkylating substances, no chemotherapeutic regimen has emerged as a standard of care. Response rates documented in literature are between 10 and 20% for all these regimens. We report about a patient with locally advanced, unresectable pleural mesothelioma treated with the nucleoside analog gemcitabine (2,2-difluorodeoxycytidine). A 54-year-old male patient with unresectable pleural mesothelioma confirmed by thoracoscopic biopsy was treated with seven cycles of gemcitabine (1000 mg/m2 on day 1, 8 and 15) over a period of 36 weeks. Restaging by thoracic computed tomography (CT) scan was performed after 8, 20 and 36 weeks. At week 36 after beginning of treatment, the CT scan exhibited a substantial partial remission with a reduction of tumor volume of over 50%. The adverse effects of the therapy were very moderate with a hematotoxicity not exceeding WHO grade I and a mild 'flu-like syndrome' during the first three cycles which responded quite well to steroids. The compliance of the patient was excellent and his general condition improved significantly under therapy. Gemcitabine seems to be an active drug for the treatment of pleural mesothelioma. Compared to other active regimens it is normally very well tolerated by the patients. Because of these characteristics gemcitabine seems a suitable antineoplastic substance, especially in palliative settings. It would be worthwhile to test its activity in pleural mesotheliomas in controlled trials.

Antimetabolites, Antineoplastic↗

Multimodal output mapping of human central motor representation on different spatial scales.

1. Non-invasive mapping by focal transcranial magnetic stimulation (TMS) is frequently used to investigate cortical motor function in the intact and injured human brain. We examined how TMS-derived maps relate to the underlying cortical anatomy and to cortical maps generated by functional imaging studies. 2. The centres of gravity (COGs) of TMS maps of the first dorsal intersosseus muscle (FDI) were integrated into 3-D magnetic resonance imaging (MRI) data sets in eleven subjects. In seven of these subjects the TMS-derived COGs were compared with the COG of regional cerebral blood flow increases using positron emission tomography (PET) in an index finger flexion protocol. 3. Mean TMS-derived COG projections were located on the posterior lip of the precentral gyrus and TMS-derived COG projections were in close proximity to the mean PET-derived COG, suggesting that the two methods reflect activity of similar cortical elements. 4. Criteria for a reliable assessment of the COG and the number of positions with a minimum amplitude of two-thirds of the maximum motor-evoked potential (T3Ps) were determined as a function of the number of stimuli and extension of the stimulation field. COGs and T3Ps were compared with an estimate of the size of the human motor cortex targeting alpha-motoneurons of forearm muscles. This comparison suggests that TMS can retrieve spatial information on cortical organization below the macroanatomic scale of cortical regions. 5. Finally, we studied the cortical representation of hand muscles in relation to facial and foot muscle representations and investigated hemispherical asymmetries. We did not find any evidence for a different ipsi- or contralateral representation of the mentalis muscle. Also, no difference was found between FDI representations on the dominant versus the non-dominant hemisphere.

Adult↗

[Testicular intraepithelial neoplasms (TIN). An indication for radiotherapy?].

BACKGROUND: Testicular intraepithelial neoplasia (TIN), synonymous for carcinoma in situ of the testis, is a rarely observed preinvasive neoplasia located within the germinative epithelium. According to the current knowledge of the biology of TIN, it is the common precursor of all testicular germ cell neoplasms except spermatocytic seminoma. MATERIAL AND METHODS: This report provides a review of histopathology, epidemiology and diagnostic procedures for TIN and discusses the therapeutic options with particular respect to radiooncological aspects. RESULTS: TIN has a 70% rate of progression to invasive cancer within 7 years. Depending on the individual therapeutic setting surgery, chemotherapy and radiotherapy are alternative treatment modalities. In case of TIN in a single testis or bilateral TIN, local radiotherapy is the standard procedure. With 20 Gy recommended as standard dose in Germany, radiotherapy yields safe eradication of TIN. However, some of the patients show significantly reduced synthesis of testicular androgens. With respect to sporadic reports in the literature, total doses well below 20 Gy might be equally efficient to treat TIN safely. Yet, up to date neither the minimum dose for efficient treatment nor the toxicity profile after consecutive chemo-radiotherapy has been established. CONCLUSIONS: The currently recommended standard dose of 20 Gy in Germany is probably in excess of the minimum dose needed for safe eradication of TIN. Thus, new radiooncological strategies should aim at reducing the total dose of treatment in order to minimize late side effects while maintaining the high efficacy of radiotherapy. This topic is under investigation in a multicenter clinical trial.

Antineoplastic Agents↗

Task-dependent changes of intracortical inhibition.

The motor-evoked potential (MEP) to transcranial magnetic stimulation (TMS) is inhibited when preceded by a subthreshold TMS stimulus at short intervals (1-6 ms; intracortical inhibition, ICI) and is facilitated when preceded by a subthreshold TMS at longer intervals (10-15 ms; intracortical facilitation, ICF). We studied changes in ICI and ICF associated with two motor tasks requiring a different selectivity in fine motor control of small hand muscles (abductor pollicis brevis muscle, APB, and fourth dorsal interosseous muscle, 4DIO). In experiment 1 (exp. 1), nine healthy subjects completed four sets (5 min duration each) of repetitive (1 Hz) thumb movements. In experiment 2 (exp. 2), the subjects produced the same number of thumb movements, but complete relaxation of 4DIO was demanded. Following free thumb movements (exp. 1), amplitudes of MEPs in response to both single and paired TMS showed a trend to increase with the number of exercise sets in both APB and 4DIO. By contrast, more focal, selective thumb movements involving APB with relaxation of 4DIO (exp. 2) caused an increase in MEP amplitudes after single and paired pulses only in APB, while a marked decrease in MEPs after paired pulses, but not after single TMS, in the actively relaxed 4DIO. This effect was more prominent for the interstimulus interval (ISI) of 1-3 ms than for longer ISIs (8 ms, 10 ms, and 15 ms). F-wave amplitudes reflecting excitability of the alpha motoneuron pool were unaltered in APB and 4DIO, suggesting a supraspinal origin for the observed changes. We conclude that plastic changes of ICI and ICF within the hand representation vary according to the selective requirements of the motor program. Performance of more focal tasks may be associated with a decrease in ICI in muscles engaged in the training task, while at the same time ICI may be increased in an actively relaxed muscle, also required for a focal performance. Additionally, our data further supports the idea that ICI and ICF may be controlled independently.

Acoustic Stimulation↗