Recurrent spontaneous "neuroleptic malignant syndrome" in the absence of neuroleptic medication in probable dementia with Lewy bodies.
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Biomedical subjects
Publications and source records attributed to J Classen.
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A prospective nonrandomised trial was performed in order to evaluate tumour control and toxicity of low-dose adjuvant radiotherapy in stage I seminoma with treatment portals confined to the para-aortic lymph nodes. Between April 1991 and March 1994, 721 patients were enrolled for the trial by 48 centres in Germany. Patients with pure seminoma and no evidence of lymph node involvement or distant metastases received 26 Gy prophylactic limited para-aortic radiotherapy. Disease-free survival at 5 years was the primary end point. With a median follow-up of 61 months, 675 patients with follow-up investigations were evaluable for this analysis. Kaplan-Meier estimates of disease-free and disease-specific survival were 95.8% (95% CI: 94.2-97.4) and 99.6% (95% CI: 99.2-100%) at 5 years and 94.9% (95% CI: 92.5-97.4%) and 99.6% (95% CI: 99.2-100%) at 8 years, respectively. A total of 26 patients relapsed. All except two were salvaged from relapse. In all, 21 recurrences were located in infradiaphragmatic lymph nodes without any 'in-field' relapse. Nausea and diarrhoea grade 3 were observed in 4.0 and 1.0% of the patients, respectively. Grade 3 late effects have not been observed so far. The results of our trial lend further support to the concept of limited para-aortic irradiation as the recently defined new standard of radiotherapy in stage I seminoma. There is no obvious compromise in disease-specific or disease-free survival compared to more extensive hockey-stick portals, which were used as standard portals at the time this study was initiated.
The intensity of adjuvant radiotherapy for stage I seminoma could be reduced substantially in recent years, achieving cure with low side effects and a low probability of late complications. Today a dose of 20 Gy is applied to the para-aortic lymphatics. Valuable treatment alternatives to radiotherapy have emerged: surveillance strategy allows 80% of patients to avoid further treatment. However, the remaining 20% will be exposed to potentially more intensive salvage therapy. Adjuvant carboplatinum chemotherapy offers similar disease-free survival to adjuvant radiotherapy. Long-term experience with late toxicity is not available. In seminoma CS IIA/B curative irradiation remains the standard treatment. Brain metastases of testicular germ cell tumors are treated with a combination of chemotherapy and cranial irradiation. In intratubular germ cell neoplasia (TIN), radiotherapy with 20 Gy will safely eliminate all TIN loci, but will destroy potential residual fertility.
Germ cell tumour is the most frequent malignant tumour type in young men with a 100% rise in the incidence every 20 years. Despite this, the high sensitivity of germ cell tumours to platinum-based chemotherapy, together with radiation and surgical measures, leads to the high cure rate of > or = 99% in early stages and 90%, 75-80% and 50% in advanced disease with 'good', 'intermediate' and 'poor' prognostic criteria (IGCCCG classification), respectively. The high cure rate in patients with limited metastatic disease allows the reduction of overall treatment load, and therefore less acute and long-term toxicity, e.g. organ sparing surgery for specific cases, reduced dose and treatment volume of irradiation or substitution of node dissection by surveillance or adjuvant chemotherapy according to the presence or absence of vascular invasion. Thus, different treatment options according to prognostic factors including histology, stage and patient factors and possibilities of the treating centre as well may be used to define the treatment strategy which is definitively chosen for an individual patient. However, this strategy of reduction of treatment load as well as the treatment itself require very high expertise of the treating physician with careful management and follow-up and thorough cooperation by the patient as well to maintain the high rate for cure. Treatment decisions must be based on the available evidence which has been the basis for this consensus guideline delivering a clear proposal for diagnostic and treatment measures in each stage of gonadal and extragonadal germ cell tumour and individual clinical situations. Since this guideline is based on the highest evidence level available today, a deviation from these proposals should be a rare and justified exception.
Low-dose radiotherapy to the testis is effective in eradicating testicular intraepithelial neoplasia (TIN, carcinoma in situ of the testis) at the risk of androgenic deficiency. The present trial was designed to define the lowest dose effective to control TIN assuming a dose-response relation of radiation-induced endocrinological damage. Patients with TIN in a solitary testicle or with bilateral TIN were treated with 18 Gy (14 patients) and 16 Gy (26 patients) (5 x 2 Gy per week). Biopsies to ascertain clearance of TIN were performed after 6 and 24 months. The median time of follow-up is 20.5 months. There were three adverse events. In one patient, relapse of TIN along with microinvasive seminoma was observed 2 years after 16 Gy irradiation. In two other patients, persistent spermatogonia were observed with the 16 and 18 Gy regimen after 6 and 24 months, respectively. All other post-treatment biopsies showed the Sertoli cell-only pattern. These results confirm that TIN is a radiosensitive lesion efficiently controlled in most cases with doses below 20 Gy. However, sporadic failures may occur. A dose of 16 Gy is probably unsafe and should no longer be used. Future investigations should not only focus on total dosage of irradiation but also on fractionation schedules.
OBJECTIVES: To test the hypothesis that cortical plasticity related to destructive tumour growth is functionally relevant. This hypothesis predicts that function is dependent on the intactness of tissue surrounding the tumour. MATERIAL AND METHODS: Eight patients underwent laser-induced interstitial thermotherapy (LITT) for minimally invasive palliative treatment of brain tumours located in eloquent frontal motor regions including the primary motor cortex. A multimodal approach was used to assess the functional outcome of patients after LITT in detail. RESULTS: Following LITT, motor function deteriorated in four patients. In three of these four patients the LITT-induced lesion involved minimal parts of adjacent non-tumorous tissue. By contrast, the other four patients whose LITT-induced signal changes were confined to the tumour, showed no functional deficits. CONCLUSION: These findings support the idea that peri-tumorous neuronal circuitry in motor competent areas may permanently take over those functions that were formerly represented in the neuronal tissue destroyed by the tumour.
In healthy individuals, motor training can elicit use-dependent plasticity. Here the authors studied six subjects in whom training alone failed to elicit this effect. Administration of a single dose of 10 mg of D-amphetamine preceding training led to use-dependent plasticity in a subgroup of these subjects. Using pharmacologic interventions to enhance the effects of motor training might help rehabilitative efforts in patients in whom training alone fails.
The potential of Mitomycin C in combination with fractionated irradiation to inhibit tumour cell repopulation of a fast growing squamous cell carcinoma after fractionated radiotherapy was investigated in vivo. A rapidly growing human squamous cell carcinoma (FaDu(dd)) was used for the study. For experiments, NMRI (nu/nu) mice with subcutaneously growing tumours were randomly allocated to no treatment, Mitomycin C, fractionated irradiation (ambient: 11 x 4.5 Gy in 15 days), or fractionated irradiation combined with Mitomycin C. Graded top up doses (clamped blood flow: 0-57 Gy) were given at day 16, 23, 30 or 37. End point of the study was the time to local tumour progression. Data were examined by multiple regression analysis (Cox). Mitomycin C alone resulted in a median time to local tumour progression of 23 (95% confidence limits: 17-43) days, fractionated irradiation in 31 (25-35) days and combined Mitomycin C plus fractionated irradiation in 65 (58-73) days (P=0.02). Mitomycin C decreased the relative risk of local recurrence by 94% (P<<0.001) equivalent to 31.7 Gy top up dose. Repopulation accounted for 1.33 (0.95-1.72) Gy per day top up dose after fractionated irradiation alone and for 0.68 (0.13-1.22) Gy per day after fractionated irradiation+Mitomycin C (P=0.018). Mitomycin C significantly reduces the risk of local recurrence and inhibits tumour cell repopulation in combination with fractionated irradiation in vivo in the tested tumour model.
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The desorption behavior of quench-condensed rare gas films has been investigated using high frequency surface acoustic waves. Measurements of pure films of argon and neon and of the binary mixture Ar(1-c)/Ne(c) have been carried out. For small and very large neon concentration c(Ne) a behavior is found which indicates the existence of a substitutionally disordered solid. In contrast, in the wide range of concentration 0.25< c(Ne)< 0.92 two discrete temperatures for neon desorption exist. The data clearly indicate the occurrence of two separate phases, one of pure neon, the other of crystallites with either Ar(2)Ne or Ar(3)Ne structure.
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Testicular intraepithelial neoplasia (TIN; also called carcinoma in situ of the testis) is the uniform precursor of testicular germ cell tumors. There is general agreement on the biological significance of TIN, however, the treatment is still a matter of dispute. The present review summarizes the treatment options currently available. In general, the management of TIN has to be adapted to the particular clinical situation of the patient. Eradication of TIN usually implies the loss of fertility. Therefore, fertility aspects should be considered before any kind of treatment is employed. Usually, patients with TIN have only small residual potential of fertility. Nonetheless, individual patients may qualify for sperm banking or cryopreservation of testicular tissue for future sperm extraction (TESE) and assisted fertilization. The most common clinical situation is the case of contralateral TIN in the presence of unilateral testicular cancer. Low dose radiotherapy to the testis with 18 Gy is the standard management option in these patients. The same procedure may be applied to solitary testicles after partial orchiectomy for germ cell tumors. During follow-up, testosterone levels should be evaluated every six months. If chemotherapy is required due to metastatic disease of the primary tumor management of TIN should be deferred. After chemotherapy 30% of TIN cases will persist and approximately 42% will recur in the later course. Repeat biopsy should be done six months after completion of chemotherapy or later. Only in cases with persistent TIN additional radiotherapy should be administered. If one testicle is afflicted with TIN while the other testis is in healthy condition (conceivable in infertility cases or patients with primary extragonadal germ cell tumors), then the TIN-bearing testis should be excised. Radiotherapy is not feasible in these cases because of shielding problems with the healthy testis.
Stage I and IIA/B testicular seminoma represent approximately 45% of all testicular germ cell tumours. Due to the availability of highly efficient salvage treatment, the disease-specific survival in stage I seminoma is approximately 100%, irrespective of the choice of adjuvant treatment. Radiotherapy with 26 Gy to the paraaortic/paracaval lymph nodes yields excellent cure rates of 95 98% with a favourable profile of acute and late toxicity. Likewise, phase-II trials with single-agent carboplatinum systemic treatment have demonstrated a rate of relapse of 3-4% on average. However, carboplatinum chemotherapy has to be regarded as experimental until data of phase-III trials are available. Surveillance in stage I disease is conflicted with a rate of relapse of approximately 20%. However, 80% of the patients will avoid potentially toxic overtreatment by the watch-and-wait policy. In stage IIA/B seminoma, "dogleg" radiotherapy with 30 Gy and 36 Gy, respectively, provides high cure rates of 90-95%. Those patients relapsing will be salvaged in almost 100% of cases. Testicular intraepithelial neoplasia (TIN) is the common precursor lesion of testicular germ cell tumours except for spermatocytic seminoma. In case of TIN in a single testis or bilateral TIN, local radiotherapy with 18 Gy is recommended as standard treatment.
Tactile apraxia is characterized by an isolated disturbance of hand movements for use of and interaction with an object (transitive movements) in the presence of preserved intransitive movements (movements without use of an object, for example repetitive movements or gestures). It is, however, still unclear whether motor and sensory abnormalities represent causal or associated features of tactile apraxia. To address this question, quantitative kinematic recordings of exploratory finger movements (transitive movements) and rapid alternating finger movements (intransitive movements) were studied in 20 healthy volunteers and 22 patients with focal lesions of the parietal, anterofrontal and motor cortex. The most severe deficits of manual object exploration were found in patients with parietal lesions, using the hand contralateral to the lesion. Patients with lesions of the anterior parietal lobe who exhibited prominent sensory deficits and astereognosia showed a decrease in frequency and regularity of exploratory finger movements and a marked increase in exploration space. Patients with posterior parietal lesions exhibiting severe astereognosia, apraxia and deficits in dexterity had a greater decrease in frequency and regularity of manipulative movements, but a less pronounced increase of exploration space than the patients with anterior parietal lesions. Although the patients with parietal lobe lesions could generate rapid alternating finger movements, the regularity of these movements was also impaired. In comparison, patients with frontal lobe lesions exhibited impaired contralesional manipulatory and rapid alternating finger movements but no sensory abnormalities or astereognosia. We conclude that tactile apraxia represents a deficit in the programming of exploratory finger movements mediated by the parietal lobe. The comparison with lesions of other regions participating in the cortical network for tactile exploration reveals that apraxia of exploratory movements in parietal lobe lesions represents a disturbance distinct from elementary motor or sensory abnormalities, but closely related to stereognostic functioning.
The primary motor cortex produces motor commands that include encoding the direction of movement. Excitability of the motor cortex in the reaction time (RT) task can be assessed using transcranial magnetic stimulation (TMS). To elucidate the timing of the increase in cortical excitability and of the determination of movement direction before movement onset, we asked six right-handed, healthy subjects to either abduct or extend their right thumb after a go-signal indicated the appropriate direction. Between the go-signal and movement onset, single TMS pulses were delivered to the contralateral motor cortex. We recorded the direction of the TMS-induced thumb movement and the amplitude of motor-evoked potentials (MEPs) from the abductor pollicis brevis and extensor pollicis brevis muscles. Facilitation of MEPs from the prime mover, as early as 200 ms before the end of the reaction time, preceded facilitation of MEPs from the nonprime mover, and both preceded measurable directional change. Compared with a control condition in which no voluntary movement was required, the direction of the TMS-induced thumb movement started to change in the direction of the intended movement as early as 90 ms before the end of the RT, and maximum changes were seen shortly before the end of reaction time. Movement acceleration also increased with maxima shortly before the end of the RT. We conclude that in concentric movements a change of the movement direction encoded in the primary motor cortex occurs in the 200 ms prior to movement onset, which is as early as increased excitability itself can be detected.
Using transcranial magnetic stimulation, the effect of riluzole (RLZ) on cortical excitability was studied in patients with amyotrophic lateral sclerosis (ALS). Paired-pulse inhibition (PPI) and paired-pulse facilitation (PPF) were reduced. RLZ partially restored deficient PPI in the first of 4 consecutive 3-month periods of testing, but left PPF unchanged. These findings substantiate the view that attenuation of glutamate-related excitotoxicity is an important factor contributing to the beneficial effect of RLZ in ALS.
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Practicing movements results in improvement in performance and in plasticity of the motor cortex. To identify the underlying mechanisms, we studied use-dependent plasticity in human subjects premedicated with drugs that influence synaptic plasticity. Use-dependent plasticity was reduced substantially by dextromethorphan (an N-methyl-d-aspartate receptor blocker) and by lorazepam [a gamma-aminobutyric acid (GABA) type A receptor-positive allosteric modulator]. These results identify N-methyl-d-aspartate receptor activation and GABAergic inhibition as mechanisms operating in use-dependent plasticity in intact human motor cortex and point to similarities in the mechanisms underlying this form of plasticity and long-term potentiation.