From classic motor imagery to complex movement intention decoding: The noninvasive Graz-BCI approach.

In this chapter, we give an overview of the Graz-BCI research, from the classic motor imagery detection to complex movement intentions decoding. We start by describing the classic motor imagery approach, its application in tetraplegic end users, and the significant improvements achieved using coadaptive brain-computer interfaces (BCIs). These strategies have the drawback of not mirroring the way one plans a movement. To achieve a more natural control-and to reduce the training time-the movements decoded by the BCI need to be closely related to the user's intention. Within this natural control, we focus on the kinematic level, where movement direction and hand position or velocity can be decoded from noninvasive recordings. First, we review movement execution decoding studies, where we describe the decoding algorithms, their performance, and associated features. Second, we describe the major findings in movement imagination decoding, where we emphasize the importance of estimating the sources of the discriminative features. Third, we introduce movement target decoding, which could allow the determination of the target without knowing the exact movement-by-movement details. Aside from the kinematic level, we also address the goal level, which contains relevant information on the upcoming action. Focusing on hand-object interaction and action context dependency, we discuss the possible impact of some recent neurophysiological findings in the future of BCI control. Ideally, the goal and the kinematic decoding would allow an appropriate matching of the BCI to the end users' needs, overcoming the limitations of the classic motor imagery approach.

Longitudinal multimodal imaging in mild to moderate Alzheimer disease: a pilot study with memantine.

OBJECTIVE: To study the feasibility of multimodal neuroimaging in mild to moderate Alzheimer disease (AD) and to estimate the size of possible treatment effects of memantine on potential functional, structural and metabolic biomarkers of disease progression. METHODS: In this randomised, double-blind, placebo-controlled pilot study, 36 patients with moderate AD received 52 weeks of memantine (20 mg/day) or placebo. Patients were re-evaluated after 26 and 52 weeks to measure the change from baseline in several outcome measures including global and regional glucose metabolism, total brain and hippocampal volumes, as well as chemical shift imaging-derived global and regional N-acetylaspartate and myoinositol concentrations. RESULTS: In the total population, global glucose metabolism decreased by 2.3% (p<0.01), total brain volume by 2.1% (p<0.001) and hippocampal volume by 2.7% (p<0.01) after 52 weeks. Chemical shift imaging (CSI) spectra were severely affected by patient-induced artefacts and highly variable. Patients receiving memantine showed less decline in glucose metabolism in all brain areas than patients on placebo. Their loss of hippocampal volume was substantially smaller (2.4% vs 4.0%). No between-group differences were seen for changes in total brain volume. CONCLUSIONS: The results support the use of multimodal imaging including MRI and positron emission tomography (PET) to monitor the progression of moderate AD. CSI yielded unreliable longitudinal results. The data suggest that memantine has potentially protective effects in AD and they can be used for planning larger confirmatory studies on the cerebral effects of memantine.

Arterial oxygen tension increase 2-3 h after hyperbaric oxygen therapy: a prospective observational study.

BACKGROUND: Inhalation of hyperbaric oxygen (HBO) has been reported to decrease arterial oxygen tension (PaO(2)) in the early period after exposure. The current investigation aimed at evaluating whether and to what extent arterial blood gases were affected in mechanically ventilated intensive care patients within 6 h after HBO treatment. METHODS: Arterial blood gases were measured in 11 ventilated subjects [nine males, two females, synchronized intermittent mandatory ventilation (SIMV) mode] undergoing HBO therapy for necrotizing soft tissue infection (seven patients), burn injury (two patients), crush injury (one patient) and major abdominal surgery (one patient). Blood gases were obtained with the patients in the supine position under continuous analgesia and sedation before the hyperbaric session (baseline), during isopression, after decompression, after each transport, and 1, 2, 3 and 6 h after exposure. Heart rates and blood pressures were recorded. Intensive care unit (ICU) ventilator settings remained unchanged. Transport and chamber ventilator settings were adjusted to baseline with maintenance of tidal volumes and positive end-expiratory pressure (PEEP) levels. The hyperbaric protocol consisted of 222.9 kPa (2.2 absolute atmospheres) and a 50-min isopression phase. The paired Wilcoxon's test was used. RESULTS: Major findings (median values, 25%/75% quartiles) as per cent change of baseline: PaO(2) values decreased by 19.7% (7.0/31.7, P < 0.01) after 1 h and were elevated over baseline by 9.3% (1.5/13.7, P < 0.05) after 3 h. SaO(2), alveolar-arterial oxygen tension difference and PaO(2)/FiO(2) ratio behaved concomitantly. Acid-base status and carbon dioxide tension were unaffected. CONCLUSION: Arterial oxygen tension declines transiently after HBO and subsequently improves over baseline in intensive care patients on volume-controlled mechanical ventilation. The effectiveness of other ventilation modes or a standardized recruitment manoeuvre has yet to be evaluated.

Evaluation of potential risk factors for early infectious complications after autologous peripheral blood stem cell transplantation in patients with lymphoproliferative diseases.

A number of risk factors for the occurrence of neutropaenic fever after haematopoietic stem cell transplantation (HSCT) have been proposed. We were interested in whether these factors remain valid for several early infection-related outcomes when applied to a homogeneous group of patients in uni- and multivariate analyses. Therefore, we analysed 144 consecutive patients with lymphoproliferative disorders receiving autologous peripheral blood HSCT. Variables tested as potential risk factors for the occurrence of fever, documented infection (DI), microbiologically documented infection (MDI) or failure of first-line antimicrobial therapy were sex, conditioning regimen, prolonged neutropaenia, low number of CD34+ cells transplanted, purging, lack of selective gut decontamination, higher age and increased body mass index. In uni- and multivariate analyses, conditioning including total body irradiation was the only risk factor for the occurrence of fever, and neutropaenia >or=10 days was the only factor associated with failure of first-line antimicrobial therapy. None of the variables tested was associated with an increased risk for DI or MDI. This analysis suggests that a number of previously proposed risk factors actually are of minor clinical relevance for early infections in the majority of patients receiving autologous HSCT.

High spontaneous colony growth in chronic myelomonocytic leukemia correlates with increased disease activity and is a novel prognostic factor for predicting short survival.

We have originally shown that spontaneous granulocyte/macrophage colony (CFU-GM) formation in semisolid medium is a characteristic in vitro feature of chronic myelomonocytic leukemia (CMML). However, the clinical significance of spontaneous CFU-GM growth in CMML is unknown so far. CFU-GM growth characteristics were studied in semisolid cultures in the absence of exogenous cytokines using peripheral blood mononuclear cells in 30 patients with CMML at first presentation. The median number of CFU-GM/10(5) MNC of all patients was 48.5 (range 0-622) with 18 patients having colony numbers below 100 (low CFU-GM growth) and 12 patients above 100 (high CFU-GM growth). Kaplan-Meier analysis revealed that patients with high CFU-GM growth had a significantly shorter survival than patients with low CFU-GM growth (median 6.5 vs. 44.5 months, p<0.00002). The probability of survival after 2 years was 60.5% for patients with low colony growth but 0% in those with high colony formation. Patients with CFU-GM >100 had a significantly higher WBC count, a higher LDH, and a higher number of blast cells in blood and bone marrow than patients with low colony growth. Moreover, patients with high colony growth had more often splenomegaly and lower platelet counts. In seven patients, in whom semisolid in vitro cultures were performed after transformation into RAEBT/AML, spontaneous colony growth was significantly increased as compared to CFU-GM growth in patients before transformation (median number/10(5) MNC 533, range 212-4553, p<0.005). This study demonstrates that high (>100) spontaneous CFU-GM formation in CMML at presentation correlates with increased disease activity and represents a novel and important prognostic factor predicting for short survival of CMML patients.

[Osteosarcoma and Ewing's sarcoma--The most frequent malignant bone tumors in children--therapy and outcome]. / Osteosarkom und Ewing-Sarkom - die häufigsten Knochentumoren bei Kindern: Therapie und Ergebnisse.

BACKGROUND: Osteosarcoma and Ewing's sarcoma are the most frequent malignant bone tumors in children and young adults with relatively poor overall survival rates. METHODS: Between January 1980 and December 1994, 175 children with osteosarcoma and 64 children with Ewing's sarcoma were treated at the author's institution. 22 children had synchronous metastases, 19 patients had a pathologic fracture. Both groups were treated systemically with chemotherapy regimens (COSS and CESS). Local therapy was amputation or tumor resection and endoprosthetic replacement or biological reconstruction with wide or radical resection margins. In case of Ewing's sarcoma in 35 patients postoperative radiation therapy was done. RESULTS: Five-year overall survival rate for osteosarcoma and Ewing's sarcoma patients is about 63 %, ten-year survival rate for osteosarcoma patients is 60.2 %, for Ewing's sarcoma patients 54.5 %. Prognostic factors significantly influencing overall survival rates are tumor response to chemotherapy (p values = 0.0056 and 0.013, respectively), surgical treatment with adequate resection margins (p value = 0.0001 for osteosarcoma patients) and development of postoperative metastases (p value = 0.0001 for both groups). CONCLUSION: For both groups of malignant bone tumors systemic chemotherapy as well as adequate surgical therapy are necessary to reduce the rates of local recurrences and to achieve better survival rates.

Improved long-term results with thymoglobuline induction therapy after cardiac transplantation: a comparison of two different rabbit-antithymocyte globulines.

BACKGROUND: The aim of this retrospective single center analysis was to compare possible long-term benefits of two different rabbit-antithymocyte globuline (ATG) induction therapies after cardiac transplantation. PATIENTS AND METHODS: A total of 484 primary cardiac transplanted patients received induction therapy with two different rabbit-ATGs (thymoglobuline: n=342, ATG-fresenius: n=142). All patients received immunosuppressive maintenance therapy with cyclosporine, azathioprine, and prednisolone. Cardiac rejection was assessed by serial endomyocardial biopsies. Surveillance of graft arteriosclerosis was performed by angiograms 1, 3, and 5 years after transplantation. RESULTS: Five-year survival was significantly better in the thymoglobuline group (76 vs. 60%). Thymoglobuline patients had a lower rate of death from rejection (2.3 vs. 10%; P<0.01) and graft arteriosclerosis (0.88 vs. 5.6%; P<0.01). After 5 years, freedom from rejection was 72% in the thymoglobuline group compared to 42% in the ATG-fresenius group (P<0.01). Graft arteriosclerosis appeared in 14% of thymoglobuline patients and in 28% of ATG-fresenius patients (P<0.01). Viral infections occurred more often in thymoglobuline patients (53 vs. 39%, P<0.05) although there was no difference in appearance of cytomegalovirus disease (17 vs. 13%). Freedom from posttransplant malignant disease was comparable between the two groups. CONCLUSION: These results suggest that there are differences between rabbit ATG products. The superior prevention of rejection with thymoglobuline may be the reason for the lower rate of graft arteriosclerosis.

Pre- and early postoperative risk factors for death after cardiac transplantation: a single center analysis.

Due to the limited number of donor organs, death on the waiting list and waiting time for cardiac transplantation have markedly increased. A pressing need of appropriate selection criteria for patients who would benefit most from transplantation is apparent. The purpose of this study is to identify pre- and early postoperative risk factors that influence long term survival after cardiac transplantation. 702 consecutive patients who underwent cardiac transplantation between 3/1984 and 12/1997 were analyzed retrospectively for the influence of different pre- and early postoperative risk factors on early (30 days) and late death (5 years). Univariate and multivariate regression analysis revealed risk factors for early as well as late death. Predictors of early death were higher preoperative PVR, retransplantation, longer ischemic time, postoperative acute kidney failure and longer intubation time. Risk factors for late death were early transplant era, previous cardiac surgery, patients awaiting transplantation in a hospital, prolonged stay in an intensive care unit, and any rejection during the first month after transplantation. These results demonstrate that pre- and early postoperative risk factors have significant influence on early and long term survival.

Combined heart and kidney transplantation using a single donor: a single center's experience with nine cases.

BACKGROUND: Simultaneous double-organ transplants comprising various organ combinations have become frequent. The purpose of this article is to report on a single center's experience of simultaneous heart and kidney transplantation (HNTX) with particular emphasis on selection criteria and patient outcome. METHODS: From September 1990 to January 1997, nine patients underwent HNTX, receiving both grafts from a single donor selected on ABO blood group compatibility and a negative lymphocytotoxic crossmatch, but without regard to HLA-antigen matching. RESULTS: One patient died of acute humoral rejection of the cardiac graft shortly after surgery. Eight patients are alive and well and have normal cardiac and renal function at a mean follow-up of 44+/-28 months. CONCLUSION: HNTX offers a compelling therapeutic solution in the treatment of advanced cardiac and renal failure in carefully selected patients. Because the heart and kidney rejection episodes were independent of each other, rejection surveillance should be carried out separately for each transplanted organ.

[Effect of betaxolol on blood pressure and heart rate in mild to moderate hypertension]. / Betaxolol hatása a vérnyomásra és a pulzusszámra enyhe és középsúlyos hypertoniában.

The efficacy and safety of daily 20 mg betaxolol monotherapy was investigated in mild-moderate essential hypertension in a four week long, open label, single blind trial (with a placebo run-in). Twenty one patients of both sexes were enrolled. The systolic blood pressure in the supine position decreased from 158 to 142 mmHg, the diastolic blood pressure from 101 to 89 mmHg. The mean systolic values of the 24 hours ambulatory blood pressure monitoring decreased from 136 to 126 mmHg, the mean diastolic values from 87 to 80 mmHg. All decreases in blood pressure were significant. The reduction of the heart rate (80/min vs 63/min) was also significant. The decrease in blood pressure during daytime was significant, during night it was moderate. The blood pressure- and heart rate reducing effect of betaxolol was detectable however in the second half of the night, before wake-up. No side effect was recorded.

Simultaneous heart and kidney transplantation as treatment for end-stage heart and kidney failure.

BACKGROUND: The aim of the present analysis was to define the role of simultaneous heart and kidney transplantation (HNTX) using organs from the same donor by evaluation of clinical strategy and achieved outcome compared with a reference group of concurrently single heart transplant (HTX) and kidney transplant (NTX) recipients. Compared with other organ combinations (pancreas-kidney, heart-lung), HNTX has been performed infrequently and is reported mainly as case records in the literature. Because of expansion of recipient selection criteria for HTX and NTX, the number of patients requiring simultaneous replacement of both organs is increasing. METHODS: Six HNTX recipients, three of them suffering from long-standing type I diabetes, received transplants between September 1990 and March 1996 and were analyzed in terms of clinical and immunological demographics and outcome. They were compared with 379 HTX and 769 NTX recipients operated upon within this period. RESULTS: Survival for HNTX is 100% with a mean follow-up of 32.7+/-21.1 months. Cold ischemic time of the kidney was significantly shorter for HNTX than for NTX (6.5+/-1.0 hr vs. 22.1+/-6.8 hr, P<0.005). Although HNTX patients received HLA-unmatched grafts, no rejection of the kidney has been observed to date. There was no difference for rejection of the heart in HNTX compared to HTX recipients. CONCLUSIONS: Satisfying results are obtained by HNTX and justify the use of two organs for one recipient. The favorable immunological behavior of the kidney despite use of HLA-unmatched grafts is most probably explained by higher immunosuppression and short cold ischemic time, although a combination effect cannot be excluded.

[Myocardial infarct and diabetes mellitus: incidence, management and prognosis]. / Myocardialis infarctus és diabetes mellitus: elöfordulás, kezelés, prognózis.

The authors analyse the data of the Myocardial and Diabetes Register, where 2436 diabetic patients (pts) and 1448 pts with acute myocardial infarction (AMI) were registered between 1st of January, 1992 and 31st of December 1994. In the history of diabetic patients previous AMI was present in 14.4% of the cases. The 21.6% of the AMI pts had diabetes mellitus as well. According to the type of diabetes (IDDM and NIDDM) the prevalence of AMI in the history of the registered persons was significantly different: among pts with NIDDM the previous AMI was found 14.8% of the pts and only 2% of pts with IDDM (p = 0.012). The clinical picture of AMI was also different of AMI pts with and without diabetes: chest pain suggesting AMI was present 10.9% of pts with proved AMI and diabetes mellitus, and 86.2% of pts with AMI without diabetes (p < 0.0001). The Streptokinase treatment was more common among AMI pts without diabetes (18.2% versus 12.5% p = 0.022). The hospital lethality was significantly higher among AMI pts with diabetes (42.8% versus 29.4% (p < 0.0001). The poorer prognosis was independent of age.

[Effect of lovastatin on serum lipids and lipoproteins. Hungarian multicenter, open-label study]. / Lovastatin kezelés hatása a serum lipidekre és lipoproteinekre. Hazai, nyitott, többcentrumos vizsgálat.

The authors studied the effects of lovastatin on the parameters of serum and lipoprotein lipids in an open multicenter trial. 160 patients with hypercholesterolemia participated in the study, 151 of whom completed the trial. After a 4 week period of dietary measures, the patients were treated with lovastatin for 12 weeks while combining standard lipid lowering diet. The initial dose of the drug was 20 mg, this was increased until serum cholesterol level decreased under 5.2 mmol/l, or to a maximal daily dose of 80 mg. By the end of the 12th week, serum cholesterol level was reduced by an average of 33% (p < 0.001), LDL-cholesterol by an average of 45% (p < 0.001), serum triglyceride concentration by an average of 22% (p < 0.001) and HDL-cholesterol increased by an average of 13% (p < 0.001). Lovastatin showed a very good safety profile, therapy had to be cancelled due to the occurrence of adverse events only in 4 cases.

Differential effects of diethylstilbestrol and estradiol-17 beta in combination with testosterone on rat prostate lobes.

Treatment of Noble rats with separate silastic implants containing testosterone (T) and estradiol-17 beta (E2) for 16 weeks has previously been shown to induce multifocal epithelial dysplasia, a putative preneoplastic lesion, consistently in the dorsolateral prostate (DLP) but not in the ventral prostate (VP). We now studied effects of diethylstilbestrol (DES) substituted for E2 on these prostate lobes under the same conditions of exogenous androgen support. Three-week treatments with one 1-cm-long silastic implant of E2 or DES were approximately equipotent in changing target-organ weights and plasma prolactin. Accordingly, rats received for 16 weeks one 1-cm-long E2 or DES implant and two 2-cm-long T implants. In contrast to T + E2, T + DES induced widespread multifocal VP dysplasia and less or no DLP dysplasia. A serum-free explant-culture assay was used to determine uptake and metabolic disposition of 3H-labeled 5 alpha-dihydrotestosterone (DHT), T, and E2. Dysplastic VP explants incubated with 1.7 microM 1 beta-3H-labeled DHT and T accumulated more 3H-labeled steroid, metabolized 69 and 50% less substrate to terminal hydroxylated metabolites, and thereby formed and retained up to eight times as much estrogenic metabolite 5 alpha-androstane-3 beta,17 beta-diol (3 beta-androstanediol) and its lipoidal derivative than control VP. Experimental DLP explants did not form or retain more 3 beta-[3H]androstanediol than control DLP irrespective of treatments. Control VP metabolized [2-3H]E2 more actively to estrone than DLP. Dysplastic VP, however, metabolized one-half and accumulated five times as much E2 as VP and did not release more 3H as a marker of the 2,3-catechol estrogen pathway. These data suggest that differential target-tissue bioavailability of the estrogen component of the protracted dual-hormone stimulus determines in which prostate lobe dysplasia develops.

Metabolism of estradiol and estrone in organ cultures of dorsolateral and ventral prostate of untreated and sex hormone-implanted rats.

Since dorsolateral but not ventral prostate undergoes estrogen-induced dysplasia in the androgen-supported Noble rat in 16 weeks, we studied estrogen metabolism by these tissues from untreated and sex hormone-implanted animals. We incubated 8.5 nM [6,7-3H]-labeled estradiol (E2) and estrone (E1) for 21 hours in serum-free, prostate-lobe cultures and 8.5 nM [2-3H]E2 with explants from untreated rats and animals treated with testosterone, 5 alpha-dihydrotestosterone, or E2 plus testosterone. Untreated rat ventral prostate metabolized 3.7 times as much E2 to E1 as dorsolateral prostate, whereas the latter tissue converted 2.5 times as much E1 to E2 as the former. After dorsolateral prostate culture with 8.5 nM [6,7-3H]-labeled E2 or E1, 0.6 M KCl-extracted, Sephadex G25-excluded nuclear protein bound preponderantly E2, whereas the counterpart nuclear protein fraction from ventral prostate explants incubated with E2 bound substrate and E1 almost equally. The combination sex hormone treatment decreased E2 metabolism and increased its uptake by the dysplastic dorsolateral prostate. Implantation of 5 alpha-dihydrotestosterone, but not of testosterone, also decreased E2 metabolism to E1 by dorsolateral prostate cultures. Treatments with E2 plus testosterone and with 5 alpha-dihydrotestosterone changed E2 uptake/E1 retention in dorsolateral prostate explants from 2.4 to 7.4 and 8.5, respectively. C-2 tritium release marking the 2,3-catechol estrogen pathway was greater for ventral than dorsolateral prostate, but was unaffected by the sex hormone treatments.(ABSTRACT TRUNCATED AT 250 WORDS)