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.

Biochemical alterations in sex hormone-induced hyperplasia and dysplasia of the dorsolateral prostates of Noble rats.

Simultaneous implantation of intact Noble (Nb) rats with testosterone and 17 beta-estradiol (E2)-filled silastic capsules for 16 weeks caused atypical hyperplasia (dysplasia) and striking enlargement exclusively in the dorsolateral prostates (DLPs) of all animals. The dysplastic lesion may be preneoplastic since long-term administration of these steroids to Nb rats is known to induce a high incidence of adenocarcinoma in the DLP. Treatment of rats with nonaromatizable 5 alpha-dihydrotestosterone (DHT) for 16 weeks caused enlargement but not dysplasia, implicating estrogen as a key factor in the genesis of the proliferative lesion. Compared with controls, the testosterone plus E2 treatment caused a 2.5-fold increase in nuclear type II estrogen binding sites which were confined to the DLP. Neither treatment significantly altered androgen content or levels of androgen receptor in the ventral prostate or DLP. Organ cultures of enlarged DLP containing foci of dysplasia metabolized more [3H]DHT than control tissue, which resulted in increased formation of the 5 alpha-androstane-3 beta, 17 beta-diol (3 beta-androstanediol) metabolite by these explants. Because 3 beta-androstanediol has previously been shown to displace [3H]E2 from cytosolic type I estrogen binding sites, the dysplasia may be caused by hyperstimulation of the DLP by the hormones and their normal metabolites produced in abnormal amounts.

C19-radiosteroid disposition in organ cultures of transplanted prostatic adenocarcinomas of the Noble rat.

This study compares the disposition of 8.5-nM C19-radiosteroids in 21-h cultures of Noble rat dorsolateral prostate (DLP) and transplanted adenocarcinomas derived from the DLP. Our purpose was to determine whether differences in androgen activation could be detected between the androgen-stimulated tumor (AST) line, an androgen-independent tumor line carried in intact (AIT-I) and castrated (AIT-C) rats and their DLP tissue of origin. No differences were found between DLP, AST, AIT-I, and AIT-C for the following parameters: 5 alpha-reduction of [3H]testosterone to dihydrotestosterone (DHT); however, conversion to total 5 alpha-reduced metabolites was lower in AIT-C than DLP cultures; explant retention of [3H]testosterone-derived DHT; tissue capacity to hydroxylate [3H]5 alpha-androstane-3 beta,17 beta-diol; total and nuclear high-affinity binding of [3H]DHT to salt-extractable explant protein, except for one AIT-C which yielded half the number of binding sites. Since AIT carried in either intact or castrated hosts is competent as regards formation, retention and high-affinity binding of [3H]DHT in organ culture, we conclude that the neoplasm possesses some of the characteristics considered essential for the expression of androgen responsiveness in vivo.

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.

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.

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.

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.

Prostatic cytosol binding of 5 alpha-androstane-3 beta, 17 beta-diol and estradiol-17 beta.

The goal of the present research was characterization of the interaction of 5 alpha-androstane-3 beta, 17 beta-diol (3 beta-diol) with prostatic estradiol-17 beta(E2) binding sites to address the role of this 5 alpha-dihydrotestosterone(DHT)a metabolite in prostatic regulation. Using dextran-charcoal assay we demonstrated specific 3 beta-diol and E2 binding sites in rat ventral prostate cytosol (RVPC) and dog prostate cytosol (DPC). In both cytosols, E2 binding is of high affinity (Ka congruent to 10(9) M-1; RVPC:68 fmol/mg protein), DPC:170 fmol/mg protein), and 3 beta-diol binding is of moderate affinity (Ka congruent to 10(8) M-1; RVPC:62 fmol/mg protein, DPC:165 fmol/mg protein). Unlabeled 3 beta-diol competes effectively for cytosolic 3H-E2 binding sites, whereas unlabeled DHT, 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-diol) and testosterone (T) are poor competitors for 3H-E2 binding sites. Using DNA-cellulose column chromatography, we separated prostatic androgen and estrogen binding activities. The E2 binding activity which adhered to DNA-cellulose was displaced by 100-fold excess 3 beta-diol but not by DHT. Thus data from two assay procedures show competition of 3 beta-diol for 3H-E2 binding sites in rat and dog prostate.

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)

[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.

[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.