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This meeting, which for the first time included BrainPET, was held in close cooperation with the International Society for Cerebral Blood Flow and Metabolism and was presided over by Dr Olaf B Paulson (Neuroscience Center, Rigshospitalet, Copenhagen, Denmark). It attracted approximately 750 registered participants from over 30 countries, with a particularly strong Japanese presence. More than 100 oral presentations were held and some 700 posters displayed.

Objective: To assess the non-cognitive symptoms in 153 consecutive dementia patients admitted to our psychiatric ward or seen at the gerontopsychiatric ambulance and Memory Clinic., Methods: We used the Global Deterioration Scale, the Hachinski Ischaemia Score, the Hamilton Psychiatric Rating Scale for Depression, and the Mini-Mental State Exam as staging tools in a cross-sectional design. A semi-quantitative 34-item questionnaire based on the Columbia University Scale for Psychopathology was employed to assess non-cognitive symptoms as reported by caregivers., Results: All patients had disturbances of affect, 95% of behavior and 71% of motivation, while 52% and 29% had delusions and hallucinations, respectively. Delusions, but not hallucinations, were correlated with verbal and physical aggressiveness. Factor analysis extracted three complex variables which accounted for 40.6 percent of the observed total variance, and which were subsequently interpreted as manifestations of agitation, burdensome behavior, and depression. Using these variables, we then identified three categories of patients: Agitated, debilitated, and depressive-anxious. Depression and anxiety were most common 3-4 years after diagnosis. Patients with Alzheimer's disease had less severe behavioral and psychotic symptoms than those with other types of dementia. Agitation, depression, and loss of competence in daily living had a greater impact on caregivers than aggression and psychotic symptoms., Conclusion: The non-cognitive symptom profile is related to the type of dementia, and shifts dynamically with disease progression.

Clomethiazole has been marketed for several years as a sedative/antiepileptic. Astra is now developing it for the potential treatment of stroke. An NDA is expected to be filed in 1999/2000. A North American phase III trial for large stroke has commenced. This will include 1200 patients. Two other smaller scale phase III studies with clomethiazole have also commenced in North America for intracerebral hemorrhage (n=200) and safety in combination with TPA (n=100 to 200) (Genentech). A large-scale phase III trial has been completed in which clomethiazole was evaluated for its ability to reduce nerve damage in acute cerebrovascular ischemia. The multicenter, international trial, called CLASS (Clomethiazole Acute Stroke Study), analyzed 1360 patients and found no significant treatment effect. However, a subgroup of patients who presented with large stroke, experienced a significant benefit. Of these (n=545), 41% treated patients were functionally independent after 90 days, compared to 30% patients on placebo. Clomethiazole reduced functional disability and brain damage in the marmoset permanent MCAO model. Clomethiazole is thought to act through a GABAergic pathway, whereby it augments GABA's depressive effect on the CNS, giving the drug both hypnotic and neuroprotectant properties.

KA-672 is a multifunctional antidementia agent under development by Schwabe as a potential agent to combat cognitive and other symptoms of Alzheimer's disease (AD), via modulation of the interplay between serotonergic, adrenergic, dopaminergic and cholinergic systems [260590]. It has also been categorized as a neuronal activator. Various studies support the notion that this compound could indeed have a broad range of nootropic properties. The compound is in phase II clinical trials [260592]. KA-672 selectively protects against NMDA-induced neurotoxicity but not against other chemoconvulsants or electroshock [260590]. At 0.3 mg/kg it inhibits the reduction in 5-HT brain levels following NMDA administration, and exacerbates the reduction in dopamine levels [260593]. It has been shown to bind to 5-HT1A, 5-HT7, a1, D2 and D3 receptors with nanomolar affinities, acting as an antagonist at a1 and D2 receptors [260592]. It also has nerve growth factor (NGF)-like activity [260591].

The authors present an overview of drugs that operate on the basis of the cholinergic hypothesis, either currently available for the palliative treatment of Alzheimer's disease or in the later stages of clinical development. Of the many conceivable strategies that are being exploited, only inhibitors of acetylcholinesterase have been shown to have sufficient therapeutic potential and manageable side-effect profiles to be turned into broadly acknowledged drugs. These compounds, and others based on the modulation of cholinergic neurotransmission, are discussed and a differentiation of their clinical potential is attempted.

In addition to a few disorders such as acute T-cell leukemia that are typically associated with the human T-cell leukemia virus (HTLV) 1 in endemic regions, this virus may also play a role in some other hematological diseases. Here, we examine the incidence of HTLV in hematological diseases from a nonendemic region in central Europe. Data obtained by PCR and/or serological techniques from a total of 730 cases showed that besides the expected presence of HTLV-1 in T-lymphoid diseases (2 of 27 cases), HTLV-1 was only detected in myelodysplastic syndrome (MDS), in which an incidence of 17% (11 of 65 cases) was found. A correlation with a history of multiple transfusions or treatment with blood products in the HTLV-1-positive MDS could not be ascertained. Cytogenetics detected the presence of del(5)(q) in six HTLV-positive cases (five MDS and one T-cell acute lymphocytic leukemia) but in only one HTLV-negative case. These data indicate that allelic deletions of a series of 5q-located genes that typically occur in MDS may be associated with HTLV infections in central Europe.

Chronic alcohol abusers show a specific pattern of cerebral damage associated with cognitive and behavioral defects known as the organic cerebral psychosyndrome, which is partially reversible upon discontinuation of ethanol consumption. To assess the potential of nootropic drug therapy in alcohol rehabilitation in a double-blind study design, 56 consecutive patients who participated in routine rehabilitation therapy received 2 x 3 mg/day dihydroergocristine or placebo in tablet form over 6-13 weeks. Forty-nine patients completed the protocol. Although significant improvement was seen in both groups, we could document a specific cognitive restitution effect attributable to dihydroergocristine. Significant differences in favor of the active drug group were demonstrated by Mini-Mental State Examination, Syndrome Brief Test, Paired Words Test, in the neuropsychiatric Brief Cognitive Rating Scale assessments, and in the Clinical Global Impression of Change rating. No significant between-group differences were found in the Digit Symbol Test and the Block Design Test as well as in the Brief Psychiatric Rating Scale (BPRS). Dihydroergocristine was equivalent to placebo in terms of subjective drug tolerance, lack of side effects, and laboratory parameters. Based on this profile of efficacy and safety, we recommend dihydroergocristine as an adjuvant drug in alcohol rehabilitation.

Serological evidence is presented for the fact that patients with the myelodysplastic syndrome exhibit a statistically significant reactivity in confirmatory assays for antibodies to human T-lymphotropic viruses types I and II (HTLV-I/II). This antibody reactivity, evident by indirect immunofluorescence and Western blot, was not confined to HTLV core antigens but extended to native and recombinant envelope glycoproteins. The effect was also observed in cases of acute myeloic leukemia, albeit to a lesser degree. It was essentially absent from patients with chronic myeloic leukemia or lymphocytic leukemias and healthy or multitransfused controls. No antibodies to human immunodeficiency viruses types 1 or 2 were detected in any of the specimens. The investigated clinical population had no known risk factor for retroviral infection other than a history of multiple platelet transfusions, and none of the specimens was seropositive for HTLV-I or HTLV-II according to recommended criteria. The cause of this cross-reactivity remains to be determined.

In the GDR annually repeated indiscriminate mass miniature radiographies (MMR) of all persons in the age of 16 years and over were performed during 3 decades. The aim was, beside finding cases of pulmonary tuberculosis, the early detection of bronchogenic carcinoma. The decrease of tuberculosis incidence and the shift of nearly all new cases to higher age groups lead to a change of this policy. The new regulation, in force since 1986, provides mass X-ray examinations of all persons in the age of 40 years and over with 2 years interval, and X-ray examinations of the lung of persons in several risk groups with shorter, mainly annual intervals. The latter became a task of the chest clinics. The experience of 2 chest clinics with the organization of these examinations and the yield of new cases of pulmonary tuberculosis and bronchogenic carcinoma are reported. It is necessary to improve the organization and to reduce the number of risk-groups to those with an acceptable balance of input and result. Otherwise, the staff of the chest clinics is impeded to fulfill more rewarding tasks in the care of patients. The results of the attempts of early detection of bronchogenic carcinoma and improvement of life expectancy by X-ray examination of risk groups and early resection were disappointing. Thus, other ways must be found. A revision of the regulation of 1986, concerning risk groups, is proposed with the aim to rationalize their surveillance.

Cyanophora paradoxa, a unicellular flagellate, contains cyanelles which are supposed to be cyanobacterial origin. DNA was isolated from subcellular fractions and separated according to density components in CsC1 density gradients. The main DNA component, comprising more than 90% of the total DNA, has a buoyant density of 1.724 g X cm-3. Several subsfractions in the range from 1.718 g X cm-3 to 1.735 g X cm-3 are contained in this component. This DNA of high complexity was considered to be host nuclear DNA. The DNA from the endosymbiotic cyanelles, which were isolated, treated with DNase, and purified by sucrose density gradient centrifugation exhibited a buoyant density of 1.692 g X cm-3 in one strain and 1.695 g X cm-3 in a second strain. Both cyanelle DNAs (cyDNA) have a complexity of approximately 126 X 10(3) base pairs and comprise about 5% of the total cellular DNA content. Two additional DNA components of low complexity were isolated from crude cyanelle pellets obtained without DNase treatment. The larger of these, approximately 48 X 10(3) base pairs in size, had a density of approximately 1.688 g X cm-3. The second component, about 15 X 10(3) base pairs in size, banded in the density range between 1.710 g X cm-3 and 1.720 g X cm-3. The latter is associated with nuclear DNA. The 48 X 10(3)-base-pair component was located in the cytosol and could be obtained after CsC1/ethidium bromide density gradient centrifugation at the position of covalently closed circular DNA. Both these components amounted to approximately 0.5-1% of total DNA. A further DNA component with a complexity of more than 150 X 10(3) base pairs, enriched in fractions where mitochondria are expected, was not characterized further. The density was intermediate between cyDNA and nuclear DNA (1.710-1.720 g X cm-3) and it amounted to 1-2% of the total DNA. Our results indicate that the DNA from cyanelles, believed to be endosymbiotic cyanobacteria, is not more complex than higher plant chloroplast DNAs.

The cyanelle DNA from two different strains of Cyanophora paradoxa (strain LB555UTEX and strain 1555) was investigated.The cyanelle DNA from both strains showed a buoyant density in neutral CsCI gradients of 1.692 g/cm(3). The total molecular weight, as judged by restriction endonuclease analysis, of the two cyanelle DNAs differed. In strain LB555UTEX the size of the cyanelle DNA was equivalent to 127 ± 1 kb whereas in strain 1555 a size of 138 ± 1 kb was consistently found. The sizes of individual DNA fragments and the number of recognition sites for a particular restriction endonuclease appeared largely unrelated.A high amount of cross hybridization, as judged by reciprocal heterologous DNA hybridizations, however indicated a high degree of sequence homology between the two cyanelle DNAs. Under comparable conditions, cyanelle DNA hybridized nearly exclusively with the dG+dC-rich rRNA transcription units from plastid DNAs. Up to now conserved restriction endonuclease recognition sites between the two cyanelle DNAs were only observed within the cyanelle rRNA genes which are present twice on both cyanelle DNAs.

The 287-bp spacer and the flanking 3'-end of the 16S- and 5'-end of the 23S-rRNA genes of the cyanelles from Cyanophora paradoxa have been sequenced and compared with the corresponding regions of cyanobacteria and chloroplasts. The spacer contains the uninterrupted genes for tRNA(ile) and tRNA(ala). All coding regions show high homology to their prokaryotic counterparts. At the 3'-end of the 16S-rDNA a CCTCCTTT sequence has been identified which is complementary to putative ribosome binding sites observed immediately upstream of the coding region of cyanelle protein genes.