Treatment of Alzheimer's disease with sabeluzole: functional and structural correlates

Sabeluzole, a new benzothiazole derivative, has been shown to be neurobiologically active preclinically and clinically appears to exert beneficial effects on memory. In this study, sabeluzole (5 or 10 mg twice daily vs. placebo) was investigated in patients with probable Alzheimer's disease over 1 year, with assessments of cognitive performance and structural changes. Cognitive performance was measured using the Alzheimer's Disease Assessment Scale periodically during treatment. Potential structural correlates in the frontal horn, caudate, third ventricle and hippocampal regions were examined by obtaining computerized tomographic (CT) images before and after treatment. Patients receiving sabeluzole evidenced greater stability than did placebo-treated patients in some cognitive measures. CT measures showed no significant changes from baseline, but some weak associations were found between relative preservation of cognitive function and smaller structural declines in the third ventricle and hippocampus. Cognitive outcome measures suggest that sabeluzole may have potential in slowing the cognitive deterioration of Alzheimer's disease. Furthermore, the method used to explore potential benefits on a morphologic level, although negative in this study, could yet have potential.     

Respiratory insufficiency in neuronopathic and neuropathic disorders

Twenty-nine patients with a neuronopathic or neuropathic disorder were referred for assessment of respiratory insufficiency between 1978 and 1994. Diagnoses included spinal muscular atrophy (6), chronic idiopathic demyelinating neuropathy (4), Vialetto-van Laere syndrome (3), hereditary motor and sensory neuropathy (3) and a miscellaneous group (5). We also describe seven patients with Guillain-Barré syndrome (GBS) who required long-term ventilatory support for over 6 months to 7 years after the initial illness. Respiratory insufficiency occurred as a consequence of respiratory muscle weakness, impaired bulbar function and restrictive lung defects. In some groups presentation was with progressive nocturnal hypoventilation culminating in acute respiratory failure. Five patients with GBS or chronic idiopathic demyelinating neuropathy were weaned from ventilatory support up to 18 months after the initial illness. The remaining 24 patients required continuous or nocturnal ventilatory support using intermittent positive-pressure ventilation (13), negative pressure ventilation (4), nasal-mask-delivered intermittent positive-pressure ventilation (4), nasal-mask-delivered continuous positive-pressure ventilation (3), mouthpiece-assisted ventilation by day (2) and rocking bed (1). None have been weaned from support after a period of ventilation ranging from one month to 10 years. Eight patients have subsequently died.     

Anterior choroidal artery aneurysm and stroke

We report the unique combination of a mid anterior choroidal artery (AChA) aneurysm and ischemic stroke presenting as a movement disorder in a young man. The mechanism for stroke in the AChA territory may either reflect a cause or an effect of aneurysm formation. We provide evidence for both arguments and speculate on the anatomic basis for the initial presentation of hemibody spasm.     

Effect of hydroxylamine hydrochloride on the bacterium Shigella dysenteriae 1 and antigens isolated from them

A study was made into the functional status of hypophysis, adrenal cortex, ovaries, and thyroid gland in patients with kraurosis and leukoplakia vulvae. The above patients demonstrated profound disturbances in the system hypophysis-ovaries, that attest to the need for applying corrective therapies to treat the disturbed hormonal homeostasis.     

Delayed cytogenetics effects of chronic irradiation of South Ural population

The aim of this study was to assess the referral pattern and the impact on long-term survival of postoperative radiotherapy in patients with adenocarcinoma of the endometrium stage I. This was a retrospective study performed in a regional cancer registry which covers a population of approximately 1,000,000 persons. All 724 patients registered between 1975 and 1992 in the Comprehensive Cancer Centre South, Eastern Section, The Netherlands, were analysed. All patients had received surgery as primary treatment which was performed in one of the seven community hospitals of the region. Radiotherapy was given in one regional department. All pathology reports were checked for data on tumour differentiation and myometrial invasion. Almost half the patients (45%) were referred for postoperative radiotherapy. The depth of myometrial invasion and the degree of tumour differentiation were the main factors (P < 0.0001) influencing referral for postoperative radiotherapy. The referral pattern varied between the different hospitals, but became more similar during 1985-1988, to diverge again in recent years. In patients younger than 60 years, the depth of myometrial invasion was significantly (P = 0.01) correlated with survival. In patients older than 60 years, tumour differentiation (P = 0.05) and age (P < 0.001) were correlated with survival, but not the depth of myometrial invasion. After adjustment for known prognostic factors, a survival benefit of postoperative radiotherapy could not be established. The studied group had an excess death rate over the normal Dutch female population. This excess death rate did not decrease during follow-up, as even after 10 years an excess death rate was found. A prospective randomised trial is ongoing in The Netherlands.     

A comparison of the detection sensitivity of lymphocyte membrane antigens using fluorescein and phosphor immunoconjugates

In Escherichia coli, UV and many chemicals appear to cause mutagenesis by a process of translesion synthesis that requires some form of DNA polymerase III and the SOS-regulated proteins UmuD, UmuC and RecA. An analysis of SOS mutagenesis offers insights into the molecular basis of induced mutagenesis and into mechanisms of DNA damage tolerance.     

Survival of patients with pathologically proven multiple system atrophy: a meta-analysis

A systematic review of the neurologic literature identified 433 cases of pathologically proven multiple system atrophy over a 100-year period. Earlier case reports included patients younger in age with more frequent cerebellar involvement. Mean age of onset was 54.2 years (range 31 to 78) and survival was 6.2 years (range 0.5 to 24). Survival analysis showed a secular trend from a median duration of 4.9 years for publications between 1887 and 1970 to 6.8 years between 1991 and 1994. Older age of onset was associated with shorter survival; the hazard ratio for patients with onset after 60 years was 1.8 (95% CI 1.4 to 2.3) compared with patients between 31 and 49 years. Cerebellar features were associated with marginally increased survival (6.1 years versus 5.4 years; p = 0.04). There were no difference in survival according to gender, parkinsonian, or pyramidal features or whether the patient was classified as striatonigral degeneration or olivopontocerebellar atrophy type. These results demonstrate the poor prognosis for patients with multiple system atrophy but may be biased toward the worst cases. Future research needs to recruit more representative samples.     

Potassium current and the effect of cesium on this current during anomalous rectification of the egg cell membrane of a starfish

The kinetics of the membrane current during the anomalous or inward-going rectification of the K current in the egg cell membrane of the starfish Mediaster aequalis were analyzed by voltage clamp. The rectification has instantaneous and time-dependent components. The time-dependent increase in the K conductance for the negative voltage pulse as well as the decrease in the conductance for the positive pulse follows first-order kinetics. The steady-state conductance increases as the membrane potential becomes more negative and reaches the saturation value at about -40 mV more negative than the K equilibrium potential, V(K). The entire K conductance can be expressed by g(K).n; g g(K) represents the component for the time-independent conductance which depends on V-V(K) and [K+]o, and n is a dimensionless number (1 is greater than or equal to n is greater than or equal to 0) and determined by two rate constants which depend only on V-V(K). Cs+ does not carry any significant current through the K channel but blocks the channel at low concentration in the external medium. The blocking effect increases as the membrane potential is made more negative and the potential-dependent blocking by the external Cs+ also has instantaneous and time-dependent components.