In order to clarify whether nocturnal hypoxaemia (arterial oxygen saturation, SaO2 < 90%) may exist in the long-term before daytime hypoxaemia (PaO2 < 8.0 kPa) occurs in chronic obstructive pulmonary disease (COPD), 21 patients with stable severe COPD without daytime hypoxaemia (PaO2 > or = 8.0 kPa) were studied prospectively. Subjects were monitored twice by polysomnography (PSG) 12 months apart. Spirometry was performed, and diffusion capacity (DLCO) and hypercapnic respiratory drive response delta PI0.1 delta PCO2(-1)) were measured during the daytime in conjunction with polysomnography. At the start of the study our subjects had FEV1 %P (FEV1 as a percentage of predicted value) of 26.1 +/- 7.2%, a mean nocturnal nadir SaO2 of 83 +/- 5%, and a mean SaO2 during nocturnal hypoxaemic episodes of 88.0 +/- 0.7%. The patients' delta PI0.1 delta PCO2(-1) was 1.8 +/- 1.4 cm H2O kPa-1 (within the normal range). For the entire study group, no significant change in any lung function or blood gas parameter was noted during the year of observation, and nocturnal SaO2 remained unaltered. Stage I sleep decreased (P < 0.05) after 12 months. Prolonged stage I sleep was associated with nocturnal hypoxaemia at the second PSG. Five subjects developed daytime hypoxaemia and they showed poorer lung function but similar nocturnal hypoxaemia and delta PI0.1 delta PCO2(-1) level compared to the rest of the patients. Patients with sudden SaO2 dips had more pronounced nocturnal hypoxaemia and prolonged wakefulness than 'non-dippers'. In conclusion, the mean level of nocturnal hypoxaemia may persist unaltered for at least 1 yr. COPD patients with exclusively nocturnal hypoxaemia have a hypercapnic drive response within the normal range. Prolonged nocturnal hypoxaemia and reduced whole night oxygenation are associated with increased superficial sleep. Sleep fragmentation and high carbon dioxide sensitivity may be important defence mechanisms against sleep-related hypoxaemia. The appearance of daytime hypoxaemia is preceded by a substantial deterioration in lung function, but by only a minor deterioration of nocturnal hypoxaemia.

The effects of a mumps virus infection on functional properties of embryonic hippocampal neurons in culture were analysed with special emphasis on voltage-dependent Ca2+ channels. Cultures with higher or lower density of glial cells (not treated or treated with mitotic inhibitor, respectively) were infected with the relatively non-cytolytic RW strain of mumps virus and currents were recorded from neurons using whole cell voltage clamp. More than 65% of neurons and glial cells contained viral antigens 1-2 days post infection (p.i.). Glial cells remained infected 6-7 days p.i., while the ratio of infected versus uninfected neurons, especially in cultures with higher glial cell density, was reduced. In both infected and uninfected cultures the somal voltage-dependent Ca2+ currents were stronger in cultures with a higher glial cell density, which indicates that these currents are influenced by glial cells. Introduction of the virus into cultures caused a selective decrease in inward Ca2+ currents, which was most marked at days 6-7 p.i., and which included both infected and unifected neurons. Spontaneous synaptic currents and other ion channel conductances appeared normal in the infected cultures. Dantrolene, which inhibits release of Ca2+ from intracellular stores, decreased the neurons that died during the infection. Taken together the results show that a mumps viral infection can selectively alter the number of function of somal voltage dependent Ca2+ channels in immature hippocampal neurons and that this may reflect a disturbed glia-nerve cell interaction.

Nocturnal hypoxaemia is often noted in COLD patients with a daytime PaO2 above 8.0 kPa. It has been assumed that ventilation-perfusion inequality contributes to nocturnal hypoxaemia. 10 patients with advanced COLD [median FEV1 0.73 (range 0.50-1.32)l], but without daytime hypoxaemia [median PaO2 8.35 (range 8.0-12.2) kPa] were investigated with regard to possible nocturnal hypoxaemia using polysomnography. Daytime lung function was assessed by spirometry and carbon monoxide diffusion capacity (DLCO). Daytime ventilation-perfusion (VA/Q) relationships were measured by the multiple inert gas elimination technique. Dispersion of perfusion and ventilation distributions was increased [log SDQ 1.01 (range 0.80-1.35) and log SDV 0.91 (range 0.69-1.86) resp.]. Around 8% of the ventilation was directed towards high VA/Q areas (10 < VA/Q < 100). All subjects reached all sleep stages, and all but one had a nadir nocturnal oxygen saturation (SaO2) of below 90%. Their median lowest nocturnal SaO2 was 84.0 (range 70-93)% and their mean oxygen saturation in the course of desaturation episodes (MminSaO2) was 86.4 (range 83.6-91.5)%. An increased mean VA/Q ratio of ventilation distribution was associated with a reduced DLCO. Increased nocturnal episodes of wakefulness and of stage I sleep correlated with increased dead space ventilation and dispersion of the ventilation distribution. Patients with deep nocturnal desaturations had a low mean VA/Q ratio of the perfusion distribution (Q mean) (r = 0.87, P < 0.01) and increased perfusion of inferior VA/Q areas (0.1 VA/Q < 0.3). Low MminSaO2 was associated with low morning PaO2 and a low Q mean. COLD patient with solely nocturnal hypoxaemia have a high degree of pulmonary hyperinflation and emphysema. Increased sleep disruption is associated with more severe small airway disease. Increased perfusion of sparsely ventilated areas is associated with more pronounced nocturnal desaturations.

Visual evoked potentials elicited by reversal of a checkerboard pattern constructed of square, red light-emitting diodes (LEDs) were compared with a conventional black and white pattern displayed on a TV monitor in control subjects and in 71 patients with established or suspected multiple sclerosis. Both stimuli elicited distinct responses in the control groups: the latencies were longer with LED stimulation while the amplitudes of the various components were differently altered. The frequency of abnormal responses among the patients was higher with LED stimulation than with TV stimulation, but the highest diagnostic yield was obtained when both methods were combined.

A temperature-sensitive mutant of vesicular stomatitis virus was inoculated intranasally into infant Sprague Dawley rats aged 9 to 1 7 days. Rats receiving the virus at 9 days of age had an extensive spread of infection throughout the brain and the animals died after a few days. Rats inoculated at day 11 postnatally survived and the infection was limited to the olfactory pathways, hypothalamus, diagonal bands and the anterior raphe nuclei. Stereological measurements showed that the volume of infected neurons constituted 67 +/- 10% of the total neuronal volume in the dorsal raphe nucleus. Double-labelling experiments revealed that both 5-hydroxytryptamine- and substance P-immunoreactive neurons contained the virus antigen. The motor stimulant effect of amphetamine was studied at 3 months post infection. The increase in amphetamine-induced frequency and duration of rearing was significantly attenuated in infected rats and the amphetamine-induced locomotion was slightly reduced.

The hamster neurotropic (HNT) strain of measles virus causes non-inflammatory encephalopathy in Balb/c mice, associated with neurodegeneration in hippocampal CA1 and CA3 regions. This loss of pyramidal cells can be prevented by twice daily systemic treatment with 1 mg/kg dizocilpine (5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclo-hepten-5, 10-imine maleate; MK-801) for 7 days. By varying the MK-801 treatment protocol, we now found that drug administration during the last 4 days prior to sacrifice (i.e. days 4-7 post inoculation, p.i.) is essential for neuroprotection. In contrast, MK-801 treatment during the first days (days 0-4 p.i.) did not prevent the neuronal necrosis. These data suggest that the concentration of an excitotoxic factor in the mouse brain increases after virus inoculation, reaching toxic levels by days 4-5 p.i. This novel 'subacute' mouse model of neurodegeneration therefore constitutes an attractive tool for mechanistic and interventional studies in excitotoxicity research.

Rat dorsal root ganglia in tissue culture, which contain an interferon-gamma (IFN-gamma)-like immunoreactive subpopulation of neurons, were infected with paramyxoviruses. Sendai virus caused a substantial neuronal lysis, while the RW strain of mumps virus caused a much less pronounced nerve cell loss. Early during infection, the subpopulation of IFN-gamma-like immunoreactive neurons was less susceptible to mumps virus. Virus antigen was rapidly lost from surviving IFN-gamma-like positive neurons infected with Sendai virus, while this remarkable self-curing effect occurred in both nerve cell populations at later time points after mumps virus infection. By quantitative enzyme-linked immunosorbent assay (ELISA) technique, increased levels of "neuronal IFN-gamma" were recorded at 10 hr and 30 hr after infection with Sendai and mumps virus, respectively. This study indicates a role for the neuronal IFN-gamma-like molecule in determining the outcome of a viral infection in sensory ganglia.

Mumps virus caused a partially lytic infection in cultivated rat embryonic dorsal root ganglion neurons with a restricted formation of viral components. The neuronal degeneration was markedly enhanced by increasing the calcium concentration of the medium and could be almost totally inhibited by the dihydropyridine calcium channel antagonist nifedipine. The drug had no effect on a productive and completely lytic Sendai virus infection of the neurons. A previous neurophysiological study has shown that a reduced calcium influx occurs during the action potential early during the infection. The present study suggests a crucial role of calcium in neurodegeneration induced by certain viruses.

CNS conduction and autonomic nervous function were investigated in 15 patients with HMSN I. Central motor conduction time (CMCT) was estimated with magnetic brain stimulation and electrical nerve root stimulation. Somatosensory evoked potential (SEP) and visual evoked potential (VEP) were used for assessment of central sensory and visual conduction. Autonomic effector organ functions were assessed with the R-R variation test for parasympathetic function, and the sympathetic skin response test (SSR) for skin sympathetic sudomotor activity. Five of the patients had prolonged CMCT. Central sensory conduction was normal in 3, and slightly prolonged in 1 of the patients, but could not be estimated in 11 due to lack of response from the cervical recording. VEP was abnormal in 2 patients. R-R variations during normal breathing were low in 8 of 15 patients, and low also during deep breathing in 1 of 15. The SSR test was pathological in 5 of 15 patients. Thus, impaired central conduction and/or autonomic dysfunction was not an uncommon finding in patients with HMSN I.

N-methyl-d-aspartate (NMDA) receptors represent a major subtype of excitatory amino acid receptors in the mammalian brain. In addition to their physiological role, NMDA receptors have been linked to the occurrence of nerve cell death in several neurodegenerative diseases. The hamster neurotropic (HNT) strain of measles virus causes non-inflammatory encephalopathy in mice. This is associated with neuronal loss in areas CA1 and CA3 of the hippocampus. Systemic treatment with the non-competitive NMDA receptor antagonist 5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclo-hepten-5,10-imine maleate (MK-801) prevented this cellular necrosis. Thus, a virus may have indirect neurodegenerative effects in the brain due to activation of NMDA receptors.

Visual evoked potentials (VEP) have been suggested to be of value in the diagnosis of subclinical and mild hepatic encephalopathy. In the present study, a comparison between VEP and four psychometric tests (number connection test A and B, digit symbol and word memory test) was periormed in 42 cirrhotic patients, 17 of whom had clinical signs of encephalopathy. The results were compared to sex- and age-matched healthy controls. The VEP latencies for P2 (the second positive wave) and N3 (the third negative wave) were 11% and 26% longer (P < 0.01–0.001) in the patients than in the controls. Moreover, the latencies for N2 (the second negative wave) and P2 were longer in the encephalopathic as compared to the non-encephalopathic patients (P < 0.05). There was a significant correlation between the latencies for N2 and number connection tests A and B and digit symbol test. However, of the patients with clinical encephalopathy, less than half had VEP latencies longer then the mean ± 2 S.D. above those for the controls. In contrast, none of the encephalopathic patients had normal results on the psychometric tests. This study demonstrates that although statistically significant differences exist between groups of cirrhotic patients and controls, VEP is not a reliable tool for the diagnosis of encephalopathy in the individual patient.