Magnetic resonance imaging correlates of depression after ischemic stroke.

BACKGROUND: Depression affects up to 40% of patients with ischemic stroke. The relationship between site and size of brain infarcts and poststroke depression is still not well characterized. Further possible contribution and interaction of white matter lesions and brain atrophy has not been studied previously. We conducted a magnetic resonance image-based study of the radiologic correlates of depression in a large, well-defined series of patients with ischemic stroke. METHODS: Modified DSM-III-R and DSM-IV criteria were used to diagnose depressive disorders during a comprehensive psychiatric evaluation in 275 of 486 consecutive patients aged 55 to 85 years 3 to 4 months after ischemic stroke. A standardized magnetic resonance imaging protocol detailed side, site, type, and extent of brain infarcts and extent of white matter lesions and brain atrophy. RESULTS: Depressive disorders were diagnosed in 109 patients (40%). Patients with depression had a higher number and larger volume of infarcts affecting the prefrontosubcortical circuits, especially the caudate, pallidum, and genu of internal capsule, with left-sided predominance. Extent of white matter lesions and atrophy did not differ in patients with and without depression. Independent correlates of poststroke depression in a logistic regression model were mean frequency of infarcts in the genu of internal capsule on the left side (odds ratio [OR], 3.2; 95% confidence interval [CI], 1.0-10.1), mean frequency of infarcts in the pallidum of any side (OR, 1.6; 95% CI, 1.1-2.3), and mean volume of infarcts in the right occipital lobe (OR, 0.98; 95% CI, 0.96-0.99). CONCLUSION: Lesions affecting the prefrontosubcortical circuits, especially on the left side, are correlates of depression after ischemic stroke.

The effects of an alpha-adrenergic agonist or antagonist on sleep during blockade of catecholamine synthesis in the cat.

The effects of clonidine (CLO) and phentolamine (PHE) on the sleep-waking cycle in the cat treated with alpha-methyl-p-tyrosine (AMPT) were investigated with continuous 16--24 h polygraphic recordings. For the evaluation of possible cholinergic interactions in the paradoxical sleep (PS) increasing effect of AMPT, an atropine pretreatment was given to a group of cats receiving AMPT. Results were compared with those from previous experiments with PHE and atropine. When given alone, AMPT (150 mg/kg) decreased waking and increased deep slow wave sleep. Consistent with other reports PS was enhanced. These results support the hypothesis that moderate inhibition of catecholaminergic transmission favors the execution of PS in the cat. Previous studies have shown that CLO inhibits and PHE increases PS in the cat. In the present study administration of AMPT (150 mg/kg) did not alter the effect of CLO (0.01 mg/kg) or PHE (20 mg/kg) on PS; if anything, a slight potentiation was observed. These results support the view that stimulation of alpha 2-adrenoceptors is of major importance in the effect of CLO on PS and that in certain situations blockade of these receptors by PHE may contribute to its PS increasing action. The increase in PS induced by AMPT was moderate when compared with PS increase after injection of PHE (20 mg/kg) which enhances significantly both the number of PS episodes and their mean length. Atropine at a small dose of 0.075 mg/kg reverses the effect of PHE on PS, whereas it did not affect the sleep pattern induced by AMPT.

Alpha-adrenoceptive influences on the control of the sleep-waking cycle in the cat.

Polygraphic 16 h sleep recording were carried out in 35 adult cats following i.p. injections of various alpha-adrenoceptors agonists, antagonists and their combinations. The direct alpha-agonists, clonidine (CLO 0.005, 0.01 and 0.02 mg/kg) and xylazine (XYL 0.5, 1 and 2 mg/kg), dose-dependently decreased paradoxical sleep (PS) and deep slow wave sleep (S2), with a respective increase mainly in drowsy waking (D). alpha-Methyldopa, precursor of the potent alpha-agonist, alpha-m-noradrenaline (alpha-m-NA) suppressed PS, with little effect on other vigilance stages. Of the alpha-antagonists only phentolamine (PHE 10 and 20 mg/kg) increased significantly the 16 h mean of PS. Thymoxamine (THY 5 mg/kg) gave a modest, temporary increment in PS between 4 and 8 h after the injection, but the effect diminished with 10 mg/kg THY. Yohimbine (YOH 2 mg/kg) induced an early increment in aroused waking (A). Tolazoline (TOL 6 mg/kg) and THY (5 and 10 mg/kg) increased D in the first 4 h epoch. Phenoxybenzamine (PBZ 10 mg/kg) significantly decreased the 16 h mean of S2 and PS. PHE antagonized the PS suppressing effect of CLO (0.01 mg/kg) already at the dose of 5 mg/kg and with 10 and 20 mg/kg its PS increasing character prevailed. TOL (6 mg/kg) and YOH (2 mg/kg) were also effective antagonists to CLO. THY (5 and 10 mg/kg) was ineffective in this respect and clearly potentiated the S2 inhibiting effect of CLO. PBZ (10 mg/kg) powerfully potentiated both PS and S2 suppressing effects of CLO. PHE (20 mg/kg) was tested against XYL (0.5 and 1 mg/kg) and alpha-methyldopa (100 mg/kg). It also antagonized the PS inhibiting action of these drugs. All the three agonists preferentially stimulate presynaptic (alpha 2) type of alpha-adrenoceptors, inhibitory to noradrenaline (NA) transmission. Furthermore, as only antagonists possessing presynaptic potency inhibited PS suppression by alpha 2-agonists, while preferential alpha 1-antagonists were either ineffective or potentiated this effect, the results favor the hypothesis of a positive involvement of NA in the mechanisms of PS. The optimal level of NA transmission for PS may, however, be postulated to lie below that for arousal, in which case the balanced blockade of alpha 1- and alpha 2-adrenoceptors by PHE might be exceptionally favorable to PS. The possible role of alpha-adrenoceptive influences on cholinergic and 5-HT neurons and their relevance to alpha 2-agonist-induced sedation and inhibition of PS and S2 are discussed.

Prazosin increases paradoxical sheep.

Prazosin 0.5 and 1.0 mg/kg i.p. induced a prompt and enduring increase in paradoxical sleep in the cat. The maximal effect, 140 percent above control was observed during the first 4 h after 1 mg/kg. In 16 h polygraphic records the respective increment was 69%. After 10 mg/kg paradoxical sleep was inhibited but it returned to control levels in 16 h. These results are discussed with reference to our previous experiments with agents having different alpha 1- and alpha 2-antagonist or agonist potency. It is concluded that selective, moderate blockade of alpha 1-receptors favours paradoxical sleep.

Effect of phentolamine on wakefulness and sleep during recovery from REM sleep deprivation in cats.

Adult cats with permanent EEG, EMG, EOG, and PGO electrodes were recorded for 24 hours started at the end of a 72-hour REMS deprivation induced by a platform-water-tank procedure and after receiving IP injections of phentolamine (20 mg/kg) or saline. Exposure of the cats to the platform-REMS deprivation procedure increased the percentage of REMS during the subsequent 24 hours. Phentolamine interacted with the platform REMS deprivation causing the peak of REMS percentage to occur during recovery hours 5-12. These findings indicate that blockade of alpha-receptors has an additive effect on platform-REMS deprivation induced REMS rebound in cats.

Evaluation of reproductive failure of female pigs based on slaughterhouse material and herd record survey.

Reproductive organs were collected from one slaughterhouse and culling data were obtained from Finnish swine herd records to determine the types and frequencies of various fertility disturbances in Finnish female pigs. Detailed information about the type and occurrence of fertility disturbances was obtained through a close examination of the slaughterhouse material. A total of 1708 reproductive organs of female pigs were examined. The following findings were recorded: no macroscopical abnormalities 52.3%, inactive ovaries 25.1%, parovarian cysts 22.9%, single ovarian cysts 3.1%, multiple ovarian cysts 3.1%, uterine disorders 1.4%, ovarian adhesions 1.1%, congenital anomalies 0.8%, tumour-like lesions in ovaries 0.8%, obstruction of oviduct 0.2%, and suppurative ovarian infection 0.1%. A large proportion, 42% of the culled gilts and 39% of the culled sows, were slaughtered because of impaired fertility based on no pregnancy, no heat or poor piglet production. The sows were removed from the herds 33 days on average after weaning.

Seasonal effects on reproduction in the domestic sow in Finland--a herd record study.

Seasonal effects on fertility of the domestic sow were assessed by retrospective analysis of the Finnish national computerised data management system covering 1081 herds in 1993. Multivariate analyses were used, where the reproductive parameter of interest (repeat breeding, weaning to oestrus interval, age of gilts at first farrowing, litter size, culling due to anoestrus or no conception) was designed as the response variable. The months of the year (each month compared with January) and all herds and breed were included in the models as explanatory variables. The study demonstrated clear seasonal effects on various aspects of fertility in the domestic sow. The poorest reproductive performance was consistently observed in late summer and autumn and was demonstrated in a number of ways. Firstly, the gilts born between December and April were older (> 5 days) at farrowing than those born during the rest of the year (p < 0.01). Secondly, the risk that a culled sow would be culled due to anoestrus was significantly increased during the autumn months (Odds Ratio (OR) ranged from 1.10 to 1.36). Thirdly, the risk of a repeat breeding was higher from July to November (OR = 1.16). Risk of a prolonged weaning-to-oestrus beyond day 10 was the highest from August to October (OR ranged from 1.70 to 1.77). Risk of a sow to be culled due to no conception was the highest in January and February (weaned in October-November). In addition, descriptive data gathered in a slaughterhouse in 1993 (a subpopulation of the sows included in the herd records) suggest that incidence of inactive ovaries is increased in summer-autumn (p < 0.05). In conclusion, a marked reduction in fertility of the domestic sow in Finland is reported between July and November.

Effects of methoxamine, and alpha-1 adrenoceptor agonist, and prazosin, an alpha-1 antagonist, on the stages of the sleep-waking cycle in the cat.

In these experiments the effects of alpha 1-adrenoceptor agonism and antagonism were studied on the stages of the sleep-waking cycle of the cat, in order to determine optimal levels of alpha 1-adrenergic transmission for these stages. Polygraphic 16-h recordings showed that prazosin, an alpha 1-adrenoceptor antagonist, at 1 mg/kg i.p., increased paradoxical sleep (PS) time from 15.3% to 26.4% (p less than 0.001) of total time, and the number of PS episodes from 30.4 to 43.6 (p less than 0.001). The effect was prompt, reaching a maximum during the first 4 h with a shortening of PS latency from 40.4 min to 11.0 min (p less than 0.001). Prazosin at doses of 0.5 and 3.0 though not at 10.0 mg/kg also slightly, but significantly, increased PS. Methoxamine, and alpha 1-adrenoceptor agonist, at doses of 0.5 and 3.0 mg/kg, increased aroused waking time (low voltage mixed frequency EEG) during the first 4 h from 23.5% to 33.3% (p less than 0.05) and to 50.3% (p less than 0.01), and decreased PS. Prazosin potentiated dose-dependently clonidine-induced drowsiness ( hypersynchronized 4-8 Hz EEG), whereas the decrease in deep slow wave sleep and PS were potentiated only at the largest dose of it. These results indicate that moderate inhibition of cerebral alpha 1-adrenergic transmission facilitates paradoxical sleep in the cat. Furthermore, they suggest that the level of cerebral alpha 1-adrenergic transmission is high during aroused waking and low during drowsy waking.

Effects of two adrenergic beta-receptor blockers on the sleep cycle of the cat.

Sixteen hour polygraphic recordings (EEG, EOG and EMG) were obtained from 14 adult cats after intraperitoneal injections of propranolol (5 mg/kg) or pindolol (0.1 or 0.5 mg/kg). All injections moderately increased waking, which consisted mainly of a sedated drowsy stage. Both drugs also decreased deep slow wave sleep, while light slow wave sleep remained at control levels. The changes were more marked after propranolol, which also significantly reduced paradoxical sleep (PS). The decrease in the deeper stages of sleep and PS is suggested as being due to blockade of the central adrenergic beta-receptors per se and/or antagonistic effects of the beta-blockers on 5-HT receptors. The results agree with the finding that beta-blockers cause insomnia in susceptible patients, but they do not suggest that intensified dreaming or nightmares reported by others are likely to be caused by increased PS.

Effects of serotonin and noradrenaline uptake blockers on wakefulness and sleep in cats.

The aim of the study was to examine the role of serotonergic (5-HT) and noradrenergic mechanisms in the regulation of wakefulness and sleep. For this purpose, adult cats with implanted electrodes for EEG, EOG and EMG were exposed to the 5-HT uptake blocker citalopram (0.1, 0.5 and 5.0 mg/kg intraperitoneally) and the noradrenaline uptake blocker prindamine (5 mg/kg intraperitoneally) at the start of continuous 16-hour sleep-wake recordings. Citalopram increased deep slow wave sleep and decreased REMS. Also prindamine decreased REMS but initially increased the proportion of time spent in the state of active wakefulness. Furthermore, to examine the interactions between 5-HT-nergic and noradrenergic mechanisms in the regulation of sleep, the administration of citalopram was preceded by intraperitoneal injections of phentolamine (10 mg/kg), an alpha-antagonist, and propranolol (5 mg/kg), a beta-antagonist. Phentolamine was totally ineffective against citalopram whereas propranolol partially counteracted the effects of citalopram on sleep. Prindamine was combined with the alpha-antagonists yohimbine (1 mg/kg), phentolamine (10 mg/kg) and prazosin (1 mg/kg) or with the beta-antagonist propranolol (5 mg/kg). Yohimbine was without any effect on REMS, phentolamine partly antagonized prindamine-induced decrease in the percentage of REMS, and prazosin only prolonged REMS latency and reduced deep SWS as well. Propranolol partially antagonized the prindamine-induced initial increase in active wakefulness time.(ABSTRACT TRUNCATED AT 250 WORDS)

Insomnia in ischemic stroke patients.

This is the first study that focuses on insomnia in stroke patients. A subgroup of 277 patients from a consecutive series of 486 stroke patients aged 55-85 years was subjected to a comprehensive psychiatric evaluation 3-4 months after ischemic stroke. Of 277 patients, 56.7% reported any insomnia complaint and 37.5% fulfilled the DSM-IV criteria of insomnia. In 38.6%, insomnia complaint/insomnia had already been present prior to the stroke and in 18.1%, it was a consequence of the stroke. Independent correlates of any insomnia complaint/insomnia were anxiety (Zung Anxiety Scale) and the use of psychotropic drug. Independent correlates of poststroke-onset insomnia complaint/insomnia were disability after stroke (Barthel Index), dementia, anxiety and use of psychotropic drug. Insomnia should be taken into consideration in treating and rehabilitating stroke patients.

Arterial haemoglobin oxygen saturation is affected by F(I)O2 at submaximal running velocities in elite athletes.

This study was conducted to determine whether arterial desaturation would occur at submaximal workloads in highly trained endurance athletes and whether saturation is affected by the fraction of oxygen in inspired air (F(I)O2). Six highly trained endurance athletes (5 women and 1 man, aged 25+/-4 yr, VO2max 71.3+/-5.0 ml x kg(-1) x min(-1)) ran 4x4 min on a treadmill in normoxia (F(I)O2 0.209), hypoxia (F(I)O2 0.155) and hyperoxia (F(I)O2 0.293) in a randomized order. The running velocities corresponded to 50, 60, 70 and 80% of their normoxic maximal oxygen uptake (VO2max). In hypoxia, the arterial haemoglobin oxygen saturation percentage (SpO2%) was significantly lower than in hyperoxia and normoxia throughout the test, and the difference became more evident with increasing running intensity. In hyperoxia, the SpO2% was significantly higher than in normoxia at 70% running intensity as well as during recovery. The lowest values of SpO2% were 94.0+/-3.8% (P<0.05, compared with rest) in hyperoxia, 91.0+/-3.6% (P<0.001) in normoxia and 72.8+/-10.2% (P<0.001) in hypoxia. Although the SpO2% varied with the F(I)O2, the VO2 was very similar between the trials, but the blood lactate concentration was elevated in hypoxia and decreased in hyperoxia at the 70% and 80% workloads. In conclusion, elite endurance athletes may show an F(I)O2-dependent limitation for arterial O2 saturation even at submaximal running intensities. In hyperoxia and normoxia, the desaturation is partly transient, but in hypoxia the desaturation worsens parallel with the increase in exercise intensity.