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1.
Burgess CR  Tse G  Gillis L  Peever JH 《Sleep》2010,33(10):1295-1304

Study Objectives:

To determine if the dopaminergic system modulates cataplexy, sleep attacks and sleep-wake behavior in narcoleptic mice.

Design:

Hypocretin/orexin knockout (i.e., narcoleptic) and wild-type mice were administered amphetamine and specific dopamine receptor modulators to determine their effects on sleep, cataplexy and sleep attacks.

Patients or Participants:

Hypocretin knockout (n = 17) and wild-type mice (n = 21).

Interventions:

Cataplexy, sleep attacks and sleep-wake behavior were identified using electroencephalogram, electromyogram and videography. These behaviors were monitored for 4 hours after an i.p.injection of saline, amphetamine and specific dopamine receptor modulators (D1- and D2-like receptor modulators).

Measurements and Results:

Amphetamine (2mg/kg), which increases brain dopamine levels, decreased sleep attacks and cataplexy by 61% and 67%, suggesting that dopamine transmission modulates such behaviors. Dopamine receptor modulation also had powerful effects on sleep attacks and cataplexy. Activation (SKF 38393; 20mg/kg) and blockade (SCH 23390; 1mg/kg) of D1-like receptors decreased and increased sleep attacks by 77% and 88%, without affecting cataplexy. Pharmacological activation of D2-like receptors (quinpirole; 0.5mg/kg) increased cataplectic attacks by 172% and blockade of these receptors (eticlopride; 1mg/kg) potently suppressed them by 97%. Manipulation of D2-like receptors did not affect sleep attacks.

Conclusions:

We show that the dopaminergic system plays a role in regulating both cataplexy and sleep attacks in narcoleptic mice. We found that cataplexy is modulated by a D2-like receptor mechanism, whereas dopamine modulates sleep attacks by a D1-like receptor mechanism. These results support a role for the dopamine system in regulating sleep attacks and cataplexy in a murine model of narcolepsy.

Citation:

Burgess CR; Tse G; Gillis L; Peever JH. Dopaminergic regulation of sleep and cataplexy in a murine model of narcolepsy. SLEEP 2010;33(10):1295-1304.  相似文献   

2.
Autonomic nervous system activity changes have been described during cataplexy as playing a role in triggering it. To confirm these previous findings, we investigated the time course of sympathetic and cardiovascular activities during cataplexy. We made for the first time microneurographic recordings of 10 cataplectic episodes in three patients with hypocretin‐deficient narcolepsy. During microneurography, muscle sympathetic nerve activity (MSNA) was recorded simultaneously with heart rate (HR), respiratory movements, arterial finger blood pressure (BP), electroencephalography, electro‐oculogram and superficial electromyogram. Results showed no significant autonomic changes before the onset of the cataplectic episodes. Cataplexy was associated with a significant increase in MSNA and BP compared with baseline, whereas HR was markedly decreased. An irregular breathing pattern mainly characterized by apnea typically occurred during the attacks. In conclusion, our findings did not show significant changes in autonomic activity prior to cataplexy onset, ruling out a triggering role of the autonomic system. However, cataplexy was associated with co‐activation of sympathetic and parasympathetic autonomic systems, a pattern reminiscent of that reported during the vigilance reaction in animals.  相似文献   

3.
Laboratory of Experimental Brain Pathology and Department of Newborn and Premature Infants, Research Institute of Pediatrics, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR M. Ya. Studenikin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 109, No. 3, pp. 217–219, March, 1990.  相似文献   

4.
The sleep-wake disorder narcolepsy with cataplexy is associated with the loss of hypocretin-(orexin-) producing neurons in the lateral hypothalamus. Several studies have reported abnormal cerebral activation in patients with narcolepsy with cataplexy. It remains unclear, however, whether these functional changes are related to structural alterations, particularly at the cortical level. To quantify structural brain changes associated with narcolepsy with cataplexy, we used high-resolution T1-weighted magnetic resonance imaging (MRI) in 12 patients compared with 12 healthy participants matched for age and gender. Subcortical and regional cortical volumes were measured using a method unbiased by non-linear registration. Further whole-brain analyses were conducted, measuring cortical characteristics, such as cortical thickness and gyrification, at thousands of points across each hemisphere using validated algorithms. Statistical analyses accounted for an effect of age and gender. We observed decreased cortical volume in the left paracentral lobule and increased cortical volume in the left caudal part of the middle frontal gyrus in narcoleptic patients compared with controls. Cortical thickness in prefrontal areas was inversely correlated with the severity of narcolepsy. Further, we observed several clusters of cortical thinning in patients with childhood or adolescent onset of narcolepsy compared with patients with adult onset of the disease. Our results suggest that specific anatomical changes may differentiate subgroups of narcolepsy patients with different clinical profiles (such as varying symptom severity or different age at onset). Future studies with larger groups of sleepy patients are required to assess whether distinct patterns of anatomical changes may distinguish narcolepsy from non-hypocretin-deficient hypersomnia disorders.  相似文献   

5.
We have studied diurnal changes in mean arterial pressure (MAP), heart rate (HR) and body temperature (Tb) during wake (W), non-rapid eye movement sleep (NREMS) and REM sleep (REMS) in the rat. Although HR and Tb show a similar sinusoidal diurnal variation during all vigilance states, the diurnal profile for the MAP is vigilance-state dependent. During W, MAP values are higher during the dark phase, during NREMS, no significant diurnal change is seen, and during REMS, the MAP exhibits a reversed diurnal change, being higher during the light phase. The low frequency component (0.25–0.725 Hz) in the power spectral density of the blood pressure, an index of sympathetic activity, is also higher during the light phase than the dark phase in REMS. The present findings suggest that diurnal changes in MAP in the rat result from the wake rhythm, and that the mechanism for the diurnal control of MAP may be different from that for HR or Tb.  相似文献   

6.
Excessive daytime sleepiness (EDS) is the core symptom of narcolepsy. However, there have been indications that fatigue – which should be separated from EDS – is also a frequent complaint. We determined the prevalence of severe fatigue in a group of narcolepsy patients and its relation with excessive daytime sleepiness, psychological distress, functional impairment and quality of life. We included 80 patients fulfilling the International Classification of Sleep Disorders (ICSD)‐2 diagnostic criteria of narcolepsy with cataplexy. Fatigue was measured using the Checklist Individual Strength (CIS). In addition psychological distress, including symptoms of depression, functional impairment and quality of life, were assessed. Comparisons were made between patients with (CIS‐fatigue score ≥ 35) and without severe experienced fatigue. Fifty patients (62.5%) reported severe fatigue. There were no sex or age differences between patients with and without severe fatigue. Both fatigued and non‐fatigued patients had the same amount of daytime sleepiness (Epworth Sleepiness Score 14.3 ± 4.2 versus 13.1 ± 4.4, P = 0.22), confirming the separation between sleepiness and fatigue. Interestingly, fatigued patients more often used stimulant medication (64% versus 40%, P = 0.02). Severe fatigue was associated with a significantly increased functional impairment, increased depressive symptoms and a lowered general quality of life. In conclusion, a majority of patients with narcolepsy suffer from severe fatigue, which can be distinguished from daytime sleepiness, and results in severe functional impairment.  相似文献   

7.
Cataplexy is pathognomonic of narcolepsy with cataplexy, and defined by a transient loss of muscle tone triggered by strong emotions. Recent researches suggest abnormal amygdala function in narcolepsy with cataplexy. Emotion treatment and emotional regulation strategies are complex functions involving cortical and limbic structures, like the amygdala. As the amygdala has been shown to play a role in facial emotion recognition, we tested the hypothesis that patients with narcolepsy with cataplexy would have impaired recognition of facial emotional expressions compared with patients affected with central hypersomnia without cataplexy and healthy controls. We also aimed to determine whether cataplexy modulates emotional regulation strategies. Emotional intensity, arousal and valence ratings on Ekman faces displaying happiness, surprise, fear, anger, disgust, sadness and neutral expressions of 21 drug‐free patients with narcolepsy with cataplexy were compared with 23 drug‐free sex‐, age‐ and intellectual level‐matched adult patients with hypersomnia without cataplexy and 21 healthy controls. All participants underwent polysomnography recording and multiple sleep latency tests, and completed depression, anxiety and emotional regulation questionnaires. Performance of patients with narcolepsy with cataplexy did not differ from patients with hypersomnia without cataplexy or healthy controls on both intensity rating of each emotion on its prototypical label and mean ratings for valence and arousal. Moreover, patients with narcolepsy with cataplexy did not use different emotional regulation strategies. The level of depressive and anxious symptoms in narcolepsy with cataplexy did not differ from the other groups. Our results demonstrate that narcolepsy with cataplexy accurately perceives and discriminates facial emotions, and regulates emotions normally. The absence of alteration of perceived affective valence remains a major clinical interest in narcolepsy with cataplexy, and it supports the argument for optimal behaviour and social functioning in narcolepsy with cataplexy.  相似文献   

8.
Narcolepsy with cataplexy is a lifelong disease resulting from the loss of hypocretin neurons in the hypothalamus; structural changes are not, however, limited only to the hypothalamus. We previously revealed an overall hippocampal volume loss in narcolepsy with cataplexy. The aim of this study is to describe the volume reduction of the anterior and posterior parts of the hippocampus in patients with narcolepsy with cataplexy in comparison with a control group. The anterior hippocampus is more involved in episodic memory and imagination, and the posterior hippocampus in spatial memory. Manual magnetic resonance imaging hippocampal volumetry was performed in 48 patients with narcolepsy with cataplexy and in 37 controls using the manual delineation technique in the ScanView program. All participants were examined on the same 1.5 T MR scanner; measurement was carried out as T1W 3D image with a slice thickness of 1.0/0 mm. There was a significant absolute loss of the total volume of the anterior hippocampus (sum of left and right) in patients with narcolepsy with cataplexy as compared with the controls (10.5%, p = .03 ANCOVA after correcting for total brain volume and multiple testing). We found a negative correlation between the total anterior hippocampus volume and the duration of the disease (R = ?0.4036, p = .016—corrected for multiple testing).  相似文献   

9.
Brief central apnoeas (CAs) during sleep are common in children and are not usually considered clinically significant unless associated with oxygen desaturation. CAs can occur spontaneously or following a movement or sigh. The aim of this study was to investigate acute cardiovascular changes associated with CAs in children. Beat‐by‐beat mean arterial pressure (MAP) and heart rate (HR) were analysed across CAs, and spontaneous and movement‐induced events were compared using two‐way analysis of variance with post hoc analyses. Fifty‐three children (28 male/25 female) aged 7–12 years referred for investigation of sleep‐disordered breathing (SDB) and 21 age‐matched healthy controls (8 male/13 female) were studied. Children underwent routine clinical polysomnography with continuous blood pressure (BP) recordings. Movement‐induced, but not spontaneous, CAs were more frequent in children with mild or moderate/severe obstructive sleep apnoea (OSA) compared with healthy controls (P < 0.05 for both). Movement‐induced CAs were associated with significantly larger MAP and HR changes across the event compared with spontaneous CAs. The percentage changes in MAP and HR between late‐event and post‐event were significantly greater for movement‐induced compared with spontaneous CAs (MAP 20.6 ± 2.3 versus 12.2 ± 1.8%, P < 0.01; HR 28.2 ± 2.6 versus 14.7 ± 2.5%, P < 0.001). This study demonstrates that movement‐induced CAs are more common in children with OSA, and are associated with significantly greater changes in HR and BP compared with spontaneous CAs. These data suggest that movement‐induced CAs should be considered when assessing the cardiovascular impact of SDB.  相似文献   

10.
Narcolepsy with hypocretin deficiency is known to alter cardiovascular control during sleep, but its aetiology is disputed. As cardiovascular control differs between sleep states, and narcolepsy affects sleep architecture, controlling for both duration and transitions of sleep states is necessary. This study therefore aimed to assess heart rate and its variability in narcolepsy during sleep taking these factors into account. The study included 12 medication‐naïve patients with narcolepsy with cataplexy and hypocretin deficiency (11 male, 16–53 years old), and 12 sex‐ and age‐matched healthy controls (11 male, 19–55 years). All subjects underwent 1‐night ambulatory polysomnography recording. Cardiovascular parameters were calculated for each 30‐s epoch. Heart rate was significantly higher in patients with narcolepsy than in controls in all sleep states and during wakefulness prior to sleep. Groups did not differ in heart rate variability measures. The effects of sleep state duration on heart rate and its variability were similar between patients and controls. In conclusion, heart rate was consistently higher in patients with narcolepsy than controls, independent of sleep stage and sleep fragmentation. A direct effect of hypocretin deficiency therefore seems probable.  相似文献   

11.
Risk for adverse cardiovascular events increases when blood pressure does not decrease at night (“non-dipping,” <10% decrease from daytime blood pressure). Shiftwork alters relationships between behaviors and endogenous circadian rhythms (i.e., circadian disruption along with variable sleep timing), and chronic shiftwork increases cardiovascular disease risk. To determine whether transitioning into shiftwork changes the overnight blood pressure dipping pattern, we leveraged a natural experiment that occurs when newly-hired bus operators transition from a daytime training schedule into an early-morning shiftwork or daywork schedule. Twenty participants were studied in a 90-day protocol upon new employment and underwent cardio-metabolic health assessments, including ambulatory blood pressure monitoring, and weekly sleep-wake diaries. Measurements were repeated after ~30 and 90 days after transitioning to a day or an early-morning shiftwork schedule. Newly-hired shiftworkers displayed dramatic changes in overnight blood pressure, with 62% converting from a healthy dipping blood pressure to the nondipping pattern, resulting in 93% of shiftworkers displaying a nondipping phenotype at 90-days. In contrast, 50% of dayworkers had a nondipping profile at baseline and this decreased to 0% at 90-days, a significant difference from shiftworkers (p = .001). At 90-days, overnight blood pressure dipping was ~7% less in shiftworkers than dayworkers (–6.3% [95%CI –3.7 to –8.8%] vs –13.1% [–10.3 to –15.9%]: p < .01), with changes in dipping associated with changes in sleep timing variability (r2 = .28, p = .03). The observed changes in overnight blood pressure dipping in newly-hired early-morning shiftworkers, which were associated with sleep timing variability, may be an early warning sign of increased cardiovascular risk among shiftworkers.  相似文献   

12.
The month of birth has been proposed as a risk factor for narcolepsy, suggesting a harmful influence during early development. Several authors have described an excess of births in March in those developing narcolepsy later. Analysis methods in published studies varied, but no study corrected completely for possible changes in seasonal birth pattern over time in the appropriate population. The present study describes changes in seasonal birth pattern of the entire Dutch population over a 79-year span and compared the monthly birth pattern of Dutch narcoleptics with the population data. Month and year of birth were noted for 307 patients with non-familial narcolepsy with cataplexy, born in the Netherlands between 1923 and 2001. The numbers of live births per month and per year from the entire Dutch population for the same period were used to calculate a virtual data set of expected births per month with exactly the number of cataplexy cases, but with the birth pattern of the Dutch population. Observed and expected numbers per month were compared using the chi-square test. In the 1970s the peak of births shifted from spring to autumn, confirming the need to correct for changing seasonal patterns. There was no significant difference between observed and expected birth numbers per month. An effect of birth month on the occurrence of narcolepsy with cataplexy was not found in a study of 307 cases after adjusting for changing birth patterns in the general population.  相似文献   

13.
SUMMARY  The prevalence of hypertension in patients with obstructive sleep apnoea (OSA) is high and blood pressure profile is characterized by nocturnal blood pressure (BP) elevation and increased nocturnal BP variability. Ambulatory 24-hour-biood pressure monitoring (ABPM) is a valid, non-invasive method to describe circadian BP variation. Circadian BP profile and nocturnal BP variability were related to OSA severity (apnoea-hypopnoea index, mean low O2), age and body mass index (BMI) in 73 patients with OSA. Prevalence of hypertension was 75%, and in 59% BMI was greater than 30 kg m-2. A nocturnal decline of at least 10% from daytime mean BP values (night/day BP ratio <0.9; dipper) was found in only 25% of hypertensive patients and 39% of normotensive patients. Comparison between dippers and non-dippers showed significant differences in apnoea severity (apnoea-hypopnoea index 32 + 19 vs. 50 + 23/h, P <0.01; mean low O2 84.5 + 4 vs. 80.2 + 5.8%, P< 0.01) but not for age and BMI. In multiple regression analyses with age, body mass index, apnoea-hypopnoea index and mean low O2 as independent and BP ratios and BP variability as dependent variables, sleep apnoea severity was the only independent predictor for circadian BP rhythm and nocturnal BP variability. The results presented here suggest that independent of age and obesity the severity of sleep apnoea is an important determinant of circadian BP variation and nocturnal BP variability.  相似文献   

14.
STUDY OBJECTIVES: To study the prevalence of and symptoms of eating disorders in patients with narcolepsy. DESIGN: We performed a case-control study comparing symptoms of eating disorders in patients with narcolepsy versus healthy population controls, using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN 2.1). To study whether an increased body mass index (BMI) could be responsible for symptoms of an eating disorder, we also compared patients with BMI-matched controls, using the SCAN as well as the Eating Disorder Examination-Questionnaire. SETTING: University hospital. PATIENTS AND PARTICIPANTS: Patients with narcolepsy/cataplexy (n = 60) were recruited from specialized sleep centers. Healthy controls (n = 120) were drawn from a population study previously performed in the Netherlands. Separately, 32 BMI-matched controls were recruited. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: In total, 23.3% of the patients fulfilled the criteria for a clinical eating disorder, as opposed to none of the control subjects. Most of these were classified as Eating Disorder-Not Otherwise Specified, with an incomplete form of binge eating disorder. On the symptom level, half of the patients reported a persistent craving for food, as well as binge eating. Twenty-five percent of patients even reported binging twice a week or more often. When compared with BMI-matched controls, the significant increases persisted in symptoms of eating disorders among patients with narcolepsy. Except for a higher level of interference in daily activities due to eating problems in patients using antidepressants, medication use did not influence our findings. CONCLUSIONS: The majority of patients with narcolepsy experience a number of symptoms of eating disorders, with an irresistible craving for food and binge eating as the most prominent features. Eating disorder symptomatology interfered with daily activities. These findings justify more attention for eating disorders in the treatment of patients with narcolepsy.  相似文献   

15.
In the absence of a golden standard for the diagnosis of narcolepsy, the clinical spectrum of disorder remains controversial. The aims of this study were (1) to determine frequency and characteristics of sleep-wake symptoms in patients with narcolepsy with cataplexy, (2) to compare clinical characteristics with results of ancillary tests, and (3) to identify factors that discriminate narcolepsy from other conditions with excessive daytime sleepiness (EDS). We prospectively studied 57 narcoleptics with cataplexy, 56 patients with non-narcoleptic hypersomnia (H), and 40 normal controls (No). Based on suggested and published criteria, we differentiated between narcoleptics with definite cataplexy (N) and narcoleptics without definite cataplexy (possible cataplexy, NpC). Assessment consisted of questionnaires [all patients and controls, including the Ullanlinna Narcolepsy Score (UNS)], polysomnography (all patients), multiple sleep latency test (MSLT) and human leukocyte antigen typing (in most narcoleptics). A new narcolepsy score based on five questions was developed. Data were compared with those of 12 hypocretin-deficient narcoleptics (N-hd). There were significant differences between N and NpC (including mean sleep latency on MSLT), but none between N and N-hd. A score of sleep propensity during active situations (SPAS) and the frequency of sleep paralysis/hallucinations at sleep onset, dreams of flying, and history of sleep shouting discriminated N from H and No (P < 0.001). Cataplexy-like symptoms in H (18%) and No (8%) could be discriminated from 'true' cataplexy in N on the basis of topography of motor effects, triggering emotions and triggering situations (P < 0.001). Our narcolepsy score had a similar sensitivity (96% versus 98%) but a higher specificity (98% versus 56%) than the UNS. Analysis of co-occurring symptoms in narcolepsy revealed two symptom complexes: EDS, cataplexy, automatic behaviors; and sleep paralysis, hallucinations, parasomnias. Low/undetectable cerebrospinal fluid hypocretin-1 levels and a history of definite cataplexy identify similar subgroups of narcoleptics. Specific questions on severity of EDS (SPAS score) and characteristics of cataplexy allow the recognition of subgroups of narcoleptics and their differentiation from non-narcoleptic EDS patients, including those reporting cataplexy-like episodes. The existence of co-occurring symptoms supports the hypothesis of a distinct pathophysiology of single narcoleptic symptoms.  相似文献   

16.
Background: There is a lack of data on the prevalence of pre-high blood pressure (PreHBP) and high blood pressure (HBP), based on recent international blood pressure references, in non-overweight children and adolescents.

Aim: To describe the prevalence of PreHBP and HBP in non-overweight children and adolescents in developed regions of China.

Subjects and methods: In total, 588?097 non-overweight children and adolescents aged 6–17?years from the National Surveys on Chinese Students’ Constitution and Health in 2015 were included.

Results: The prevalence of PreHBP was 13.41% and subjects in urban areas had a higher prevalence of PreHBP (14.14%) than those in rural areas (12.92%). Subjects in regions with a high (13.56%) or moderate (13.61%) socioeconomic status showed a higher prevalence of PreHBP than those in regions with a relatively low socioeconomic status (12.76%). A similar pattern was found for the prevalence of HBP, and the prevalence of HBP was 18.25% for all participants, 20.55% for subjects in urban areas, 16.71% in rural areas, 18.76% in high socioeconomic areas, 18.62% in moderate socioeconomic areas and 16.70% in relatively low socioeconomic areas.

Conclusion: A large proportion of non-overweight children and adolescents had elevated blood pressure and there were urban–rural and socioeconomic disparities in the prevalence of elevated blood pressure.  相似文献   

17.
18.
Many diabetics are cold-intolerant and experience dramatic changes in normal systemic function during hypothermia. Little is known of the cardiovascular adjustments in diabetics exposed to an acute cold stress. In an effort to identify the alterations in mean arterial blood pressure (MAP) and heart rate (HR) in the diabetic during environmental cooling (10 ± 2 °C), we compared the in vivo MAP and HR responses of urethane-anaesthetized (1.5 g kg?1), streptozotocin-diabetic (STZ, 65 mg kg?1, n = 12) and control (CON, n = 10) rats during acute hypothermia. MAP was measured directly via an indwelling carotid artery cannula and HR was calculated from the peak systolic pressure waves. Overall, the STZ rats were more cold-intolerant than CON as evidenced by the greater rate of decline in colonic temperature (Tc) from 36 to 28 °C (STZ, 0.16 °C min?1 vs. CON, 0.06 °C min?1; P < 0.05). Prior to cooling, HR was significantly lower (P < 0.05) in STZ (282 ± 9 beats min?1) than in CON rats (399 ± 24 beats min?1); however, during the acute hypothermic period, HR displayed a similar rate of decline in both groups. With respect to MAP, both groups demonstrated similar pre-experimental pressor responses (CON, 81.7 ± 5.4 vs. STZ, 83.2 ± 5.1 mmHg, P > 0.05). During progressive hypothermia, MAP gradually increased (P < 0.05) in the CON group from baseline (Tc = 36 °C) and reached peak values (118.4 ± 2.5 mmHg) at Tc = 30 °C, while the STZ group failed to exhibit any cold pressor response. At the conclusion of the experiment (Tc = 28 °C), the STZ group pressor response to hypothermia was not different from baseline (Tc = 36 °C, 83.2 ± 5.1 vs. Tc = 28 °C, 77.4 ± 3.4 mmHg; P > 0.05). The absence of any pressor response in the diabetic group during progressive hypothermia reflects the poor overall vasoconstrictive capacity to cooling and could partially explain the rapid decline of core temperature in this group.  相似文献   

19.
肥胖儿童血压及其与X线心脏大小的关系   总被引:1,自引:0,他引:1  
目的:探讨不同判定标准下3~7岁单纯肥胖儿童高血压发生率,以及血压与心脏大小的相关性。方法:体质测量、血压测量、X线测量心脏大小,对有关数据的相关性进行统计学分析。结果:肥胖儿童血压及不同标准下高血压检出率显著地高于正常儿童。高血压肥胖儿童心脏大小10个指标均大于非高血压肥胖者。血压与心脏面积、心脏体积呈低~中度相关。结论:高血压肥胖儿童心脏向各个方向增大,与非高血压者有显著差异。血压与心脏体积指数关系不密切,血压升高,会引起心脏增大和受累。  相似文献   

20.
Chronobiological Laboratories, University of Minnesota, Minneapolis, USA. Department for Newborn and Premature Infants, Research Institute of Pediatrics, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR M. Ya. Studenikin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 112, No. 8, pp. 202–205, August, 1991.  相似文献   

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