Horizontal optokinetic ocular nystagmus in wildtype (B6CBA+/+) and weaver mutant mice

Summary Horizontal optokinetic nystagmus (OKN) evoked by a random dot pattern moving at a constant speed around the animal was investigated in wild-type mice and Weaver mutants (cerebellar impairment) by means of chronically implanted EOG-electrodes. The shape of OKN in the homozygotic Weaver mouse was clearly different from that in normal mice. The OKN in the mutant showed inconstant velocity during the slow phase. Nystagmus frequency of the mutant was significantly below that of normal controls for velocities of 1.4 to 25 degrees · s^-1. In one group of normals the mean slow-phase gain was relatively constant for stimulus angular velocities between 1.4 and 15 degrees · s^-1 and declined thereafter. In a second group the mean slow-phase gam decreased gradually between stimulus angular velocities from 1.4 to 15 degrees · s^-1 and thereafter with a steeper slope. In mutants gain decreases with increasing stimulus velocity over the entire range tested (1.4 to 42 degrees · s^-1). Normals and mutants with one eye occluded exhibited strong OKN when the pattern was moved in a temporonasal direction; little response was obtained by stimuli moving in a naso-temporal direction.     

Effekte einer Captopriltherapie auf die Natrium- und Wasserausscheidung bei Patienten mit Leberzirrhose und Aszites

Summary Ascites in patients with cirrhosis of the liver frequently is refractory to diuretic treatment. It was postulated that vasoconstriction of the renal cortex, mediated by activation of the renin-angiotensin-aldosterone-system (RAAS), may be one course of the disturbed sodium- and water-excretion in these patients. We therefore investigated in 14 cirrhotic patients with ascites under constant diuretic treatment the effects of low-dose captopril therapy on urinary sodium- and potassium-excretion, body weight, abdominal girth, serum-sodium,-potassium, creatinine-clearance, plasma-renin-activity (PRA), plasma-aldosterone (PA) and mean arterial pressure (MAP). After a control period of 4 days the patients received 2 × 6.25 mg/d captopril for 5 days and 4 × 6.25 mg/d for further 5 days. Treatment was followed by a second control period without captopril.PRA increased significantly after 2 days of captopril treatment. 2 × 6.25 mg/d captopril induced a significant increase in sodium excretion and a significant decrease of body weight. MAP decreased slightly but significantly without clinical signs of hypotension. 4 × 6.25 mg/d captopril resulted in a further reduction of body weight and a further enhancement of sodium excretion. Three days after withdrawal of captopril sodium output was significantly reduced again. Conclusion: In cirrhotic patients low-dose captopril seems to be efficient in the treatment of ascites resistant to diuretics without causing major side effects.

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Abkürzungen ACE Angiotensin-Converting-Enzym - A-II Angiotensin II - C_{H 2 O} Frei-Wasser-Clearance - C_Krea Kreatinin-Clearance - C_Osmo Osmolale Clearance - g Gramm - h Stunde - kg Kilogramm - l/d Liter pro Tag - MAP Mittlerer arterieller Blutdruck - mg Milligramm - mg/d Milligramm pro Tag - ml/min Milliliter pro Minute - mmHg Millimeter Quecksilbersäule (Torr) - mmol/d Millimol pro Tag - NaCl Natriumchlorid - ng/ml/h Nanogramm pro Milliliter und Stunde - PA Plasma-Aldosteron - pg/ml Picogramm pro Milliliter - PRA Plasma-Renin-Aktivität - RAAS Renin-Angiotensin-Aldosteron-System - SEM Standardfehler des Mittelwertes - S_Krea Kreatininkonzentration im Serum - S_Osm Serum-Osmolalität - U_Krea Kreatininkonzentration im Urin - U_Osm Urin-Osmolalität - V Urinminutenvolumen - vgl. vergleiche - µmol/l Micromol pro Liter     

盐酸多奈哌齐对轻、中型脑外伤患者认知障碍的治疗作用

目的 探讨盐酸多奈哌齐对轻、中型脑外伤患者认知障碍及临床预后的影响。方法 78例轻、中型脑外伤并认知障碍患者被随机分成治疗组和对照组，治疗组应用盐酸多奈哌齐10mg／d，对照组应用吡拉西坦8mg，一日3次服用，两组的治疗周期为12周。治疗前及治疗后12周，分别应用简明精神状态检测量表（MMSE）、国人修订成人韦氏智利量表（WAIS-RC）和格拉斯哥预后评分（GOS）评价疗效。结果 两组在治疗后12周，MMSE和WAIS-RC评分均较治疗前提高（P〈0．05）。治疗后12周，治疗组MMSE和WAIS-RC评分较对照组高（P〈0．05），治疗组GOS预后优良率明显优于对照组（P〈0．05）。结论 盐酸多奈哌齐对轻、中型脑外伤后认知障碍有积极治疗作用，并能改善临床预后。     

A mutational hot spot in the KCNQ4 gene responsible for autosomal dominant hearing impairment

Several different mutations in the KCNQ4 K+ channel gene are responsible for autosomal dominant nonsyndromic hearing impairment (DFNA2). Here we describe two additional families originating from Europe and Japan with a KCNQ4 missense mutation (W276S) that was previously found in one European family. We compared the disease-associated haplotype of the three W276S-bearing families using closely linked microsatellite markers and intragenic single nucleotide polymorphisms. Differences between the haplotypes were found, excluding a single founder mutation for the families. Therefore, the W276S mutation has occurred three times independently, and most likely represents a hot spot for mutation in the KCNQ4 gene.     

The Recuperative Effects of REM Sleep and Stage 4 Sleep on Human Performance After Complete Sleep Loss: Experiment 1

Twelve young (17–21 yrs) male Navy recruits volunteered for a sleep loss study. After 4 baseline days, the Ss were completely deprived of sleep for 2 days and nights. Next followed an experimental phase of 2 days and nights after which all Ss received 2 nights of uninterrupted sleep. During the experimental phase, the 4 Ss in the REM-deprived group were aroused whenever they showed signs of REM sleep. The 4 Ss of the stage 4-deprived group were aroused whenever they showed signs of entering stage 4 sleep, and the 4 Ss of the Control group had uninterrupted sleep. All tests (speed and accuracy of addition, speed and accuracy of self-paced vigilance, errors of omission in experimenter paced vigilance, immediate recall of word lists, and mood) showed significant impairment after the first night of complete sleep loss. But during the experimental (sleep-stage-deprivation) and recovery phases, all three groups showed equal rates of recovery. Depriving the S of stage REM or stage 4 during recovery sleep does not affect the recuperation rate. Frequent arousals (50–100 per night) also do not impair recovery. The amount of sleep is probably more important than the kind of sleep.     

脑卒中后抑郁及其对神经功能康复的影响

目的:观察脑卒中后抑郁(Post-Stroke Depression,PSD)的发生率和相关因素;探讨选择性5-HT抑制剂对脑卒中后抑郁神经功能康复的影响.方法:选取急性脑脑卒中患者132例(脑梗死78例,脑出血54例),分别在病程2周、1,3,6,12月时给每一位入组患者行PSD诊断、神经功能缺损评分、日常生活能力评分(Activity of Daily Living Scale,ADL)、汉密尔顿抑郁量表(Hamilton Depression Scale,HAMD)评分;同时完成Zung's抑郁自评量表(Self-Rating Depression Scale,SDS)和焦虑自评量表(Self-Rating Anxiety Scale,SAS).结果:①脑卒中患者中约44.70%出现抑郁症状;②脑卒中类型和性别与PSD发生率无相关性(P＞0.05);③PSD的发生率和严重程度与神经功能缺损和日常生活能力下降程度有关.④PSD与病变部位、病灶大小、病灶单侧性均无明显相关(P＞0.05);⑤氟西汀抗抑郁治疗能明显改善病程3、6个月时的神经功能缺损,病程12月时不仅抑郁症状减轻,日常生活能力改善,神经功能缺损减轻尤为显著.结论:脑卒中后抑郁是急性脑血管病患者常见的长期并发症,并可影响患者功能康复的速度和程度.抗抑郁剂治疗能在抑郁症状明显改善的同时,促进患者日常生活能力和神经功能的恢复.     

Prevalence of mitochondrial DNA mutations in childhood/congenital onset non-syndromal sensorineural hearing impairment

Genetic factors are the major causes of childhood hearing impairment. Whereas autosomal recessive mutations account for the majority of prelingual non-syndromic sensorineural hearing impairment (NSSHI), the relative contribution of mitochondrial DNA (mtDNA) mutations to childhood onset NSSHI has not been established.
We screened 202 subjects with congenital/childhood onset NSSHI, consisting of 110 sporadic cases, 75 sib pairs, and 17 families with affected subjects in more than one generation, in order to determine the prevalence of mtDNA mutations associated with NSSHI.
mtDNA mutations were found in three of 10 families (30%) in whom the affected members were related through the maternal lineage. One sporadic case (0.9%) was also found to have a known mtDNA mutation but none was found in the sib pairs.
Although the prevalence of mtDNA mutations was low in the group as a whole (2%), we suggest that screening should be considered in cases of childhood hearing impairment when it is progressive and particularly in families where transmission is compatible with maternal inheritance.


Keywords: mitochondrial DNA; point mutation; hearing impairment     

Pharmacokinetics and effects on blood pressure of a single oral dose of milrinone in healthy subjects and in patients with renal impairment

Summary Milrinone, a new, nonglycosidic inotropic agent with peripheral vasodilating properties, was given as a single oral 5 mg dose to 7 healthy subjects, 7 patients with moderate renal impairment (CRI I, creatinine clearance 30–63 ml/min) and 7 patients with severe renal impairment (CRI II, creatinine clearance 9–29 ml/min). All except one of the patients with renal impairment had hypertension. The mean urinary recovery of milrinone was 82% in healthy subjects, the renal clearance was 288 ml/min and the plasma half-life (t_1/2) was 0.94 h. In CRI the mean plasma t_1/2 was prolonged (CRI I 1.78 h, CRI II 3.24 h). There was a significant linear relationship between creatinine clearance and the elimination rate constant, and between creatinine clearance and the renal clearance of milrinone. During the study day there was a tendency to a decrease in supine BP from 1 to 6–8 h after dosing, with the maximal decrease at 2–3 h (healthy subjects 118/71107/56, CRI 159/95136/79 mmHg). The same degree of change was seen in standing BP. A slight rise in standing HR was seen from 2–6 h after dosing. Changes in BP and HR are difficult to evaluate since the study was not placebo-controlled.The plasma elimination rate of milrinone was decreased in CRI and dose adjustment may be necessary. Placebo-controlled studies of milrinone in hypertensive patients would be required to validate its possible antihypertensive effect.     

Dose-dependent impairment in the performance of a go-no go successive discrimination by chlordiazepoxide

After learning a light-cued, go-no go successive discrimination to criterion, male Sprague-Dawley rats received 0, 5, or 10 mg/kg chlordiazepoxide on six performance sessions, followed by two drug-recovery (saline) sessions. Chlordiazepoxide impaired discrimination performance in a dose-dependent manner, with animals in the 5 mg/kg dose condition demonstrating tolerance to the drug after two performance sessions. The degree of discrimination impairment in both drug dose conditions paralleled an increase in responding during no-go phases of the performance task. These findings are consistent with a disinhibitory hypothesis of performance impairment and suggest that CDP-drugged animals have difficulty in withholding incorrect responses.These data were presented at the Annual Meeting of the Psychonomic Society, San Antonio, Texas, 1984     

血管性认知障碍肾阳虚证的调查研究及DNA甲基化本质

目的：在病证结合背景模式下,调查血管性认知障碍肾阳虚证的分布情况并从DNA甲基化角度探讨血管性认知障碍肾阳虚证的生物学内涵,为未来中医药治疗该病证提供表观遗传学层面的靶点。方法：2020年9月至2022年11月,通过量表对北京社区居民进行认知障碍筛查,对血管性认知障碍（VCI）患者进行证候分析;后纳入VCI肾阳虚证患者与健康对照者,采集外周血,采用Illumina Human Methylation 850K BeadChip对受试者的外周静脉血进行全基因组DNA甲基化检测,筛选差异甲基化基因并对其进行生信分析。结果：研究共调查1 902人,患有VCI的人数为201例,占总调查人数的10.57%,其中肾阳虚证者占72.14%;甲基化结果显示,与正常组比较,VCI组有386个差异甲基化位点,可注释到136个基因。京都基因与基因组百科全书（KEGG）信号通路富集分析显示,两组间差异基因主要涉及哺乳动物雷帕霉素靶蛋白（mTOR）信号通路、雌激素（Estrogen）信号通路、环磷酸腺苷（cAMP）信号通路等通路。蛋白质-蛋白质相互作用（PPI）网络分析显示,表皮生长因子受体（EGFR）、EGF...