危重新生儿应激性高血糖及其预后分析

目的探讨危重新生儿预后与应激性高血糖之间的关系。方法对85例危重新生儿入院后即采静脉血用葡萄糖氧化酶法测血糖,血糖>7mmol/L诊断为高血糖,此后应用微量血糖仪进行动态监测。结果入院时高血糖者56例,占65.9%,治愈组与死亡组的血糖值分别为7.38±2.70、17.8±8.50mmol/L(P<0.01);无脏器功能衰竭、单器官及多器功能衰竭患儿的血糖分别为6.02±2.82、10.8±3.85、14.1±4.80mmol/L(P<0.01)。高血糖与器官功能衰竭关系密切,血糖越高,病情越严重,预后越差。结论危重新生儿血糖水平可作为预后判断的一项依据。     

Alcohol consumption and impaired glycoregulation results in a population of 6665 salaried employees

Alcohol consumption and glycosuria were found to be associated (p < 0.001) in a population of 6571 salaried employees who underwent a systematic examination. The prevalence of glycosuria was found to range from 1.3% among 2609 non-drinkers to 5% among 816 heavy drinkers (six glasses or more of alcoholic beverage daily). This association was still significant after adjustement for age, sex and body mass index. Similarly, a positive association was observed between fasting glycemia and alcoholic intake in a subgroup of 998 subjects when such a result was available (p < 0.05).     

Focal ischemia of the rat brain,with special reference to the influence of plasma glucose concentration

Summary Focal cerebral ischemia was induced by occlusion of the right middle cerebral artery in hypoglycemic, normoglycemic, as well as in acute and chronic diabetic rats. The brain damage was studied after 4 days. The volume of infarction was decreased in hypoglycemia (29±19 mm³ (mean±SD) versus 58±35 mm³,P<0.0046), unaltered in acute diabetes (61±45 mm³), and increased in chronic diabetes (91±22 mm³,P<0.0463). The cortex adjacent to the infarct showed selective neuronal injury affecting the cortical layers 2 and 3. The damage was enhanced by hypoglycemia and prevented in most of the diabetic animals. The findings indicate that different mechanisms cause infarction and selective neuronal injury outside infarcts, but that both are influenced by the plasma glucose concentration.     

Cell volume regulation: a review of cerebral adaptive mechanisms and implications for clinical treatment of osmolal disturbances: II

Cerebral cell volume regulatory mechanisms are activated by sustained disturbances in plasma osmolality. Acute hypernatremia causes a predictable shrinkage of brain cells due to the sudden imposition of a plasma-to-cell osmolal gradient. However, during chronic hypernatremia cerebral cell volume is maintained close to the normal range as a result of the accumulation of electrolytes and organic osmolytes including myo-inositol, taurine, glutamine, glycerophosphorylcholine, and betaine. The increased cytosolic level of these molecules is generally accomplished via increased activity of sodium (Na⁺)-dependent cotransport systems. The slow dissipation of these additional osmotically active solutes from the cell during treatment of hypernatremia necessitates gradual correction of this electrolyte abnormality. Acute hyponatremia leads to cerebral cell swelling and severe neurological dysfunction. However, prolonged hyponatremia is associated with significant reductions in brain cell electrolyte and organic osmolyte content so that cerebral cell volume is restored to normal. While acute hyponatremia can be treated with the administration of moderate doses of hypertonic saline in order to control seizure activity, chronic hyponatremia should be corrected slowly in order to prevent subsequent neurological deterioration. If the rate of correction exceeds 0.5 mmol/l per hour, or if the total increment in serum [Na⁺] exceeds 25 mmol/l in the first 48 h of therapy, then there is an increased risk of the development of cerebral demyelinating lesions. Chronic hyperglycemia activates the brain cell volume regulatory adaptations in the same manner as hypernatremia. Therefore, during the treatment of diabetic ketoacidosis, it is imperative to restore normoglycemia gradually in order to prevent the occurrence of cerebral edema. It is possible that excessive administration of electrolyte-free solutions and high doses of insulin may increase the risk of this complication. While there are some data to suggest that brain cell size is disturbed during acute uremia, additional work is necessary to clarify the role of cerebral cell volume regulation during acute and chronic uremia.     

高血糖导致肾脏高灌注的机制研究

探讨了高血糖对整体大鼠和离体灌注鼠肾（ＩＰＲＫ）血流动力学的影响及其机制。结果显示：高血糖在整体大鼠和ＩＰＲＫ均可引起肾血浆流量（ＲＰＦ）、肾小球滤过率（ＧＦＲ）的增加；在ＩＲＰＫ阻断管－球反馈后，高血糖不再能诱发上述改变；结构和葡萄糖相似的Ｄ－α－甲基－葡萄糖苷在ＩＰＲＫ可引起与相同渗透浓度的葡萄糖相似的ＲＰＦ，ＧＦＲ增加；血红蛋白不改变高血糖对肾血流动力学的影响。提示：高血糖可支接引起肾脏高灌注、高滤过，其机制主要是对管一球反馈的抑制，此抑制效应可能与葡萄糖的结构相关。内皮由来性舒张因子（ＥＤＲＦ）在高血糖导致的ＩＰＲＫ高灌注中不起主要作用。     

Diabetic and nondiabetic hyperglycemia in the ICU

Hyperglycemia is a common feature in critically ill patients, whether they are diabetic or not, and it is associated with unfavorable outcome. The more severe the underlying disease, the more important the hyperglycemia appears to be although, we still cannot define whether hyperglycemia is just a marker of the severity of the acute illness or rather an active contributor to poor outcome. The review of the literature on this subject published from 2001 up today conveys a massive amount of information the interpretation of which is equivocal, due to the heterogeneity of patients (nondiabetic vs. diabetic, medical intensive care unit (ICU) pts vs. surgical ICU pts) and of interventions (dose and modality of insulin infusion).The association between high glucose level and mortality is strong in critically ill patients without a previous history of diabetes. Admission hyperglycemia seems to be an independent risk factor of in-hospital mortality in patients both with and without diabetes in cardiac, cardiothoracic and neurosurgical ICUs. No data are still available on general surgical ICU patients.Tight control of blood glucose levels has been demonstrated to improve outcome in both diabetic and nondiabetic critically ill patients. In surgical ICUs, tight glucose control improves mortality and reduces morbidity only among patients admitted in ICU for more than 5 days, while outcome is not improved in patients who stay in ICU for less than 3 days.However, it is not yet understood if such favorable effect is secondary to glucose control itself or if insulin plays a part, by means of its nonglucose, anabolic effects. More randomized controlled trials are needed, addressing specific issues—such as the optimal target glucose concentration and the most effective insulin regimen—especially in the general surgical patient.     

Immunological blockade of endogenous thyrotropin-releasing hormone impairs recovery from hyperglycemia in mice

Administration of antiserum to thyrotropin-releasing hormone (TRH) into the lateral cerebral ventricle of mice significantly attenuated recovery from hyperglycemia induced by treatment with 2-deoxyglucose but had no effect on the plasma glucose of saline-treated mice. TRH, injected centrally together with the anti-TRH antibody, reversed the effect of the antiserum and blocked the development of hyperglycemia. These findings suggest that activation of TRH neurons in the central nervous system may be a physiological event influencing recovery from hyperglycemia.     

急性脑卒中患者应激性高血糖危险因素分析

目的 探讨重症监护室（ICU）急性脑卒中患者应激性高血糖的危险因素。方法对50例急性（发病5d内1非糖尿病脑卒中患者监测血糖7-14d，比较高血糖及正常血糖两组患者年龄、糖皮质激素、临床肺部感染评分等对血糖的影响。结果高血糖组临床肺部感染评分（CPIS）为4．77±2．11，显著高于正常血糖组的3．36±2．36（P〈0．05），急性生理学及慢性健康状况评分（APACHEⅡ）高血糖组为16．23＋5．40，也显著高于正常血糖组的12．43±3．83，有显著性差异（P〈0．01）。结论CHS和APACHEⅡ升高可能是ICU非糖尿病卒中后应激性高血糖的危险因素。     

Inhibitory effect of ketamine on phosphorylation of the extracellular signal-regulated kinase1/2 following brain ischemia and reperfusion in rats with hyperglycemia

To determine if the inhibitory effects of ketamine on the extracellular signal-regulated kinase (ERK) 1/2 are involved in reduction of the hyperglycemia-exaggerated cerebral ischemic lesion, rats with normoglycemia, hyperglycemia, or hyperglycemia supplemented with ketamine were subjected to 15 min of forebrain ischemia, and then, reperfusion for 0.5, 1, and 3h. Phosphorylation of ERK1/2 in the brain tissues was assessed by immunohistochemistry and Western blot analysis. In rats with normoglycemia, we demonstrated a moderate increase of the ERK1/2 phosphorylation in the cingulum cortex and hippocampus CA3 following an ischemic intervention. It quickly dropped to control levels after reperfusion for 0.5h. In rats with hyperglycemia, however, the increase of the ERK1/2 phosphorylation in these areas was significantly higher in all animals reperfused. The neuronal death, detected by the TdT-mediated-dUTP nick end labeling assays, was found in the cingulum cortex (5.23+/-2.34, per high power feild) and hippocampus CA3 areas (6.29+/-3.68, per 1mm(2)) in hyperglycemic group after reperfusion for 3h. With ketamine treatment, the ERK1/2 phosphorylation in cingulum cortex and hippocampus CA1 and CA3 areas was found to be the same as that in normoglycemia rats. Our results suggest that hyperglycemia may increase the ischemic insult through modulation of the signal transduction pathways involving ERK1/2. The inhibitory effects of ketamine on the hyperglycemia-activated ERK1/2 phosphorylation are probably through inhibition of the N-methyl d-aspartate-mediated calcium influx, which subsequently reduce the hyperglycemia-exaggerated cerebral damage.     

Substantia nigra damage induced by ischemia in hyperglycemic rats

Summary Preischemic hyperglycemia induced by feeding or glucose infusion worsens the brain damage and the clinical outcome following ischemia of a given duration and density, and characteristically causes postischemic seizure activity. Light microscopy has previously showed that, in the rat, transient hyperglycemic ischemia induced by bilateral carotid occlusion in combination with arterial hypotension causes a uni- or bilateral lesion in the pars reticulata of the substantia nigra. Since this region has a central role in preventing seizure discharges the present study was carried out to determine the ultrastructural characteristics of this lesion. In rats with 10 min of transient hyperglycemic ischemia followed by recirculation for 1 to 18 h, the pars reticulata of the substantia nigra showed signs of status spongiosus, as well as extensive nerve cell alterations. These changes were observed after all recovery periods studied. The spongiotic appearance was mainly caused by swelling of dendrites and, to a lesser degree, by astrocytic swelling. The dendrites were expanded at all recovery times but the severity increased during the later periods of recirculation. These swollen dendrites contained severely expanded mitochondrias and endoplasmic reticulum. The cytoskeletal elements showed disordered lining of microtubules. Two major types of nerve cell alterations were present: a pale and a dark variety. The pale type was the most frequent cell alteration. It occurred in all experimental groups and at all time points. Redistribution of the nuclear chromatin and of cytoplasmic organelles as well as swelling of the same type as in the dendrites were the essential changes. The dark neurons were much fewer in number and occupied a peripheral position in the pars reticulata. Astrocytic foot processes appeared to be dilated around the dark neurons. Swelling of astrocyte processes was most pronounced in the 1 h recovery animals. Both types of neurons showed severe mitochondrial alterations of the type observed in dendrites. Occasionally, mitochondrial alterations were found in astrocytic processes as well. Blood vessel alterations were lacking. Previous studies have shown that in this model of ischemia the substantia nigra has a relatively well-preserved blood perfusion. In view of this the extensive histopathological lesions are surprising. We speculate that the lesions primarily involve excitotoxic damage to dendrites, with pronounced lactic acidosis playing a contributory role in causing axonal and glial pathology as well.Supported by grants from the Swedish Medical Research Council (project 12X-03020 and project 14X-263) and from the U.S. Public Health Service via the N.I.H. (grant No. 5 RO1 NS07838)