金尔伦治疗急性重型脑外伤的临床研究

目的　探讨金尔伦治疗急性重型颅脑损伤患者的疗效和安全性。方法　 13 1名急性重型颅脑伤病人随机分成金尔伦治疗组 (n =62 )和对照组 (n =69) ,观察治疗早期病人GCS评分变化和远期疗效。结果　金尔伦组患者GCS评分在用药后第 5d开始明显优于对照组 (P <0 0 5 ) ;金尔伦组病死率 2 4 2 % ,对照组病死率 5 0 7% ,两组相比有显著性差异 (P <0 0 1)。结论　金尔伦可以降低急性重型颅脑外伤病人颅内压的升高幅度 ,缩短昏迷时间 ,降低伤残率 ,促进病人神经功能恢复 ,改善预后。     

金尔伦(盐酸纳洛酮)治疗急性颅脑损伤病人随机双盲多中心前瞻性临床研究

背景：本试验是由中华医学会神经外科学会和中华神经外科杂志部组织，国内18家医院实施，完成金尔伦（盐酸纳洛酮）对受试患者的疗效和用药安全性观察，目的，证明金尔伦在治疗急性中，重型颅脑损伤患者的治疗和安全性，方法：设计并实施了随机双盲前瞻性临床对照试验计划，比较大剂量金尔伦和生理盐水安慰剂的疗效差异，每位受试得接受为期10天随机分组治疗和3个月随访，分析对比治疗前后和治疗过程中患者的病情和重要辅助检查指标的变化,趋势并同时对比随访结束时患者神经功能恢复情况和生活质量状况，全部试验结束后进行揭盲并对结果进行统计学分析,结果，实际完成530例，有效病例511例，其中金尔伦组256例，安慰剂组255例，金尔伦组和安慰剂组死亡率分别为治疗组12．5％，有效病例12．5％，安慰剂组17．3％（P＜0．05），金尔伦组患者GCS评分在用药后第5天开始明显优于安慰剂组（P＜0．05），治疗结束后金尔伦组患者GOS评分明显优于安慰剂组（P＜0．05），金尔伦组患者语言功能评分和生活质量状况评分也明显优于安慰剂组（P＜0．05），另外，过程中未发现因用药造成的毒副反应，结论：早期应用大剂量金尔伦能明显降低急性颅脑损伤患者死亡率，促进脑神经功能恢复，改善远期生活质量状况，并且具有相当可靠的安全性。     

亚低温治疗重型脑外伤的神经电生理研究

目的　探讨亚低温对急性重型脑外伤的疗效。方法　选择受伤后 10小时内入院的急性重型脑外伤患者(GCS≤ 8) 44例 ,按伤情轻重分为GCS 6～ 8分和GCS 3～ 5分两组 ,各组再随机分成亚低温组和对照组。亚低温组(3 2～ 3 4℃ )于降温前、降温后 4、2 4、48、72、96、12 0小时及复温后监测正中神经短潜伏期体感诱发电位 (SLSEP)的N2 0 波幅和脑干听觉诱发电位 (BAEP)的I、V波幅比值 ;对照组在同样的时段监测上述指标 ,并行统计学分析比较。结果　GCS 6～ 8分的亚低温组降温 2 4小时及其后的两个诱发电位 (EP)指标较对照组有显著性差异 ,前者存活比例 (10 /14 )亦高于后者(3 /10 )。GCS 3～ 5分组有无亚低温治疗者 ,其EP检测结果及存活比例两组间均无显著性差异。结论　从EP监测显示 :亚低温对于重型脑外伤中GCS 6～ 8分者有显著的治疗作用 ,对 3～ 5分的病例则无明显疗效。     

金尔伦(盐酸纳洛酮)治疗急性重型脑外伤的临床研究

目的：探讨金尔伦（盐酸纳洛酮）在急性重颅脑外伤中的运用效果及其机制,方法:146列急性重型颅脑损伤病人随机分成金洋伦治疗组（n=75)和对照组（n=71),观察治疗早期病人生命体征,颅内压,头颅CT变化和远期疗效,以及治疗前后血,脑脊液中β－内肽变化情况,结果,金尔伦治疗组早期病人呼吸循环较快恢复稳定,呼吸异异常（29．3％）,心律异常（30．7％）,及伤后1周颅内压显著升高（20％）和重度脑水肿者（20％）均较对照组明显减少（P＜0．01）,金尔伦组1周后意识;转清醒率（54．7％）及伤后3个月恢复良好率（42．7％）,显著高于对照组（P＜0．05）,重残及死亡率（37．3％）明显减少（P＜0．05）,金尔伦组病人β－内啡肽下降程度及速度较对照组显著加快（P＜0．01）,结论：金尔伦可以降低急性重型颅脑外伤病人颅内压的升高幅度,缩短昏迷时间,降低伤残率,促进病人神经功能恢复,改善预后,其机制可能是拮工抑制伤后β－内啡肽的释放。     

盐酸纳洛酮治疗大鼠急性颅脑损伤的药效学观察

目的观察盐酸纳洛酮(金尔伦)在大鼠急性颅脑损伤实验模型中促进神经功能恢复的治疗作用,并做量效分析。方法SD大鼠250只,采用Feenly自由落体撞击法建立颅脑损伤模型,随机分成六组,于损伤后30min开始给药。前四组每天分别给予金尔伦0.3mg/kg、1mg/kg、3mg/kg和9mg/kg腹腔注射;阳性对照组:给予胞磷胆碱钠2mg/只腹腔注射;阴性对照组:给予0.5ml/只生理盐水腹腔注射。每天进行MNSS神经功能评分,最长疗程为14d。伤后2d和4d每组随机取8只大鼠,通过干—湿重法计算脑组织的含水量。结果金尔伦治疗组大鼠的神经功能恢复情况明显优于其他两组(P<0.01)。金尔伦1、3、9mg/kg三组的情况优于0.3mg/kg组(P<0.05),而这三组之间没有显著性差异(P>0.05)。金尔伦治疗组大鼠的脑含水量明显低于对照组(P<0.05);金尔伦内部各实验组之间,0.3mg/kg组的脑含水量高于其他三组(P<0.05),其他三组之间无显著性差异(P>0.05)。结论金尔伦能够降低大鼠急性颅脑损伤后的脑水肿,对大鼠的神经功能恢复有明显的促进作用,并在一定范围内随着剂量的增加效果更显著。     

金尔伦治疗急性颅脑损伤的剂量效应研究

目的探讨金尔伦(盐酸纳洛酮)在治疗大鼠液压脑损伤后神经功能恢复和病理损害程度的剂量效应.方法将104只SD大鼠随机分为4组,伤后早期分别腹腔注射0.03 mg/Kg(小剂量组)、0.3 mg/Kg(中剂量组)、3 mg/Kg(大剂量组)金尔伦和等量生理盐水(对照组),连续7 d.结果中、大剂量组动物伤后脑神经功能恢复、脑水肿减轻程度及光、电镜检查显著优于对照组及小剂量组.结论伤后早期使用中剂量和大剂量金尔伦(盐酸纳洛酮)对大鼠液压颅脑损伤有明显的治疗效果.     

金尔伦（盐酸纳洛酮）对重型头伤后脑组织内Ca^2＋、Mg^2＋、EAA及血浆ET变化影响与意义

目的：探讨金尔伦（盐酸纳洛酮）对重型头伤后脑组织内Ca^2 ,Mg^2 ,EAA及血浆ET变化的影响及临床意义,方法：DS大鼠72只,随机分为治疗组,对照组及空白组,参照Feeny自由落体撞击法建立头伤模型,伤后半小时,治疗组大鼠于腹腔注射金尔伦10mg/kg,对照组大鼠则于腹腔注射生理盐水10mg/kg,空白组不作任何处理,按伤后处理时间各组再分为4小组,每组6只,分别于伤后1小时,2小时,4小时,8不时处死1小组,检测缶伤区脑组织内Ca^2 ,Mg^2 ,EAA及ET含量,结果,治疗组伤后Ca^2 ,EAA和ET含量轻度升高,Mg^2 含量不和不明显,与对照组相比有统计学差异。结论：金尔伦通过竞争性拮抗内源性阿片肽受体,能明显逆转实验动物重型头伤后损伤区脑组织内Ca^2 ,EAA和ET含量的增高及Mg^2 的下降,具有脑保护作用,其详细机理有待进一步研究。     

金尔伦(盐酸纳洛酮)治疗急性重症脑外伤的临床观察

目的：针对重度颅脑外伤后血浆,脑脊液和脑区内源性阿片肽,特别是β－内啡肽明显升高,应用金尔伦（盐酸纳洛酮）探讨对重症颅脑外伤的临床疗效,方法选择GCS5－8分患者30例每天应用金尔伦4．8毫克,随机以30例同等伤情未用金尔伦药物治疗病例为对照组,观察意识觉醒,血液流变学及临床征象,结果,觉醒天数缩短,外伤后脑血管痉 发生率,血液粘滞度降低,致残率减少,结论：金尔伦对于内源性阿片肽引起的生理功能的应激性疾病起效快,作用可靠,其使用安全,治疗过程中未见有毒副作用。     

静脉注射结合脑室内部灌注金尔伦（盐酸纳洛酮）治疗重型颅脑损伤

本文报告在静脉滴注盐酸纳洛酮 (金尔伦 ) 4mg/d的基础上 ,于手术时在脑损伤创面上灌注金尔伦 4mg ,此后每隔 8小时向脑室内灌注金尔伦 7～ 10mg ,取得了较好疗效。纳洛酮为脂溶性 ,易透过血脑屏障 ,脑外伤后血脑屏障通透性增加 ,药物更易通过血脑屏障 ,因此有无必要在脑损伤局部及脑室内灌注金尔伦需行进一步研究 ,应有充分证据说明局部或脑室内用药优于静脉内给药。文献报告 (BehavNeurosci,2 0 0 0 ,114 :1183 1190 .DevPsychobiol,2 0 0 0 .3 7:12 9 14 3 .) 向动物脑室内、枕大池或鞘内灌注纳洛酮未引起不良反应。但在临床应用中还需慎重考虑用药途径 ,以免误导 ,造成不良反应事件。     

金尔伦(盐酸纳洛酮)对重型头伤后脑组织内Ca~(2 )、Mg~(2 )、EAA及血浆ET变化影响与意义

目的　探讨金尔伦 (盐酸纳洛酮 )对重型头伤后脑组织内Ca2 、Mg2 、EAA及血浆ET变化的影响及临床意义。方法　SD大鼠 72只 ,随机分为治疗组、对照组及空白组。参照Feeny自由落体撞击法建立头伤模型 ,伤后半小时 ,治疗组大鼠于腹腔注射金尔伦 10mg/kg;对照组大鼠则于腹腔注射生理盐水 10mg/kg ;空白组不作任何处理。按伤后处理时间各组再分为 4小组 ,每组 6只 ,分别于伤后 1小时 ,2小时 ,4小时 ,8小时处死 1小组 ,检测损伤区脑组织内Ca2 、Mg2 、EAA及ET含量。结果　治疗组伤后Ca2 、EAA和ET含量轻度升高 ,Mg2 含量下降不明显 ,与对照组相比有统计学差异。结论　金尔伦通过竞争性拮抗内源性阿片肽受体 ,能明显逆转实验动物重型头伤后损伤区脑组织内Ca2 、EAA和ET含量的增高及Mg2 的下降 ,具有脑保护作用。其详细机理有待进一步研究。     

Effects of phenobarbital on EEG and sensory evoked potentials in normal cat brain

In adult cats, authors studied changes in parameters obtained by the recordings of sensory evoked potentials following cumulative intravenous administration of phenobarbital. P1 and N1 of cortical SEP showed gradual tendencies to decrease in amplitude and to increase in latency with increasing barbiturate dose. These changes preceded to the appearance of burst-suppression activity on electroencephalogram. At this point I-II and III-IV interpeak latencies of BAEP showed statistically significant increase. BAEP and all early components of SEP (I.II.III) persisted in the extremely high serum concentration of phenobarbital. Furthermore, II-III interpeak latency of BAEP showed no statistically significant increase. These experimental results suggest that sensory evoked potentials will provide useful information in the assessment of the brainstem function in patients under deep coma.     

Effects of thiopental on sensory evoked potentials in the cat

Noninvasive electrophysiological evaluation with sensory evoked potentials would be of clear diagnostic and prognostic value in evaluating comatose patients with stroke or severe head injury. In order to protect the brain from such kinds of insults, barbiturate coma therapy has been employed and its effectiveness has been already established. However, in the barbiturate coma therapy, it is occasionally difficult to distinguish the pharmacological effect of barbiturate from the preexisting brain dysfunction caused by the underlying process of the disease. In adult cats, authors studied changes of sensory evoked potentials following cumulative intravenous administration of thiopental which is used clinically for barbiturate coma therapy. P1 and N1 of cortical SEP showed tendency of gradual decrease in amplitude. However, no significant changes occurred in latency by stepwise increment of thiopental dose. Changes in amplitude of P1 and N1 of cortical SEP preceded to the flattening on electroencephalogram. Around at the level of the concentration where EEG changes began, I-II interpeak latency of BAEP and latency of wave I of short latency SEP started to increase. BAEP and early components of SEP (I.II.III.IV) persisted even in by far the higher level of serum concentration of thiopental than that of clinical use. Furthermore, most of these parameters showed no statistically significant change neither in amplitude nor in latency. These experimental results suggest that sensory evoked potentials will provide us with useful information in the assessment of the brainstem function in patients under thiopental induced deep coma.     

N20-P25、N18消失在深昏迷预后判断中的价值

目的评价短潜伏期体感诱发电位(shortlatencysomatosensoryevokedpotentials,SLSEP)N20P25、N18消失在深昏迷患者预后判断中的作用。方法运用便携式诱发电位仪,对95例深昏迷患者进行SLSEP检测,记录脑皮质电位N20P25和周围电位N13,44例患者同时记录脑皮质下电位N18。结果95例患者N20P25均消失(100%),8例患者因有周围神经损伤未记录到周围电位N13;44例患者中脑皮质下电位N18消失者38例(86.4%)。结论95例患者SLSEP检查结果与临床判断完全吻合。在脑功能判断中,N20P25敏感性较高,N18特异性较高,二者均消失高度提示脑功能预后不良。     

多模式诱发电位对缺氧性脑病的研究

目的应用多模式诱发电位评估缺氧性脑病脑功能损伤程度和预测预后的准确性。方法对44例心肺复苏后、低血压和(或)低血氧导致的昏迷患者进行体感诱发电位、脑干听觉诱发电位监测,并根据Judson、Hall、Cant、Haupt标准进行单模式、多模式以及单模式与多模式之间的比较。结果单模式和多模式各分级标准与预后均有显著相关性,级别越高,预后越差。体感诱发电位预测准确性(Judson标准为84.1%)高于脑干听觉诱发电位(Hall标准为79.5%)。多模式诱发电位预测准确性(Cant标准为88.4%)高于单模式诱发电位。结论多模式诱发电位能更好地反映缺氧性脑病的脑功能损伤程度,Cant标准简便易行,预测准确性高,适于临床推广应用。     

中潜伏期体感诱发电位预测重症脑卒中患者预后的应用价值

目的 探讨中潜伏期体感诱发电位(middle-latency somatosensory evoked potentials,MLSEP)预测急性重症脑卒中患者预后的应用价值.方法 对70例症状出现7 d内的重症脑卒中患者行格拉斯哥昏迷评分(Glasgow Coma Scale,GCS)、短潜伏期体感诱发电位(short-latency somatosensory evoked potentials,SLSEP)和MLSEP检测,6个月后采用改良Rankin评分和生存与死亡两个预后标准进行预后评估.健康对照组20名行SLSEP和MLSEP检测.统计学分析MLSEP、SLSEP和GSC与预后的一致性及预测的准确性.结果 健康对照组均记录到双侧N20、N35和N60,脑卒中组患者MLSEP波形有缺失,而且病灶侧MLSEP各波消失比例明显高于对侧.双侧N60消失与预后不良(Kappa=0.828,P＜0.01)和死亡(Kappa=0.686,P＜0.01)的一致性均最好.预测准确性分析显示:病灶侧N60消失预测不良预后和死亡的敏感性高达100%,较病灶侧N20消失的敏感性(85.7%)提高了14.3%;双侧N60消失预测预后不良的特异性为100%,与双侧N20消失一致;但预测死亡的特异性为82.9%,不如双侧N20消失(97.1%).结论 MLSEP可反映脑损伤程度,预测预后不良的敏感性高于SLSEP,建议将MLSEP和SLSEP联合用于重症脑损伤后的评估与预后的预测.

Abstract：

Objective To explore the effectiveness of using middle-latency somatosensory evoked potentials (MLSEP) to predict the prognosis in patients with acute severe stroke. Methods MLSEP, shortlatency somatosensory evoked potentials (SLSEP), and Glasgow Coma Scale (GCS) were recorded in 70 acute severe supratentorial stroke patients within 1 week after onset. All patients were evaluated with modified Rankin Scale (mRS) and follow-up in 6 months after onset. SLSEP and MLSEP were recorded in 20 normal controls. The consistency between MLSEP, SLSEP, GCS and prognosis, as well as the prognostic authenticity of MLSEP, SLSEP, and GCS were analyzed. Results Bilateral N20, N35, and N60 exited in all normal controls. Some waves of MLSEP were absent in stroke patients, and the proportion of absent waves in ipsilateral MLSEP was higher than in contralateral MLSEP. The consistency between bilateral absence of N60 and unfavorable outcome ( Kappa = 0.828, P ＜ 0.01 ), and between bilateral absence of N60 and death ( Kappa = 0.686, P ＜ 0.01 ) was satisfactory. By using the prognostic authenticity analysis of predictors, the ipsilateral absence of N60 showed the highest sensitivity ( 100% ) for unfavorable outcome and death, which added 14.3% compared with the sensitivity of ipsilateral absence of N20 ( 85.7% ). Bilateral absence of N60 showed a high specificity of 100% for unfavorable outcome, which equaled bilateral absence of N20.However, it showed a lower specificity ( 82.9% ) for death, than bilateral absence of N20 (97.1% ).Conclusions MLSEP was able to reflect the degree of brain injury and showed higher sensitivity than SLSEP for predicting unfavorable outcomes. Therefore combined use of MLSEP and SLSEP in evaluating and predicting the outcomes in brain injuries is suggested.     

EEG and evoked potentials in HIV-infected children.

Forty-seven HIV-seropositive children were investigated by EEG and evoked potentials (BAEP, SEP). Twenty-three children were symptomatic (P2), 8 seropositive without symptoms (P1), and 16 children were less than 15 months of age (P0). Some of them were investigated at different stages of HIV infection. During the neonatal period, 7 newborns of drug-addicted mothers had seizures and frequent spikes and sharp waves in their EEGs. Among (P2) children 6/23 showed background slowing and 1 had rhythmic theta activity (6 with and 1 without neurological symptoms). In BAEP, bilateral prolonged interpeak latencies (IPL) were found in 1 child with severe AIDS encephalopathy. Side differences greater than or equal to 0.4 ms in IPL were seen in 2 (P2), 1 without and 1 with neurological symptoms. A late onset was seen in 2 (P1) and 4 (P2) children. Median SEPs were normal in 24/26 patients; N20/N13 amplitude ratio was reduced in 2 (P1) patients. EEG and BAEP revealed nonspecific abnormal features in HIV encephalopathy. The the progression of the disease. However, also in the symptomatic group, normal results of EEG and BAEP dominated. SEP in the symptomatic group revealed only normal values. For monitoring the effectiveness of AZT treatment in HIV encephalopathy, EEG seems to be a relevant investigation; for evoked potentials more data and experience are needed.     

脑干听觉诱发电位在后循环脑梗死中的临床应用价值研究

目的 通过分析急性和慢性后循环脑梗死患者脑干听觉诱发电位变化特点,探讨脑干听觉诱发电 位（brainstem auditory evoked potential,BAEP）在后循环脑梗死早期识别和诊断方面的临床应用价值。 方法 选择2018年8月-2019年3月在上海第六人民医院神经内科就诊的后循环脑梗死患者为研究 对象,分为急性脑梗死组和慢性脑梗死组,同时设立健康对照组。比较3组BAEP的Ⅰ、Ⅲ、Ⅴ各波峰 潜伏期（peak latency,PL）,Ⅰ～Ⅲ波、Ⅲ～Ⅴ波和Ⅰ～Ⅴ波峰间潜伏期（interpeak latency,IPL）,Ⅲ～Ⅴ波 /Ⅰ～Ⅲ波I PL的比值等指标的特点。 结果 研究共入组急性脑梗死组患者36例,慢性脑梗死组32例,健康对照组32例。急性脑梗死组 Ⅲ波、Ⅴ波PL较慢性脑梗死组（P＜0.001、P =0.005）和对照组（均为P＜0.001）均延长;慢性脑梗死组 Ⅴ波PL较对照组延长（P＜0.001）。急性脑梗死组Ⅰ～Ⅲ波、Ⅰ～Ⅴ波I PL较慢性脑梗死组延长（P＜0.001、 P =0.029）;急性脑梗死组Ⅰ～Ⅲ波（P＜0.001）、Ⅲ～Ⅴ波（P =0.006）和Ⅰ～Ⅴ波（P＜0.001）IPL较对照 组延长;慢性脑梗死组Ⅲ～Ⅴ波I PL（P =0.003）较对照组延长。慢性脑梗死组Ⅲ～Ⅴ/Ⅰ～Ⅲ波IPL比值 异常者有9例（25.0%）,急性脑梗死组2例（6.3%）,两组差异有统计学意义（P =0.001）。 结论 ①BAEP检查能灵敏地检测出急性和慢性后循环脑梗死患者的听觉感觉通路的电生理异常。 ②急性脑梗死患者BAEP的Ⅲ波和Ⅴ波PL、Ⅰ～Ⅲ波和Ⅰ～Ⅴ波IPL均显著延长,以Ⅲ波PL、Ⅰ～Ⅲ波IPL延 长为主;慢性脑梗死患者BAEP以Ⅴ波PL、Ⅲ～Ⅴ波IPL的延长为主。     

合并糖尿病对后循环短暂性脑缺血发作患者脑干听觉诱发电位的影响

目的使用诱发电位仪检测后循环短暂性脑缺血发作（transient ischemic attack,TIA）患者脑干听觉诱发电位（Brainstem auditory evoked potential,BAEP）的变化,探讨合并糖尿病（DM）的后循环TIA患者受损部位的特点。方法入组后循环TIA病例共58例,其中合并糖尿病组20例,无糖尿病组38例,使用诱发电位仪分别检测其BAEP的变化。结果2组后循环TIA患者的Ⅲ波、Ⅴ波波峰潜伏期（Peaklatency,PL）,Ⅰ～Ⅲ波、Ⅲ～Ⅴ波峰间潜伏期（Interpeak latency,IPL）均较正常值延长,其中合并DM组Ⅲ波PL、Ⅰ～Ⅲ波IPL与无DM组的Ⅲ波PL、Ⅰ～Ⅲ波IPL比较有显著性差异（P〈0.05）,而无DM组的Ⅲ-Ⅴ波IPL与合并DM组的Ⅲ～Ⅴ波IPL比较有显著性差异（P〈0.05）。结论合并DM的后循环TIA患者听神经及脑桥下段较无DM的TIA患者更容易受到缺血性损伤。     

Stage II sleep alters infants' short latency somatosensory evoked potentials

To evaluate the effects of stage II sleep on short latency somatosensory evoked potentials (SLSEP) to median nerve stimulation, we studied 16 normal infants from two to twelve months of age. SLSEP were recorded during waking and stage II sleep. Four channels of parasagittal EEG and behavioral observations were used to classify states. Compared with SEP in the waking state, cerebral potentials in stage II sleep were of much lower amplitude, even vanishing entirely in several infants. In addition, the change from waking to stage II sleep produced significantly longer latencies of the peaks N1, P1, and P2. We suggest performing SLSEP in infants in the waking state in order to assess cerebral somatosensory function.     

Evaluation of central neuropathy in type II diabetes mellitus by multimodal evoked potentials

The electrophysiological results in 51 patients with diabetes mellitus type II were compared with those in 30 age and sex matched healthy control subjects. Peripheral and cortical latencies of median and tibial somatosensory evoked potentials (SEP), bilateral I-III and I-V interpeak latencies (IPL) of brainstem auditory evoked potentials (BAEP), bilateral P100 latency of visual evoked potentials (VEP) and bilateral cortical latency and central motor conduction time of motor evoked potentials (MEP) were evaluated. We observed prolonged latencies suggestive of central neuropathy in DM type II. It has been shown that most of the electrophysiological parameters in patients with DM type II correlate with the duration of the disease, some of them with the age of the patient, and few of them with the onset of the disease. To our knowledge, there is no correlation between the electrophysiological parameters and the level of glycemia or the degree of metabolic control. We conclude that central and peripheral neuropathies in DM are related to the duration of the disease and not to the degree of hyperglycemia and metabolic control.