Interleukin-6 and development of vasospasm after subarachnoid haemorrhage

The authors characterized the role of interleukins in the cerebrospinal fluid (CSF) in the development of vasospasm after subarachnoid haemorrhage (SAH), particularly interleukin-6 (IL-6). Concentrations of interleukin-1 beta (IL-1 beta), IL-6, and interleukin-8 (IL-8) were measured serially in CSF of 24 patients and in serum of 9 patients with SAH and correlated clinically. Additionally, the effects of the same cytokines on the cerebral arteries of dogs were analyzed on angiograms after intracisternal injection. Changes in levels of eicosanoids, angiogenic factors, and soluble cell adhesion molecules were investigated in the CSF of injected dogs. CSF concentrations of IL-6 and IL-8 were elevated significantly above control levels from the acute stage of SAH until the chronic stage. Patients with symptomatic vasospasm had significantly higher levels of IL-6 as well as IL-8 in CSF on days 5 and 7. Intracisternal injection of IL-6 induced long-lasting vasoconstriction in five out of eight dogs, while IL-8 did not. The diameter of canine basilar artery after IL-6 was reduced 29 +/- 5% from pretreatment diameter at 8 hours. Prostaglandins E2 and I2 were elevated in CSF for the first 4.5 hour of this IL-6-induced vasospasm. Neither angiogenic factors such as platelet-derived growth factor-AB and vascular endothelial growth factor nor soluble cell adhesion molecules were significantly elevated in CSF. IL-6, which increases to very high concentrations in CSF after SAH, may be important in inducing vasospasm, as IL-6 produced long-lasting vasoconstriction in the canine cerebral artery, which may be partly related to activation of the prostaglandin cascade.     

S-100 protein plasma levels after aneurysmal subarachnoid haemorrhage

We investigated the level of S-100 protein in blood as an indicator of brain damage in 71 patients suffering from subarachnoid haemorrhage (SAH) due to ruptured aneurysms. Concentrations of S-100 protein were determined by micro-titre based immunofluorometic assay detecting predominantly S-100b on blood samples obtained 24 hours, 3 days and 7 days after onset of symptoms in patients with SAH and from 120 healthy control subjects. Neurological status was assessed using the Hunt and Hess (HH) scale on admission and by the Glasgow Outcome Scale (GOS) 6 months later. Mean concentrations of S-100 protein in blood were significantly (p < 0.0001) higher in patients 24 hours (0.263 +/- 0.387 microgram/l), 3 days (0.192 +/- 0.288 microgram/l) and 7 days (0.256 +/- 0.442 microgram/l) after onset of SAH symptoms compared to controls (0.050 +/- 0.081 microgram/l). More severe neurological symptoms (higher HH scale scores) on admission correlated with higher S-100 levels on admission (R = 0.70) and Day 3 (R = 0.66) (p < 0.0001). Worse outcome (lower GOS score) 6 months after SAH was also associated with higher plasma concentration of S-100 in the first week after SAH. In summary, this study showed that in patients with SAH due to ruptured aneurysm, S-100 protein levels correlate with early neurological deficit and are as sensitive as HH scores in predicting neurological outcome (GOS scores). Measurement of S-100 protein in blood is a reliable non-invasive method and may be clinically useful to screen for and monitor progression of central nervous system diseases of various origins.     

Vasopressin receptor antagonist OPC-31260 prevents cerebral oedema after subarachnoid haemorrhage

The effects of the non-peptide vasopressin V2 receptor antagonist, 5-dimethylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrah ydro-1 H-benzazepine hydrochloride (OPC-31260) on the cerebral oedema induced by subarachnoid haemorrhage were studied in rats. Subarachnoid haemorrhage induced significant water retention after water loading, increased the brain content of water and Na+ and increased plasma vasopressin levels. The water retention and brain water and Na+ accumulation were prevented by OPC-31260 administration, but the plasma vasopressin levels were further enhanced by OPC-31260. These results demonstrate the important role of vasopressin in the development of antidiuresis and disturbances in brain water and electrolyte balance in response to subarachnoid haemorrhage. The subarachnoid haemorrhage-induced cerebral oedema was significantly reduced following oral OPC-31260 administration. The protective mechanism exerted by OPC-31260 stems from its influence on renal tubular function: it blocks the renal vasopressin V2 receptors. These observations might suggest a new, effective approach to the treatment of subarachnoid haemorrhage-induced cerebral oedema in humans.     

Indications for cisternal irrigation with urokinase in postoperative patients with aneurysmal subarachnoid haemorrhage

The melatonin binding sites in membrane preparations of the young mouse thymus were studies using [125I] iodomelatonin as the radioligand. Effect of epinephrine (E) on melatonin receptor (MR) of young mouse thymus were investigated. Results: (1) E had inhibitory effect on MR of mouse thymus; (2) Propranolol could reverse the inhibitory effect of E but phentolamin could not; (3) cAMP had inhibitory effect on MR. These results indicate that E has the inhibitory effect on MR of the mouse thymus and the effect was mediated by beta-adrenergic receptor.     

The need for repeat angiography in subarachnoid haemorrhage

OBJECTIVE: To determine the actual use of 'statin' therapy for primary and secondary prevention and the potential effect of using the Sheffield Table for primary prevention of coronary heart disease upon 'statin' use in a consultant-run Hypertension and Cardiovascular Risk Clinic. DESIGN: Prospective audit of the current use of cholesterol-lowering therapy and the effect of implementing the criteria used in the Sheffield Table and the Scandinavian Simvastatin Study for cholesterol lowering in 'at risk' patients upon statin use in a consultant-led cardiovascular risk clinic. SETTING: The Aberdeen Hypertension Clinic. RESULTS: A total of 1500 patients were reviewed of which 416 (27.7%) had experienced at least one clinical manifestation of atherosclerotic cardiovascular disease (CVD) and 392 (94%) of these had a total cholesterol measured of whom 298 (76%) had a total cholesterol >5.5 mmol/l. Only 11.2% of eligible patients were actually receiving lipid-lowering treatment for secondary prevention. A total of 1084 patients with no prior cardiovascular disease were identified, 97 (8.9%) were excluded because of age. Using the Sheffield Table, 92 (9.4%) of these patients were eligible for statin therapy and only six of the 92 patients were actually receiving treatment. CONCLUSIONS: The results of this study reveal that even in a consultant-led cardiovascular prevention clinic there is a significant discrepancy between optimal evidence-based management and the actual delivery of clinical care. Seventy-two per cent and 9.3% of patients attending the clinic were eligible for statin treatment for secondary and primary prevention, respectively. However, only 11.2% of patients suitable for secondary prevention and 6.5% of patients suitable for primary prevention were actually receiving appropriate lipid-lowering therapy. Considering the proven benefit of this form of medical intervention the results of this study are of real importance to practising clinicians and patients alike.     

Headache characteristics in subarachnoid haemorrhage and benign thunderclap headache

One third of patients with aneurysmal subarachnoid haemorrhage (ASAH) present with headache only. A prompt diagnosis is crucial, but these patients must be distinguished from patients with non-haemorrhagic benign thunderclap headache (BTH). The headache characteristics and associated features at onset in subarachnoid haemorrhage and benign thunderclap headache were studied to delineate the range of early features in these conditions. In this prospective study, one of two observers interviewed 102 patients with acute severe headache by means of a standard questionnaire. The patients were alert on admission and had no focal deficits. ASAH was subsequently diagnosed in 42 patients, non-aneurysmal perimesencephalic haemorrhage (PMH) in 23 patients, and BTH in 37 patients. Headache developed almost instantaneously in 50% of patients with ASAH, 35% of patients with PMH, and 68% of patients with BTH and within 1 to 5 minutes in 19%, 35%, and 19%, respectively. Loss of consciousness was reported in 26% of patients with ASAH, 4% of patients with PMH and 16% of patients with BTH, and transient focal symptoms in 33%, 9%, and 22% respectively. Seizures and double vision had occurred only in ASAH. Vomiting and physical exertion preceding the onset of headache were more frequent in patients with ASAH (69% and 50%) and those with PMH (83% and 39%) than in those with BTH (43% and 22%). Headache developed almost instantaneously in only half the patients with aneurysmal rupture and in two thirds of patients with benign thunderclap headache. In patients with acute severe headache, female sex, the presence of seizures, a history of loss of consciousness or focal symptoms, vomiting, or exertion increases the probability of ASAH, but these characteristics are of limited value in distinguishing ASAH from BTH. Aneurysmal rupture should be considered even if focal signs are absent and the headache starts within minutes.     

False-negative angiograms in subarachnoid haemorrhage due to intracranial aneurysms

In occupational epidemiology, the need to consider the age factor properly influences the choice of study design and analytical techniques. In most studies, age is viewed as a potential confounder. Age is strongly associated with end points of interest in occupational epidemiology (diseases, physiological characteristics, doses of xenobiotics, etc), but to measure age as a confounder it must be associated with the exposure under study. When the exposure of interest is time related-for example, duration of employment, time since first exposure, cumulative exposure-a strong intrinsic association with age can be anticipated, and age will behave as a (usually strong) confounder. When occupational exposures without a direct relation with age-for example, job, department, type of exposure-are evaluated, the degree and direction of confounding bias cannot be anticipated. Control of the confounding effect of age can be accomplished in the design phase of a study by way of randomisation, restriction, and matching. Randomisation is seldom viable in occupational settings. Restriction is rarely used in the case of age. Matching is often used in a case-control study as a method to increase the study efficiency, but it must be followed by proper matched or stratified analysis. Options for age adjustment in the analysis phase involve stratification and regression methods. In longitudinal studies the modified life table analysis is used to take into account the fact that subjects cross categories of age as the study proceeds. Stability of relative measures of effect over age strata favoured the greater use of relative risks than risk differences. In the presence of effect modification the influence of age should not be eliminated; its interaction with exposure should be explicitly considered.     

Endothelin and aneurysmal subarachnoid haemorrhage: a study of subarachnoid cisternal cerebrospinal fluid

A single poroid neoplasm composed of three histologically distinct lesions (hidroacanthomas simplex, eccrine poroma, and dermal duct tumor) is reported. Comparative histologic, histochemical, and electron-microscopic studies revealed that each tumor subtype contained varying proportions of poroid cells, clear cells, and cuticular cells. The major component of all three neoplasms was poroid cells, which, under the electron microscope, were characterized by a few, small, poorly developed desmosomes, and were histochemically characterized by a positive succinic dehydrogenase reaction. The dermal duct tumor was cultured, and showed similar histochemical findings to the in vivo poroid cells. These results suggest that poroid cells play the most important role in the histogenesis of these three neoplasms.     

Effect of ultra-early referral on management outcome in subarachnoid haemorrhage

A study was conducted to clarify whether ultra-early referral of patients with subarachnoid haemorrhage (SAH) is effective for improving the management outcome. The subjects were 455 patients who were admitted within 6 h after initial SAH. Of these patients, 289 were treated surgically, 159 of them within 24 h. At 6 months, 228 patients (50%) had a favourable outcome including good recovery or moderate disability, 37 (8%) had severe disability, and 190 (42%) had an unfavourable outcome including vegetative state or death. Of 214 patients with an admission grade IV or V, 47 (22%) had a favourable outcome. In 10 patients, emergency procedures such as haematoma removal or ventriculostomy were definitely effective, and in 13, early surgery may have been the reason for the improved outcome. However, in 24 patients, the reasons for a favourable outcome were not related directly to ultra-early referral; in 19 of them, there was spontaneous improvement of clinical grade and/or no SAH on computed tomography. Of 218 patients with admission grade I or II, 30 (14%) had an unfavourable outcome, and in 12 of them, this was ascribed to rebleeding. The rebleeding rate and severity of vasospasm were not significantly reduced by surgery carried out within 24 h after SAH, in comparison with surgery carried out between 24 and 48 h, and there was no significant difference in surgical outcome between them. It is concluded that although ultra-early referral of patients with SAH was expected to improve the outcome in emergency cases, no substantial improvement in overall management outcome seems to have been achieved by this policy.     

Changes of cerebrovascular CO2 reactivity during normal aging

BACKGROUND AND PURPOSE: During the past decade, transcranial Doppler sonography has widely been used to assess blood flow velocities in the basal intracranial arteries and cerebrovascular reactivity (CR) to various stimuli. Although numerous studies have shown a decline of cerebral blood flow velocity with age, the age dependency of CR, including cerebrovascular CO2 reactivity, however, is controversial. Recently, we have reported a significant sex-related difference in CR, stressing the need to study the relation between normal aging and CR in both sexes separately. METHODS: By means of transcranial Doppler sonography, CR was determined in 100 healthy, nonsmoking volunteers (age 20 to 70 years, 10 men and 10 women per decade). RESULTS: In men, no change of CR with increasing age could be observed (P=0.98). In contrast, CR in women declined significantly, with a step decrease from the 4th to the 5th decades (F=4.413; P<0.01) and was significantly higher in the 3rd and 4th compared with the 5th, 6th, and 7th decades (P<0.05). Information on hormone replacement therapy (HRT) in women of the 6th and 7th decades was obtained retrospectively. HRT was associated with enhanced CR (HRT, n = 7 versus non-HRT, n = 13; P<0.001), with values similar to those found in premenopausal women. CONCLUSIONS: There are no changes of CR during normal aging in men, whereas CR declines significantly from the 4th to the 5th decades in women. HRT in postmenopausal women appears to enhance CR.     

CO2 reactivity testing without blood pressure monitoring?

The authors present a family with Binswanger's disease (BD) and antiphospholipid antibody syndrome (APAS). In one patient from this family, lupus anticoagulant and high levels of hemostatic markers were detected. The presence of BD and the clinicobiological improvements observed after antithrombin treatment in this patient are peculiar to this familial case of APAS.     

Role of the pneumo-encephalogram in the diagnosis of spontaneous subarachnoid haemorrhage

The authors have collected eighteen cases of primary intraventricular lesions revealed by a subarachnoid haemorrhage. Among these cases, the most important are the choroid plexus papillomas followed by ependymomas; some cases have no precise histological interpretation. Generally speaking, cerebral arteriography gives only indirect evidence of ventricular dilation and thus does not confirm the presence of a lesion. On the contrary, the pneumoencephalogram is consistantly positive, but does not give the differential diagnosis between intraventricular tumours and primary intraventricular haemorrhages. This test should therefore be given the same importance as spinal cord arteriography in the exploration of subarachnoid haemorrhages with negative cerebral angiograms.     

Outcome after aneurysmal subarachnoid haemorrhage: the use of a graphical model in the assessment of risk factors

In 102 consecutive prospectively identified patients with subarachnoid haemorrhage (SAH) we have analysed the severity of the initial haemorrhage and the direct and indirect effects of adverse factors on outcome. The data we recorded included delay in diagnosis, risk groups, Doppler measurements, angiographic findings, surgical events and outcome at 1 year. By using a temporal graphical chain model, the associations between all variables and possible causal pathways were statistically determined. The severity of the initial haemorrhage, as determined by means of a clinical assessment and CT scanning, allowed low-, medium- and high-risk patient groups and a statistically predictable outcome to be identified. The overall management mortality was 13.7% at 1 year; 70.6% had a favourable outcome and 15.7% were severely disabled. Outcome was directly associated with risk group (p = 0.0038) and rebleeding (p = 0.0000). Delayed diagnosis led to a poorer outcome (p = 0.014)--an indirect association probably due to rebleeding. Adverse surgical events led to a significantly poorer outcome in high-risk patients. No significant relationship was found either between age and risk group (p = 0.7784) or between age and outcome (p = 0.6418). Preoperative clinical (WFNS) grade was unreliable in predicting outcome. It is the particular risk group, determined by the initial SAH, that indicates the individual patient's outcome. Management strategies can reduce preventable adverse events such diagnostic delay and rebleeding. Future studies should stratify patients according to risk group, delay in diagnosis and rebleeding in order to enable a clearer comparison to be made of treatment methods.     

Determination of tranexamic acid (AMCA) and fibrin/fibrinogen degradation products in cerebrospinal fluid after aneurysmal subarachnoid haemorrhage

Six patients with recently ruptured intracranial aneurysms were treated preoperatively with tranexamic acid (AMCA). Two patients received 6 g daily in i.v. infusion, two had 6 g daily by i.v. injection, and two patients were given AMCA 9 g daily by mouth during the first week after bleeding. Serial assays of AMCA and fibrin/fibrinogen degradation products (FDP) in cerebrospinal fluid (CSF) were performed during 6--13 days after the initial subarachnoid haemorrhage (SAH). Judged from the decline in CSF-FDP, an assumed therapeutic level of greater than or equal to 1 mg/l of AMCA in CSF was reached within 24--36 hours after the first dose when the drug was administered intravenously and within 48 hours when the drug was given orally.     

重新认识高炉用焦炭与CO2的反应性

简要介绍了现行焦炭反应性试验方法的来源,主要表达焦炭在高炉内进入风口回旋区前抗CO2,气化能力以及反应后的抗粉化能力,是一种规范性试验方法。回顾了国内外对焦炭反应性的认识和变化,20世纪认为反应性表达焦炭在高炉抗CO2,的气化能力,反应性高反应后强度低对高炉生产不利。进入21世纪,新日铁提出反应性只是表达了焦炭的活性,认为提高反应性可以提高高炉反应效率,对高炉生产有利,不同时期认识水平不同认知也会完全相反。通过CO2,含量和反应温度对焦炭反应性影响试验和高炉碳平衡计算,分析了喷吹煤粉高炉内焦炭的行为．确定了焦炭进入风口回旋区前的反应失重率。提出现行国家标准“焦炭反应性及反应后强度试验方法”的反应性表达的是焦炭与CO2,反应的活性,高炉内焦炭反应失重率控制因素是矿石的还原性能和未燃煤粉率,与焦炭实验室测定的反应性无关。     

Effect of subarachnoid haemorrhage on micro-circulation in hypothalamus and brain stem of dogs

In order to investigate the relationship between cerebral vasospasm and microvasculature in the hypothalamus and brain stem, colloidal carbon was infused into the vertebral artery at various time intervals after experimental subarachnoid haemorrhage in dogs. Experiments which demonstrated vasospasm on angiogram were always accompanied by ischaemic changes in serial sections taken from the anterior hypothalamus to the brain stem. However, when it was demonstrated by angiography that the vasospasm had disappeared, the micro-circulation was restored to normal. Electron microscopy of the hypothalamus 48 hours and one week after subarachnoid haemorrhage, demonstrated swelling of the endothelial cells, enlargement of the perivascular glia and increase in number of the pinocytic vesicles in the cytoplasm, thus showing vasogenic oedema in this area. It is assumed that in addition to the vasogenic substance in extravasated blood, changes in irritability of cerebral vessels through the vasomotor pathways in the hypothalamus and brain stem might play an important role in the production of cerebral vasospasm.     

A transcranial doppler ultrasonography study of cerebrovascular CO2 reactivity in mitochondrial encephalomyopathy

BACKGROUND AND PURPOSE: To elucidate the pathogenic role of vascular involvement such as mitochondrial angiopathy in patients with mitochondrial encephalomyopathy (MEM). we used the transcranial Doppler sonography (TCD) method to detect impairment of cerebrovascular CO2 reactivity. METHODS: The cerebral perfusion reserve in 13 MEM patients, including 6 with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes) was studied by TCD for different CO2 partial pressures. For the parameter of mean flow velocity, the mean spatial Doppler frequency (fm) was obtained from the right and left middle cerebral arteries and basilar artery under conditions of normocapnia, hypercapnia, and hypocapnia in cases in which hyperventilation was possible. By fitting the obtained fm and the end-tidal CO2 partial pressure (PETCO2) to the exponential formula fm = a x e(K < PETCO2), where a is the theoretical fm at a PETCO2 of 0 mm Hg, the parameter K, an index of CO2 reactivity, was calculated. RESULTS: The K value was lower than control values at at least one site of the middle cerebral arteries and basilar artery of all patients with MELAS as well as the other MEM patients except for one patient with myoclonic epilepsy with ragged-red fiber and one with Kearns-Sayer syndrome. CONCLUSIONS: Our results suggest that there is a high incidence of impairment of cerebrovascular CO2 reactivity in MEM patients. Moreover, the noninvasive TCD method was found useful for evaluation of cerebral hemodynamics in MEM patients.