Poor-grade aneurysmal subarachnoid hemorrhage: relationship of cerebral metabolism to outcome

OBJECT: The majority of patients with poor-grade subarachnoid hemorrhage (SAH), that is, World Federation of Neurosurgical Societies (WFNS) Grades IV and V, have high morbidity and mortality rates. The objective of this study was to investigate cerebral metabolism in patients with low- compared with high-grade SAH by using bedside microdialysis and to evaluate whether microdialysis parameters are of prognostic value for outcome in SAH. METHODS: A prospective investigation was conducted in 149 patients with SAH (mean age 50.9 +/- 12.9 years); these patients were studied for 162 +/- 84 hours (mean +/- standard deviation). Lesions were classified as low-grade SAH (WFNS Grades I-III, 89 patients) and high-grade SAH (WFNS Grade IV or V, 60 patients). After approval by the local ethics committee and consent from the patient or next of kin, a microdialysis catheter was inserted into the vascular territory of the aneurysm after clip placement. The microdialysates were analyzed hourly for extracellular glucose, lactate, lactate/pyruvate (L/P) ratio, glutamate, and glycerol. The 6- and 12-month outcomes according to the Glasgow Outcome Scale and functional disability according to the modified Rankin Scale were assessed. In patients with high-grade SAH, cerebral metabolism was severely deranged compared with those who suffered low-grade SAH, with high levels (p < 0.05) of lactate, a high L/P ratio, high levels of glycerol, and, although not significant, of glutamate. Univariate analysis revealed a relationship among hyperglycemia on admission, Fisher grade, and 12-month outcome (p < 0.005). In a multivariate regression analysis performed in 131 patients, the authors identified four independent predictors of poor outcome at 12 months, in the following order of significance: WFNS grade, patient age, L/P ratio, and glutamate (p < 0.03). CONCLUSIONS: Microdialysis parameters reflected the severity of SAH. The L/P ratio was the best metabolic independent prognostic marker of 12-month outcome. A better understanding of the causes of deranged cerebral metabolism may allow the discovery of therapeutic options to improve the prognosis, especially in patients with high-grade SAH, in the future.     

Pulmonary air embolism in severe head injury

Entry of air into the venous system leading to intracardiac air and pulmonary air embolism (PAE) has been reported in various clinical settings such as neurosurgical interventions in the sitting position and in autopsies on patients with head and neck injuries. We report the case of a 29-year-old male who developed severe pulmonary dysfunction after severe head injury in a high-velocity car accident. Chest X-ray showed bilateral diffuse patchy infiltrates. Pneumothorax, haemothorax, pulmonary aspiration, various forms of pulmonary oedema and pulmonary contusion could be excluded. Furthermore, there was an open laceration of the frontal sinus and maxillo-facial fractures. The history of spontaneous respiration in sitting position at the scene, rapid improvement of pulmonary function within 30 h, small amounts of air in the brain parenchyma, and circulatory shock despite elevated central venous pressure in the initial phase led to the diagnosis of PAE as the primary cause of pulmonary dysfunction. The diagnostic approach and basic therapeutical principles in patients with PAE are described. In conclusion, the case presented emphasizes the importance of considering PAE as a possible cause of respiratory failure in patients with severe head injury.     

Gewebeersatz (tissue engineering) von Dermis und Epidermis

Zusammenfassung Die Transplantation kultivierter autologer Keratinozyten als mehrlagige dünne Häutchen (cultivated epithelial autografts, CEAs) stellt seit über 20 Jahren das bei weitem am häufigsten geübte Verfahren bei der klinischen Anwendung von Hautersatz durch "tissue engineering" dar. Die nach wie vor unbefriedigenden Kurz- und Langzeitresultate, in Bezug auf Stabilität und Narbenbildung, verlangen jedoch nach Alternativen. Die Transplantation von Keratinozyten als Einzelzellsuspension in einer Fibrinmatrix wurde am Model der athymischen Nacktmaus standardisiert. Mit diesem Verfahren können Wunden zuverlässig innerhalb von 14 Tagen reepithelisiert werden. Darüber hinaus ist eine Kombination mit azellulärer Fremdhaut als dermale Matrix mit dem Ziel "tissue engineering" von Haut einschließlich einer dermalen Komponente erfolgreich am Wundheilungsmodell des Schweines gezeigt worden. Die Potenz subkonfluent kultivierter Keratinozyten (welche schon nach kurzer Kultivierungszeit erhältlich sind) zur Erzielung eines dauerhaften Wundverschlusses, wird durch die simultane Kotransplantation mit einer dermalen Matrix verstärkt.     

Effects of LY379268, a selective group II metabotropic glutamate receptor agonist on EEG activity,cortical perfusion,tissue damage,and cortical glutamate,glucose, and lactate levels in brain-injured rats

Activating presynaptic group II metabotropic glutamate (mGlu II) receptors reduces synaptic glutamate release. Attenuating glutamatergic transmission without blocking ionotropic glutamate receptors, thus avoiding unfavorable psychomimetic side effects, makes mGlu II receptor agonists a promising target in treating brain-injured patients. Neuroprotective effects of LY379268 were investigated in rats following controlled cortical impact injury (CCI). At 30 min after CCI, rats received a single intraperitoneal injection of LY379268 (10 mg/kg/body weight) or NaCl. Changes in EEG activity and pericontusional cortical perfusion were determined before trauma, at 4, 24, and 48 h, and 7 days after CCI. Brain edema and contusion volume were determined at 24 h and 7 days after CCI, respectively. Before brain removal pericontusional cortical glutamate, glucose, and lactate were measured via microdialysis. During the early period following CCI, EEG activity and cortical perfusion were significantly reduced in rats receiving LY379268. At 7 days, cortical perfusion was significantly increased in rats treated with LY379268, while EEG activity was depressed as in control rats. While brain edema remained unchanged at 24 h, cortical contusion was significantly decreased by 56% at 7 days after CCI. Cortical glutamate, glucose, and lactate were not influenced. Significant reductions in EEG activity and contusion volume by LY379268 do not appear mediated by attenuated excitotoxicity and energetic impairment. Overall, an additional decrease in cortical perfusion seems to interfere with the anti-edematous potential of LY379268 during the early period following CCI, while an increase in perfusion in LY379268-treated rats at 7 days might contribute to tissue protection.     

Continuous monitoring of intracranial compliance after severe head injury: relation to data quality, intracranial pressure and brain tissue PO2

The objective of the present study was to test the new continuous intracranial compliance (cICC) device in terms of data quality, relationship to intracranial pressure (ICP) and brain tissue oxygenation (PtiO2). A total of 10 adult patients with severe traumatic brain injury underwent computerized monitoring of arterial blood pressure, ICP, cerebral perfusion pressure, end-tidal CO2, cICC and PtiO2 providing a total of 1726 h of data. (1) The data quality assessed by calculating the 'time of good data quality' (TGDQ, %), i.e. the median duration of artefact-free time as a percentage of total monitoring time reached 98 and 99% for ICP and PtiO2, while cICC measurements were free of artefacts in only 81%. (2) Individual regression analysis showed broad scattered correlation between cICC and ICP ranging from low (r = 0.05) to high (r = 0.52) correlation coefficients. (3) From 225 episodes of increased ICP (ICP > 20 mmHg > 10 min), only 37 were correctly predicted by a preceding decline in cICC to pathological values (< 0.5 ml/mmHg). (4) In all episodes of cerebral hypoxia (PtiO2 < 10 mmHg > 10 min), cICC was not pathologically altered. Based on the present results, we conclude that the current hardware and software version of the cICC monitoring system is unsatisfactory concerning data quality, prediction of increased ICP and revelance of cerebral hypoxic episodes.     

New N-terminal modified proctolin analogues

Five proctolin analogues modified in position 1 of the peptide chain by Cit (I), Lys (II), His (III), Phe(p-NH₂) (IV) and γ-Abu (V) were synthesized by conventional liquid phase method. Biological activity of the obtained peptides was investigated by the cardioexcitatory test on two insect species, cockroach, Periplaneta americana L. and yellow mealworm, Tenebrio molitor L.     

Kidney transplantation in recipients with mental retardation: clinical results in a single-center experience

Mental retardation has been a controversial relative contraindication to organ transplantation. Currently, there are few data available in the literature that describe the outcome of kidney transplantation in mentally retarded patients. In a series of 1,271 kidney transplantations performed between January 1968 and March 1996, we identified eight patients (0.6%) with significant mental retardation (IQ < 70). Only cooperative patients supervised by a reliable long-term caregiver, with long life expectancy, and able to take medication under supervision, were accepted as candidates, independent of the IQ level. At a mean follow-up of 7.3 years, seven patients are alive with functioning grafts, and one lost the kidney to chronic rejection 10 years after transplantation and died of sepsis after resuming dialysis. The 1- and 5-year patient and graft survival are thus 100%. Compliance with immunosuppressive treatment and clinical follow-up was excellent in all of the recipients. The patient quality of life and health were judged by the support persons as highly improved after transplantation in comparison to dialysis. We conclude that kidney transplantation in properly selected patients with mental retardation provides excellent patient and graft survival rates and improves quality of life. In such patients, the presence of mental retardation should not be considered a contraindication to kidney transplantation.     

Tumor angiogenesis is accompanied by a decreased inflammatory response of tumor-associated endothelium

We previously showed that endothelial cells (EC) from the vasculature of human solid tumors have a decreased expression of intercellular adhesion molecule-1 (ICAM-1) and ICAM-2 as compared with normal tissue EC. This effect is explained by EC exposure to angiogenic factors. It is known that upregulation of endothelial adhesion molecules (EAM) is a sign of EC activation in inflammatory responses. We therefore tested the effect of angiogenic factors on upregulation of EAM on tumor EC and human umbilical vein EC (HUVEC) by proinflammatory cytokines. Incubation of tumor-derived EC in tumor necrosis factor alpha (TNF alpha) did result in expression levels of only 20% of the level of similarly treated normal tissue-derived EC. Pretreatment of HUVEC with 10 ng/ml basic fibroblast growth factor (bFGF) for 3 days, before TNF alpha- or interleukin-1 alpha (IL-1 alpha) stimulation, resulted in ICAM-1 levels of only 30% to 60% of cells without pretreatment. Also, the induction of vascular EC adhesion molecule-1 (VCAM-1) and E- selectin by TNF alpha was significantly inhibited by prior exposure to bFGF. Vascular endothelial growth factor had similar but less prominent effects. The effect of transforming growth factor-beta and IL-8 was studied as well. The functional relevance of the finding of a decreased EC inflammatory response was confirmed by adhesion assays. Our results show that tumor angiogenesis induces EC anergy. This may serve as a tumor-protecting mechanism by impairing the development of an efficient leukocyte infiltrate in tumors.     

The kallikrein-kinin system as mediator in vasogenic brain edema. Part 3: Inhibition of the kallikrein-kinin system in traumatic brain swelling

Evidence has previously been provided that administration of kinins to the cerebrum causes edema and opening of the blood-brain barrier. It has further been shown that these highly active compounds are formed in the brain under pathophysiological conditions. Their formation was enhanced when cerebral blood flow became compromised by an increase in intracranial pressure. Final evidence, however, was not available as to whether specific inhibition of the kallikrein-kinin (KK) system has a therapeutic function in acute head injury. The authors have demonstrated in rabbits that inhibition of the activating enzyme kallikrein by aprotinin or by aprotinin plus soybean trypsin inhibitor (SBTI), which interfere with plasma and tissue kallikrein, is associated with a decrease in formation of posttraumatic swelling after a standardized cold lesion to the brain. Saline-treated control animals with cerebral cold-induced injury had an increase in hemispheric weight 24 hours later of 13.0% +/- 0.8% (standard error of the mean) in the damaged hemisphere compared to the contralateral nondamaged hemisphere. Administration of aprotinin or aprotinin plus SBTI led to a significant reduction of hemispheric swelling of 10.1% +/- 0.7% or 10.4% +/- 0.7%, respectively. In animals receiving SBTI only, hemispheric swelling evolving from cold injury was not significantly reduced. Therapeutic reduction of brain edema by aprotinin cannot be attributed to a nonspecific effect on the blood pressure, which in the experimental groups remained almost normal as compared to the control animals. Failure of SBTI to influence posttraumatic brain swelling may have resulted from disturbances in intravascular coagulation. Measurements of aprotinin in plasma and tissue demonstrate that the inhibitor doses employed are within an effective therapeutic range. Attenuation of brain edema by specific inhibition of the KK system provides evidence for a mediator role of kinins in vasogenic edema. Clinical trials with inhibitors of the KK system in acute forms of traumatic lesions associated with vasogenic edema appear worthwhile.