Cerebral microdialysis monitoring: determination of normal and ischemic cerebral metabolisms in patients with aneurysmal subarachnoid hemorrhage.

OBJECT: The success of treatment for delayed cerebral ischemia is time dependent, and neuronal monitoring methods that can detect early subclinical levels of cerebral ischemia may improve overall treatment results. Cerebral microdialysis may represent such a method. The authors' goal was to characterize patterns of markers of energy metabolism (glucose, pyruvate, and lactate) and neuronal injury (glutamate and glycerol) in patients with subarachnoid hemorrhage (SAH), in whom ischemia was or was not suspected. METHODS: By using low-flow intracerebral microdialysis monitoring, central nervous system extracellular fluid concentrations of glucose, pyruvate, lactate, glutamate, and glycerol were determined in 46 patients suffering from poor-grade SAH. The results in two subgroups were analyzed: those patients with no clinical or radiological signs of cerebral ischemia (14 patients) and those who succumbed to brain death (five patients). Significantly lower levels of energy substrates and significantly higher levels of lactate and neuronal injury markers were observed in patients with severe and complete ischemia when compared with patients without symptoms of ischemia (glucose 0 compared with 2.12+/-0.15 mmol/L; pyruvate 0 compared with 151+/-11.5 micromol; lactate 6.57+/-1.07 compared with 3.06+/-0.32 mmol/L; glycerol 639+/-91 compared with 81.6+/-12.4 micromol; and glutamate 339+/-53.4 compared with 14+/-3.33 micromol). Immediately after catheter placement, glutamate concentrations declined over the first 4 to 6 hours to reach stable values. The remaining parameters exhibited stable values after 1 to 2 hours. CONCLUSIONS: The results confirm that intracerebral microdialysis monitoring of patients with SAH can be used to detect patterns of cerebral ischemia. The wide range from normal to severe ischemic values calls for additional studies to characterize further incomplete and possible subclinical levels of ischemia.

High-level endothelial expression of human CD59 prolongs heart function in an ex vivo model of xenograft rejection.

BACKGROUND: Hyperacute rejection of discordant xenografts is dependent on activation of the complement system of the recipient. Transgenic expression of recipient complement regulatory factors in donor tissue has proved to be a promising approach to dealing with hyperacute rejection, although the relationship between the level of complement regulatory factor expression and the degree of protection is not well established. Here, we examine this relationship using CD59 transgenic mouse hearts in an ex vivo model of xenograft rejection. METHODS: The level of expression of CD59 in two lines of transgenic mice, in which CD59 is expressed under the control of either the murine H2Kb (MHC class I) promoter (line CA-17) or the endothelium-specific human intercellular adhesion molecule-2 promoter (line 237-7), was compared by immunohistochemistry and flow cytometry. Hearts from both groups and wild-type controls were perfused ex vivo with human plasma, and mean heart work for each group was compared over a 60-min period. RESULTS: CD59 expression on cardiac endothelial cells isolated from homozygous CA-17 mice was 25- to 30-fold lower than that on cardiac endothelial cells from heterozygous 237-7 mice. CA-17 hearts perfused with 6% human plasma exhibited a reduction in deposition of the membrane attack complex, but not a prolongation of function, compared with nontransgenic mouse hearts. In contrast, 237-7 hearts showed significantly prolonged function during perfusion with 20% plasma. CONCLUSIONS: High-level endothelial-specific expression of CD59 was effective in prolonging the function of mouse hearts perfused with 20% human plasma, whereas low-level, broader expression did not provide protection from 6% plasma.

Combination of decay-accelerating factor expression and alpha1,3-galactosyltransferase knockout affords added protection from human complement-mediated injury.

BACKGROUND: Hyperacute rejection (HAR) currently prevents the use of pigs as organ donors for humans. It is now generally accepted that the key instigators of HAR are naturally occurring xenoantibodies against the terminal disaccharide galactose alpha1,3-galactose (Gal), and the species incompatibility between human complement and porcine complement regulatory molecules. Using two in vitro models and an ex vivo mouse heart perfusion model, we have shown previously that cells and tissues from Gal knockout (Gal KO) and transgenic mice expressing the human cell surface complement regulator decay-accelerating factor (DAF/CD55) are partially, but not completely, protected from human complement-mediated injury. METHODS: In the present study, Gal KO mice were crossed with DAF transgenic mice and bred to homozygosity (DAF/Gal KO). Isolated splenocytes were incubated with human serum, and the protective effect of DAF and Gal KO was assessed by measuring complement deposition and cell lysis. Hearts perfused ex vivo with human plasma were examined for human antibody and complement deposition, and assessed functionally by measuring work performed by the heart. RESULTS: Splenocytes from DAF/Gal KO mice were found to be more resistant to complement-mediated injury than cells from either DAF transgenic or Gal KO mice. In addition, hearts from DAF/Gal KO mice, when perfused with human plasma, displayed prolonged survival compared with hearts from Gal KO mice. This was associated with a reduction in the extent of endothelial deposition of IgG, IgM, and complement C3b. CONCLUSIONS: These findings demonstrate that expression of human DAF in association with elimination of the Gal epitope provides added protection from complement-mediated injury in these models of HAR.

Use of recombinant factor VIIa in surgery in factor-VII-deficient patients.

Patients suffering from severe factor VII deficiency may present with serious bleeding problems. No clear guidelines exist regarding therapy in such patients in case of a large bleeding or surgery. Indeed, it has been postulated that some patients with severe factor VII deficiency may never present with overt bleeding problems. However, in factor-VII-deficient patients who have previously demonstrated a clinical tendency to bleed, surgery is expected to cause excessive bleeding. We present two females suffering from a severe factor VII deficiency (FVII:C < 0.01 U mL(-1) ) with a distinct history of haemorrhagic diathesis. Due to recurrent bleeding in the past, or for circumstantial reasons, surgery was demanded over a 4-year period on a total of seven occasions. To assist haemostasis during and after joint surgery on five occasions and for embolization and subsequent removal of a large haemangioma of the occipital region, recombinant factor VIIa (NovoSeven) was utilized in doses approximating 20 µg kg(-1) b.w. every 6 h beginning immediately before surgery and continued until 30 h to 13 days postoperatively, depending of the size of the respective procedure. Using this approach, we observed normal haemostasis, and there were no signs of excessive postoperative bleeding or wound haematoma. No adverse reactions or side-effects were observed, and there were no complaints or clinical signs indicative of thrombotic complications. As judged from the clinical course of these seven minor and major surgeries, recombinant factor VIIa appears to be highly efficaceous and safe in the treatment patients with severe factor VII deficiency undergoing surgery.

"Subdural' pressure measurement during craniotomy. Correlation with tactile estimation of dural tension and brain herniation after opening of dura.

In 30 patients subjected to craniotomy, subdural pressure was measured with a 22G/0.8 mm Venflon cannula connected to a pressure transducer system. The measurements were performed after removal of the bone flap and just before opening of the dura. The subdural pressure was correlated with the tactile estimation of dural tension and the tendency to brain herniation after opening the dura. The results indicate that generally there is a poor agreement between the tactile feeling of dural tension and subdural pressure. Thus, in some patients with a relatively high dural pressure the dural tension was evaluated as relaxed. At subdural pressure below 6 mmHg brain herniation never occurred. On the other hand, at tensions over 7 mmHg some brain herniation occurred in all patients, and at tension over 11 mmHg pronounced brain herniation occurred. The method of subdural pressure used in this study is simple, the duration of the measurement is less than 1 min. It is concluded that measurement of subdural pressure before opening of the dura gives important information.

The alpha-1,3-galactosyltransferase knockout mouse. Implications for xenotransplantation.

Organ xenografts in discordant combinations such as pig-to-man undergo hyperacute rejection due to the presence of naturally occurring human anti-pig xenoantibodies. The galactose alpha(1,3)-galactose epitope on glycolipids and glycoproteins is the major porcine xenoantigen recognized by these xenoantibodies. This epitope is formed by alpha(1,3)-galactosyltransferase, which is present in all mammals except man, apes, and Old World monkeys. We have generated mice lacking this major xenoantigen by inactivating the alpha(1,3)-galactosyltransferase gene. These mice are viable and have normal organs but develop cataracts. Substantially less xenoantibody from human serum binds to cells and tissues of these mice compared with normal mice. Similarly, there is less activation of human complement on cells from mice lacking the galactose alpha(1,3)-galactose epitope. These mice confirm the importance of the galactose alpha(1,3)-galactose epitope in human xenoreactivity and the logic of continuing efforts to generate pigs that lack this epitope as a source of donor organs.

[Meningeal carcinomatosis in solid tumors]. / Meningeal karcinomatose ved solide tumorer.

Meningeal carcinomatosis (MC) originating from non-haematological tumours is a late event in the course of a malignant disease. MC must be suspected in patients with disperse neurological symptoms from at least two of the following three parts of the central nervous system: the brain, the cranial nerves, and the spinal cord, and if a discrepancy between symptoms and objective findings is found. A suspicion of MC must be confirmed by lumbar puncture and/or MR with Gadolinium in patients where a confirmation of MC will lead to active therapy. Therapy depends on tumour type, performance status of the patient, and present status of the malignant disease. Patients with good performance status and with a chemo-sensitive tumour are offered a combination of radiotherapy and chemotherapy. Median survival is one to three months and active therapy does not prolong survival with certainty. Therefore, therapy primarily aims at an improvement of quality of life for the patient.

[Premature craniosynostosis. Diagnosis and treatment]. / Praematur kraniesynostose. Diagnostik og behandling.

The incidence of premature craniosynostosis is 1:2000-1:4000. Ninety percent of these are simple synostosis with premature closure of one or more of the cranial sutures causing reduced or arrested growth perpendicular to the closed suture(s). Ten percent are more complex craniofacial syndromes, where hypoplasia of the maxilla is also of importance to the development of the orbits. The reduced intracranial volume may result in an increased intracranial pressure and is a contributing factor to the rather high frequency of mental retardation seen in patients with premature craniosynostosis. Early correction is necessary in order to achieve a satisfactory cosmetic result as well as prevention of secondary damage to the brain. Craniofacial syndromes with facial hypoplasia require a staged multi-disciplinary treatment. Patients with simple craniosynostosis have to be treated within the first six months after birth.

[Intraoperative use of ultrasound in neurosurgery]. / Peroperativ anvendelse af ultralyd i neurokirurgi.

Modern ultrasound technique, as in other specialities, has provided the neurosurgeon with an adjuvant which may be employed intraoperatively and which supplements the neuroradiological methods of investigation. The technique provides the surgeon with the possibility of direct visualization, localization and characterization of the pathological and normal structures intracranially and intraspinally by scanning directly on the surfaces of the dura or brain or medulla. The technique provides a good possibility for planning and controlling the extent of tumour resection. By means of a stand with guiding of the cannula, tissue biopsies may be obtained with great certainty and cysts and abscesses may be punctured and evacuated. Placing of a drain in the ventricular system or cysts may be carried out precisely and can be documented by ultrasonic guidance. The technique is employed in approximately one third of the total number of operations in a department of neurosurgery. The technique is simple to use, reasonable inexpensive, does not require addition running costs and may, in addition, be employed as an alternative to CT in neonatal diagnosis and control of hydrocephalus, in particular, by scanning via the fontanelles.

Anterior sacral meningocele. Case report.

One woman (aged 20) and two men (aged 57 and 29, respectively) presented with various urinary and abdominal symptoms, all of which were found at operation to have been caused by anterior sacral meningoceles. All three recovered uneventfully, though the woman was left with some residual numbness of the thigh. Anterior sacral meningocele is a rare condition in which a dural sac herniates into the pelvic region through a congenital defect in the sacrum. Since 1837 182 cases have been reported, and most of them presented with gastroenterological or urogenital signs and symptoms. We have reviewed their symptomatology, pathogenesis and treatment.

Anterior sacral meningocele occurring in one family. An autosomal dominantly inherited condition.

Anterior sacral meningocele is a rare congenital condition. Among 177 individuals familial occurrence was reported only seven times. In this report a family in which five members had anterior sacral meningoceles is presented and an autosomal dominant inheritance is suggested.

Danish experience with the one-piece shunt. A long-term follow-up.

A review of the efficacy and complications of the simple one-piece ventriculoperitoneal shunt is given, based on a consecutive series of 61 children with nontumorous hydrocephalus. Control of the hydrocephalic state was satisfactory but was, however, complicated by a rather high frequency of slit ventricles and subdural effusions. No significant increase in the complication rate was observed among premature babies. The infection rate was low (3%) and no visceral perforations were observed. The one-piece shunt can be recommended, especially for smaller children with hydrocephalus.