Local anticoagulation of the extracorporeal circuit with heparin and subsequent neutralization with protamine during immunoadsorption.

A regimen of local anticoagulation of an immunoadsorption device was studied. The extracorporeal circuit was anticoagulated with citrate (5.5%) and a continuous infusion of heparin (2,000 U/h or 1,500 U/h), which was neutralized by a continuous infusion of protamine chloride (75% of the heparin dose) before reinfusion in 23 patients treated with low-density lipoprotein or immunoglobulin apheresis. Sufficient anticoagulation of the extracorporeal circuit was obtained (activated partial thromboplastin time [APTT] > 180 seconds; thrombin time [TT] > 120 seconds; anti-Xa activity, 1.05 +/- 0.21 U/mL) during the entire treatment of 190 minutes, whereas coagulation parameters in the patients' blood stayed within the normal range. In a control group without heparin neutralization, full systemic anticoagulation of the patients occurred (APTT, 157.8 +/- 30.6 seconds; TT, 119.8 +/- 0.4 seconds; anti-Xa activity, 0.88 +/- 0.21 U/mL). No side effects or clotting of the system were observed. Our data show that this regimen of local anticoagulation is a safe protocol for extracorporeal circulation without exposing the patients to anticoagulants.

Long-term basal forebrain cholinergic-rich grafts derived from trisomy 16 mice do not develop beta-amyloid pathology and neurodegeneration but demonstrate neuroinflammatory responses.

Patients with Down syndrome (human trisomy 21) develop neuropathological and cholinergic functional defects characteristic of Alzheimer's disease, which has been attributed to the location of the Alzheimer beta-amyloid precursor protein on chromosome 21. Due to the partial genetic homology between mouse chromosome 16 and human chromosome 21, murine trisomy 16 was used as a model to study functional links between increased expression of the amyloid precursor protein, neurodegeneration and neuroinflammatory responses. Basal forebrain cholinergic-rich tissue derived from trisomy 16 mice at embryonic age of day 16 was transplanted into the lateral ventricle of adult normal mice. At 1, 3, 6, 9 and 12 months after transplantation, the grafts were characterized by immunocytochemistry, molecular biological analysis, and stereological methods. Grafts survived up to one year and still demonstrated immunoreactivity for cholinergic, GABAergic and astroglial cells. Though a 1.5-fold neuronal over-expression of amyloid precursor protein was detected in brains from trisomy 16 embryos by Northern analysis, beta-amyloid deposits were found neither in control nor trisomic grafts. Detailed stereological analysis of trisomic grafts did not reveal any neurodegeneration or morphological changes of cholinergic and GABAergic neurons during the course of graft maturation up to one year, as compared to grafts derived from euploid tissue. However, both euploid and trisomic grafts demonstrated a strong infiltration with T- and B-lymphocytes and a significant micro- and astroglial activation (hypertrophic astrocytes) within and around the grafts. These observations further suggest that the trisomy 16-induced neurodegeneration is seemingly due to a lack of neuron supporting factors which are provided by either the metabolic interaction of trisomic graft with surrounding healthy host tissue or by cells of the immune system infiltrating the graft.

Direct adsorption of lipoproteins (DALI) from whole blood: first long-term clinical experience with a new LDL-apheresis system for the treatment of familial hypercholesterolaemia.

BACKGROUND: The DALI (direct adsorption of lipoproteins) LDL-apheresis system is a novel device for the removal of lipoproteins from whole blood. METHODS: We report the first long-term treatment experience (16.7 +/- 12.6 months; 57 +/- 43 treatments/patient) using different DALI adsorber sizes (DALI-500, DALI-750, DALI-1000) in seven patients with homozygous (n = 1) and severe heterozygous familial hypercholesterolaemia. For each treatment, 1.6 fold of the calculated blood volume was processed. Treatments were scheduled at weekly or two-weekly intervals. RESULTS: The smallest DALI-500 configuration was unable to achieve sufficient removal of LDL cholesterol, with the adsorber being exhausted already at desorption of 65% of the calculated blood volume. In contrast, both larger adsorber systems effectively removed lipoproteins until the end of treatment. Therefore, the DALI-750 device was used for long-term treatment. LDL cholesterol (mean pretreatment value: 179 +/- 44 mg/dl) was reduced by 73.4 +/- 7.7% and Lp(a) levels (mean pretreatment value: 43 +/- 33 mg/dl) by 69.5 +/- 8.3%. HDL cholesterol (mean pretreatment value: 47 +/- 15 mg/dl) was reduced by 16.3 +/- 8.0% during the treatment. In the long term, LDL cholesterol was reduced by 54.0 +/- 10.5%--from 259 +/- 101 mg/dl to 119 +/- 19 mg/dl. No serious side effects occurred during the treatment. Long-term evaluation of other laboratory parameters showed a reduction in haemoglobin due to treatment-associated blood loss despite frequent iron supplementation. CONCLUSION: Sufficient reductions in LDL cholesterol and Lp(a) were achieved using the DALI-750 system and the treatment was well tolerated. The easy use and short period of 153 +/- 22 minutes required for each treatment are the major advantages of the DALI system as compared to other available LDL-apheresis devices. Potential particle release from the adsorber into the circulation must be ruled out before the system can be introduced in clinical routine.

Laser-induced thermotherapy of neoplastic lesions in the brain--underlying tissue alterations, MRI-monitoring and clinical applicability.

Laser-induced thermotherapy (LITT) is a minimally invasive neurosurgical approach to the stereotactic treatment of brain tumors in poorly accessible regions. Its clinical applicability has been shown in several experimental and clinical studies under on-line monitoring by magnetic resonance imaging (MRI). This review characterizes LITT as an alternative neurosurgical approach with specific focus on the typical histological alterations and ultrastructural cellular changes following laser irradiation in the central nervous system. The spatial and temporal pattern of these changes is discussed in their relevance to the neurosurgical treatment of neoplastic lesions using LITT.

Coagulopathy and outcome in patients with chronic subdural haematoma.

OBJECTIVE: The coincidence of coagulatopathy and chronic subdural haematoma (CSH) requires correction of coagulation to facilitate surgery. We investigated the correlation between coagulopathy and outcome in CSH patients. MATERIAL AND METHODS: We analysed past medical history, surgical treatment and coagulation parameters of 114 patients. RESULTS: Coagulation disorders were found in 42%. Preoperative treatment with prothrombin complex concentrate was necessary in 14%. A significant difference (P < 0.05) of the preoperative level of platelets was found between recurrent CSH and non-recurrent group. Totally, we had to perform re-operations in 17.5%. Eighty-one patients presented with Glasgow coma scale (GCS) > or = 13. After surgery GCS was > or = 13 in n = 92. There was an improvement of GCS in 46 cases, 61 patients maintained GCS score levels. Outcome was significantly worse in the alcoholic group (P < 0.001), and in the recurrent group (P < 0.05). In patients with substitution of coagulation factors, outcome was worse in the group with post-operative substitution only (P < 0.05). CONCLUSION: In CSH, the coagulation parameters and a subtle correction of coagulation are of special interest, regarding the worse outcome in patients with recurrent CSH and in those requiring post-operative substitution.

Intravenous immunoglobulin application following immunoadsorption: benefit or risk in patients with autoimmune diseases?

OBJECTIVE: To evaluate infection rates, side-effects and autoantibody resynthesis after immunoadsorption with and without intravenous immunoglobulin substitution. METHODS: Thirty-five patients with autoimmune diseases who were on long-term immunoadsorption therapy participated in a prospective, randomized study. Results and conclusions. Infections were rare but similar in frequency in patients receiving combined immunoadsorption and intravenous immunoglobulins (intervention group, n=17, 1.3 infections per patient-year) and in a control group (n=18, 0.9 infections per patient-year) treated by immunoadsorption alone. The reduction in IgG achieved with two immunoadsorptions within 3 days was 95.0+/-2.5%. The extent of removal of pathogenic autoantibodies was similar to the removal of IGG: Substitution of immunoglobulins was not associated with an increased circulating IgG level before the following immunoadsorption. Infusion of immunoglobulins at a dose of 0.14 g/kg (interquartile range 0.12-0.16) body weight in patients in whom circulating immunoglobulins had been depleted was associated with a high incidence of serious side-effects; these necessitated the termination of treatment in 24% of the patients. No evidence was found that immunoglobulin administration had any beneficial effect with respect to autoantibody resynthesis after immunoadsorption.

Outcome and prognostic factors of hemicraniectomy for space occupying cerebral infarction.

OBJECTIVE: To determine long term functional outcome and length of survival of patients undergoing decompressive craniectomy for space occupying infarction of the middle cerebral artery (MCA), and to identify risk factors associated with death and unfavourable outcomes METHODS: Databases of patients undergoing decompressive craniectomy for space occupying MCA infarction compiled at eight neurosurgical departments (1996-2001) were merged, and 188 patients were evaluated. Mortality was calculated by the Kaplan-Meier method. Clinical outcome was rated using the Glasgow outcome scale (GOS). The prognostic impact of patient related covariates on length of survival and the GOS was analysed multivariately. RESULTS: The unadjusted 3, 6, and 12 month mortality rates were 7.9%, 37.6%, and 43.8%, respectively (median follow up, 26 weeks). In the "best" multivariate model, age >50 years (p<0.02) and the involvement of two or more additional vascular territories (p<0.01) had an unfavourable impact on length of survival. The adjusted six month mortality was as low as 20.0% (no risk factor) and as high as 59.7% (two risk factors). A GOS score of 50 years (p<0.0003): 34.9% of the patients 3, as compared with 12.0% of the elderly subpopulation. The side of the infarct did not have prognostic relevance. CONCLUSIONS: Results of surgical treatment in patients <50 years of age undergoing decompressive craniectomy are encouraging. The effectiveness of decompressive craniectomy for patients >50 years remains questionable and should be analysed in the framework of a prospective randomised study.

[Preoperative imaging as the basis for image-guided neurosurgery]. / Präoperative Bildgebung. Grundlage der navigationsgestützten Neurochirurgie.

With the progressive development of soft- and hardware, the acceptance of image-guided neurosurgery has increased dramatically. Additional image data are required to analyze the nature and the dimensions of pathological processes and the surrounding tissue. In this context, fMRI, SPECT, PET, as well as special modalities of CT and MR imaging, are routinely used. Secondary post-processing options are used to detect intracerebral lesions as well as adjacent functional eloquent regions in the parenchymatous organ pre- and intraoperatively. The integration of different image information guarantees the precise planning and realization of surgical maneuvers. The segmentation of interesting structures and risk structures, as well as their implementation in the neuronavigation systems, help to avoid additional intraoperative traumatization and offer a higher level of safety and precision. In this article the value and limitations of presurgical imaging will be discussed.