Assessment of adjacent-segment mobility after cervical disc replacement versus fusion: RCT with 1 year's results.

Disc prostheses have been designed to restore and maintain cervical segmental motion and reduce the accelerated degeneration of the adjacent level. There is no knowledge about the reaction of the neighboured asymptomatic segments after implantation of prostheses or fusion. The effects of these procedures to segmental movement of the uninvolved vertebrae have not been subjected to studies so far. The objective of this study was to compare the segmental motion following cervical disc replacement versus fusion and the correlation to the clinical outcome. Another aim was to compare the segmental motion of the asymptomatic segments above the treated ones and to compare both with Roentgen stereometric analysis (RSA) including the asymptomatic segments. 20 patients with one-level cervical radiculopathy scheduled for surgery were randomized to arthroplasty (10 patients, study group) or anterior cervical discectomy and fusion (10 patients, control group). Clinical results were evaluated using Visual Analogue Scale and Neck Disability Index. RSA was performed immediately postoperative, after 6 and 12 months. The adjacent segment showed a significantly higher segmental motion in all three-dimensional axes in comparison to the segment treated with prostheses (P < 0.05). In the fusion group the segmental motion of the adjacent segment was significantly higher in all three-dimensional axes (P < 0.05) at each examination time. When the adjacent level of both groups is compared, the fusion group could show a higher segmental motion in all three-dimensional axes, but without significant difference (P > 0.05) 1 year after surgery. Regarding the clinical results, there was no significant difference in pain relief between both groups (P > 0.05). In conclusion, the adjacent segment could show a higher segmental motion, when compared with the segment either treated with prostheses or fusion. There was no significant difference in segmental motion adjacent to prosthesis or fusion. Clinical results did also show no significant difference in pain relief between both groups.

Combining gene expression signatures and autoantibody profiles in human meningioma.

Gene expression profiling has emerged as powerful technique for studying the mechanisms of tumor genesis and development. Seroreactivity profiling of tumor antigens is a more recent technique that further contributes to the understanding of tumors and that offers itself for noninvasive tumor diagnosis. We performed expression profiling of 55,000 transcripts and expressed-sequence-tags for 24 meningiomas and related these data to autoantibody profiles of more than 50 antigens immunogenic in the autologous patients. The expression values of antigens in WHO grade I meningioma were significantly higher if the patients' sera reacted with these antigens as confirmed by a two-tailed Wilcoxon-Mann-Whitney test. Specifically, KIAA1344 that was previously identified as frequent antigen marker in meningioma, showed increased expression if antigens against KIAA1344 were detected in autologous patients. Our study is the first to combine genome-wide expression signatures and comprehensive seroreactivity patterns toward a more complete view on tumor immunology, especially concerning the overall role of the level of gene expression on the immunogenicity of meningioma antigens.

Increased intracranial pressure caused by non-space-occupying arachnoid cysts: report of two patients.

In this article we report on two patients with arachnoid cysts previously treated by shunt implantation presenting with clinical signs of an increased intracranial pressure i. e., papilledema, headache and nausea. Repeated MRI scans showed no alteration of the cerebrospinal fluid circulation and no space-occupying effect of the cysts. Although neuroimaging showed no signs of increased intracranial pressure, neurosurgical exploration was performed and revealed a distinctly increased pressure in both arachnoid cysts. After replacement of the shunt a prompt reduction of papilledema and relief of symptoms was observed.

Accuracy of ultrasound-guided puncture of the ventricular system.

OBJECTS: Puncture of the ventricular system as one of the most frequently performed operative procedures in neurosurgery is usually done in a freehand way without guiding devices. The objective of this study is to examine whether ultrasonic guidance is able to heighten the accuracy of ventricular tapping. METHODS: Real-time imaging via a single burr hole approach is achieved by aid of a bajonet-like shaped transducer with a footprint of 8x8 mm only (EUP-NS32, Hitachi Medical Systems). The needle is advanced towards the frontal horn along a displayed guideline. 51 punctures in 48 patients were performed with ultrasonic guidance and compared to 85 punctures in 67 patients without a guiding device. CONCLUSION: The presented ultrasound method was not able to heighten the access rate of ventricular tapping, but it improved correct positioning of the catheter tip inside the frontal horn of the ventricular system significantly.

Biomechanical effect of different lumbar interspinous implants on flexibility and intradiscal pressure.

Interspinous implants are used to treat lumbar spinal stenosis or facet joint arthritis. The aims of implanting interspinous devices are to unload the facet joints, restore foraminal height and provide stability especially in extension but still allow motion. The aim of this in vitro study was to compare four different interspinous implants--Colfex, Wallis, Diam and X-Stop--in terms of their three-dimensional flexibility and the intradiscal pressure. Twenty-four human lumbar spine specimens were divided into four equal groups and tested with pure moments in flexion/extension, lateral bending and axial rotation: (1) intact, (2) defect, (3) after implantation. Range of motion and the intradiscal pressure were determined. In each implant-group the defect caused an increase in range of motion by about 8% in lateral bending to 18% in axial rotation. Implantation had similar effects with all four implants. In extension, Coflex, Wallis, Diam, and X-Stop all overcompensated the instability caused by the defect and allowed about 50% of the range of motion of the intact state. In contrast, in flexion, lateral bending and axial rotation the values of the range of motion stayed about the values of the defect state. Similarly the intradiscal pressure after implantation was similar to that of the intact specimens in flexion, lateral bending and axial rotation but much smaller during extension. All tested interspinous implants had a similar effect on the flexibility: they strongly stabilized and reduced the intradiscal pressure in extension, but had almost no effect in flexion, lateral bending and axial rotation.

Hypoxic pulmonary blood flow redistribution and arterial oxygenation in endotoxin-challenged NOS2-deficient mice.

Sepsis and endotoxemia impair hypoxic pulmonary vasoconstriction (HPV), thereby reducing arterial oxygenation and enhancing hypoxemia. Endotoxin induces nitric oxide (NO) production by NO synthase 2 (NOS2). To assess the role of NO and NOS2 in the impairment of HPV during endotoxemia, we measured in vivo the distribution of total pulmonary blood flow (QPA) between the right (QRPA) and left (QLPA) pulmonary arteries before and after left mainstem bronchus occlusion (LMBO) in mice with and without a congenital deficiency of NOS2. LMBO reduced QLPA/QPA equally in saline-treated wild-type and NOS2-deficient mice. However, prior challenge with Escherichia coli endotoxin markedly impaired the ability of LMBO to reduce QLPA/QPA in wild-type, but not in NOS2-deficient, mice. After endotoxin challenge and LMBO, systemic oxygenation was impaired to a greater extent in wild-type than in NOS2-deficient mice. When administered shortly after endotoxin treatment, the selective NOS2 inhibitor L-NIL preserved HPV in wild-type mice. High concentrations of inhaled NO attenuated HPV in NOS2-deficient mice challenged with endotoxin. These findings demonstrate that increased pulmonary NO levels (produced by NOS2 or inhaled at high levels from exogenous sources) are necessary during the septic process to impair HPV, ventilation/perfusion matching and arterial oxygenation in a murine sepsis model.

Sustained pulmonary hypertension and right ventricular hypertrophy after chronic hypoxia in mice with congenital deficiency of nitric oxide synthase 3.

Chronic hypoxia induces pulmonary hypertension and right ventricular (RV) hypertrophy. Nitric oxide (NO) has been proposed to modulate the pulmonary vascular response to hypoxia. We investigated the effects of congenital deficiency of endothelial NO synthase (NOS3) on the pulmonary vascular responses to breathing 11% oxygen for 3-6 wk. After 3 wk of hypoxia, RV systolic pressure was greater in NOS3-deficient than in wild-type mice (35+/-2 vs 28+/-1 mmHg, x+/-SE, P < 0.001). Pulmonary artery pressure (PPA) and incremental total pulmonary vascular resistance (RPI) were greater in NOS3-deficient than in wild-type mice (PPA 22+/-1 vs 19+/-1 mmHg, P < 0.05 and RPI 92+/-11 vs 55+/-5 mmHg.min.gram.ml-1, P < 0.05). Morphometry revealed that the proportion of muscularized small pulmonary vessels was almost fourfold greater in NOS3-deficient mice than in wild-type mice. After 6 wk of hypoxia, the increase of RV free wall thickness, measured by transesophageal echocardiography, and of RV weight/body weight ratio were more marked in NOS3-deficient mice than in wild-type mice (RV wall thickness 0.67+/-0.05 vs 0.48+/-0.02 mm, P < 0.01 and RV weight/body weight ratio 2.1+/-0.2 vs 1.6+/-0.1 mg. gram-1, P < 0.05). RV hypertrophy produced by chronic hypoxia was prevented by breathing 20 parts per million NO in both genotypes of mice. These results suggest that congenital NOS3 deficiency enhances hypoxic pulmonary vascular remodeling and hypertension, and RV hypertrophy, and that NO production by NOS3 is vital to counterbalance pulmonary vasoconstriction caused by chronic hypoxic stress.

Worsening of long-term myocardial function after successful pharmacological pretreatment with cyclosporine.

Pretreatment with cyclosporine (CsA) decreases infarct size 24h after myocardial ischemia/reperfusion (I/R). The goal of this study was to determine effects of CsA pretreatment on long-term cardiac function after I/R-injury. Rats were randomly assigned to group-1: vehicle-only, group-2: CsA-5mg/kg/day, and group-3: CsA-12.5mg/kg/day given orally for three days prior to I/R-injury (30 min of left anterior descending coronary artery occlusion). Post-I/R survival and cardiac function were evaluated 14 days after I/R-injury by echocardiography and invasive hemodynamic measurements. Rats with I/R-injury showed increased left ventricular pressure (LVEDP) compared to rats without I/R-injury (p<0.005). Although CsA initially decreased infarct size, no differences of LVEDP were seen 14 days after I/R-injury (vehicle: 21.2+/-8.9 mmHg, CsA-5mg/kg/day: 21.5+/-0.7 mmHg, CsA-12.5mg/kg/day: 20.5+/-9.4 mmHg). Ejection fraction and fractional shortening were decreased compared to baseline, but showed no differences between groups. On day 14, a dose-dependent increase in left ventricular end diastolic diameter was seen (p<0.001). CsA pretreatment was associated with a dose-dependent decrease in post-I/R-survival (vehicle: 56%, CsA-5mg/kg/day: 32%, CsA-12.5mg/kg/day: 16%; p=0.017). CsA pretreatment did not improve long-term cardiac function despite decreased infarct size 24h after I/R-injury, but increased post-I/R mortality significantly. Poor cardiac function after CsA pretreatment might be caused by left ventricular dilation.

The histochemical profile of the rat extensor digitorum longus muscle differentiates after birth and dedifferentiates in senescence.

Age dependent motor unit dedifferentiation is a key component of impaired muscle function in advanced age. Here, we tested the hypothesis that rat muscle histochemical profile during the lifespan of an individual has an age-specific pattern since comprehensive longitudinal studies of muscle differentiation after birth and dedifferentiation in advanced age are scarce. Our results show that extensor digitorum longus muscle (EDL) is comprised only of two fiber types after birth, type slow-oxidative (SO) and type SDH-intermediate (SDH-INT), the latter being indicative for the presence of polyneuronal innervation. In contrast to the constantly growing cross-sectional area of the muscle fibers, a dramatic decrease in SDH-INT proportion occurs between day 14 and 21 after birth resulting in a complete loss of fiber type SDH-INT at the age of 90 days (p<0.05). At the age of 270 days, the fiber type composition of rat EDL dedifferentiates as shown by the reappearance of the SDH-INT type with a further increase at the age of 540 days (p<0.05). These changes in histochemical fiber type spectra are brought about by fiber type conversion within the fast twich fibers. The findings of the present study provide further evidence that fiber type conversion is a basic mechanism leading to motor unit differentiation and dedifferentiation during ontogenesis. Fiber type conversion shows a distinct time specific pattern and is also characteristic for motor unit regeneration after peripheral nerve repair. Factors that influence fiber type conversion and thereby motor unit organization may provide a future therapeutic option to enhance the regenerative capacity of motor units.

Segmental kinematics and adjacent level degeneration following disc replacement versus fusion: RCT with three years of follow-up.

STUDY DESIGN: Prospective, randomized and controlled clinical and radiological study. OBJECTIVE: The aim of this study was to assess the segmental kinematics and clinical outcome of disc replacement with ProDisc C versus anterior cervical discectomy and fusion (ACDF) for monosegmental disease 3 years after surgery. SUMMARY OF BACKGROUND DATA: Anterior cervical discectomy and fusion (ACDF), including plate fixation, is an accepted technique for treatment of symptomatic degenerative disc disease (DDD). However, various studies could show that fusion of a relative mobile spinal segment leads to heightens of stresses on the discs below and above fusion, which is manifested as adjacent level degeneration. Intervertebral disc replacement has been attempted to restore intervertebral disc height and to maintain segmental motion, which may be thought to avoid the accelerated degeneration to the adjacent level. In earlier studies, we could show that ProDisc C could maintain segmental motion for 1 year after surgery. METHODS: 49 patients with cervical disc herniation underwent arthroplasty of a single level using ProDisc C disc prosthesis or received fusion using a cage and anterior titanium plate fixation. Clinical outcome was assessed using the visual analogue scale (VAS) and the neck disability index (NDI). Radiostereometry was performed immediately postoperative and then after 1, 2, and 3 years after surgery to quantify the segmental kinematics. RESULTS: The range of motion of the treated segment with prosthesis remained unchanged 3 years after surgery in comparison to the 1-year result. The prosthesis shows a significant segmental motion in contrast to the fusion group at each RSA examination time (p < 0.05). After both procedures, a significant pain reduction in neck and arm was observed, without significant differences between both groups. During the course of the 3 years follow-up, no patients of the prosthesis group required further surgical intervention.

Analysis of spinal kinematics following implantation of lumbar spine disc prostheses versus fusion: radiological study.

STUDY DESIGN: This is a prospective controlled study comparing lumbar spine disc replacement versus fusion for monosegmental degenerative disc disease (DDD). SUMMARY OF BACKGROUND DATA AND OBJECTIVE: Fusion has been reported to be the standard therapy by DDD of the lumbar spine. Due to unsatisfactory long-term results of fusion by progressive adjacent level degeneration, disc replacement was developed and thought to reduce pain while restoring disc height and motion at the affected level. The expected long-term advantage of disc replacement over fusion is the preservation of motion. This again is very difficult to judge; therefore the aim of the current study was to analyze segmental motion following disc replacement versus fusion. METHODS: Patients meeting inclusion criteria were consented for the study. This analysis includes data up to 12 months from the first included patients. There were 13 patients who underwent disc replacement, and 11 patients had fusion procedures. Radiostereometric analysis was done 1 and 6 weeks and 3, 6, and 12 months after surgery. RESULTS: The mobility provocation RSA showed a significant segmental motion in the disc replacement group in comparison to fusion. CONCLUSIONS: Disc replacement using Active L prostheses preserves segmental motion during the period examination time of 12 months.

Outcome predictors for normal-pressure hydrocephalus.

The objective of this prospective study was to find outcome predictors for better selection for treatment of normal-pressure hydrocephalus (NPH) patients. A total of 125 patients were evaluated and provided with a gravitational shunt. Cerebrospinal fluid hydrodynamics provided better predictive values if an algorithm to shunt all patients with a pressure/volume index of < 30 mL or resistance to outflow > 13 mmHg/mL x min was used. In general, outcome became worse with increasing anamnesis duration, worse preoperative clinical state, and increasing comorbidity. If one of these parameters was lower than a critical value, the shunt-responder rate was about 90% and the normally negative influence of older age was not seen. The well-known paradigm of a worse prognosis with NPH is not the result of the hydrocephalus etiology itself, but the consequence of a typical accumulation of negative outcome predictors as a consequence of the misinterpretation of normal aging and delayed adequate treatment.

PHF3-specific antibody responses in over 60% of patients with glioblastoma multiforme.

Glioblastoma multiforme (GBM), a malignant astrocytic tumour, represents the most frequent tumour of the human brain. Nevertheless, its molecular pathology is not well understood. We utilized the immune system, which contributes to cancer protection, to help identify new GBM-related genes. By screening a human GBM cDNA library with autologous patient serum (SEREX-approach), we isolated a gene termed PHF3 (PHD finger protein 3). The gene product of PHF3 is immunogenic in GBM as tested in an allogenic patient serum screening demonstrating antibodies in 24 of 39 (61.53%) sera, whereas none of the 14 healthy persons had antibodies against PHF3. While previous SEREX studies revealed allogenic antibody responses up to 40%, our results for PHF3 represent the highest reported rate for a specific antibody response. We show that GBM patients with an antibody response against PHF3 show significant better survival than patients without PHF3-specific antibodies. Because the amino acid sequence of PHF3 contains a PHD finger (also termed LAP motif), a TFIIS homology, a proline rich region and nuclear localization signals, it supposedly functions as a transcription factor. A polyclonal antibody generated against PHF3 shows nuclear expression in most investigated formalin-fixed, paraffin embedded tissues. In GBM, PHF3 expression is concentrated in cells surrounding necroses.

Amplification and expression of splice variants of the gene encoding the P450 cytochrome 25-hydroxyvitamin D(3) 1,alpha-hydroxylase (CYP 27B1) in human malignant glioma.

PURPOSE: Recently, we reported the isolation of six novel genes termed glioma-amplified sequences (GASs) from the glioblastoma cell line TX3868 using microdissected mediated cDNA capture (U. Fischer et al., HUM: MOL: GENET:, 5: 595-600, 1996). The aim of this study was to further characterize the gene GAS89. EXPERIMENTAL DESIGN: To determine the amplification frequency, we performed comparative PCR studies and Southern blot hybridization experiments. To identify full-length clones of GAS89 we screened a HybriZAP library. Reverse transcription-PCR was performed to isolate splice variants and to determine expression levels. RESULTS: We identified for the gene GAS89 an amplification frequency of 25% in 28 examined glioblastoma multiforme samples. Screening a HybriZAP library, we isolated an incomplete gene sequence showing identity with the gene for 25-hydroxyvitamin D(3) 1,alpha-hydroxylase. Different full-length clones were then isolated using PCR primers chosen from the 3'- and 5'-untranslated regions. As determined by sequencing, the clones represent various splice variants of the 25-hydroxyvitamin D(3) 1,alpha-hydroxylase gene. The clones encode truncated proteins but also one potentially functional enzyme variant. Reverse transcription-PCR studies revealed overexpression of several variants in glioblastoma samples with GAS89 amplification in comparison with normal brain RNA and glioblastoma without GAS89 amplification. CONCLUSIONS: This is the first report of gene amplification for 25-hydroxyvitamin D(3) 1,alpha-hydroxylase and the appearance of mRNA splice variants in glioblastoma multiforme. The endogenous expression of the 25-hydroxyvitamin D(3) 1,alpha-hydroxylase gene and the appearance of alternative splice variants reveal a new feature of the molecular pathogenesis of glioblastoma and may represent a new target for glioma therapy.

Novel tankyrase-related gene detected with meningioma-specific sera.

In many meningiomas, alterations of chromosome 22 can be found, and the NF2 (neurofibromatosis type 2) gene, in particular, is of great interest as a putative gene involved in meningioma. Because the NF2 gene is not mutated in all meningiomas, additional genes may be involved. Instead of looking for alterations directly at the DNA level, we used the immune response of meningioma patients to identify immunogenic antigens that may be associated with the disease. We screened a fetal brain cDNA expression library with sera pools from different patients bearing meningioma classified according to the three WHO grades, using the serological identification of antigens by recombinant expression cloning immunological screening method. Here, we report the finding of a new tankyrase-related protein. We found 16 overlapping clones with homologies to tankyrase when we screened the library with the common-type meningioma sera pool and 2 such clones when we screened the library with the atypical meningioma sera. The anaplastic meningioma sera did not identify any tankyrase-related clones. We tested some of the newly identified clones with 13 single sera, 6 of which (37.5%) reacted positively with the tankyrase-related clones. In addition, we screened the tankyrase-related clone with six sera pools from individuals without obvious disease. Although 1 of 24 (4.2%) normal sera reacted with the tankyrase-related clone, we found a striking difference in the frequency of reactivity to this clone by sera from patients bearing tumors corresponding to the three WHO meningioma grades; common-type sera was the most frequently reactive. Northern blot analysis demonstrates expression of the novel tankyrase gene in two common-type meningiomas from patients with immune response.

Deletion of chromosome 1p and loss of expression of alkaline phosphatase indicate progression of meningiomas.

Meningiomas are cytogenetically characterized by loss of one chromosome 22 as a typical primary aberration and progression-associated secondary chromosome changes, of which monosomy 1p is the most common. The aim of this study was to evaluate the significance of monosomy 1p and enzyme activity loss of tissue nonspecific alkaline phosphatase (ALPL), whose gene maps to chromosome 1p36.1-p34, as parameters for the diagnosis of progression-prone meningiomas. We analyzed smear preparations of 56 meningiomas and additional paraffin sections of 17 of the cases by two-color fluorescence in situ hybridization (FISH) using the D1Z1 and D1Z2 probes and by a metaphase cytogenetic analysis of 30 of these tumors. The results were compared to clinical and morphological parameters and the expression of ALPL. Smear preparations showed deletion of 1p36 in 27% of common-type, 70% of atypical (intermediate-type), and 100% of anaplastic meningiomas. Monosomy 1p, as detected by FISH or the karyotype, was strongly associated with complete loss of ALPL activity. Intermediate-type and anaplastic meningiomas of younger patients displayed an increasing rate of cells with trisomy 1q and relative loss of 1p. The highly significant correlation of FISH results and ALPL histochemistry with clinical parameters gives evidence of their strong prognostic relevance. The complete activity loss of ALPL and the immunologically detected loss of ALPL protein in areas of meningiomas with monosomy 1p indicate a cytogenetically undetectable inactivation of the homologous Alpl allele. The apparently homozygous loss of expression of ALPL supports the notion that Alpl is a candidate tumor suppressor gene in meningiomas.

Gravitational shunt management of long-standing overt ventriculomegaly in adult (LOVA) hydrocephalus.

OBJECTIVES: Recently a new subtype of chronic hydrocephalus was described: long-standing overt ventriculomegaly in adults (LOVA). Experience to date has indicated that shunt therapy was contraindicated, due to over-drainage. Therefore we investigated whether this problem could be overcome using gravitational shunts. MATERIALS AND METHODS: Thirty macrocephalic adults (17-72 years of age), suffering from progressive hydrocephalus were managed with two different gravitational shunts. The post-operative observation period was 5-87 months. RESULTS: Only two patients developed hygromas, and only one of these required surgical shunt revision. Eighty-seven percent of patients had a long-lasting clinical improvement. Ventricular size was only slightly reduced in 29 patients. There was no correlation between reduction in ventricular size and clinical improvement. CONCLUSION: Contrary to clinical guidelines issued to date, we demonstrate that LOVA can be treated reliably with gravitational shunts, making them a genuine alternative to endoscopic third ventriculostomy (ETV).

Simple decompression or subcutaneous anterior transposition of the ulnar nerve for cubital tunnel syndrome.

The purpose of this prospective randomised study was to evaluate which operative technique for treatment of cubital tunnel syndrome is preferable: subcutaneous anterior transposition or nerve decompression without transposition. This study included 66 patients suffering from pain and/or neurological deficits with clinically and electromyographically proven cubital tunnel syndrome. Thirty-two patients underwent nerve decompression without transposition and 34 underwent subcutaneous transposition of the nerve. Follow-up examinations evaluating pain, motor and sensory deficits as well as motor nerve conduction velocities, were performed 3 and 9 months postoperatively. There were no significant differences between the outcomes of the two groups at either postoperative follow-up examination. We recommend simple decompression of the nerve in cases without deformity of the elbow, as this is the less invasive operative procedure.

Loss of alkaline phosphatase activity in meningiomas: a rapid histochemical technique indicating progression-associated deletion of a putative tumor suppressor gene on the distal part of the short arm of chromosome 1.

Apart from defined histomorphologic features, increased Ki-67 indices and various numeric and structural chromosome aberrations, meningiomas of the intermediate (WHO grade II, atypical meningioma) and anaplastic type (WHO grade III) are cytogenetically distinguished from common-type meningiomas (WHO grade I) by frequent loss of the distal part of the short arm of one chromosome 1 (1p-), which formerly proved to be an independent predictor of shorter recurrence-free intervals. Histochemically, loss of alkaline phosphatase activity (ALPL, liver/bone/kidney type, EC 3.1.3.1) was another frequent, specific finding in meningiomas with signs of dedifferentiation. In a prospective study including 66 meningiomas, all common-type meningiomas except one case (18/19) were reactive for ALPL, whereas 75% (30/39) of intermediate type and all anaplastic meningiomas (8/8) showed loss of enzyme activity in large areas of the tumor. Exclusively, the ALPL negative phenotype was associated with 1p loss (15/19). Our data suggest that ALPL, which is coded as a single copy gene on chromosome 1p36.1-p34, is a useful marker enzyme for the loss of a putative regulatory (tumor suppressor) gene on chromosome 1p, or that ALPL itself represents a new tumor suppressor gene homozygously inactivated in meningiomas.

Changes in regional energy metabolism after closed head injury in the rat.

We examined in the present investigation regional ATP, glucose, and lactate content in the cortical and subcortical structures, in a rat model of closed head injury (CHI). In serial tissue sections bioluminescence imaging of ATP, glucose, and lactate was performed at 4 h, 12 h and 24 h (n = 4/5 per time point with) after the induction of CHI or sham surgery. Bioluminescence images were analyzed by computer-assisted densitometry, at the lesion site, in remote cortical areas, and in the subcortical structures (thalamus and caudate nucleus). ATP content was significantly decreased at the lesion site after 4 h and in the remote cortex at 12 h post-injury. At 12 h, the ATP content reached baseline levels on the ipsilateral side and at 24 h also at remote lateral parietal sites. In the contralateral cortex, ATP increased transiently above the baseline at 12 h. No significant changes in ATP were found in the thalamus and caudate nucleus. Cortical glucose and lactate contents could not be discerned over time. Following CHI there is an acute and progressive, yet transient, ischemic cortical profile, which is not reflected in subcortical areas.