Biomedical subjects

K Roosen

Publications and source records attributed to K Roosen.

At least 19 recordsLinked to original sources

PubMed1998

DNA ploidy and cell-cycle analysis in intracranial meningiomas and hemangiopericytomas: a study with high-resolution DNA flow cytometry.

Although various DNA flow-cytometric studies have been performed on meningiomas, the role of DNA ploidy and the S-phase fraction (SPF) in predicting biological tumor behavior remains unresolved. Discrepant results in earlier studies might be due to different preparing, staining and measuring techniques; different quality standards; and lack of sophisticated computer software. In this study, high-resolution DNA flow cytometry using the DNA-specific dye DAPI (4', 6'-diamidino-2-phenylindol) was performed on stored frozen tissue from 128 microsurgically resected meningiomas and 7 hemangiopericytomas, including 17 recurrent meningiomas and 4 recurrent hemangiopericytomas. The computer software Multicycle 2.5 was used to determine the ploidy level and to perform cell-cycle analysis. DNA aneuploidy and SPF were significantly higher in atypical, anaplastic and recurrent meningiomas and correlated well with histopathological features such as focal necrosis, infiltration of dura mater and mitotic activity. Among 128 meningiomas, 42 had additional DNA aneuploid stem lines. No association between hypo- and hyperploidy and either histological subtype or clinical outcome was found. In 7 hemangiopericytomas, SPF was significantly higher compared to the benign meningioma group, while only 1 tumor was aneuploid. In all 42 DNA aneuploid tumors, cell-cycle analysis was performed separately for the euploid and aneuploid stem lines. The proliferation parameters (SPF, G2/M phase) were significantly higher in the DNA aneuploid stem lines. DNA ploidy and SPF are thus useful indicators of different biological behavior within identical histological subgroups in meningiomas.

Aneuploidy↗

PubMed1998

Bilateral monitoring of CBF and tissue oxygen pressure in the penumbra of a focal mass lesion in rats.

The continuous monitoring of cerebral microcirculation is aimed at preventing secondary ischemic brain damage subsequent to severe head injury. Interrelations between bilateral changes of cortical Laser Doppler Flowmetry (LDF) and intraparenchymal, subcortical p(ti)O2 values were continuously monitored in the forebrain of rodents. A trauma group of 8 animals received an unilateral, focal parietal mass lesion by an expanding epidural balloon. 10 animals served as a sham group. In the sham-operated group the drift of median LDF values was 10.8% in the left and 9.6% in the right hemisphere. The absolute median p(ti)O2 showed values of 31.2 mm Hg (27.9-34.9) in the left and 30.1 mm Hg (27.5-31.7) in the right hemisphere. During maximum brain compression median LDF values decreased ipsilateral to 18.6% (13.3-24.4%) and contralateral to 23.4% (17.1-56.6%) of the baseline values. P(ti)O2 decreased ipsilateral to absolute values of 4.6 mm Hg (3.2-6.7 mm Hg) and contralateral to values of 7.1 mm Hg (6.1-8.5 mm Hg). After balloon deflation cortical LDF was restored much faster but did not reach baseline values [ipsilateral 55.2% (42.6-67.8%); contralateral 67% (53.4-82%) of baseline values]. The p(ti)O2 values reached ipsilateral 77.4% (72.0-93.3%) and contralateral 88.8% (86.0-97.4%) of baseline values. Both parameters showed a significant correlation (r = 0.57; p < 0.02). P(ti)O2 measurements supplement on-line cortical CBF monitoring and by far outscore discontinuous alternative measurement techniques in detecting hemodynamically relevant events. The small spatial resolution of the p(ti)O2 probes, however, which in the small animal model may be of negligible influence, does raise the question whether the values gained offer a general overview of the microcirculatory situation.

Animals↗

PubMed1998

Decompressive craniectomy in patients with uncontrollable intracranial hypertension.

There has been controversial discussion about the benefits of decompressive craniectomy in patients with critically raised intracranial pressure (ICP) after severe head injury. The aim of this retrospective study was to analyze the results of secondary decompressive craniectomy in patients with uncontrollable raised ICP after maximum aggressive medical treatment. The data of 28 patients (mean age 22 years, range 8-44 years) with severe head injury and posttraumatic cerebral edema were analyzed retrospectively. Surgery was not indicated in patients with vast primary lesions, hypoxia, ischemic infarction, brainstem injuries and central herniation. The outcome was classified according to the Glascow Outcome Scale (GOS) after one year. The decompressive crainectomy was performed an average of 68 hours after trauma, and ICP (< 25 mm Hg) decreased always while cerebral perfusion pressure (CPP > 75 mm Hg) improved as well as cerebral blood flow and microcirculation to normal values. 15 patients (56%) had a good outcome after one year (GOS 4 + 5). 5 patients (18%) were severely disabled, 4 patients (14%) remained in vegetative state and 3 patients (11%) died. Decompressive craniectomy should be kept in mind as the last therapeutic step, especially in young patients with head injury and raised ICP, which is not controllable with conservative methods.

Adolescent↗

PubMed1998

Intraoperative microdialysis and tissue-pO2 measurement in human glioma.

The amino acid glutamate is one of the major neurotoxins in the pathogenesis of neuronal death after ischemia or trauma. Microdialysis studies in both man and animal have shown elevated extracellular levels after primary lesions. Monitoring of cerebral tissue oxygenation (p(ti)O2) has been used in recent years to detect and prevent episodes of low cerebral oxygenation, e.g. after trauma or subarachnoid hemorrhage. Intraoperative monitoring of p(ti)O2 combined with microdialysis in the peritumoral edema has been chosen to study the responses of glutamate and oxygen levels during resection. In 7/9 patients p(ti)O2 was below "critical" 10 mm Hg. Elevating inspiratory oxygen concentration to 100% led to an increase of p(ti)O2 by 2.5-4 fold and a decrease of glutamate and aspartate by 50-80%. A close correlation between p(ti)O2 and microdialysis glutamate levels was not clearly shown due to frequent intraoperative manipulations.

Aspartic Acid↗

PubMed1998

Multimodal hemodynamic neuromonitoring--quality and consequences for therapy of severely head injured patients.

Fifty-five head injured patients (GCS < 8) were studied at an average of 7.5 +/- 3.4 days on the ICU to check quality of hemodynamic monitoring and the consequences for therapy. Multimodal neuromonitoring included intracranial pressure (ICP), mean arterial pressure (MAP), cerebral perfusion pressure (CPP), endtidal CO2 (EtCO2) as well as brain tissue--pO2 (p(ti)O2), regional oxygen (rSO2) and jugular venous oxygen saturation (SjO2). Regional p(ti)O2 as well as global SjO2 were sensitive technologies to detect hemodynamic changes. However analyzing reliability and good data quality regional p(ti)O2 (up to 95%) was superior to jugular bulb oximetry (up to 50%). Longterm-measurements of rSO2 using near infrared spectroscopy reached, if possible, a restricted reliability (good data quality up to 70%) and sensitivity in comparison to p(ti)O2. Especially p(ti)O2 enabled detection of critical p(ti)O2 (< 15 mm Hg) in up to 50% frequency during the first days after trauma and a second peak after day 6 to 8 according to evidence of CPP insults. Knowledge of baseline p(ti)O2 and CO2-reactivity allowed minimizing risk of ischemia by induced hyperventilation and improvement on cerebral microcirculation after mannitol administration could be individually recognized.

Blood Pressure↗

PubMed1998

Clinical and pathophysiological significance of severe neurotrauma in polytraumatized patients.

INTRODUCTION: Traumatic brain injury (TBI) is present in up to two-thirds of multiply injured patients. The degree of TBI influenced the mortality and morbidity of multiple trauma significantly. RESULTS: Important prognostic predictors are: injury severity score (ISS); Glasgow coma score [(GCS), motor score]; pupil size and reactivity; coma grade and duration; age; morphological primary brain lesion; and pathophysiological changes leading to secondary brain damage. The time course of brain edema, raised intracranial pressure and, especially, pathophysiology of disturbed cerebral blood flow and metabolism characterizes early and late periods of ischemic vulnerability. CONCLUSION: These should be taken into consideration when planning operative procedures in multiple-trauma patients. Avoidance of secondary ischemic brain damage by reducing the number of systemic insults (hypovolemia, hypotension, hypoxia) will improve prognosis of critically ill polytraumatized patients with head injury.

Brain Edema↗

PubMed1998

Intra-operative colour-duplex-sonography in the surgical management of cerebral AV-malformations.

In this prospective study the role of intra-operative Colour-Duplex-Sonography (= CDS) during surgery of arteriovenous malformations (= AVM) is evaluated. During the last three years 20 consecutive patients with supratentorial AVMs were examined by intra-operative CDS in order to evaluate the potential of CDS to 1) localize the AVM, 2) differentiate between embolized and perfused parts, 3) identify feeding and draining vessels and 4) control the complete excision of the AVM. All AVMs were localized supratentorially, 9 were grade I and II (according to Spetzler and Martin [31]), 8 grade III and 3 grade IV. 11 were partly embolized and 8 associated with an intracerebral bleeding. In all cases the nidus was correctly localized sonographically by its typical bidirectional flow pattern in Colour-mode. CDS guided the surgeon directly to all (11 cases) deep-seated AVMs (2 to 4 cm subcortically). The smallest nidus measured 10 mm. 28 of 34 angiographically defined main feeding and 18 of 23 draining vessels were identified. 14 patients were controlled sonographically at the end of the resection regarding the completeness of excision. In 11 patients CDS was negative and was confirmed by either postoperative angiography or MRI in 10 patients. In one case residual AVM tissue was missed by CDS. Positive CDS findings in 3 cases were all confirmed by microscopic re-inspection, angiography and CCT. Our results suggest that CDS is able to localize AVMs intra-operatively with minimal instrumentation. It allows safe navigation to deep-seated malformations with high accuracy. Feeding and draining vessels can be identified and completeness of resection can be controlled.

Adolescent↗

PubMed1998

Expression of matrix metalloproteinases in human glioma cell lines in the presence of IL-10.

Matrix metalloproteinases have been implicated to play a vital role in glioma invasion as they degrade extracellular matrix to facilitate the subsequent migration of tumor cells into the surrounding brain tissue. The cytokine Interleukin-10 (IL-10) was detected recently in glial tumors in vivo. Expression of specific IL-10 mRNA as well as blood serum levels of IL-10 in glioma patients increased with malignancy suggesting a functional role of IL-10 in glioma progression. Moreover, glioma cell migration in vitro was enhanced in the presence of IL-10. We therefore investigated the expression of the matrix metalloproteinases (MMPs) stromelysin-1 (MMP-3), 72-kDa collagenase (MMP-2), 92-kDa collagenase (MMP-9), matrilysin (MMP-7) and the human macrophage metalloelastase (MMP-12). In addition, a possible relation between exposure of glioma cells to IL-10 and invasiveness of these cells due to MMP expression was analyzed. Experiments with Matrigel coated Boyden chambers revealed a pronounced dose dependent effect of IL-10 on glioma invasiveness. The synthetic MMP-inhibitor Marimastat markedly reduced cell invasion in the Boyden chambers confirming the significance of MMPs in the process of invasion. Subsequently, the expression level of MMPs and the serine protease uPA was investigated in 7 glioma cell lines (U373, GaMG, U251, GHE, SNB19, U138 and D54) by RT-PCR. In all but one cell line no enhancement of MMP expression by IL-10 was detected. Matrilysin in U373 cells was the only protease found to be upregulated in the presence of IL-10 dependent on cell density. The present data suggest that IL-10 related effects on the invasive properties of the cell lines are not directly mediated by an upregulation of matrix metalloproteinase expression.

Brain Neoplasms↗

PubMed1998

Hypothermia influences time course of intracranial pressure, brain temperature, EEG and microcirculation during ischemia-reperfusion.

Time-related effects of hypothermia on intracranial pressure (ICP), brain (Tbr) and rectal temperature (Tc), cortical (LDF) and subcortical microcirculation (ti-pO2) were assessed following a unilateral balloon induced epidural focal mass lesion in rats. Results of injured but normothermia animals (Group A, n = 6) were compared with hypothermia animals (Group B, n = 6). Parameters were recorded during balloon expansion (BE) to an ICP of 60 mmHg followed by a period of sustained inflation (SI) of 30+/-2 min. Animals in Group B were then cooled to 31.7+/-0.4 degrees C (Tbr) during SI. After reperfusion animals were monitored 178+/-4 min. The study protocol concluded with a rewarming phase of the hypothermic animals. Balloon expansion led to a Cushing response and flattening of the EEG. In both groups Tbr decreased during inflation of the balloon 0.5-0.8 degrees C below Tc and during SI in Group A 1.7 degrees C below Tc. During SI and reperfusion Tbr decreased below Tc in Group A but remained above Tc in Group B (p < 0.003). During sustained inflation LDF decreased in group A to 21% and in Group B to 45% of baseline values. After 178+/-4 min of reperfusion LDF reached 68% of baseline values in Group A and 97% in Group B (p < 0.001). During sustained inflation ti-pO2 showed median values of 0.8 mmHg in Group A and 5.5 mmHg in Group B. After reperfusion ti-pO2 reached normal values in both groups (p < 0.3) but ti-pO2 showed 18% higher values before rewarming. After reperfusion the secondary increase of ICP was reduced (p < 0.006) and CPP was improved by 20% in Group B. EEG restored quicker in Group B than Group A (106+/-11 min vs. 188+/-25 min). Intra-ischemic hypothermia improved cerebral microcirculation, prevented a secondary increase of ICP and improved restoration of EEG after ischemia-reperfusion.

Animals↗

PubMed1998

Clinical experience with 118 brain tissue oxygen partial pressure catheter probes.

OBJECTIVE: We assessed the technical and diagnostic reliability of partial pressure of oxygen (PO2) of brain tissue (P(ti)O2) monitoring. The monitoring system and the catheter probes were tested in vitro, and clinical experiences obtained with 118 brain P(ti)O2 catheter probes, used in 101 patients, are reported. METHODS: The polarographic (LICOX; Medical Systems Corp., Greenvale, NY) P(ti)O2 catheter probe lies 22 to 27 mm below the dura level; its PO2-sensitive surface is 7.1 mm2. For 10 patients, the adaptation time (with initially unreliable signals after insertion) was determined. For 27 patients, the probe was removed in a stepwise fashion (three increments of 5 mm) and the heterogeneity of brain P(ti)O2 levels was investigated. After removal of the catheter probes, their PO2 and zero display error values were determined and compared with probe performance data obtained in vitro with unused PO2 catheter probes. RESULTS: Small iatrogenic hematomas were observed for two patients (1.7%). No infection occurred after 6.7 +/- 3.9 days (mean +/- standard deviation) of monitoring. The technical complication (dislocation or defect) rate was 13.6%. The mean adaptation time was 79.0 +/- 51.7 min. A flow chart is presented, which helps to rule out artifacts. The mean P(ti)O2 measured at 22 to 27 mm below the dura was 23.8 +/- 8.1 mm Hg, at 17 to 22 mm was 25.7 +/- 8.3 mm Hg, at 12 to 17 mm was 33.0 +/- 13.3 mm Hg (P < 0.01, compared with the initial value), and at 7 to 12 mm was 33.3 +/- 13.3 mm Hg (P < 0.01). Recent catheter probe versions exhibited a PO2 display error of -1.2 +/- 5.1% (mean +/- standard deviation, n = 38) and a mean zero display error of 1.1 +/- 0.9 mm Hg (n = 34). The greatest PO2 display errors were measured during the first 4 days of continuous monitoring. In the in vitro test (of 12 unused catheter probes), the maximal probe display error was 1.07 +/- 2.14%, tested at temperatures between 22 degrees C and 37 degrees C and tested at oxygen pressures of 0, 44, and 150 mm Hg. In vitro, the zero display error was -0.21 +/- 0.25 mm Hg. CONCLUSION: Brain P(ti)O2 monitoring, reflecting an area 17 to 27 mm below the dura, is a safe and reliable technique for monitoring cerebral oxygenation. Excluding the first 1 hour after insertion, data are reliable, with almost 100% good data quality.

Artifacts↗

PubMed1998

Brain tissue pO2 and outcome after severe head injury.

Although the use of on-line monitoring of brain ti-pO2 is increasing, so far the critical level of 10 mmHg is derived from animal experiments and clinical analyses: no hard proof on outcome basis has been given until now. The authors present an outcome analysis of 35 patients with severe head injury. Inclusion criteria were: start of ti-pO2 monitoring < or = 40 h post-injury, the probe lying in CT scan normal tissue and the GOS at 6 months being available. The good outcome group (GOS 4 + 5, n = 17) showed a 17.7+/-9.1 h delay from the injury to the monitoring compared to the bad outcome group (GOS 1-3, n = 18) with (14.2+/-9.1 h) (p < 0.05). Age and initial Glasgow Coma Score were not different. In the bad outcome group there were more patients with a diffuse injury type 3 and 4. The distribution of the ti-pO2 values show in all the examined time intervals (day 0-6, 0-72 h, 0-48 h and 0-24 h) a left shift in the bad outcome group with most pronounced difference for ti-pO2 < or = 10 mmHg. For the period from 0-48 h and even more from 0-24 h post-injury, the difference between both groups was significant (p = 0.036 and p = 0.013). In the bad outcome group 35.5% of the values from 0-24 h were < 10mmHg (compared to 10.6% in the good outcome group. ti-pO2 values > or = 50 mmHg were seen more often in the bad outcome group; this occurred mainly after 48-72 h post-injury. The authors concluded that brain ti-pO2 monitoring is able to detect the occurrence of early hypoxic insults. Brain ti-pO2 monitoring is an important parameter in the multimodality monitoring system.

Adult↗

PubMed1997

Fast blue, a fluorescent tracer in glioma cell culture, affects cell proliferation and motility.

The azo-dye, Fast Blue (FB), initially employed for retrograde neuronal tracing is increasingly used in cell invasion and migration studies to detect living cells in monolayer and glioma tumor cell spheroid models. As yet, it is assumed that a cell stained with a tracker dye retains the characteristics of the original cell. The following experiments compared the adhesion, migration and proliferation properties of the cell lines U373 and GaMG with and without FB staining. FB staining reduced cell adhesion (P < 0.01) and proliferative activity (P < 0.01) and also had a significant inhibitory effect on cell migration (P < 0.001). From the results presented it follows that FB staining markedly influences basic cell characteristics.

Amidines↗

PubMed1997

Pleomorphic xanthoastrocytoma: report of six cases with special consideration of diagnostic and therapeutic pitfalls.

BACKGROUND: Pleomorphic xanthoastrocytoma (PXA) is a rare clinicopathologic entity that occurs typically in young patients. Improved neuroradiologic techniques, especially gadolinium-enhanced magnetic resonance imaging (MRI), reveal a characteristic tumor appearance. METHODS: We present six cases of PXA operated on with unusual clinical course, elucidating different clinical implications. RESULTS: Two patients showed subsequent progression into a malignant glioma, one case was a primary anaplastic PXA. The latter case had not previously been reported in the literature. Increased mitotic activity seems to indicate a worse clinical course; whereas focal infiltration of the brain does not necessarily lead to malignant transformation. CONCLUSIONS: Surgical removal is the treatment of choice. A consequent follow-up is mandatory in order to detect a potentially malignant recurrence as early as possible and to select patients who need additional therapy.

Adolescent↗

PubMed1997

Brain tissue pO2-monitoring: catheterstability and complications.

The authors report on the stability and complications of 73 LICOX brain ti-pO2-microcatheters in 70 patients. Mean monitoring time was 7.5 +/- 4.0 days. Patients prone to cerebral hypoxia (after severe head injury (GCS < 9) or a subarachnoid hemorrhage) had a ti-pO2-microcatheter inserted next to the ICP-probe in the typical frontal position. After the first 15 insertions, instead of the 3-way-screw (needing a 6 mm burrhole), a 1-way-screw (needing a 2.7 mm burrhole) was used for fixation in the bone; by doing so, the procedure can be performed in the ICU and takes only 15 min. Whenever possible a calibration at room air (to determine the sensitivity-drift) and in oxygen free solution (to determine the zero-drift) was performed after removal of the catheters. Ideally the expected pO2 at room air was around 154 mmHg (temperature dependent) and at zero calibration 0 mmHg. Mean sensitivity-drift for 54 catheters was -8.5 +/- 15.4%. Dividing the catheters into groups, depending on the duration of monitoring (1-4, 5-8 and 9-16 days), revealed that the greatest part of the (negative) sensitivity-drift occurred during day 1-4 after insertion. After 1 week of monitoring sometimes a positive drift occurred (being far less than the negative drift during the first 4 days). Compared to the old catheters (-10.3 +/- 17.3%) (on the first half of the patients) the new ones showed a lower sensitivity-drift (-6.8 +/- 13.4%). The zero-drift of 56 catheters was low with mean drift after 7.5 +/- 4.0 days of 1.5 +/- 1.5 mmHg. Here also the highest drift occurred on day 1-4 after insertion. No infection was seen and 2 times (2.7%) a small hematoma, not needing evacuation occurred. As the ti-pO2-catheter (having a smaller diameter) and the ICP-catheter were inserted at the same time, one cannot distinguish which catheter caused the hematoma. A possible explanation for the occurrence of the two hematomas is the insertion of the catheters too close to the midline. The authors conclude that LICOX ti-pO2-monitoring is a safe and reliable method. Further decrease of the complication rate and increase of the catheter-stability may be expected.

Brain Chemistry↗

PubMed1997

Influence of body position on tissue-pO2, cerebral perfusion pressure and intracranial pressure in patients with acute brain injury.

It is a common practice to position head-injured patients in bed with the head elevated above the level of the heart in order to reduce intracranial pressure (ICP). This practice has been in vivid discussion since some authors argue a horizontal body position will increase the cerebral perfusion pressure (CPP) and therefore improve cerebral blood flow (CBF). However, ICP is generally significantly higher in the horizontal position. The aim of this study was to evaluate changes in regional microcirculation using tissue pO2 (ti-pO2), as well as changes in cerebral perfusion pressure (CPP) and intracranial pressure induced by changes in body position in patients with head injury. The effect of 0 degree and 30 degrees head elevation on ti-pO2. CPP, ICP and arterial blood pressure (MABP) was studied in 22 head injured patients during day 0-12 after trauma. The mean ICP was significantly lower at 30 degrees head elevation than at 0 degree (14.1 + 8.6 vs. 19.9 + 8.3 mmHg). While MABP was unaffected by head elevation, CPP was slightly higher at 30 degrees than at 0 degree (76.5 + 13.5 vs. 71.5 + 13.2 mmHg). However, regional ti-pO2 was unaffected by body position (30 degrees vs. 0 degree: 24.9 + 13.1 vs. 24.7 + 12.9 mmHg). In addition, there was no change in the time course after trauma concerning these findings in the individual patients. The data indicate that a moderate head elevation of 30 degrees reduces ICP without jeopardizing regional cerebral microcirculation as monitored using a polarographic ti-pO2 microcatheter.

Acute Disease↗

PubMed1997

Arachnoid cysts associated with subdural hematomas and hygromas: analysis of 16 cases, long-term follow-up, and review of the literature.

OBJECTIVE: Subdural hematomas and hygromas are infrequently encountered complications of arachnoid cysts of the middle cranial fossa and are particularly rare with cysts of other regions. Reports in the literature focus on casuistic observations. Therapeutic recommendations often include fenestration or extirpation of the cyst wall, in addition to evacuation of the space-occupying lesion. This study evaluates the results of and rationale for a more conservative approach, usually without cyst removal. METHODS: Sixteen cases of complicated arachnoid cysts, from a total of 658 patients with subdural hematomas or hygromas, were analyzed retrospectively together with 75 other cases reported in the literature. Additionally, 94 magnetic resonance imaging scans from 89 patients with untreated arachnoid cysts, from a total of 11,487 examinations, were reviewed for signs of hemorrhagic complications. RESULTS: Arachnoid cysts of the middle cranial fossa were found in 2.43% of patients with chronic subdural hematomas or hygromas. This indicated a fivefold greater prevalence of arachnoid cysts, compared with our magnetic resonance imaging-examined patient group. Only two patients with untreated cysts showed signs of hemorrhage in magnetic resonance imaging scans. An excellent or good therapeutic result was achieved with evacuation of the subdural fluid by drainage or craniotomy in 13 cases and with conservative treatment in two cases. Only one patient underwent additional fenestration of the cyst wall. No additional symptoms from the arachnoid cysts occurred in a follow-up period of up to 14 years after therapy. CONCLUSIONS: We do not generally consider it necessary to perform cyst diversion or fenestration at the time of drainage of a hematoma or hygroma in previously asymptomatic arachnoid cysts.

Adolescent↗

PubMed1997

Inverse correlation of cell proliferation and expression of progesterone receptors in tumor spheroids and monolayer cultures of human meningiomas.

OBJECTIVE: The progesterone receptor (PgR) can be detected in 60 to 70% of meningiomas using immunohistochemistry] in situ. Whereas in monolayer tissue cultures the PgR is only rarely expressed, we were able recently to demonstrate the preservation of the PgR in fragment spheroid cultures of meningiomas. The aim of the present study was to evaluate the stability of PgR expression in meningioma spheroids in vitro and the correlation of PgR expression and cell proliferation in spheroids and whether meningioma cells reaggregated to spheroids from monolayer cultures to reexpress the PgR again. METHODS: Tumor fragment spheroids (Weeks 1-6) and cell monolayers (Passages 1 and 3) of 15 PgR-positive meningiomas were investigated by immunohistochemistry for the expression of PgRs and their proliferative activity, as demonstrated by positivity for the proliferation-related antigen Ki-67. To study PgR reexpression in reaggregated spheroids, Northern blots were performed. In addition, a reverse transcriptase-polymerase chain reaction technique was established and evaluated in combination with immunohistochemistry. Growth of meningioma spheroids was quantified in the presence of progesterone and the specific antagonist onapristone. RESULTS: The PgR remained stable in spheroids for 6 weeks in 9 of 13 cases that were able to be evaluated. All tumor fragment spheroids exhibited a proliferation index of 5 to 40% Ki-67-positive cells. Monolayer cell cultures, on the other hand, failed to express PgRs but revealed higher proliferation indices (40-90%) to a significant extent. The detection of PgR messenger ribonucleic acid in reaggregated spheroids by means of reverse transcriptase-polymerase chain reaction correlated to the nuclear expression of PgR in immunohistochemistry. Neither progesterone nor its antagonist onapristone altered spheroid growth in vitro. CONCLUSION: The expression of the PgR in meningiomas is preserved in spheroid cultures with low proliferation indices for at least 6 weeks, whereas monolayer cell cultures with a high proliferative activity lack PgR expression. The inverse pattern of Ki-67-positive cells in the outer regions of the spheroids and PgR-expressing tumor cells in the spheroid centers leads us to the conclusion that proliferating meningioma tumor cells do not express PgRs. This might also explain why tumor cell growth in vitro was neither affected by progesterone nor by onapristone. Monolayer cell cultures can be reaggregated to spheroids, the consequence being a reexpression of PgRs and, therefore, a down-regulation of proliferation.

Antineoplastic Agents↗

PubMed1997

Intraoperative color duplex sonography of basal arteries during aneurysm surgery.

This prospective study aimed at (1) characterizing the duplex sonographic appearance of cerebral aneurysms, (2) visualizing their location, and (3) ensuring the complete occlusion of the aneurysm as well as the patency of the basal arteries during aneurysm surgery. During 9 months 30 craniotomies for aneurysm clipping in 29 patients were monitored intraoperatively by B-mode and color-coded duplex sonography. Following craniotomy the aneurysm and the preaneurysmatic and postaneurysmatic arteries were sonographically visualized before and after clipping and removal of the spatulas. Twenty-seven (90%) of 30 aneurysms appeared as a hypoechoic structure. Together with the typical dichromatic picture in the color mode and the characteristic bidirectional flow pattern in the duplex mode, 29 (97%) of 30 aneurysms were identified and localized anatomically correctly. Eighty (99%) of 81 relevant vessels were visualized and measured with the Doppler mode. After clipping, flow was detectable in all major arteries except 3 middle cerebral artery (MCA) branches. In 1, occlusion was confirmed by postoperative angiography. In the other 2, early postoperative computed tomography showed an infarction of the corresponding MCA territories. This study demonstrated the potential of color duplex sonography to visualize and characterize cerebral aneurysms and adjacent basal arteries before and after clipping. It offers a noninvasive intraoperative method to control the patency of basal arteries and complete occlusion of the aneurysm.

Aneurysm↗