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Biomedical subjects

E Markakis

Publications and source records attributed to E Markakis.

At least 19 recordsLinked to original sources

mRNA quantification and clinical evaluation of telomerase reverse transcriptase subunit (hTERT) in intracranial tumours of patients in the island of Crete.

Telomerase is a reverse transcriptase that maintains telomeres by adding telomeric TTAGGG repeats to the ends of human chromosomes. The aim of this study was to evaluate quantitatively the mRNA expression of telomerase catalytic subunit (hTERT) in different types of intracranial tumours in relation to their histologic pattern and grade and correlate it with progression-free (PFS) and overall survival (OS) of patients. Human telomerase reverse transcriptase mRNA levels were estimated by the use of real time RT-PCR in 68 samples of intracranial tumours. It revealed statistical correlation between hTERT mRNA expression levels and the grade of the tumours (P<0.001). Patients having negative expression of hTERT mRNA had statistically longer PFS (P=0.031) and OS (P=0.047). Cox univariate regression analysis revealed that hTERT mRNA-positive patients had a high and statistically significant risk of relapse (hazard ratio (HR) of 2.24 and P=0.038). In the Cox multivariate regression model, the levels of hTERT mRNA were adjusted for tumour grade and patients age, and since there was statistically significant relationship between the levels of hTERT mRNA and the grade of the tumours (P=0.003 or P=0.006, respectively), hTERT mRNA levels could not be considered as an independent prognostic factor for PFS or OS.

Brain Neoplasms↗

Intrinsic brainstem tumours in adults: results of microneurosurgical treatment of 16 consecutive patients.

Intrinsic brainstem tumours in adults have a poor prognosis and surgical resection is rarely performed. Encouraged by successful operations on children performed in our department, we began a more aggressive strategy of open operations. Between 1986 and 1997, we operated upon 16 consecutive patients over 16 years of age (five female, 11 male, mean age 36.9 years) who were suffering from intrinsic tumours located in the pons and/or medulla oblongata. The extent of first open resection was 80 - 100% in two of the cases and more than 50% in nine cases. The mean survival time after the first occurrence of symptoms was 88.1 (median 34.5) months, and 39.9 (median 11) months after the first open operation. The rate of 5-year survival from the first occurrence of symptoms was 37.5% (25% after the first open surgical procedure). Thirteen out of 16 patients died within the follow-up period of at least 6.3 years, two of them within the immediate postoperative period. Eleven patients experienced a postoperative deterioration of symptoms from which only four recovered. Eight patients had from WHO grade II astrocytoma and a similar course as patients with higher-grade gliomas (n = 4). Our results indicate that open microneurosurgery for intrinsic brainstem tumours is of questionable benefit for the patient. Although surgery offers the advantages of reliable confirmation of histopathology and may be associated with prolonged survival, neurological deterioration was common and, unlike in paediatric patients, often irreversible.

Adolescent↗

A pair of clamps for a safe removing and repositioning of beta and gamma angular settings of Brown-Roberts-Wells stereotactic system during operation.

The Brown-Roberts-Wells arc system is a non-target-centered design, i.e., without an independent approach angle. The approach angle of this system strictly depends on precalculated values (entry and target point). Therefore, some components of the system used sometimes prevent a direct insight into the operation field. Once the entry point has been set, the arc system normally has to be taken off to permit an unimpeded approach to the burr hole. To facilitate rotation and return to the primary beta and gamma angular settings during stereotactic craniotomy and other surgery, a pair of clamps was designed for the BRW arc system. These clamps help the approach to the entry point in such a way that some components of the arc (e.g., the guide block holder) are removed from the surgical field, thus giving wide visual access for the stereotactic approach. Consequently, it is no longer necessary to remove the entire arc system, resulting in an increased operation safety and shorter operation times.

Equipment Design↗

Quantitative proton magnetic resonance spectroscopy of focal brain lesions.

The diagnostic value of single-voxel proton magnetic resonance spectroscopy (2 T, stimulated echo acquisition mode, TR = 6,000 ms, TE = 20 ms, 4-5 mL volumes-of-interest) was assessed for a differentiation of focal brain lesions of unknown etiology in 17 patients 1-14 years of age. Absolute metabolite concentrations were compared with age-matched control subjects and an individual control region. Most of the brain tumors were characterized by strongly reduced total N-acetylaspartyl compounds and marked increases of myo-inositol and choline-containing compounds, consistent with a lack of neuroaxonal tissue and a proliferation of glial cells. Lactate was elevated in only four patients. When using this pattern for a metabolic discrimination of brain tumors from other focal lesions, proton spectroscopy correctly identified 14 of 17 abnormalities, as confirmed by histologic examination after neurosurgical intervention. One false-positive tumor diagnosis was a severe reactive gliosis mimicking a typical tumor spectrum. Two inconclusive cases comprised an astrocytoma with moderately elevated myo-inositol but reduced choline-containing compounds and a patient with an abscess leading to a marked reduction of all metabolites but strong contributions from mobile lipids. In summary, quantitative proton spectroscopy has considerable clinical value for preoperative characterization of focal brain lesions.

Adolescent↗

Peroperative cardiovascular stability during brainstem surgery. The use of high-dose methylprednisolone compared to dexamethasone. A retrospective analysis.

BACKGROUND: In neurosurgical procedures within brainstem structures, corticosteroids are routinely administered to prevent oedema and to reduce intraoperative trauma. After replacing the routine administration of dexamethasone (DX) by high-dose methylprednisolone (MP) during surgery for tumours within brainstem structures, a decreased incidence of intraoperative haemodynamic instability events was observed. To test this hypothesis, a retrospective analysis was performed. METHODS: Peroperative data of 62 surgical procedures of brainstem tumours were retrospectively analysed with respect to haemodynamic instability requiring changes in surgical strategy and/or emergence medication with vasoactive drugs. Severe changes in haemodynamic parameters were defined as a significant increase or decrease in heart rate and/or mean arterial blood pressure greater than 30% compared to baseline values. From 1988 to 1994, intravenous dexamethasone was given peroperatively in 33 patients. After a bolus of 1 mg kg(-1) body weight (BW) 30 min preoperatively, 0.2 mg kg(-1) were given every 4 h. From 1994 until now, methylprednisolone was administered instead of dexamethasone in 29 patients. After an initial bolus of 30 mg kg(-1) BW immediately before surgery, 5.4 mg kg(-1) h(-1) were given 23 h postoperatively. RESULTS: The results of this retrospective analysis suggest that the number of operations with episodes of bradycardia, arterial hypotension (P<0.05), tachycardia and arterial hypertension (P<0.005) was significantly decreased in the group of patients treated with high-dose methylprednisolone. CONCLUSION: The retrospective analysis of the clinical data showed that the routine use of high-dose methylprednisolone was associated with a decreased incidence of haemodynamic instability in a selected group of patients undergoing brainstem surgery. This finding has to be proven in prospective double-blind controlled studies.

Adolescent↗

The influence of airway pressure changes on intracranial pressure (ICP) and the blood flow velocity in the middle cerebral artery (VMCA).

OBJECTIVE: Due to the exponential shape of the intracranial volume-pressure relation, simple measurement of epidural, parenchymal or intraventricular intracranial pressure (ICP) in traumatic brain injury (TBI) often fails to early recognize patients with a fulminant development of intracranial hypertension even during recently available methods of tissue PO2 and microdialysis measurements. One approach to this problem could be repetitive intracranial volume provocations to evaluate a trend of the intracranial elastance. Several previously published methods use invasive volume challenge through access to the cerebrospinal fluid (CSF). This pilot study describes changes in intracranial pressure due to variations of airway pressure with BIPAP ventilation maneuvers. PATIENTS AND METHODS: Ten patients with severe TBI were enrolled and completed the study. The inclusion was based on radiologic signs due to TBI in the first CT-scan and the clinical indication for insertion of an ICP monitoring device. Patients with elevated ICP above 20 mm Hg were excluded. The epidural ICP response together with haemodynamic parameters in relation to defined airway pressure changes (delta PAW) was detected. The influence of the duration of delta PAW was evaluated additionally. Data of central venous pressure (CVP), ICP, mean arterial pressure (MAP), cerebral perfusion pressure (CPP), airway pressure (PAW) and blood flow velocity of the middle cerebral artery (VMCA) were analyzed on the basis of differences between the maximum (inspiration) and minimum PAW values (expiration). RESULTS: Elevations of PAW in the range of 20 to 35 cm H2O resulted in changes of the ICPmean from 4.1 to 6.0 mm Hg (r = 0.9, p < 0.05). A correlation was estimated for the changes of systolic arterial pressure (Part) and CPPmean due to PAW variations which ranged between 4.5 and 11.6 mm Hg (r = 0.99, p < 0.05). Concerning the transcranial doppler measurements the data of changes of the blood flow velocity of the middle cerebral artery (VMCA) revealed a positive correlation to PAW with a r = 0.99, p < 0.05. CONCLUSIONS: Elevation of the venous outflow resistance and a transient increase in cardiac output have to be considered as mechanisms for transduction of transthoracic pressure changes to intracranial pressure variations. We conclude, that trends of changes in elastance can be derived from intermittent airway pressure variations. This can be useful in easy and on line dynamic monitoring of ICP in traumatic brain injury.

Air Pressure↗

Venous intracranial haemodynamics in children undergoing operative treatment for the repair of craniosynostosis. A prospective study using transcranial colour-coded duplex sonography.

To evaluate intracranial venous haemodynamics in craniosynostosis noninvasively, we measured the blood flow velocities and pulsatility indices in the superior sagittal sinus (SSS) and the middle and the anterior cerebral artery during the perioperative course in 21 children undergoing repair of craniosynostosis involving the midline sutures, using transcranial colour-coded duplex sonography (TCCS). An age-matched group of 12 healthy children was examined in like manner for comparison. In the healthy group, the mean pulsatility index (PI) in the SSS was 0.22 and the mean resistance index (RI) 0.20. The mean preoperative PI and RI in the synostosis group were significantly higher [0.41 and 0.34, respectively (P<0.01)], but fell to 0.19 and 0.17 (P<0.01) in the postoperative course. Our results indicate that in craniosynostosis there is an altered venous haemodynamics in the SSS, which can be observed noninvasively by TCCS.

Blood Flow Velocity↗

Recurrent pain after lumbar discectomy: the diagnostic value of peridural scar on MRI.

The association between peridural scarring and recurrent pain after lumbar discectomy is much debated. A recently published study found that patients with extensive peridural fibrosis were 3.2 times more likely to experience recurrent radicular pain than those with less extensive scarring. This finding may lead to an overestimation of peridural fibrosis in clinical practice. In a retrospective study we analyzed the records of 53 patients who underwent a lumbar MRI because of recurrent pain after first unilateral microdiscectomy. Patients were classified as those with radicular or non-radicular pain according to history and clinical findings. The diagnosis was confirmed by spinal anesthetic block. The extension of scarring was compared between the two groups of patients. The amount of epidural fibrosis was examined on contrast-enhanced MRI in axial slices subdivided into four quadrants. The amount of fibrosis was divided into four stages in each affected quadrant. We found no differences regarding the amount of peridural fibrosis between patients with radicular pain and patients with non-radicular pain. We conclude that the extent of peridural scarring as defined by MRI is of minor value in the differential diagnosis of recurrent back and leg pain after lumbar microdiscectomy.

Case-Control Studies↗

c-myc oncogene family expression in glioblastoma and survival.

BACKGROUND: In gliomas, c-myc proto-oncogene expression has been found to correlate with the grade of malignancy, with low expression in Grade I and II and high expression in Grade III and IV tumors. We aimed to discover if myc expression is of prognostic significance in glioblastomas. METHODS: Expression of the c-myc, N-myc, and L-myc proto-oncogenes and of the max gene was investigated in 46 supratentorial glioblastomas from adult patients using in situ hybridization. RESULTS: Seventy-eight percent of the tumors expressed c-myc m-RNA, 84% max m-RNA, 57% N-myc m-RNA, and 57% L-myc m-RNA. The postoperative survival of patients over 60 years of age and that of patients under 60 years of age were analyzed separately, since advancing age was found to be negatively correlated with the duration of postoperative survival (p = 0.004). There was no significant difference in postoperative survival in either age group between patients whose tumors expressed either c-myc, N-myc, or L-myc, respectively, and those whose tumors did not exhibit this characteristic. A difference in postoperative survival, however, was found in the over 60-year age group between patients whose tumors expressed max to an equal or lesser extent than c-myc and those whose tumors expressed max to a greater extent than c-myc or neither max nor c-myc. CONCLUSION: The biologic behavior of glioblastomas in older patients may depend on the relative, but not on the absolute content of the c-myc protein and interacting proteins.

Adult↗

Elevated cerebral perfusion pressure and low colloid osmotic pressure as a risk factor for subdural space-occupying hygromas?

BACKGROUND: Space-occupying subdural hygromas are a late complication of severe traumatic brain injury (TBI) and may delay the patient's recovery. To evaluate the risk factors involved, we performed a semiretrospective, -prospective analysis of three groups of patients, which differed with regard to the techniques used in the management of their cerebral perfusion pressure (CPP) and colloid osmotic pressure (COP) to determine the occurrence of space-occupying subdural hygromas. PATIENTS AND METHODS: Between 1989 and 1997 we examined 696 patients after a severe TBI: Group 1. 1989-1994 mean CPP: 67 (elevated for therapeutic reasons by catecholamines, if necessary), mean COP: 19. Group 2. January 1995-October 1996, mean CPP: 77, mean COP: 20. Group 3. November 1996-December 1997, mean CPP: 79, mean COP: 23 (elevated for therapeutic reasons by infusions of colloids). The groups were comparable for other criteria. RESULTS: Compared to Group 1, Group 2, with a high CPP but lower COP, showed a significantly higher (p < 0.01; chi2-test with correction of Yates) percentage of posttraumatic subdural hygromas with space-occupying aspects, clinical signs of bradycardia, hypertension and impaired consciousness requiring surgery (Group 1: 1.75%; Group 2: 10.46%; Group 3: 0%). In Group 3 we saw no patient with a space-occupying hygroma. CONCLUSION: We conclude that iatrogenic elevated CPP, which has been reported to be helpful in preventing secondary ischemic damage after a severe TBI, may be harmful to a patient if the COP is not maintained within physiological ranges.

Adult↗

Cisternal S100 protein and neuron-specific enolase are elevated and site-specific markers in intractable temporal lobe epilepsy.

In the brain, S100 protein and neuron-specific enolase (NSE) are mainly found in glial cells and neurons, respectively. We investigated concentrations of S100 protein and NSE in cisternal cerebrospinal fluid obtained during implantation of foramen ovale electrodes in eight patients with temporal lobe epilepsy (TLE). In addition, the meningeal markers cystatin-C and beta-trace as well as total protein were measured. Patients with trigeminal neuralgia (TN) undergoing glycerol rhizotomy served as controls. S100 protein and NSE levels ipsilateral to the site of seizure onset were significantly higher than in TN. Contralateral TLE values were also markedly but not significantly elevated. The meningeal markers cystatin-C and beta-trace protein as well as total protein did not differ in TLE and TN. We conclude that interictal temporal lobe dysfunction corresponds with neuronal and glial marker elevations in the extracellular space and that site-specific elevations may predict the site of seizure origin biochemically.

Adult↗

Postoperative intracranial abscess--clinical aspects in the differential diagnosis to early recurrence of malignant glioma.

Out of 2941 patients who received a clean, major craniotomy, 39 patients (1.3%) developed the complication of an intracranial deep infection, i.e. abscess or empyema. A total of 14 patients with a postoperative abscess were initially operated upon intracerebral malignant glioma (WHO III or IV) and could be compared to a matched group of patients with recurrent malignancy concerning clinical and radiological aspects. A statistically significant elevation of median values was seen for erythrocyte sedimentation rate (ESR), fibrinogen and body temperature in the study group. C-reactive protein (CRP) was not investigated in the control group and could not be compared, but it was elevated in all abscess patients when measured. CT-scan did not allow a safe differentiation between infection and recurrent glioma. Local signs like suppuration of the wound could be observed in 71% of patients with intracranial infection. Postoperative abscesses had been diagnosed in all cases within 3 months, whereas none of the early recurrences of intracerebral malignoma became symptomatic before 12 weeks after initial operation. Therefore, the course of time seems to be another important factor in this differential diagnosis.

Brain Abscess↗

The value of transcranial duplex sonography in the management of patients subsequent to surgery for middle cerebral artery aneurysms.

OBJECTIVE: We intended to evaluate the value of transcranial color-coded duplex sonography (TCCS) in the management of patients after clipping of an aneurysm of the middle cerebral artery. Question was whether this method was able to predict poor clinical outcome by detection of local circulation disorders in the postoperative course. METHODS: A series of 15 consecutive patients was examined daily by TCCS. Special attention was paid to the branches of the middle cerebral artery distal from the clip (M2 branches). We correlated the TCCS results to the clinical outcome and occurrence of infarction on CCT. RESULTS: In six patients, one or more M2 branches could not be found in the immediate postoperative course, but reappeared after a period of 1-12 days in five patients. The three patients with a missing signal for more than 4 days suffered from infarction of the dependent territory and permanent neurological deficit not due to vasospasm of the middle cerebral artery. In the nine patients with constant TCCS signals, there was only one infarction due to pre-hospital systemical hypotension. CONCLUSION: TCCS cannot give exact postoperative information about incidental vessel occlusion during surgery for MCA aneurysms because M2 branches can remain invisible for some days without being occluded, but this invisibility seems to be coupled with ischemic complications.

Adult↗

MiniMATCH: a simple method for local data transfer between MRI and CT scan sets.

A comparison of the spatial position of distinct locations within cranial MRI and CT scan sets can easily be done with a simple algorithm designed as a computer program. After determination of a basic system formed by the coordinates of anatomical landmarks in CT and MRI, arbitrary points can be identified on one scan set and transferred quantitatively to the other. Pros and cons of the method are discussed and opposed to the properties of specifically designed image processing systems.

Algorithms↗

Optimized evaluation of a pulsed 2.09 microns holmium:YAG laser impact on the rat brain and 3 D-histomorphometry of the collateral damage.

Since more than 20 years CO2 and Nd:YAG lasers are established in the microsurgery of the nervous system. CO2 lasers can be used handheld, but may be focused on the target area by mirror optics and sideports of the operating microscope's micromanipulator. Nd:YAG lasers have the disadvantage of deep penetration into the brain and provocation of a large collateral damage. The need is for a fibre conducted solid system for surgery in delicate areas as for brain stem surgery. Fibre conduction of near infrared lasers allows better exposure of the target area compared to hollow wave guides or mirror equipment. Fibres can be tapered and modified according to the purpose. The holmium:YAG (Ho:YAG) laser has acquired interest by introducing the system into microsurgery of parenchymal tissue. They have not been proven yet sufficiently for neurosurgical tasks. The effort to minimalize the collateral tissue damage has to be maximalized in the surgery of nervous tissue and functional low redundant brain stem or spinal cord tissue. Volumetric data may be more precise in comparison to depth and width data of the laser lesion even when the different levels of the tissue interaction have to be analyzed for estimation of the real side effects in nervous tissue. We have used 50-800 ml delivered Ho:YAG single pulses in cortical areas of Sprague-Dawley rats and investigated the different lesion zones by volumetric data. The functional lesion zone was detected and measured by immunohistological staining of the heat shock protein HSP 72. For further reduction of the focus area, we have used tapered 400 to 200 microns fibres.

Animals↗

Visually evoked potentials in 52 children requiring operative repair of craniosynostosis.

We evaluated the prevalence of pathological visually evoked potentials (VEP) before the appearance of papilledema or other signs of elevated intracranial pressure in children suffering from craniosynostosis. In 52 children (19 girls, 33 boys, median age 7.6 months, mean age 7.6 months, range from 3 to 34 months) preoperative VEP were analyzed. In 13 patients, pathological VEP were observed. In all children, both eyes were involved. Only 1 child suffered from papillar anomalies. Latency was pathological in 12 children, whereas the amplitude was suppressed in only 2 children. In all children with preoperative pathological VEP, postoperative controls (n = 4) were improved or normal. Thus, VEP may be the first test for neuronal damage in craniosynostosis.

Child, Preschool↗

[Trigeminal neuralgia as symptom of an infratentorial space-occupying process].

UNLABELLED: Despite excellent technical means of imaging the posterior fossa by magnetic resonance imaging (MRI), some infratentorial space-occupying processes still remain undiscovered, especially if they present only slight symptoms or imitate typical different diseases. METHODS: We analysed the data of 334 patients who were admitted because of infratentorial space-occupying processes in the years 1986 to 1995. RESULTS: There were six patients with trigeminal neuralgia caused by infratentorial tumors. In only one was the tumour previously diagnosed. All suffered from tic douloureux; two had undergone operative treatment. Mean latency from first symptoms until diagnosis was 48 months. On admission all patients presented at least slight neurological deficits. Postoperatively, the patients remained pain-free. CONCLUSION: Because the prognosis of operative treatment and the occurrence of postoperative deficits depend on tumour size, we advocate MRI examination in every patient presenting tic douloureux, even without additional neurological signs.

English Abstract↗