Combined effects of resveratrol and radiation in GH3 and TtT/GF pituitary adenoma cells.

OBJECTIVE: Resveratrol and radiation decrease viability in various tumor cells. This study aims to investigate combined effects of resveratrol and radiation on viability, induction of apoptosis and necrosis, and expression of apoptosis modulators in rodent GH3 and TtT/GF pituitary adenoma cells in vitro. METHODS: Cells were incubated with 10-100 µM resveratrol. Medium and medium with ethanol served as controls. After 2 h, cells were irradiated with 0-5 Gray (Gy) and further incubated for 48-72 h. Cell viability was quantified using a hemocytometer. Cell death was assessed with an enzyme-linked immunosorbent assay (ELISA) that detects free nucleosomes in cell lysates and free nucleosomes released to the culture medium. Expression of B-cell lymphoma-2 protein (BCL-2) and BCL-2 associated Xprotein (BAX) was measured using quantitative real time-polymerase chain reaction (qRT-PCR) to analyze changes in BAX/BCL-2 ratio. RESULTS: Resveratrol and irradiation with 4 Gy alone and in combination significantly decreased cell viability (p = 0.017 and less). In the ELISA, 10 µM resveratrol significantly induced apoptosis in TtT/GF cells at 0 Gy (p < 0.001), but not at 3 or 5 Gy. In the ELISA, 10 µM resveratrol significantly induced necrosis in GH3 cells at 0, 3 and 5 Gy (p < 0.001). While qRT-PCR did not demonstrate a significant effect of 10 µM resveratrol or radiation on expression of BAX or BCL-2, a significant increase in the BAX/BCL-2 ratio was found after irradiation with 5 Gy in GH3 cells (p = 0.0027). CONCLUSION: While moderate irradiation solely led to inhibited proliferation, resveratrol induced cell death in rodent pituitary adenoma cells.

Decerebrate posturing following traumatic brain injury: MRI findings and their diagnostic value.

AIM: To determine the pathomorphological and clinical background to decerebrate posturing in humans following serious traumatic brain injury. MATERIALS AND METHODS: One hundred and twenty patients who had been unconscious for more than 24 h underwent diagnostic MRI within 8 days after trauma. The presence of decerebrate rigidity as the clinical parameter was correlated to MRI findings, such as traumatic lesions in defined brain areas. Significance was presumed as p < 0.05. RESULTS: On the day of MRI 43 (36%) patients exhibited decerebrate posturing: 19 (23%) cases were unilateral and 24 (77%) bilateral. There was a significant correlation between midbrain lesions and the presence of rigidity. If a midbrain lesion was found in the absence of pontine lesions, decerebrate rigidity could be concluded (p < 0.05). There was no significant correlation to the rigidity in the case of midbrain lesions accompanied by pontine lesions, and no correlation to the rigidity could be detected for other regions of the brain. Both the occurrence of decerebrate posturing and the detection of brainstem lesions at MRI correlated with the Glasgow Outcome Scale. The combination of both parameters improved the probability of predicting the outcome. CONCLUSION: The rate of decerebrate posturing increases significantly in the presence of midbrain lesions. The presence of pontine lesions appears to be of secondary importance. The chances of predicting the Glasgow Outcome Scale are improved by the combination of clinical information (decerebrate posturing) and radiological parameters (type of brainstem lesion).

[Collaboration of general surgeons with neurosurgeons: what does a general surgeon need to know about neurosurgery?]. / Zusammenarbeit der Neurochirurgie mit der Allgemeinchirurgie: Was muss der Allgemeinchirurg von der Neurochirurgie wissen?

BACKGROUND: The most freq+uent disorders and injuries requiring the joint attention of general surgeons and neurosurgeons are presented and analysed in this review. METHODS: The priorities and prognosis concerning diagnostic and surgical measures for patients in coma with multiple injuries, extra- and intraspinal tumours and brain metastases are analysed. RESULTS: The urgency of general surgical and neurosurgical measures is not ruled by a preformatted pattern but by the vital needs of the individual patient. CONCLUSION: The differentiation of vital from non-vital operations or with regard to prognosis necessary from inadequate general surgical and neurosurgical measures is of fundamental importance. The successive order of general surgical and neurosurgical interventions must be adjusted to the needs of each individual patient.

[Comparison of younger and elder patients after multiple trauma]. / Vergleich jüngerer und älterer Unfallopfer nach Mehrfachverletzun.

The purpose of this study was to clarify any influences by age on the outcome after multiple trauma. 520 patients (age > 20 years) were analysed after inclusion in a 3-year national multi-centre study for polytrauma injured subjects. The patients were recruited from 10 German neurosurgical university departments. Criteria for inclusion were head injury and coma at the time of admittance. The elderly were mostly injured by falls, and showed more often intracranial injuries and fractures of the pelvis. The majority of intracranial injuries were characterised by acute subdural haematomas in the elderly and contusions in younger patients. Hence, craniotomy within the first 24 hours was found more often in the elderly. There was a significant trend towards a craniotomy and placement of a pressure catheter in younger patients compared with the elderly. There were significantly lower values for the Glasgow Outcome Scale (GOS) in the elderly, especially in terms of lethality. The depth of coma was a strong predictor for GOS in both groups.

[Cranial magnetic resonance imaging and serum marker S-100 for expert opinions in severe brain injuries]. / Kranielle Kernspintomographie und S-100 Serumdiagnostik in der Begut- achtung schwerer Schädelhirntraumen.

Detailed imaging of the brain is necessary to come to an expert opinion on the consequences of severe brain injuries (BI). As lesions are not visualised on computerised tomography, magnetic resonance imaging (MRI) data and serum marker S-100 are currently favoured. Our study analyses the predictive qualities of MRI and S-100 for the outcome in severe BI in 100 patients. The location of brain stem lesions identified with the aid of MRI significantly correlated with the outcome. Special types of brain stem lesions could be distinguished. S-100 was a rough measure for the amount of destruction of CNS tissue, but the exact location of the destroyed tissue appeared to be more significantly related with the outcome than its volume. For an expert opinion on severe BI, follow up MRI after brain injury can definitely not exclude relevant lesions. Early MRI is recommended.

The predictive value of ICP as compared to magnetic resonance imaging in comatose patients after head injury.

INTRODUCTION: While highly increased intracranial pressure (ICP) is of high predictive value indicating a fatal outcome, the predictive value of moderately increased ICP early after head injury remains uncertain. We compared the predictive value of ICP to the predictive value of magnetic resonance imaging (MRI) early after head injury. METHODS: 55 patients with a Glasgow Coma Scale (GCS) of less than 8, for more than 24 hours after head injury were investigated. Outcome was classified according to the Glasgow Outcome Scale (GOS). All patients received registration of ICP upon arrival at the hospital and an initial cranial computerized tomography scan. An MRI study was subsequently performed within 10 days of admission. The highest mean ICP registered within one hour in the first day of admission and the location of lesions as identified by MRI were related with outcome. RESULTS: ICP was neither related with mortality nor with GOS of survivors. The location of lesions as depicted by MRI proved to be statistically significantly related with the GOS (p < 0.001). Age proved to be clearly and significantly related with outcome (p = 0.019). CONCLUSIONS: Our current MRI findings suggest that the location of the initial brain injury lesion correlates with outcome at 6 months. No such correlation could be identified for intracranial pressure on the first day after head injury (p = 0.766).

Precursor T-lymphoblastic lymphoma within a recurrent pituitary adenoma.

Only single examples of lymphoma associated with pituitary adenoma have been reported. In our patient, a precursor T-lymphoblastic lymphoma developed within a recurrent pituitary adenoma 17 years after the first resection. Histomorphologically, lymphoma and adenoma components were tightly admixed. The features harbour remarkable similarity to the previous report by Kuhn et al.. In both patients the lymphomas were composed of T-cells, there was no evidence of further sites involved, and both adenomas expressed follicle-stimulating hormone. The hormone may have posed a proliferative and transforming effect on lymphatic cells and could have played a crucial role in "lymphomagenesis" as an exceptional phenomenon.

Multicentre approach to epidemiological aspects of craniosynostosis in Germany.

We know of no current published data on the prevalence of craniosynostosis in Germany, so our objective in this study was to contribute to the limited knowledge of its epidemiology by assessing time trends, the frequency of prenatal diagnosis, and the timing of diagnosis and treatment. Data were collected in Saxony-Anhalt during the period 2000-17, and we designed a retrospective multicentre cohort study. The prevalence was 4.8 cases of craniosynostosis/10 000 births, and did not increase during that time. We compared the data of 91 patients with those of 273 controls. There were 75 boys and 16 girls (ratio 4.7:1). Fifty-one children had isolated craniosynostosis, consisting of 46 with a single-suture, and five with a multisuture, synostosis. Twenty-nine were associated with other congenital malformations, and 11 were syndromic. Three cases had been diagnosed prenatally, and 34 had skull deformities diagnosed immediately after birth at a mean (SD) age of 3.4 (4.7) months. The mean (SD) age at the time of first admission to hospital in one of the three surgical centres of Saxony-Anhalt was 5.9 (5.5) months, and 65 patients were operated on at a mean age of 9.1 (6.3) months. In contrast to published reports we found a prevalence of 4.8 cases of craniosynostosis/10 000 births that did not increase during the period 2000-16. Although we found a low prenatal detection rate, the diagnosis and treatment in this cohort study seemed timely.

Guidelines for the Treatment of Head Injury in Adults.

The workshop of scientific medical faculties (Arbeitsgemeinschaft wissenschaftlicher medizinischer Fakultäten [AWMF]) of Germany has asked societies of specific medical disciplines to jointly publish guidelines on the treatment of diseases and injuries. On behalf of the Deutsche Gesellschaft für Neurochirurgie, its commission on guidelines initiated an interdisciplinary approach to publish guidelines on the treatment of head injury in adults. These guidelines were published in German by the AWMF in late 2015. Because these guidelines have received widespread attention in Germany and became fundamental for research in head injuries, we have translated the German version into English to make it accessible to the international scientific community.

Immunohistochemical determination of five somatostatin receptors in meningioma reveals frequent overexpression of somatostatin receptor subtype sst2A.

Meningioma is one of a variety of human tumors that exhibit a very high density of somatostatin receptors and in many cases show a true positive somatostatin receptor scintigraphy. However, the level of expression of individual somatostatin receptor proteins in meningioma has not been investigated. We have recently developed a panel of somatostatin receptor subtype-specific antibodies that effectively stain formalin-fixed, paraffin-embedded tumor tissue (S. Schulz et al., Clin. Cancer Res., 4: 2047-2052, 1998). In the present study, we have used these antibodies to determine the somatostatin receptor status of 40 randomly selected meningiomas. Immunoreactive staining for all somatostatin receptors was clearly located at the plasma membrane of the tumor cells and completely blocked with antigenic peptide. The vast majority of tumors (29 cases; 70%) were positive for sst2A immunoreactivity; among these, 20 (69%) tumors showed high levels of sst2A immunoreactivity. In contrast, all other somatostatin receptors were only detected sporadically, and none of these cases revealed a particularly strong staining. However, it is uncertain to what extent somatostatin receptor-immunoreactive staining intensity may translate into somatostatin receptor protein expression on the tumor cells. Therefore, in a prospective study, 16 surgically removed meningiomas were collected, and the level of sst2A expression was determined using Western blot analysis. Whereas sst2A was readily detectable as a broad band migrating at Mr 70,000 in 12 (75%) of these tumors, 8 tumors (50%) showed particularly high levels of immunoreactive sst2A receptors. There was an excellent correlation (P < 0.001) between the level of sst2A protein expression detected in Western blots and the sst2A- immunoreactive staining seen in tissue sections. Thus, the frequent overexpression of the sst2A receptor may explain the high tracer uptake often observed in meningioma patients during somatostatin receptor scintigraphy. Moreover, this simple immunohistochemical method could prove useful in identifying those cases of recurrent disease that may possibly respond to therapy with sst2-selective agonists.

Elective percutaneous dilatational tracheostomy. A new simple bedside procedure; preliminary report.

The development by the senior author (P.C.) of percutaneous tracheostomy from cricothyroidostomy and subcricoid fingertip tracheostomy is traced, and the technique and patient material of percutaneous subcricoid tracheostomy is presented. This new technique consists of inserting a tracheostomy tube by the use of a J guide wire inserted through a cannula into the tracheal lumen. Tapered dilators follow the guide wire and dilate the opening in the tracheal walls. A tracheostomy tube snugly fitted over a dilator is then passed into the trachea between the cricoid cartilage and the first tracheal ring. This procedure avoids the immediate and postoperative complications of "standard" tracheostomy. An experience of 134 tracheostomies of various types culminated in the development of the percutaneous technique. To date 26 such operations on 24 patients have been done with no significant complications due to the operation. The percutaneous technique should reduce the severity and incidence of intraoperative complications. Late complications, which have been no problem to date, are being evaluated with longer follow-up and with a greater patient population.

Penetration of M cells and destruction of Peyer's patches by Yersinia enterocolitica: an ultrastructural and histological study.

Yersinia enterocolitica is enteropathogenic for man and rodents. Previous studies provided evidence that Y. enterocolitica invades the lymphoid follicles of the Peyer's patches (PP) of the small intestine. In this study Y. enterocolitica-induced tissue alterations of the follicle-associated epithelium (FAE) and the underlying PP tissue were analysed by scanning (SEM) and transmission electron microscopy (TEM) as well as by conventional histological examination. For this purpose, an experimental mouse infection model including orogastric infections as well as ileal loop experiments were used. A rapid and selective colonisation of the FAE after orogastric yersinia infection was observed by SEM. TEM studies confirmed that Y. enterocolitica adhered closely to the FAE including M cells and enterocytes. Histological studies and TEM revealed that Y. enterocolitica selectively invaded the PP via M cells but not via other cells of the FAE. One day after Y. enterocolitica infection the FAE was altered and small micro-abscesses comprising yersiniae expressing the major outer-membrane protein YadA were observed immediately beneath the FAE. Adjacent villi were dilated from lymphangiectasis and transmigrating polymorphonuclear leucocytes (PMNL) were found within the epithelium. At 5-7 days after infection the FAE and parts of PP were destroyed. Profound alterations of the cyto-architecture of the PP were due to the enormous recruitment of PMNL. By day 5 after infection, abscesses were found in the mesenteric lymph nodes. However, TEM studies revealed evidence that Y. enterocolitica may disseminate from the PP not only via the lymphatics but also by invasion of blood vessels. Taken together, the results of this study demonstrate that the FAE is the primary site of host-pathogen interaction in Y. enterocolitica infection and that this pathogen penetrates M cells and subsequently induces destruction of the PP.

Growth rate of incidental meningiomas.

A meningioma was incidentally identified with computerized tomography (CT) in 17 patients without relevant clinical signs. The tumor was not removed, but biopsy confirming a meningioma was obtained from one patient. Tumor growth rate was calculated from repeat CT scans or follow-up magnetic resonance imaging. The annual growth rate ranged from less than 1% to 21%. It is concluded that in nonsymptomatic meningiomas with a low growth rate a nonsurgical approach may be warranted.

Venous opthalmodynamometry: a noninvasive method for assessment of intracranial pressure.

OBJECT: The goal of this study was to examine the potential use of ophthalmodynamometry in the noninvasive assessment of intracranial pressure (ICP). Under normal conditions, pressure within the central retinal vein is equal to or greater than ICP, because the central retinal vein basses through the optic nerve before it drains into the cavernous sinus. The optic nerve sheath is the place where ICP affects retinal venous pressure. Suction ophthalmodynamometry is an established method of investigation in ophthalmology to determine the pressure of the central retinal artery. Although observations of papilledema and lack of venous pulsations are commonly used to provide a vague assessment of ICP, ophthalmodynamometry may be used to determine the pressure of the central retinal vein. This venous pressure has never been compared with ICP. METHODS: In this study the pressure of the central retinal vein was recorded in 22 patients who underwent continuous simultaneous registration of ICP for various reasons, mainly for suspected hydrocephalus. A comparison of the two pressures was made. The results indicated a highly significant linear correlation between central retinal vein pressure and ICP. These results are of great practical value because up-to-date reliable ICP monitoring has only been possible by using invasive means, by placing a probe extradurally or subdurally into the brain parenchyma or a ventricle. CONCLUSIONS: Ophthalmodynamometry can be relevant for momentary assessment and is not suitable for continuous monitoring. However, this technique can easily be repeated and may be used whenever increased ICP is suspected in a patient suffering from hydrocephalus, brain tumors, or head injury.

Postoperative magnetic resonance imaging artifacts. Report of three cases.

Artifacts are occasionally encountered on magnetic resonance imaging after operation. These may be due to minute metallic particles from neurosurgical instruments. Particles not detectable on plain x-ray films or computerized tomography scans may cause local change of magnetic resonance activity, resulting in a deceptive magnetic resonance appearance. Three illustrative case reports are presented.

Early magnetic resonance imaging of brainstem lesions after severe head injury.

OBJECT: The availability of magnetic resonance (MR) imaging data obtained in comatose patients after head injury is scarce, because MR imaging is somewhat cumbersome to perform in patients requiring ventilation and because, in the first hours after injury, its relevance is clearly inferior to computerized tomography (CT) scanning. The authors assessed the value of MR imaging in the early postinjury period. METHODS: In this prospective study MR imaging was performed in 61 consecutive patients within 7 days after they suffered a severe head injury. An initial CT scan had already been obtained. To understand the clinical significance of the lesions whose morphological appearance was identified with MR imaging, brainstem function was assessed by registration of somatosensory and auditory evoked potentials. Brainstem lesions were visualized in 39 patients (64%). Bilateral pontine lesions proved to be 100% fatal and nonbrainstem lesions carried a mortality rate of 9%. In singular cases circumstances allowed for a clear clinical distinction between primary and secondary brainstem lesions. On MR imaging all lesions were hyper- and hypointense after intervals longer than 2 days. Within shorter intervals (< 2 days) after the injury, primary lesions appeared isointense on MR imaging. In one secondary brainstem lesion there were no traces of blood. CONCLUSIONS: Because mean intracranial pressure (ICP) levels in patients without brainstem lesions were similar to those in patients with brainstem lesions, the authors conclude that it was not mainly increased ICP that accounted for the high mortality rates in patients with brainstem lesions. The authors also conclude that brainstem lesions are more frequently found in severe head injury than previously reported in studies based on neuropathological or CT scanning data. Early MR imaging after head injury has a higher predictive value than CT scanning.

Russel bodies-containing cells in the Harderian gland of the chicken in relation to different immune conditions.

The modulation of the number of Russel bodies-containing plasma cells in the Harderian gland under different experimentally induced immune conditions is reported. The findings support the conception of an immunologic function of the Harderian gland which is similar to the function of the thymus on the one hand, and to the function of the bursa of Fabricius on the other.

Multimodal evoked potentials after subarachnoid haemorrhage.

In 59 comatose patients after subarachnoid haemorrhage somatosensory, visual, auditory and magnetic motor evoked potentials were registered. Evoked potentials proved to be of much less predictive value than in other causes of coma, such as head injury and others. While loss of cortical function was a safe predictor of a fatal outcome, preservation of evoked potentials has little prognostic relevance.

Early dynamics of acute extradural and subdural hematomas.

In a retrospective study volumes of 42 extradural and 102 subdural traumatic hematomas were evaluated. Results were related with the time interval between injury and initial CT scan, outcome, coma grade and subject age. Mean volumes were found to increase with time after the injury. In the first hour volumes of 8 intracranial hematomas were hardly space consuming, while they became clearly space consuming in the second and in later hours after the injury. It was therefore concluded that it should not take longer than one hour until a CT scan be performed when an intracranial post-traumatic hematoma is suspected in the comatose patient.