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T Mathiesen

Publications and source records attributed to T Mathiesen.

At least 19 recordsLinked to original sources
PubMed1999

Long-term intracerebral inflammatory response after experimental focal brain injury in rat.

Head injury is a risk factor for development of the sporadic form of Alzheimer's disease (AD) and chronic anti-inflammatory treatment reduces the prevalence of AD. This study was undertaken to test the hypothesis that inflammatory reactions persist in the long term. Rats were subjected to moderate focal brain injury. The brains were analyzed after 3 months by immunohistochemistry. Persistent major histocompatibility complex (MHC)-II up-regulation, mononuclear phagocytes, interleukin (IL)-1-beta and tumor necrosis factor (TNF)-alpha synthesis (p < 0.01) were detected in large areas of the ipsilateral hemisphere. The fact that a long-term inflammation is detectable following experimental brain injury corroborates the hypothesis that persistent post-traumatic inflammation is a possible factor in the causative chain of traumatically induced dementia.

Animals↗
PubMed1999

Neuropsychological effects associated with exposure to mercury vapor among former chloralkali workers.

OBJECTIVES: This investigation studied possible neuropsychological effects among former chloralkali workers with past exposure to mercury vapor. METHODS: Seventy-five formerly exposed workers who had been examined with an extensive neuropsychological test battery were compared with 52 referents frequency-matched for age. The tests measured general cognitive function, motor and psychomotor function, attention, memory, and learning. The groups were similar in educational level, age, and verbal comprehension. The mean exposure time to mercury vapor in the index group was 7.9 (range 1.1-36.2) years with an annual mean urinary mercury concentration of 539 (range 41-2921) nmol/(l x year). The mean time since the cessation of exposure was 12.7 (range 1.0-35.0) years. RESULTS: Performance on the grooved pegboard (dominant hand 75.8 versus 70.9 seconds, P<0.05; nondominant hand 82.2 versus 76.3 seconds, P=0.02) and the Benton visual retention test (mean number of correct reproductions 6.9 versus 7.5, P<0.05) was poorer among the formerly exposed workers when compared with the referents. In addition the subjects who had experienced the highest intensity of exposure [cumulative urinary mercury index > or =550 nmol/(l x year)] had a poorer performance on the trailmaking test, part A and B, on the digit symbol test, and on the word pairs test (retention errors). CONCLUSIONS: The presented results suggest a slight persistent effect of mercury vapor exposure on the central nervous system, mainly involving motor functions and attention, but also possibly related to the visual system. Previous exposure does not seem to have affected the workers' general intellectual level or their ability to reason logically.

Adult↗
PubMed1998

Identification of a consistent region of allelic loss on 1p32 in meningiomas: correlation with increased morbidity.

Meningioma is a common tumor of the central nervous system. Deletions of the short arm of chromosome 1 (1p) are the second most commonly observed chromosomal abnormality in these tumors. Here, we analyzed tumor and normal DNAs from 157 meningioma patients using PCR-based polymorphic loci. Loss of heterozygosity (LOH) for at least one informative marker on 1p was observed in 54 cases (34%), whereas LOH on 1q occurred in only 9 cases (8%). High-resolution deletion mapping defined a consensus region of deletion flanked distally by D1S2713 and proximally by D1S2134, which spans 1.5 cM within 1p32. LOH in this region has also been observed in several other malignancies, suggesting the presence of a tumor suppressor gene or genes that are important for several types of cancer. Statistical analysis revealed that 1p LOH was associated with chromosome 22 deletions and with abnormalities of the NF2 gene in meningioma. In addition, unlike other clinical and molecular characteristics, only 1p LOH was shown to be significantly associated with recurrence-free survival.

Alleles↗
PubMed1998

Intracerebral inflammation after human brain contusion.

OBJECTIVE: This study was undertaken to analyze the inflammatory components in contused human brain tissue to compare the findings with previous experimental data regarding the pathogenesis of brain contusions. METHODS: Contused brain tissue biopsies were obtained from 12 consecutive patients undergoing surgery for brain contusions 3 hours to 5 days after trauma. Inflammatory and immunological components were analyzed by immunohistochemistry. RESULTS: In patients undergoing surgery less than 24 hours after trauma, the inflammatory response was limited to vascular margination of polymorphonuclear cells. In patients undergoing surgery 3 to 5 days after trauma, however, a massive inflammatory response consisting of monocytes/macrophages, reactive microglia, polymorphonuclear cells, and CD4- and CD8-positive T lymphocytes was detected. Human lymphocyte antigen-DQ was expressed on reactive microglia and infiltrating leukocytes in the late patient group. In addition, CD1a, which is a marker for antigen-presenting dendritic cells, was detected in a subgroup of microglial cells. CONCLUSION: The results corroborated hypotheses derived from experimental data. In the early phase after contusional trauma, inflammation is mainly intravascular and dominated by polymorphonuclear cells. The inflammation was parenchymal in patients undergoing surgery 3 to 5 days after trauma. The brain swelling seemed to be biphasic, the delayed phase correlating with a parenchymal inflammation. The inflammatory cells may produce several potentially harmful effects, such as acute cellular degeneration; they may also lead to degenerative long-term effects.

Adolescent↗
PubMed1997

A high ratio of insulin-like growth factor II/insulin-like growth factor binding protein 2 messenger RNA as a marker for anaplasia in meningiomas.

Insulin-like growth factors (IGFs) I and II have been implicated as autocrine or paracrine growth promoters. These growth factors bind to specific receptors, and the response is modulated by interaction with IGF-binding proteins (IGFBPs). We observed a strong correlation between anaplastic/atypical histopathology and a high IGF-II/IGFBP-2 mRNA ratio in a set of 68 sporadic meningiomas. A strong correlation was also found between clinical outcome and IGF-II/IGFBP-2 ratio, whereas previously used histochemical markers were less correlated to outcome. We suggest that a high IGF-II/IGFBP-2 mRNA ratio may be a sign of biologically aggressive behavior in meningiomas that can influence treatment strategies. We propose that low IGFBP-2 levels in combination with increased levels of IGF-II would result in more free IGF-II and consequently greater stimulation of proliferation.

Adult↗
PubMed1997

MK-801 inhibits the cortical increase in IGF-1, IGFBP-2 and IGFBP-4 expression following trauma.

Cerebral contusions increase cortical expression of insulin-like growth factor 1 (IGF-1), IGF binding protein-2 (IGFBP-2) and IGFBP-4, mRNA levels increase at the contusion site (IGF-1, IGFBP-2 and -4) and along the ipsilateral cortex (IGFBP-2 and -4). Here we explore whether this upregulation is glutamate dependent. Rats were treated with the non-competitive N-methyl-D-aspartate (NMDA) antagonist MK-801 or the non-NMDA antagonist CNQX before and after trauma, and analysed using quantitative in situ hybridization. The induction of IGF-1 expression was completely blocked by MK-801 or CNQX. IGFBP-2 mRNA levels remained high at the contusion site in the presence of either drug, but the increase was blocked in the cortex temporal to the impact by MK-801. The increase in IGFBP-4 mRNA was blocked by MK-801 but not by CNQX.

Animals↗
PubMed1997

Adult nestin-expressing subependymal cells differentiate to astrocytes in response to brain injury.

The adult brain contains a small population of central nervous system (CNS) cells in the subependyma which, like embryonic CNS progenitor cells, express the intermediate filament nestin. In this report, the differentiation capacity in vivo of these cells was analysed following a standardized trauma. Before the trauma, the subependymal cells expressed nestin but not the astrocytic and neuronal differentiation markers glial fibrillary acidic protein (GFAP) and neurofilament respectively. In response to injury, the majority of the subependymal cells coexpressed nestin and GFAP, but never nestin and neurofilament. Furthermore, cells coexpressing nestin and GFAP were found progressively further away from the subependyma and closer to the lesion at later time points after the injury, indicating that these cells migrate towards the lesion. Nestin was in addition re-expressed in reactive astrocytes near the lesion and in non-reactive astrocytes very far from the lesion throughout the ipsilateral cortex. In conclusion, our data indicate that the nestin-positive subependymal cells are an in vivo source for the generation of new astrocytes but not neurons after injury, and that nestin re-expression in astrocytes following traumatic stimuli can be used as a sensitive marker for astroglial activation.

Animals↗
PubMed1997

Third ventricle colloid cysts: a consecutive 12-year series.

A continuous follow-up review of colloid cysts including aspects of natural history and evaluation of treatment options is necessary to optimize individual treatment. Thirty-seven consecutive patients with colloid cyst of the third ventricle seen at Karolinska Hospital between 1984 and 1995 were reviewed. Five patients were admitted in a comatose state, and two died despite emergency ventriculostomy. Three had recurrent cysts following previous aspiration procedure. During the study period, patients underwent a total of 10 ventriculostomies, 10 aspirations, 26 microsurgical operations, and two shunt operations. Twenty-four of 26 microsurgical operations were transcallosal and two were transcortical. Twenty-four operations (22 transcallosal and two transfrontal approaches) without permanent morbidity were performed by four surgeons. Transient memory deficit from forniceal traction was noted in 26%. The remaining two transcallosal operations, which led to permanent morbidity or mortality, were performed by two different surgeons. Aspiration of cysts performed by four different surgeons carried a 40% risk of transient memory deficit (10% permanent) and an 80% recurrence rate. One patient was found to be cured on radiological studies obtained at the 5-year follow-up review. Seven cysts were followed by means of radiological studies with no treatment for 6 to 37 months. Five of these cysts grew, indicating that younger patients with colloid cysts will probably need surgical treatment. The main causes of unfavorable results were: 1) failure to investigate symptoms that proved fatal; 2) subtotal resection; and 3) surgical complications. Transcallosal microsurgery produced excellent results when performed by experienced surgeons. A colloid cyst of the foramen of Monro is a disease that should be detected before permanent neurological damage has occurred. Permanent morbidity or mortality should not be accepted in modern series of third ventricle colloid cysts.

Adolescent↗
PubMed1997

Delayed cytokine expression in rat brain following experimental contusion.

Proinflammatory cytokines mediate brain injury in experimental studies. This study was undertaken to analyze the production of proinflammatory cytokines in experimental contusion. A brain contusion causing delayed edema was mimicked experimentally in rats using a weight-drop model. Intracerebral expression of the cytokines interleukin (IL)-1 beta, tumor necrosis factor-alpha (TNF alpha), IL-6, and interferon-gamma (IFN gamma) was studied by in situ hybridization and immunohistochemistry. The animals were killed at 6 hours or 1, 2, 4, 6, 8, or 16 days postinjury. In the injured area, no messenger (m)RNA expression was seen during the first 2 days after the trauma. On Days 4 to 6 posttrauma, however, strong IL-1 beta, TNF alpha, and IL-6 mRNA expression was detected in mononuclear cells surrounding the contusion. Expression of IFN gamma was not detected. Immunohistochemical double labeling confirmed the in situ hybridization results and demonstrated that mononuclear phagocytes and astrocytes produced IL-1 beta and that mainly astrocytes produced TNF alpha. The findings showed, somewhat unexpectedly, a late peak of intracerebral cytokine production in the injured area and in the contralateral corpus callosum, allowing for both local and global effects on the brain. An unexpected difference in the cellular sources of TNF alpha and IL-1 beta was detected. The cytokine pattern differs from that seen in other central nervous system inflammatory diseases and trauma models, suggesting that the intracerebral immune response is not a uniform event. The dominance of late cytokine production indicates that many cytokine effects are late events in an experimental contusion: Different pathogenic mechanisms may thus be operative at different times after brain injury.

Animals↗
PubMed1997

Cerebrospinal fluid interleukin-1 receptor antagonist and tumor necrosis factor-alpha following subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) causes an inflammatory reaction and may lead to ischemic brain damage. Experimental ischemia has been shown to be connected with the alarm-reaction cytokines interleukin-1 receptor antagonist (IL-1Ra) and tumor necrosis factor-alpha (TNF alpha). Increased levels of these cytokines, however, have not been detected thus far in patients following an SAH event. For this reason daily cerebrospinal fluid (CSF) samples were collected from 22 consecutively enrolled patients with SAH and from 10 non-SAH patients (controls). The CSF samples were studied using immunoassays for IL-1Ra and TNF alpha to investigate whether an SAH caused increased cytokine levels. The mean IL-1Ra levels were significantly higher in patients with SAH who were in poor clinical condition on admission than in those who were in good condition (318 pg/ml vs. 82 pg/ml, p < 0.02). The IL-1Ra levels increased during delayed ischemic episodes and after surgery in patients who were in poor clinical condition. Significant increases in IL-1Ra and TNF alpha were detected during Days 4 through 10 in patients suffering from SAH who eventually had a poor outcome (p < 0.05). Patients with good outcomes and control patients had low levels of these cytokines. The levels of IL-1Ra increased after surgery in patients with Hunt and Hess Grades III through V, but not in those with Grade I or II. This finding indicates that patients in poor clinical condition have a labile biochemical state in the brain that is reflected in increased cytokine levels following the surgical trauma. Both IL-1Ra and TNF alpha are known to induce fever, malaise, leukocytosis, and nitric oxide synthesis and to mediate ischemic and traumatic brain injuries. The present study shows that levels of these cytokines increase after SAH occurs and that high cytokine levels correlate with brain damage. It is therefore likely that fever, leukocytosis, and nitric oxide synthesis are also mediated by IL-1 in patients suffering from SAH and it is probable that the inflammatory mediators contribute to brain damage.

Adult↗
PubMed1997

Guidelines for treatment of head injury in adults. Opinions of a group of neurosurgeons.

There are a number of parallel activities world wide to devise guidelines for the treatment of head injuries. A Group of neurosurgeons from various European countries worked on guidelines during three informal meetings, which may serve as a base for discussion of national or local protocols. Three levels of certainty were distinguished: Measures that must be taken which such a high degree of certainty, that they have not seriously been challenged-principles. Measures, that should be taken, as there is reasonable evidence in the literature about its efficacy-recommendations and measures that may be taken, but proof of its efficacy is lacking-optional measures. Protocols based on these guidelines are felt to help young neurosurgeons in training, define neurosurgical needs for other specialities and enhance the general efficacy of care for the head injured patient including multiple injuries.

Adult↗
PubMed1996

Dexamethasone and colchicine reduce inflammation and delayed oedema following experimental brain contusion.

The effect of anti-inflammatory treatment on monocyte/macrophage infiltration, major histocompatibility complex molecules (MHC) class II expression and delayed oedema following experimental brain contusion was studied by immunohistochemistry and tissue-specific gravity measurement in 44 rats. Colchicine, chloroquine and dexamethasone administered once daily for five days after the trauma reduced inflammation and oedema. The difference was statistically significant with colchicine and dexamethasone. The findings comprise further evidence of a pathogenetically important inflammation after experimental contusion. It is probable that anti-inflammatory agents may prevent secondary neurological damage due to elevated intracranial pressure and cell to cell- or cytokine-mediated neuronal degeneration and demyelination.

Animals↗
PubMed1996

Microsurgery with the Steiner-Lindquist stereotaxic guide.

The Steiner-Lindquist microsurgical stereotaxic guide was used for operations for intra-axial lesions in 15 patients. The lesions were identified by stereotaxic CT or MRI and stereotactic co-ordinates were then calculated and set for the guiding laser beam. The beam was used for planning the craniotomy and its path followed during the microsurgical dissection, until the lesion was reached. Seven lesions were situated in eloquent areas of the brain and could not have been safely attacked without the aid of stereotaxic localization. Five of these and two other lesions were quite small, and would have been difficult to find without jeopardizing normal brain structures. For the remaining lesions the stereotaxic laser guide was facilitatory, but not indispensible. Radical removal was achieved in 11 of the 15 lesions. The Steiner-Lindquist microsurgical guide incorporates the freedom of standard microsurgical techniques with the safety of operating in a stereotaxically defined space.

Adolescent↗
PubMed1996

Cerebrospinal fluid and blood lymphocyte subpopulations following subarachnoid haemorrhage.

Lymphocyte subpopulations from 10 patients who had had a subarachnoid haemorrhage were analysed. In CSF, an increase of CD3 cells was found in two of ten, CD4 in one of ten, CD8 in three of ten, and CD19 in three of ten patients. Three patients with delayed ischaemic deficit (DID) showed a statistically significant increase of intrathecal suppressor/cytotoxic/NK-cells. The cellular inflammation had been modulated within the CNS indicating a pathogenic role in the biochemical cascades following SAH.

Adult↗
PubMed1996

Recurrence of cranial base meningiomas.

OBJECTIVE: Long-term data on the natural history of traditionally treated cranial base meningiomas are necessary to judge the benefit of modern cranial base techniques for individual patients and to understand when nonradical surgery of a meningioma is in the interest of the patient. The only available means of obtaining such data is investigation of patients treated before the present surgical era. METHODS: The records of 315 patients who were operated on at Karolinska Hospital between January 1, 1947, and December 31, 1982, were reviewed. Of the patients, 10.8% died perioperatively and 9.7% died within 10 years. The remaining patients were followed for 10 to 36 years (mean, 18 yr). RESULTS: The 5-year recurrence rate was 4% for patients undergoing radical surgery (Grades 1 and 2) and 25 to 45% for patients undergoing Grade 3 or 4 operations. Follow-up periods longer than 5 years revealed that 16% of Grade 1 and 20% of Grade 2 patients had symptomatic recurrences, whereas a majority of Grade 4 and 5 patients showed symptomatic progression. Forty-two of 69 patients who underwent Grade 4 or 5 operations died as a result of their tumors, usually within 10 years after the first operation. No patients who underwent Grade 4 or 5 operations were free from symptomatic progression after 20 years. The tumor progression or recurrence was usually detected within the 1st 10 years, but late recurrences were seen < or = 25 years after the operation. The worst outcome was found in medial sphenoid wing/clinoidal meningiomas and in tumors invading the cavernous sinus. Subfrontal tumors showed unexpectedly high recurrence rates, with a mortality rate < or = 14% in the late phase. CONCLUSION: The findings emphasized the necessity to plan the management of patients with cranial base meningiomas according to a 10- to 20-year perspective. Patients must be followed to evaluate the treatment results and to detect recurrences. Nonradical surgery must be viewed as a temporizing or palliative measure; a continued search for means of radical tumor treatment is warranted in these often surgically difficult tumors.

Combined Modality Therapy↗
PubMed1995

Biphasic edema development after experimental brain contusion in rat.

The time course of edema development following experimental brain contusion was studied by measuring cortex specific gravity 1 and 12 h after the trauma, and thereafter once daily until 7 days after the trauma. A biphasic development of edema was observed; the specific gravity decreased to a minimum on day 2 (P < 0.001), increased to an almost normal level on day 4 and thereafter decreased again to a second minimum 6 days after the trauma (P < 0.01). Delayed edema formation has been recognized in clinical settings, but has not been described in experimental studies. This study, with a prolonged daily follow-up, clearly demonstrates that a secondary phase of edema is an experimentally reproducible entity. The model will enable study of the pathogenetic mechanisms.

Animals↗
PubMed1995

Intracerebral inflammatory response to experimental brain contusion.

The inflammatory reaction following experimental brain contusion was studied by immunohistochemistry in 22 rats during the first 16 days after trauma. An inflammatory mononuclear cell response was evident on day 2, with a maximum on days 5-6 and signs remained still 16 days after the trauma. The time course of the cellular infiltration adjacent to the lesion correlated with blood brain barrier dysfunction in the contralateral side of the traumatized hemisphere. The cellular infiltrate comprised NK cells, T-helper cells and T-cytotoxic/suppressor cells as well as monocytes/macrophages. Most of the macrophages appeared to be activated by T-cells. Surprisingly, polymorphonuclear cells appeared less engaged than mononuclear cells in the inflammation. The demonstration of immunocompetent cells and the induction of MHC-1 and MHC-II antigen provides a substrate for inflammatory reactions similar to those that cause neurological damage in inflammatory diseases such as viral infections, multiple sclerosis and experimental allergic encephalitis. Our observations indicate that the role of the inflammatory reactions may have a role, hitherto neglected, in the pathogenesis of secondary traumatic brain injury.

Animals↗