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Biomedical subjects

Morten Lund-Johansen

Publications and source records attributed to Morten Lund-Johansen.

12 recordsLinked to original sources

[A 90-year-old woman with acute hemiparesis].

A right-handed woman of 90, taking aspirin 160 mg daily, suffered acute neck pain radiating to the shoulders, with right side hemiparesis and numbness occurring minutes thereafter. On admission 2.5 hrs later, examination showed paresis and hyporeflexia of the right limbs accompanied by neck stiffness and vertebral tenderness in level C7. Acute stroke was the initial working diagnosis. Cerebral CT was normal. Symptoms progressed with left arm numbness and left ancle clonus, and eight hours after symptom onset there was bilateral plantar inversion, reduced skin prick sensibility below C4, bladder paresis and anal sphincter hypotonia. CT myelography revealed an intraspinal mass extending from C2 to C6. 14 hours after symptom onset, a spinal epidural haematoma was removed by spinal laminectomy. Recovery and functional outcome was good. Symptoms, work-up and treatment are discussed with reference to previous publications.

Acute Disease↗

[Surgical treatment of hormone-producing pituitary adenomas].

BACKGROUND: Transsphenoidal surgical treatment is established as a treatment of hormonally active pituitary tumours, except prolactinomas. The cure rates in studies of large series of patients are varying. The volume of patients at Haukeland University Hospital, Bergen is limited, and in order to maintain sufficient experience, one surgeon performs all procedures. The aim of this study was to study the rates of cure and complications in patients who had undergone this procedure. METHODS: We did a retrospective survey evaluating the operative results of one surgeon operating hormonally active pituitary tumours from 1993 through 2002 at Haukeland University Hospital. Data were collected from medical and surgical case records. RESULTS: Primary surgery cured 37 out of 57 patients. There were 13 complications, including one death in hospital. Twenty patients received additional treatment with surgery, radiation therapy, or adrenalectomy. Thirteen of these patients received medical treatment with either somatostatin analogues or dopamine agonists. INTERPRETATION: Our study indicates that one surgeon can achieve results for transsphenoidal surgery that are on par with results reported from larger centres.

Adenoma↗

[Endogenous Cushing's syndrome].

BACKGROUND: Untreated endogenous Cushing's syndrome is a serious condition with high morbidity and mortality. New diagnostic procedures make today's assessment more accurate. We describe which tests should be done when there is suspicion of the syndrome. Treatment options are mentioned. MATERIAL AND METHODS: The paper is based on current international literature and reflects the experience of the authors. RESULTS AND INTERPRETATION: Endogenous Cushing's syndrome is caused by elevated cortisol levels. The reason can be overproduction of ACTH or an adrenocortical pathology. It should be considered when combinations of symptoms like central obesity, proximal muscle weakness, striae and menstrual irregularities are seen. Osteoporosis and impotence are other important symptoms. Diagnosis of Cushing's syndrome is often challenging. Measurement of urinary free cortisol or overnight dexamethasone suppression test has usually been performed initially. Midnight salivary cortisol seems promising as an alternative. The final diagnosis is often made after a combined evaluation of dynamic tests. The first-line treatment of endogenous Cushing's syndrome is surgery.

Adrenocorticotropic Hormone↗

Untreated vestibular schwannomas: vertigo is a powerful predictor for health-related quality of life.

OBJECTIVE: The aim of the present study was to characterize the relation between quality of life (QOL) and the four major complaints (hearing loss, tinnitus, vertigo, and unsteadiness) caused by unilateral vestibular schwannomas (VS) in a cohort of well-characterized untreated patients. METHODS: One hundred ninety-nine consecutive patients (91 men, 108 women) with a mean age of 56.9 years were studied prospectively during the 4-year period from 2001 to 2004. The average length of time from symptom onset to the radiological diagnosis was 4.2 years. The patients were subject to a standardized examination including magnetic resonance imaging, evaluation of hearing acuity, balance function by stabilimetry, and a visual analogue scale self-evaluation of tinnitus and vertigo. Furthermore, the patients responded to two questionnaires: Short-Form 36 and the Glasgow Benefit Inventory. A reference population was recruited from 80 adults who visited Haukeland University Hospital as nonpatients or nonstaff members. All data were recorded prospectively in a customized case report form. Statistical analysis was performed with SPSS software. RESULTS: The response rates of the Short-Form 36 and Glasgow Benefit Inventory questionnaires were 91.5 and 89.9%, respectively. According to the Short-Form 36 questionnaire, the patients scored significantly below that of expected norms with the exception of physical function and mental health. Patients report negative benefit on the general and physical sections of the Glasgow Benefit Inventory questionnaire. Regression analysis showed that vertigo had a strong negative impact on QOL, whereas unilateral hearing loss and tinnitus had less impact on QOL. CONCLUSION: Vertigo is the symptom causing the most pronounced negative effect on QOL in patients with VS. The more frequent VS symptoms, unilateral hearing loss and tinnitus, seem to be less important in the patients' perception of QOL as evaluated by the questionnaires used in this study. If vertigo could be relieved by treatment, this symptom should be a primary focus when discussing treatment options in small- to medium-sized VS.

Adult↗

Secretoglobins in the human pituitary: high expression of lipophilin B and its down-regulation in pituitary adenomas.

Secretoglobins are small secreted proteins, the expression of which has mostly been associated with secretory mucosal epithelia. Several secretoglobins have been implicated in the development of various human cancers. Allelic deletions of chromosome 11q13 correlates with the invasiveness of pituitary tumors. Intriguingly, several secretoglobin genes are located on 11q13; however, for most of these genes the expression in the pituitary and pituitary tumors have not been investigated. Antibodies specific for the secretoglobin lipophilin B (SCGB1D2, BU101) were developed and used in an immunohistochemical analysis of a human normal tissue microarray. Prominent lipophilin B immunoreactivity was found in the secretory cells of the anterior pituitary. Eight of nine analyzed pituitary adenomas showed a reduction in lipophilin B immunoreactivity compared to normal pituitary. However, there was no apparent association between lipophilin B immunoreactivity and hormone production or tumor invasiveness. Expression of eight different secretoglobin mRNAs were analyzed in normal pituitary and the pituitary adenoma cell line HP75 by highly specific quantitative real-time reverse transcription-PCR assays. Lipophilins B and C (SCGB2A1, mammaglobin B) were the most prominently expressed secretoglobin mRNAs in the pituitary. No secretoglobin mRNA was detected in the HP75 cells. The present report demonstrates, for the first time, lipophilin B expression in the pituitary and its apparent down-regulation in pituitary adenomas.

Adenoma↗

Vestibular schwannomas: clinical results and quality of life after microsurgery or gamma knife radiosurgery.

OBJECTIVE: The aim of the present study was to evaluate the overall treatment efficacy (tumor control, facial nerve function, complications) and quality of life for patients treated primarily for unilateral vestibular schwannomas of 30 mm or less, either by microsurgery or by gamma knife (GK) radiosurgery. The results for the two treatment groups are compared with each other, with main emphasis on the long-term quality of life. METHODS: This is a retrospective study of 189 consecutive patients, 86 treated by microsurgery and 103 by gamma knife. The mean observation time was 5.9 years. All patients had a magnetic resonance imaging scan and clinical evaluation performed toward the end of the study. To evaluate the quality of life, we used two standardized questionnaires, the Glasgow Benefit Inventory and Short-Form 36. The questionnaires were sent to the 168 living patients. The reply rate was 83.3%. RESULTS: A total of 79.8% of the patients in the microsurgery group and 94.8% of the GK patients had a good facial nerve function (House-Brackmann Grade 1-2). Hearing was usually lost after microsurgery, whereas the GK patients had preserved hearing, which often became reduced over the years after the treatment. The treatment efficacy, defined as no need for additional treatment, was similar for the two treatment modalities. Quality of life was reduced compared with normative data, being most reduced in the microsurgery group. Some of the quality of life questions showed an association with facial nerve function and sex. CONCLUSION: Posttreatment facial nerve function, hearing, complication rates, and quality of life were all significantly in favor of GK radiosurgery.

Adult↗

Prospects for delivery of recombinant angiostatin by cell-encapsulation therapy.

Implantation of encapsulated nonautologous cells that have been genetically modified to secrete proteins with tumor suppressor properties represents an alternative nonviral strategy to cancer gene therapy. We report an approach to raise the yield of recombinant proteins from encapsulated cells substantially. We hypothesized that by optimizing the encapsulation procedure, the production efficacy from the encapsulated cells could be increased. HEK 293 EBNA cells were genetically engineered to produce angiostatin. Encapsulation was performed by varying bead size, cellular density, homogeneity, and ion composition of the gel. The morphology and viability of the cells and the release of angiostatin were studied. Computer software was developed for three-dimensional imaging and quantification of cell viability. Angiostatin production was assessed at 3, 6, and 11 weeks using enzyme-linked immunosorbent assay (ELISA). Inhomogeneous gels facilitated cell growth and viability. The most efficient inhomogeneous microcapsules were generated by reducing the size and cellular density of the beads. The viability and the production of angiostatin were 3 to 5 times higher than in the homogeneous capsules. Significant amounts of viable cells were present in both homogeneous and inhomogeneous beads after 6 months of culture. The stability of the alginate matrix was greatly enhanced by gelling in the presence of barium. In conclusion, the viability and production efficacy of recombinant angiostatin from alginate-encapsulated cells can be increased considerably by optimizing the encapsulation procedure. The development of such optimized microcapsules brings cell-encapsulation therapy further towards clinical use in cancer therapy.

Alginates↗

[Hormonally inactive pituitary adenomas].

BACKGROUND: This paper surveys hormonally inactive pituitary tumours on the basis of the current international literature; it also reflects the experience of the authors. INTERPRETATION: Pituitary tumours are frequently diagnosed and usually show a low potential for growth. Although benign they may invade adjacent structures such as the cavernous and sphenoid sinuses. The diagnosis is usually made on the basis of pituitary failure or visual problems, or incidentally. Tumour debulking or removal, usually by transsphenoidal surgery, is indicated if there is a compression of the optic chiasm or if the tumour shows signs of growth on consecutive MRI scans. Surgery is an effective treatment of these tumours, with little risk of complications. Repeated surgery, either transsphenoidally or by craniotomy, is indicated if chiasmal decompression is not achieved initially. Fractionated single beam irradiation or stereotactic radiosurgery is indicated in cases where there is a residual of growing tumours that may not be removed surgically.

Acromegaly↗

Mechanisms of tumor cell invasion and angiogenesis in the central nervous system.

Despite extensive progress in characterizing the genetic events involved in the development of gliomas, the cellular origin and the defined molecular mechanisms that lead to their occurrence are still unclear. It is known that tumours are of monoclonal origin. This is contrasted by the fact that gliomas frequently express features of different glial cell lineages. With the identification of pluripotent neural stem cells and the growth factors that control neural cell development, we are now making early inroads towards understanding glial cell migration as well as the neural cell plasticity within the adult central nervous system (CNS). Gliomas share several fetal antigens with immature brain cells. It is therefore tempting to speculate that the migration of neural precursor cells actually represents the normal counterpart of glioma cell migration. The migratory behavior of gliomas may be due to a predetermined interplay between normal brain tissue and the migrating cells, where the brain represents a permissive tissue for guiding cells with certain phenotypic traits to migrate along specific anatomical structures. Malignant progression is also accompanied by extensive angiogenesis which is especially prominent in glioblastoma multiforme (GBM). For cell proliferation to take place, several cell signaling cues mediated by specific growth factors are shared between the glioma cells and the endothelial cells while others are unique for endothelial cells. Therefore the endothelial cell compartment represents a promising target for novel therapeutic strategies including gene therapy and cell-based therapies.

Animals↗

Imaging of experimental rat gliomas using a clinical MR scanner.

BACKGROUND: Studies of brain tumor development in experimental animal models have to date mostly been based on post-mortem histological examinations. The use of magnetic resonance imaging (MRI) may provide a non-invasive technique for studying tumor growth and treatment effects in such animal models. However, most of these studies have been performed on purpose-dedicated small bore magnetic resonance (MR) systems, of high cost and limited availability. The purpose of this study was thus to obtain high-resolution images of experimental gliomas in the rat brain, using a clinical 1.5 T MR scanner. METHODS: Anesthesized rats bearing BT4C brain tumors were positioned into a specially designed immobilizing device, and a small circular coil was positioned onto the skulls. Two T1 weighted series were acquired before and after subcutaneous contrast injections. A T2 weighted series was also obtained. The rats were then sacrified, the brains removed, and the histological tumor volumes were compared to the volumes obtained on MRI. RESULTS: There were visible tumors in 10 of 13 animals scanned on MR. The rim of the tumors were visualized on T1 weighted series without contrast. On T1 images with contrast, the tumors were seen as high signal intensity areas. The T2 weighted images showed peritumoral edema. No necrosis or cystic parts of the tumors were detected. There was a consistency between the MR and the histology findings, showing a high degree of correlation between the two volume determination methods. CONCLUSIONS: High-resolution images of experimental rat gliomas can be obtained using a clinical MR scanner and a commercially available RF coil. This MRI technique may also be expanded to extraneural rat tumor models, for studies of tumor development and treatment.

Animals↗

Progress and challenges for cell encapsulation in brain tumour therapy.

Cell encapsulation provides a method to circumvent the host immune system by encapsulating cells or tissues in immunoisolating, semipermeable membranes before implantation. The technology has been widely studied with an aim of developing bio-organs transplantable into patients without the need of immunosuppression, and in cancer therapy, the principle of cell encapsulation may be further exploited. Encapsulated recombinant cells represent factories or bioreactors for the production of therapeutic proteins. By implanting the bioreactors in the vicinity of the tumour, long-term local de novo delivery of the therapeutic proteins may be achieved. Malignant brain tumours such as glioblastoma multiforme (GBM) remain highly lethal neoplasms, refractory to current therapies. Researchers and medical professionals are working on developing translational therapies to combat these aggressive tumours. Numerous clinical trials on gene therapy for glioma patients have been conducted over the last decade, but the results have largely been disappointing. Cell encapsulation represents an alternative method for local delivery of therapeutic proteins with antineoplastic properties to glioma patients. The concept has not yet reached clinical trials, but encouraging results have been achieved in rats bearing gliomas when implanting endostatin-secreting encapsulated cells into the rat brain. This review primarily focuses on the recent progress that has been made with cell encapsulation technology. In addition, the challenges this field faces before clinical application in brain tumour patients is discussed.

Alginates↗

Expression of extracellular matrix components in a highly infiltrative in vivo glioma model.

This work demonstrates the expression of extracellular matrix (ECM) components in a highly infiltrative brain tumor model developed by simple inoculation of spheroids from five human glioma biopsy tissues directly into the brains of immunodeficient rats. Non-invasive tumors derived from one glioblastoma biopsy specimen and two glioma cell lines (D-54MG and U-251MG) were also included in this study. The extent of tumor cell infiltration was studied using a pan-human monoclonal anti-vimentin antibody. The cellular origin for several of these ECM components was identified using human-specific monoclonal antibodies and polyclonal antibodies detecting epitopes from both species. Immunostaining revealed a diffuse parenchymal staining of glioma-produced tenascin, whereas vitronectin was produced mainly by the invading glioma cells. ECM components such as laminin, fibronectin and collagen type IV were most probably produced by the host and were mainly associated with the blood vessels in the tumors. However, some parenchymal staining with regional variations was observed. The expression pattern of these components was different in cell lines tumors as compared to the biopsy specimen tumors. The alpha3 and beta1 integrin subunits were mainly observed in areas of tumor cell invasion in the invasive tumors. In conclusion, the observed staining patterns clarify the cellular origin and indicate the possible biological function of tenascin, vitronectin, laminin, fibronectin and collagen type IV in these highly invasive malignant tumors of glial origin.

Animals↗