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Biomedical subjects

T Mathiesen

Publications and source records attributed to T Mathiesen.

At least 37 records · Page 2Linked to original sources

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

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

Traumatic intracerebral lesions without extracerebral haematoma in 218 patients.

218 of the 852 patients in the HIT-2 study of head injury had intracerebral lesions only. They were analysed to get more information on the optimal treatment of these severely injured patients. The initial CT scans were reviewed to exclude patients with extracerebral lesions, and to make a radiological diagnosis of contusion, contusion under a depressed fracture, diffuse axonal injury, or intracerebral haematoma. Deterioration after admission to hospital was seen in 71% of patients. Patients with contusions, and contusions from depressed fractures in particular showed a worse outcome than expected, while patients with diffuse injury had a tendency to improve rather than to deteriorate. Patients with intracerebral haematoma seemed to improve if the mass was evacuated. Nimodipine had an impact only in patients with contusions. Our findings mandate surgical evacuation of contusions and intracerebral haematomas in patients with lesions larger than 20 ml who also have radiological signs of a mass effect. Regardless of an apparently good clinical state in the early phase, intracerebral lesions larger than 50 ml seemed to benefit from surgery as compared to nonsurgical treatment. The findings indicated that a further refinement of diagnostic criteria may enable individually tailored head injury treatment to interfere with most important pathogenic mechanisms. More accurate diagnoses will improve head injury treatment and outcome, and are a prerequisite for making successful pharmaceutical trials of head injury in the future.

Adult

Intracranial traumatic and non-traumatic haemorrhagic complications of warfarin treatment.

An increased referral of patients with anticoagulation related haemorrhages necessitated an analysis of causes and outcome of these complications in a patient group that reflected Swedish therapeutic traditions of anticoagulation treatment. Prospectively, all patients from Stockholm evaluated for warfarin related intracranial haemorrhage occurring during 1987 were analysed and their 6 month outcome recorded. Sixty-eight patients were included. The results of intracranial haemorrhagic complications were catastrophic with a 77% mortality rate. Their incidence was much higher than expected. Forty-one patients had non-traumatic intracerebral haematomas, 1 had a non-traumatic subarachnoid haemorrhage and 26 had traumatic injuries. In the 42 patients with non-traumatic haemorrhages, the indications for anticoagulation were cerebral ischaemic events in a majority (27/42). The remaining 15 patients had different indications for anticoagulation. They also had an increased frequency of hypertension (p < 0.05). In the 26 patients with traumatic haematomas, only 6/26 patients had previous cerebral ischaemic injuries (p < 0.01). Valvular heart prosthesis was their most common indication (11/26) for anticoagulation. Caution in instituting anticoagulation therapy in patients with hypertension or cerebrovascular disease, which is an important indication for anticoagulation in Sweden, is mandatory. Adherence to strict treatment regimens and their continuous reevaluation may help to avoid complications. The finding of more patients than expected with haemorrhagic complications is not compatible with the risk evaluations used to justify anticoagulation therapy in the patient groups studied. Clinical practice must have changed with time, showing that risk evaluations from controlled trials or retrospectively collected clinical data from selected patients are not necessarily applicable for long-term clinical practice.

Adult

Ear tumours induced by experimental carcinogenesis in the rat: excision prevents early death.

1,2-dimethylhydrazine (DMH) is widely used to induce colorectal tumours in rodents. Some of the animals develop ear as well as colorectal tumours. Rats with large, ulcerated ear tumours are usually sacrificed before the completion of the experiment. In this experiment, fourty-six male Spraque-Dawley rats were injected with 1,2-dimethylhydrazine (21 mg/kg body weight) once a week for 27 weeks to study the histogenesis of colorectal carcinoma. Thirty-six developed ear tumours. Fourteen of the 36 tumours were larger than 2 cm in diameter. These developed between 20-26 weeks and were surgically excised 1-5 weeks later. Four rats died postoperatively. The surgical removal of large ear tumours permitted the completion of the large bowel experiment on schedule (i.e. 27 weeks) in 10 (28%) of the 36 rats with ear tumours.

1,2-Dimethylhydrazine

Increased interleukin-6 levels in cerebrospinal fluid following subarachnoid hemorrhage.

Serum and cerebrospinal fluid (CSF) samples from 12 patients were analyzed for interleukin (IL)-6, soluble IL-2 receptor (IL-2R), and soluble CD8 levels in order to determine the immune activation profile following subarachnoid hemorrhage (SAH). Dramatically increased levels of IL-6 and moderate increases of soluble IL-2R were detected in the CSF in 11 of the 12 patients; slightly elevated levels of soluble CD8 were observed in six patients. The IL-6 levels were higher on Day 6 than on Days 3 and 9. The increases in IL-6, soluble IL-2R, and soluble CD8 levels in the CSF samples were not paralleled by increased values in the serum samples, and thus probably reflected an intrathecal synthesis of the cytokine. Passive transfer of IL-6 across the blood-brain barrier seemed not to occur since the serum and CSF levels of IL-6 showed a negative correlation. The findings suggest a severe inflammatory affection of the central nervous system that could be of importance in understanding the clinical course in patients following SAH.

Adult

High recurrence rate following aspiration of colloid cysts in the third ventricle.

Sixteen patients treated between 1969 and 1989 for a colloid cyst of the foramen of Monro by stereotactically guided aspiration (not stereotactic extirpation) were evaluated to assess the long-term outcome of the procedure. Thirteen of these patients required reoperation due to an acute comatose state, failure to achieve permanent reduction of the cyst, or symptomatic hydrocephalus. Of these 13, six were treated twice and two were treated three times by stereotactic aspiration. Five patients underwent microsurgical extirpation and three had a shunt placed following a failed aspiration. Failure of the first procedure was detected within the first 2 months after treatment in eight patients and after more than 6 years in seven. Following stereotactic aspiration, three patients experienced a temporary memory deficit and confusion and one patient suffered a central pain syndrome. Eleven of the 26 procedures were followed by a recurrence 6 to 15 years after treatment; seven recurrent cysts were detected after more than 8 years. Of the patients with recurrences, three did not undergo repeat surgery but showed an increase in cyst size at the latest follow-up examination. It is suggested that radical removal by open or stereotactically guided microsurgery is the method of choice since stereotactic aspiration fails to offer a radical or permanent treatment for colloid cysts of the third ventricle.

Adolescent

Immunoglobulin G subclasses and lymphocyte stimulatory responses to cytomegalovirus in transplant patients with primary cytomegalovirus infections.

The early activation of T- and B-cell responses to cytomegalovirus was studied in immunosuppressed patients. Primary lymphocyte stimulation to cytomegalovirus (CMV) antigen, a measure of T-helper activity, and anti-CMV IgG subclass responses were analyzed. Ten patients suffering from primary CMV infection following renal transplantation were studied. Of the ten, nine became positive for CMV induced lymphocyte proliferation 5-40 weeks after transplantation. Nine showed an almost simultaneous appearance of anti-CMV IgG1 and three at 3-32 weeks after transplantation, while one patient synthesized only low levels of anti-CMV IgG1. The lymphocyte proliferation assays have limited diagnostic value for primary CMV infection in renal transplant patients. The humoral and cellular immune responses seemed to be independent of each other.

Adolescent

Induction of MHC class I antigen expression following infection of a human esthesioneuroblastoma cell line with cytomegalovirus and human immunodeficiency virus.

Productive infections with cytomegalovirus (CMV) and human immunodeficiency virus (HIV) were established in the Tp41ON cell line derived from a human esthesioneuroblastoma. HIV antigen expression was highest in cultures coinfected with CMV and HIV. Viral infection caused increased MHC class I antigen expression while class II and CD4 antigens remained undetectable using immunofluorescence methods. Uninfected cultures showed 10% and coinfected cultures 80% class I antigen positive cells. In coinfected cultures, CMV and HIV antigens were detected in 4% and 8% of the cells, respectively. The detection of CMV antigens in some multinucleated cells suggests coinfection with both viruses in these cells, as multinucleated cells were not found in cultures infected with CMV only. The study shows that a cell line showing neuronal differentiation in vitro can be infected with CMV and HIV and that this infection increases MHC class I antigen expression.

Antigens, Neoplasm

Brain damage caused by hydrogen sulfide: a follow-up study of six patients.

Hydrogen sulfide (H2S) poisoning involves a risk of hypoxic brain damage. Six patients who lost consciousness due to H2S poisoning are described. The symptoms varied from anosmia in the patient with the shortest but highest exposure to delayed neurological deterioration in the patient with the longest exposure. The two patients with the most serious symptoms developed pulmonary edema, which may have prolonged the hypoxia. The patients were reexaminated 5 years or more after the poisoning. The five patients who had been unconscious in H2S atmosphere for from 5 to 15-20 min showed persisting impairment at neurological and neuropsychological re-examination. Memory and motor function were most affected. One patient was seriously demented. Recent reports of large groups of H2S-poisoned workers probably underestimate the risk of sequelae, due to the inclusion of cases with exposure of short duration and lack of follow-up.

Adult

[Polymyalgia rheumatica. A disease in general practice].

In retrospective investigation from a group practice with 4,100 registered patients, the number of cases of giant cell arthritis (polymyalgia rheumatica and temporal arteritis) diagnosed during the period 1978-1988 was calculated. Possible diagnostic criteria and a proposal for a therapeutic plan are discussed. Twenty-eight patients (40% men and 60% women) participated in the investigation. This gives an incidence of 0.56/1,000 which is higher than in previous Danish investigations. Problems involved in excluding infectious diseases and malignant conditions are illustrated by means of a review of the reasons for consultation, the examinations performed and the treatments during a period of six months prior to commencement of steroid therapy. The diagnostic delay was found to be two months. 35% of the patients were hospitalized in the course of the disease. The average duration of treatment was 22.5 months. The importance of good information to the patients and the necessary of good cooperation between general practice and the hospital sector is emphasized.

Aged

Fine analysis of intrathecally synthesized anti-HIV IgG1-4 by peptide mapping.

ELISAs utilizing HIV-derived synthetic peptides as antigen were used to analyze serum and CSF IgG1-4 from 15 HIV infected patients. Intrathecally synthesized IgG1-4 reactive to one or several HIV-derived peptides were detectable in 12 of 15 patients. Intrathecally synthesized anti-peptide IgG was more common in patients with neurological symptoms than in those without. CSF reactivity not paralleled by serum reactivity was detected to HIV-peptides in 4 patients. IgG1-4 to gp41 was relatively more frequent in the CNS than IgG1-4 to gag. Intrathecal IgG synthesis to the gp120 peptide was not detected in any patient. The anti-peptide responses were dominated by IgG1. Intrathecal IgG2 and 4 synthesis was found in 2 and 5 patients, respectively. IgG3 synthesis intrathecally was not detected in any of the patients. ELISAs detecting IgG1-4 to HIV-derived synthetic peptides are feasible to analyze the fine specificities of intrathecal IgG. The mapping of idiotypes and isotypes of IgG synthesized in the CNS will increase the possibilities of elucidating B-cell regulation in the CNS and which viral components evoke immune responses.

Gene Products, gag

Aberrant IgG subclass distribution to measles in healthy seropositive individuals, in patients with SSPE and in immunoglobulin-deficient patients.

Sera from healthy seropositive donors, patients with acute measles, subacute sclerosing panencephalitis, common variable immunodeficiency, and CH gene deletions were analysed for anti-measles IgG1-4. Compared with other anti-viral immune responses of IgG1 and IgG3, an unusual predominance of specific IgG1 prevailed; only four out of a total of 68 patients showed anti-measles IgG3. Of the 17 healthy, measles seropositive serum donors, all showed specific IgG1, none showed IgG3 and six had IgG4. Eight out of 10 patients with SSPE showed an anti-measles IgG1 and IgG4 response while IgG3 was not seen. The IgG1 and IgG4 subclass patterns had some exceptions. Anti-measles IgG3 was found in five out of five patients with deletion of the gamma-1 encoding gene segments and in four out of 15 patients with recent measles antigen stimulation. The subclass pattern was suggested to reflect the immunological compromise associated with measles infections.

Adolescent

Specific in vitro IgG subclass synthesis and lymphocyte proliferation responses in herpes virus encephalitis.

Cerebrospinal fluid, peripheral blood lymphocytes (PBL) and sera from 5 patients with herpes simplex encephalitis (HSVE), 3 with varicellae zoster (VZV) meningoencephalitis and 5 with encephalitis of unknown origin (NUD) were analyzed. Lymphocytes from both blood and CSF were shown to synthesize anti-VZV IgG subclasses in VZV meningoencephalitis and anti-HSV IgG subclasses in HSVE. The subclass patterns of CSF and in vitro synthesized anti-viral IgG were similar, suggesting that a considerable portion of the antiviral IgG subclasses detected are synthesized in the CNS compartment. Antigen presentation in vitro seemed to produce a heterologous IgG4 and/or 3 response in 3 patients. Lymphocyte proliferation was detectable in response to HSV and VZV, respectively.

Antibodies, Viral