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Biomedical subjects

T Kossmann

Publications and source records attributed to T Kossmann.

At least 55 records · Page 3Linked to original sources
PubMed1997

Experimental diffuse axonal injury induces enhanced neuronal C5a receptor mRNA expression in rats.

Several studies suggest the involvement of the complement system in the pathophysiology of traumatic brain injury (TBI). Since the intrathecal generation of anaphylatoxin C5a has been shown to mediate inflammatory effects within the central nervous system, we sought to characterize the cellular expression of the mRNA for the C5a receptor (C5aR, CD88) in brains of rats with experimental diffuse axonal injury (DAI) by in situ hybridization. Infiltrating leukocytes expressing C5aR mRNA were seen in meninges and lateral ventricles as early as 4 h after induction of DAI. The number of infiltrating C5aR-positive cells increased gradually up to 24 h after trauma. Within the brain parenchyma, up-regulation of C5aR mRNA expression was first seen in cerebellar Purkinje cells within 8 h. At 24 h after TBI, expression of C5aR mRNA was widespread bilaterally throughout the cortex and cerebellum, the cellular expression being restricted to pyramidal neurons and Purkinje cells. The intensity of C5aR transcript signals on neurons increased further up to 96 h after trauma. Ligand binding of C5a to its receptor on neurons might mediate previously unknown functions, thus possibly leading to neurotoxicity and secondary neuronal damage after TBI.

Animals↗
PubMed1997

[Neurochemical changes and current pharmacological approaches in craniocerebral trauma].

In recent years, our knowledge concerning pathophysiological changes in brain metabolism after traumatic brain injury (TBI) has greatly expanded. This, in turn, has enabled the development of specific pharmacological strategies for the supplementary treatment of brain-injured patients with the aim of reducing secondary brain damage. The present article focuses on the pathophysiology of TBI and the possibilities for pharmacological intervention. While some of the substances reviewed and presently used in the treatment of TBI, others are under experimental and clinical evaluation at different stages.

Animals↗
PubMed1997

Elevated levels of the complement components C3 and factor B in ventricular cerebrospinal fluid of patients with traumatic brain injury.

Immunological events occurring in the central nervous system (CNS) as a result of head trauma are largely unexplored. We report here that the levels of the alternative pathway complement proteins C3 and factor B are elevated in the cerebrospinal fluid (CSF) of head-injured patients. C3 and factor B indices suggest that changes in C3 and factor B levels in CSF are most likely due to altered blood-brain barrier integrity and not to intrathecal synthesis. These data demonstrate, for the first time, elevated levels of complement proteins in CSF of patients with severe traumatic brain injury. Elevated complement levels in brain injury may contribute to secondary damage.

Adolescent↗
PubMed1997

Detection of erythropoietin in human liquor: intrinsic erythropoietin production in the brain.

Until now, erythropoietin (EPO) was thought to be produced exclusively in fetal liver and adult kidney and to regulate mammalian erythropoiesis. However, we recently showed that steady state levels of EPO mRNA could be induced up to 100-fold in primary mouse astrocytes cultured under hypoxic conditions, and also reported the presence of mRNA for EPO and its receptor in the brain of mouse, monkey and human. In extending these studies on humans we now show that immunoreactive EPO is present in ventricular cerebrospinal fluid (CSF) of 5 patients with traumatic brain injuries: EPO was found in 15 out of 15 CSF samples. There was no correlation between the serum EPO concentration and the concentration in the CSF. However, EPO concentrations in CSF correlated with the degree of blood-brain-barrier dysfunction. This suggests that EPO does not cross the intact blood-brain-barrier, implying that EPO is produced in the brain itself, most probably by astrocytes in an oxygen-dependent manner. In view that neuronal cells carry the EPO receptor, we propose that EPO acts in a paracrine fashion in the central nervous system and might function as a protective factor against hypoxia-induced damage of neurons.

Adult↗
PubMed1997

Production of cytokines following brain injury: beneficial and deleterious for the damaged tissue.

A profound inflammatory response is initiated immediately following traumatic brain injury (TBI) and is characterized by the release of several cytokines with pro- and anti-inflammatory functions. In order to elucidate which cytokines are released in the human brain in response to injury as well as in the peripheral compartment, IL-1, IL-6, IL-8, IL-10, TNF-alpha and TGF-beta were monitored in CSF and serum of severely brain-injured patients. Furthermore, we investigated the possible modulation of systemic reactions by IL-6 and the ability of IL-6 and IL-8 to promote the synthesis of nerve growth factor.

Animals↗
PubMed1997

Neurotransmitters in cerebrospinal fluid reflect pathological activity.

The excitatory transmitters glutamate and aspartate become toxic whenever their extracellular levels are increased because of neuronal, glial and endothelial impairment. Taurine, a volume-regulating amino acid, is released upon excitotoxin-induced cell swelling. Our aim was to investigate if glutamate and aspartate in cerebrospinal fluid (CSF) reveal neuropathology in neurological patients, and if taurine unmasks glutamate-mediated toxicity. Glutamate and aspartate are doubled in viral meningitis, acute multiple sclerosis (MS) and myelopathy compared with control subjects and patients with peripheral facial nerve palsy. These levels do not coincide with a disturbed blood-brain barrier, as estimated by the albumin ratio, are independent of their precursors (glutamine, asparagine) and are not associated with cell lysis. Taurine is significantly increased in meningitis, acute MS, and myelopathy, suggesting glutamate-mediated toxicity. Analysis of transmitters in lumbar CSF can be used to identify patients with cerebral and spinal pathology who might benefit from specific receptor-modulating agents.

Adult↗
PubMed1997

Interleukin-8 released into the cerebrospinal fluid after brain injury is associated with blood-brain barrier dysfunction and nerve growth factor production.

Interleukin (IL) 8 was measured in CSF of 14 patients with severe traumatic brain injury. IL-8 levels were significantly higher in CSF (up to 8,000 pg/ml) than serum (up to 2,400 pg/ml) (p < 0.05), suggesting intrathecal production. Maximal IL-8 values in CSF correlated with a severe dysfunction of the blood-brain barrier. Nerve growth factor (NGF) was detected in CSF of 7 of 14 patients (range of maximal NGF: 62-12,130 pg/ml). IL-8 concentrations were significantly higher in these patients than in those without NGF (p < 0.01). CSF containing high IL-8 (3,800-7,900 pg/ml) induced greater NGF production in cultured astrocytes (202-434 pg/ml) than samples with low IL-8 (600-1,000 pg/ml), which showed a smaller NGF increase (0-165 pg/ml). Anti-IL-8 antibodies strongly reduced (52-100%) the release of NGF in the group of high IL-8, whereas in the group with low IL-8, this effect was lower (0-52%). The inability of anti-IL-8 antibodies to inhibit the synthesis of NGF completely may depend on cytokines like tumor necrosis factor alpha and IL-6 found in these CSF samples, which may act in association with IL-8. Thus, IL-8 may represent a pivotal cytokine in the pathology of brain injury.

Adolescent↗
PubMed1996

Interleukin-6 released in human cerebrospinal fluid following traumatic brain injury may trigger nerve growth factor production in astrocytes.

Cytokines are involved in nerve regeneration by modulating the synthesis of neurotrophic factors. The role played by interleukin-6 (IL-6) in promoting nerve growth factor (NGF) after brain injury was investigated by monitoring the release of IL-6 and NGF in ventricular cerebrospinal fluid (CSF) of 22 patients with severe traumatic brain injuries. IL-6 was found in the CSF of all individuals and remained elevated for the whole study period. NGF appeared in the CSF if IL-6 levels reached high concentrations and was often detected simultaneously with or following an IL-6 peak. The amounts of NGF correlated with the severity of the injury, as indicated by the clinical outcome of the patients. The functional relationship of IL-6 and NGF was investigated utilizing cultured mouse astrocytes. The CSF of 8 patients containing IL-6 induced NGF production in astrocytes, whereas control CSF without IL-6 had no effect. The induction of NGF was inhibited up to 100% by adding anti-IL-6 antibodies. These results were corroborated when astrocytes were exposed to recombinant IL-6 at different concentrations resulting in NGF production. Thus, the production of IL-6 within the injured brain may likely contribute to the release of neurotrophic factors by astrocytes.

Adult↗
PubMed1996

[Intramedullary nailing in closed femoral fractures].

Intramedullary nailing of femoral fractures has gone through a revival in the past few years because of improvements in both materials and design. Axial forces are tolerated very well by the nail; however, its stiffness in both rotation and bending is related inversely to its working length. Fractures of the middle shaft can be stabilized without problems due to elastic contact forces that result in a tight grip inside the bone. Reaming and interlocking extend the indications to more complicated fractures. The development of solid nails with augmented stiffness, but smaller diameter, permits unreamed nailing with reduced damage to the medullary cavity and the avoidance of dead space. The AO developed a modular solid nail system with a variety of interlocking possibilities. With respect to soft tissue injury and biomechanics, nailing is the procedure of choice for femoral fractures.

Biomechanical Phenomena↗
PubMed1995

Intrathecal and serum interleukin-6 and the acute-phase response in patients with severe traumatic brain injuries.

Patients with severe traumatic brain injury (TBI) show a profound acute-phase response. Because interleukin-6 (IL-6) is an important mediator of these pathophysiological changes, IL-6 levels were monitored in the cerebrospinal fluid (CSF) and serum of 20 patients with severe isolated TBI. All patients received indwelling ventricular catheters for intracranial pressure monitoring and for release of CSF when intracranial pressure exceeded 15 mmHg. CSF and blood samples were drawn daily for up to 14 days. The CSF/serum albumin ratio (QA) served as a parameter of blood brain barrier dysfunction. Differential blood counts as well as the acute-phase proteins C-reactive protein, alpha 1-antitrypsin, and fibrinogen were recorded. IL-6 was detected in all CSF samples and reached values of up to 31,000 pg/mL, while serum levels remained significantly lower (alpha < or = .01) and never exceeded 1,100 pg/mL the entire study period. A correlation between CSF and serum IL-6 was found initially after the trauma and corresponded to a severe dysfunction of the blood brain barrier (r = .637, p = .001). Maximum IL-6 concentrations in serum correlated with peak levels of acute-phase proteins (C-reactive protein, alpha 1-antitrypsin, and fibrinogen). With regard to blood cell count, an initial leukocytosis combined with a borderline lymphocytopenia was observed. Thrombocytes decreased to a subnormal level during the first few days, but reached supranormal numbers by the end of the study period. Our results show that the increase of IL-6 levels in CSF and serum is followed by a profound acute-phase response in patients with TBI. Because cytokine concentrations are significantly lower in serum compared with CSF, we hypothesize that IL-6 produced in the central nervous system may play a role in initiating the acute-phase response.

Acute-Phase Proteins↗
PubMed1994

[Necrotizing soft-tissue infections of the extremities].

The term "Necrotizing soft tissue infections" describes a group of limb- and sometimes lifethreatening infections mostly of the limbs. The necrotizing soft tissue infections are classified, depending on the involved tissue level, microbiology and clinical course: 1. primarily located in the subcutaneous level and fascia: 1.1 hemolytic streptococcal gangrene, 1.2 necrotizing fasciitis, 1.3 gram-negative, synergistic, necrotizing cellulitis, 1.4 clostridial cellulitis, 1.5 anaerobic nonclostridial-cellulitis; 2. primary located in the muscle: 2.1 clostridial myonecrosis, 2.2 streptococcal myositis. Between 1989 and 1992 17 patients with necrotizing soft tissue infections were treated at the Department of Surgery, University Hospital of Zurich. Incipient necrotizing soft tissue infections are underestimated easily due to atypical or minor initial signs. The infections may be caused by a variety of bacteria, spread rapidly and can lead to a critical condition. The surgical treatment has to be aggressive with extensive debridement of the affected areas supported by intensive care. Delayed or even omitted surgical treatment, inappropriate therapeutic concepts and incomplete debridement with compromises may have fatal consequences. Repeated debridement as well as amputation of the affected limb is justified to guarantee the patient's survival.

Adult↗
PubMed1994

[Necrotizing soft tissue infection of the extremities].

The term "necrotizing soft tissue infections" describes a group of limb and life-threatening infections. Depending on the tissue level, microbiology and clinical course the necrotizing soft-tissue infections are classified in primary located infections to the subcutaneous level and fascia--like hemolytic streptococcus gangrene, necrotizing fasciitis, gram-negative synergistic necrotizing cellulitis, clostridium-cellulitis, anaerobic non-clostridium-cellulitis and in primary located infections to the muscle--like clostridium myonecrosis and streptococcal myositis. Between 1989 and 1992, 17 patients with necrotizing soft-tissue infections were treated at the Department of Surgery, University Hospital of Zurich. These infections originated from small traumatic injuries or operative wounds ("neglected wounds"). 11 patients suffered from debilitating diseases like diabetes mellitus, drug or alcohol abuse or were compromised by tumors. The average age was 42 years (21-84 years). Following bacteria were found: Staphylococcus aureus, hemolytic Streptococcus, Enterococcus, E. coli, Streptococcus milleri. 2 patients had a mixed infection with more than 3 different bacteria, 6 patients with 2, and 9 patients had a monoinfection. In 14 patients the infection was on the subcutaneous and fascia level, 3 patients showed a myositis or myonecrosis. No patient died, amputation of the limb was necessary in 4 cases. The average hospitalisation was 41 days (13-137 days) whereas 10 patients required between 4 and 53 days intensive care (average 18.3 days). Necrotizing soft-tissue infections are severe illnesses which are underestimated in the primary phase due to atypical or minor primary signs. The infections can be caused by a variety of bacteria and are spreading rapidly.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

[Blunt and penetrating diaphragmatic injuries].

Between 1987 and 1992, 17 patients sustaining injury of the diaphragm were treated at our institution. All patients had associated injuries. Blunt diaphragmatic rupture (n = 13) was mostly diagnosed by chest X-ray, additional diagnostic procedures (contrast radiography, sonography) confirmed a suspected diaphragmatic rupture. In all 4 cases with penetrating injury the diagnosis was found by explorative laparotomy. In 2 patients sustaining blunt diaphragm rupture the diagnosis was delayed by 2 and 6 days. 3 patients (all sustaining blunt diaphragm rupture) died related to their associated injuries. All patients sustaining blunt or penetrating thoracoabdominal trauma, specially in high-velocity road accidents and injuries by shots or knives, are suspicious for diaphragmatic injury.

Diagnosis, Differential↗
PubMed1993

[Infection of the shoulder joint. Etiology, diagnosis and therapy].

Acute infections of the shoulder joint have to be considered as an emergency and must be treated immediately. The significance of an infected glenohumeral joint is demonstrated by the functional results, which are poorer than other in joint infections. Irreversible cartilage damage is already observable after one week, and impairment of motion resulting in invalidity may result. Early functional physiotherapy is necessary to avoid shoulder ankylosis. The etiology, characteristic clinical findings, radiologic examinations and different forms of therapy are summarized. By early diagnosis, with immediate and adequate therapy, it is possible to avoid devastating results.

Arthritis, Infectious↗