Search PubMed⌕ Search

Biomedical subjects

Erik Waage Nielsen

Publications and source records attributed to Erik Waage Nielsen.

15 recordsLinked to original sources
PubMed2006

Candidate inhibitors of porcine complement.

Therapeutic complement inhibition is a promising strategy for treatment of a number of diseases as judged from rodent studies. The species distance from rodents to humans may limit the clinical relevance of these studies. The pig is an alternative animal for studies of human diseases like sepsis and ischemia/reperfusion injury. However, available complement inhibitors for use in pigs are scarce. The aim of the present study was to investigate and compare the efficacy of selected candidate inhibitors of porcine complement in vitro for possible future application in vivo. Sera from three different pigs were each incubated with three different activators of the complement system (zymosan, heat-aggregated immunoglobulin G (HAIGG) and Escherichia coli). Three groups of complement inhibitor candidates were tested: serine protease inhibitors (FUT-175 and C1-inhibitor), monoclonal antibodies (anti-factor B (fB) and anti-factor D (fD)) and a recombinant regulatory protein (vaccinia virus complement control protein (VCP)). Read-out was the terminal C5b-9 complement complex (TCC). The serine protease inhibitors FUT-175 and C1-inhibitor dose-dependently inhibited TCC formation in zymosan-, HAIGG- and E. coli-activated porcine sera, but with different efficacy. Complete inhibition of TCC was obtained using 0.2 mg/mL FUT-175, but required 16 mg/mL of C1-inhibitor. The monoclonal anti-fB and -fD antibodies both inhibited TCC formation dose-dependently, but in different ways. Anti-fB at high dose (1 mg/mL) completely inhibited TCC formation in sera activated with zymosan and virtually completely in sera activated with HAIGG, but not in sera activated with E. coli. Anti-fD inhibited all three activators at low dose (0.05 mg/mL), and approximately 50% TCC reduction was obtained. The recombinant complement regulatory protein VCP efficiently and dose-dependently inhibited TCC formation with a complete inhibition found at 0.05 mg/mL for all three activators. All candidates tested inhibited porcine complement activation, but in different ways and to different degrees. Of the complement-specific candidates, VCP inhibited all activators completely at low doses.

Animals↗
PubMed2006

Effect of supraphysiologic levels of C1-inhibitor on the classical, lectin and alternative pathways of complement.

C1-inhibitor is increasingly used experimentally and clinically in inflammatory conditions like septicemia and ischemia-reperfusion injury. Several mechanisms may account for the anti-inflammatory effects of C1-inhibitor, including inhibition of complement. The aim of the present study was to investigate and compare the supraphysiologic effect of C1-inhibitor on the three complement pathways. Novel assays for specific evaluation of the classical, lectin and alternative pathways were employed using normal human serum supplemented with increasing concentrations of C1-inhibitor. Solid-phase classical- and lectin pathway activation was dose-dependently and significantly reduced up to 85% in the range of 2-28 times physiologic C1-inhibitor concentration. The lectin pathway was more potently inhibited than the classical at low doses. A functional lectin pathway assay demonstrated a significant reduction of C4 deposition up to 86% even at low concentration of C1-inhibitor and documented the effect to be at the level of MBL/MASPs. In contrast, C1-inhibitor had no effect on solid-phase alternative pathway activation, but significantly reduced cobra venom factor-induced fluid-phase activation up to 88%. The negative controls albumin and IgG had no effect on complement activation. The positive inhibitory controls compstatin (C3 inhibition), EDTA- or MBL-deficient sera reduced complement activation by 82-100%. We conclude that C1-inhibitor in high physiologic doses differentially inhibits all three-complement pathways. The inhibition pattern was strikingly different in the classical and lectin pathway, compared to the alternative. Previous studies interpreting the effects of C1-inhibitor as only due to classical pathway inhibition needs reconsideration. The data has implications for the therapeutic use of C1-inhibitor.

Complement C1 Inhibitor Protein↗
PubMed2006

[A new tool for retrieving clinical data from various sources].

BACKGROUND: A doctor's tool for extracting clinical data from various sources on groups of hospital patients into one file has been in demand. For this purpose we evaluated Qlikview. MATERIAL AND METHODS: Based on clinical information required by two cardiologists, an IT specialist with thorough knowledge of the hospital's data system (www.dips.no) used 30 days to assemble one Qlikview file. Data was also assembled from a pre-hospital ambulance system. RESULTS: The 13 Mb Qlikview file held various information on 12430 patients admitted to the cardiac unit 26,287 times over the last 21 years. Included were also 530,912 clinical laboratory analyses from these patients during the past five years. Some information required by the cardiologists was inaccessible due to lack of coding or data storage. Some databases could not export their data. Others were encrypted by the software company. A major part of the required data could be extracted to Qlikview. Searches went fast in spite of the huge amount of data. Qlikview could assemble clinical information to doctors from different data systems. Doctors from different hospitals could share and further refine empty Qlikview files for their own use. When the file is assembled, doctors can, on their own, search for answers to constantly changing clinical questions, also at odd hours.

Cardiology Service, Hospital↗
PubMed2005

EEG should be performed during induced hypothermia.

Induced hypothermia has improved neurological outcome after cardiac arrest. Even though anoxic insults to the brain often provoke epileptic activity, it is unclear whether EEG monitoring is necessary in these patients. We report the case of a 53-year-old female who suffered cardiac arrest. During induced hypothermia extensive shivering was managed by sedation and curare. After their discontinuation convulsions appeared and status epilepticus was disclosed on EEG recording, and was treated by thiopental infusion for 10 days. The patient recovered slowly and has now regained independent living (CPC 1). In induced hypothermia several factors including the use of curare, may conceal clinical signs of epileptic activity. We therefore suggest a broader use of EEG in these patients.

Curare↗
PubMed2004

[Drug interactions in an intensive care unit].

BACKGROUND: A new computerised interaction database in Norwegian is available at www.druid.uio.no and in some computer physician order entry systems. The scope of this paper was to assess drug use and examine the potential usefulness of DRUID in an intensive care unit. MATERIAL AND METHODS: Drugs given patients during their first 24 hours in our mixed surgical intensive care unit over one year were entered into DRUID. RESULTS: 191 patients received 1413 drugs (median 7). According to DRUID, 110 patients (58%) had 274 potential drug interactions (median 2) of 72 classes. No interaction was of grade A (should not be combined) or C (absorption of oral drugs), 153 were of grade B (take precautions), and 121 were of grade D (academic interest). Of grade B interactions, 51% were in two and 49% in 39 classes of drug interactions. Of grade D interactions, 60% in 4 and 40% in 27 classes. INTERPRETATION: Surprisingly few serious drug interactions were found. However, in every fourth patient precautions should be taken (e.g. dose adjustments). Electronic prescribing systems might give fewer adverse effects.

Databases, Factual↗
PubMed2004

Olanzapine-induced pancreatitis: a case report.

CONTEXT: The antipsychotic agent clozapine has been linked to several cases of pancreatitis. The newer, but related, olanzapine was believed to have fewer side effects. CASE REPORT: A 42-year-old man in good physical condition gradually developed hypertriglyceridemia, hypercholesterolemia, elevated alanine aminotransferase, diabetes and, ultimately, acute pancreatitis after 19 months of olanzapine monotherapy. Due to multiorgan failure, he was in the intensive care unit and surgical ward for 29 days. He made a full recovery. The olanzapine was discontinued. Glucose, triglyceride and cholesterol levels normalized as did pancreas and liver function. CONCLUSIONS: We report olanzapine as the probable cause of acute pancreatitis in a patient without any known predisposing factors. Olanzapine-treated patients should be monitored with glucose, lipid, pancreatic function and liver function tests, and the olanzapine should be discontinued if the results of these tests worsen.

Adult↗
PubMed2004

[Unexplained circulatory collapse after a motorcycle accident].

BACKGROUND: Cardiac valve injury caused by non-penetrating chest trauma is unusual but may occur even after moderate injuries. MATERIAL AND METHODS: A 19-year-old man sustained blunt trauma to the chest and abdomen in a motorcycle crash. He was able to walk, removed his jacket and helmet and called for help via his mobile phone. He had bilateral lung contusions and multiple rib fractures. A rupture of the spleen was managed conservatively. On day 4 he needed mechanical ventilatory support and a left chest tube was inserted. Transthoracic echocardiography showed a mitral valve insufficiency grade 3 of 4, increased pulmonary artery systolic pressure of 50 mm Hg, tricuspidal insufficiency and moderate amounts of pericardial fluid. His situation deteriorated on day 12. Pulmonary catheter measurements led to decrease of noradrenaline infusion and increase in cardiac output, but his symptoms of pericardial tamponade worsened. RESULTS: Open-heart surgery was performed. Pericardial fluid under pressure was evacuated and because of a malfunctioning white elongated anterior papillary muscle, a 27 mm mechanical mitral valve was inserted. He recovered uneventfully. INTERPRETATION: A low threshold for echocardiography in these cases is advocated. Earlier use of a pulmonary catheter could have optimised treatment and time of surgery.

Accidents, Traffic↗
PubMed2004

[A 71-year-old man with Cushing reflex].

BACKGROUND: The Cushing reflex in comatose intensive care patients usually indicates that intracranial perfusion is about to be abolished. MATERIAL AND METHODS: A 71-year-old man suffered an attack during which he became comatose. After 14 hours he developed polyuria, dilated fixed pupils and Cushing reflex. The cause was believed to be a global anoxic brain oedema. Coma, apnoea and absent brain stem reflexes suggested brain death. RESULTS: Angiography with contrast injected into the aortic arch showed preserved circulation in both internal carotid, middle and anterior cerebral arteries, but absence of basilar artery circulation. A cerebral CT scan was initially normal, but 14 hours later a new scan demonstrated infarction of the brain stem, cerebellum and occipital lobes. The Norwegian criteria for organ donation were not fulfilled as these require stop of all intracranial circulation. The respirator was disconnected and the patient died. INTERPRETATION: The Cushing reflex can be seen after profound ischaemia in the posterior cerebral circulation with preserved circulation to the forebrain. Ischaemia of the brain stem alone may be sufficient to elicit the Cushing reflex.

Aged↗
PubMed2004

Hereditary and acquired angioedema: problems and progress: proceedings of the third C1 esterase inhibitor deficiency workshop and beyond.

Hereditary angioedema (HAE), a rare but life-threatening condition, manifests as acute attacks of facial, laryngeal, genital, or peripheral swelling or abdominal pain secondary to intra-abdominal edema. Resulting from mutations affecting C1 esterase inhibitor (C1-INH), inhibitor of the first complement system component, attacks are not histamine-mediated and do not respond to antihistamines or corticosteroids. Low awareness and resemblance to other disorders often delay diagnosis; despite availability of C1-INH replacement in some countries, no approved, safe acute attack therapy exists in the United States. The biennial C1 Esterase Inhibitor Deficiency Workshops resulted from a European initiative for better knowledge and treatment of HAE and related diseases. This supplement contains work presented at the third workshop and expanded content toward a definitive picture of angioedema in the absence of allergy. Most notably, it includes cumulative genetic investigations; multinational laboratory diagnosis recommendations; current pathogenesis hypotheses; suggested prophylaxis and acute attack treatment, including home treatment; future treatment options; and analysis of patient subpopulations, including pediatric patients and patients whose angioedema worsened during pregnancy or hormone administration. Causes and management of acquired angioedema and a new type of angioedema with normal C1-INH are also discussed. Collaborative patient and physician efforts, crucial in rare diseases, are emphasized. This supplement seeks to raise awareness and aid diagnosis of HAE, optimize treatment for all patients, and provide a platform for further research in this rare, partially understood disorder.

Angioedema↗
PubMed2003

[Infrared temporal thermometry].

BACKGROUND: Thermometry at other body sites than the rectum may have its advantages. Some studies have shown that infrared tympanic measurement has poor sensitivity in febrile patients. We evaluated a new infrared temporal thermometer that calculates core temperature by measuring skin temperature and ambient temperature over the superficial temporal artery. MATERIAL AND METHODS: During two periods in 2002, 164 consecutive intensive care patients were measured by both digital rectal and infrared temporal thermometry. RESULTS: The average difference between rectal and temporal measurements was 0.3 degrees C. Fever was defined as a rectal temperature of 38 degrees C and was present in 70 patients. The temporal scanner detected fever in 33 of those patients, which gives a sensitivity of 53 % (95% CI 41-65%) and a specificity of 96 % (95% CI 90-99%). The positive predictive value was 90% (95% CI 77-97%) and the negative predictive value 73% (95% CI 64-81%). INTERPRETATION: The results are better than for infrared tympanometry. The sensitivity of the infrared temporal thermometer for detecting rectally measured fever is too low to recommend its use in adult intensive care patients.

Adult↗
PubMed2002

[Acute intermittent porphyria].

BACKGROUND: Acute intermittent porphyria is an autosomal dominant disease caused by a mutation in the gene coding for the porphobilinogen deaminase enzyme in the haem biosynthesis. The prevalence varies geographically. MATERIAL AND METHODS: This article presents a literature-based review of acute intermittent porphyria with emphasis on epidemiology and diagnostic and therapeutic strategies. RESULTS: The 50% reduced activity of porphobilinogen deaminase enzyme found in heterozygote persons is sufficient for basal conditions, but during attacks, stimulation of haem synthesis upstream produces toxic spillover products that give a purple colour to the urine. Many causes: common drugs, alcohol, starvation, pregnancy or menstruation, can lead to attacks of abdominal pain, motor and/or sensory polyneuropathy autonomic dysfunction, hyponatraemia, mental changes and seizures. Hepatic carcinoma may develop in older patients with acute intermittent porphyria. Acute attacks are treated with glucose or haem arginate intravenously. Preliminary results indicate a prevalence of 600/100,000 for acute intermittent porphyria in the municipality of Saltdal in Norway compared to 1-2/100,000 in Europe generally. A W198X mutation is found in the porphobilinogen deaminase enzyme gene in members of a family in Saltdal, shared by some families in northern Sweden. INTERPRETATION: The high prevalence of acute intermittent porphyria in specific geographic areas emphasizes the importance of correct diagnosis, the first crucial step in avoiding attacks and associated diseases.

Female↗
PubMed2002

[Rescue helicopter service in Bodö--advanced emergency service or alternative transportation?].

BACKGROUND: An increase in fatal accidents in helicopter ambulance missions in Norway has put focus on the guidelines for use. METHODS: Ambulance records from the physician-staffed SeaKing rescue helicopter in Bodø, Northern Norway, from 1988 to 1998 were analysed retrospectively. RESULTS: 2,498 ambulance missions carried 2,590 patients. Median time to lift-off was 29 minutes, and one-way median flying time was 26 minutes. Four local communities with a total of 12,000 residents (6.3% of the population served by the helicopter) ordered 70% of the missions. 35% of the patients suffered from cardiovascular disease, 12% were in labour, 3.2% were seriously traumatized, while 20% had minor injuries. A total of 107 patients (4%) received advanced pre-hospital emergency treatment. Thirty-eight (1.5%) were intubated and received cardiopulmonary resuscitation, of whom two survived to discharge. Over a period of 11 years, 53 patients were intubated by the anaesthesiologist. Oxygen or intravenous lines as the only treatment effort were given to 72%. INTERPRETATION: It takes about an hour to reach remote locations by rescue helicopter. A substantial amount of the transports could have been carried out by ground ambulance without loss of health benefit. We question the need for an on-board anaesthesiologist.

Accidents↗