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Biomedical subjects

D Hansen

Publications and source records attributed to D Hansen.

At least 37 records · Page 2Linked to original sources
PubMed1999

Efegatran sulfate as an adjunct to streptokinase versus heparin as an adjunct to tissue plasminogen activator in patients with acute myocardial infarction. ESCALAT Investigators.

BACKGROUND: Previous clinical studies have shown that direct antithrombins can accelerate clot lysis after treatment with streptokinase in acute myocardial infarction (MI). Efegatran is a new direct antithrombin, which in experimental animals has been shown to enhance thrombolysis, reduce rate of reocclusion, and limit infarct size. This study was designed to compare the efficacy of efegatran plus streptokinase versus heparin plus accelerated tissue plasminogen activator (TPA) in coronary reperfusion in acute MI. METHODS AND RESULTS: In this randomized, dose-finding study (n = 245), we initially explored 4 doses of efegatran sulfate in combination with streptokinase (1.5 million U) given intravenously within 12 hours of symptom onset. The optimal dosage group of 0.5 mg/kg per hour was expanded and compared with heparin plus accelerated TPA. The primary end point was complete patency (Thrombolysis In Myocardial Infarction [TIMI] grade 3) at 90 minutes after thrombolytic therapy, assessed in a core angiographic laboratory. Infarct-related vessel patency (TIMI grade 2 or 3) and complete patency (TIMI grade 3) were 73% and 40% in the efegatran/streptokinase group versus 79% and 53% in the heparin/TPA group (P = not significant). In-hospital mortality rate was 5% for the efegatran/streptokinase group versus 0% for the heparin/TPA group (P = not significant). Major bleeding occurred in 23% of patients in the efegatran/streptokinase group versus 11% in the heparin/TPA group (P = not significant). No intracranial hemorrhage occurred. CONCLUSIONS: The combination of efegatran plus streptokinase is not superior to the current therapy of heparin and accelerated TPA in achieving early patency. In addition, there is no indication that this experimental treatment can achieve better clinical outcome.

Antithrombins↗
PubMed1999

Treatment of distal femoral fractures with intramedullary supracondylar nails in elderly patients.

30 acute fractures of the distal femur in 29 elderly patients were treated with a Russell-Taylor intramedullary supracondylar nail (IMSC). 26 of the 30 fractures (87%) united in 2-8 months. Two patients died before fracture union for reasons unrelated to the fracture. Two patients were reoperated upon, in one case the fracture was not adequately reduced at the first operation; in the other patient the nail broke 4 months after operation. In all patients knee flexion reached at least 90 degrees. No infections or thromboembolic complications were seen. The IMSC nail provided the necessary stable fixation with only a few complications in this group of elderly patients without the need to prolonged immobilisation.

Adult↗
PubMed1999

Efficacy of topical silver against fungal burn wound pathogens.

BACKGROUND: Fungal infections of burn wounds have become an important cause of burn-associated morbidity and mortality. The nature of fungal infections dictates aggressive treatment to minimize the morbidity associated with these infections. Persons with large total body surface area burns are particularly susceptible to fungal infections and are treated in such a manner as to minimize their risk of infection. METHODS: This study examined the in vitro fungicidal efficacy of a variety of different topical agents. By placing fungal inocula in contact with mafenide acetate, silver nitrate, silver sulfadiazine, and a nanocrystalline silver-coated dressing, we determined the kill kinetics of these topical agents against a spectrum of common burn wound fungal pathogens. RESULTS: The topical antimicrobials that were tested demonstrated varying degrees of efficacy against these pathogens. CONCLUSION: The nanocrystalline silver-based dressing provided the fastest and broadest-spectrum fungicidal activity and may make it a good candidate for use to minimize the potential of fungal infection, thereby reducing complications that delay wound healing.

Antifungal Agents↗
PubMed1999

Sex and the single worm: sex determination in the nematode C. elegans.

The study of sex determination in model organisms has been especially fruitful in increasing our understanding of developmental biology, gene regulation and evolutionary mechanisms. The free living nematode, Caenorhabditis elegans, can develop as one of two sexes; male or self-fertilizing hermaphrodite. Here we discuss the progress toward a genetic and molecular understanding of that decision. Numerous genetic loci have been identified that affect sexual fate, and epistasis analysis of these genes has led to a model of a regulatory hierarchy with stepwise negative interactions. It is becoming evident that many of the genes have numerous levels of regulation. We also discuss the apparent rapid rate of evolution that many of the sex determination proteins have undergone. Protein sequences of homologues from closely related species are more divergent than homologues of proteins involved in other developmental processes. Rapid evolution of sex determination genes may be a common theme throughout the animal kingdom.

Animals↗
PubMed1999

GERp95, a membrane-associated protein that belongs to a family of proteins involved in stem cell differentiation.

A panel of mAbs was elicited against intracellular membrane fractions from rat pancreas. One of the antibodies reacted with a 95-kDa protein that localizes primarily to the Golgi complex or the endoplasmic reticulum (ER), depending on cell type. The corresponding cDNA was cloned and sequenced and found to encode a protein of 97.6 kDa that we call GERp95 (Golgi ER protein 95 kDa). The protein copurifies with intracellular membranes but does not contain hydrophobic regions that could function as signal peptides or transmembrane domains. Biochemical analysis suggests that GERp95 is a cytoplasmically exposed peripheral membrane protein that exists in a protease-resistant complex. GERp95 belongs to a family of highly conserved proteins in metazoans and Schizosaccharomyces pombe. It has recently been determined that plant and Drosophila homologues of GERp95 are important for controlling the differentiation of stem cells (Bohmert et al., 1998; Cox et al., 1998; Moussian et al., 1998). In Caenorhabditis elegans, there are at least 20 members of this protein family. To this end, we have used RNA interference to show that the GERp95 orthologue in C. elegans is important for maturation of germ-line stem cells in the gonad. GERp95 and related proteins are an emerging new family of proteins that have important roles in metazoan development. The present study suggests that these proteins may exert their effects on cell differentiation from the level of intracellular membranes.

Amino Acid Sequence↗
PubMed1999

The alveolar-arterial difference in oxygen tension increases with temperature-corrected determination during moderate hypothermia.

UNLABELLED: Moderate hypothermia (32-33 degrees C) occurs in anesthetic practice. However, intrapulmonary gas exchange and the effect of temperature correction of blood gases on oxygen and carbon dioxide exchange have not been investigated in these patients. We investigated alveolar-arterial difference in oxygen tension (AaDO2) and arterial to end-tidal difference in carbon dioxide (Pa-ETCO2) during rewarming of eight ASA physical status I patients from hypothermia of 32 degrees C. Anesthesia was maintained with fentanyl/propofol. AaDO2 and Pa-ETCO2 were assessed by analyzing arterial blood gases and saturated water vapor pressure, uncorrected or corrected to actual body temperature. The respiratory quotient (RQ) was measured by calorimetry. After temperature correction of blood gases and water vapor pressure, the AaDO2 was significantly higher at 33 and 32 degrees C compared with 36 degrees C (56 +/- 13 and 64 +/- 14 vs 39 +/- 10 mm Hg; P < 0.05 and P < 0.01). The deterioration of pulmonary oxygen exchange was not detected if arterial blood gases and water vapor pressure were not corrected. The RQ did not change during moderate hypothermia compared with 36 +/-C. The temperature-corrected Pa-ETCO2 was not affected by hypothermia. We conclude that AaDO2 is increased during moderate hypothermia. This is only detected when water vapor pressure and arterial blood gases are corrected to actual body temperature. IMPLICATIONS: We investigated intrapulmonary oxygen and carbon dioxide exchange during moderate hypothermia (32 degrees C) in eight patients. If oxygen, carbon dioxide, and water vapor pressure were corrected to actual body temperature, the alveolar-arterial oxygen tension difference was increased during hypothermia. The carbon dioxide tension difference and the respiratory quotient were unaffected by hypothermia.

Adult↗
PubMed1999

The effects of three graded doses of meperidine for spinal anesthesia in African men.

UNLABELLED: The intrathecal injection of 0.7-1 mg/kg meperidine provides spinal anesthesia of only short duration. In this study, we investigated the effects of three different doses of meperidine for spinal anesthesia on the duration and level of sensory block and the incidence of side effects. Forty-five African men were randomly allocated to receive one of three doses of intrathecal meperidine: Group A = 1.2 mg/kg, Group B = 1.5 mg/kg, and Group C = 1.8 mg/kg. The duration of sensory block was significantly longer after 1.5 mg/kg compared with 1.2 mg/kg meperidine (112 +/- 19 vs 79 +/- 27 min; P = 0.001). Increasing the dose to 1.8 mg/kg did not further increase the duration of block. The level and the onset of the block were not affected by the dose. Common side effects were fatigue (27%), pruritus (20%), and nausea (7%). Seven patients had respiratory depression and seven had a decrease of systolic arterial blood pressure (SAP) >30% from baseline. There was no difference in the incidence of any side effect among groups. Respiratory depression and decreases in SAP were observed 5-50 min after meperidine injection. Twenty-two patients had no pain after the sensory block had terminated. We conclude that increasing the dose of meperidine from 1.2 to 1.5 mg/kg increased the duration, but not the level, of sensory block without an increase in side effects. IMPLICATIONS: Intrathecal meperidine 1 mg/kg provides surgical anesthesia for only 40-90 min. We investigated the effects of three larger doses of meperidine in 45 African men. The 1.5 and 1.8 mg/kg doses provide a longer duration of anesthesia compared with 1.2 mg/kg. Nausea, pruritus, and respiratory depression were common in all dose groups. We conclude that increasing the dose of meperidine from 1.2 to 1.5 mg/kg increased the duration, but not the level, of sensory block without an increase in side effects.

Analgesics, Opioid↗
PubMed1999

Effect of profound normovolemic hypotension and moderate hypothermia on circulating cytokines and adhesion molecules.

Hypotension caused by hypovolemic, hemorrhagic shock induces disturbances in the immune system that may contribute to an increased susceptibility to sepsis. The effect of chemically induced hypotension on circulating cytokines and adhesion molecules has not been investigated yet. In 21 patients scheduled for resection of malignant choroidal melanoma of the eye the perioperative serum levels of the cytokines IL-1beta, IL-6, IL-10, TNF-alpha, and the adhesion molecules sE-Selectin and sICAM-1 were investigated. Moderate hypothermia of 32 degrees C was induced in all patients. In 14 patients profound hypotension (mean arterial blood pressure 35-40 mmHg, hypotension group) was induced by enalapril and nitroglycerin for a mean duration of 71 min. In 7 patients the tumor was not resectable, and hypotension was not induced (controls). We did not detect significant differences in serum levels of cytokines or sE-Selectin perioperatively in patients with profound hypotension compared with controls. In both groups IL-6 serum levels increased significantly and reached a maximum after rewarming (17 +/- 6 and 16 +/- 5 pg/dL, respectively, P < 0.001). IL-1beta, IL-10, and TNF-alpha did not change perioperatively in both groups. On the first postoperative day sICAM-1 serum levels were significantly increased in both groups (mean increase of 96 and 54 ng/mL, respectively, P < 0.01 and P < 0.05). We conclude from this study that profound normovolemic arterial hypotension does not seem to have effects on serum levels of circulating IL-1beta, IL-6, IL-10, TNF-alpha, and sE-Selectin. Perioperative moderate hypothermia may be the reason for the postoperative increase in sICAM-1 levels independent of the blood pressure.

Cytokines↗
PubMed1999

The rat Subcutaneous Air Sac model: a quantitative assay of antiangiogenesis in induced vessels.

A new in vivo experimental model--the Subcutaneous Air Sac (SAS) model-has recently been presented to replace a previous in vivo rabbit cornea assay where neovascularisation was induced by chemical injury of the cornea or by implantation of tumour cells intracorneally, a methodology which is believed to cause severe pain to the animals. In the SAS model, an air sac is induced by injection of air subcutaneously on the back of the animal. After 10-14 days the air sac appears as an almost transparent avascular membrane in which induction of new vessels can be studied. We present recent developments of this technique: In the SAS-tumour technique, vascular endothelial growth factor-producing tumour cells are inoculated subcutaneously directly on the membrane, and the formation of new vessels is measured 8 days later. In the SAS-pellet technique, slow-release pellets containing angiogenic factors, basic fibroblast growth factor or vascular endothelial growth factor are implanted on the subcutaneous membrane by a simple operation. The formation of new vessels is measured 10 days later. The ability of the SAS-tumour- and SAS-pellet techniques to detect an antiangiogenic effect of a systemically administered compound was investigated using the fumagillin analogue TNP-470 (o-chloroacetyl-carbamoyl)-fumagillol) as a positive control given subcutaneously for 7 and 9 days, respectively. At a dose of 10 mg TNP-470/kg/day the angiogenesis was reduced by approximately 70% in the SAS-tumour technique and by 40-60% in the SAS-pellet technique. The animals were unaffected by the SAS methodology. The SAS-tumour and SAS-pellet models are considered complementary and make use of simple and almost similar techniques which facilitate the evaluation.

Air Sacs↗
PubMed1999

Thyroid function, morphology and autoimmunity in young patients with insulin-dependent diabetes mellitus.

OBJECTIVE: An association between insulin-dependent diabetes mellitus (IDDM) and autoimmune thyroid disease is well recognized. We have studied the prevalence of thyroid dysfunction, autoimmunity and morphological abnormalities by ultrasonography in young diabetics. SUBJECTS AND METHODS: Among young IDDM patients less than 18 years old and living in the county of Funen, Denmark, 105 of 116 eligible patients participated. They were compared with 105 healthy children matched for sex and age. Routine thyroid function parameters (thyroxine (T4), tri-iodothyronine (T3), T3 resin uptake and TSH) and thyroid autoantibodies (anti-thyroid peroxidase, TPOab, and thyroglobulin antibodies, Tgab) were measured. Thyroid size and morphology were determined by ultrasonography. RESULTS: Two of the diabetics had previously diagnosed hypothyroidism and three new cases of subclinical hypothyroidism were found. There were no significant differences in thyroid function variables or thyroid volume between diabetics and controls. Thyroid volume correlated significantly with age and weight in both groups. Among diabetics, 17 had thyroid autoantibodies (13 with TPOab, 14 with Tgab and 10 with both) compared with 2 children in the control group (P<0.001). Forty-four with IDDM as opposed to 11 of the controls (P<0.001) had morphological abnormalities at ultrasonography. Most of them had various degrees of hypoechogenicity thought to be a marker of thyroid autoimmunity. Among the 17 diabetics with autoantibodies, 10 had morphological abnormalities at ultrasonography. CONCLUSIONS: A high proportion of young IDDM patients without any clinical signs of thyroid disease have markers of thyroid autoimmunity. Many have thyroid autoantibodies, but even more have abnormalities by thyroid ultrasonography.

Adolescent↗
PubMed1998

Molecular evolution of a sex determination protein. FEM-2 (pp2c) in Caenorhabditis.

Somatic sex determination in Caenorhabditis elegans involves a signal transduction pathway linking a membrane receptor to a transcription factor. The fem-2 gene is central to this pathway, producing a protein phosphatase (FEM-2) of the type 2C (PP2C). FEM-2 contains a long amino terminus that is absent in canonical PP2C enzymes. The function of this domain is difficult to predict, since it shows no sequence similarity to any other known proteins or motifs. Here we report the cloning of the fem-2 homologue from Caenorhabditis briggsae (Cb-fem-2). The sequence identity is much higher than that observed for other C. briggsae homologues of C. elegans sex determination proteins. However, this level is not uniform across the entire lengths of the proteins; it is much lower in the amino termini. Thus, the two domains of the same protein are evolving at different rates, suggesting that they have different functional constraints. Consistent with this, Cb-FEM-2 is able to replace some, but not all, of the Ce-FEM-2 in vivo function. We show that removal of the amino terminus from Ce-FEM-2 has no effect on its in vitro phosphatase activity, or its ability to replace the in vivo function of a yeast PP2C enzyme, but that it is necessary for proper FEM-2 function in worms. This demonstrates that the amino terminus is not an extended catalytic domain or a direct negative regulator of phosphatase activity.

Amino Acid Sequence↗
PubMed1998

Capital budgeting techniques.

The cost of new medical imaging equipment for a radiology practice is a major capital purchase. Due to rapid advances in technology and imaging techniques, the management decision to purchase new capital equipment can present itself every few years. The present report explains various financial management techniques that are generally used by corporations worldwide to determine their cost of capital. The cost of capital is the return on a capital investment project required by the providers of the capital. The published financial accounts of Sonic Healthcare Limited, Australia's largest pathology company, are reproduced as a numerical example of how the financial accounts of a business may be used to determine its cost of capital. The cost of capital forms an integral part of management's financial decision-making process.

Accounting↗
PubMed1998

Are causes of death predictable?

A random sample of death records of adult males from 1967 to 1970 was chosen from the South Australian Registry of Births, Deaths, and Marriages. The natural parents of these individuals were identified by cross-reference to birth certificates, and an extensive search was made of the death records for these parents. In this manner random families were selected for which, where possible, the cause of death and length of life of each family member were determined. From the information pertaining to the stated cause of death, each individual was assigned to one of five death categories.

Adult↗
PubMed1998

Suxamethonium-induced cardiac arrest and death following 5 days of immobilization.

The present report describes a case of cardiac arrest and subsequent death as a result of hyperkalaemia following the use of suxamethonium in a 23-year-old Malawian woman. Five days after the onset of the symptoms of meningitis, the patient aspirated stomach contents and needed endotracheal intubation. Forty seconds after injection of suxamethonium, bradycardia and cardiac arrest occurred. Attempts to resuscitate the patient were not successful. The serum level of potassium was observed to be 8.4 mequiv L-1. Apart from the reduction in the patient's level of consciousness, there were no signs of motor neurone damage or of any of the other known predisposing conditions for hyperkalaemia following the administration of suxamethonium. It is postulated that her death was caused by hypersensitivity to suxamethonium, associated with her 5-day immobilization.

Adult↗
PubMed1997

Making HMOs credible.

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Health Maintenance Organizations↗
PubMed1997

[Intrauterine growth retardation and premature delivery. The effect of smoking and psychosocial factors].

The purpose of the study is to investigate the influence of psychosocial stress, maternal schooling, social support, psychological well-being, alcohol and smoking on intrauterine growth retardation and premature delivery. At a Copenhagen university hospital 2432 consecutive Danish-speaking women in 20th week of pregnancy completed a questionnaire including the General Health Questionnaire and Severity of Psychosocial Stressor Scale and questions about social network, education, smoking and drinking habits. In 212 cases (8.7%) the women delivered before day 259 of gestation. In a multiple logistic regression model, pre-term delivery proved to be associated with psychosocial stress and poor school education. In 152 cases (6.3%) infants had a birth weight below the defined 10th percentile. In a multiple logistic regression model, IUGR was associated with smoking. In preventive programmes, such as anti-smoking campaigns, it should be kept in mind that women who smoke are also the least educated and have the poorest support from a social network.

Adult↗
PubMed1997

Deep halothane anaesthesia compared with halothane-suxamethonium anaesthesia for tracheal intubation in young children.

A double-blind and randomized study design was used to investigate 100 healthy children, aged 1-5 years. Intubating conditions and cardiovascular changes during deep halothane anaesthesia, defined as an end-tidal concentration of 2%, were compared with those changes during 1% halothane and suxamethonium relaxation. Intubating conditions were graded according to the ease of laryngoscopy, vocal cord position, coughing and jaw relaxation. In each group 96% of the children demonstrated acceptable intubating conditions. Jaw relaxation was worse in the 1% halothane/-suxamethonium group (P < 0.01). When anaesthesia with 2% or 1% halothane was compared there was a more pronounced decrease in systolic blood pressure (18 vs. 8%, P < 0.001). Junctional rhythm occurred more frequently during deep halothane anaesthesia (46 vs. 18%, P < 0.01). Intravenously (i.v.) administered atropine attenuated blood pressure depression significantly and reinstituted sinus rhythm in most cases.

Anesthesia, Inhalation↗