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Biomedical subjects

E S Hansen

Publications and source records attributed to E S Hansen.

At least 109 records · Page 6Linked to original sources

15-Hydroxy-eicosatetraenoic acid (15-HETE) inhibits carrageenan-induced experimental arthritis and reduces synovial fluid leukotriene B4 (LTB4).

15-Hydroxy-eicosatetraenoic acid (15-HETE), a product of arachidonic acid, has no proinflammatory capacity, but can inhibit the formation and the chemotactic response of neutrophils to leukotriene B4 (LTB4), a potent mediator of inflammation. The purpose of the present study was to determine whether intraarticular administration of 15-HETE in carrageenan-induced acute arthritis might decrease the levels of LTB4 in synovial fluid and modify the arthritis. A bilateral acute knee joint arthritis was established in 7 dogs by intraarticular injections of carrageenan every third day. To the right joints, 15-HETE was administered both concomitantly with the carrageenan injections and continuously via an osmotic pump. In samples of synovial fluid obtained on day 0, 3 and 10 PGE2 and LTB4 were determined using reversed phase high performance liquid chromatography combined with radioimmunoassays and neutrophil chemokinesis. In the presence of 15-HETE the clinical severity of arthritis was significantly reduced and the volume of synovial effusate was decreased on an average by 42%. Furthermore, the relative number of neutrophils in histological sections of synovial tissue was decreased by 58%. Intraarticular caragheenan injections induced LTB4 formation, and maximum levels were obtained on day 3 (279.2 +/- 148.2 pg/joint). PGE2 was also present on day 3, but maximum levels were detected on day 10 (9.5 +/- 4.8 ng/joint). In joints injected with both carragheenan and 15-HETE the levels of LTB4 on days 3 and 10 were inhibited by 90% and 83%, respectively. For PGE2 a small but insignificant decrease was found on both day 3 and on day 10. These results show that LTB4 may be an important mediator of acute arthritis induced by carragheenan in dogs, and that intraarticular administration of 15-HETE can modify this arthritis by inhibiting LTB4 formation.

Animals↗

Effect of hemorrhage and resuscitation on subcutaneous, conjunctival, and transcutaneous oxygen tension in relation to hemodynamic variables.

Subcutaneous (PscO2), conjunctival (PcjO2), and transcutaneous (PtcO2) oxygen tension values were measured in anesthetized dogs subjected sequentially to hemorrhage and reinfusion of the shed blood. Intravascular pressure, hemodynamic variables, and oxygen transport variables were measured simultaneously. During hemorrhage, PscO2 was the first of the PO2 measurements, and among the first set of hemodynamic variables that differed significantly from control values. During continuous bleeding, PscO2 and PcjO2 fell rapidly, the decline of PscO2 and PcjO2 was similar and significantly higher than that found for PtcO2. After reinfusion of shed blood, PscO2 was the last of PO2 measurements, and among the last set of hemodynamic variables, to return to control values. While PaO2 remained constant, PvO2 decreased significantly during hemorrhage and normalized during resuscitation. Unheated instruments for measuring PscO2 and PcjO2 are reliable indicators of peripheral perfusion during hemorrhage and resuscitation. Subcutaneous oxygen monitoring, in particular, seems capable of assessing early blood loss and adequacy of resuscitation after acute hemorrhage, and may be clinically useful.

Animals↗

Cancer mortality in the asphalt industry: a ten year follow up of an occupational cohort.

A historical cohort study was conducted to study the possible risk of cancer associated with exposure to asphalt. Altogether 1320 unskilled workers employed in the asphalt industry were followed up over a ten year period and compared with 43,024 unskilled men in terms of cause specific mortality. Both groups were identified from census records and followed up by an automatic record link that had been established previously between the census register, National Register, and Death Certificate Register. The cancer mortality was significantly increased in asphalt workers aged 45 or more, when five years' latency from enrolment into the study was allowed for (SMR for cancer: 159, 95% confidence interval: 106-228). Non-significant increases were seen for respiratory, bladder, and digestive cancers but a significant increase was seen for brain cancer (SMR = 500, 95% CI: 103-1461). Components of asphalt fumes may have been important to the observed association between risk of cancer and employment in the asphalt industry.

Adolescent↗

Hemodynamic effects of knee-joint tamponade. 99mTc-diphosphonate scintimetry in growing dogs.

We studied the influence of joint effusion on juxtaarticular vascularity and bone metabolism of the immature knee in puppies by dynamic and static 99mTc-diphosphonate scintimetry. Unilateral joint tamponade of 10 KPa (75 mmHg), introduced by intraarticular dextran-70 infusion, resulted in quantitatively similar scintimetric changes in an angiographic Phase I (0-20 sec), a blood pool Phase II (20-256 sec), and a bone-uptake Phase III (2 h). The uptake was reduced by 20 percent in the distal femoral epiphysis, by 15 percent in the distal femoral growth plate in Phases II-III, and by 8 percent in the proximal tibial growth plate in Phase III. The main part of scintimetric changes during joint tamponade could be ascribed to altered epiphyseal and metaphyseal intraosseous hemodynamics.

Animals↗

99mTc-DPD uptake in juvenile hemarthrosis. Scintimetry and autoradiography of the knee in dogs.

The pathogenesis of subchondral bone lesions and growth plate affection in hemophilic arthropathy was studied in puppies by means of repeated regional 99mTc-diphosphonate scintimetry and contact autoradiography. Unilateral hemarthrosis of the knee was induced by biweekly intraarticular injections of autologous blood for 12 weeks. Hemarthrosis caused an early (2 to 4 weeks) decrease in uptake of 99mTc-diphosphonate in the juxtaarticular growth plates (ratio 0.7) and a delayed (8 to 10 weeks) increase in epiphyseal uptake (ratio 1.5). In a recovery phase after hemarthrosis, growth plate uptake returned to normal, while the epiphyseal uptake remained elevated for 8 to 10 weeks. By contact autoradiography, the growth plate uptake was localized to the calcification layer at the metaphyseal aspect of the growth plates, while the epiphyseal uptake mainly was seen in the thin subchondral and subsynovial bone layer and around osteophytes. The changes in uptake of 99mTc-diphosphonate following hemarthrosis for 3 months were reversible and could be ascribed to the presence of synovial inflammation.

Animals↗

Cancer incidence in an occupational cohort exposed to bitumen fumes.

This study was conducted to investigate whether bitumen fumes should be considered carcinogenic to human beings. A historical cohort of heavily exposed mastic asphalt workers was followed from 1959 through 1984 (inclusive) with regard to cancer incidence. A total of 679 Danish men were included in the study cohort. Among these, 75 new cases of cancer were observed within the period studied. The cancer incidence observed among the group significantly exceeded that of the total Danish male population, the standardized morbidity ratio (SMR) being 195 (95% confidence interval (95% CI) 153-244). Significant increases were seen for cancer of the mouth (SMR 1111, 95% CI 135-4014), the esophagus (SMR 698, 95% CI 144-2039), the rectum (SMR 318, 95% CI 128-656), and the lung (SMR 344, 95% CI 227-501). It is suggested that exposure to cracking products in the fumes of heated bitumen has contributed to the elevated cancer incidence observed.

Adolescent↗

Mortality of auto mechanics. A ten-year follow-up.

This study was set up to investigate whether work in car repair workshops is associated with an increased risk of ischemic heart disease and specific malignant neoplasms. For this purpose, a cohort of auto mechanics has been followed through 10 years with regard to cause-specific mortality. Comparisons were made with another cohort of skilled male workers who were not exposed to asbestos or petrochemical substances. The auto mechanics' mortality was increased for ischemic heart disease [standardized mortality ratio (SMR) 121, 95% confidence interval (95% CI) 102-145], other cardiovascular diseases (SMR 112, 95% CI 82-150), cancer (SMR 115, 95% CI 97-136), other diseases (SMR 119, 95% CI 94-149), and external causes (SMR 131, 95% CI 113-153). For specific cancer sites, increases were seen for pancreatic cancer, urinary cancer outside the bladder, and pleural mesothelioma.

Adolescent↗

Effect of prostaglandin E2 and indomethacin on blood flow in the lower urinary tract of the rabbit.

The effect of the cyclooxygenase system on lower urinary tract blood flow was investigated in a standardized rabbit model with empty bladder. Twenty-eight New-Zealand white rabbits were separated into 3 groups. The first group received 1 mg per kg b.w. s.c. daily of PGE2 for 4 days. The second group received 10 mg per kg of indomethacin perorally daily for 7 days. The third group served as controls. The experiments were undertaken in general anaesthesia. Regional blood flow of the lower urinary tract was measured with 141Ce-labeled microspheres and plasma volume was assessed by the equilibrium distribution of 125I-labeled fibrinogen in tissues. Peroral treatment with indomethacin caused a significant increase in blood flow in the trigone. No difference in whole bladder blood flow was found and no differences were found among groups with respect to plasma volume.

Animals↗

Hemoglobin and hematocrit as risk factors in below-the-knee amputation for incipient gangrene.

The relationship between complication rate and preoperative levels of hemoglobin and hematocrit was investigated in 186 consecutive below-the-knee amputations for incipient gangrene. Arteriosclerotic amputations had successively higher rates of wound complications and reamputation with increasing hemoglobin and hematocrit. No such association was found among diabetics. Thus, hemoglobin greater than or equal to 7.0 mmol/l and hematocrit greater than or equal to 40 were significant preoperative risk factors in below-the-knee amputation for arteriosclerotic incipient gangrene.

Aged↗

Continuous monitoring of tissue oxygen tension during hyperoxia and hypoxia: relation of subcutaneous, transcutaneous, and conjunctival oxygen tension to hemodynamic variables.

Subcutaneous, transcutaneous, and conjunctival oxygen tensions (PscO2, PtcO2, and PcjO2, respectively) were measured in anesthetized dogs subjected sequentially to normoxia, hyperoxia, and hypoxia. Intravascular pressure, hemodynamic and oxygen transport variables were measured simultaneously. PtcO2 and PcjO2 closely paralleled PaO2 during normoxia, hyperoxia, and hypoxia over a wide range of arterial oxygen tensions. PtcO2 was reliable over the widest range of PaO2, with a correlation coefficient of .94. The PcjO2/PaO2 index fell at very low PaO2. The PscO2/PaO2 index decreased at both very low and very high PaO2. Only minor changes were found in hemodynamic and oxygen transport variables during hyperoxia. During hypoxia, however, cardiac output and other central hemodynamic measurements increased, while PscO2, PtcO2, and PcjO2 fell. Oxygen delivery and oxygen consumption were maintained or only slightly changed during hypoxia. All three continuous measurements of oxygen tension are reliable indices of PaO2 over a wide range under normovolemic conditions. The instruments for measuring PscO2 and PcjO2 are unheated and therefore may have advantages for human application.

Animals↗

Lipoxygenase products in experimental septic arthritis in dogs.

Induction of an experimental septic arthritis was performed in the juvenile dog knee by an intra-articular injection with Staphylococcus aureus. From plasma, lipoxygenase (LO) products of arachidonic acid were separated by reversed-phase high-performance liquid chromatography (RP-HPLC) after extraction of lipids. The plasma samples did not contain UV-detectable amounts of LO products other than the LTB4 metabolite 20-COOH-LTB4, and 12-HETE. Small amounts of chemokinetically active material were found coeluting with the eluate fraction of 20-COOH-LTB4, LTB4 and 12-HETE after RP-HPLC. After 48 hours of septic arthritis, resulting in a massive acute joint inflammation, no significant changes in LO products were observed.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Changes in lipoxygenase products from synovial fluid in carrageenan induced arthritis in dogs.

A non-suppurative chronic arthritis was induced in the juvenile dog knee by intra-articular instillations with Carrageenan. Lipoxygenase products of arachidonic acid were separated from synovial fluid by reversed-phase high-performance liquid chromatography (RP-HPLC). After ten weeks we observed an accumulation of leukotriene B4 (LTB4) in synovial fluid in five out of six experimental knees (0.94 to 5.5 ng/ml), as judged by integrated optical density. Biological activity of LTB4 was confirmed by chemokinesis. LTB4 was not detected in control knees. The 15-lipoxygenase products, 15-hydroxyeicosatetraenoic acid (15-HETE) and 13-hydroxy-9,11-octadecadienoic acid (13-HODD), being inhibitors of 5-lipoxygenase, were found in relatively high levels in the control knees compared to the arthritic knees. The results denote LTB4 as a pro-inflammatory local mediator during carrageenan-induced arthritis; possibly, the decreased levels of 15-HETE and 13-HODD in the arthritic knees may have a regulatory function, thus facilitating LTB4 generation.

Animals↗

Urinary iodine excretion is low and serum thyroglobulin high in pregnant women in parts of Denmark.

In the Randers area of Denmark urinary iodine excretion (which reflects iodine intake) was found to be much lower than recommended intake levels, both in women in late pregnancy [52(23-118) micrograms iodine/g creatinine, median, range, n = 20] and in non-pregnant controls [42(23-71), n = 20]. Serum thyroglobulin which is high in iodine deficiency was 32.5 micrograms/l (median) (range 10.5-78.0) in the control women and considerably higher in the pregnant women [67.0 micrograms/l (9.0-385)]. This increase was probably due to the extra iodine requirement of pregnancy which was not satisfied with an adequate increase in iodine intake. The results may suggest that pregnant women in this area should receive iodine supplementation and that a general program of iodine supplementation should be considered.

Adult↗

Cerebral blood flow and metabolism during isoflurane-induced hypotension in patients subjected to surgery for cerebral aneurysms.

Cerebral blood flow and cerebral metabolic rate for oxygen were measured during isoflurane-induced hypotension in 10 patients subjected to craniotomy for clipping of a cerebral aneurysm. Flow and metabolism were measured 5-13 days after the subarachnoid haemorrhage by a modification of the classical Kety-Schmidt technique using xenon-133 i.v. Anaesthesia was maintained with an inspired isoflurane concentration of 0.75% (plus 67% nitrous oxide in oxygen), during which CBF and CMRO2 were 34.3 +/- 2.1 ml/100 g min-1 and 2.32 +/- 0.16 ml/100 g min-1 at PaCO2 4.1 +/- 0.1 kPa (mean +/- SEM). Controlled hypotension to an average MAP of 50-55 mm Hg was induced by increasing the dose of isoflurane, and maintained at an inspired concentration of 2.2 +/- 0.2%. This resulted in a significant decrease in CMRO2 (to 1.73 +/- 0.16 ml/100 g min-1), while CBF was unchanged. After the clipping of the aneurysm the isoflurane concentration was reduced to 0.75%. There was a significant increase in CBF, although CMRO2 was unchanged, compared with pre-hypotensive values. These changes might offer protection to brain tissue during periods of induced hypotension.

Adult↗

The effect of isoflurane on cerebral blood flow and metabolism in humans during craniotomy for small supratentorial cerebral tumors.

Fourteen patients were studied during craniotomy for small supratentorial cerebral tumors. Cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) were measured twice by a modification of the Kety-Schmidt technique using 133Xe intravenously. Anesthesia was induced with thiopental 5-7 mg X kg-1, fentanyl 0.2 mg, and pancuronium, and maintained with 0.75% inspired isoflurane concentration in 67% nitrous oxide, and moderate hypocapnia. In one group of patients (n = 7), the inspired isoflurane concentration was maintained at 0.75% throughout anesthesia. One hour after induction of anesthesia, CBF and CMRO2 averaged 31 +/- 3 ml X 100 g-1 X min-1 and 2.1 +/- 0.2 ml O2 X 100 g-1 X min-1 (X +/- SEM), respectively. During repeat studies 1 h later, CBF and CMRO2 were unchanged. In a second group of patients (n = 7), an increase in the inspired isoflurane concentration from 0.75% to 1.5% was associated with a significant decrease in CMRO2 from 2.4 +/- 0.1 to 1.9 +/- 0.1 ml O2 X 100 g-1 X min-1, and no change in CBF. It is concluded that this anesthetic regimen is safe to use in patients with small supratentorial tumors in whom only a small midline shift has occurred.

Adult↗