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Additional file 1. Structured interview. Structured interview conducted in September 2019 in all studied herds, on the antibiotic usage during the last 12 months.

Additional file 2. Statistics. Herd level statistical analyzes using one-tailed Fisher’s exact test, comparing resistance (Yes/No) to any of the antibiotics included in the panels, resistance to single selected antibiotic substances (tetracycline and penicillin/ampicillin) and the presence of multi-drug resistance, to the herd size and treatment regimens.

The 12-lipoxygenase (12LO) pathway is a promising target to reduce islet dysfunction, adipose tissue (AT) inflammation and insulin resistance. Optimal pre-clinical models for the investigation of selective12LO inhibitors in this context have not yet been identified. The objective of this study was to characterize the time course of 12LO isoform expression and metabolite production in pancreatic islets and AT of C57BLKS/J-db/db obese diabetic mouse in a pre-diabetic state in order to establish a suitable therapeutic window for intervention with selective lipoxygenase inhibitors. Mice have 2 major 12LO isoforms -the leukocyte type (12/15LO) and the platelet type (p12LO) and both are expressed in islets and AT. We found a sharp increase in protein expression of 12/15LO in the pancreatic islets of 10-week old db-/- mice compared to 8- week old counterparts. Immunohistochemistry showed that the increase in islet 12/15LO parallels a decline in islet number. Analysis of 12- and 15-hydroperoxytetraeicosanoid acids (HETE)s showed a 2-3 fold increase especially in 12(S)-HETE that mirrored the increase in 12/15LO expression in islets. Analysis of AT and stromal vascular fraction (SVF) showed a significant increase of platelet 12LO gene expression along with 12- and 15- HETEs. The data demonstrate that the db/db mouse is a suitable model for investigation of 12/15LO inhibitors in the development of inflammatory mediated type 2 diabetes, with a narrow window of therapeutic intervention prior to 8 weeks of age.

Aims The purposes were to evaluate the detection of low levels of Campylobacter in water by dead‐end ultrafiltration (DEUF) to determine the sensitivity and suitability for use under field condition. Methods and Results The DEUF technique followed by detection according to ISO 10272 was tested on artificially and naturally contaminated water. Campylobacter were detected in all samples spiked with more than 10 CFU 60 l−1 and in four of nine samples with a concentration below 10 CFU 60 l−1 water. Naturally contaminated water from five different broiler producers was analysed. Campylobacter were detected in four of 12 samples from ponds near the houses and in three of 24 samples from water pipes inside the broiler houses, but not in tap water sampled at the entrance of the broiler houses. Conclusions The results indicate that DEUF is useful for detection of low numbers of Campylobacter in large volumes of water. Significance and Impact of the Study Contaminated water is an important source for transmission of Campylobacter to broilers and humans. The concentration of Campylobacter is usually low with a high level of background microbiota. This study shows the advantages of DEUF both in the laboratory and under field conditions.

The individual weight loss response to obesity treatment is diverse. Here we test the hypothesis that the weight loss response to the CB1 receptor antagonist rimonabant is influenced by endogenous levels of receptor agonists. We show that baseline anandamide levels and body weight independently contribute to predict the treatment response to rimonabant in rodents, demonstrating that addition of biomarkers related to mode of action is relevant for a personalized health care approach to obesity treatment.

Introduction of new myeloma therapies offers new options for patients refractory to immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs). In this multicenter study, patients with relapsed multiple myeloma, who have received at least three prior lines of therapy, are refractory to both an IMiD (lenalidomide or pomalidomide) and a PI (bortezomib or carfilzomib), and have been exposed to an alkylating agent were identified. The time patients met the above criteria was defined as time zero (T 0). Five hundred and forty-three patients diagnosed between 2006 and 2014 were enrolled in this study. Median age at T 0 was 62 years (range 31-87); 61% were males. The median duration between diagnosis and T 0 was 3.1 years. The median number of lines of therapy before T 0 was 4 (range 3-13). The median overall survival (OS) from T 0 for the entire cohort was 13 (95% confidence interval (CI) 11, 15) months. At least one regimen recorded after T 0 in 462 (85%) patients, with a median (95% CI) progression-free survival and OS from T 0 of 5 (4, 6), and 15.2 (13, 17) months, respectively. The study provides the expected outcome of relapsed multiple myeloma that is refractory to a PI and an IMiD, a benchmark for comparison of new therapies being evaluated. © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.

Lipid extraction from biological samples is a critical and often tedious preanalytical step in lipid research. Primarily on the basis of automation criteria, we have developed the BUME method, a novel chloroform-free total lipid extraction method for blood plasma compatible with standard 96-well robots. In only 60 min, 96 samples can be automatically extracted with lipid profiles of commonly analyzed lipid classes almost identically and with absolute recoveries similar or better to what is obtained using the chloroform-based reference method. Lipid recoveries were linear from 10–100 µl plasma for all investigated lipids using the developed extraction protocol. The BUME protocol includes an initial one-phase extraction of plasma into 300 µl butanol:methanol (BUME) mixture (3:1) followed by two-phase extraction into 300 µl heptane:ethyl acetate (3:1) using 300 µl 1% acetic acid as buffer. The lipids investigated included the most abundant plasma lipid classes (e.g., cholesterol ester, free cholesterol, triacylglycerol, phosphatidylcholine, and sphingomyelin) as well as less abundant but biologically important lipid classes, including ceramide, diacylglycerol, and lyso-phospholipids. This novel method has been successfully implemented in our laboratory and is now used daily. We conclude that the fully automated, high-throughput BUME method can replace chloroform-based methods, saving both human and environmental resources.

This study investigated the effects of rosuvastatin on plaque progression and in vivo coronary artery function in apolipoprotein E-knockout (ApoE-KO) mice, using noninvasive high-resolution ultrasound techniques. Eight-week-old male ApoE-KO mice ( n = 20) were fed a high-fat diet with or without rosuvastatin (10 μmol·kg−1·day−1) for 16 wk. When compared with control, rosuvastatin reduced total cholesterol levels ( P < 0.05) and caused significant retardation of lesion progression in the brachiocephalic artery, as visualized in vivo using an ultrasound biomicroscope ( P < 0.05). Histological analysis confirmed the reduction of brachiocephalic atherosclerosis and also revealed an increase in collagen content in the statin-treated group ( P < 0.05). Coronary volumetric flow was measured by simultaneous recording of Doppler velocity signals and left coronary artery morphology before and during adenosine infusion. The hyperemic flow in response to adenosine was significantly greater in left coronary artery following 16 wk of rosuvastatin treatment ( P < 0.001), whereas the baseline flow was similar in both groups. In conclusion, rosuvastatin reduced brachiocephalic artery atherosclerotic plaques in ApoE-KO mice. Coronary artery function assessed using recently developed in vivo ultrasound-based protocols, also improved.

Ischemic heart disease is a major cause of death and morbidity and the search for novel therapeutic targets is still required. We have previously shown that the enzyme arachidonate 15 lipoxygenase (ALOX15), which catalyzes the conversion of arachidonic acid to 15-hydroxy eicosatetraenoic acid (15-HETE), is highly expressed in ischemic heart tissue, but its role in the pathogenesis of ischemic heart disease is unclear. Here we showed that expression of ALOX15, but not ALOX12 or ALOX15B, was increased in ischemic versus non-ischemic human heart biopsy samples. A similar ALOX expression pattern was found in hypoxic human cardiomyocytes and cardiac endothelial cells. We also showed that levels of 15-HETE were significantly higher in ischemic versus non-ischemic human heart biopsy samples and showed a tendency to increase in serum from the patients with ischemic heart disease. Moreover, hypoxia increased the production of 15-HETE levels from human cardiomyocytes and cardiac endothelial cells. The hypoxia-induced increase in 15-HETE levels from human cardiomyocytes was inhibited by the ALOX15 inhibitor baicalein. Finally, by using intrinsic rotational thromboelastometry, we showed that human whole blood clotted faster in the presence of 15-HETE. In summary, we propose that increased ALOX15 expression in heart tissue under ischemic conditions may lead to increased production of 15-HETE, potentially contributing to thrombosis.

This experiment was designed to describe the accuracy of the EU-reference dissection method, and to describe the types of factors influencing the accuracy and assess their size. The experiment was conducted in four different European countries at two abattoirs within each country. A total of 128 carcasses was selected according to carcass weight, fat class and sex, and 8 butchers from different countries dissected the carcasses. Due to the experimental design of the experiment a variation in pig type was found between countries. The accuracy was expressed by the repeatability and reproducibility standard deviation, which were found to be 0.87 and 1.10, respectively, and by the reliability, found to be 0.87. This indicates a high accuracy, although a significant effect was found on the estimation of lean meat percentage (LMP) of butcher, and also that jointing of the carcass was of overall importance to the accuracy of the EU-reference dissection method.

Objective— Macrophage-mediated oxidation of low-density lipoprotein (LDL) by enzymes, such as the lipoxygenases, is considered of major importance for the formation of oxidized LDL during atherogenesis. Macrophages have been identified in hypoxic areas in atherosclerotic plaques. Methods and Results— To investigate the role of hypoxia in macrophage-mediated LDL oxidation, we incubated human monocyte-derived macrophages with LDL under normoxic (21% O 2 ) or hypoxic (0% O 2 ) conditions. The results showed that hypoxic macrophages oxidized LDL to a significantly higher extent than normoxic cells. Interestingly, the mRNA and protein expression of 15-lipoxygenase-2 (15-LOX-2) as well as the activity of this enzyme are elevated in macrophages incubated at hypoxia. Both the unspliced 15-LOX-2 and the spliced variant 15-LOX-2sv-a are found in macrophages. In addition, 15-LOX-2 was identified in carotid plaques in some macrophage-rich areas but was only expressed at low levels in nondiseased arteries. Conclusions— In summary, these observations show for the first time that 15-LOX-2 is expressed in hypoxic macrophages and in atherosclerotic plaques and suggest that 15-LOX-2 may be one of the factors involved in macrophage-mediated LDL oxidation at hypoxia.

The effects of a dietary astaxanthin from the microalgae Haematococcus pluvalis on broiler performance during an experimental infection with Campylobacter jejuni were studied. The experiment included 960 female broiler chickens, divided into 48 floor pens with free access to food and water. Half the number of birds were inoculated at 10 days of age with C. jejuni . The experimental diets were supplied with either 0, 7, 36, or 179 mg astaxanthin/kg feed (0, 350, 1 800 and 8 950 mg algae meal/kg feed, respectively), giving an intake of approximately 0, 1, 5 or 25 mg astaxanthin per bird and per day at 5 weeks of age. In addition, two different application methods of the astaxanthin were studied. The first method mixed the algal meal into the mash prior to pelleting. The second method mixed the meal with oil and was then sprayed on top of the pellets. Generally, there were no differences in bird live weight, feed intake or feed conversion ratio between different inclusion levels of astaxanthin or application methods. The results indicated that algal meal could reduce caecal colonization of Clostridium perfringens , whereas caecal colonization of C. jejuni was unaffected. Tissue astaxanthin and carotenoid concentrations increased with increasing levels of algal meal inclusion. The algal meal mixed with oil and sprayed onto the pellet resulted in higher tissue concentrations than the algal meal added prior to pelleting. Inoculation with C. jejuni significantly increased tissue astaxanthin concentrations in the kidney, intestine and breast muscle compared to non-inoculated birds. Coefficient of total tract apparent digestibility of astaxanthin was calculated to 0.882±0.048 for the upper intestine (between the end of the duodenal loop and Meckel’s diverticulum), 0.925±0.032 for the lower intestine (between Meckel’s diverticulum and the ileo-caecal junction), and 0.938±0.018 for the total tract. There were no significant differences in digestibility between application methods of the algal meal.

The presence of cholesterol oxidation products (COP) in the diet is a health concern for their various known adverse effects. It is important that the generation of COP be assessed during different stages of production, handling, and storage of meats and meat products so that relevant measures can be taken to minimize the production of COP. In a preliminary study, we investigated the content of COP in the lipids of raw meatballs (50% prok+50% beef), prefried meatballs (50% pork +50% beef), raw hamburger (100% beef), and prefried burger (50% pork+50% beef). Six of the common COP, viz 7α- and 7β-hydroxycholesterol, 7-ketocholesterol, 5α,6α-epoxycholestanol, 5β,6β-epoxycholestanol, and cholestanetriol, were analyzed by gas chromatography (GC) and GC-mass spectroscopy. The total content of these COP was in the range of 7 to 10 μg/g lipids in raw meatballs, prefried meat balls, and raw hamburger, after frying these samples for consumption. The prefried hamburger had ca. 8μg/g lipids of the total COP before frying, and this amount increased to 29 μg/g lipids after frying. During the storage of this fried sample, the total COP increased to 42 and 50 μg/g lipids, after 1 and 2 wk of storage, respectively. The results of this study show that freshly prepared meat products are a minor source of COP in the diet. However, if semiprepared frozen meat products are fried once and then stored for future consumption, the levels of COP can increase considerably, and this may be of concern for certain groups of consumers.

Most models of lipoprotein oxidation by free radi- cals have excluded macromolecular plasma components from the system. This limits their biological significance because oxidation of lipoproteins appears to occur in the intima in the presence of a plasma ultrafiltrate. Hemin, a product of in vivo hemoglobin degradation, binds and oxidizes purified lipo- proteins. However, it is not known whether this occurs in the presence of plasma components that may sequester hemin. We found that hemin in serum diluted to protein levels of the extracellular fluid (10-30%) binds to low and high density lipoproteins (LDL, HDL) with association constants in the nmol/L range. In the presence of H 2 O 2 , hemin oxidizes both lipoproteins in diluted serum with formation of conjugated dienes, thiobarbituric acid reacting substances, and F 2 -iso- prostanes. This appeared to be caused by the high affinity of hemin with LDL and by the Fe 3 1 liberated that remains asso- ciated with the particles after hemin is degraded. Spectropho- tometric and fluorescence experiments and electrophoresis of porphyrins complex with LDL indicated that the heme ring is buried in the lipoprotein surface-monolayer with the carboxylic groups in contact with positive regions of the pro- tein and the solvent. Human macrophages associated and de- graded 3- to 4-times more hemin-oxidized LDL in diluted se- rum than native LDL. It is possible then that at sites of LDL accumulation in the extracellular intima, hemin and H 2 O 2 production could cause oxidation with potential atherogenic consequences for cellular lipoprotein processing. This may occur even when other macromolecules of the extracellular

The current study extends previously reported PPARα agonist WY 14,643 (30 µmol/kg/day for 4 weeks) effects on circulating amino acid concentrations in rats fed a 48% saturated fat diet. Steady-state tracer experiments were used to examine in vivo kinetic mechanisms underlying altered plasma serine, glycine and arginine levels. Urinary urea and creatinine excretion were measured to assess whole-body amino acid catabolism. WY 14,643 treated animals demonstrated reduced efficiency to convert food consumed to body weight gain while liver weight was increased compared to controls. WY 14,643 raised total amino acid concentration (38%), largely explained by glycine, serine and threonine increases. 3H-glycine, 14C-serine and 14C-arginine tracer studies revealed elevated rates of appearance (Ra) for glycine (45.5 ± 5.8 versus 17.4 ± 2.7 µmol/kg/min) and serine (21.0 ± 1.4 versus 12.0 ± 1.0) in WY 14,643 versus control. Arginine was substantially decreased (-62%) in plasma with estimated Ra reduced from 3.1 ± 0.3 to 1.2 ± 0.2 µmol/kg/min in control versus WY 14,643. Nitrogen excretion over 24 hours was unaltered. Hepatic arginase activity was substantially decreased by WY 14,643 treatment. In conclusion, PPARα agonism potently alters metabolism of several specific amino acids in the rat. The changes in circulating levels of serine, glycine and arginine reflected altered fluxes into the plasma rather than changes in clearance or catabolism. This suggests that PPARα has an important role in modulating serine, glycine and arginine de novo synthesis.

Introduction With the arrival of the potent P2Y12 antagonists, ticagrelor and prasugrel, the need for co-treatment with aspirin in acute coronary syndromes must be re-examined. This study assessed whether high-dose aspirin: a) provides additional anti-platelet efficacy, assessed in vivo and ex vivo, when combined with P2Y12 inhibition; and/or b) has a negative effect on vascular function. Materials and Methods Using an anaesthetized dog model of thrombosis, the effects of aspirin (50 mg/kg) in addition to clopidogrel and ticagrelor were evaluated at two levels of P2Y12 inhibition, maximal (≥ 96%) and sub-maximal (~ 80%), as assessed by ex vivo ADP-induced whole blood impedence aggregometry. Results In the absence of aspirin, maximal and sub-maximal P2Y12 inhibition inhibited arachidonic acid-induced platelet aggregation by approximately 80% and 24%, respectively, without affecting platelet TXA2 formation. During maximal P2Y12 inhibition, aspirin provided less additional inhibition of ex vivo arachidonic acid- and collagen-induced platelet aggregation, as compared with sub-maximal P2Y12 inhibition, without additional anti-thrombotic effect in vivo. Aspirin significantly decreased in vivo PGI2 production (27%) and increased vascular resistance (16%), independently of P2Y12 antagonism. Conclusion In the dog, P2Y12 antagonists inhibit TXA2-mediated platelet-aggregation independently of aspirin. Aspirin provides less additional anti-platelet effects during maximal compared with sub-maximal P2Y12 inhibition but increases vascular resistance.

Endothelial cells (EC) produce prostacyclin (PGI 2 ) in high quantities which at the luminal surface decreases platelet aggregation and adhesion and basal to the cell relaxes smooth muscle cells (SMC). Connections have been reported between prostacyclin production, hypertension and the degree of adrenergic activation. The present study tested the hypothesis that prostacyclin production by EC could be regulated by adrenergic mechanisms. EC were isolated from human umbilical cord veins. Washed cells were seeded and grown to confluency on tissue culture dishes. The test drugs were simultaneously added to parallel dishes. Samples were collected from the conditioned medium and analyzed for 6-keto-PGF 1a with RIA technique. Endothelial cells pretreated with the betaadrenoeceptor blocking drugs metoprolol or propranolol synergistically increased basal prostacyclin production when exposed to betaadrenergic stimulation. However, using isomers with high or low betaadrenoblocking effect, this synergism was demonstrated not to be associated to the betaadrenoceptor blocking effect of the drugs per se. These findings may have implications on the arterial hypertensive state characterized by high sympathetic tonus and low PGI 2 production. The data may offer an explaination why hypertensive individuals react with increased PGI 2 production, upon betaadrenoceptor blocking therapy.

Excessive amounts of cobalt are cardiotoxic, although the mechanism for this toxicity remains unclear. We studied the effects of acute cobalt exposure on the activities of free radical scavengers in the myocardium in 5 groups of rats. Six rats served as a control group and were given a daily subcutaneous injection of 1 ml saline for 8 days. The other 4 groups of rats received a daily injection subcutaneously of cobalt chloride in doses of 1 mg/kg bw, 5 mg/kg bw, 20 mg/kg bw and 50 mg/kg bw, respectively for 8 days. There was a marked and dose-dependent accumulation of cobalt in the myocardium of the cobalt exposed rats. Creatine kinase, copper-zinc superoxide dismutase (CuZn-SOD) and alpha-tocopherol content did not differ between the control and the cobalt exposed groups. The activity of glutathione peroxidase increased, while the activity of manganese-superoxide dismutase (Mn-SOD) was significantly reduced in the cobalt exposed groups. There was an inverse relationship (r = 0.60, P0.0001) between the cobalt content and Mn-SOD activity in the myocardium. These results suggest that acute cobalt cardiotoxicity may involve a reduction of intrinsic scavengers resulting in an increased vulnerability to oxygen free radical toxicity.

To investigate the gastrointestinal secretory and enzymatic responses to a liquid meal during in vivo perfusion of the proximal human jejunum. Human intestinal fluid was collected from the proximal jejunum by single-pass in vivo perfusion (Loc-I-Gut). The fluid was quantitatively collected at 10-min intervals during 90 min while perfusing a nutritional drink at 2 mL/min. Quantification of lipids in the fluid leaving the segment was performed by using novel chromatographic methods. The overall bile acid concentration varied between 0.5 and 8.6 mM with a peak level 40 min after the start of the liquid meal perfusion. The total concentration of phospholipids was between 0.1 and 3.9 mM and there was a rapid degradation of phosphatidylcholine to lysophosphatidylcholine. The tri-, di-, monoglycerides and free fatty acid levels increased sharply in the beginning and reached steady-state levels between 7 and 9.5 mM. There is a rapid secretion of bile in response to food. Most of the dietary lipids are found in the form of their degradation products in vivo in human jejunum. This novel in vivo characterization, based on direct and high-recovery sampling of intestinal fluids, forms a basis for further development of improved in vitro drug dissolution test media.

This paper presents Salmonella data from animals, feedstuffs and feed mills in Sweden between 1993 and 1997. During that period, 555 isolates were recorded from animals, representing 87 serotypes. Of those, 30 serotypes were found in animals in Sweden for the first time. The majority of all isolates from animals were S. Typhimurium (n = 91), followed by S. Dublin (n = 82). There were 115 isolates from cattle, 21 from broilers, 56 from layers and 18 from swine. The majority of these isolates were from outbreaks, although some were isolated at the surveillance at slaughterhouses. The number of isolates from the feed industry was similar to that of the previous 5-year period. Most of those findings were from dust and scrapings from feed mills, in accordance with the HACCP programme in the feed control programme. It can be concluded that the occurrence of Salmonella in animals and in the feed production in Sweden remained favourable during 1993–97.

BACKGROUND: The etiology and pathogenesis of microscopic colitis is unknown. Whether genetic predisposition is of importance, as in many other gastrointestinal diseases, is unknown. Familial occurrence of collagenous colitis has earlier been reported only in two families. METHODS: Familial occurrence of microscopic colitis was searched for in a Swedish national microscopic colitis register. RESULTS: Familial occurrence of microscopic colitis was identified in five families. In all families a sister-sister relationship was found. Two sisters with collagenous colitis had been living apart in different Nordic countries for many years before developing the disease. In one pair, the smoking sister had collagenous colitis and the never smoking sister had lymphocytic colitis. CONCLUSIONS: Considering the relative rarity of microscopic colitis, these findings indicate that a genetic predisposition may be of importance. (Less)

Twenty-three reindeer bulls, aged 2-3 years, fed during two winter months at the Vuolda reindeer research station in Arjeplog, Sweden, were used in the study. The first group of eight reindeer was moved from their feeding corral to a selection corral, captured by lasso and stunned with a captive bolt outside the selection corral. The second group of seven reindeer was moved to the selection corral, captured by lasso and restrained, after which they were loaded onto a lorry- and transported for 1 hour and then slaughtered. The third group of eight reindeer was moved to the selection corral and herded directly onto the lorry, without any manual handling. They were transported for 5 h and then slaughtered. In both transport groups, four reindeer were fitted with pre-programmed automatic blood sampling equipment (ABSE). ABSE sampled blood at predetermined times via a jugular vein catheter. Ultimate pH-values in three muscles (Mm. longissimus, triceps brachii and biceps femoris) were significantly lower in the group carefully handled and transported for 5 h compared with the other two groups. The physiological mechanisms behind these results are discussed. Samples from M. semimembranosus were collected at slaughter and after 2, 6 and 10 days of refrigerated storage (+4 °C). The samples were analysed for total counts of aerobic bacteria (pour-plated in Tryptone Glucose Extract Agar, Difco, incubated at 20 °C and 30 °C, respectively for 72 h), coliform bacteria 37 °C (pour-plated in Violet Red Bile Agar, Oxoid, incubated at 37 °C for 24 h), Enterococci (surface-plated onto Slantez and Bartley Agar, Oxoid, incubated at 44 °C for 48 h) and Bacillus cereus (surface-plated onto Blood Agar Plates (Blood Agar Base, Difco, supplemented with 5% defibrinated horse blood) 30 °C for 24 h). All samples fell in the range 'fit for consumption'. At slaughter, there was no difference in ASAT activity, urea and Cortisol concentrations between the two transported groups. However, the plasma ASAT activity and urea concentrations at slaughter were significantly lower in the non-transported group. In both transport groups, the plasma Cortisol concentrations increased during loading onto and unloading from the lorry. Abomasal lesions were observed in all treatment groups. It was concluded that reindeer showed an acute stress response to manual handling and transport.

Most models of lipoprotein oxidation by free radicals have excluded macromolecular plasma components from the system. This limits their biological significance because oxidation of lipoproteins appears to occur in the intima in the presence of a plasma ultrafiltrate. Hemin, a product of in vivo hemoglobin degradation, binds and oxidizes purified lipoproteins. However, it is not known whether this occurs in the presence of plasma components that may sequester hemin. We found that hemin in serum diluted to protein levels of the extracellular fluid (10-30%) binds to low and high density lipoproteins (LDL, HDL) with association constants in the nmol/L range. In the presence of H2O2, hemin oxidizes both lipoproteins in diluted serum with formation of conjugated dienes, thiobarbituric acid reacting substances, and F2-isoprostanes. This appeared to be caused by the high affinity of hemin with LDL and by the Fe3+ liberated that remains associated with the particles after hemin is degraded. Spectrophotometric and fluorescence experiments and electrophoresis of porphyrins complex with LDL indicated that the heme ring is buried in the lipoprotein surface-monolayer with the carboxylic groups in contact with positive regions of the protein and the solvent. Human macrophages associated and degraded 3- to 4-times more hemin-oxidized LDL in diluted serum than native LDL. It is possible then that at sites of LDL, accumulation in the extracellular intima, hemin and H2O2 production could cause oxidation with potential atherogenic consequences for cellular lipoprotein processing. This may occur even when other macromolecules of the extracellular fluid are present.

Six hundred seven trochanteric fractures (563 patients) were treated with a sliding-screw technique and followed clinically and roentgenographically for at least one year. Of 351 patients admitted from their homes, 209 (60%) were discharged to their homes after an average of 18 days in the hospital. During the first year another 61 (17%) patients returned home after rehabilitation in a geriatric ward. Of 446 patients walking without support or with one cane before surgery, 360 (80%) had regained the same mobility after one year. The one-year mortality rate was 18%, while the ten-year rate was 74%. Compared with a control cohort, the mortality rate was increased during the first two years after fracture. The increase in mortality was influenced by advanced age, admission from long-term care institutions, male gender, and ambulatory or nonambulatory status before surgery. Forty-five (7.4%) were reoperated, 17 because of technical complications, three because of infection, and three because of nonunion. No further nonunions occurred. The deep infection rate was nine of 339 (2.7%) before and two of 268 (0.8%) after the introduction of antibiotic prophylaxis. Thromboembolic complications decreased from 4.1% to 1.2% after the introduction of dextran 70 as thromboembolic prophylaxis.

A review of roentgenograms and charts was made of 532 trochanteric fractures treated by the sliding-screw technique. According to Evans' modified classification, 65% of the fractures were unstable. There was no breakage or bending of implants. Twenty (3.8%) reoperations were performed because of technical complications or nonunion. The Singh index revealed more unstable fractures and technical complications in hips with Grades 1-3 than in hips with Grades 4-6. Reoperation was more frequent if the screw tip was within 8 mm from the subchondral line in the superolateral quadrant or in the anteroproximal quadrant than if the screw ended farther from the subchondral line. Fifty-five (10.8%) of the lag screws migrated 2 mm or more. Postoperatively, the neck-shaft angle decreased more in unstable fractures than in stable fractures. The decrease in neck-shaft angle was less when the proximal fragment impinged medially on the shaft fragment. Unstable fractures with this type of reduction also impacted less than hips with anatomic reduction or medial reduction of the shaft fragment. Weight bearing did not significantly influence the degree of impaction.

Two different methods for determination of leg growth, the tetracycline method and roentgen stereophotogrammetry, were applied simultaneously in 41 young rabbits and compared 1 and 2, and 21 and 22 days after insertion of pins or balls of tantalum as markers. The tetracycline method gave slightly higher values than the other method, the difference varying between 77 and 6 micrometer/d on the first 2 days after marker insertion and between 32 and 1 micrometer/d after 3 weeks. When ball markers were used, agreement between the two methods was obtained 3 weeks after insertion. The difference between the methods used is due to that the two methods did not measure growth in precisely identical regions.

The longitudinal bone growth in 1922 consecutively hypophysectomized and surviving rats was determined with oxytetracycline. The longitudinal bone growth of proximal tibia during the first 15 postoperative days and the width of the fluorescent tetracycline band at 15 days after the operation were found to correlate well with the microscopical examination of serial sections of sella turcica. These growth parameters, when considered together, can be used as a means of screening whether hypophysectomy is complete. As a result microscopical examination of serial sections of the sella turcica to ascertain the completeness of the operation can be reduced to about the 10% of the animals where there remains some doubt.

Cavitation erosion on aluminium in water flow during the very first part of the incubation period is examined. The erosion is studied by scanning electron microscopy and by optical microscopy. The material damage caused by collapse of single cavities is correlated to the cavities observed during the erosion experiments and to theoretical models of cavity collapse. The development of the erosion process during the initial stage is discussed.

Progressive growth retardation and varus tilting were observed in a child with an ankle fracture of supination-adduction type initially treated by closed reduction and pinning. The patient was later operated with the Langenskiöld procedure. Preoperatively, roentgen stereophotogrammetric analysis showed decreasing growth rates especially medially in the distal tibia, radionuclide scintimetry manifested reduced activity on the injured side, and tomograms showed a bony bridge medially. The evidence of growth in the distal tibia indicated the existence of an osseofibrous bridge between the epiphysis and the metaphysis. This was also confirmed by the findings at the operation and partly by microscopical investigation of the removed osseofibrous bridge. Postoperative stereophotogrammetric analysis showed reduction of the varus position in two steps. Roentgen stereophotogrammetry permits early detection of a growth disturbance, and evaluation of the effects of therapy.

The growth stimulating effect of different growth hormone and prolactin preparations on the longitudinal bone growth in thyroxine-treated hypophysectomized rats was determined by the tetracycline method. The effect of the hormone preparations was compared with that of the 1st International Standard for growth hormone. The potency calculation showed that the tested human growth hormone preparations have a higher potency than the bovine, ovine and porcine growth hormone preparations. Also potency differences were found between hormones from the same species but prepared by different methods. The prolactin preparations have a considerably lower growth promoting activity than the growth hormone preparations. The bioassay method used in the present investigation has a favourable mean precision (λ = 0.172) and sensitivity compared with the earlier bioassay methods. The present method increases the possibility of determining the biological effects of various growth promoting substances.

Small tantalum pins (0.50 x 1.5 mm and 0.32 x 1.2 mm), used as intraosseous radio-opaque markers, were investigated for their effect on growth in 62 young rabbits. The tetracycline growth method was used and a difference in daily growth rate between the marked right leg and the unmarked left leg indicated a slight growth stimulation. The growth rate was slightly stimulated (at most, 26 mum/day) on days 1 and 2 after insertion, only if the larger markers were used. No growth effects were detectable on days 12 and 21.

A transmission electron microscope investigation has been performed on the adhesion properties of fine gold particles (typical radius 20–30 nm). The adhesion process is found to be intimately related to the crystallography of the particles and consists both of an elastic part and a plastic part, where twinning plays an important role. The main driving force in adhesion is due to the surface energy, but electrostatic forces might also be of importance.

Residual stresses can cause a severe reduction of the lifetime of components exposed, for example, to varying loads which lead to fatigue. Measuring residual stresses is therefore of vital importance. X-ray diffraction is one of the techniques which can be used for this purpose. This method has the advantage of measuring stresses to a depth of only a few micrometres (in steel approximately 10 μm). Therefore it is possible to determine stress gradients within the material but, in order to do so, material must be removed before each measurement. When material containing or subjected to internal stresses is removed, the stress distribution in the remaining material is changed and it is therefore necessary to correct the measured stresses. Two correction methods are available for this purpose. The first and simplest is based on elastic beam theory and the second, which is developed by the present authors, is based on calculations with the finite element method (FEM). The latter is discussed in this paper together with the results of the calculations. The results show a significant difference between the corrections calculated by the two methods. It is particularly important to use the FEM-based method when considering measurements of residual stresses in coatings with elastic properties differing from those of the substrate material.

The effect of cavitation erosion on metals is considered. A model is proposed which offers a relative measure of the cavitation erosion resistance and of the length of the incubation period for different metals. The model predicts that the energy absorbed by the plastic deformation of the material depends upon the hardness of the material, and it finds a qualitative difference between cavitation erosion in different apparatus types. In the case of flow induced cavitation the model finds the cavitation erosion to be proportional to the 5th-7th power of the flow velocity.

This investigation into the fatigue of a commercial austenitic stainless steel (UHB 3 MM) at ultrasonic frequencies (20 and 25 kHz) has been primarily concerned with the initial stages of the fatigue process prior to fatigue crack initiation. Results have been obtained using equipment in which it is possible to superimpose ultrasonic push pull stresses upon a static tensile stress. Microstructural examination of the specimen surface and of the internal deformation rearrangements by means of electron microscopy, has revealed fatigue damage which is comparable to that occurring during conventional, low frequency, fatigue. Thus, in contrast to other investigators, we have obtained evidence of dislocation dipole and deformation band formation together with regularly spaced slip band markings from tests at low amplitudes. Higher amplitude cycling has indicated the formation of dislocation tangles and cells. The results do not suggest a significant change in fatigue mechanism upon changing the testing frequency into the ultrasonic regime.

The aims of this study were to estimate the incidence of acute confusional state (ACS), its predisposing factors and consequences in 111 consecutive patients operated for fractured neck of the femur. The incidence of ACS was 61 percent and the predicting factors were old age and dementia. Drugs with anticholinergic effect, depression, and previous stroke were factors that seemed to be associated with the development of ACS. Ninety-two percent of the patients who had severe perioperative blood pressure drops developed ACS. The consequences of ACS were prolonged ward-stay at the orthopedic department, a greater need for long-term care after discharge, and poor walking ability at discharge and six months after surgery. The confused patients also had more complications, such as urinary problems, feeding problems and decubital ulcers, as compared with the nonconfused patients.