Massive Blood Transfusion in Patients with Ruptured Abdominal Aortic Aneurysm.

OBJECTIVES: The aim was to study blood transfusions and blood product ratios in massively transfused patients treated for ruptured abdominal aortic aneurysms (rAAAs). METHODS: This was a registry based cohort study of rAAA patients repaired at three major vascular centres between 2008 and 2013. Data were collected from the Swedish Vascular Registry, hospitals medical records, and local transfusion registries. The transfusion data were analysed for the first 24 h of treatment. Massive transfusion (MT) was defined as 4 or more units of red blood cell (RBC) transfused within 1 h, or 10 or more RBC units within 24 h. Logistic regression was used to calculate the odds ratio of 30 day mortality associated with the ratios of blood products and timing of first units of platelets (PLTs) and fresh frozen plasma (FFP) transfused. RESULTS: Three hundred sixty nine rAAA patients were included: 80% men; 173 endovascular aneurysm repairs (EVARs) and 196 open repairs (ORs) with median RBC transfusion 8 units (Q1-Q3, 4-14) and 14 units (Q1-Q3, 8-28), respectively. A total of 261 (71%) patients required MT. EVAR patients with MT (n = 96) required less transfusion than OR patients (n = 165): median RBC 10 units (Q1-Q3, 6-16.5) vs. 15 units (Q1-Q3, 9-26) (p = .002), FFP 6 units (Q1-Q3, 2-14.5) vs. 13 units (Q1-Q3, 7-24) (p < .001), and PLT 0 units (Q1-Q3, 0-2) vs. 2 units (Q1-Q3, 0-4) (p = .01). Median blood product ratios in MT patients were FFP/RBC (EVAR group 0.59 [0.33-0.86], OR group 0.84 [0.67-1.2]; p < .001], and PLT/RBC (EVAR 0 [0-0.17], OR 0.12 (0-0.18); p < .001]. In patients repaired by OR a FFP/RBC ratio close to 1 was associated with reduced 30 day mortality (p = .003). The median PLT/RBC ratio was higher during the later part of the study period (p < .001, median test), whereas there was no significant difference in median FFP/RBC ratio (p = .101, median test). CONCLUSION: The majority of rAAA patients undergoing EVAR required MT. EVAR patients treated with MT had lower FFP/RBC and PLT/RBC ratios than OR patients with MT. The mortality risk was lower with FFP/RBC ratio close to 1:1 in open repaired patients requiring MT. The 24 h PLT/RBC ratio increased over the study period.

Variable supplemental oxygen during recovery does not reduce retinal neovascular severity in experimental ROP.

PURPOSE: To test the hypothesis that variable supplemental oxygen (VSO) during recovery is not as effective as constant supplemental oxygen treatment at reducing retinal neovascular severity in the newborn rat model of retinopathy of prematurity (ROP). METHODS: The ROP model consists of raising newborn rats in variable oxygen for 14 days and then allowing them to recover during the next 6 days (until day 20). During this recovery period, two VSO protocols were examined: 1) 24 hr cycled (28% for 24 hr and 21% for 24 hr) as a control, and 2) interrupted (28% for 23.75 hr and 21% for 0.25 hr). On day 20, retinas from both eyes of each animal were dissected, stained with ADPase, and analyzed for neovascular (NV) incidence, severity, and peripheral avascularity. RESULTS: No significant differences (P > 0.05) in NV incidence and severity were found between the 24 hr cycled (control) (95% (38/40), median 5 clockhrs, range 0.5-9, n = 38) and interrupted VSO groups (89% (40/45), 3.5 clockhrs, 0.5-10.5, n = 40). However, retinal NV severity from both VSO groups were significantly greater (P < 0.05) than that previously reported for constant supplemental oxygen treatment. Percent peripheral avascularities were not significantly different (P > 0.05) between the two VSO groups. CONCLUSIONS: These results support our hypothesis since both VSO conditions were significantly less effective at reducing retinal NV than constant supplemental oxygen during recovery. The possible application of these results to STOP-ROP trial is discussed.

Effects of dietary fats on red blood cell membrane insulin receptor in normo- and hypercholesterolemic miniature swine.

It has been demonstrated that the type of dietary fat affects insulin receptors in various tissues in normal humans and animals by altering membrane fluidity. This study compares the effects of n-3 fatty acids from fish oil and n-6 fatty acids from corn oil on red blood cell membrane insulin receptors in normal and hypercholesterolemic minipigs. A group of minipigs were made hypercholesterolemic by feeding cholesterol and lard for 2 months; the other group served as controls and was fed stock diet. Both groups were then fed experimental diets containing either corn oil or menhaden oil or a mixture of the two for 23 additional weeks. Blood was collected at 0, 2, 12 and 23 weeks after the start of the experimental diets and membranes were prepared from the red blood cells. Insulin binding to red blood cell membranes was measured by radioreceptor assay. Plasma insulin was measured by radioimmunoassay. Insulin binding to red blood cell membrane was compared with the fluidity of the membrane measured and reported earlier. There was no significant effect of cholesterol feeding on plasma insulin concentrations. After 23 weeks on experimental diet plasma insulin was significantly higher in minipigs fed menhaden oil compared to those fed corn oil. No such effect was observed in hypercholesterolemic minipigs. No significant effect of either hypercholesterolemia or fish oil was observed on red blood cell insulin binding. A significant negative relationship was observed between insulin binding and anisotropy at 4°C for all probes but at 37°C significant negative relationship was observed only with polar probes. The data suggest that n-3 fatty acids from fish oil significantly increases plasma insulin in minipigs compared to n-6 fatty acids from corn oil. However, the unsaturation has no significant effect on insulin receptors on erythrocytes. Similarly, prior hypercholesterolemic state also has no effect on plasma insulin levels or the insulin binding to red blood cell membranes.

Postmastectomy lymphoedema. Treatment and a five-year follow-up study.

BACKGROUND: Lymphoedema of the arm is a common problem after mastectomy and radiotherapy of mammary cancer. In a prospective 5-year follow-up study we investigated the development of arm oedema and the effect of conservative compression treatment. METHODS: Two hundred and twenty-six patients who had undergone mastectomy were investigated. Oedema formation was estimated by recording displaced water volume of both arms preoperatively and six times post-operatively. One hundred fifty-seven patients (70%) could be followed for five years. An inter-arm difference of 100 ml or more was defined as oedema. Three types of treatment were given: (1) Compression with stockings in 28 patients, (2) intermittent compression (Flowtron) in 8 and (3) intermittent compression (Lympha-Press) and compression sleeves in 19 patients. RESULTS: A total of 46 patients (20%) developed post-operative oedema, 17 within six months and 29 one year postoperatively. The average oedema volume was 418 ml. Most patients with a moderate or severe oedema had irradiation therapy. Severe lymphoedema (750 ml or more) occurred in patients with irradiation postoperatively and lymph node engagement. There was no correlation between patient age and oedema formation. Compression therapy with stockings reduced oedema in 15 out of 28 patients (54%) and prevented further swelling. Therapy with stockings and Lympha Press reduced the arm volume in 13 out of 19 patients (68%). Four out of eight patients treated with Flowtron showed oedema reduction. In most patients cessation of treatment resulted in relapse of swelling to the same degree as before. CONCLUSIONS: Compression therapy is beneficial to control postmastectomy arm swelling. This applies to different modalities and prolonged periods of treatment are required to check progression. Application of stockings is the simplest way to treat postoperative oedema. In most cases postoperative oedema appeared during the first year after surgery and the most severe cases occurred after irradiation.

Dietary menhaden and corn oils and the red blood cell membrane lipid composition and fluidity in hyper- and normocholesterolemic miniature swine.

Fatty acids in the diet are readily incorporated into lipids in various tissues. However, it is not clear whether all tissues have the same level of incorporation. Second, (n-6) unsaturated fatty acids increase the fluidity of membranes, but this has not been shown for (n-3) fatty acids. In this study, we measured the incorporation of (n-6) and (n-3) fatty acids into erythrocyte membrane lipids and studied their effects on the fluidity of erythrocyte membranes. One group of female miniature swine was made hypercholesterolemic by feeding the swine cholesterol and lard for 2 mo; the other group served as controls and was fed a stock diet. Both groups were then fed either corn oil or menhaden oil or a mixture of the two for 23 additional weeks. Blood was collected at 0, 2, 4, 12 and 23 wk after initialization of the experimental diets, and fatty acid composition of phospholipids was assessed. Membrane phospholipids of pigs fed menhaden oil had elevated (n-3) fatty acids (20:5 and 22:6), and lower 18:2 than those fed corn oil. There was no difference in 20:4 content. The fatty acid changes occurred as early as 2 wk after consumption of the corn oil or menhaden oil in pigs previously fed a stock diet, but it took longer in pigs previously fed lard + cholesterol, indicating residual effects of pretreatment. Menhaden oil increased anisotropy (indicating decreased fluidity) more than corn oil for the nonpolar probe diphenylhexatriene (DPH) at earlier time points, but not at 23 wk. Erythrocyte membrane fluidity was significantly related to membrane polyunsaturate content, with (n-6) fatty acids having a greater influence than (n-3) fatty acids. A comparison of the present red blood cell fatty acid compositions with brain synaptosome fatty acid compositions for the same animals showed poor correlations for some of the fatty acids. There was no significant direct relationship between docosahexaenoate (DHA) concentrations in erythrocyte membranes with DHA concentrations in brain synaptosomes from cerebellum, forebrain and caudate nucleus.

Vitamin E levels and susceptibility to lipid peroxidation increase with aging in heart plasma membrane from miniature swine.

Age-related changes in heart plasma membrane fatty acid composition, vitamin E content, membrane fluidity, susceptibility to lipid peroxidation, and the subcellular distribution of vitamin E were observed in male and female Hormel-Hanford miniswine over a wide range of ages: prepubertal, < 0.5 years; young, 0.5-2.5 years; middle-aged, 5.9-10 years; and old, 11.5-13.9 years. Pigs were continuously fed the same low-fat, cholesterol-free, vitamin E-adequate stock diet at restricted maintenance levels. Membrane lipid peroxidation tended to increase in middle-aged and elderly pigs, but not significantly, perhaps being somewhat ameliorated by the significantly increased membrane vitamin E in middle-aged and old pigs. Mid-bilayer membrane fluidity was significantly increased in old pigs, but fluidity of the polar headgroup domains decreased with age. Thus, lipid peroxidation tended to increase over the long life span of miniswine even when they are food restricted.

Fatty acid modification of membrane fluidity in Chinese hamster ovary (TR715-19) cells.

Dietary saturated fatty acids, especially lauric (12:0), myristic (14:0) and palmitic (16:0) acids, which are hypercholesterolemic, influence cell membrane fatty acid composition and affect LDL receptor function. When membrane phospholipid fatty acids in Chinese hamster ovary cells, containing the human LDL receptor, were modified (Hannah J. S. et al., 1995 Metabolism 44, 1428-1434), LDL receptor function was affected, but correlations with DPH-determined membrane fluidity were weak. The role of fluidity in various membrane domains with respect to the LDL receptor is examined here. Membrane fluidity was assessed by measuring steady-state fluorescence polarization of diphenylhexatriene (DPH) and its polar propionic acid (DPH-PA) and trimethylammonium (TMA-DPH) derivatives from 38 to 4 degrees C in fatty acid modified Chinese hamster ovary cells. Fatty acid changes modulated mid-bilayer fluidity as determined with DPH, but fluidity in phospholipid headgroup domains, assessed with DPH-PA and TMA-DPH, was independent of fatty acyl composition. The DPH fluidity was related to membrane unsaturation (P < 0.02), oleate contents (P < 0.009) in particular, but inversely related (P < 0.0002) to the longer chain (> or = 20 C atoms) unsaturated fatty acids with from four to six double bonds. The LDL binding was independent of fluidity, but there were weak relations between LDL internalization and DPH-PA anisotropy and between LDL degradation and TMA-DPH anisotropy. It was concluded that LDL binding was not related to mid-bilayer fluidity, but the results with the polar probes suggest a role of fluidity in modulating vertical displacement of the LDL/LDL receptor complex across the plasma membrane.

In vitro regulation of low-density lipoprotein receptor interaction by fatty acids.

Low-density lipoprotein (LDL) receptor binding is the initial step in receptor-mediated clearance. Dietary fat composition is known to affect LDL clearance, but the mechanism of the effect is unknown. We have examined the effects of altered membrane fatty acid composition, as might occur when specific dietary fats are consumed, on LDL binding using a Chinese hamster ovary (CHO) line that constitutively expresses the human LDL receptor. Binding of pooled human LDL to its receptor was compared in cells enriched with various fatty acids. Binding affinity was greater (lower Kd) for cells grown in 16:0-, 18:0-, or 18:1-enriched media than for those grown in 18:2 (P < .0001). The apparent receptor number (Bmax) was lower for cells enriched in saturated fatty acids and 18:1. Fluidity was assessed by measuring diphenylhexatriene (DPH) fluorescence anisotropy (rs). Cells enriched in 18:1 or 18:2 were the most fluid (P < .003). The correlation between binding and fluidity (r = .24, P = .27) was weak and did not appear to explain the effects of fatty acid modification on LDL receptor binding. Thus, it appears that cellular enrichment in 16:0, 18:0, and 18:1 increases binding affinity by affecting properties other than membrane fluidity. Changes in Bmax may also contribute to the observed differences in LDL binding.

Selective responses of hormones involved in carbohydrate and lipid metabolism and properties of erythrocyte membranes during the menstrual cycle in premenopausal women consuming moderate amounts of alcohol.

The effects of chronic consumption of moderate amounts of alcohol on hormones associated with lipid and carbohydrate metabolism, plasma concentrations of triacylglycerol and cholesterol, insulin receptors on erythrocyte membranes, and erythrocyte membrane fluidity were studied during three phases of the menstrual cycle in 37 premenopausal women. Subjects were given either 30 g ethanol or an equienergetic fruit juice for three menstrual cycles in a crossover design. Blood samples were analyzed during the luteal, midcycle, and follicular phases. Administration of alcohol induced a significant rise in plasma glucagon and cortisol uniformly across the entire menstrual cycle. A similar rise in plasma growth hormone was observed at midcycle during the period when subjects consumed alcohol. A marginal effect was observed on cholesterol and somatomedin C concentrations. Insulin binding to erythrocyte ghosts was not affected by either alcohol or menstrual-cycle phase. Erythrocyte membranes were more fluid during the follicular phase than during the luteal phase of the menstrual cycle when the women were consuming the alcohol. There were no perceptible interactions between alcohol and phases of the menstrual cycle for the indexes studied, except membrane fluidity.

Spasmolytic activity of medicinal plants used to treat gastrointestinal and respiratory diseases in the Highland of Chiapas.

Methanolic extracts of 141 different botanical species, used in traditional medicine in the Highland of Chiapas for the treatment of gastrointestinal and respiratory diseases, were submitted to pharmacological testing in order to evaluate the spasmolytic action on electrically-stimulated guinea pig ileum. Of these species, 33.3% showed an inhibition of reflex greater than 80% at a bath concentration of 250 µg/ml. Of the active species, 40.4% belong to the Asteraceae family. Of the active samples, 59.5% were obtained from leaves. The results identify a group of interesting plants, that could be considered for future experimental investigation.

Heart and liver fatty acid composition and vitamin E content in miniature swine fed diets containing corn and menhaden oils.

Female miniature swine, 4-11 yr, were fed 15% fat diets containing n-3 and/or n-6 polyunsaturated fat for 6 months, at 1.95 g fat/kg body weight. Liver lipids from menhaden oil-fed minipigs were elevated in the n-3 fatty acids: 20:5, 22:5 and 22:6, but heart lipids only in 20:5 and 22:6. Liver cell plasma membrane was elevated in 20:5, 22:5 and 22:6 and lowered in the n-6 acids 18:2 and 20:4 in menhaden oil-fed animals, to a greater extent than in the total tissue lipids. Liver alpha-tocopherol tended to decrease upon feeding menhaden oil, but heart alpha-tocopherol concentrations were not affected.

Anthropological issues in medical ethnobotany.

While ethnobotany has emerged as an important discipline in the search for new drugs, this economic impetus should in no way distract from a more ethnobiological and equally critical goal--the codification and promotion of indigenous medical systems as a major factor in the conservation of biocultural diversity. Codification of indigenous medical systems requires a holistic view which entails (1) in-depth understanding of the recognized health conditions in the native system and how they might be described in terms of Western biomedicine; (2) comprehensive inventories of medicinal species employed in the native system, descriptions of their modes of preparation and administration and giving priority to those species most likely to merit pharmacological testing; and (3) identification of the pharmacological properties of these species with the goal of discovering how they might be effective in the treatment of the health conditions for which they are employed. Promotion of indigenous medical systems requires the development of local training programmes aimed at the active conservation and enhancement of traditional herbal medicinal therapies that have been shown to be pharmacologically effective in the treatment of symptoms of recognized health conditions. The establishment of such programmes is critical at a time when traditional medical systems are often disparaged as worthless by the national societies in which indigenous peoples live, as well as by younger members of the native populations themselves.

Me' winik: discovery of the biomedical equivalence for a Maya ethnomedical syndrome.

Investigation of the correspondence of ethnomedical illness syndromes and biomedical disease classification has led to the identification of a high prevalence of gallbladder disease among the Tzeltal and Tzotzil Maya populations of Highland Chiapas. This condition, known to demonstrate exceptionally high rates among North American Indians, has not previously been described among the Highland Maya. The failure to recognize this serious health problem has been due primarily to cultural differences in understanding the anatomy and difficulties arising from communication of symptomatology. A focus on the interface of ethnomedicine and biomedicine is shown to have significance from both theoretical and applied perspectives.

Dietary fish oil-induced changes in the distribution of alpha-tocopherol, retinol, and beta-carotene in plasma, red blood cells, and platelets: modulation by vitamin E.

Healthy men (ages 24-57 y) were fed a controlled basal diet supplemented with 15 g/d of placebo oil (PO) for 10 wk followed by 15 g/d of fish-oil concentrate (FO) (fortified with 15 mg all-rac-tocopherol) for 10 wk without additional alpha-tocopherol and the last 8 wk with 200 mg alpha-tocopherol/d (FO+E). Compared with PO, FO raised plasma malondialdehyde; lowered alpha-tocopherol in plasma, red blood cells, and platelets; and raised plasma and platelet beta-carotene. Supplementation with additional alpha-tocopherol (FO+E) not only restored tocopherol concentrations but also reversed the rise in beta-carotene. The response in retinol, particularly in platelets, showed an inverse relationship to beta-carotene, alpha-tocopherol exhibiting a modulating effect on these changes. From these observations it is postulated that platelets may be a significant extraintestinal site of retinol formation from beta-carotene.

Effect of lithocholic acid feeding on plasma lipoproteins and binding of radioiodinated human lipoproteins to hepatic membranes in rats.

1. Male Sprague-Dawley rats fed diets containing 0.25% lithocholic acid for 6 weeks exhibited elevated serum cholesterol. 2. The rats were fed diets containing 5 or 20% fat with and without the lithocholate and/or oxytetracycline-HCl. 3. The cholesterol elevation was associated with high density lipoprotein (HDL) and not very low density lipoprotein (VLDL) or low density lipoprotein (LDL). 4. Specific binding of human [125I]HDL to hepatic membranes was lowered in lithocholate-fed rats, but binding of human [125I]LDL to these membranes was not affected.

Effects of omega 3 fatty acids and vitamin E on hormones involved in carbohydrate and lipid metabolism in men.

Forty healthy men were fed diets providing 40% of energy from fat and a minimum of 25 mg vitamin E for 28 wk. During the first 10 wk diets were supplemented with placebo, 15 g mixed fat/d. During the second 10 wk placebo was replaced by 15 g fish-oil concentrate/d. During the last 8 wk 200 mg vitamin E/d was added to fish oil. Compared with placebo, fish-oil feeding significantly increased plasma glucose and decreased triacylglycerol, insulin, glucagon, growth hormone, and somatomedin C. The changes in plasma cholesterol, cortisol, and dehydroepiandrosterone sulphate (DHEA-S) were not significant. Fish oil plus vitamin E further decreased insulin, growth hormone, and DHEA-S and reversed the effect of fish-oil on somatomedin C. The changes in glucose, glucagon, growth hormone, and cortisol were not significant. Thus, changes in plasma glucose and lipids caused by dietary fish oil alone and with fish oil plus vitamin E appear to be due to alterations in hormones involved in carbohydrate and lipid metabolism.

Dietary fat and hormonal influences on lipoprotein fluidity and composition in premenopausal women.

LDL and HDL became more fluid when health, free-living, premenopausal women were fed reduced fat diets with higher proportions of polyunsaturated fatty acids. Lipoproteins were isolated from plasma of 31 female subjects fed one of two sets of diets from typical U.S.A. foods with P/S ratios of 0.3 or 1.0. All subjects were fed high-fat diets (40% of energy) for the duration of four menstrual cycles followed by low-fat diets (20% of energy) for the next four cycles. Blood samples were collected during mid-follicular and mid-luteal phases of the fourth menstrual cycle of each diet period to assess interactive dietary and hormonal control of lipoprotein fluidity. LDL was significantly more fluid, as determined by DPH fluorescence, upon reducing fat consumption from 40 to 20% of energy for subjects eating foods with P/S = 1.0 or 0.3. Generally LDL was more fluid during the follicular phase than the luteal phase of the cycles, thus indicating hormonal influences on LDL fluidity. HDL results were similar but not as pronounced as with LDL. Lipoprotein phospholipid (PL) and cholesteryl ester (CE) fatty acyl compositions were also subject to dietary and hormonal influences. Effects were noted in several fatty acids depending upon diet and hormonal state; however, generally diet fat reduction resulted in reduced linoleate and increased oleate contents. Regression analyses showed that fluidity was more dependent upon the lipoprotein cholesterol content than upon fatty acyl composition.

Dietary fat and cholesterol induced modification of minipig lipoprotein fluidity and composition.

1. Miniature swine were fed a low (2.7%) fat control stock diet alone or supplemented with either 20% lard plus 1% cholesterol or 20% lard alone for periods of up to 6 months. 2. Cholesterol feeding reduced VLDL fluidity drastically and LDL fluidity minimally but had no effect on HDL fluidity. 3. Lard feeding had no effect on lipoprotein fluidity. 4. The rigid VLDL produced by cholesterol feeding was enriched in cholesterol and phospholipid contents, similar to beta-VLDL. 5. Plasma cholesterol concentrations were increased by 1.5 to 5-fold in pigs fed stock diets supplemented with 20% lard, with or without added cholesterol, but plasma triacylglycerol concentrations were not affected by either diet modification. 6. Diet effects were complete within 4 weeks with no further changes for periods up to 6 months. 7. Regression of the induced hypercholesterolemia was also accomplished within one month of removing cholesterol from the diet.

Relative effects of feeding saturated fats and cholesterol on fluidity of rabbit lipoproteins.

1. The effects of saturated fat and cholesterol on lipoprotein fluidity were tested in New Zealand white rabbits fed diets containing corn oil (CO) or cocoa butter (CB) with and without added 0.2% cholesterol. 2. Saturated fats had little effect on fluidity in any lipoprotein fraction. 3. Cholesterol feeding dramatically reduced fluidity in VLDL and LDL, but minimal change was noted in HDL. 4. Cholesterol-fed rabbits were hypercholesteroloemic throughout the 10-month study. 5. The rabbits became adapted to cholesterol feeding as VLDL became more fluid with time.