The Helsinki Declaration, research guidelines and regulations: present and future editorial aspects.
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Biomedical subjects
Publications and source records attributed to M Salo.
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The present study evaluated the effects of propofol and its solvent Intralipid on the immune response and in vivo prostaglandin E2 production in patients during induction of anaesthesia and in healthy volunteers after Intralipid injection. Fifteen female patients (median age 48 years, ASA 1-2) scheduled for uterine dilatation and curettage were randomly assigned to two groups. In group 1 propofol (median dose 3.1 mg.kg-1) and in group 2 thiopentone (median dose 6.0 mg.kg-1) were injected intravenously over 60 s. Surgery was started after collection of the last blood sample. In the second part of this study, Intralipid 10% 0.3 ml.kg-1 was injected intravenously in eight healthy volunteers (four women and four men, median age 32 years) over 60 s. Plasma bicyclo-PGE2 concentrations increased during anaesthesia induction in both anaesthetic groups (p < 0.01). By contrast, no changes were seen in plasma bicyclo-PGE2 concentrations after Intralipid injection in volunteers. Lymphocyte proliferative responses to mitogens did not change during anaesthesia induction in patients. In volunteers, Intralipid injection caused a slight increase in T-cell percentages (p < 0.01) and unstimulated lymphocyte proliferative responses (p < 0.05), but it did not affect other lymphocyte subsets and immunoglobulin production. Intralipid and propofol were not found to be immunosuppressive at clinical doses used during anaesthesia induction.
Earlier studies on propofol have shown increased percentages of T helper cells after minor surgery. In this study, the effects of propofol infusion anaesthesia on the immune response were compared with those of combined isoflurane anaesthesia in 30 patients (median age 47 years, ASA 1-2) undergoing major surgery. The total dose of propofol in the propofol infusion group of 15 women was 860 mg (range 540-1520 mg) and the median end-expiratory isoflurane concentration in the combined isoflurane group of 15 women was 0.6% (range 0.5-0.8). The following were measured; leucocyte and differential counts; percentages of lymphocyte subpopulations (CD3, CD4, CD8, CD19, CD16 and HLA-DR+CD3); phytohaemagglutinin-, concanavalin A-, and pokeweed mitogen-induced and unstimulated lymphocyte proliferation; plasma interleukin-6; serum group II phospholipase A2, C-reactive protein and cortisol concentrations. Measurements were made pre-operatively, at the end of the operation and on the first and fifth postoperative days. No statistically significant overall differences were observed in the immune response between the groups. The serum cortisol response was weaker in the propofol group than in the isoflurane group (p < 0.05). Time-related changes were seen within the groups.
Autologous red blood cells processed by autotransfusion devices have become increasingly common in major surgery. The finished product, however, often contains varying amounts of leucocytes. We compared leucocyte and their differential counts of blood processed by three autotransfusion devices (Haemonetics Cell Saver IV, Dideco Stat and Dideco Stat-P) during open-heart operations on 25 patients. In addition, a zymosan-induced, luminol-enhanced chemiluminescence method was used to evaluate the activity of neutrophils in prepared autologous blood. High leucocyte counts (3.6-10.9 x 10(9)l-1) were found in all saved red blood cell concentrates. The leucocyte counts of autologous blood produced by the Haemonetics device were lowest (P < 0.01) and about one third of the patients' haematocrit-corrected counts. The proportions of neutrophils were higher in salvaged blood than in the blood circulation before anaesthesia or before retransfusion (P < 0.01). However, no general activation of neutrophils was seen, but the increase in chemiluminescence activity of about 30% that was seen in four patients may suggest an increased risk of reperfusion injury in such patients after aortic declamping. In conclusion, all three autotransfusion devices left leucocytes in the processed red blood cell concentrates, although great differences occurred between the devices.
We compared the effects of a centrifugal pump with those of a roller pump on immune responses in 26 coronary artery bypass surgery patients during cardiopulmonary bypass (CPB). The patients were randomly allocated into a (Biomedicus) centrifugal pump group and a (Stöckert) twin roller pump group. Leucocyte and differential counts; percentages of lymphocyte subpopulations (CD3-, CD4-, CD8-, CD16-, CD20- and CD25-positive lymphocytes) and monocytes (CD14); phytohaemagglutinin-, concanavalin A-, and pokeweed mitogen-induced and unstimulated proliferation of separated lymphocytes; unstimulated and pokeweed mitogen-stimulated production of IgG, IgM, or IgA; and plasma fibronectin, C-reactive protein and serum albumin concentrations were measured preoperatively, immediately before CPB, immediately before aortic declamping and on the first postoperative morning. Significant changes were seen in these variables, but no differences occurred between the groups.
Various molecular descriptors, including connectivity indices, sums of the intrinsic state values, electrotopological state indices, topological equivalence indices, kappa indices, normalized Bonchev-Trinajstic and Shannon information indices, Wiener and Platt's F numbers and molecular weight, were calculated for 73 retinoids, whose structures and properties were taken from the literature. A novel methodology using statistical analyses (cluster, factor and stepwise regression) in selecting relevant molecular descriptors for quantitative structure-property relationship (QSPR) studies has been developed. The analyses were used in correlating molecular structure with affinity, pharmacokinetic properties and reversed-phase retention of retinoids.
Lymphocytes and their subset counts were determined in 30 cardiac surgery patients during cardiopulmonary bypass (CPB) with or without use of an autotransfusion device. In the autotransfusion group, centrifuged and washed autologous red blood cells (median 400 mL [range 200-770 mL]) and in the control group corresponding amounts of homologous packed red blood cells (median 500 mL [range 250-750 mL]) were transfused after declamping the aorta. The percentages of T lymphocytes (CD3) and T cytotoxic cells (CD8) increased in both groups (CD3 up to 5%, P < 0.05 and CD8 up to 35%, P < 0.01), but the percentage of T helper cells (CD4) did not change. The ratio of CD4/CD8 cells decreased (up to 34%, P < 0.01). The percentage of naive resting T cells (CD45RA) increased slightly (up to 8%, P < 0.05) whereas the percentages of memory T cells (CD45RO), T cells with IL-2 receptor (CD25), and natural killer cells (CD16) remained unaltered. The percentage of HLA-DR positive lymphocytes increased during CPB (up to 18%, P < 0.05), but it was decreased thereafter (up to 16%, P < 0.05). The percentage of monocytes (CD14) decreased first during CPB in both groups (up to 32%, P < 0.01), but it was higher in the autotransfusion device group (decreased 29% from initial value) than in the control group (decreased 65% from initial value) at the end of CPB (P < 0.05). This study shows that extracorporeal circulation has an effect on lymphocytes and their subset counts. The changes were slightly immunosuppressive. By contrast, use of autotransfusion devices had only minor effects.
This study was set up to evaluate the effects of propofol infusion anaesthesia on immunological function in minor surgery. Twenty-seven patients (median age 51 years, ASA 1-2) scheduled for minor breast surgery were randomly assigned to two groups. Anaesthesia was induced in group 1 with propofol 2.5 mg.kg-1 and maintained with propofol 12 mg.kg-1 x h-1 and 30% O2 in air, whereas in group 2 anaesthesia was induced with thiopentone 4 mg.kg-1 and maintained with 70% N2O in O2. Fentanyl and vecuronium were used in both groups. The percentages of T cells (p < 0.001), B cells (p < 0.01) and memory T cells increased (p < 0.01) in both groups. T helper cell percentages increased in the propofol but not in the thiopentone group (p < 0.05). The percentages of natural killer cells decreased from pre-induction values in both groups (p < 0.001). No changes were seen in lymphocyte proliferative responses. Minor breast surgery under propofol or conventional combined anaesthesia had only minor effects on the immune response. The higher percentage of T helper cells after propofol anaesthesia compared to conventional combined anaesthesia is beneficial, but its clinical importance remains to be determined.
OBJECTIVE: To test propofol lipid emulsion formulation for its immunosuppressive effects. DESIGN: Propofol lipid emulsion and the emulsion alone were tested at increasing concentrations and compared to initial values and between each other. Propofol alone could not be tested due to its insolubility into the culture medium. PATIENTS AND PARTICIPANTS: Lymphocytes from 12 surgical intensive care (ICU) patients (median APACHE score 16 and median TISS score 28) and 12 healthy volunteers. MEASUREMENTS: Phytohaemagglutinin-, concanavalin A- and pokeweed mitogen-induced lymphocyte proliferative responses were measured in the presence of increasing concentrations of propofol lipid emulsion formulation or the lipid emulsion. RESULTS: Lymphocyte proliferative responses from ICU patients were in general on a lower level than in the volunteers. The propofol lipid emulsion formulation (Diprivan) decreased pokeweed mitogen-induced proliferative responses of lymphocytes from ICU patients at propofol concentrations found in the circulation (1-10 micrograms/ml) and the lipid emulsion alon at 100 micrograms/ml triglyceride concentrations while the other mitogen-induced responses were not affected. No changes were observed in the mitogen-induced responses of lymphocytes from healthy volunteers. CONCLUSIONS: Propofol emulsion formulation decreased in surgical intensive care patients pokeweed mitogen-induced lymphocytic responses in vitro at clinically found concentrations, indicating the need for further studies to test B-lymphocyte functions and T-B-lymphocyte co-operation during propofol lipid emulsion administration. (ICU) patients is widespread because of its good control of sedation. Propofol is currently administered in fat emulsion which is considered immunosuppressive during bolus injection or rapid infusion. Therefore, effects of a propofol fat emulsion formulation on proliferative responses of lymphocytes were studied in blood samples obtained from healthy volunteers and ICU patients known to be immunosuppressed.
Mononuclear cell (MNC), polymorphonuclear cell (PMNC) and serum zinc levels were studied in 17 oral surgical patients with intermaxillary fixation. Serum copper, iron, selenium and bromide concentrations were also measured together with common indices of nutritional status. Nine patients received nutritional counselling. Eight patients had, in addition, oral supplementation with a commercial formula. No changes in intracellular or serum zinc levels were seen during the study period. A statistically significant decrease was seen in mean body weight with subsequent changes in anthropometry. Maximal mean weight loss was 6.0 +/- 3.8% in control group and 3.8 +/- 2.7% in supplemental group. The impaired oral intake due to intermaxillary fixation does not interfere significantly with zinc status as estimated by MNC, PMNC or serum zinc levels. The reduction in body weight and anthropometric indices in the relatively short fixation period may be clinically significant in some patients. Supplementation with a commercial formula helps to maintain the nutritional status of these patients.
Alterations have been found to occur in every component of immune response during anaesthesia and surgery. These alterations represent the body's general physiological responses and are mainly dependent on the extent of surgery, as well as other factors such as the patient's age and health status, medication and blood transfusion. Anaesthetic and operative complications have profound effects on these responses. Basically, the immune response to anaesthesia and surgery is a beneficial reaction, needed in local host defences and wound healing and in preventing the body from making autoantibodies against its own tissues. The responses may, however, contribute to the development of postoperative infections and spread of malignant disease. During uncomplicated conventional surgery, the immune response usually passes clinically unnoticed without any harmful effects. Absent responses and excessively high responses, on the other hand, harm the patient. Our understanding of immunological phenomena and our possibilities of controlling mediator activation are now lagging behind the technical advances made in operative treatment. If we want to decrease operative morbidity and mortality to below their present levels, more attention should be directed to immune responses to major surgery, injuries and operative complications with massive mediator release which place the surgical patient at risk. Experimental evidence suggests that results of treatment in injured and operated patients can in the future be improved by controlling immune responses and their mediator systems. Our current level of knowledge of immune responses is already helping us to avoid many immune-mediated complications. However, routine interference with these responses is not indicated.
The aim was to describe the energy intake and composition of the diet of 1200 9-, 12-, 15-, 18-, 21- and 24-year-old Finns in 1986 and changes in their diet from 1980 to 1986. Data on food consumption were collected using the 48 h recall method. In 1980 protein accounted for 14%, fat for 38% and carbohydrates for 48% of total energy intake, and in 1986 for 15%, 38% and 47%, respectively. The mean P/S ratio increased from 0.24 to 0.31 while the regional differences in the intakes of fatty acids remained unchanged, the P/S ratio being higher in urban than in rural areas and higher in western than in eastern Finland. In 1986 the diet of 15-, 18- and 24-year-old males contained more fat, saturated fatty acids and monounsaturated fatty acids but less sucrose than that of females. The difference in the diet between young men and women, if continued, might increase the male/female ratio at risk for coronary heart disease, which is already pronounced in Finland.
Plasma fibronectin is an important opsonic protein of the mononuclear phagocyte system (MPS). In this study, plasma fibronectin concentrations were measured in stored and fresh whole blood, fresh frozen plasma and AGH cryoprecipitate. Stored whole blood had the lowest concentrations (151 +/- 50 mg/l). The concentrations in fresh whole blood plasma (227 +/- 66 mg/l) and fresh frozen plasma (224 +/- 78 mg/l) were similar but significantly higher than in stored whole blood (p less than 0.05). In contrast, AHG cryoprecipitate had the highest fibronectin concentrations (3249 +/- 502 mg/l) (p less than 0.001). In correcting fibronectin deficiency the best results can thus be expected from an infusion of cryoprecipitate, but fresh whole blood and fresh frozen plasma may also increase depressed fibronectin levels.
Regional anaesthesia has many advantages over general anaesthesia in hip surgery. When the effects of total hip replacement under spinal or general anaesthesia were compared in 22 patients, the only difference between the groups occurred in PHA-induced lymphocyte proliferative responses. In contrast, no differences between the groups were observed in leucocyte or differential counts, lymphocyte or subtype counts, most mitogen-induced lymphocyte proliferative responses, NK-cell activity, IgG, IgM or IgA production by unstimulated or PWM-stimulated lymphocytes, proliferative responses of control lymphocytes with 15% patient serum, or chemiluminescence values in phagocytosis of zymosan opsonized with patient serum. Thus, regional anaesthesia is indicated in total hip replacement for reasons other than the immune response.
Plasma fibronectin is important for host defences as an opsonin of the mononuclear phagocyte system (MPS). The effects of three types of plasma substitutes, crystalloid, gelatin and dextran solutions, on plasma fibronectin levels were studied in patients undergoing abdominal surgery in relation to serum total protein and serum C-reactive protein (CRP) levels. Plasma fibronectin levels decreased during induction of anaesthesia and infusion of an electrolyte solution before infusion of the plasma substitute, and they were further decreased during operation after infusion of plasma substitutes and remained depressed on the first postoperative day in all study groups (P less than 0.05-0.01). In the crystalloid and dextran groups, plasma fibronectin levels exceeded preoperative levels by the 4th-5th postoperative day (P less than 0.05-0.01), but in the gelatin solution group they remained depressed (P less than 0.01). Serum total protein levels remained lower than preoperative values throughout the study period (P less than 0.05-0.01), whereas CRP levels were many times higher on days 1 and 4-5 postoperatively in all groups (P less than 0.01).
The possibility of a relation between plasma antioxidants such as vitamins C and E and selenium, and mortality from coronary heart disease (CHD) was examined. A cross-sectional survey was undertaken of random population samples of apparently healthy middle-aged men in four European regions with differing mortalities from CHD [rate/100,000 for men aged 40-49]: north Karelia (eastern Finland) (n = 99) [212/100,000]; south-west Finland (n = 85) [146/100,000]; Scotland (n = 131) [140/100,000]; and south Italy (n = 80) [43/100,000]. Median (5th-95th percentile) plasma vitamin C concentrations were lower in Scotland: 18.2 (5.7-61.3) microM than in other regions: north Karelia 28.4 (6.2-85.2); south-west Finland 33.5 (5.7-76.6); south Italy 38.0 (10.2-69.8) microM (P less than 0.001). The median levels in the four areas did not however reflect the regional CHD mortality rates. Regional differences in plasma vitamin E levels were also observed: Scottish levels were low 20.0 (12.1-29.3) microM (P less than 0.001) and did not differ between the other areas: 23.0 (16.7-35.1), 22.5 (13.7-31.6) and 23.9 (15.6-41.3) microM respectively. The vitamin E gradient could be explained in part by differences in serum cholesterol. However, cholesterol-adjusted vitamin E levels were low in the three high CHD areas: Scotland 3.41 (2.41-4.62); north Karelia 3.53 (2.67-5.18); south-west Finland 3.53 (2.58-4.92); Italy 4.81 (3.25-5.99) mumol/mmol cholesterol (P less than 0.001). Cholesterol-adjusted vitamin E was not lower in north Karelia, the higher CHD mortality area in Finland. Serum selenium values also varied with the area examined and reported low levels in Finland were confirmed. Nevertheless, selenium levels did not correlate with the reported mortality rates of CHD. Thus in our small cross-cultural study the evidence did not support our hypothesis that plasma antioxidants explain regional differences in CHD mortality.
Thiopentone is known to depress several granulocyte and lymphocyte functions. This study assessed the effects of thiopentone on IgG, IgM and IgA production by pokeweed mitogen-activated lymphocytes as a measure of B-lymphocyte function. Thiopentone decreased IgG production at greater than or equal to 25 micrograms ml-1 (91 mumol litre-1) concentrations and that of IgM and IgA at greater than or equal to 50 micrograms ml-1 (182 mumol litre-1) concentrations over 7 days of culture. Preincubation of lymphocytes for 1 h with thiopentone 0-500 micrograms ml-1 (0-1820 mumol litre-1) had no effect on immunoglobulin production, whereas incubation for 2 and 3 h decreased IgG and IgM production with toxic thiopentone concentrations of 500 micrograms ml-1. Hydrocortisone-sensitive suppressor cells and concanavalin A-inducible suppressor cells were more sensitive to high concentrations of thiopentone than the other cell populations. These findings may be important in patients receiving barbiturate treatment for cerebral protection.