Ectopic beats in heart rate variability analysis: effects of editing on time and frequency domain measures.

BACKGROUND: Various methods can be used to edit biological and technical artefacts in heart rate variability (HRV), but there is relatively little information on the effects of such editing methods on HRV. METHODS: The effects of editing on HRV analysis were studied using R-R interval data of 10 healthy subjects and 10 patients with a previous myocardial infarction (MI). R-R interval tachograms of verified sinus beats were analyzed from short-term ( approximately 5 min) and long-term ( approximately 24 hours) recordings by eliminating different amounts of real R-R intervals. Three editing methods were applied to these segments: (1) interpolation of degree zero, (2) interpolation of degree one, and (3) deletion without replacement. RESULTS: In time domain analysis of short-term data, the standard deviation of normal-to-normal intervals (SDANN) was least affected by editing, and 30%-50% of the data could be edited by all the three methods without a significant error (< 5%). In the frequency domain analysis, the method of editing resulted in remarkably different changes and errors for both the high-frequency (HF) and the low-frequency (LF) spectral components. The editing methods also yielded in different results in healthy subjects and AMI patients. In 24-hour HRV analysis, up to 50% could be edited by all methods without an error larger than 5% in the analysis of the standard deviation of normal to normal intervals (SDNN). Both interpolation methods also performed well in the editing of the long-term power spectral components for 24-hour data, but with the deletion method, only 5% of the data could be edited without a significant error. CONCLUSIONS: The amount and type of editing R-R interval data have remarkably different effects on various HRV indices. There is no universal method for editing ectopic beats that could be used in both the time-domain and the frequency-domain analysis of HRV.

Fatty acids in substitute formulas for cow's milk allergy.

BACKGROUND: The role of dietary fats in food-related allergic symptoms is increasingly being investigated, since the pivotal role of fat-derived inflammatory substances, e.g., leukotrienes, has been realized. The objective of this study was to describe the fatty acid composition of several commercially available infant formulas that are used as substitutes for adapted cow's milk formulas. METHODS: Samples of nine formulas (two soy, two extensively hydrolyzed casein, three extensively hydrolyzed whey, and two amino-acid-based formulas) and human milk as control were analyzed by gas chromatography. RESULTS: The quantity of fatty acids in the formulas was within the breast-milk range. The percentage of energy derived from fat was below the European Society for Pediatric Gastroenterology and Nutrition recommendations in two cases, but, in the others, it roughly met the recommendations. The percentage of energy derived from linoleic acid was as recommended in all but two cases, where it was higher than recommended. As indicated by a quality indicator, the linoleic to alpha-linolenic acid ratio, altogether four formulas were within either the recommendations or the analyzed breast-milk range. In three cases, it was 1.5-2.5 and in two cases 4-5 times higher than recommended. CONCLUSIONS: There are recommendations for infant formulas to meet nutritional requirements of fat intake, and the analyzed formulas are in most cases within the suggested ranges. However, little is known of requirements in allergic or inflammatory conditions, and whether these described fatty acid compositions are pro- or anti-inflammatory.

Elimination diet in cow's milk allergy: risk for impaired growth in young children.

OBJECTIVE: The objective of this study was to evaluate the nutritional impact of therapeutic elimination diets and to identify risk factors predisposing infants with food allergy to poor growth. STUDY DESIGN: We studied 100 children (mean age 7 months) with atopic dermatitis and challenge-proven cow's milk allergy and evaluated their growth during the symptomatic period before diagnosis and during the therapeutic elimination diet. RESULTS: Clinical control of symptoms was achieved in all patients. The mean length SD score and weight-for-length index of patients decreased compared with those in healthy age-matched children, p < 0.0001 and p = 0.03, respectively. Low serum albumin was present in 6% of the patients, 24% had an abnormal urea concentration, and 8% had a low serum phospholipid docosahexaenoic acid. The delay in growth was more pronounced in a subgroup of patients with early onset than in those with later of symptoms (F = 6.665, p < 0.0001). The duration of breast-feeding correlated positively with the sum of n-3 polyunsaturated fatty acids (r = 0.39, p = 0.001) and with the relative amount of docosahexaenoic acid (r = 0.36, p = 0.002). CONCLUSION: A delicate balance exists between the benefits and the risks of elimination diets.

Impact of solid food on plasma arachidonic and docosahexaenoic acid status of term infants at 8 months of age.

We studied healthy term infants at 6 and 8 months of age to assess the effect of fat-containing solid foods (mashed veal, chicken, and pork provided in ready-to-feed cans) on plasma long-chain polyunsaturated fatty acid (LCP) status. Twenty-one infants were breast-fed and 49 were formula-fed. The fat of the formula contained 16.2% linoleic acid and 2.3% alpha-linolenic acid but no LCPs. The solid-food intake was assessed with a 7-day dietary record. Blood samples were obtained at 6 and 8 months of age, and the fatty acid composition of plasma cholesteryl esters (CE) and phospholipids (PL) were analyzed with capillary gas liquid chromatography. The solid food-derived fat intake was higher in the formula-fed than in the breast-fed group at 6 months, and it increased significantly in both groups (from 0.15 to 0.39 g/kg/day and from 0.24 to 0.43 g/kg/day in breast-fed and formula-fed groups, respectively). The relative plasma concentrations of arachidonic acid (20:4n-6) and docosahexaenoic acid (22:6n-3) were significantly lower in the formula-fed than in the breast-fed group at both 6 and 8 months. In the formula-fed group at 8 months, the proportion of solid food-derived fat correlated positively with plasma 20:4n-6, and the mean percentage of PL-20:4n-6 were 8.0% (95% confidence interval, 7.4-8.5) and 9.0% (8.3-9.7) in its lowest and highest quartiles, respectively. In the breast-fed group, solid food-derived fat intake had no effect on plasma 20:4n-6. The two groups were similar in that solid-food fat had no effect on plasma PL- or CE-22:6n-3. In conclusion, the introduction of meat containing solid foods to formula-fed infants increases their plasma 20:4n-6, but not to levels found in breast-fed infants. Further studies are needed to establish an optimal fatty acid composition of solid foods during weaning.

Leucocyte content in blood processed by autotransfusion devices during open-heart surgery.

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.

Effects of propofol and Intralipid on immune response and prostaglandin E2 production.

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.

Effects of cardiopulmonary bypass on lymphocytes and their subset counts with or without use of autotransfusion devices.

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.

Blood transfusion with autologous and leukocyte-depleted or standard allogeneic red blood cells and the immune response to open heart surgery.

Allogeneic blood transfusions have been associated with impaired outcome in surgical patients. This effect may be mediated by leukocytes. Animal experiments have shown that at least some of the effect can be modified by removal of leukocytes from transfused blood. Therefore, we compared the effects of autologous + leukocyte-depleted against standard allogeneic red blood cell transfusion on postoperative immunosuppression in 24 men undergoing coronary artery bypass surgery. In the autologous + leukocyte-depleted red blood cell transfusion group, patients received 800 +/- 200 mL (mean +/- SD) autologous blood and 2.2 +/- 2.0 units (mean +/- SD) of leukocyte-depleted saline-adenine-glucose-mannitol (SAGM) red blood cells. In the standard red blood cell transfusion group, patients were transfused with 5.5 +/- 1.4 units (mean +/- SD) of SAGM red blood cells. Leukocyte and differential counts; percentages of lymphocyte subpopulations (CD3-, CD4-, CD8-, CD16-, CD20-, CD25-, and B5-positive lymphocytes) and monocytes (CD14); phytohemagglutinin-, concanavalin A-, and pokeweed mitogen-induced and unstimulated proliferation of separated lymphocytes; unstimulated and pokeweed mitogen-stimulated production of IgG, IgM, or IgA; and serum interleukin-6, interleukin-1 beta, and serum C-reactive protein concentrations were measured preoperatively and on postoperative Days 1, 7, and 21. Significant changes were seen in these variables, but there were no differences between the groups. Three of the 12 patients in the allogeneic leukocyte-containing red blood transfusion group became human lymphocyte antigen (HLA) alloimmunized. No infections or other complications occurred in any patients. We conclude that HLA alloimmunization was the only effect that could be modified by use of autologous blood.

The effect of intermaxillary fixation on leukocyte zinc, serum trace elements and nutritional status of patients undergoing maxillofacial surgery.

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.

Serum trace element concentrations and iron metabolism in allogeneic bone marrow transplant recipients.

Serum trace element concentrations, parameters of iron metabolism and serum protein concentrations were investigated in thirteen adult recipients of bone-marrow transplants receiving total parenteral nutrition. Six of the patients died during the four weeks follow-up. Serum zinc concentrations were initially low but increased during the treatment. They also tended to be lower in dying patients than in survivors. Concentrations of serum copper and selenium remained unaltered. Serum iron started to increase during the preconditioning and remained raised for three weeks. No significant changes occurred in serum transferrin levels. Transferrin saturation increased during the preconditioning and started to return to normal after day +14. Serum ferritin was greatly raised from the start and increased further during the procedure. Routine trace element substitution seemed to be sufficient during total parenteral nutrition with the possible exception of zinc. A return to normal transferrin saturation after day +14 may be an early favourable sign that the graft is taking and hematopoietic recovery commencing.

The effect of postoperative radiotherapy on leukocyte zinc, serum trace elements and nutritional status of breast cancer patients.

Mononuclear (MNC) and polymorphonuclear cell (PMNC) zinc content was determined together with serum zinc, copper, selenium and iron concentrations in 24 operable breast cancer patients during and after postoperative radiotherapy. Anthropometric and biochemical indices of nutritional status were measured as background data. The measurements were carried out in the years 1987-1988. Nine patients used unconventional multivitamin or trace element preparations. A steady but statistically insignificant decrease in PMNC zinc was seen during treatment. No changes occurred in MNC zinc. Serum copper levels increased in five patients possibly due to tamoxifen treatment, but no other alterations occurred in serum trace element levels. Appetite was well maintained and nutritional status remained unaltered. Postoperative radiotherapy for breast carcinoma had thus no effect on either trace element or nutritional status. Patient-initiated alternative treatments did not significantly affect their trace element levels. This was probably due to small supplementation doses or irregular use of the preparations.

Plasma antioxidants and coronary heart disease: vitamins C and E, and selenium.

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.

Serum iron, zinc, copper, selenium, and bromide concentrations after coronary bypass operation.

The effect of surgical trauma on serum trace elements was studied in 10 patients undergoing coronary bypass surgery. After the initial decrease due to the hemodilution during operation serum iron, zinc, copper and selenium remained depressed for the immediate postoperative period. Zinc was still at significantly lower level 2 months after the operation. Low serum iron values were also observed. Changes in trace element concentrations were parallel with changes in the concentrations of their transport and binding proteins in the serum. The multielemental technique also measured nonessential bromide, which returned to initial levels in 7 days. Effects of trauma on metabolism, acute phase reaction with redistribution of zinc and copper and losses via increased urinary excretion explain the above changes. Development of a subclinical deficiency of zinc and possibly iron is suggested by the persistence of low serum levels during recovery after operation.

Altered physiological responsiveness and decreased cyclic AMP levels in rat atria after dietary cod liver oil supplementation and its possible association with an increased membrane phospholipid n-3/n-6 fatty acid ratio.

Rats were given a cod liver oil supplemented diet and a standard diet for 4 months. The cod liver oil supplementation resulted in a marked increase in the 20:5(n-3) and 22:6(n-3) fatty acids and a marked decrease in the 20:4(n-6) fatty acid in phosphatidylcholine and ethanolamine of the atrial membrane. Atria from the cod liver oil treated rats showed a marked decrease in contractile force, heart rate and cyclic AMP (cAMP) levels under basal conditions. Stimulation with noradrenaline (1 X 10(-6) M) during high oxygen saturation and reoxygenation resulted in an equal increase in the mechanical responses of the two groups in spite of the significantly different levels of cAMP, whereas in hypoxia, both the cAMP level and the contractile force were significantly lower in the cod liver oil treated group. These results indicate that changes in the fatty acid composition of heart membrane phospholipids is associated with changes in adenylate cyclase activity and physiological function of the rat heart and that an increase in the n-3/n-6 fatty acid ratio in membrane phospholipids of the heart results, when oxygen is abundant in enhanced cAMP-independent contractile activity.

Stability of plasma fatty acids at -20 degrees C and its relationship to antioxidants.

The fatty acid composition of cholesteryl esters (CE), triglycerides (TG) and phospholipids (PL) was analysed with gas chromatography before and after 3 years' storage of EDTA plasmas at -20 degrees C. In the three lipid fractions the proportion of polyunsaturated fatty acids (PUFA) with 3 or more double bonds decreased by 14% to 46%, while the proportions of saturated and monounsaturated fatty acids and also of linoleate (18:2 omega 6) showed an increasing trend. The changes tended to be relatively greatest in TG and smallest in PL. The initial concentration of vitamin A correlated negatively with reductions of all 20- to 22-carbon PUFA in CE and with that of arachidonate (20:4 omega 6) and docosahexaenoate (22:6 omega 3) in TG. The change in CE-18:2 omega 6 tended to be inversely correlated with vitamin A. The initial concentration of beta-carotene and the change in CE- and TG-18:3 omega 3 and CE-22:6 omega 3 showed also inverse correlations. Vitamin C, alpha-tocopherol and selenium had only occasional and mostly insignificant associations with the fatty acid alterations. In freshly analysed samples the concentration of vitamin A correlated negatively with the percentage of 18:2 omega 6 in plasma CE, TG and PL and with that of 20:4 omega 6 in platelets, and beta-carotene and alpha-tocopherol had positive correlations with 18:2 omega 6 in most plasma lipid fractions and platelets. Vitamin C and selenium correlated positively with 22:6 omega 3 in plasma, and selenium also with that in platelets.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma concentrations of lidocaine (lignocaine) after cranial subcutaneous injection during neurosurgical operations.

After cranial subcutaneous injection of lidocaine 0.8-3.7 mg/kg+adrenaline (epinephrine) 1:200,000 in neurosurgical patients, fast drug absorption was found with peak plasma concentrations of 0.6-1 microgram/ml in 5-10 min. However, the concentrations remained above the lowest effective antiarrhythmic level of 0.6 microgram/ml for only about 10 min. In one patient, simultaneously administered intravenous lidocaine had an additive effect on those levels. Induced hypotension (sodium nitroprusside) during aneurysm operations decreased the arterial plasma level of lidocaine and was followed by a new peak after discontinuation. Thus the absorption of a drug during induced hypotension from subcutaneous tissue is often erratic.

Plasma lidocaine concentrations after different methods of releasing the tourniquet during intravenous regional anaesthesia.

Different methods of tourniquet release have been proposed to decrease the concentrations of local anaesthetic released into the systemic circulation at the end of intravenous regional anaesthesia. The effect of releasing the tourniquet intermittently with 5 seconds (group I) and 30 seconds (group II) deflation periods or at once (group III) was studied in 25 adult patients after intravenous regional anaesthesia with 40 ml of 0.5% lidocaine. The venous plasma lidocaine concentrations from the contralateral arm were measured by gas chromatography. There was no leakage of lidocaine from the occluded arm into the systemic circulation. The mean maximum plasma lidocaine concentration in group I 1.99 +/- 1.45 (SD) microgram/ml, in group II 1.33 +/- 0.54 microgram/ml and in group III 1.56 +/- 0.88 microgram/ml (P greater than 0.05) was below the toxic concentrations reported in the literature. There were subjective complaints such as dizziness and ringing in the ears in 4 out of the 7 patients in group I, in 2 out of the 9 patients in group II and in one of the 9 patients in group III (P greater than 0.05). There was no correlation between the duration of tourniquet time (range 12-87 minutes) and the maximum plasma lidocaine concentration. The intermittent release of the tourniquet did not decrease the venous plasma lidocaine concentrations in the contralateral arm; neither did comparing the lidocaine pharmacokinetics in 5 patients of group II after tourniquet release and in the 5 healthy volunteers after a single 100 mg intravenous lidocaine injection reveal any differences.

Effect of anaesthesia and surgery on the number of and mitogen-induced transformation of T- and B-lymphocytes.

Lymphocyte responses are affected by anaesthesia and surgery. 52 patients were studied to ascertain the affect on lymphocytic responses of thiopentone +N2O +O2, combined, diethyl ether +N2O +O2, and local anaesthesia in connection with surgery. The variables followed were: the leucocyte and differential count, the T- and B-lymphocyte count, and lymphocyte transformation by phytohaemagglutinin (PHA), concanavalin A (Con A), pokeweed mitogen (PWM), and purified protein derivative of tuberculin (PPD) in cultures using separated lymphocytes and whole blood. Thiopentone +N2O +O2 anaesthesia together with uterine curettage caused a decrease in the total lymphocyte and T-lymphocyte counts. The Con A response of separated lymphocytes decreased, but the response to other mitogens increased. Combined anaesthesia with thiopentone +N2O +O2 + analgesic + muscle relaxant together with surgery decreased the total lymphocyte and T-lymphocyte counts. The separated lymphocytic and whole blood cultures revealed throughout a decrease in the mitogen and PPD responses. Diethyl ether +N2O +O2 and local anaesthesia, both together with surgery, produced no statistically significant changes in the total lymphocyte or in the T- and B-lymphocyte counts. The mitogen and PPD responses in these groups showed throughout a fall in lymphocyte transformation. Neither patient's age, sex, nor the duration of the anaesthesia or operation affected the magnitude of the changes. The increase in the leucocyte count and in the percentage of neutrophils and the decrease in the percentage of eosinophils and lymphocytes and in the mitogen- and PPD-induced lymphocytic responses increased with the severity of the operative trauma. A new finding was the correlation observed between the changes in the leucocyte and differential counts and the decrease of lymphocytic responses in whole blood culture. The findings in this study indicate that operative trauma determine the decrease in lymphocytic responses associated with anaesthesia and surgery.