Lessons from the Nordic ICD pilot study.
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Biomedical subjects
Publications and source records attributed to J Koistinen.
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The traditional methods of analyzing heart rate (HR) variability have failed to predict imminent ventricular fibrillation (VF). We sought to determine whether new methods of analyzing RR interval variability based on nonlinear dynamics and fractal analysis may help to detect subtle abnormalities in RR interval behavior before the onset of life-threatening arrhythmias. RR interval dynamics were analyzed from 24-hour Holter recordings of 15 patients who experienced VF during electrocardiographic recording. Thirty patients without spontaneous or inducible arrhythmia events served as a control group in this retrospective case control study. Conventional time- and frequency-domain measurements, the short-term fractal scaling exponent (alpha) obtained by detrended fluctuation analysis, and the slope (beta) of the power-law regression line (log power - log frequency, 10(-4)-10(-2) Hz) of RR interval dynamics were determined. The short-term correlation exponent alpha of RR intervals (0.64 +/- 0.19 vs 1.05 +/- 0.12; p <0.001) and the power-law slope beta (-1.63 +/- 0.28 vs -1.31 +/- 0.20, p <0.001) were lower in the patients before the onset of VF than in the control patients, but the SD and the low-frequency spectral components of RR intervals did not differ between the groups. The short-term scaling exponent performed better than any other measurement of HR variability in differentiating between the patients with VF and controls. Altered fractal correlation properties of HR behavior precede the spontaneous onset of VF. Dynamic analysis methods of analyzing RR intervals may help to identify abnormalities in HR behavior before VF.
Lipophilic organic compounds originating from kraft pulping and papermaking were identified by straight gas chromatography/mass spectrometry (GC/MS) analyses. Samples analyzed included a primary clarifier effluent (PE) and a secondary clarifier effluent (SE) from the activated sludge treatment plant of a Finnish ECF-bleached (Elementally Chlorine Free) kraft pulp and paper mill. Liquid-liquid extraction composition of PE was compared with solid phase extraction (SPE) and dialysis of a semipermeable membrane device (SPMD) exposed to PE. Dichloromethane extracts of particulate material isolated from PE, sludges from both the primary and secondary clarifier, a sediment collected in the vicinity of the mill and whitefish subacutely exposed to the secondary treatment effluent were also investigated. Typical pulp mill-related compounds such as terpenes, terpenoids and aromatic compounds were identified in PE whereas these were non-detectable in SE. For example, thunbergene, thunbergol, squalene, longifolene and derivatives of abietic acid were observed in PE. Alkylated polycyclic aromatics were major compounds identified in the sediment sample with retene (C4-alkyl phenanthrene) as a predominant component.
Dynamics analysis of RR interval behavior and traditional measures of heart rate variability were compared between postinfarction patients with and without vulnerability to ventricular tachyarrhythmias in a case-control study. Short-term fractal correlation of heart rate dynamics was better than traditional measures of heart rate variability in differentiating patients with and without life-threatening arrhythmias.
Polychlorinated diphenyl ethers (PCDEs), 2,3,7,8-substituted polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) were analyzed in seals from the Gulf of Finland and in sediments from the Gulf of Finland and near Gotland. The sediments included one surface core from both sampling sites. The seal material consisted of 14 ringed seals and 6 grey seals that all were found dead and examined for pathology. The main aims were to scrutinize levels and patterns of PCDEs for the first time in seals from the Baltic Sea and to estimate whether chlorinated compounds mentioned have an influence on an exceptional high mortality that occurred among ringed seals in the Gulf of Finland in late 1991. The concentrations of 50 congeners of tetra- through deca-CDEs analyzed ranged from < 0.3 to 62 ng/g lipid weight (lw) in seal blubber, but in the sediments PCDEs were non-detectable (tetra- through hepta-CDEs < 0.1 ng/g dry weight (dw)). In ringed seals with good nutritional status, the concentrations of almost all PCDE congeners were greater in two adult females than in specimens of younger age groups. The concentrations of PCDDs and PCDFs as TCDD-equivalents exceeded those of the coplanar (non-ortho) PCBs in sediments, whereas non- and monoortho PCBs constituted greater toxic loads as those calculated for PCDDs and PCDFs in seals. However, the levels revealed do not explain the high mortality of ringed seals.
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A follow-up study of anti-IgA antibodies in 159 healthy blood donors with severe deficiency of serum IgA (< 0.05 mg/L) and in 45 donors with decreased serum IgA levels (0.05-799 mg/L), identified in 1971-1980, was carried out. Initially anti-IgA antibodies were determined by a hemagglutination (HA) method and two reexaminations were done in 1990-1992 by an enzyme immunoassay. The median follow-up period was 19 years, during which anti-IgA level was changed considerably in only four persons, increased in two, and high level antibodies (> 1/1000 by HA) appeared in two. In reexaminations anti-IgA antibodies were found in 30 (19%) subjects with severe IgA deficiency and the antibody levels remained relatively constant in those who had high and medium antibody levels. Anti-IgA antibodies were not found in subjects with decreased, but detectable serum IgA. Thus it seems that only those healthy adults who have severe IgA deficiency develop anti-IgA antibodies and their anti-IgA levels remain fairly constant. Of the 159 subjects with severe IgA deficiency, 66 had a history of IgA exposure, but no correlation to anti-IgA development was noted.
Finnish human samples from the Helsinki area and Arctic cod samples from Vestertana Fjord (Norway) were analyzed for polychlorinated diphenyl ethers (PCDE) and 2,3,7,8-chloro substituted dibenzo-p-dioxins (PCDD) and dibenzofurans (PCDF). The PCDE, PCDD and PCDF contents in human and animal samples from Finland and elsewhere were briefly reviewed. PCDEs were non-detectable in human liver and testis, but some PCDE congeners were identified in human adipose tissue and fat of boiled Arctic cod liver composite. The contents of PCDEs in Finnish human samples were similar to those reported in the literature for human tissues from North America. The estimated concentrations of PCDEs 99, 147 + 153 (coeluting) and 206 ranged between 2 and 8 ng/g lipid weight (lw) in one Finnish human adipose tissue. The concentrations of PCDE congeners identified in the cod liver fat were between 0.4 and 5 ng/g lw. Of toxic PCDDs and PCDFs, hepta- and octa-CDDs dominated in human. The concentrations of PCDD and PCDF congeners varied from < 2 to 7700 pg/g lw in human. In Arctic cod samples analyzed (muscle tissues of an air dried cod and cod liver fat), 2,3,7,8-tetra-CDF was nearly the only congener of PCDD/PCDFs detected.
Magnesium may be beneficial in the control of ventricular ectopy and supraventricular tachyarrhythmias after coronary artery bypass graft (CABG) surgery, but it is not known whether a high-dose magnesium regimen is superior to a regimen keeping the patient normomagnesemic. A prospective randomized and double-blind clinical comparison was performed in 81 elective CABG patients in order to assess the effects of two different magnesium infusion regimens on electrolyte balance and postoperative arrhythmias. Forty-one patients (high-dose group, H) received 4.2 +/- 0.7 g (mean +/- SD), of magnesium sulfate before cardiopulmonary bypass, followed by an infusion of 11.9 +/- 2.8 g of magnesium chloride until the first postoperative (PO) morning, and a further 5.5 +/- 1.0 g until the second PO morning. Forty patients (low-dose group, L) received magnesium sulfate only after bypass to a total of 2.9 +/- 0.5 g at the first, and 1.4 +/- 0.1 g at the second PO morning. A blood cardioplegia technique was used in both groups, including bolus doses of magnesium chloride to a total of 2.4 +/- 0.6 g and 2.3 +/- 0.6 g to H and L patients, respectively. Continuous Holter tape-recording was used for 12 to 15 hours preoperatively, and for 48 hours postoperatively. Serum magnesium peaked in H patients on the first PO morning at 1.60 +/- 0.25 mmol/L, whereafter it declined to the normal level on the third PO morning. Patients in the L group were normomagnesemic, except after the start of bypass.(ABSTRACT TRUNCATED AT 250 WORDS)
OBJECTIVE: The goal of this study was to assess the effects of a combination of glucose-insulin-potassium (GIK) and the amino acids aspartate and glutamate upon perioperative hemodynamics in coronary surgery patients with unstable angina and/or compromised left ventricular function. DESIGN: Prospective, randomized, and double-blind clinical study. SETTING: Operating theatre and intensive care unit (ICU) of a university hospital. PATIENTS: 44 coronary artery bypass graft (CABG) patients with unstable angina and/or compromised left ventricular function. INTERVENTIONS: 22 patients (group A) were given 1l of an infusion with 250g glucose, 100 I.U. fast-acting human insulin, 72 mmol potassium, 32 mmol magnesium, 20 mmol phosphate, 65 mmol aspartate, and 65 mmol glutamate, while another 22 patients (group C) were given 1l of an infusion with 50 g glucose, 72 mmol potassium, 32 mmol magnesium, and 8 mmol phosphate. The infusion rate was 1.2 ml/kg/h from the anesthesia induction onward to the commencement of cardiopulmonary bypass, when it was reduced to 0.8 ml/kg/h. When 11 had been infused, but not later than 4 a.m., the infusion was continued by giving 10% glucose at the same rate to both groups. Additional insulin (median: 14.2 I.U., range: 0-41.5) or saline was given during bypass to the A and C patients, respectively. A blood cardioplegia technique containing aspartate and glutamate was used in both groups. RESULTS: At aortic cannulation, the cardiac index (CI) had increased from the pre-anesthetic level by 15.3% (mean) (SD: 31.7%) in group A and decreased by 7.7% (15.1%) in C patients, p = 0.0069. Also the changes in stroke index (SI; p = 0.022), left (LVSWI; p = 0.0037) and right ventricular stroke work index (RVSWI; p = 0.0097) were more favorable in group A. Despite longer aortic cross-clamp, p = 0.031, and perfusion times, p = 0.042, in A patients, the change in cardiac index was also better in this group after bypass: At decannulation, the difference between mean values was 31.8%, p = 0.0001, and at arrival in the ICU it was 16.1%, p = 0.028. The same was also seen 8 h postoperatively and on the 1st and 2nd postoperative mornings; p = 0.034, 0.040, and 0.037, respectively (Wilcoxon test). Favorable changes were seen for the A patients also regarding SI at decannulation (p = 0.0002) and after 8 h (p = 0.017); LVSWI at decannulation (p = 0.0002), at arrival in the ICU (p = 0.0023), and after 8 h (p = 0.0011); and RVSWI at decannulation (p = 0.0027), at the ICU (p = 0.021), after 8 h (p = 0.014), and on the 1st postoperative morning (p = 0.039). However, the response to a hemodynamic loading test (6% hydroxyethyl starch 5 ml/kg) was similar in the 2 groups, and there was no difference in the need for inotropic support. CONCLUSIONS: Amino acid-enriched GIK infusion improves hemodynamic function in CABG patients with unstable angina and/or compromised left ventricular function.
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A follow-up study of 204 healthy blood donors with IgA deficiency, identified between 1971 and 1980, was carried out. Sera were initially screened by a double diffusion method and 182 were retested by a more sensitive haemagglutination inhibition method. A reexamination was performed in 1990 and, again, in 1991-1992 using an enzyme immunoassay (EIA) developed for the measurement of very low concentrations of IgA. The median follow-up period was 19 years, and in 159 (78%) subjects no serum IgA could be detected in any of the measurements. In 42 (21%) subjects, serum IgA was detectable (> 0.18 mg/L), but the level was below the lower limit of the reference range for adults (800 mg/L) and remained relatively constant. Three subjects showed minute amounts of IgA by EIA (0.2-3 mg/L) in one of the follow-up samples in 1990-1992, but the level was below the detection limit of the EIA (0.05 mg/L) in the other sample. Thus, not only does primary IgA deficiency appear to be permanent, but also lower than normal serum IgA levels remain the same in healthy adults.
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The frequency of low erythrocyte porphobilinogen deaminase (PBGD) activity was investigated in 2234 blood donors and in 30 patients with acute intermittent porphyria. The mean enzyme activities (+/- SD) were 3.38 +/- 0.58 U and 1.82 +/- 0.41 U, respectively. Eighteen blood donors without any history of symptoms of porphyria or haematological disease had low PBGD activity (less than 2.20 U), and they were studied further. All of them also had subnormal concentrations of the erythrocyte enzyme protein, as determined by an immunological method. Lymphocyte PBGD activity was within the normal range, but this parameter does exhibit a wide overlap between normal and porphyric values. Urinary excretion of porphobilinogen was moderately increased in two of the blood donors. In four of the 18 families of the blood donors with low PBGD activity several first-degree relatives had low erythrocyte enzyme activity, consistent with a dominant mode of inheritance. The 5-aminolaevulinic acid loading-test was normal in the blood donors with familial occurrence of low erythrocyte PBGD. It is concluded that inherited defects in erythrocyte PBGD occurred among Finnish blood donors with a frequency of about 1 in 500. The defects may be identical with those in acute intermittent porphyria (AIP), but other mechanisms are also possible, e.g. a mutation in the erythroid-specific part of the PBGD gene.
A flow cytometer-based microbead immunoassay (MIA) was employed to detect anti-IgA antibodies in patients with IgA deficiency. 3 microns latex particles were coated with purified IgA and serum anti-IgA antibodies of the IgG class were detected with FITC-conjugated anti-human IgG. Antibodies against three different IgA preparations were tested from 22 patients samples as well as 20 controls and compared with a conventional enzyme-linked immunosorbent assay (ELISA) and a passive hemagglutination assay (HA). There was a very close correlation between the results obtained with the MIA and the ELISA assay and between MIA and the HA. Because of the low intra-assay variation and good linearity of the assay, the analysis of one single serum dilution was sufficient to determine the anti-IgA level of a patient and no titration series was required. We conclude that MIA is a satisfactory alternative method for routine anti-IgA antibody determinations. For laboratories already equipped with a flow cytometer the assay is cost effective.