Simulated impact of a fish based shift in the population n--3 fatty acids intake on exposure to dioxins and dioxin-like compounds.

Due to the favourable health effects of LC n-3 PUFAs, marine products have been recognised as a food group of special importance in the human diet. However, seafood is susceptible to contamination by lipophilic organic pollutants. The objective of this study was to evaluate intake levels of PCDDs, PCDFs and dioxin-like PCBs, by a probabilistic Monte Carlo procedure, in relation to the recommendation on LC n-3 PUFAs given by Belgian Federal Health Council. Regarding the recommendation, two scenarios were developed differing in LC n-3 PUFAs intake: a 0.3 E% and a 0.46 E% scenario. Total exposure to dioxins and dioxin-like substances in the 0.3 E% LC n-3 PUFAs scenario ranges from 2.31 pg TEQ/kg bw/day at the 5th percentile, over 4.37 pg TEQ/kgbw/day at the 50th percentile to 8.41 pg TEQ/kgbw/day at the 95th percentile. In the 0.46 E% LC n-3 PUFAs scenario, 5, 50 and 95th percentile are exposed to 2.74, 5.52 and 9.98 pg TEQ/kgbw/day, respectively. Therefore, if the recommended LC n-3 PUFAs intake would be based on fish consumption as the only extra source, the majority of the study population would exceed the proposed health based guidance values for dioxins and dioxin-like substances.

A reference data base for multilead electrocardiographic computer measurement programs.

In an effort to standardize and evaluate the performance of electrocardiographic computer measurement programs, a 15 lead reference library has been developed based on simultaneously recorded standard 12 lead and orthogonal XYZ lead data. A set of 250 electrocardiograms (ECGs) with selected abnormalities was analyzed by a group of five referee cardiologists and 11 different 12 lead and 6 XYZ computer programs. Attention was focused on the exact determination of the onsets and offsets of P, QRS and T waves. The referees performed their task on highly amplified, selected complexes from the library in a two round process. Median results of the referees coincided best with the median derived from all programs. An analysis of stability proved that the combined program median was a robust reference. However, some individual program results were widely divergent. Paired t tests demonstrated earlier onset for P and QRS (p less than 0.001), as well as later offset for P and T waves in the median 12 lead than in the XYZ results. Significant differences also existed among results obtained by programs analyzing all standard ECG leads at one time, the so-called multilead programs, and those obtained by the conventional standard three lead analysis programs. As a consequence, the derived P, PR, QRS and QT interval measurements varied quite widely among the various programs. Significant differences were also observed among measurements of Q, R and S duration. Some programs showed Q waves that were on the average 6 ms (p less than 0.001) longer than those of others. This may significantly influence diagnostic performance.(ABSTRACT TRUNCATED AT 250 WORDS)

Criteria for intraventricular conduction disturbances and pre-excitation. World Health Organizational/International Society and Federation for Cardiology Task Force Ad Hoc.

In an effort to standardize terminology and criteria for clinical electrocardiography, and as a follow-up of its work on definitions of terms related to cardiac rhythm, an Ad Hoc Working Group established by the World Health Organization and the International Society and Federation of Cardiology reviewed criteria for the diagnosis of conduction disturbances and pre-excitation. Recommendations resulting from these discussions are summarized for the diagnosis of complete and incomplete right and left bundle branch block, left anterior and left posterior fascicular block, nonspecific intraventricular block, Wolff-Parkinson-White syndrome and related pre-excitation patterns. Criteria for intraatrial conduction disturbances are also briefly reviewed. The criteria are described in clinical terms. A concise description of the criteria using formal Boolean logic is given in the Appendix. For the incorporation into computer electrocardiographic analysis programs, the limits of some interval measurements may need to be adjusted.

Risk assessment of dietary acrylamide intake in Flemish adolescents.

Acrylamide has recently been found in a range of heat treated food items. As it is a neurotoxic agent and a probable, human carcinogen (IARC 2A), human exposure to this chemical might constitute an important public health issue. The purpose of the study was to estimate the acrylamide intake in Flemish adolescents (based on 7-day food record) and to evaluate the possible health risks due to the exposure. The Belgian Federal Agency for the Safety of the Food Chain collected 150 food items from different supermarkets and restaurants to analyse the acrylamide level. The limit of quantitation was 30 microg acrylamide/kg foodstuffs. Exposure modelling was based on Monte Carlo simulations. The estimated dietary intake of acrylamide per person given as the 5th, 50th and 95th percentile were 0.19, 0.51 and 1.09 mircog/kg bw/d. Bread, despite its low acrylamide content, is relevant as a source of acrylamide exposure at the lower percentiles. At higher percentiles the contribution of French fries and crisps is more important. It must be emphasised that the exposure assessment has several limitations. Risk of neurotoxicity seems negligible. The relevance of current intake levels in terms of cancer risk remains a subject of debate.

Severe linear growth retardation in rural Zambian children: the influence of biological variables.

BACKGROUND: The prevalence of stunting in preschool children in Zambia is high; stunting has detrimental effects on concurrent psychomotor development and later working capacity. OBJECTIVE: Our objective was to investigate biological variables that may contribute to linear growth retardation in preschool children in Samfya District, Zambia. DESIGN: Children aged 6-9 mo (n = 108) and 14-20 mo (n = 102) attending mother-and-child health clinics were included. With a mixed-longitudinal design, they were followed up 9 and 21 mo later. Height and weight of children and their mothers were measured. Biochemical measures (eg, serum zinc, retinol, thyrotropin, iron, and acute phase protein concentrations), malaria parasitemia, and intestinal parasitosis were assessed. RESULTS: Height-for-age z scores (HAZ) were low, indicating a high prevalence of stunting (36-79%). Ninety percent of the children were anemic, 53-71% had elevated acute phase proteins, and 80% had malaria parasitemia. Regression analyses showed that maternal height predicted the children's height at 6-9 mo (regression coefficient = 0.05; 95% CI: 0.02, 0.08). The children's height at an early age (6-9 and 14-20 mo) showed a strong relation with their height at later ages (22-30 and 34-41 mo). Serum micronutrient status did not show a significant relation with later HAZ. CONCLUSION: Unlike other studies, we did not identify specific biological factors, such as health and micronutrient status, which contribute to the retardation of linear growth. The normal zinc and iodine statuses of the children suggest that at least these factors are not causal.

Leigh's encephalomyelopathy in a patient with cytochrome c oxidase deficiency in muscle tissue.

A patient is described with subacute necrotizing encephalomyelopathy proven by autopsy. A slight increase of blood pyruvate and lactate levels with an increased lactate/pyruvate ratio and frequently increased beta-hydroxybutyrate/acetoacetate ratio suggested a disorder of mitochondrial oxidation. A cytochrome c oxidase deficiency was shown in peripheral muscle tissue with some residual cytochrome c oxidase activity in heart muscle. Normal cytochrome c oxidase activity was present in liver tissue. Because of the markedly higher levels of pyruvate and lactate in CSF compared with blood and an increased lactate/pyruvate ratio in CSF, there may also have been defective activity of cytochrome c oxidase in brain tissue. After a period of apparently normal development, the child's clinical condition gradually deteriorated and she died at age 6 years due to respiratory insufficiency. This study illustrates the fact that Leigh's disease is not linked to a single inherited molecular defect.

Comparison of the classification ability of the electrocardiogram and vectorcardiogram.

Controversy exists over the classification ability of the standard 12-lead electrocardiogram (EGG) and the vectorcardiogram (VCG). In this study the diagnostic information content and classification performance of the ECG and VCG were examined using multivariate statistical techniques and a large validated data base of 3,266 cases. Logistic classification models were developed to differentiate between 7 diagnostic entities: normal (n = 538), left (n = 557), right (n = 323) and biventricular (n = 437) hypertrophy, and anterior (n = 390), inferior (n = 657) and combined (n = 364) myocardial infarction. The models were obtained from a learning sample (n = 2,446) using an optimal set of computer derived ECG and VCG measurements. They were subsequently applied to a test sample (n = 820). In the learning sample, the discrimination models resulted in a total correct classification rate of 69.6% for the ECG and 69.4% for the VCG. The total accuracy rate was slightly lower in the test set: 66.3% for the ECG and 67.1% for the VCG. The combined use of the best ECG and VCG variables did not increase total diagnostic accuracy. When cases with biventricular hypertrophy and combined infarction were deleted, accuracy rates of more than 80% were achieved for both lead systems. Differences in the classification rates for the subgroups were not statistically significant. Thus, the conventional 12-lead ECG is as good as the VCG for the differential diagnosis of 7 main entities, provided identical procedures are used in the design of the classifiers.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina pectoris and coronary artery disease in severe aortic regurgitation.

A consecutive series of 198 patients (148 men and 50 women, mean age 51 years, range 18 to 76) with pure, isolated, severe aortic regurgitation was retrospectively studied to determine the prevalence of angiographically significant coronary artery disease (CAD) and its relation to angina pectoris and coronary risk factors. Significant CAD (coronary diameter stenoses greater than 50%) was found in 28 patients (14%). Typical angina was present in 18% and atypical chest pain in 16%. Angina alone had a sensitivity of 57% to detect significant CAD. The predictive accuracy of a positive history of angina was 46% and that of a negative test 93%. By using multivariate logistic regression, a risk score could be calculated that increased the sensitivity to 74% at equal specificity. Almost 40% of the total population had a risk score of less than -2.9 (only 1 patient in this group had CAD). It is concluded that coronary arteriography can safely be omitted in many patients with severe aortic regurgitation if they have no symptoms of myocardial ischemia or risk factors known to increase its incidence.

Frequency of angina pectoris and coronary artery disease in severe isolated valvular aortic stenosis.

A consecutive series of 192 patients (121 men and 71 women, mean age 59 years, range 28 to 82) with isolated, severe valvular aortic stenosis was with isolated, severe valvular aortic stenosis was analyzed retrospectively to determine the relation of angina pectoris and coronary risk factors to angiographically significant coronary artery disease (CAD). Significant CAD (diameter reduction greater than or equal to 50%) was found in 47 patients (24%). Angina was present in 83% of them, but it was also found in 61% of the non-CAD patients. This symptom had as a result a low positive predictive value (31%). Of the patients without angina (n = 65) 12% had significant CAD. The negative predictive value of angina alone was thus 88%. By using multivariate logistic regression, a risk score could be calculated based on angina, age and sex, which increased the negative predictive value to 95%. It was concluded that coronary arteriography can only be omitted in severe aortic valvular stenosis, when patients have no angina and when they are less than 40 years of age for men and less than 50 years for women. For all other cases, coronary arteriography should be recommended.

Coronary arterial lesions in young men who survived a first myocardial infarction: clinical and electrocardiographic predictors of multivessel disease.

An analysis was made of clinical and electrocardiographic prognostic determinants of multiple vessel disease in 100 men, aged under 45 years, who survived a myocardial infarction. All patients underwent selective coronary arteriography within 1 year after sustaining a myocardial infarction. Multivessel disease was present in 64 patients; 33 patients had single vessel disease and 3 had either normal coronary arteries or minimal lesions. Exercise stress testing, electrocardiographic location of the infarction, total serum cholesterol and clinical features including body build, arterial blood pressure, smoking habits, family history of coronary artery disease and the presence of angina pectoris either before or after the acute event proved to be poor predictors of multiple vessel disease. Only 74 percent of the patients were correctly classified by a discriminant function analysis. Thus, for prognostic reasons, coronary arteriography seems warranted in young patients after acute myocardial infarction, even in the absence of residual angina or multiple risk factors.

First derivative of the apex cardiogram and systolic time intervals in evaluation of myocardial contractility in man.

The sensitivity of various systolic ... myocardial contractility.

Improvement of automated electrocardiographic diagnosis by combination of computer interpretations of the electrocardiogram and vectorcardiogram.

In the international project "Common Standards for Quantitative Electrocardiography" (CSE), diagnostic results of different computer programs for the interpretation of the electrocardiogram (ECG) and of the vectorcardiogram (VCG) were combined, and it was shown that the "combined program" performs better than each program separately. Because the program MEANS (Modular ECG Analysis System) comprises 2 different classification programs--one for the ECG, the other for the VCG--this allowed investigation of whether the combined interpretations would yield a better diagnostic result than either one separately. This approach requires that a VCG always be recorded in addition to the ECG. To circumvent this complication, the VCG was reconstructed from the simultaneously recorded ECG leads. This reconstructed VCG was then interpreted by the VCG classification program, whereupon the diagnostic interpretations of the ECG and the reconstructed VCG were combined. For the validation, the CSE database of documented ECGs and VCGs (n = 1,220) was used. The combination of the ECG and VCG interpretations yielded a better diagnostic result than each interpretation program separately (total accuracy 74.2% (ECG + VCG) vs 69.8% (ECG) and 70.2% (VCG), p less than 0.001 in both cases). The results for the reconstructed VCG (total accuracy 70.5%) are comparable to those for the ECG and the VCG (p greater than 0.10 in both cases). The performance of the combined interpretations of ECG and reconstructed VCG (total accuracy 73.6%) is approximately the same as that of the combined ECG and VCG (p greater than 0.10). Thus, the performance of an ECG computer program can be improved by incorporating both ECG and VCG classificatory knowledge, using only the ECG itself.

Immediate and short-term results of a 1988-1989 coronary angioplasty registry.

To determine the relevance of recent refinements in angioplasty technology to our particular practice, the records of 507 consecutive patients undergoing a first percutaneous transluminal coronary angioplasty (PTCA) at our center between October 1988 and May 1989 were reviewed. At the time of PTCA, 41% of these patients had class IV angina and 44% were identified as having multivessel disease. Dilatation was attempted in 734 lesions (mean 1.5 per patient), of which 95 (13%) were chronic total occlusions. Overall, 69% of the 734 lesions were judged anatomically complex, and, in dilating these lesions, a rail-type device was used almost exclusively. Successful dilatation was achieved in 659 of the 734 (90%) attempted lesions. There were low incidences of the major complications of death (0.4%), myocardial infarction (1.8%) and emergency bypass surgery (1.8%). Acute rethrombosis occurred in 54 patients (11%). In these patients, initial strategy of repeat dilatation was successful in 38 of 47 patients (81%). Overall, primary clinical success at PTCA was achieved in 480 patients (95%). At a mean follow-up of 7.5 +/- 1.5 months in 497 of the study patients, the event-free rate (freedom from cardiac death, myocardial infarction, repeat PTCA or coronary bypass surgery or recurrence of severe [class III to IV] angina) was 71%. In conclusion, despite the often complex coronary disease in patients currently presenting to our center, a high initial success rate and acceptable short-term outcome of PTCA was achieved.

Immediate and follow-up results of the conservative coronary angioplasty strategy for unstable angina pectoris.

To assess the results of a conservative coronary angioplasty strategy in unstable angina pectoris, the records of 1,421 consecutive patients without previous myocardial infarction undergoing a first percutaneous transluminal coronary angioplasty (PTCA) between 1986 and 1990 were reviewed. Of these patients, 631 had unstable and 790 had stable angina pectoris. Only after an intense effort to medically control symptoms, the unstable patients underwent PTCA at an average of 15.4 days (range 1 to 76) after hospital admission. Primary clinical success was achieved in 91.7% of patients with unstable and in 94.4% of those with stable angina pectoris (p = not significant). In-hospital mortality rates were 0.3 and 0.1%, respectively (p = not significant). Nonfatal in-hospital event rates for acute myocardial infarction, cerebrovascular accident and coronary bypass surgery were only slightly higher in patients with unstable angina pectoris; however, the difference from the stable group was significant when all events were combined (9 vs 5.9%; p less than 0.04). During 6-month follow-up, no significant difference in adverse events was found between the groups. The respective rates for the unstable and stable groups were 0.4 and 0.2% for death, 5.5 and 5.1% for major nonfatal events, and 17.7 and 20.1% for repeat PTCA. These results suggest that use of a conservative PTCA strategy in the treatment of patients with unstable angina pectoris results in favorable and similar immediate and 6-month outcomes compared with those in patients with stable angina pectoris.

Coronary hemodynamics and coronary flow reserve after intracoronary diltiazem in humans.

To analyze the effect of the calcium antagonist diltiazem on coronary hemodynamics, epicardial coronary artery diameter, coronary blood flow and coronary blood flow velocity were assessed at baseline and after a 0.5 mg intracoronary bolus of diltiazem in nonstenotic coronary arteries of awake humans. Patients (n = 20) were first randomized to pretreatment with either placebo (n = 10) or isosorbide dinitrate (0.5 microgram/kg/min infusion; n = 10), and coronary flow reserve was measured before and after administration of diltiazem. There were significant increases in epicardial coronary artery diameter (10%; p = 0.0001) and coronary blood flow (30%; p = 0.0001) in all patients after administration of diltiazem. Whereas basal coronary blood flow velocity increased only slightly (7%; p = not significant), there was a significant decrease in coronary flow reserve (10%; p = 0.004). Increases in coronary diameter and blood flow after diltiazem were comparable in patients pretreated with placebo or nitrates. However, the decrease in coronary flow reserve was significant only in patients pretreated with placebo (19%; p = 0.0008). This reduction in coronary flow reserve could be due to "raising the floor" (increased baseline coronary blood flow) or "lowering the ceiling" (reduction of maximal coronary blood flow).

Hypotension produced by intravenous apomorphine in the anaesthetized dog is not centrally mediated.

1 Intravenous administration of apomorphine (1.25 to 20 microgram/kg) in the anaesthetized dog produced a dose-dependent decrease in blood pressure which was antagonized by haloperidol but not influenced by propranolol or atropine. 2 Intracarotid administration of apomorphine produced a systemic hypotension which was significantly smaller than that seen with intravenous injection. 3 Doses of apomorphine that caused a decrease in blood pressure on intravenous injection, had no effect on blood pressure or caused retching accompanied by an increase in blood pressure on intravertebral or intracisternal administration. The animals showed a marked hypotension on intravertebral or intracisternal injection of clonidine. 4 From these results it is concluded that the hypotension seen with intravenous apomorphine cannot be explained by a central site of action.

Dopamine-induced neurogenic vaso-dilatation in the intact hindleg of the dog.

1 The dopamine-induced neurogenic vasodilation, previously described in the isolated perfused hindleg of the dog, has been studied in anaesthetized dogs with intact circulation in the hindleg. Dopamine was administered intravenously and/or intra-aortically, either as a bolus injection of 4 or 1l mug/kg, or as a continuous infusion of 4, 8, 16 or 32 mug kg-1 min-1. 2 Dopamine, given as a bolus injection or by infusion reversibly inhibited synaptic transmission in the paravertebral lumbar ganglia, studied with preganglionic stimulation at 1Hz. The inhibitory effect decreased gradually when the frequency of stimulation was increased to 16 Hz. The inhibition by dopamine was also present when spontaneous postganglionic activity was recorded. These effects were more pronounced on intra-aortic than on intravenous administration of dopamine. 3 In about half of the animals studied, injection or infusion of dopamine elicited a decrease of vascular resistance in the innervated femoral artery, whereas systemic blood pressure either did not change or decreased. In the denervated femoral artery, an increase in vascular resistance was alway observed. 4 The decrease in femoral vascular resistance was considered to correspond with neurogenic vasodilation caused by paravertebral ganglionic inhibition since (i) it only occurred in the innervated hindleg, (ii) blood pressure did not rise, (iii) this decrease was insensitive to atropine or propranolol and (iv) it was blocked by small doses of haloperidol. When hypovolemic shock was produced, the incidence of the neurogenic decrease of vascular resistance was smaller. 5 Dopamine also increased renal blood flow. This increase was not reduced by the occurrence of the neurogenic vasodilation in the inervated femoral artery. 6 These results are consistent with the idea that the dopamine-induced neurogenic vasodilation, originally described in the isolated perfused hindleg of the dog, also occurs when the circulation to the hindleg is intact. This suggests that, in the dog, also occurs when the circulation to the hindleg is intact. This suggests that, in the dog. the inhibitory effect of dopamine on sympathetic ganglia modulates its peripheral vasoconstrictor effects. In hypovolemic shock, where sympathetic nervous activity is high, the inhibitory effect of dopamine on sympathetic ganglia disappears and its direct vasoconstrictor effect on the vessels dominates.

Stereoselective phosphonylation of human serum proteins by soman.

Phosphonylation has been reported as part of the degradation of soman in human serum. The concentration of phosphonylation sites can be quantified by comparing the degradation in serum, preincubated with soman (all sites occupied), with the degradation in serum not preincubated. The mean value of 73 nM of phosphonylation sites is in agreement with the concentration of active sites of butyrylcholinesterase (EC 3.1.1.8.), which is known to be phosphonylated by soman. Hence, it is concluded that butyrylcholinesterase accounts for all the phosphonylation sites present in human serum. The stereoselectivity of the reaction was investigated by using epimeric pairs of soman, in casu C(+)P(+/-)- and C(-)P(+/-)-soman. In a first approach enzymatic hydrolysis was blocked and the ratios of phosphonylation rate constants, C(+)P(+)/C(+)P(-) and C(-)P(+)/C(-)P(-), were determined to be 0.15 and 0.31, respectively. In a second approach, in untreated serum, the bimolecular phosphonylation rate constants of C(+)P(-)- and C(-)P(-)-soman were determined, neglecting their small hydrolysis rate and taking advantage of the fast enzymatically catalysed disappearance of their respective P(+)-epimeric counterparts. Values for C(+)P(-)- and C(-)P(-)-soman are 3.6 X 10(7) and 0.6 X 10(7) M-1.min-1, respectively. Using a combination of both approaches, a relative ranking of phosphonylation rates of the four isomers was found to be C(+)P(-) much greater than C(+)P(+) approximately equal to C(-)P(-) greater than C(-)P(+).

In vitro degradation of the four isomers of soman in human serum.

Starting from racemic soman (1,2,2-trimethylpropyl methylphosphonofluoridate), the degradation of its four stereoisomers in human serum (25 degrees, pH 8.8), has been studied at the nM level. Phosphylation of serum proteins is eliminated by preincubation of the serum with soman. A capillary gas chromatographic method with nitrogen-phosphorous detection allows the separation of the diastereoisomers. The total hydrolysis (enzymatic and non-enzymatic) rate constants of the isomers can then be resolved indirectly on the basis of the important rate difference between P(+) and P(-) isomers. The enzymatic hydrolysis rate constants are obtained by subtracting, for each isomer, the spontaneous (non-enzymatic) rate constant from the total hydrolysis rate constant. The non-enzymatic part of the hydrolysis is obtained from experiments in serum ultrafiltrate (30,000 NMWL). Enzymatic hydrolysis of C(+) P(+) soman occurs so rapidly that only a lower limit of the rate constant can be given. The other enzymatic rate constants are 0.016 min-1 for C(+)P(-), 0.74 min-1 for C(-)P(+) and 0.028 min-1 for C(-)P(-).

Stereoselective hydrolysis of soman in human plasma and serum.

The contribution of various human serum and plasma fractions to the total hydrolysis rate constants of the four isomers of soman is studied. Spontaneous hydrolysis (as measured in buffer) occurs at a faster rate for the C(+)P(+)- and C(-)P(-)-isomers. A stereoselectively catalyzed hydrolysis of soman occurs in serum fractions IV and V (albumin). In fraction V the C(+)P(+)- and C(-)P(-)-isomers are hydrolyzed at a faster rate than their respective epimers, while in fraction IV-1 a stereoselective effect towards C(+)P(+)-soman is found. All the forementioned contributions, however, are negligible in comparison with the stereoselective enzymatic hydrolysis of the P(+)-isomers. The latter reaction is characterized by a significant lowering of the activation energy as compared with the spontaneous hydrolysis of the P(+)-isomers. Such a lowering in activation energy is not found for the hydrolysis of the P(-)-isomers in whole serum or plasma; hence it can be concluded that a phosphorylphosphatase hydrolyzes the P(+)-isomers in a stereoselective way, the P(-)-isomers either not being affected by this (these) enzyme(s) or the mechanism of catalysis being fundamentally different. This conclusion is in agreement with the observations on the influence of Hg2+ on the hydrolysis of soman in serum; the hydrolysis of the P(+)-isomers is significantly inhibited by 1 mM of Hg2+ while the P(-)-hydrolysis is unaffected by this concentration of Hg2+. The action of some potential inhibitors on this phosphorylphosphatase activity was studied. Iodoacetate did not inhibit nor did Ba2+, Sr2+, Co2+ or Mn2+ show a significant effect on the hydrolysis of the P(+)-isomers. On the other hand the hydrolytic activity in serum was nearly completely inhibited by EDTA but restored upon addition of Ca2+. These findings suggest that this enzymatic activity can be classified as an arylesterase (paraoxonase). Finally, the influence of pH on the hydrolytic activity shows a different pattern for C(+)P(+)- and C(-)P(+)-soman, which may suggest that more than one enzyme is involved in the degradation of soman.