Showing papers by "Maastricht University published in 1988"

Length of excitation wave and susceptibility to reentrant atrial arrhythmias in normal conscious dogs.

Abstract: We calculated the wavelength of the atrial impulse in chronically instrumented conscious dogs by measuring both conduction velocity and refractory period: wavelength = refractory period X conduction velocity. Implantation of multiple stimulating and recording electrodes allowed wavelength determination at four different areas: the right and left parts of Bachmann's bundle and the free walls of the right and left atria. During programmed electrical stimulation, three types of arrhythmias were observed: rapid repetitive responses, atrial flutter, and atrial fibrillation. During normal rhythm, the wavelength of the atrial impulse varied between 14 and 18 cm. Premature beats had a shorter wavelength, depending on the degree of prematurity. Premature beats that evoked rapid repetitive responses showed a critical shortening of the wavelength below 12.3 cm. Episodes of atrial flutter were induced at a wavelength below 9.7 cm, while fibrillation occurred at wavelengths shorter than 7.8 cm. We correlated the induction of these arrhythmias with the values of refractory period, conduction velocity, and wavelength during control and during administration of several drugs. Intravenous administration of acetylcholine shortened the wavelength by 30-40%, mainly because of refractory period shortening. Both propafenone and lidocaine had strong but opposite effects on refractoriness and conduction and, consequently, little effect on the wavelength. Quinidine markedly prolonged the refractory period, but prolongation of wavelength was less because of a simultaneous decrease in conduction velocity. d-Sotalol also increased refractory period, but because it had no appreciable effect on conduction velocity, this drug was the most effective in prolongation of wavelength. Linear discriminant analysis of the data showed that the refractory period and the conduction velocity each were poor parameters to predict the occurrence of the different arrhythmias (predictive value 48% and 38%, respectively). The combination of both properties, however, as expressed in the wavelength, was a more reliable index that predicted the induction of the different arrhythmias correctly in 75% of the cases. We conclude that the wavelength is a useful parameter for evaluating antiarrhythmic drugs.

Overtraining in elite athletes. Review and directions for the future.

Abstract: Overtraining is an imbalance between training and recovery. Short term overtraining or ‘over-reaching’ is reversible within days to weeks. Fatigue accompanied by a number of physical and psychological symptoms in the athlete is an indication of ‘stateness’ or ‘overtraining syndrome’. Staleness is a dysfunction of the neuroendocrine system, localised at hypothalamic level. Staleness may occur when physical and emotional stress exceeds the individual coping capacity. However, the precise mechanism has yet to be established. Clinically the syndrome can be divided into the sympathetic and parasympathetic types, based upon the predominance of sympathetic or parasympathetic activity, respectively. The syndrome and its clinical manifestation can be explained as a stress response. At present, no sensitive and specific tests are available to prevent or diagnose overtraining. The diagnosis is based on the medical history and the clinical presentation. Complete recovery may take weeks to months.

Cause-effect relationships and partially defined Boolean functions

Abstract: This paper investigates the use of Boolean techniques in a systematic study of cause-effect relationships. The model uses partially defined Boolean functions. Procedures are provided to extrapolate from limited observations, concise and meaningful theories to explain the effect under study, and to prevent (or provoke) its occurrence.

Effect of the notochord on the differentiation of a floor plate area in the neural tube of the chick embryo.

Abstract: The role of a notochord fragment on the origin of an additional floor plate area in the neural tube is investigated by quantitative morphological methods. In 1.5 to 2 day chick embryos a notochordal fragment was implanted in close apposition to the lateral wall of the neural groove in the region between prospective wing and leg bud. At 4 days, adjacent to the implant a distinct area of the neural wall was present, which resembled the natural floor plate with respect to its thickness, the abluminal location of elongated nuclei and the absence of neuroblasts. The mitotic density of this area was reduced. This “additional floor plate” was distinct when the experiment was performed at 1.5 days but was hardly recognizable when it was carried out at 2 days. From these results it is concluded that a) the notochord induces floor plate like structures and diminishes proliferation, and b) that the period of floor plate induction by the notochord is very restricted.

A multivariate analysis of pathologic prognostic indicators in large bowel cancer.

Abstract: A multivariate analysis of the pathologic data of 350 patients with primary colorectal cancer was performed. In addition to conventional parameters such as shape and size of the primary tumor, central node involvement, angioinvasive growth, grade, and stage, new variables such as the immunoreactivity patterns of carcinoembryonic antigen (CEA), CA 19-9, mucin, serotonin, secretory component (SC), and the DNA index were tested for their potential prognostic value. Every variable except CA 19-9, serotonin, and DNA showed significant prognostic information in univariate analysis. However, in the multivariate analysis stage was the predictive factor with the highest hazard ratio, but absence of central node involvement, tumors with diameters between 3.5 cm and 6 cm, exophytic tumor growth, well-differentiated tumors, tumors with CEA immunoreactivity, absence for staining with serotonin, and diploid tumors also were included in the relative risk model. Thus, the aforementioned variables appear to play a role in the establishment of a prognostic index.

Wall shear rate in arterioles in vivo: least estimates from platelet velocity profiles

Abstract: Velocity profiles, as determined in vivo in rabbit mesenteric arterioles with fluorescently labeled platelets as natural flow markers, were used to calculate least estimates of the actual wall shea...

Regression analysis of prognostic factors in colorectal cancer after curative resections

Abstract: The clinical, laboratory, and pathologic data of 310 patients who had curative resections were prospectively collected and analyzed in a multiple step wise regression model. Although several factors (i.e., venous invasion) were of importance in univariate analysis, the following conclusions reflect the outcome and relative importance of the regression analysis only. Blood loss as an initial symptom and duration of symptoms were associated with a better prognosis. Location of the primary tumor, age, and sex did not appear to have prognostic value. Observations during operation such as palpable lymph nodes, fixity to adjacent organs, and tumor spill were related to a diminished tumor-free survival. Laboratory data (hemoglobin, leukocytes, ESR, GGTP, SGOT, SGPT, LDH, total protein, CEA) were tested for their potential prognostic values. Only a preoperative low protein level or an elevated CEA level were associated with an increased risk of death due to recurrent tumor. The histopathologic features (stage and grade), with the exception of venous invasion, were of relative importance in the determination of prognosis. The aforementioned variables can be included in a prognostic index on the base of which high-risk groups suitable for adjuvant studies can be identified.

Epidural Spinal Cord Electrical Stimulation Improves Microvascular Blood Flow in Severe Limb Ischemia

Abstract: Epidural spinal cord electrical stimulation (ESES) was performed on 10 patients with severe limb ischemia due to atherosclerotic disease. Microcirculatory parameters were assessed before and after ESES. Bright field microscopy was used to assess capillary diameters and red blood cell (RBC) velocity in the dorsum of the foot. Fluorescein microscopy was used with intravenously injected sodium fluorescein to study capillary density and sodium fluorescein appearance time in the dorsum of the toe. The systolic ankle/arm pressure ratio and toe pressure measurements were used as macrocirculatory parameters. After ESES, clinical improvement was confirmed by intravital microscopy. Capillary density increased (p less than 0.001), RBC velocity in capillaries already perfused before ESES increased from 0.054 mm/sec to 0.762 mm/sec (p less than 0.001), and sodium fluorescein appearance time decreased from 72 to 45 seconds (p less than 0.001). Capillary diameter did not change significantly so that the increase in RBC velocity may be interpreted as enhanced volume flow. Systolic ankle/arm pressure ratios and digital arterial pressure did not change significantly. The current results show that in patients with severe occlusive arterial disease of the lower limbs, ESES recruits capillaries not perfused in the control situation and enhances skin blood flow, improvements that may explain the beneficial clinical effects of ESES.

Weekly recall and dairy estimates of alcohol consumption in a general population survey.

Abstract: Diary and weekly recall measures of alcohol consumption in a representative sample (N = 399) of the Dutch population are compared. The weekly recall method consisted of a personal interview with questions about actual alcohol consumption on the previous 7 days. The diary consisted of 14 daily self-reports of consumption and followed the interview. The diary method yields estimates of consumption that are on average 22% higher than those based on weekly recall measures, reducing total undercoverage by about 11%. The difference between the two methods cannot be attributed to a variation of consumption over weeks but seems to stem from a difference in accuracy of recall. There was an increase in glasses underreported at the upper levels of consumption, but underreporting did not seem to be of a nonlinear nature. Considering the large individual variation in consumption over weeks, the ranking of individuals according to their self-reports is relatively stable across method.

Comparison of doubly labeled water with respirometry at low- and high-activity levels.

Abstract: In previous studies the doubly labeled water method for measuring energy expenditure in free-living humans has been validated against respirometry under sedentary conditions. In the present investigation, energy expenditure is measured simultaneously with doubly labeled water and respirometry at low- and high-activity levels. Over 6 days, five subjects were measured doing mainly sedentary activities like desk work; their average daily metabolic rate was 1.40 +/- 0.09 (SD) times sleeping metabolic rate. Four subjects were measured twice over 3.5 days, including 2 days with heavy bicycle ergometer work, resulting in an average daily metabolic rate of 2.61 +/- 0.25 (SD) times sleeping metabolic rate. At the low-activity level, energy expenditures from the doubly labeled water method were on the average 1.4 +/- 3.9% (SD) larger than those from respirometry. At the high-activity level, the doubly labeled water method yielded values that were 1.0 +/- 7.0% (SD) lower than those from respirometry. Results demonstrate the utility of the doubly labeled water method for the determination of energy expenditure in the range of activity levels in daily life.

The innervation of the spinal dura mater: anatomy and clinical implications.

Abstract: The nerves supplying the spinal dura mater were studied in four human foetuses (16–22 weeks) with the acetylcholinesterasein toto staining method.

Computer aided design and evaluation of limiting and serial dilution experiments

Abstract: Two computer programs are presented which can be used for the determination of the design and the statistical evaluation of data in the context of limiting and serial dilution analysis. The first program (DESIGN) gives the experimenter the opportunity to set up different designs, to improve a design according to several suggestions, to make a picture of a design and to evaluate the results of artificial data, obtained from a random experiment corresponding with the chosen design, until (s)he is convinced of having a suitable design for a particular experiment. The second program (EVALUATE) evaluates the experimental data. The design method and the statistical methods used in the programs have been chosen on practical and theoretical grounds.

Functional aspects of peritoneal macrophages in endometriosis of women

Abstract: Peritoneal fluid was collected in the periovulatory phase of the cycle from 25 women undergoing laparoscopy. Endometriosis was diagnosed in 13 patients (AFS score 1, N = 9; AFS score 2, N = 4) and 12 patients without endometriosis served as controls. In endometriosis patients the total peritoneal fluid cell number and cell concentration was significantly higher than in controls, indicating peritoneal irritation by endometrial implants. Peritoneal fluid macrophages in patients with endometriosis showed significantly increased erythrophagocytosis and lower chemiluminescence than in controls, suggesting an advanced differentiation of the macrophages in endometriosis patients. The macrophages in this stage of differentiation may interfere with gametes and embryos and thus contribute to endometriosis-associated subfertility.

Mechanisms of supraventricular tachycardia

Abstract: Programmed electrical stimulation of the heart in combination with intracardiac recordings has contributed a wealth of new information on the mechanisms and pathways of supraventricular tachycardia in humans. This knowledge has resulted in better treatment approaches to these patients. Questions still remain, however, about the mechanisms of atrial flutter and fibrillation and of some types of atrial tachycardia. The location of the circuit in paroxysmal atrioventricular nodal tachycardia also continues to puzzle investigators. The use of refined mapping techniques during cardiac surgery should provide answers to these questions in the near future.

Prothrombin activation on phospholipid membranes with positive electrostatic potential.

Abstract: The conversion of prothrombin into thrombin, which is a crucial reaction in hemostatic plug formation, is greatly stimulated by phospholipids plus calcium ions. It has been proposed that phospholipid surfaces which promote blood coagulation should have a negative surface charge [Bangham, A. D. (1961) Nature (London) 192, 1197-1198]. However, the experiments that led to this proposal were carried out with one kind of anionic phospholipid (dicetyl phosphate). Here we report that membranes, which contain phosphatidylserine (PS) as the anionic phospholipid, can be made positively charged by incorporation of stearylamine and still exhibit almost full procoagulant and prothrombin-converting activity. This suggests that electrostatic forces contribute negligibly to the binding of coagulation factors to PS-containing membranes. Introduction of stearylamine in membranes containing phosphatidyl-beta-lactate (PLac) causes considerable inhibition of their prothrombin-converting activity. Since PLac and PS only differ by the presence of an amino group in the polar head group, the much higher procoagulant activity of PS-containing vesicles is indicative of an important function of the amino group of PS in the interaction with coagulation factors. We propose that the association of coagulation factors with PS-containing membranes results from complex formation between Ca2+ ions and ligands supplied by the protein and by PS molecules. The ability to form such a complex may well explain why cell membranes with PS have such excellent procoagulant properties.

Heterogeneity in Panel Data: Are There Stable Production Functions?

Abstract: We estimate separate productions functions for approximately 450 manufacturing firms each in France and the United States and for 850 manufacturing firms in Japan, covering the 13 year period 1967-1979, and focus on the wide dispersion in the estimated slope coefficients in all three countries The main question asked Is: "Is this dispersion real?" Could it be just a reflection of sampling variability or is it an indication of real heterogeneity? We estimate the "true" dispersion using three different approaches: Maximum Likelihood, regressions of squares and cross-products of residuals, and Swamy's "residual" method, and try to interpret the somewhat different answers which emerge In particular, we investigate the "reality" of the estimated heterogeneity by looking at its stability over time and by relating it to differences in capital shares and the industrial structure We conclude that the observed heterogeneity is not "real" It is caused by some non-stable misspecification of our simple model, implying that we are unlikely to discern different but stable individual production relations in samples of this size which contain only a limited number of the economically relevant variables

Mortality and quality of life after intensive care for critical illness.

Abstract: Early and late mortality of 313 ICU patients and the quality of life of 118 long term ICU survivors was studied to assess the effectiveness of intensive care for critically ill patients. The survival rate at discharge from the ICU was 76%, falling to 61% at 6 months and to 58% at 1 year. A simplified acute physiology score (SAPS) was recorded on ICU admission, as well as age, length of ICU-stay and the number of complications during intensive care. Information on housing, drug use, hospital admissions, physical condition and functional status 2 years after ICU discharge was collected by means of a questionnaire. No changes in housing occurred, but drug use and the number of hospital admissions were significantly increased. In 21% of the patients a deteriorated physical condition was found, 77% remained unchanged and 2% were improved 2 years after ICU discharge, compared to their condition prior to the acute illness. Major functional impairment was found in 38% of the patients. Although the longterm physical condition and functional status correlated with SAPS and age on ICU admission, the best indicator for quality of life after intensive care proved to be the health status prior to the acute illness.

Determination of total gastric volume, gastric secretion and residual meal using the double sampling technique of George.

Abstract: In literature several techniques are described for the measurement of gastric emptying. One of these is the double sampling technique of George which has the advantage that it enables multiple measurements of total gastric volume in one experiment. In order to estimate net gastric emptying, however, it is important to differentiate between the test meal volume present in the stomach and gastric secretion. In the present study George's technique was extended with a calculation procedure to estimate gastric secretion and net test meal outflow. An in vitro experiment was carried out which showed an accuracy of 5-10% for this method. An in vivo comparison was made with Hunt's chloride technique, which is used for estimating gastric secretion. Sixteen subjects participated in a 60 minute test with water as a test meal. Regression analysis showed a high degree of correlation (R2 = 0.99) between Hunt's method and the proposed method. The data obtained indicate that the proposed method gives a reliable estimation of net gastric emptying and is simple to do as no further measurements have to be carried out other than those needed for George's method.

Cytomegalovirus alters the von Willebrand factor content in human endothelial cells.

Abstract: Cultured human endothelial cells were infected with human cytomegalovirus AD 169 and Kerr. The infection resulted in the appearance of viral antigens in the nuclei of about 10% of the endothelial cells and in the concomitant disappearance of vWF from the infected cells. No differences were observed between endothelial cells from different sources (umbilical cord veins or arteries, adult veins).

Prescription sequence analysis: a new and fast method for assessing certain adverse reactions of prescription drugs in large populations.

Abstract: Prescription sequence analysis (PSA) uses pharmacy-based prescription drug histories to detect a subset of drug effects: those that are themselves indications for changes in the prescribing of another drug. Dutch pharmacy practice ensures virtually complete drug histories. With a database of 25,000 patients, we used PSA to test an alleged link between the use of the anti-vertigo drug flunarizine and mental depression. The temporal sequence of anti-depressant use among flunarizine users shows no clustering that would suggest a causal link. PSA can be run within a few days, which may make it helpful in resolving certain of the periodic controversies about adverse drug reactions.

Comparison of heart rate as a non-invasive determinant of anaerobic threshold with the lactate threshold when cycling.

Abstract: In 9 trained athletes and 4 sedentary subjects the anaerobic threshold was assessed on a cycle ergometer, using the deflection point of heart rate in a protocol in which the workload increased by 10 W every 45 s. The workload at which plasma lactate concentration equalled 4 mmol · l−1 was assessed under steady state conditions on separate occasions. In addition, in 3 subjects the non-invasive anaerobic threshold and the 4 mmol · l−1 lactate level under steady state conditions were assessed on a treadmill. On the cycle ergometer 6 subjects demonstrated a deflection point in the heart rate record, whereas the others failed to do so. The workload at which heart rate departed from linearity in the progressive protocol did not coincide with the steady state 4 mmol · l−1 workload but occurred at a higher workload. On the treadmill no deflection in heart rate was observed. It is concluded that in cyclists a deflection in heart rate does not always occur, and when it does, it does not coincide with the anaerobic threshold determined under steady state conditions.

Assessment of mutagenic activity of repeatedly used deep-frying fats.

Abstract: Mutagenic activity of repeatedly used deep-frying fats was evaluated in relation to chemical characteristics. Deep-frying fat samples were collected from local restaurants and snack bars after sensory indication of abuse. A total of 20 deep-frying fat samples and 2 unused control fat samples was tested. Fat samples were fractionated into non-polar and polar compounds by column chromatography. Amounts of polar compounds obtained ranged from 2% (by weight) for unused fat to 44% for used deep-frying fat. Levels of di- and poly-meric triglycerides (DPTG) were determined using gel-permeation chromatography. DPTG concentrations of 13 used deep-frying fat samples exceeded the treshold level of 10% above which fats are rejected for use. In addition thiobarbituric acid-reactive substances (TBA-RS) were measured. Amounts of TBA-RS were just above detection levels for most fat samples. Five used fat samples, however, contained relatively high concentrations of TBA-RS, ranging from 82 to 177 moles malondialdehyde/g. Non-polar and polar fractions were screened for mutagenic activity using the Ames mutagenicity assay. Mutagenic activity was found predominantly in polar fractions at doses higher than 1 mg/plate in strains TA97, TA100 and TA104, variously with and without metabolic activation. The highest number of mutagenic samples was detected by strain TA97, which appeared to be most sensitive. Some samples exhibited toxic effects. Chromatography blanks, consisting of solvents processed according to the same procedures as used for fat samples, were not mutagenic. Mutagenic activity was also detected in polar material obtained from unused frying fat. Non-polar fractions of unused frying fats showed no mutagenicity. A frying experiment carried out under laboratory conditions indicated that during repeated and prolonged use of deep-frying fat mutagenic polar substances were formed. Fat samples taken after 20 and 40 h of frying contained increasing amounts of polar compounds. Mutagenic activity was highest after 20 h of frying but was slightly decreased after 40 h of frying. At this stage, however, mutagens also appeared in the non-polar fraction. Mutagenic activity of polar fractions of used deep-frying fats in strain TA97 was positively correlated with levels of TBA-RS, which may indicate the involvement of lipid oxidation products in mutagenicity of used deep-frying fats. No significant correlations were found with other chemical characteristics. In the process of deep-fat frying numerous degradation products are formed, which may include mutagenic heterocyclic amines and other pyrolysates. At present the specific nature of mutagens formed during deep fat frying is unclear.

Do personal computers make doctors less personal

Abstract: Ten months after the installation of a computer in a general practice surgery a postal survey (piloted questionnaire) was sent to 390 patients. The patients9 views of their relationship with their doctor after the computer was introduced were compared with their view of their relationship before the installation of the computer. More than 96% of the patients (n=263) stated that contact with their doctor was as easy and as personal as before. Most stated that the computer did not influence the duration of the consultation. Eighty one patients (30%) stated, however, that they thought that their privacy was reduced. Unlike studies of patients9 attitudes performed before any actual experience of use of a computer in general practice, this study found that patients have little difficulty in accepting the presence of a computer in the consultation room. Nevertheless, doctors should inform their patients about any connections between their computer and other, external computers to allay fears about a decrease in privacy.