Transmission of angiosarcomas from a common multiorgan donor to four transplant recipients.

We describe the donor tumor transmission of metastatic angiosarcomas to four transplant recipients through transplantation of deceased-donor organs, i.e. kidneys, lung and liver, from an apparently unaffected common female multiorgan donor. Fluorescent in situ hybridization of angiosarcoma cells confirmed that the tumor was of female donor's origin in male kidney recipients. Recent literature associated increased urokinase-plasminogen-activator-receptor (uPAR) and plasma soluble urokinase-plasminogen-activator-receptor (suPAR) levels with metastatic malignancies. Now we found that, compared to baseline levels, both deceased-donor kidney recipients showed increased uPAR transcripts in mononuclear cells as well as increased plasma suPAR levels after the diagnosis of metastatic angiosarcomas, i.e. 4 months after donor tumor transmission. These results show an association of uPAR/suPAR in donor tumor transmission of metastatic angiosarcomas in humans.

Cardiac metabolic and hemodynamic effects of insulin in patients with coronary artery disease.

To assess the effects of insulin in stable coronary artery disease (CAD), 2 U i.v. insulin was given to 9 control and 10 CAD patients during coronary sinus catheterization. Hemodynamic and metabolic data were obtained before and for 90 min after insulin injection. Insulin induced no changes in heart rate, mean aortic pressure, rate-pressure product, coronary sinus flow, or coronary resistance. Metabolic changes were similar in both groups and included 1) 30% decrease of arterial glucose (P less than .001) and 3-fold increase of myocardial glucose uptake (P less than .001), 2) 1.5- to 2.5-fold elevation of arterial lactate (P less than .001) and myocardial lactate usage (P less than .001), respectively, 3) 50-70% suppression of arterial levels (P less than .001) and myocardial uptake of free fatty acids (P less than .01), and 4) 10% reduction of myocardial net oxygen consumption (P less than .05). Myocardial citrate efflux increased in the CAD patients (P less than .05), whereas alanine release rose only in control patients (P less than .01), suggesting that glucose enters glycogen production in the CAD patients and pyruvate production in the control patients to a high degree. Myocardial glutamate uptake remained unchanged. In conclusion, insulin sensitivity was not altered in CAD. The insulin-induced shift from myocardial free fatty acid to carbohydrate usage may be beneficial to the ischemic heart by increasing glycogen stores, saving oxygen, and inhibiting an excess free-fatty acid concentration, which may be toxic during ischemia.

Comparison of non-collagen protein and total creatine as reference for determination of energy stores in endomyocardial biopsies.

OBJECTIVE: The aim was to establish a reliable reference system for biochemical measurements in endomyocardial biopsies. METHODS: Myocardial tissue samples were obtained from pigs before and after cardioplegic arrest and reperfusion. Non-collagen protein content was evaluated as a non-specific reference system and compared with total creatine content representing a specific myocardial reference system. The influence of base strength, extraction temperature, and extraction time on protein yields was determined in tissue precipitates redissolved in NaOH. Interference from protein of collagenous origin was excluded by hydroxyproline determinations. Variability of myocardial ATP content in relation to non-collagen protein and total creatine was compared in endomyocardial biopsies taken before and after cardioplegic arrest and reperfusion. RESULTS: The two methods showed comparable analytical precision. Apart from an interference in 1.0 mol.litre-1 NaOH for extended extraction periods at high temperatures, myocardial protein yields increased with increasing base strength, extraction temperature, and extraction time. During cardioplegic arrest and reperfusion heart weight increased due to oedema. Simultaneously, myocardial non-collagen protein content decreased. No change in total creatine was found during cardioplegic arrest but there was a significant loss of creatine after reperfusion. Comparison of variability in myocardial ATP content with non-collagen protein or total creatine as reference systems revealed no difference. CONCLUSIONS: Determination of non-collagen protein can be optimised with standardised conditions for protein extraction in tissue precipitates. Employment of total creatine as a reference system does not reduce variability of myocardial metabolite determinations in endomyocardial biopsies compared with non-collagen protein. Loss of myocardial creatine may in itself provide additional information about myocardial injury but this makes it unsuitable as a reference system for measuring metabolic changes during reperfusion. Multiple biopsies seem necessary for estimation of myocardial energy stores.

Determination of high energy phosphates and glycogen in cardiac and skeletal muscle biopsies, with special reference to influence of biopsy technique and delayed freezing.

OBJECTIVE: The aim was to clarify the influence of biopsy technique and the effects of temporal delay between sampling and freezing on tissue contents of labile metabolites. METHODS: Cardiac and skeletal muscle concentrations of adenine nucleotides, phosphocreatine, creatine, and glycogen in pigs were determined in endomyocardial and transmural myocardial biopsies and in skeletal muscle biopsies obtained with either endomyocardial bioptome or Tru-cut needle. The influence of the temporal delay between biopsy sampling and freezing was evaluated by keeping the biopsies at room temperature for varying intervals up to 300 s before freezing. RESULTS: Skeletal muscle showed higher concentrations of creatine compounds and lower contents of ADP and AMP than cardiac muscle, whereas ATP, total adenine nucleotide pool, and glycogen were similar. Lower phosphocreatine contents were found both in endomyocardial biopsies and in skeletal muscle biopsies obtained with bioptome compared to transmural myocardial biopsies and skeletal muscle biopsies obtained with Tru-cut needle, respectively. Other metabolites were unaffected by the biopsy technique. With extended delays between biopsy sampling and freezing, an increase in skeletal muscle phosphocreatine averaging 26% after 5 min was observed. In the heart, a decrease in glycogen content averaging 42% after 5 min was found. These changes were not related to the biopsy procedure and were not observed within the period usually required to freeze biopsies in experimental as well as clinical settings. CONCLUSIONS: There are essential metabolic differences between cardiac and skeletal muscle. Low endomyocardial phosphocreatine levels are influenced by the biopsy technique, compromising the use of endomyocardial biopsies for establishing myocardial phosphocreatine content. Reliable measurements of adenine nucleotides and glycogen can be obtained with endomyocardial biopsies.

Microbial phytase addition resulted in a greater increase in phosphorus digestibility in dry-fed compared with liquid-fed non-heat-treated wheat-barley-maize diets for pigs.

The objective was to evaluate the effect of microbial phytase (1250 FTU/kg diet with 88% dry matter (DM)) on apparent total tract digestibility (ATTD) of phosphorus (P) in pigs fed a dry or soaked diet. Twenty-four pigs (65±3 kg) from six litters were used. Pigs were housed in metabolism crates and fed one of four diets for 12 days; 5 days for adaptation and 7 days for total, but separate collection of feces and urine. The basal diet was composed of wheat, barley, maize, soybean meal and no mineral phosphate. Dietary treatments were: basal dry-fed diet (BDD), BDD with microbial phytase (BDD+phy), BDD soaked for 24 h at 20°C before feeding (BDS) and BDS with microbial phytase (BDS+phy). Supplementation of microbial phytase increased ATTD of DM and crude protein (N×6.25) by 2 and 3 percentage units (P<0.0001; P<0.001), respectively. The ATTD of P was affected by the interaction between microbial phytase and soaking (P=0.02). This was due to a greater increase in ATTD of P by soaking of the diet containing solely plant phytase compared with the diet supplemented with microbial phytase: 35%, 65%, 44% and 68% for BDD, BDD+phy, BSD and BSD+phy, respectively. As such, supplementation of microbial phytase increased ATTD of P in the dry-fed diet, but not in the soaked diet. The higher ATTD of P for BDS compared with BDD resulted from the degradation of 54% of the phytate in BDS by wheat and barley phytases during soaking. On the other hand, soaking of BDS+phy did not increase ATTD of P significantly compared with BDD+phy despite that 76% of the phytate in BDS+phy was degraded before feeding. In conclusion, soaking of BDS containing solely plant phytase provided a great potential for increasing ATTD of P. However, this potential was not present when microbial phytase (1250 FTU/kg diet) was supplemented, most likely because soaking of BDS+phy for 24 h at 20°C did not result in a complete degradation of phytate before feeding.

Importance of diet and sex in prevention of coronary artery disease, cancer, osteoporosis, and overweight or underweight: a study of attitudes and practices of Danish primary care physicians.

General practitioners (GPs) in Denmark (n = 374) answered a questionnaire on attitudes toward including information on diet and sex in the prevention of coronary artery disease, cancers, osteoporosis, and weight problems. Risk factors for disease were ranked as follows: smoking, alcohol, stress, diet, physical exercise, heredity, and hygiene. Patients' lack of motivation, insufficient time for each patient, and inadequate knowledge about nutrition were listed by GPs as barriers to dietary counseling. GPs stated that the sex of the patient was important only for counseling on osteoporosis. Lack of time and insufficient knowledge were perceived as barriers to including sex-specific issues in prevention. One-half of the GPs were questioned about the issue of prevention on the basis of female case stories and the other half on the basis of male case stories with identical wording. Responses to the case stories indicated that GPs would give dietary guidance and recommend loss of weight to slightly overweight male patients to a much greater degree than to overweight female patients for prevention of coronary artery disease, give dietary counseling and recommend loss of weight and exercise to female patients more than to male patients for prevention of cancers, recommend a supplement of calcium and vitamin D for prevention of osteoporosis to female patients, and recommend weight gain and discuss psychosocial issues more with underweight female patients than with underweight male patients. Female GPs included measures of prevention such as dietary counseling, exercise prescription, dietary supplement prescription, and discussion of psychosocial issues to a greater extent than did male GPs.

Cardiac energy metabolism in patients with chest pain and normal coronary angiograms.

In 70 patients (94% were a consecutive series) with angina pectoris and normal coronary angiograms, we measured cardiac exchange of lactate, glucose, free fatty acids (FFAs), glutamate, alanine, citrate, and oxygen together with coronary sinus blood flow and blood pressure in response to pacing (150 beats/min). Twelve patients had an abnormal exercise stress test; 26 developed ST depression and 46 had chest pain in response to pacing. Sixteen patients had no ST changes (exercise/ pacing) and no pain during pacing. Pacing induced an increase in cardiac carbohydrate extraction and a decrease in FFA extraction in the entire group of patients. Less than 3% of patients had significant cardiac lactate release in response to pacing, and there were no consistent differences in the cardiac metabolic or hemodynamic responses between patient groups. The pacing-induced shift from FFA to carbohydrate extraction probably reflects the cardiac response to an acute workload. A definite sign of cardiac ischemia (lactate production) was a rare finding in these patients and not confined to the demonstration of electrocardiographic signs of ischemia.

Metabolic and hemodynamic effects of nicardipine during pacing-induced angina pectoris.

During repeat exercise testing in 10 patients with stable angina, individual optimal doses of nicardipine were determined. Hemodynamic values and cardiac metabolism were studied during 2 pacing periods carried out before and after this dose (mean 5.3 mg). Postpacing ST-segment depression diminished (1 mm) after nicardipine administration (p less than 0.05), whereas pacing time to onset of angina did not change. Nicardipine administration increased heart rate 16% (p less than 0.005) and reduced systolic (10%) and diastolic (8%) blood pressures (both p less than 0.005). Coronary blood flow increased 16% (p less than 0.05) and coronary vascular resistance decreased 24% (p less than 0.01). Myocardial oxygen consumption was unchanged despite an 11% decrease in rate-pressure product during pacing (p less than 0.02). In the control state before nicardipine administration, metabolic signs of ischemia included release of lactate across the heart in 7 patients, decreased mean free fatty acid and glutamate uptake and alanine release during pacing, together with increased glucose uptake and citrate release during recovery. After nicardipine lactate release decreased in 5 of the 7 patients, pacing no longer changed free fatty acid, glutamate and alanine uptake/release from the level at rest. During recovery glucose uptake was reduced and citrate release was unaffected. The hemodynamic data indicate that nicardipine is a systemic and coronary vasodilator, increasing oxygen supply to the ischemic myocardium. The metabolic results indicate a change in substrate utilization toward that of normal heart, suggesting improved aerobic energy supply.

Altered global myocardial substrate preference at rest and during pacing in coronary artery disease with stable angina pectoris.

In 21 control subjects with atypical chest pains and normal coronary arteries and in 64 patients with stable angina and coronary artery disease (CAD), myocardial exchanges of free fatty acids, glucose, lactate, citrate, glutamate, alanine and oxygen were determined before, during and after pacing. At rest, myocardial uptake of fatty acids was 50% lower in CAD patients than in the control subjects (p less than 0.001), whereas uptakes of glucose and lactate were twice as high (p less than 0.01). CAD patients showed increased myocardial glutamate uptake (p less than 0.001) and alanine release (p less than 0.001). In control subjects, myocardial fatty acid uptake was directly related (r = 0.54, p less than 0.01), whereas uptakes of glucose (r = -0.42, p less than 0.05) and lactate (r = -0.46, p less than 0.05) were inversely related to arterial fatty acid levels. Citrate release was inversely related to glucose uptake (R = 0.44, p less than 0.05). These relations were absent in CAD patients. Glutamate consumption correlated only with glucose uptake in CAD patients (p less than 0.001) but did so with lactate uptake and alanine release in all individuals (p less than 0.001). Pacing caused angina in the CAD patients but not in the control subjects. Pacing induced no metabolic changes among control subjects but provoked myocardial lactate release in 40 CAD patients, including an additional decrease of fatty acid uptake (p less than 0.05) and increase of glucose uptake (p less than 0.05) compared with resting levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Antiischemic and metabolic effects of glutamate during pacing in patients with stable angina pectoris secondary to either coronary artery disease or syndrome X.

The effects of glutamate on anginal threshold, cardiac metabolism and hemodynamics were studied in 11 patients with stable angina pectoris, positive stress test results, and pacing-induced myocardial lactate release due to coronary artery disease (CAD) (n = 9) or syndrome X (n = 2). Data were obtained before, during and after 2 identical periods of coronary sinus pacing, the second being preceded by an intravenous injection of monosodium glutamate 1.2 (n = 7) or 2.5 (n = 4) mg/kg body weight. After glutamate administration, pacing time to onset of angina increased from mean +/- standard deviation 103 +/- 53 to 166 +/- 71 seconds (p less than 0.01) and ST-segment depression after pacing decreased from 2.3 +/- 1.0 to 1.6 +/- 1.1 mm (p less than 0.01). Arterial glutamate concentration increased 60% (p less than 0.01) after the low dose and 150% (p less than 0.01) after the high dose of glutamate. Regardless of dose, myocardial glutamate uptake increased by 25% (p less than 0.01). Pacing-induced cardiac release of lactate diminished 50% (p less than 0.05), whereas the releases of xanthine and hypoxanthine were unchanged by glutamate. Arterial free fatty acids decreased 20% (p less than 0.01). Circulating levels and cardiac exchanges of alanine, glucose and citrate were unchanged. Glutamate did not influence heart rate, arterial blood pressure, coronary blood flow, coronary vascular resistance or myocardial oxygen consumption. One patient complained of short-lasting burning sensations after receiving the high glutamate dose. In conclusion, augmented provision of glutamate enhances pacing tolerance in stable angina, presumably by a metabolic improvement of cardiac energy production during ischemia.

Effects of glutamate on exercise tolerance and circulating substrate levels in stable angina pectoris.

The effects of glutamate on exercise tolerance, ischemic threshold and venous substrate concentrations were studied in 20 patients with stable angina pectoris and positive stress tests. Each patient underwent 4 upright bicycle exercise tests on consecutive days. The first and fourth tests were performed without medication while the second and third tests were preceded by a low and high bolus dose of monosodium glutamate, either 0.8 and 1.5 mg/kg body weight intravenously (10 patients) or 40 and 80 mg/kg orally (10 patients). Comparison of the first and fourth tests revealed good reproducibility of electrocardiographic, hemodynamic and metabolic data. Glutamate increased exercise duration (p less than 0.05) in a dose-related way when given intravenously (59 +/- 14 and 153 +/- 14 seconds) and when given orally (53 +/- 21 and 90 +/- 23 seconds; all data are mean +/- standard error of the mean). It also delayed the onset of ST-segment depression (p less than 0.05) by 73 +/- 19, 120 +/- 23, 62 +/- 27 and 80 +/- 30 seconds, respectively. Hemodynamics were not changed by glutamate at rest or at comparable workloads, but at onset of ST-segment depression the heart rate-blood pressure product was increased (p less than 0.05). Glutamate administration induced dose-related 1.5- to 10-fold elevations in plasma glutamate, 15 to 50% decreases in plasma free fatty acids (p less than 0.05) and 5 to 30% increases in plasma alanine contents. Circulating levels of glucose, lactate, citrate and albumin were not modified by glutamate.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of intravenous glutamate on substrate availability and utilization across the human heart and leg.

To study the effect of monosodium glutamate on hemodynamics and on substrate metabolism in cardiac and skeletal muscle, an intravenous (IV) dose of 1.2, 2.5, or 5.0 mg/kg body weight was administered to 27 patients during arterial-coronary sinus catheterization (15 patients) or arterial-femoral vein catheterization (13 patients). Data were obtained for 25 minutes after the injection. Arterial glutamate concentrations increased 2.5-5 fold in a dose-related manner. Glutamate administration reduced arterial levels of free fatty acids by 25% (P less than .001), of lactate by 13% (P less than .05), and of alanine by 6% (P less than .05). Arterial glucose increased by 10% (P less than .001) and arterial insulin was increased threefold (P less than .01). Myocardial uptake of free fatty acids decreased by 25% (P less than .001), whereas uptakes of glutamate and glucose increased by 60% (P less than .001) and 100% (P less than .001), respectively. Cardiac release of citrate increased transiently (P less than .05), whereas consumption of lactate and releases of alanine were unchanged by the glutamate. Across the leg, the arteriovenous differences of glutamate were elevated threefold to eightfold (dose-related) (P less than .001), and that of glucose was doubled (P less than .01). The release of citrate increased (P less than .01). Arterial-femoral vein gradients of free fatty acids, lactate, and alanine remained unchanged. Heart rate, blood pressure, coronary sinus flow, coronary vascular resistance, and cardiac oxygen uptake were unmodified by glutamate. Six patients complained of short-lasting burning sensations after the highest glutamate doses. In conclusion, glutamate administration stimulates insulin secretion and changes substrate availability and utilization in human cardiac and skeletal muscle from free fatty acids toward glucose and glutamate.

Simultaneous determination of citalopram, fluoxetine, paroxetine and their metabolites in plasma by temperature-programmed packed capillary liquid chromatography with on-column focusing of large injection volumes.

A miniaturized temperature-programmed packed capillary liquid chromatographic method with on-column large volume injection and UV detection for the simultaneous determination of the three selective serotonin reuptake inhibitors citalopram, fluoxetine, paroxetine and their metabolites in plasma is presented. An established reversed-phase C8 solid-phase extraction method was employed, and the separation was carried out on a 3.5-microm Kromasil C18 0.32x300 mm column with temperature-programming from 35 (3 min) to 100 degrees C (10 min) at 1.3 degrees C/min. The mobile phase consisted of acetonitrile-45 mM ammonium formate (pH 4.00) (25:75, v/v). The non-eluting sample focusing solvent composition acetonitrile-45 mM ammonium formate (pH 4.00) (3:97, v/v) allowed injection of 10 microl or more of the plasma extracts. The method was validated for the concentration range 0.05-5.0 microM, and the calibration curves were linear with coefficients of correlation >0.993. The limits of quantification for the antidepressants and their metabolites ranged from 0.05 to 0.26 microM. The within and between assay precision of relative peak height were in the range 2-22 and 2-15% relative standard deviation, respectively. The within and between assay recoveries were in the 61-99 and 54-92% range for the antidepressants, respectively, and between 52-102 and 51-102% for the metabolites.

Improved outcome of coronary arterial bypass surgery in a small center after identification and modification of peroperative risk factors.

By uni- and multivariate analysis, predictors of surgical mortality and postoperative angina were identified retrospectively in 189 patients having had coronary arterial bypass surgery over the period 1978-1984. After modification of these risk factors, surgical outcome was followed up in another 178 patients undergoing operation from 1985 to 1987. The surgical mortality of 7% in the first series was closely associated with postoperative signs of acute myocardial injury. All deaths occurred in patients having at least 3 out of 5 pre- and peroperative risk factors: triple vessel/left main coronary arterial disease, incomplete revascularization, no propranolol treatment, Bretschneider cardioplegia other than "HTP"-solution with blood preperfusion and perioperative vasopressor support. The procedures of cardiac protection were modified. St Thomas multidose potassium cardioplegia and general hypothermia were introduced, perioperative propranolol treatment increased and bypass time decreased. Improved cardiac protection with this regime was seen in the patients operated in 1985-1987 when compared with the first series with regard to perioperative vasopressor support (8 vs 33%, P less than 0.001), spontaneous operative defibrillation (72 vs 52%, P less than 0.001), postoperative arrhythmias (20 vs 43%, P less than 0.001), peak levels of serum enzymes (P less than 0.001), myocardial infarction (7 vs 19%, P less than 0.001) and hospital mortality (2 vs 7%, P less than 0.05). The incidence of freedom from symptoms at 3 months was also increased in the patients undergoing operation from 1985 to 1987 (72 vs 61%, P less than 0.05). Even small centers can improve their surgical outcome by carefully analysing their own results and modifying the identified risk factors.

Cardiac metabolic effects of heparin differentiate between patients with normal and stenotic coronary arteries.

We studied the effects of heparin, given as 12,500 units intravenously, on cardiac metabolism during catheterization of the coronary sinus at rest and during repeated rapid atrial pacing in 8 patients with stable angina pectoris, positive stress tests and coronary arterial disease and in 8 patients with normal coronary arteries without objective signs of ischemic heart disease. Heparin did not influence angina, ST-segment depression or myocardial lactate production induced by pacing in the group with diseased coronary arteries. In both groups, heparin increased the arterial levels (70%) and the myocardial uptake (40-50%) of free fatty acids, the latter only during non-ischemic conditions. Myocardial net uptakes of glucose, lactate and glutamate and the release of alanine were reduced by heparin in the subjects with normal coronary arteries but not in those with ischemic heart disease. Myocardial oxygen consumption was unchanged. In the patients with normal coronary arteries, the levels of free fatty acid in the arteries were positively related to myocardial uptake of fatty acids and the release of citrate but inversely related to cardiac uptake of lactate and glucose. These relations were lacking in the patients with diseased coronary arteries. The metabolic effects of heparin on the heart, therefore, were diminished in patients with ischemic heart disease when compared to controls. This is probably due to an altered regulation of substrate preference in ischemic hearts.

Atrial natriuretic peptide during pacing in controls and patients with coronary arterial disease.

At rest, during cardiac catheterization, aortic plasma levels of immunoreactive atrial natriuretic peptide did not differ between 10 controls with atypical chest pains and normal coronary arteries and 9 patients with stable angina pectoris and coronary arterial disease (55.2 +/- 19.8 vs. 64.8 +/- 19.8 pg/ml, NS). Nor did atrial natriuretic peptide values differ between the two groups during or after atrial pacing (150 beats/minute), which induced electrocardiographic and metabolic signs of acute myocardial ischaemia in the patients with coronary arterial disease but in none of the controls. Pacing, when carried out for more than 300 seconds, induced an increase of plasma atrial natriuretic peptide that correlated with duration of pacing (r = 0.80, P less than 0.001), and similarly in controls and patients with coronary arterial disease. In a second part of the study, which included 2 controls and 2 patients with coronary arterial disease, post-pacing coronary sinus concentrations of atrial natriuretic peptide were 10-20 times higher than peripheral levels (415- greater than 890 pg/ml). The concentration of atrial natriuretic peptide rose as blood from the caval veins (34 +/- 7 pg/ml) entered the right atrium (56 +/- 24 pg/ml), but thereafter was unchanged in the pulmonary artery (51 +/- 3 pg/ml) and the aorta (46 +/- 9 pg/ml). In conclusion, the results gave no evidence for ischaemic heart disease without congestive cardiac failure to be associated with altered levels of atrial natriuretic peptide. It was confirmed that atrial pacing stimulates the secretion of atrial natriuretic peptide which is produced by the heart and released via the coronary sinus into the circulation.

Exploitation of elasticity as a biomechanical property in the production of graphic stroke sequences.

In the present study we report several findings which indicate that subjects exploit elasticity of muscles and tendons as a biomechanical property of the motor system in the execution of graphic stroke sequences. The drawing movements of 15 right-handed subjects were analyzed, who copied a geometrical pattern consisting of four line segments. Three of these segments were connected by an acute and an obtuse angle. A first analysis concerning stroke-direction preferences shows that subjects tended to produce final strokes in preferred movement directions and obeyed an end-state stability constraint. Subsequently, we analyzed the copying movements with respect to (1) pauses at acute and obtuse angles, (2) local deviations in angle size, and (3) size variations of the strokes surrounding the angles. The results reveal a higher incidence of pauses at obtuse than at acute angles. Furthermore, a local sharpening of angles was found which was most pronounced at obtuse angles. Finally, systematic size variations of the strokes surrounding the angles were found. The results are considered to reflect the functional use of elasticity during task performance. It is concluded that biomechanical properties of the motor system significantly influence higher-order preparatory processes involved in multi-trajectory control.

Low-frequency periodicity in the coordination of progressive handwriting.

The paper addresses the question how the effector segments are coordinated during handwriting, in particular as a function of the left-to-right progression within words. It studies the phase relations between wrist and finger-joint rotations during a repetitive graphic task (long words consisting of letters 'e'), and it subjects the resulting continuous phase-relation plots to autocorrelation analysis. A novel phenomenon, viz. that of low-frequency (1-Hz) periodicity, is observed which presumably reflects adjustments of the coordination pattern about once per second, i.e., after every three or four letters 'e'. Moreover, word length and word position are found to affect this periodicity in a predictable manner. These results are related to those of an earlier study which used an ad-hoc method of analysing wrist-finger coordination adjustments. The paper underlines the value of phase-relation analysis for certain graphic tasks, but it also points out its limitations for this purpose.

Phonological and orthographic demands in the production of handwriting.

In an experimental handwriting task, with two parts, we varied the phonological and orthographic complexity of visually presented nonwords. Twelve adult subjects had to write these nonwords in shorthand as well as in Latin script. Phonological complexity was varied by presenting a nonword which included two identical vowel characters. These were either phonologically similar (simple condition) or phonologically different (complex condition). Orthographic complexity was varied by using nonwords which either have a graphemic format for shorthand that corresponds with the graphemic format that is applied for Latin script (simple condition) or a graphemic format for shorthand which is discrepant from the Latin script format (complex condition). It appeared that a higher degree of phonological and orthographic complexity led to a slower and less fluent performance in graphemes that preceded the actual locus of complexity of the nonword. Furthermore, complexity effects were by far the strongest under the production of shorthand. The results are interpreted from the point of view of a psychomotor theory of handwriting, which assumes that the spelling process of visually presented nonwords may follow a phonological or an orthographic (sublexical) route. The finding that orthographic complexity interferes with the production of a phonologically oriented task such as shorthand is interpreted as evidence in favour of an interactive transmission of information between these two processing routes.

Functional properties of graphic workspace: assessment by means of a 3D geometric arm model.

Computer simulations aimed at assessing functional characteristics of the graphic workspace are presented. The simulations involve a 10-df kinematic model of the distal part of the writing arm, and yield the effective workspace of the pen tip under two types of kinematic constraints. The first constraint involves fixing the forearm under various pronation angles, the second governs the protrusion of the pen tip from the finger tips. The effective workspace is analyzed in terms of the effort required to reach the various locations in it, where effort is defined in terms of the joint angles adopted by the wrist and fingers to reach each location. The simulation results show agreements between the distribution of required effort over the workspace and known stroke-direction preferences in drawing. Furthermore, they predict shifts in the biases that are thought to lead to these preferences as a function of both hand pronation and pen protrusion.