Attention in essential tremor: evidence from event-related potentials.

Clinically subtle executive dysfunctions have recently been described in essential tremor (ET), though the presence of attentional deficits is still unclear. We investigated the psychophysiological aspects of attention in ET, using event-related potentials (ERPs). Twenty-one non-demented patients with ET and 21 age- and sex-matched healthy controls underwent a psychophysiological evaluation. P300 components and the Contingent Negative Variation (CNV) were recorded. The latencies and amplitudes of the P3a and P3b subcomponents and CNV areas were evaluated. Possible correlations between clinical parameters and ERP data were investigated. P3a latency was significantly longer in the ET group (p < 0.05), while no differences emerged between patients and controls in P3b latency. No differences were observed between the two groups in the CNV parameters. ET patients display a difficulty in the response to novelty and in the recruitment of prefrontal attentive circuits, while the memory context-updating process appears to be spared. This selective cognitive dysfunction does not appear to interfere with the attentional set linked to the expectancy evaluated during a complex choice-reaction time task, which is preserved in ET. This multitask psychophysiological approach reveals the presence of a peculiar attentional deficit in patients with ET, thus expanding the clinical features of this disease.

Psychophysiological aspects of voluntary skilled movement after stroke: a follow-up study.

OBJECTIVES: The aim of the study was to follow the psychophysiological evolution of a self-paced voluntary skilled movement in hemiparetic subjects after ischemic stroke by means of a skilled performance task (SPT). The task consisted in starting a sweep of an oscilloscope trace by pushing one button with the left index finger (trigger point), and in stopping it within a central area on the oscilloscope screen, between 40 and 60 ms (correct performance) after the start of the sweep, by pushing the other button with the right index finger. A SPT yields a considerable amount of information on the electrophysiological components, which reflect pre-programming activity (Bereitschaftspotential--BP), control strategies (Skilled Performance Positivity--SPP) and behavioural response (Correct Performances). The study was also aimed at detecting any longitudinal changes in the psychophysiological pattern, as evaluated by the clinical examination and specific motility scales, that parallel motor recovery. METHODS: Movement related potentials (MRPs) were recorded in 12 control subjects and 9 patients in the acute phase, before the start of neurorehabilitation (time 0), when the patients were able to execute an index finger press with the affected hand. The patients (mean age = 62.33 years, SD = 8.17) presented a mild to moderate central arm paresis caused by a first-ever unilateral supratentorial and subcortical ischemic lesion. The subsequent recordings were carried out respectively 3, 9 and 12 months later. RESULTS: At the first recording, hemiparetic patients achieved a significantly lower percentage of correct performances and had a lower BP amplitude than controls (p < 0.001); SPP was absent. The number of correct performances did not improve significantly during the subsequent recordings. BP amplitude showed a mild increase in the second, third and fourth recordings (p < 0.05), while SPP amplitude revealed a slight improvement at the second and a marked improvement at the third and fourth recordings, when there was no longer a statistically significant difference from controls. CONCLUSIONS: Our findings point to an early recovery of pre-programming activity and a delayed improvement in control activity. The delayed development of control activity in the absence of procedural learning, i.e. skill learning through practice, forces patients to exploit attentional strategies to compensate for their procedural learning impairment. SPT shows that the efficacy of physical therapy aimed at motor ability recovery in hemiparetic patients does not keep up with the slow recovery process of an automatic motor level.

Intercepting Parkinson disease non-motor subtypes: A proof-of-principle study in a clinical setting.

The construct of non-motor symptoms (NMS) subtyping in Parkinson Disease (PD) is emerging as a line of research in the light of its potential role in etiopathological interpretation of PD heterogeneity. Different approaches of NMS subtyping have been proposed: an anatomical model suggests that NMS aggregate according to the underpinning pathology; other researchers find aggregation of NMS according to the motor phenotype; the contribution of genetic background to NMS has also been assessed, primarily focusing on cognitive impairment. We have analyzed NMS burden assessed through an extensive clinical and neuropsychological battery in 137 consecutive non-demented PD patients genotyped for MAPT haplotypes (H1/H1 vs H2 carriers) in order to explore the applicability of the "anatomo-clinical", "motor" or "genetic" models for subtyping PD in a clinical setting; a subsequent independent analysis was conducted to verify a possible cluster distribution of NMS. No clear-cut NMS profiles according to the previously described models emerged: in our population, the autonomic dysfunctions and depressive symptoms represent the leading determinant of NMS clusters, which seems to better fit with the hypothesis of a "neurotransmitter-based" model. Selective preferential neurotransmitter network dysfunctions may account for heterogeneity of PD and could address translational research.

Functional and structural abnormalities in patients with dilated cardiomyopathy.

Passive diastolic properties of the left ventricle were determined in 10 control subjects and 12 patients with dilated cardiomyopathy. Simultaneous left ventricular angiography and high fidelity pressure measurements were performed in all patients. Left ventricular chamber stiffness was calculated from left ventricular pressure-volume and myocardial stiffness from left ventricular stress-strain relations with use of a viscoelastic model. Patients with dilated cardiomyopathy were classified into two groups according to the diastolic constant of myocardial stiffness (beta). Group 1 consisted of seven patients with a normal constant of myocardial stiffness less than or equal to 9.6 (normal range 2.2 to 9.6) and group 2 of 5 patients with a beta greater than 9.6. Structural abnormalities (percent interstitial fibrosis, fibrous content) in patients with dilated cardiomyopathy were assessed by morphometry from right ventricular endomyocardial biopsies. Heart rate was similar in the three groups. Left ventricular end-diastolic pressure was significantly greater in patients with cardiomyopathy (18 mm Hg in group 1 and 22 mm Hg in group 2) than in the control patients (10 mm Hg). Left ventricular ejection fraction was significantly lower in groups 1 (37%) and 2 (36%) than in the control patients (66%). Left ventricular muscle mass index was significantly increased in both groups with cardiomyopathy. The constant of chamber stiffness (beta*) was slightly although not significantly greater in groups 1 and 2 (0.58 and 0.58, respectively) than in the control group (0.35). The constant of myocardial stiffness beta was normal in group 1 (7.0; control group 6.9, p = NS) but was significantly increased in group 2 (23.5). Interstitial fibrosis was 19% in group 1 and 43% (p less than 0.001) in group 2 (normal less than or equal to 10%). There was an exponential relation between both diastolic constant of myocardial stiffness (beta) and interstitial fibrosis (IF) (r = 0.95; p less than 0.001) and beta and fibrous content divided by end-diastolic volume index (r = 0.93; p less than 0.001). It is concluded that myocardial stiffness can be normal in patients with dilated cardiomyopathy despite severely depressed systolic function. Structural alterations of the myocardium with increased amounts of fibrous tissues are probably responsible for the observed changes in passive elastic properties of the myocardium in patients with dilated cardiomyopathy. The constant of myocardial stiffness (beta) helps to identify patients with severe structural alterations (group 2), representing possibly a more advanced stage of the disease.

Abnormal head nociceptive withdrawal reaction to facial nociceptive stimuli in Parkinson's disease.

INTRODUCTION: Trigemino-cervical-spinal reflexes (TCSRs) are complex brainstem stereotyped nociceptive responses involved in a defensive withdrawal reaction of the head from facial nociceptive stimuli. OBJECTIVE: The present study was undertaken to collect data on possible TCSR abnormalities in idiopathic Parkinson's disease (PD) and investigate any correlation with motor signs and L-DOPA administration. METHODS: TCSRs were registered from the semispinalis capitis and biceps brachii muscles after electrical stimulation of the supraorbital nerve in 18 patients with PD and 24 controls. The latency (L) and area (A), as well as the sensory (ST), painful (PT) and reflex (RT) thresholds were measured during the 'off' and 'on' state, and possible correlations with the UPDRS III total score, selected subscores (tremor, neck rigidity, upper limb rigidity, akinesia, rising from a chair, posture and posture instability) and duration of illness were investigated. RESULTS: Significant changes between controls and PD patients were found in the L, A, PT and RT of TCSRs. These results were not significantly influenced by L-DOPA treatment. A significant correlation was found between neck rigidity, postural instability scores and duration of illness and the TCSR L and A values in PD patients in the 'off' state. CONCLUSIONS: TCSRs abnormalities, combined with dopamine resistance, are consistent with a primary loss of brainstem neurons mediating a complex sensory-motor integration including neck muscle tone and postural control as well as the head withdrawal reaction to the nociceptive stimuli. SIGNIFICANCE: TCSRs may represent a useful tool for the assessment of brainstem sensory-motor function in PD as well as other movement and degenerative disorders.

Dry Eye Syndrome in Non-Exophthalmic Graves' Disease.

BACKGROUND: The present study aims to assess qualitative and quantitative characteristics of tear film and corneal related impairment and to evaluate the quality of life in a cohort of non-exophthalmic Graves' disease (GD) patients. METHODS: The series comprised 50 eyes from 25 newly diagnosed GD patients with no proptosis. As control group, 56 eyes of 28 thyroid disease-free subjects were enrolled. RESULTS: The results of Schirmer I and II, break-up time, and Oxford scheme showed a significant difference between GD and controls. By ocular surface disease index (OSDI) questionnaire, eleven (44%) GD patients had normal ocular surface, while two (8%) had mild, four (16%) had moderate, and eight (32%) had severe dry eye. The mean score of the OSDI in the GD group was significantly (p < 0.001) higher with respect to the control group. CONCLUSIONS: This study shows that the tear film and cornea are damaged in newly non-exophthalmic GD subjects.

Insulin-like growth factors I and II stimulate extracellular matrix production in human glomerular mesangial cells. Comparison with transforming growth factor-beta.

An enhanced paracrine/autocrine activity of the insulin-like growth factor (IGF) system within the glomerulus has been implicated together with up-regulation of transforming growth factor-beta (TGFbeta) in the pathogenesis of diabetic glomerular disease. This would imply their ability to modulate extracellular matrix (ECM) and cell turnover at the mesangial level, but the direct effects of IGFs on ECM production have not been demonstrated to date. These experiments in cultured human mesangial cells were aimed at assessing the effects of IGF-I and IGF-II, compared with those of TGFbeta, on 1) ECM medium accumulation and gene expression, and 2) total protein synthesis and cell proliferation. Human mesangial cells were grown to subconfluence, growth arrested for 48 h, and then exposed for 4-24 h to serum-free medium containing IGF-I (10(-7) - 10(-11) M), IGF-II (10(-7) - 10(-11) M), TGFbeta (10(-9) - 10(-11) M), or various combinations of two of these growth factors (10(-9)M). All three growth factors dose dependently increased ECM protein and messenger RNA levels. The combination of either IGF-I or IGF-II with TGFbeta, but not the two IGFs together, produced additive effects on matrix production. Total protein synthesis was also increased by IGF-I, IGF-II, and TGFbeta, although to a lesser extent than ECM production, whereas cell proliferation was enhanced by IGFs but not by TGFbeta. These results demonstrate that IGF-I and IGF-II are effective, although less potent than TGFbeta, in stimulating the production of the ECM components that accumulate in the mesangial region during the course of diabetic glomerular disease.

Electroencephalography and visually evoked potentials during moderate hypoglycemia.

The effects of hypoglycemia per se on the electroencephalogram (EEG) and visually evoked potentials (VEPs) were studied in eight normal young adults. The EEG and VEPs were recorded before and during hypoglycemic clamp studies, carried out at plasma insulin and glucose concentrations of about 287 pmol/L and 2.38 mmol/L, respectively. From the mean power EEG spectra obtained during each testing condition, several parameters in each frequency band considered were compared statistically. During the eyes closed recording, the mean frequency of the alpha-band (8-13 Hz) decreased from 10.1 +/- 0.2 (+/- SE) Hz in both the right and left frontal leads during euglycemia to 8.8 +/- 0.2 and 8.8 +/- 0.1 Hz (left and right frontal leads, respectively; P less than 0.05) during hypoglycemia. In the same leads, the peak frequency decreased from 10.6 +/- 0.4 and 10.3 +/- 0.4 Hz to 9.6 +/- 0.4 and 9.5 +/- 0.3 Hz, respectively (P less than 0.05). A similar pattern of variation was found during the eyes open recording. In contrast, mean VEP latencies did not vary significantly; they were 118 +/- 3 ms (smallest image size; square wave signals subtending 30 min of arc) and 116 +/- 3 ms (largest image size; square wave signals subtending 60 min of arc) during euglycemia to 121 +/- 3 and 119 +/- 3 ms, respectively, during hypoglycemia. This study demonstrates that the earliest hypoglycemia-induced EEG alterations occur in the frontal regions and can be quantified in terms of decreased mean and peak frequencies of the alpha-band. VEP latency is less sensitive. If confirmed in diabetic patients, these data may provide a theoretical basis for developing a portable device to detect early hypoglycemia in those patients who lack warning symptoms.

Increased insulin sensitivity in patients with idiopathic reactive hypoglycemia.

We performed a euglycemic hyperinsulinemic glucose clamp in 20 patients selected from a large number of subjects referred to our clinic with symptoms suggesting reactive hypoglycemia. Diagnosis was made on the basis of blood glucose measurements during symptoms in their daily life and confirmed by a 5-h oral glucose tolerance test. The patients were divided into the following groups: 8 patients with idiopathic reactive hypoglycemia (IRH), i.e. biochemical hypoglycemia associated with symptoms and plasma insulin concentrations in the normal range; 6 patients with nonhypoglycemia (NH), i.e. patients experiencing the symptoms evoking hypoglycemia at essentially normal plasma glucose levels; and 6 patients with alimentary hypoglycemia secondary to previous gastric surgery (GS). Eight normal volunteers formed the control group (N). Hypoglycemia in this study was considered to be present when plasma glucose concentrations were below 2.5 mmol/L. The peak cortisol levels after glycemic nadir were higher (2P less than 0.05) in IRH compared to GS and N. In the same group, a partially deficient glucagon response to hypoglycemia was noted. During the euglycemic clamp, the glucose uptake appeared to be significantly greater in the IRH group than in NH, GS, and N groups (8.13 +/- 0.49 vs. 7.02 +/- 0.35, 6.48 +/- 0.22, and 6.66 +/- 0.42 mg/kg.min, respectively; 2P less than 0.05). Therefore, our data suggest that increased insulin sensitivity represents a feature of idiopathic reactive hypoglycemia.

Mitochondrial myopathy, parkinsonism, and multiple mtDNA deletions in a Sephardic Jewish family.

The authors describe a family of Sephardic Jews with progressive external ophthalmoparesis, skeletal muscle weakness, and parkinsonism. Autosomal recessive inheritance was suggested by many consanguineous marriages, although a dominant disorder could not be excluded. No linkage to known progressive external ophthalmoparesis locus was found. The presence of cytochrome c oxidase-negative ragged-red fibers, biochemically reduced respiratory chain complexes, and multiple mitochondrial DNA deletions in muscle biopsies from four patients suggested a new mitochondrial disorder of intergenomic communication.

The tau gene in progressive supranuclear palsy: exclusion of mutations in coding exons and exon 10 splice sites, and identification of a new intronic variant of the disease-associated H1 haplotype in Italian cases.

Mutations in coding exons or exon 10 5'-splice-site of the gene for microtubule-associated protein tau can cause chromosome 17-linked frontotemporal dementia and parkinsonism (FTDP-17). We sequenced the 11 coding exons plus exon-intron boundaries of the tau gene in 15 cases of progressive supranuclear palsy (PSP), and found no mutations in coding exons or exon ten 5'-splice sites. These data indicate that typical PSP is not associated with tau gene mutations similar to those causing FTDP-17. We also observed a +39deltaG base change in the intron following exon 4 in three out of 69 PSP cases (all three Italians), whereas it was not found in 150 Dutch controls and once in 112 Italian controls. The +39deltaG variant arose in the context of the PSP-associated tau H1 haplotype. Although a pathogenic role cannot be entirely excluded, +39deltaG is likely to be a rare polymorphism that may be in linkage disequilibrium with a biologically relevant locus inside or near to the tau gene.

Mismatch Negativity in essential tremor: role of age at onset in pre-attentive auditory discrimination.

OBJECTIVE: To investigate whether pre-attentive auditory discrimination is impaired in patients with essential tremor (ET) and to evaluate the role of age at onset in this function. METHODS: Seventeen non-demented patients with ET and seventeen age- and sex-matched healthy controls underwent an EEG recording during a classical auditory MMN paradigm. RESULTS: MMN latency was significantly prolonged in patients with elderly-onset ET (>65 years) (p=0.046), while no differences emerged in either latency or amplitude between young-onset ET patients and controls. CONCLUSIONS: This study represents a tentative indication of a dysfunction of auditory automatic change detection in elderly-onset ET patients, pointing to a selective attentive deficit in this subgroup of ET patients. SIGNIFICANCE: The delay in pre-attentive auditory discrimination, which affects elderly-onset ET patients alone, further supports the hypothesis that ET represents a heterogeneous family of diseases united by tremor; these diseases are characterized by cognitive differences that may range from a disturbance in a selective cognitive function, such as the automatic part of the orienting response, to more widespread and complex cognitive dysfunctions.

Reversible diffusion MRI abnormalities and transient mutism after liver transplantation.

Transient mutism was observed in a liver transplant patient under immunosuppressant therapy with cyclosporine A and antifungal prophylaxis with amphotericin B. Fluid-attenuated inversion recovery and diffusion-weighted images revealed reversible bilateral symmetric hyperintensity located in the frontal motor cortex and corticospinal tracts. These MRI abnormalities may be caused by acute edema, possibly a combination of cytotoxic and vasogenic edema, which resolved with a prompt change in therapy.

Hemodynamic study of intravenous propionyl-L-carnitine in patients with ischemic heart disease and normal left ventricular function.

Propionyl-L-carnitine was given intravenously to ten patients with chronic ischemic heart disease who had normal left ventricular function and had not had a previous myocardial infarction. Subsequently, pulmonary and systemic circulation, left ventricular function, and the relationship between the ventricle and afterload were evaluated. This drug, at a dose of 15 mg/kg, improves ventricular function by easing the load and by enhancing cardiac efficiency. The ejection impedance is reduced with a consequent increase in stroke volume as a result of a) a decrease in systemic and pulmonary resistance and b) an increase in arterial compliance. Arterial pressure is maintained due to an increase in total external heart power. Since the tension time index shows a proportionally smaller increase in the energy requirement, it follows that cardiac efficiency has been improved and ventricle-afterload matching is optimal. These results suggest but do not prove that propionyl-L-carnitine exhibits a positive inotropic property.

Right ventricular dysplasia: an ultrastructural study.

Ultrastructural observations on myocardial biopsies from patients developing clinical and/or echocardiographic and haemodynamic signs of dysplasia of the right ventricle did not reveal morphological defects of the myocardiocyte contraction apparatus, but showed evidence of fibrosis of the myocardial interstitium and modifications of the structures involved in the transmission of the action potential into the cardiac cells as well as of the junctional system between them. Interstitial adipocytes and intracellular lipid droplets were not increased in number.

[Effect of intracoronary and intravenous administration of propranolol on coronary vasomotility at rest and during exercise]. / Effetto della somministrazione endocoronarica ed endovenosa di propranololo sulla vasomotilità coronarica a riposo e durante esercizio.

The effect of intracoronary and intravenous propranolol on coronary vasomotion was evaluated in 30 patients with coronary artery disease. Luminal area of a normal and a stenotic coronary segment was determined at rest, during supine bicycle exercise and 5 min after 1.6 mg sublingual nitroglycerin administered at the end of the exercise test using biplane quantitative coronary arteriography. Patients were divided into 3 groups: Group I (n = 12) served as control Group II consisted of 10 patients with intracoronary administration of 1 mg propranolol and Group III of 8 patients with intravenous administration of 0.1 mg/kg propranolol prior to the exercise test. In the control Group there was coronary vasodilation (+23%, p less than 0.01) of the normal and coronary vasoconstriction (-29%, p less than 0.001) of the stenotic vessel segment during bicycle exercise. After sublingual administration of 1.6 mg nitroglycerin there was vasodilation of both normal (+40%, p less than 0.001 vs rest) and stenotic (+12%, NS vs rest) segments. In Group II intracoronary propranolol was not accompanied by a change in coronary area but both normal (+13%, p less than 0.05) and stenotic (+22%, p less than 0.05) segments showed coronary vasodilation during bicycle exercise. After sublingual nitroglycerin there was further vasodilation of both normal (+31%, p less than 0.001 vs rest) and stenotic (+45%, p less than 0.01 vs rest) arteries. In Group III intravenous administration of propranolol was associated with a decrease in coronary luminal area of both normal (-24%, p less than 0.001) and stenotic (-41%, p less than 0.001) segments. During dynamic exercise there was coronary vasodilation of both segments when compared to the data after intravenous injection of propranolol but there was no change in luminal area (normal vessel-2%, NS vs rest; stenotic vessel-3%, NS vs rest) when compared to the resting data. After sublingual administration of 1.6 mg nitroglycerin both normal (+21%, p less than 0.001) and stenotic (+46%, p less than 0.001) segments showed coronary vasodilation. It is concluded that supine bicycle exercise in patients with coronary artery disease is associated with vasodilation of the normal and vasoconstriction of the stenotic coronary arteries. Intravenous administration of propranolol is followed by coronary vasoconstriction of both normal and stenotic coronary arteries probably due to secondary mechanisms (reduction in heart rate and contractility) because it is not observed after intracoronary injection of propranolol and it is overridden by bicycle exercise and sublingual nitroglycerin.

Right ventricular dysplasia: angiographic study.

At the moment, the most reliable method for diagnosing right ventricular dysplasia is considered to be angiography. Morphological alterations such as the presence of akinetic/dyskinetic areas, aneurysmatic dilatations and deep anteroapical fissuring, not necessarily associated with an increase in ventricular volume, are understood to be angiographic criteria indicating dysplasia. To verify their diagnostic value, these abnormalities have been evaluated in: (1) 33 patients suspected of having dysplasia because of PVBs with LBBB morphology and with 'borderline' involvement of the right ventricle or without instrumental evidence of cardiac disease (Group A); (2) 16 subjects with no arrhythmia and normal left ventricular angiography, coronary and bioptic findings (Group B); (3) 36 patients with a clinical, angiographic and bioptic diagnosis of dilated idiopathic cardiomyopathy (Group C). In 48.5% of the patients in Group A, angiography showed localized akinesia/dyskinesia (12 patients), small conical outpouchings persisting during systole (10 patients) and apical deep fissuring (two patients). In 81% of these patients, endomyocardial biopsy showed the presence of fibrous and/or adipose tissue in at least 20% of the examined sample. Angiographic abnormalities suggesting dysplasia were found in none of the normal subjects and only in two of the 36 patients with dilated cardiomyopathy (5.5%).

[Abnormal coronary vasomotility in subjects with normal coronary arteries and reduced reserve of coronary flow]. / Abnorme vasomotilità coronarica in soggetti con coronarie normali e ridotta riserva di flusso coronarico.

A reduced coronary flow reserve has been reported in patients with ischemia-like symptoms and normal coronary arteries. In 13 such subjects both coronary vasomotion and flow reserve were studied. The luminal area of the proximal and distal third of the left anterior descending and left circumflex artery were determined by biplane quantitative coronary arteriography using a computer-assisted system. Subjects were studied at rest, during submaximal supine bicycle exercise (4.0 min, 116 W) and 5 min after sublingual administration of 1.6 mg nitroglycerin. Heart rate, mean pulmonary and aortic pressure as well as the percent change of both proximal and distal luminal area were determined. In 10 of the 13 subjects, coronary sinus blood flow was measured by coronary sinus thermodilution technique at rest and after dipyridamole infusion (0.5 mg/Kg in 15 min) 10 +/- 5 days after quantitative coronary arteriography. Coronary flow ratio (dipyridamole/rest) and coronary resistance ratio (rest/dipyridamole) were determined in these subjects. Subjects were divided into 2 groups according to the behaviour of the coronary vessels during exercise (vasodilation = Group 1, vasoconstriction = Group 2). Coronary vasodilation of the proximal (luminal area + 26%; p less than 0.001) and distal (+ 45%; p less than 0.001) artery was observed in 7 subjects (Group 1) during exercise and after sublingual nitroglycerin (+46%; p less than 0.001 and +99%; p less than 0.001, respectively). In Group 2 (n = 6), however, there was coronary vasoconstriction of the distal vessel segments (-24%; p less than 0.001) during exercise, whereas the proximal coronary artery showed vasodilation (+ 26%; p less than 0.001) during exercise. Following sublingual nitroglycerin, both vessel segments elicited vasodilation (distal coronary + 44%; p less than 0.001, proximal coronary artery +47%; p less than 0.001). Coronary flow ratio amounted to 2.5 in Group 1 and to 1.2 in Group 2 (p less than 0.05) and coronary resistance ratio to 2.7 in Group 1 and to 1.2 in Group 2 (p less than 0.05), respectively. Thus, among subjects with ischemia-like symptoms and normal coronary arteries there is a subgroup of patients (Group 2) with an abnormal dilator response of the distal coronary arteries to the physiologic dilator stimulus of exercise and a reduced dilator capacity of the resistance vessels after dipyridamole (= abnormal coronary vasodilator syndrome). The nature of this exercise-induced distal coronary vasoconstriction is not clear but might be due to an abnormal neurohumoral tone which may cause or contribute to the blunted vascular response during exercise.