Psychophysical evidence of taste dysfunction in burning mouth syndrome

Because subjects with burning mouth syndrome (BMS) frequentlyreport impaired taste, the present study was carried out on47 BMS subjects and 27 age–and sex-matched control subjectsto determine if there was any psychophysical evidence of tastedysfunction in BMS. Taste detection thresholds and taste intensityscaling for the modalities of sweet, salt, bitter and sour wereobtained. Compared with control subjects, BMS subjects as awhole displayed statistically significant alterations in sensorydysfunction both at threshold (for sweet) and at suprathresholdlevels (for sweet and sour). The BMS subjects were subsequentlydivided into those subjects who reported a dysgeusic tase (–75and 60% of the BMS subjects tested at threshold and suprathresholdlevels, respectively) and those without a dysgeusic taste ({smalltilde}24 and 40% of the subjects tested at threshold and suprathresholdlevels, respectively). When the data of these two groups werecompared with those of the control subjects, it became evidentthat at suprathreshold levels, differences in taste functionoriginated mainly from those BMS subjects with complaints ofa dysgeusic taste. These findings therefore indicate that psychophysicalevidence of taste dysfunction can be demonstrated in BMS andthat the changes in taste perception are particularly evidentin those BMS subjects with a self-reported symptom of dysgeusia.     

Behavior of plasma cortisol during testing with insulin and with LVP in obese subjects compared to normal subjects after resperine administration]

The behaviour of plasma cortisol levels was studied in fifteen overweight subjects with comparison to normal subjects. In eight subjects the insulin hypoglycemic test was performed before and after medication with reserpine (4mg/24HR); the other seven subjects were tested with LVP before and after treatment with reserpine. In both cases, premedication with reserpine significantly reduce the cortisolemic response. This behaviour is similar to the response observed in normal subjects.     

Postural neurocognitive and neuronal activated cerebral blood flow deficits in young chronic fatigue syndrome patients with postural tachycardia syndrome

Neurocognition is impaired in chronic fatigue syndrome (CFS). We propose that the impairment relates to postural cerebral hemodynamics. Twenty-five CFS subjects and twenty control subjects underwent incremental upright tilt at 0, 15, 30, 45, 60, and 75° with continuous measurement of arterial blood pressure and cerebral blood flow velocity (CBFV). We used an n-back task with n ranging from 0 to 4 (increased n = increased task difficulty) to test working memory and information processing. We measured n-back outcomes by the number of correct answers and by reaction time. We measured CBFV, critical closing pressure (CCP), and CBFV altered by neuronal activity (activated CBFV) during each n value and every tilt angle using transcranial Doppler ultrasound. N-back outcome in control subjects decreased with n valve but was independent of tilt angle. N-back outcome in CFS subjects decreased with n value but deteriorated as orthostasis progressed. Absolute mean CBFV was slightly less than in control subjects in CFS subject at each angle. Activated CBFV in control subjects was independent of tilt angle and increased with n value. In contrast, activated CBFV averaged 0 in CFS subjects, decreased with angle, and was less than in control subjects. CCP was increased in CFS subjects, suggesting increased vasomotor tone and decreased metabolic control of CBFV. CCP did not change with orthostasis in CFS subjects but decreased monotonically in control subjects, consistent with vasodilation as compensation for the orthostatic reduction of cerebral perfusion pressure. Increasing orthostatic stress impairs neurocognition in CFS subjects. CBFV activation, normally tightly linked to cognitive neuronal activity, is unrelated to cognitive performance in CFS subjects; the increased CCP and vasomotor tone may indicate an uncoupling of the neurovascular unit during orthostasis.     

In vivo and in vitro sodium pump activity in subjects with thyrotoxic periodic paralysis.

OBJECTIVE--To examine whether sodium pump activity plays a part in the pathogenesis of thyrotoxic periodic paralysis. DESIGN--Measurement of platelet sodium-potassium ATPase and in vivo sodium pump activities in healthy subjects and thyrotoxic subjects with and without paralysis. SETTING--University hospital in Hong Kong. SUBJECTS--21 healthy subjects, 23 untreated thyrotoxic subjects, 13 untreated men with periodic paralysis, seven treated thyrotoxic subjects, and six treated men with periodic paralysis. MAIN OUTCOME MEASURES--Platelet Na+, K(+)-ATPase activity and plasma rubidium concentration after oral loading. RESULTS--Median (range) platelet Na+, K(+)-ATPase activity in thyrotoxic subjects was 253 (169-821) mumol inorganic phosphate/h/g protein--significantly higher than that in healthy subjects (134 (81-180) mumol/h/g protein; p less than 0.001). Na+, K(+)-ATPase activity in those with periodic paralysis was 374 (195-1196) mumol/h/g protein, again significantly higher than that in healthy subjects (p less than 0.001) and that in other thyrotoxic subjects (p less than 0.01) despite similar degrees of hyperthyroidism. Activities in treated thyrotoxic subjects with and without periodic paralysis were 148 (110-234) and 131 (86-173) mumol/h/g protein respectively. Mean (95% confidence interval) plasma rubidium concentration five hours after oral administration in thyrotoxic subjects (7.0 (6.6 to 7.5) mumol/l) was significantly lower than in healthy subjects (10.2 (9.5 to 10.9) mumol/l; p less than 0.001) and higher than in those with periodic paralysis (6.0 (5.7 to 6.3) mumol/l; p less than 0.01). CONCLUSIONS--Sodium pump activity in untreated subjects with periodic paralysis is higher than in other thyrotoxic subjects, and this may be responsible for the hypokalaemia.     

Age-Related Circadian Rhythm of DHEAS Plasma Levels in Male Subjects

The aging influences the endocrine temporal structure, including DHEAS which can be considered as a biomarker of aging, since its levels gradually decrease in older subjects. The aim of this work was to observe the circadian rhythms of DHEAS, prolactin, cortisol and body temperature, in healthy elderly male subjects (73.7 ± 2.5 years) compared with healthy young subjects (27.2 ± 6.6 years). The results documented that in our subjects no significant age-related differences in prolactin levels existed. In elderly subjects cortisol levels were weakly enhanced in comparison with young subjects. DHEAS showed a preserved circadian rhythm, but markedly lower rhythm adjusted mean (74.38 ± 10.29 versus 273.63 ± 26.39) (p < 0.001) and decreased amplitude of oscillation (p < 0.001), when expressed as absolute value, in elderly subjects when compared with young subjects. In elderly subjects the DHEAS circadian rhythm modifications could represent an impairment of of the endocrine temporal structure.     

High incidence of cardiovascular complications in pheochromocytoma

Excess of catecholamines in pheochromocytoma is usually accompanied with classical symptoms and signs. In some cases, severe cardiovascular complications (e. g., heart failure, myocardial infarction) may occur. We performed a retrospective analysis focused on the incidence of cardiovascular complications (classified as follows: arrhythmias, myocardial involvement or ischemia and atherosclerosis, cerebrovascular impairment) before the establishment of diagnosis of pheochromocytoma among 145 subjects treated in our hospital. Cardiovascular complications occurred in 28 subjects, but these subjects did not differ significantly from subjects without complications in age, gender, body mass index, paroxysmal symptoms, symptom duration, tumor dimension, catecholamine secretory phenotype, and incidence of hypertension or diabetes mellitus. Arrhythmias occurred in 15 subjects (2 arrhythmia types in 2 subjects): atrial fibrillation in 9 subjects, supraventricular tachycardia in 3 cases, and ventricular tachycardia in 2 patients. Significant bradycardia was noted in 3 cases. Five subjects presented with heart failure with decreased systolic function (takotsubo-like cardiomyopathy found in 2 cases). One subject suffered from hypertrophic obstructive cardiomyopathy. Seven subjects presented with non-ST-segment elevation myocardial infarction, 2 patients with ST-segment myocardial infarction, and 1 subject underwent coronary artery bypass grafting. Two subjects suffered from significant peripheral atherosclerosis. Among cerebrovascular complications, transient ischemic attack was found in 3 cases, 2 subjects suffered from stroke, and subarachnoidal bleeding occurred in 1 patient. One subject suffered from diffuse neurological impairment due to multiple ischemic white matter lesions. These data show relatively high incidence of cardiovascular complications (19.3%) in subjects with pheochromocytoma. Early diagnosis is mandatory to prevent severe complications in pheochromocytoma.     

Sleep apneic activity in older healthy subjects

The percentage of subjects with sleep apneic activity was significantly greater in a group of 60 healthy subjects who were 50 yr and older compared with a control group of 69 subjects who were younger than 50 yr. Sixteen of the older subjects (26.7%) and six of the younger subjects (8.7%) met the criteria for sleep apneic activity, i.e., 3-29 episodes per night. However, only one of the older subjects (1.7%) had enough sleep apneic activity (30 or more episodes in a night) to meet the definition of the condition of sleep apnea. In both age groups, sleep apneic activity (SAA) was slightly more prevalent in males than females. Older subjects with SAA were not significantly heavier than those without SAA but were so when compared with the younger subjects with SAA. In the 29 older subjects for whom hemoglobin O2 saturation (Sao2) was recorded, those with SAA had a significantly lower mean minimum Sao2 value (87%) than those without (92%).     

Hypertriglyceridemia is associated with prebeta-HDL concentrations in subjects with familial low HDL

Prebeta-HDL particles act as the primary acceptors of cellular cholesterol in reverse cholesterol transport (RCT). An impairment of RCT may be the reason for the increased risk of coronary heart disease (CHD) in subjects with familial low HDL. We studied the levels of serum prebeta-HDL and the major regulating factors of HDL metabolism in 67 subjects with familial low HDL and in 64 normolipidemic subjects. We report that the subjects with familial low HDL had markedly reduced prebeta-HDL concentrations compared with the normolipidemic subjects (17.4 +/- 7.2 vs. 23.4 +/- 7.8 mg apolipoprotein A-I/dl; P < 0.001). A positive correlation was observed between prebeta-HDL concentration and serum triglyceride (TG) level (r = 0.334, P = 0.006). In addition, serum TG level was found to be the strongest predictor of prebeta-HDL concentration in subjects with familial low HDL. The activities of cholesteryl ester transfer protein and hepatic lipase were markedly increased in subjects with familial low HDL without a significant correlation to prebeta-HDL concentration. Our results support the hypothesis that impaired RCT is one mechanism behind the increased risk for CHD in subjects with familial low HDL.     

Evaluation of Oxidative Stress in Overweight Subjects With or Without Metabolic Syndrome

Although oxidative stress is considered the underlying mechanism by which dysfunctional metabolism occurs in obese subjects, there are few studies on oxidative stress in overweight subjects. The objective of this study was to verify the influence of metabolic syndrome (MetS) on oxidative stress and antioxidant defense in overweight subjects. There were 123 subjects (50 in the control group and 73 in the overweight group) chosen to participate in this cross‐sectional study. The control group included 50 healthy individuals with a BMI between 20 and 24.9 kg/m² and without MetS. The overweight group included 73 subjects with a BMI between 25 and 29.9 kg/m². Overweight subjects were divided into two groups: with MetS (29 subjects) and without MetS (44 subjects). Control group and overweight group subjects without MetS showed no differences in oxidative stress parameters and total antioxidant capacity (TRAP). Overweight subjects with MetS had higher hydroperoxide concentrations measured by chemiluminescence compared to the control group (P < 0.05), higher hydroperoxide and hydrogen peroxide concentrations determined by ferrous oxidation‐xylenol orange assay compared to overweight subjects without MetS (P < 0.001), and higher advanced oxidation protein product (AOPP) concentrations (P < 0.001) compared to the other groups. AOPP was directly correlated with uric acid concentrations. Overweight subjects with MetS had lower TRAP concentrations compared to the control group (P < 0.001). In conclusion, this study showed that overweight subjects with MetS, in contrast to overweight subjects without MetS, have a redox imbalance characterized by increased plasma oxidation and reduced antioxidant capacity.     

Insulin sensitivity in pancreatitis, liver diseases, steroid treatment and hyperthyroidism assessed by glucose, insulin and somatostatin infusion

In order to assess insulin sensitivity for glucose utilization in the other type of diabetes, insulin sensitivity tests were performed in subjects with pancreatitis, liver disease, steroid treatment and hyperthyroidism. Insulin sensitivity for glucose utilization decreased in subjects with liver disease, steroid treatment and hyperthyroidism irrespective of the presence or absence of glucose intolerance. Hyperinsulinism was associated in most of the subjects with liver disease and steroid treatment, but even in normo-insulinemic subjects, insulin insensitivity was observed. Obesity was associated with only 2 cases in both pancreatitis and liver diseases and therefore was excluded as a major cause for insulin insensitivity in subjects studied. In subjects with pancreatitis, insulin sensitivity was not significantly decreased. It is to be noted that 4 out of 5 subjects with diabetic OGTT (oral glucose tolerance test) exhibited normal insulin sensitivity. The results indicate that in pancreatitis, tissue insulin sensitivity for glucose metabolism is not altered and therefore can be used as a marker to differentiate the other type of diabetes due to pancreatitis from type 1 or 2 diabetes. Although hyperinsulinemia may be attributable to insulin insensitivity in subjects studied at least in part, steroid and thyroid hormone are thought to act directly antagonistically with insulin for glucose metabolism.     

Hyperinsulinemia and impaired leptin-adiponectin ratio associate with endothelial nitric oxide synthase polymorphisms in subjects with in-stent restenosis

Little is known about the association of endothelial nitric oxide synthase (NOS3) gene polymorphisms and the presence of insulin resistance and the early evolution of atherosclerosis in nondiabetic subjects with cardiovascular disease (CAD) and stent implantation. The present study was performed in an attempt to better understand whether metabolic, endothelial, and angiographic findings characteristic of subjects with cardiovascular disease and in-stent restenosis are related to NOS3 variants. This is a case-control study performed from 2002 to 2006. All subjects admitted to the study were recruited in the Nord-Centre of Italy, most from Milan and its surrounding towns. Measures of glucose tolerance, insulin sensitivity, markers of endothelial dysfunction, forearm vasodilation, and adipokine levels were determined and associated to the frequency of two single-nucleotide polymorphisms of NOS3, i.e., Glu298Asp (rs1799983, G/T) and rs753482 (intron 18 A/C). A total of 747 subjects, not known to have diabetes, were evaluated: 333 subjects had asymptomatic CAD, 106 subjects had unstable angina and were evaluated for in-stent restenosis 6 mo after stent placement, and 308 were control subjects. The presence of TT and CC minor alleles was significantly greater in case groups compared with control subjects. At phenotypic level, subjects with the polymorphisms were characterized by hyperinsulinemia and reduced reactive hyperemia, whereas increased leptin and decreased adiponectin levels were present in subjects with restenosis in the presence of reduced minimal lumen diameter and length of stenosis almost doubled. Hyperinsulinemia, endothelial dysfunction, and a more atherogenic profile seem to be peculiar features of subjects with asymptomatic CAD and restenosis carrying NOS3 gene variants.     

Contribution of BRCA1 and BRCA2 mutations to breast and ovarian cancer in Pakistan

The population of Pakistan has been reported to have the highest rate of breast cancer of any Asian population (excluding Jews in Israel) and one of the highest rates of ovarian cancer worldwide. To explore the contribution that genetic factors make to these high rates, we have conducted a case-control study of 341 case subjects with breast cancer, 120 case subjects with ovarian cancer, and 200 female control subjects from two major cities of Pakistan (Karachi and Lahore). The prevalence of BRCA1 or BRCA2 mutations among case subjects with breast cancer was 6.7% (95% confidence interval [CI] 4.1%-9.4%), and that among case subjects with ovarian cancer was 15.8% (95% CI 9.2%-22.4%). Mutations of the BRCA1 gene accounted for 84% of the mutations among case subjects with ovarian cancer and 65% of mutations among case subjects with breast cancer. The majority of detected mutations are unique to Pakistan. Five BRCA1 mutations (2080insA, 3889delAG, 4184del4, 4284delAG, and IVS14-1A-->G) and one BRCA2 mutation (3337C-->T) were found in multiple case subjects and represent candidate founder mutations. The penetrance of deleterious mutations in BRCA1 and BRCA2 is comparable to that of Western populations. The cumulative risk of cancer to age 85 years in female first-degree relatives of BRCA1-mutation-positive case subjects was 48% and was 37% for first-degree relatives of the BRCA2-mutation-positive case subjects. A higher proportion of case subjects with breast cancer than of control subjects were the progeny of first-cousin marriages (odds ratio [OR] 2.1; 95% CI 1.4-3.3; P=.001). The effects of consanguinity were significant for case subjects with early-onset breast cancer (age <40 years) (OR=2.7; 95% CI 1.5-4.9; P=.0008) and case subjects with ovarian cancer (OR=2.4; 95% CI 1.4-4.2; P=.002). These results suggest that recessively inherited genes may contribute to breast and ovarian cancer risk in Pakistan.     

Diabetic neuropathy is related to joint stiffness during late stance phase

The majority of plantar ulcers in the diabetic population occur in the forefoot. Peripheral neuropathy has been related to the occurrence of ulcers. Long-term diabetes results in the joints becoming passively stiffer. This static stiffness may translate to dynamic joint stiffness in the lower extremities during gait. Therefore, the purpose of this investigation was to demonstrate differences in ankle and knee joint stiffness between diabetic individuals with and without peripheral neuropathy during gait. Diabetic subjects with and without peripheral neuropathy were compared. Subjects were monitored during normal walking with three-dimensional motion analysis and a force plate. Neuropathic subjects had higher ankle stiffness (0.236 N.m/deg) during 65 to 80% of stance when compared with non-neuropathic subjects (-0.113 N.m/deg). Neuropathic subjects showed a different pattern in ankle stiffness compared with non-neuropathic subjects. Neuropathic subjects demonstrated a consistent level of ankle stiffness, whereas non-neuropathic subjects showed varying levels of stiffness. Neuropathic subjects demonstrated lower knee stiffness (0.015 N.m/deg) compared with non-neuropathic subjects (0.075 N.m/deg) during 50 to 65% of stance. The differences in patterns of ankle and knee joint stiffness between groups appear to be related to changes in timing of peak ankle dorsiflexion during stance, with the neuropathic group reaching peak dorsiflexion later than the non-neuropathic subjects. This may partially relate to the changes in plantar pressures beneath the metatarsal heads present in individuals with neuropathy.     

Memory B cells and pneumococcal antibody after splenectomy

Splenectomized patients are susceptible to bloodstream infections with encapsulated bacteria, potentially due to loss of blood filtering but also defective production of anticarbohydrate Ab. Recent studies propose that a lack of Ab is related to reduced numbers of IgM(+) CD27(+) memory B cells found after splenectomy. To test this, we analyzed CD27(+) memory B cell subsets, IgG, and IgM pneumococcal Ab responses in 26 vaccinated splenectomized subjects in comparison to memory B cell subsets and Ab responses in healthy controls. As shown previously, the splenectomized autoimmune subjects had fewer total, isotype switched, and IgM(+) CD27(+) memory B cells as compared with controls, but there was no difference in memory B cells subsets between controls and splenectomized subjects with spherocytosis. There was no difference between the geometric mean IgG Ab response between normal controls and splenectomized subjects (p = 0.51; p = 0.81). Control subjects produced more IgM Ab than splenectomized autoimmune subjects (p = 0.01) but the same levels as subjects with spherocytosis (p = 0.15.) There was no correlation between memory B cell subsets and IgG or IgM Ab responses for controls or splenectomized subjects. These data suggest that splenectomy alone may not be the sole reason for loss of memory B cells and reduced IgM antipneumococcal Ab. Because subjects with autoimmunity had splenectomy at a significantly older age than participants with spherocytosis, these data suggest that an age-related loss of extra splenic sites necessary for the maintenance or function of memory B cells may lead to impaired immunity in these subjects.     

Selected contribution: Ventilatory response to CO2 in high-altitude natives and patients with chronic mountain sickness.

The ventilatory responses to CO(2) of high-altitude (HA) natives and patients with chronic mountain sickness (CMS) were studied and compared with sea-level (SL) natives living at SL. A multifrequency binary sequence (MFBS) in end-tidal Pco(2) was employed to separate the fast (peripheral) and slow (central) components of the chemoreflex response. MFBS was imposed against a background of both euoxia (end-tidal Po(2) of 100 Torr) and hypoxia (52.5 Torr). Both total and central chemoreflex sensitivity to CO(2) in euoxia were higher in HA and CMS subjects compared with SL subjects. Peripheral chemoreflex sensitivity to CO(2) in euoxia was higher in HA subjects than in SL subjects. Hypoxia induced a greater increase in total chemoreflex sensitivity to CO(2) in SL subjects than in HA and CMS subjects, but peripheral chemoreflex sensitivity to CO(2) in hypoxia was no greater in SL subjects than in HA and CMS subjects. Values for the slow (central) time constant were significantly greater for HA and CMS subjects than for SL subjects.     

Using support vector machines with multiple indices of diffusion for automated classification of mild cognitive impairment

Few studies have looked at the potential of using diffusion tensor imaging (DTI) in conjunction with machine learning algorithms in order to automate the classification of healthy older subjects and subjects with mild cognitive impairment (MCI). Here we apply DTI to 40 healthy older subjects and 33 MCI subjects in order to derive values for multiple indices of diffusion within the white matter voxels of each subject. DTI measures were then used together with support vector machines (SVMs) to classify control and MCI subjects. Greater than 90% sensitivity and specificity was achieved using this method, demonstrating the potential of a joint DTI and SVM pipeline for fast, objective classification of healthy older and MCI subjects. Such tools may be useful for large scale drug trials in Alzheimer's disease where the early identification of subjects with MCI is critical.     

In vivo activation of ROCK1 by insulin is impaired in skeletal muscle of humans with type 2 diabetes

To determine whether serine/threonine ROCK1 is activated by insulin in vivo in humans and whether impaired activation of ROCK1 could play a role in the pathogenesis of insulin resistance, we measured the activity of ROCK1 and the protein content of the Rho family in vastus lateralis muscle of lean, obese nondiabetic, and obese type 2 diabetic subjects. Biopsies were taken after an overnight fast and after a 3-h hyperinsulinemic euglycemic clamp. Insulin-stimulated GDR was reduced 38% in obese nondiabetic subjects compared with lean, 62% in obese diabetic subjects compared with lean, and 39% in obese diabetic compared with obese nondiabetic subjects (all comparisons P < 0.001). Insulin-stimulated IRS-1 tyrosine phosphorylation is impaired 41-48% in diabetic subjects compared with lean or obese subjects. Basal activity of ROCK1 was similar in all groups. Insulin increased ROCK1 activity 2.1-fold in lean and 1.7-fold in obese nondiabetic subjects in muscle. However, ROCK1 activity did not increase in response to insulin in muscle of obese type 2 diabetic subjects without change in ROCK1 protein levels. Importantly, insulin-stimulated ROCK1 activity was positively correlated with insulin-mediated GDR in lean subjects (P < 0.01) but not in obese or type 2 diabetic subjects. Moreover, RhoE GTPase that inhibits the catalytic activity of ROCK1 by binding to the kinase domain of the enzyme is notably increased in obese type 2 diabetic subjects, accounting for defective ROCK1 activity. Thus, these data suggest that ROCK1 may play an important role in the pathogenesis of resistance to insulin action on glucose disposal in muscle of obese type 2 diabetic subjects.     

Binge Size Increases with Body Mass Index in Women with Binge-Eating Disorder

Objective: To determine whether meal size is related to body mass index (BMI) in obese subjects with binge-eating disorder (BED). Research Methods and Procedures: Five groups of subjects each consumed two laboratory-test meals on nonconsecutive days. Forty-two women, categorized by BMI and BED diagnosis, were instructed to “binge” during one meal and to eat “normally” during another. Eighteen women had BMI values >38 kg/m² (more-obese) and 17 had BMI values between 28 to 32 kg/m² (less-obese). Twelve of the more-obese and nine of the less-obese individuals met Diagnostic and Statistical Manual (DSM)-IV criteria for BED. Seven normal-weight women also participated as controls. Results: Subjects with BED ate significantly more in both meals than subjects without BED. Binge meals were significantly larger than normal meals only among subjects with BED. The more-obese subjects with BED ate significantly more than the less-obese subjects with BED, but only when they were asked to binge. Intake of the binge meal was significantly, positively correlated with BMI among subjects with BED. Subjects with BED reported significantly higher satiety ratings after the binge than after the normal meal, but subjects without BED reported similar ratings after both meals. Regardless of instructions and diagnosis, obese subjects consumed a significantly higher percentage of energy from fat (38.5%) than did normal-weight subjects (30.8%). Discussion: During binge meals, the energy intake of subjects with BED is greater than that of individuals of similar body weight without BED and is positively correlated with BMI.     

Altered autonomic cardiac regulation in individuals with Down syndrome

We tested the hypothesis that individuals with Down syndrome, but without congenital heart disease, exhibit altered autonomic cardiac regulation. Ten subjects with Down syndrome (DS) and ten gender-and age-matched healthy control subjects were studied at rest and during active orthostatism, which induces reciprocal changes in sympathetic and parasympathetic traffic to the heart. Autoregressive power spectral analysis was used to investigate R-R interval variability. Baroreflex modulation of sinus node was assessed by the spontaneous baroreflex sequences method. No significant differences between DS and control subjects were observed in arterial blood pressure at rest or in response to standing. Also, R-R interval did not differ at rest. R-R interval decreased significantly less during standing in DS vs. control subjects. Low-frequency (LFNU) and high-frequency (HFNU) (both expressed in normalized units) components of R-R interval variability did not differ between DS and control subjects at rest. During standing, significant increase in LFNU and decrease in HFNU were observed in control subjects but not in DS subjects. Baroreflex sensitivity (BRS) did not differ between DS and control subjects at rest and underwent significant decrease on going from supine to upright in both groups. However, BRS was greater in DS vs. control subjects during standing. These data indicate that subjects with DS exhibit reduced HR response to orthostatic stress associated with blunted sympathetic activation and vagal withdrawal and with a lesser reduction in BRS in response to active orthostatism. These findings suggest overall impairment in autonomic cardiac regulation in DS and may help to explain the chronotropic incompetence typically reported during exercise in subjects with DS without congenital heart disease.