Peripheral circulatory disorders in essential thrombocythemia.

A significant number of patients with essential thrombocythemia (ET) complain of symptoms including distal parts of the extremities (e.g., paresthesias or Raynaud's phenomenon). The aim of the present study was to examine peripheral circulation in the upper extremities of individuals with ET. The study included 45 ET patients and 30 control subjects. All participants were subjected to thermography, photoplethysmography, impedance plethysmography, and applanation tonometry pulse wave analysis. The patients with ET differed significantly from the control subjects in terms of 3rd finger skin temperature (mean 31.04 vs. 32.45°C), skin temperature gradient (mean 1.82 vs. 0.11°C), photoplethysmographic amplitude (median 0.25 vs. 0.74%), and pulse waveform in the radial artery (more frequent occurrence of type B waveform). Pulse wave parameters correlated with the skin temperature gradient. The study findings imply the altered regulation of peripheral circulation in ET, including a decreased flow and an increased resistance.

Altered plasma fibrin clot properties in essential thrombocythemia.

Patients with increased thromboembolic risk tend to form denser fibrin clots which are relatively resistant to lysis. We sought to investigate whether essential thrombocythemia (ET) is associated with altered fibrin clot properties in plasma. Ex vivo plasma fibrin clot permeability coefficient (Ks), turbidimetry and clot lysis time (CLT) were measured in 43 consecutive patients with ET (platelet count from 245 to 991 × 10(3)/µL) and 50 control subjects matched for age, sex and comorbidities. Fibrinolysis proteins and inhibitors together with platelet activation markers were determined. Reduced Ks (-38%, p < 0.0001) and prolonged CLT (+34%, p < 0.0001) were observed in ET. The differences remained significant after adjustment for fibrinogen and platelet count. ET was associated with a slightly shorter lag phase (-5%, p = 0.01) and higher maximum absorbency of the turbidimetric curve (+6%, p < 0.001). The ET patients had higher plasma P-selectin by 193% (p < 0.00001) and platelet factor 4 (PF4) by 173% (p < 0.00001), with higher P-selectin observed in 19 (44%) patients with JAK-2 gene V617F mutation. Higher t-PA (+20%, p < 0.001), 23% higher plasminogen activator inhibitor-1, PAI-1 (+23%, p < 0.01) and unaltered thrombin-activatable fibrinolysis inhibitor, plasminogen and α2-antiplasmin activity were found in the ET group. Ks inversely correlated with fibrinogen, PF4 and C-reactive protein. CLT positively correlated only with PAI-1. Patients with ET display prothrombotic plasma fibrin clot phenotype including impaired fibrinolysis, which represents a new prothrombotic mechanism in this disease.

Proteins from the 18 glycosyl hydrolase family are associated with kidney dysfunction in patients with diabetes type 2.

OBJECTIVES: To investigate chitotriosidase (CHIT1) activity and chitinase-3-like protein 1 (YKL-40) concentration in plasma of type 2 diabetic patients and evaluate their relationship with kidney dysfunction. MATERIALS AND METHODS: 94 diabetic subjects and 33 controls were enrolled in the study. Plasma CHIT1 activity and YKL-40 concentration were measured along with routine laboratory parameters. RESULTS: Levels of CHIT1 and YKL-40 in plasma of type 2 diabetic patients increased progressively with the degree of albuminuria. CHIT1 discriminated normoalbuminuric subjects from those with abnormal albuminuria better than YKL-40. CONCLUSIONS: CHIT1represent a supportive biomarker connected with development of diabetic vascular complications, especially kidney dysfunction.

PPARs in Clinical Experimental Medicine after 35 Years of Worldwide Scientific Investigations and Medical Experiments.

This year marks the 35th anniversary of Professor Walter Wahli's discovery of the PPARs (Peroxisome Proliferator-Activated Receptors) family of nuclear hormone receptors. To mark the occasion, the editors of the scientific periodical Biomolecules decided to publish a special issue in his honor. This paper summarizes what is known about PPARs and shows how trends have changed and how research on PPARs has evolved. The article also highlights the importance of PPARs and what role they play in various diseases and ailments. The paper is in a mixed form; essentially it is a review article, but it has been enriched with the results of our experiments. The selection of works was subjective, as there are more than 200,000 publications in the PubMed database alone. First, all papers done on an animal model were discarded at the outset. What remained was still far too large to describe directly. Therefore, only papers that were outstanding, groundbreaking, or simply interesting were described and briefly commented on.

The influences of selected clotting and fibrinolysis factors on survival of patients with kidney tumors - a prospective study.

Introduction: Multiple studies suggest that cancer leads to activation of clotting and fibrinolysis pathways, elevating the risk of thromboembolic events. Kidney cancer is often complicated by clotting disorders. In this study, we hypothesized that preoperative clotting and fibrinolysis parameters are altered in healthy volunteers and kidney tumor patients. We also hypothesized that these differences may be associated with survival in patients who have undergone operations due to kidney tumors. Material and methods: In this study, 96 patients with kidney tumors and 30 healthy volunteers were recruited at a single university center. All patients were assessed for pre-operative serum concentrations of tissue factor (TF), tissue factor pathway inhibitor (TFPI, total TFPI, full-length TFPI, truncated TFPI), plasmin-antiplasmin complex (PAP), thrombin-antithrombin complex (TAT), von Willebrand factor (vWF), clotting factor XIII A1 (FXIIIA1), D-dimers, and fibrinogen. Additionally, standard peripheral blood morphology was evaluated. Results: Malignant kidney tumors were diagnosed in 85 of 96 tumor patients. In patients with kidney tumors, there were statistically significantly higher concentrations of fibrinogen, D-dimers, TAT, PAF, TF, TFPI, vWF, FXIIIA1, and leukocyte counts compared to the control group. Statistically significant correlations were found between multiple parameters. This points to significant clotting system alterations. Cox stepwise hazard analysis showed that pre-operative fibrinogen and D-Dimer concentrations were significantly associated with survival. Conclusions: In patients with kidney tumors, multiple clotting and fibrinolysis parameters are significantly altered. Routine pre-operative measures should include determination of fibrinogen and D-dimer concentrations as these markers aid in prediction of survival probability.

Imaging difficulties in Takayasu arteritis - case report and review of the literature.

BACKGROUND: Takayasu arteritis is an inflammatory disease of large-diameter arteries. Aorta and its branches are most frequently affected. Takayasu arteritis occurs mainly in young women and, if left untreated, leads to fatal complications. Digital subtraction angiography (DSA) is considered the gold standard in imaging of Takayasu arteritis. CASE REPORT: A thirty-five-year-old woman was admitted to the hospital with transient loss of consciousness, effort-associated vertigo, upper limb weakness and temporary vision problems. On admission, there was no pulse on the left radial artery while there were bruits over subclavian arteries. Imaging of the aortic arch (computed tomography angiography, DSA) revealed stenoses of its main branches, indicating Takayasu arteritis. CONCLUSIONS: Computed tomography angiography (CTA) performed with a 64-slice unit revealed high effectiveness in localization of vascular wall and lumen pathologies resulting from Takayasu arteritis. Thanks to this fast diagnostic method, it is now possible to perform successful monitoring of patients with Takayasu arteritis and to plan possible interventional treatment.

Single nucleotide polymorphisms within functional regions of genes implicated in insulin action and association with the insulin resistant phenotype.

Type 2 diabetes and insulin resistance (IR) are characterized by severe anomalies in genes expression rate including genes involved in insulin signal transduction. Post-transcriptional regulation of gene expression is crucial for many physiological processes and is mediated mainly by untranslated region (UTR). Present study concentrated on the search for correlation between single nucleotides polymorphisms in UTRs of the INSR, PIK3R1, PTPN1, and SLC2A4 genes and IR. 130 unrelated diabetic patients and 98 healthy controls were analyzed in present study. Genotyping was performed by multiplex minisequencing preceded by multiplex PCR. Two single nucleotide polymorphisms (SNPs) showed significant differences in genotype frequencies between analyzed groups. Statistical significance was received for rs3745551 located in 3'-UTR of the INSR and rs3756668 located in 3'-UTR of the PIK3R1 gene with higher number of G/G genotype in insulin resistant subjects. Furthermore, patients carrying G/G genotype of those SNPs displayed higher BMI value, higher fasting glucose and insulin levels and were more insulin resistant assessed by HOMA-IR and QUICKI. Present study provides evidence for association between SNPs in UTRs of the INSR and PIK3R1 genes and insulin resistant phenotype.

[Serum level of sL-selectin and leukocyte surface expression of L-selectin in patients with type 2 diabetes]. / Stezenie sL-selektyny w surowicy krwi oraz ekspresja L-selektyny na powierzchni leukocytów chorych z cukrzyca typu 2.

UNLABELLED: The aims of the study were assessment of serum level of sL-selectin and leukocyte (neutrophil and monocyte) surface expression of L-selectin in peripheral blood. Subjects and methods. Eighty patients with type 2 diabetes were enrolled in the study. The diabetic patients were divided into three groups: group A--diabetic micro-angiopathy, group B--diabetic macroangiopathy and group C--patients without vascular complications. The control group included 20 healthy volunteers. Serum level of sL-selectin was determined by immunoenzymatic assay. Flow cytometry was used to analyse surface expresion of L-selectin. Results. In patients with type 2 diabetes sL-selectin level was significantly decreased in comparison with control group. Serum level of sL-selectin did not significantly vary between diabetic groups. In patients with diabetic microangiopathy and macroangiopathy leukocyte expression of L-selectin was significantly lower in comparison with the healthy control and patients without vascular complications. CONCLUSIONS: Serum level of sL-selectin is decreased in patients with type 2 diabetes. The development of chronic vascular complications, diabetic micro- and macroangiopathy, is accompanied by decrease of leukocyte surface expression of L-selectin.

Lack of evidence of the correlation between plasma Asymmetrical Dimethylarginine correlation and IMT in type 2 diabetic patients with chronic vascular complication.

INTRODUCTION: Patients with type 2 diabetes represent 50% of all sudden cardiac deaths. Disseminated arteriosclerotic lesions are the cause of vascular incidents that cause permanent disability resulting from lower limb amputations. OBJECTIVES: Our study was designed to investigate the relationship between asymmetrical dimethylarginine (ADMA), symmetric dimethylarginine (SDMA) plasma concentration and intima-media thickness (IMT) in subjects with diabetes mellitus without vascular complications (group A) and a group of diabetic patients diagnosed with diabetes micro- and macroangiopathy (group B). PATIENTS AND METHOD: The experimental groups included 42 diabetic patients. Group A - 22 patients (9 W and 13 M), free from vascular complications (mean age 55.83±7.37 years), group B - 20 patients (6 W, 14 M) with accompanying micro- and macropathic changes (mean age 63.80±8.79 years). Group C (n=22), the control group, consisted of healthy volunteers (12 W and 10 M), between the ages of 40 to 60 (mean age 51.16±6.39), selected in reference to the age and sex of the research group. The carotid artery intima-media complex thickness (IMT) was evaluated with the use of a duplex ultrasound. CONCLUSIONS: There was no correlation between ADMA and the maximal or mean intima-media thickness (IMT) of the common carotid artery (CCA) and internal carotid artery (ICA). We demonstrated a correlation between symmetric dimethylarginine (SDMA) concentration and CCA IMT. The results suggest that ICA IMT may serve as a marker of vascular complication among patients with diabetes.

[Chronic lower limb ischemia--clinical symptom element of atherosclerosis--actual guideline]. / Przewlekle niedokrwienie konczyn dolnych--element obrazu klinicznego miazdzycy tetnic--aktualne zalecenia.

Peripheral atherosclerosis is the leading cause of chronic lower limb ischemia (PAD). In European populations the disease occurs frequently. In the early stages often does not cause obvious symptoms. Since the PAD coexists with other areas of vascular activity is associated with high cardiovascular risk (myocardial infarction, cerebral stroke, sudden death). The article discusses the symptoms, diagnosis and treatment of the main aspects of the PAD, useful in medical practice primary care. Diagnostic strategy of patients with claudication punctuation depends on the clinical situation, the size of claudication distance and the impact this symptom on quality of life of the patient. The treatment should include modification of risk factors for atherosclerosis. Important are: smoking cessation, control of blood pressure and lipid disorders and the desire for normalization of body weight. The conservative treatment is a key consideration in antiplatelet therapy and rehabilitation.

[Paraoxonase--important enzyme of the lipid metabolism and potential ally in the antiatherosclerotic treatment]. / Paraoksonaza--wazny enzym przemian lipidowych i potencjalny sprzymierzeniec w leczeniu przeciwmiazdzycowym.

In composed process of atherogenesis take part different classes of lipoproteins. Atherogenic are low density lipoproteins (LDL), especially their modified, like oxidized, particles. Different role have high density lipoproteins (HDL): those molecules could protect arterial wall. This effect depends eg. on the presence paraoxonase 1 (PON 1) in HDL molecules. PON 1 is the enzyme with hydrolase activity. PON 1 protects lipoproteins against oxidative stress and makes possible to metabolize lipid peroxides. Several polymorphisms of the gene PON 1 have been identified. The most important for enzyme activity seem to be two polymorphisms: in the position 55 (L55M) and in the position 192 (R192Q). For instance the genotype PON 1 55 MM is connected with low enzyme serum level. Gene polymorphisms of PON could be one of the possibilities genetic conditioning of atherosclerosis.

Diabetic autonomic neuropathy of the gastrointestinal tract.

Diabetes is a metabolic disease leading to the development of numerous health complications. In developed countries, it is the main cause of blindness, end-stage renal disease, and non-traumatic amputation of the lower limbs. Neuropathy is the most common chronic complication of diabetes. A long-term course of a metabolically unbalanced disease causing damage to the autonomic nervous system of the digestive tract results in the development of many complications, such as intensification of gastro-oesophageal reflux disease, gastroparesis, chronic diarrhoea or faecal incontinence.

Advanced glycation end products derived from serum albumin modification by glucose (AGE-1) reflect clustering of lipid-associated metabolic abnormalities and are decreased in patients treated with acarbose: A cross-sectional study.

BACKGROUND: Advanced glycation end products (AGEs) are formed during protein modification by a reduction of sugars or reactive aldehydes. Depending on the pathology, various AGEs may be formed. They are stable compounds and are considered as potential diseases markers. OBJECTIVES: The objective of this study was to assess glucose-mediated albumin modification that yields non-standard epitopes of AGEs (AGE-1) in diabetes and in associated metabolic abnormalities. MATERIAL AND METHODS: The AGE-1, expressed as median AGE-1 level and AGE-1 positivity, was determined in 246 individuals (198 with prediabetes/diabetes) using a new slot-dot-blot method (allowing for detection of barely traceable analytes) and related to the presence of diabetes-associated metabolic abnormalities and complications, and treatment. RESULTS: The AGE-1 level was higher in patients with prediabetes/diabetes than in controls. Its elevation was associated with metabolic syndrome (MetS), obesity, hyperlipidemia, and non-alcoholic fatty liver disease (NAFLD) but not with diabetic control or microand macroangiopathy, except for atherosclerotic plaques formation in carotid arteries. The AGE-1-positive patients had higher triglycerides and lower high-density lipoprotein (HDL)-cholesterol. In patients untreated with aspirin, AGE-1 positivity was associated with higher C-reactive protein (CRP) level. Treatment with aspirin, sulfonylureas and gliptins was associated with higher AGE-1 level and with dyslipidemia medications with higher AGE-1 positivity. In patients with abnormal glucose metabolism, acarbose treatment was associated with lower AGE-1 positivity. Multivariate analysis showed MetS, carotid artery plaques, NAFLD, and treatment with aspirin and acarbose to be independently associated with AGE-1 positivity. CONCLUSIONS: Unlike standard AGEs, AGE-1 is more tightly associated with abnormalities in lipid than glucose metabolism, and lower in patients treated with acarbose but not with other antidiabetics.

Non-standard AGE4 epitopes that predict polyneuropathy independently of obesity can be detected by slot dot-blot immunoassay.

BACKGROUND: Advanced glycation end-products (AGEs) are formed during cascade reactions between reducing sugars or reactive aldehydes and proteins, lipids or DNA molecules. They constitute a group of various stable compounds. Advanced glycation end-products are considered potential biomarkers of metabolic disorders. However, so far only a few methods to determine the level of individual AGEs have been developed. OBJECTIVES: The aim of the study was to compare the efficiency of the slot-dot blot method and direct enzyme-linked immunosorbent assay (ELISA) in detecting non-standard epitopes of methylglyoxal (MGO)-modified proteins (AGE4) found in diabetes serum in trace amounts, and to assess AGE4 in diabetes and associated metabolic abnormalities. MATERIAL AND METHODS: The presence of AGE4 was detected using 2 methods: direct ELISA and the slot-dot blot method - a newly developed immunoassay based on monoclonal, commercially available antibody detection of non-standard AGE epitopes. AGE4 quantification, expressed as median AGE4 in arbitrary units (AU) and AGE4 positivity (the percent of samples with detectable AGE4) was related to diabetes-associated metabolic abnormalities, complications and treatment. RESULTS: Slot-dot blot was significantly more efficient than ELISA in detecting non-standard AGE4 epitopes. AGE4 positivity was less frequent in patients with microangiopathy and in those with polyneuropathy. In patients with abnormal glucose metabolism, metformin treatment was associated with higher AGE4. AGE4 positivity was significantly lower in gliptin-treated patients. Multivariate analysis showed that polyneuropathy and obesity were independently associated with AGE4 positivity, with odds ratios (ORs) of 0.21 and 3.02, respectively. Moreover, logistic regression showed that AGE4 positivity and HbA1c are independent predictors of polyneuropathy. Considering both indicators allows correct classification of 70.4% of cases with a general accuracy of 76%. CONCLUSIONS: The slot dot-blot method detects compounds found in serum in trace amounts. Accumulation of AGE4 was associated with glucose metabolism abnormalities. A tendency toward AGE4 positivity was less frequent in patients with microangiopathy and in non-treated and gliptin-treated diabetes patients.

Susceptibility to apoptosis of lymphocytes from patients with peripheral arterial disease.

PURPOSE: To determine, in vitro, the susceptibility to apoptosis of lymphocytes from patients with peripheral arterial disease (PAD) in the presence of a low culture medium serum concentration, and to evaluate the correlation of the degree of apoptosis and the serum lipid levels. METHODS: Lymphocytes were isolated from the venous blood of PAD patients with lower limb ischemia secondary to obliterative atherosclerosis of Fountain stage IIb. None of the patients had received hypo-lipemic therapy. The lymphocytes were incubated for 48 hr in media containing reduced concentrations of fetal calf serum. The study group consisted of 10 patients (7 men and 3 women), with a mean age of 67.0 +/- 4.0 yr. The control group consisted of ten healthy volunteers, of the same mean age and sex proportion as the study group. RESULTS: The percentage of non-apoptotic lymphocytes was lower (by 17%) and the percentage of late apoptotic lymphocytes was higher (by 33%) in the PAD patients than in the healthy donors when comparing the slopes of regression lines describing the relation between frequency of apoptotic lymphocytes in culture media containing reduced concentration of fetal calf serum The percentage of late apoptotic lymphocytes was correlated with the levels of total cholesterol (rs=0.93; P < 0.01) and LDL cholesterol (rs=0.80; P < 0.01) , and negatively correlated with the level of triglycerides (rs=-0.71; P < 0.05). CONCLUSION: The results of this study of lymphocyte apoptosis are important in understanding of the disease pathogenesis and should be taken into account in elaboration of treatment strategies.

[Evaluation of proinflammatory cytokines in chronic lower limb ischaemia diabetic macroangiopathy and arteriosclerosis obliterans]. / Ocena wybranych cytokin prozapalnych w przewleklym niedokrwieniu konczyn w przebiegu makroangiopatii cukrzycowej i miazdzycy zarostowej.

UNLABELLED: Proinflammatory cytokines play the crucial role in the arising and progression of atherosclerotic changes. Between them are: tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6). The significant role in the atherosclerotic changes play adhesive molecules produced by endothelium as the answer to the cytokines stimulation. THE AIM OF THE STUDY was the evaluation of the serum concentration of TNF-alpha, IL-6 and selectin E in the patients with chronic lower limb ischaemia with and without diabetes type 2. All patients had antropometric measurements (BMI) as well as the standard biochemic evaluations and the angiologic diagnosis were performed. MATERIAL AND METHODS: The 17 patients with chronic peripheral arterial disease (the mean age 55.9+/-7.8 years) and 23 with chronic arterial ischaemia and diabetes (the mean age 61.8+/-7.6 years) were included into the final evaluation. The control group consist of 14 healthy volunteers; mean age 43.9+/-11.5 years. RESULTS: The concentration of TNF-alpha in both groups was statistically significant higher in comparison to control group. High concentration of IL-6 was in patients with arteriosclerosis, and selectin E in the group with diabetes and chronic arterial ischaemia in course of macroangiopathy. CONCLUSIONS: At the satisfactory metabolic glicemic compensation and without obesity the statistically significant differences at level of analyzed cytokines in the both groups were not shown. The high level of selectin E in the diabetes group shows for the more activation of endothelium cells.

[Neutrophil surface expression of adhesion molecule CD11b in patients with type 2 diabetes]. / Ekspresja czasteczki adhezyjnej CD11b na powierzchni granulocytów obojetnochlonnych u chorych na cukrzyce typu 2.

AIMS: 1. Assessment of cell surface expression of adhesion molecule CD11b on peripheral blood neutrophils in patients with type 2 diabetes without vascular complications. 2. Analysis of serum levels of soluble adhesion molecules: E-selectin (sE-selectin), soluble Intercellular Adhesion Molecule-1 (sICAM-1), soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1) and von Willebrand Factor (vWF). 3. Evaluation of systemic inflammatory markers: Interleukin-6 (IL-6), soluble Interleukin-6 Receptor (IL-6Rs), high sensitivity C-Reactive Protein (hsCRP), fibrinogen and leptin. METHODS: 22 patients with type 2 diabetes were enrolled in the study (10-female, 12-male), aged from 40 to 65 yrs, diabetes duration mean 5.32 +/- 1.70 yrs. The control group included 20 healthy volunteers. Flow cytometry was used to analyse neutrophil expression of CD11b. Both inflammatory markers and soluble adhesion molecules were determined by immunoenzymatic assay. RESULTS: Neutrophil surface CD11b expression did not vary between groups. Significantly higher concentrations of sE-selectin, hsCRP, leptin and IL-6 were found in diabetic patients in comparison with the control group, sICAM-1, sVCAM-1, fibrinogen, vWF and IL-6Rs concentrations did not significantly vary between groups. In the diabetic group--a positive correlation was established between neutrophil CD11b expression and hsCRP, HOMA IR, BMI, leptin and fibrinogen. CONCLUSIONS: Type 2 diabetes without vascular complications is not accompanied by increase in CD11b expression on peripheral blood neutrophils. The degree of neutrophil activation is correlated with an increase in leptin serum levels. Obtained results confirm mutual connections between obesity, type 2 diabetes and chronic inflammatory process.

Receptor GP IIb/IIIa as an Indicator of Risk in Vascular Events.

Type 2 diabetes causes a significant risk of cardiovascular diseases, leading to 70% of deaths in patients with diabetes. The effective treatment of diabetes significantly reduces the risk of requiring the involvement of specialists from various fields of medicine. This research aimed to assess the risk of cardiovascular events based on selected biochemical parameters (glycoprotein [GP] IIb/IIIa, von Willebrand factor [vWf], fibrinogen) and their changes in response to physical exercise. The research group consisted of 52 patients with type 2 diabetes with micro- or macro-angiopathy at a mean age of 63.80 years (8.79). The control group consisted of 50 healthy volunteers (17 women and 33 men) at a mean age of 51.16 years (6.39). All the patients consented to have their venous blood tested to measure complete blood counts. Activated GP IIb/IIIa receptors were labeled and analyzed by flow cytometry. Mean values of vWF factor were higher when compared with the control group (196.59% [80.32%] vs 148.06% [90.34%], respectively). The GP IIb/IIIa receptor expression was much higher in test patients than in the control group (3.91% [2.91%] vs 2.79% [2.51%]). Physical exercise had a positive influence on GP IIb/IIIa receptor expression and vWF, decreasing their baseline percentage values.

Analysis of peripheral nerve and autonomic nervous system function and the stage of microangiopathy in patients with secondary Raynaud's phenomenon in the course of connective tissue diseases.

BACKGROUND: The pathogenesis of secondary Raynaud's phenomenon (SRP) associated with connective tissue diseases (CTD) is not entirely understood. Nervous system dysfunction and microangiopathy are considered to be causes of this pathology. OBJECTIVES: Peripheral and autonomic nervous system function, the stage of microangiopathy, and the relationships between these in patients with SRP were analyzed. MATERIAL AND METHODS: In the study, 20 patients with CTD-related SRP and 30 healthy controls were subject to capillaroscopy, standard conduction velocity tests and conduction velocity distribution (CVD) tests in ulnar and peroneal nerves, heart rate variability (HRV), and sympathetic skin response (SSR) tests. RESULTS: There were no significant differences in the standard motor and sensory conduction velocity tests, or in CVD tests in the ulnar and peroneal nerves in SRP patients compared with the controls. The patients with SRP had a significantly lower SSR amplitude and longer latency in hands and feet. The patients with CTD-related SRP had a significantly lower mean HRV with higher low frequency (LF) values in the spectral analysis and expiration/inspiration ratio (E/I) during deep breathing. There was no correlation between the stage of microangiopathy and neurophysiological test results. CONCLUSIONS: Correct standard conduction velocity and CVD testing in patients with SPR suggest that vasomotor disturbances may occur in CTD regardless of peripheral neuropathy. The lack of relationship between SSR and microangiopathy could confirm that these 2 processes occur independently in patients with CTD-related SRP. Autonomic nervous system impairment together with normal peripheral nerve function suggest the central origin of CTD-related SRP.