Raynaud's Disease Patients Research Articles

Development and validation of the RQLQ: a Raynaud's disease-specific measure of health-related quality of life.

The aim of this study was to develop and validate the Raynaud Specific Quality of Life Questionnaire (RQLQ) for assessing health-related quality (HRQOL) of life in patients with Raynaud's disease (RD). The questionnaire was developed and validated in three stages. Initially, semi-structured interviews with 28 RD patients identified domains of everyday life affected by RD, leading to the creation of the initial RQLQ. In the first quantitative stage, 101 patients completed the RQLQ, and exploratory factor analysis assessed dimensionality and factor structure. After removing poorly performing items, the final RQLQ was tested with 102 patients. This stage also evaluated convergent, divergent, and discriminant validity, as well as internal reliability. From the interviews, 135 items were generated, with factor analysis refining the measure to 29 items across five subscales, showing good internal consistency. The RQLQ demonstrated significant correlations with self-rated quality of life and physical and mental health outcomes, confirming convergent and divergent validity. It also showed discriminant validity for different levels of disease activity. The RQLQ is the first specific HRQOL measure for RD patients, proving to be a psychometrically sound, reliable, and valid tool for clinical research and practice. Key Points • The Raynaud Specific Quality of Life Questionnaire (RQLQ) is an important scale that evaluates the quality of life of patients with Raynaud's disease. • The questionnaire showed good validity and reliability a capturing disease-specific quality of life. • This tool may aid in clinical research and practice.

Exaggerated local hand sympathetic but not renin–angiotensin system activation in patients with primary Raynaud's phenomenon

In Raynaud's disease (RD), an overactivity of sympathetic nervous system (SNS) was hypothesized but only indirect proofs were obtained. Complex interactions between the renin–angiotensin system (RAS) and SNS were reported without clear demonstrations of a RAS involvement. Recently, the use of ACE inhibitors and AT1 receptor antagonists in RD patients showed mixed results. The study of total and regional kinetics of tritiated noradrenaline (NA) and the measurements of local Angiotensin (Ang) I and II arterial–venous gradient were performed in 10 RD patients and 10 controls both in rest conditions and following a cold pressor test (CPT). Hand blood flow (HBF) was measured by strain-gauge plethysmography. Baseline HBF was slightly lower in patients than in controls, but during CPT, it significantly decreased only in RD patients ( P < 0.01). Total ( 3H)-NA clearance and spillover were similar in the two groups throughout the study. On the contrary, baseline hand NA spillover was higher in RD patients than in controls and the difference further increased during CPT. Hand NA spillover was linearly related to HBF ( P < 0.001). Arterial–venous Ang I and Ang II gradients were positive without difference between controls and patients throughout the study. In conclusion in RD patients, a pathological waste of NA from sympathetic nervous endings of the hand region, exaggerated by sympathetic stimulation, occurs but an enhanced local Ang II formation was not demonstrable.

Erythrocyte transport efficacy of human blood: a rheological point of view

Large-scale epidemiological studies have demonstrated that both anaemia and polycytaemia are independent cardiovascular risk factors. This was substantiated by the Framingham study, which demonstrated a U-shaped relation between haemoglobin concentration and mortality. It was previously noted that delineating the corresponding haematocrit/blood viscosity ratios in the function of haematocrit provided a distribution of an inverted U-shaped curve. The peak appeared physiologically important because it denotes a healthy balance between a relatively high oxygen binding capacity and a moderately low blood viscosity. It was the aim of this study to examine the mathematical relationship between the haematocrit and haematocrit/blood viscosity ratio. In a retrospective study, the haemorheological data of 32 healthy controls, 52 outpatients with hyperlipidaemia and 120 outpatients with Raynaud's disease were analyzed. Whole blood viscosity was measured with Hevimet 40 capillary viscometer at 37.0 degrees C and at shear rates of 10 s(-1), 90 s(-1) and 200 s(-1). Haematocrit/blood viscosity ratios in the function of haematocrit values showed a Gaussian association in the healthy subjects, hyperlipidaemic and Raynaud's disease outpatient groups. Peak values (i.e. the rheologically optimal haematocrit) were shear-rate and group dependent and were found at 44.3%, 43.5% and 38.3% in controls, hyperlipidaemic and Raynaud's disease patients, respectively, at a shear rate of 90 s(-1). This is one of the first reports in which a theoretically optimal haematocrit value was determined using the haematocrit/blood viscosity ratio. Further studies are needed to examine the potential clinical usefulness of this approach.

Increased tyrosine phosphorylation mediates the cooling‐induced contraction and increased vascular reactivity of Raynaud's disease

Increased levels of protein tyrosine kinase (PTK) are mechanistically associated with increased contractile responsiveness to cooling. This study tests the hypothesis that increased PTK activity mediates the increased vascular reactivity to agonists and cooling associated with primary Raynaud's disease (RD). The response of dermal arterioles isolated from control (n = 29) and RD (n = 29) subjects to contractile and dilatory agents at 37 degrees C and 31 degrees C was characterized using the microvessel perfusion technique. Fluorescence immunohistochemistry was used to measure tyrosine phosphorylation. At 37 degrees C, arteries from RD patients exhibited similar sensitivity to the specific alpha(2)-adrenergic agonist UK 14,304, to serotonin, and to angiotensin II. At 31 degrees C, however, the response to all 3 agonists was greater in the arterioles from the RD patients than in those from the control subjects. Agonist-induced contraction at both temperatures was reversed by cumulative addition of the PTK inhibitors genistein (1-30 microM) and tyrphostin 47 (0.1-10 microM). All arterioles from control subjects relaxed slightly in response to cooling, whereas more than half of those from RD patients contracted. This cooling-induced contraction was reversed by the cumulative addition of genistein. The 3 agonists elicited large increases in tyrosine phosphorylation only in arterial segments from RD patients at 31 degrees C. Cooling from 37 degrees C to 31 degrees C elicited a large increase in tyrosine phosphorylation in arterioles from RD patients, but not those from control subjects. All increases in tyrosine phosphorylation could be prevented by genistein. Increased tyrosine phosphorylation mediates cooling-induced contraction and the increased vascular reactivity of skin arterioles from individuals with RD.

Impaired cholinergic dilator response of resistance arteries isolated from patients with Raynaud's disease.

We examined the effect of cooling on the response to the endothelium-dependent and -independent dilators, acetylcholine (ACh) and sodium nitroprusside (SNP), respectively, in human microvessels in vitro, and compared the responses between Raynaud's disease (RD) patients and controls, in order to assess the pathogenic role of the endothelium in RD. Subcutaneous resistance arteries were dissected from gluteal fat biopsies taken from patients with RD (n=18) and from age-and sex-matched control subjects (n=17). Vessels were cannulated in a small vessel arteriograph, in which a pressure of 50 mmHg was maintained across the vessel wall. Cumulative concentration-response curves for ACh (10-10-10-4 m ) and SNP (10-10-10-3 m ) were generated in vessels at either 37 degrees C or 24 degrees C, with endothelium intact for ACh and removed for SNP (n=6 per group). Neither dilator showed significant differences in sensitivity when comparing responses between vessels from RD patients and controls, at either temperature, but the maximal relaxation to ACh was depressed in vessels from RD patients compared with controls at 37 degrees C (Emax=45+/-13 in RD vs 89+/-4 in controls; P=0.004). These results support the hypothesis that impaired endothelium-dependent vasodilatation is involved in the pathophysiology of RD.

Physiological mechanisms of temperature biofeedback

Research on the physiological mechanisms of finger temperature biofeedback with normal subjects and Raynaud's disease patients is reviewed. Studies conducted in the author's laboratory have shown that feedback-induced vasodilation is mediated through a non-neural, beta-adrenergic mechanism rather than through reductions in sympathetic nervous system activation. In contrast, feedback-induced vasoconstriction is mediated through the traditional, sympathetic nervous pathway. When used with primary Raynaud's disease patients, feedback-induced vasodilation has achieved reductions in reported symptom frequency ranging from 66% to 92% in controlled investigations. Future research directions are discussed.

Nonneural beta-adrenergic vasodilating mechanism in temperature biofeedback.

Although finger temperature feedback has been used to produce digital vasodilation in normal persons and those with Raynaud's disease, the mechanism and site of this effect have not been studied. In the present investigation, feedback-induced vasodilation was attenuated by brachial artery infusions of propranolol in infused, but not contralateral, hands and was not affected by digital nerve blockade. Quantitative measurements of finger blood flow demonstrated that this vasodilation occurred in arteriovenous shunts in normal persons and in the finger capillary bed in those with Raynaud's disease. Raynaud's disease patients who received finger temperature feedback reported 80 fewer percent symptoms 1 and 2 years after treatment and retained the ability to increase finger temperature and capillary blood flow at these times. These effects were not shown by patients given autogenic training, a relaxation procedure.

Colour changes during 'Raynaud's phenomenon' and finger blood supply during direct and indirect cooling procedures.

Summary The influence of body (indirect cooling) and local linger cooling on finger blood pressure and blood flow was examined in 48 patients claiming Raynaud's phenomenon. Twenty-four were suffering from generalized scleroderma (GS) and 24 from Raynaud's disease (RD). Skin blood flow was measured by laser Doppler flowmetry and blood pressure measurement at different temperatures was performed by a ‘digit-cooling’ system, Colour changes during Raynaud arracks, as described b the patients, were noted. The patients could be divided into three groups: (1) Mild cases where combined finger and body cooling was needed to elicit flow arrest (Raynaud attack), or flow arrest could not be elicited in the laboratory (79% of RD and 33% of GS). Flow stop in these cases seemed to occur distally to the digital arteries. This finding was highly correlated to attacks described as pallor followed by varying degrees of rubor. (2) More severe cases, where flow arrest could be elicited after local finger cooling alone (50% of the GS and 19% of the RD patients). Here, flow stop seemed to occur at the level of the digital arteries. This finding was highly correlated to attacks described as pallor followed by cyanosis, and rubor in varying degrees. (3) The most severe cases where finger circulation stopped after body cooling (indirect cooling) alone. This was seen in 25% of GS patients. The finding was correlated with attacks described as finger cyanosis as an isolated finding, which was only seen in GS. Therefore, observing any form of finger cyanosis during Raynaud's attacks in patients should lead one to suspect an underlying disease, which may often be a connective tissue disease.

Effects of general and thematically relevant stressors in Raynaud's disease

Emotional Stress has been reported to cause vasospastic attacks in some patients with idiopathic Raynaud's disease. In the present study, the physiological and subjective responses of 32 Raynaud's disease patients and 22 normal subjects to three imagined scenes were compared. Both groups responded similarly to a neutral and a generally stressful scene. However, a scene having content thematically relevant to Raynaud's disease produced decreased finger temperature in these patients but not in normal controls. These findings are discussed in terms of stimulus specificity and social learning theories.

Biofeedback treatment of Raynaud's disease and phenomenon.

Six Raynaud's disease and four Raynaud's phenomenon patients were treated with 12 sessions of finger temperature biofeedback. The mean frequency of vasospastic attacks was reduced to 7.5% of that reported during the pretreatment baseline and was maintained for a 1 year follow-up period. Significant control of digital temperature was demonstrated during laboratory training sessions. Raynaud's phenomenon patients showed significantly greater temperature increases during feedback periods than Raynaud's disease patients. Correlations between finger temperature and other physiological measures suggested that results could not be attributed to general physical relaxation. The role of imagery in self-control of digital temperature is considered.