An Experimental Phototherapy Device for Studying the Effects of Blue Light on Patients with Raynaud's Phenomenon.

Raynaud's phenomenon (RP) is a condition that causes decreased blood flow to areas perfused by small blood vessels (e.g., fingers, toes). In severe cases, ulceration, gangrene, and loss of fingers may occur. Most treatments focus on inducing vasorelaxation in affected areas by the way of pharmaceuticals. Recently, animal studies have shown that vasorelaxation can be induced by non-coherent blue light (wavelength ~ 430-460 nm) through the actions of melanopsin, a photoreceptive opsin protein encoded by the OPN4 gene. To study this effect in humans, a reliable phototherapy device (PTD) is needed. We outline the construction of a PTD to be used in studying blue light effects on Raynaud's patients. Our design addresses user safety, calibration, electromagnetic compatibility/interference (EMC/EMI), and techniques for measuring physiological responses (temperature sensors, laser Doppler flow sensors, infrared thermal imaging of the hands). We tested our device to ensure (1) safe operating conditions, (2) predictable, user-controlled irradiance output levels, (3) an ability for measuring physiological responses, and (4) features necessary to enable a double-blinded crossover study for a clinical trial. We also include in the Methods an approved research protocol utilizing our device that may serve as a starting point for clinical study. We introduced a reliable PTD for studying the effects of blue light therapy for patients suffering from Raynaud's phenomenon and showed that our device is safe and reliable and includes the required measurement vectors for tracking treatment effects throughout the duration of a clinical study.

ARTERIAL INSUFFICIENCIES: Hyperbaric Oxygen Therapy for Selected Problem Wounds.

The use of hyperbaric oxygen (HBO2) for the treatment of selected problem wounds has focused almost entirely on the diabetic foot ulcer (DFU) in recent years. The prevalence of DFUs in today's patient population and the reimbursement available for the treatment of DFUs have given it priority status in discussions about problem wounds, but there are sound fundamental reasons why additional oxygen may have benefits in the treatment of non-DFU wounds.

The complementary effects of galvanic current electrical stimulation associated with conservative treatment to increase vasodilation in patients with Raynaud's phenomenon: a randomized trial.

OBJECTIVE: To analyze the effectiveness of an electrotherapy intervention with galvanic current on symptoms associated with Raynaud's phenomenon. DESIGN: Single-blind randomized controlled trial, parallel design (1:1 ratio) and intention-to-treat analysis. SETTING: Virgen de las Nieves Hospital, Granada, Spain. SUBJECTS: Thirty-four participants with Raynaud's phenomenon, with a mean (SD) age of 43.43 (17.62) years. INTERVENTIONS: The patients were randomly assigned to a control group with conservative treatment (anti-inflammatory, vasodilatory and analgesic drugs) or an intervention group that received conservative treatment and vasodilatory electrical stimulation during seven weeks, three times/week for a total of 20 sessions. MAIN MEASURES: The primary outcome was the number of attacks. Secondary outcomes were pain, peripheral blow flow, oxygen saturation, upper limb disability, central sensitization, pain catastrophizing and temperature recovery. All outcomes were assessed at baseline, posttreatment and at two months of follow-up. RESULTS: The galvanic current electrotherapy group showed significantly greater improvements in the number of attacks (mean difference = 26.3, 95% confidence interval (CI) = 14.4 to 38.3), pre-cold stress pain (95% CI = 0.6 to 2.4), radial artery blood flow (95% CI = -7.8 ⩾ x ⩽ 1.3), ulnar artery blood flow (95% CI = -8.63 to 0.60), oxygen saturation (95% CI = -1.7 ⩾ x ⩽ -0.29), upper limb disability (95% CI = 1.1 to 22.3), central sensitization (95% CI = 6.7 to 18.2) and temperature recovery (95% CI = -5.7 ⩾ x ⩽ -0.32) than the conservative treatment group. CONCLUSION: This study suggests that a complementary treatment with galvanic current in combination to conservative approach is superior to conservative applied as isolate, in reducing the clinical manifestations and disability in Raynaud's phenomenon.

"Beet" the cold: beetroot juice supplementation improves peripheral blood flow, endothelial function, and anti-inflammatory status in individuals with Raynaud's phenomenon.

Raynaud's phenomenon (RP) is characterized by recurrent transient peripheral vasospasm and lower nitric oxide (NO) bioavailability in the cold. We investigated the effect of nitrate-rich beetroot juice (BJ) supplementation on 1) NO-mediated vasodilation, 2) cutaneous vascular conductance (CVC) and skin temperature (Tsk) following local cooling, and 3) systemic anti-inflammatory status. Following baseline testing, 23 individuals with RP attended four times, in a double-blind, randomized crossover design, following acute and chronic (14 days) BJ and nitrate-depleted beetroot juice (NDBJ) supplementation. Peripheral Tsk and CVC were measured during and after mild hand and foot cooling, and during transdermal delivery of acetylcholine and sodium nitroprusside. Markers of anti-inflammatory status were also measured. Plasma nitrite concentration ([nitrite]) was increased in the BJ conditions (P < 0.001). Compared with the baseline visit, thumb CVC was greater following chronic-BJ (Δ2.0 flux/mmHg, P = 0.02) and chronic-NDBJ (Δ1.45 flux/mmHg, P = 0.01) supplementation; however, no changes in Tsk were observed (P > 0.05). Plasma [interleukin-10] was greater, pan endothelin and systolic and diastolic blood pressure (BP) were reduced, and forearm endothelial function was improved, by both BJ and NDBJ supplementation (P < 0.05). Acute and chronic BJ and NDBJ supplementation improved anti-inflammatory status, endothelial function and blood pressure (BP). CVC following cooling increased post chronic-BJ and chronic-NDBJ supplementation, but no effect on Tsk was observed. The key findings are that beetroot supplementation improves thumb blood flow, improves endothelial function and anti-inflammatory status, and reduces BP in people with Raynaud's.NEW & NOTEWORTHY This is the first study to examine the effect of dietary nitrate supplementation in individuals with Raynaud's phenomenon. The principal novel findings from this study were that both beetroot juice and nitrate-depleted beetroot juice 1) increased blood flow in the thumb following a cold challenge; 2) enhanced endothelium-dependent and -independent vasodilation in the forearm; 3) reduced systolic and diastolic blood pressure, and pan-endothelin concentration; and 4) improved inflammatory status in comparison to baseline.

No significant effect of ginkgo biloba special extract EGb 761 in the treatment of primary Raynaud phenomenon: a randomized controlled trial.

BACKGROUND: Medicinal treatment of vasospastic Raynaud phenomenon is limited to primarily vasodilator medicines. OBJECTIVE: To explore the possible beneficial effects and tolerability of 120 mg two times a day of Ginkgo Biloba special extract EGb 761 in patients suffering from Raynaud disease (RD) (primary Raynaud phenomenon). METHODS: In a placebo-controlled, double-blind, pilot study, 41 patients with RD were randomized to either the active treatment group (EGb 761, n = 21) or placebo group for 10 weeks, after an initial 2-week run-in phase. The primary efficacy variables were self-reported changes of the frequency, duration, and severity of vasospastic attacks between the placebo-controlled run-in phase and the end of the study. RESULTS: Most of the patients were female, and both groups were perfectly matched with respect to demographic characteristics. The frequency of daily attacks reduced from 3.6 ± 2.3 to 2.4 ± 2.6 (-33%) in the EGb 761 group and from 2.9 ± 2.0 to 2.0 ± 1.8 (-31%) in the placebo group with no significant difference according to the ordinary least squares test (P = 0.3564). Furthermore, no significant differences were found with respect to the duration and severity of vasospastic attacks between the EGb 761 and placebo groups (P = 0.4392 and P = 0.7187, respectively). In all, 17 adverse events (AEs) were reported, 6 AEs from 5 patients in the EGb 761 group and 11 AEs from 8 patients in the placebo group. Serious AEs did not occur. CONCLUSION: EGb 761 treatment showed an excellent safety profile in patients with RD but could not demonstrate a statistically significant reduction in clinically relevant symptoms compared with placebo.

25. Ischemic pain in the extremities and Raynaud's phenomenon.

Two important groups of disorders result from an insufficient blood supply to the extremities: critical vascular disease and the Raynaud's phenomenon. The latter can be subdivided into a primary and a secondary type. Critical ischemic disease is often caused by arteriosclerosis due to hypertension or diabetes. Primary Raynaud's is idiopathic and will be diagnosed as such if underlying systemic pathology has been excluded. Secondary Raynaud's is often a manifestation of a systemic disease. It is essential to try to establish a diagnosis as soon as possible in order to influence the evolution of the disease. A sympathetic nerve block can be considered in patients with critical ischemic vascular disease after extensive conservative treatment, preferably in the context of a study (2B±). If this has insufficient effect, spinal cord stimulation can be considered in a selected patient group (2B±). In view of the degree of invasiveness and the costs involved, this treatment should preferably be applied in the context of a study and with the use of transcutaneous pO(2) measurements. In case of primary Raynaud's, life style changes are the first step. Sympathectomy can be considered as a treatment of Raynaud's phenomenon (2C+), but only after multidisciplinary evaluation of the patient and in close consultation with the patient's rheumatologist, vascular surgeon or internist.

[The experience with thoracoscopic sympathectomy for the treatment of distal lesions of limb arteries].

The study included 107 patients with distal lesions of limb arteries treated with the use of thoracoscopic sympathectomy. The best results in the early postoperative period were obtained in patients with Raynaud's disease. Modifications introduced into the methods of its treatment permitted to retain effectiveness of sympathectomy till the late postoperative period in 90% of the patients. Surgery for obliterative endarteritis and atherosclerosis was viewed as a possibility to preserve the supporting function of the limb. This purpose was attained in 73.2 and 62.5% of the patients respectively in the early and in 62 and 25% in the late postoperative periods.

Peripheral blood perfusion correlates with microvascular abnormalities in systemic sclerosis: a laser-Doppler and nailfold videocapillaroscopy study.

OBJECTIVE: To investigate possible correlations between fingertip blood perfusion (FBP) status, assessed by laser Doppler flowmetry (LDF), and morphological microvascular abnormalities, detected by nailfold videocapillaroscopy (NVC), in patients with systemic sclerosis (SSc). The effects on FBP of intravenous (IV) treatment with the prostacyclin analog iloprost were also investigated. METHODS: Thirty-four consecutive patients with SSc and 16 healthy subjects were evaluated. LDF was performed by analyzing blood perfusion at the fingertips in both hands. Patients with SSc were distributed into the appropriate NVC pattern of microangiopathy (early, active, and late). Iloprost was administered to inpatients with SSc by 24-hour IV infusion for 7 consecutive days (4 microg/h). RESULTS: FBP was significantly lower in patients with SSc (p < 0.05) compared to controls. Heating of the LDF probe at 36 degrees C induced a significant increase of FBP in all subjects (p < 0.001), but the slope of variation was significantly lower in patients with SSc compared to controls (p < 0.05). Patients with SSc showing the late NVC pattern of microangiopathy had significantly lower FBP than patients with the active and early NVC patterns (p < 0.05). A negative correlation was observed between FBP and NVC rating of the microvascular damage (p < 0.05). After iloprost treatment, a significant increase of FBP was observed in patients with SSc (p < 0.05). CONCLUSION: Patients with SSc show a decreased FBP partially reversible by local skin heating. The FBP correlated negatively with the extent of nailfold microvascular damage, and IV iloprost treatment increased the FBP.

Percutaneous upper thoracic radiofrequency sympathectomy in Raynaud phenomenon: a comparison of T2/T3 procedure versus T2 lesion with phenol application.

BACKGROUND AND OBJECTIVES: Percutaneous radiofrequency (RF) thoracic sympathectomy is an alternative method to surgical procedures for the treatment of acral ischemia in Raynaud phenomenon. The procedure is indicated if conservative therapy fails to provide sufficient relief. The aim of this study was to compare classic T2 and T3 RF thermolesioning with a less invasive procedure at the level of T2 only. METHODS: Fifty adult patients, American Society of Anesthesiologists (ASA) classification I to III, were randomly assigned to 1 of 2 groups. T2 and T3 thoracic RF thermolesion was performed in 1 group, whereas T2 thermolesion with local application of 0.5 mL of 6% phenol was delivered in the second group. Changes in cold perception, pain, and quality of life were assessed using a questionnaire. Blood circulation in the upper extremity was evaluated using infrared thermography. Patients were observed for a period of 3 months. RESULTS: A significant decrease in pain according to visual analog scale (P < 0.001), increase in peripheral temperature in the upper extremities (P < 0.001), and improvement in quality of life were observed in both groups of patients after the procedure. Susceptibility to cold-provoked vasospasm was not significantly affected in either group. There was no significant difference between the 2 groups in any parameter apart from the duration of the procedure. CONCLUSIONS: Thoracic RF upper sympathectomy is an effective method in the treatment of resistant forms of Raynaud phenomenon. A single-shot procedure at the level of T2 may be preferable because of the shorter procedure duration of this technique.

Effects of the myofascial release in diffuse systemic sclerosis.

OBJECTIVE: To improve breathing and functionality of the temporomandibular joint (TMJ) and hands, by increasing the range of motion (ROM), and to reduce the level of pain. METHOD: Twenty myofascial release (MR) sessions in 2002 with assessments (chest expansion, mouth opening, ROM of wrist and fingers). Between the 19th and the 20th session there was a break of 110 days. Every winter, 1-3 sessions have been made. RESULTS: Chest: expansion increased by 3.5 cm and pain was eliminated at the scar from a biopsy; TMJ: an 8mm increase in mouth opening with pain eliminated; hands and fingers: increase of ROM in all joints of fingers and wrists, of up to 100%, reduction in ulcerations and recovery of nail growth. CONCLUSION: The connective tissue affected by diffuse systemic sclerosis (dSSc) is subject to remodeling through MR, receding when the work is interrupted. Resuming the treatment on a regular basis increased the ROM in joints, reduced the effects of the Raynaud Phenomenon and the pain.

Fenómeno de Raynaud / Raynaud’s Phenomenon

El fenómeno de Raynaud se caracteriza por una disminución de la circulación sanguínea, fundamentalmenteen los dedos de las manos y de los pies, con dolor y cambios de coloración en la piel deuna forma secuencial: blanco, azul y rojo. Es más frecuente en las mujeres, en la 2ª y 3ª décadasde la vida. Se desconoce cuál es su causa, pero guarda relación con el consumo de tabaco, alcohol,y fundamentalmente con los cambios de temperatura y alteraciones emocionales. Se asocia aenfermedades del tejido conectivo, entre las que Esclerodermia y Lupus son las más frecuentes. ElNifedipino es el fármaco de primera elección(AU)

Raynaud’s phenomenon is characterized by a decrease in blood circulation mainly in the fi ngers andtoes, with pain and changes in skin colour which follow a characteristic pattern white, blue and red. Itis more common in women, in the 2nd and 3rd decade of life. The cause is unknown, but is related tosmoking and alcohol consumption, and particularly body temperature changes and emotional stress.It is associated with connective tissue diseases amongst which scleroderma and lupus are the mostfrequent. Nifedipine is the treatment of choice(AU)

Vascular response of Raynaud's phenomenon to nifedipine or herbal medication (duhuo-tisheng tang with danggui-sini tang): a preliminary study.

BACKGROUND: Raynaud's phenomenon (RP) is a common manifestation in connective tissue diseases. Calcium channel antagonists are most effective and frequently used for treating RP. This study compared the efficacy, digital vascular response, and tolerability between nifedipine and a combination of 2 Chinese herbal medications (duhuo-tisheng tang and danggui-sini tang) for treating RP. METHODS: This open-label non-randomized clinical trial included 47 connective tissue disease patients with RP. The herbal group and the nifedipine group included 26 and 21 patients, respectively. The duration of therapy was 4 weeks. Baseline and posttreatment laser Doppler blood flow imaging of both hands were performed at room temperature and after cold challenge. Nailfold capillary microscopy was performed at the baseline and after 4 weeks of therapy. Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), prostaglandin E2 (PGE2), nitrite (NO2), and nitrate (NO3), and plasma levels of endothelin-1 (ET-1) were also measured. Self-reported symptoms, using a visual analog scale (VAS) and a physician global assessment (PGA), were recorded at the baseline and after treatment. RESULTS: After 4 weeks of treatment, VAS scores improved (p = 0.0035) and the physician's global assessment of RP severity decreased in the nifedipine group (p = 0.0078) but not in the herbal group. Episodes of RP attacks decreased in the nifedipine group after treatment (p = 0.008). The nifedipine group had increased laser Doppler flow (116.3 +/- 70.7 AU) compared to the baseline (72.4 +/- 49.0 AU, p = 0.0008). Laser Doppler images improved at various time points after cold challenge in the nifedipine group after therapy. Laser Doppler flow in the herbal group did not significantly change with therapy. Capillary microscopy demonstrated no significant difference in enlargements, avascularity, or hemorrhagic spots between groups. Serum NO2 concentrations were higher in the nifedipine group than in the herbal group. Levels of sICAM-1, PGE2, NO3, and ET-1 after therapy were similar to those at the baseline in both groups. CONCLUSIONS: The digital vascular response in RP improved with nifedipine but was unchanged with a combination of the Chinese medicines Duhuo-Tisheng Tang and Danggui-Sini Tang.

Nerve conduction velocities in the lower extremity in patients with Raynaud's phenomenon and clinical applications.

BACKGROUND AND PURPOSE: The purpose of the study is to study the nerve conductivity of the tibial motor, peroneal motor, peroneal sensory, and sural nerves in patients with primary and secondary Raynaud's phenomenon (RP). SUBJECTS: Twenty each: primary RP, secondary RP, and normal controls. METHODS: Electromyography using distal latency (DL) and nerve conduction velocity (NCV) as dependent variables. RESULTS: Peroneal nerve DLs were slower and NCVs were weaker for the secondary RP group compared to the primary RP group and controls. Tibial motor nerve DLs from slowest to fastest were: primary RP, secondary RP, and controls. NCV strength order was: secondary RP weakest, primary RP, and controls. DISCUSSION: Patients with secondary RP generally had the slowest DLs and the weakest NCVs, with differences most pronounced in the motor nerves. With the exception of the tibial motor nerve, patients with primary RP had similar NCVs to the control group. Neural mobilization techniques can be applied to assist with patient symptoms.

Efficacy of myofascial release techniques in the treatment of primary Raynaud's phenomenon.

OBJECTIVE: This study investigated whether myofascial release techniques performed on upper body connective tissue could mitigate the frequency, duration or pain intensity associated with primary Raynaud's phenomenon. METHODS: Five treatments were administered over a 3-week treatment period on a 35-year-old female experiencing primary Raynaud's phenomenon for the past 12 years. A log was kept documenting frequency, duration and severity of pain. The myofascial work targeted the upper back, neck and arms according to hypothetical fascial meridian lines. RESULTS: Symptom duration was the one characteristic that showed improvement. After the first treatment, the duration of the subject's vasospastic episodes was reduced by almost half and continued to decrease throughout the 3 weeks of treatments. Neither the frequency or number of affected digits varied significantly from the pre-treatment weeks. CONCLUSIONS: The results suggest that by releasing restricted fascia, myofascial techniques may influence the duration and severity of the vasospastic episodes experienced in primary Raynaud's phenomenon.

[The treatment of neurospastic vascular diseases in Raynaud phenomenon].

The efficacy of proposed methods for cardiovascular diseases with Raynaud phenomenon manifestations treatment was estimated. After application of the author method the patients extremities temperature had raised by 2 .50 degreesC. They had noted the pain and the extremities oedema elimination, trophic ulcers healing. According to Doppler investigation data the blood flow linear speed increase by 30 0% in comparison with pretreatment one was noted. The posttreatment complications were absent. Fair and good results were observed in 306 (82.3%) patients, in 21 (5.6%) patients the treatment was repeated in conditions of severe ischemia and the blood flow decompensation present. In 14 (3.8%) patients a high epidural blockade of sympathic nodes in portion of high thoracic and lower cervical vertebra according to the author method was performed. In far-remote period (in 3-10 years) the positive effect was prolonged in 298 (80.1%) patients.

A case of spinal cord stimulation in Raynaud's Phenomenon: can subthreshold sensory stimulation have an effect?

Spinal cord stimulation is currently used to treat a variety of chronic intractable painful conditions. We report a case of severe Raynaud's phenomenon in the hands refractory to conservative treatment and responsive to diagnostic stellate ganglion block that was effectively treated with a spinal cord stimulator placed in the cervical epidural space. After capturing the affected areas with paresthesias, blood flow in the left hand and fingers significantly improved as evidenced by an increase in skin temperature, a change from cyanotic to pink appearance and concomitant reduction in pain. Moreover, the patient reported that limb ischemia and pain could be managed overnight with stimulation intensities that were below sensory perception thresholds. Thus it seems, at least in the overnight period, paresthesias were not required to maintain pain relief. This case presents a potential divergence between a requirement for paresthesias and pain relief in spinal cord stimulation therapy for the treatment of Raynaud's phenomenon. The possible role of the sympathetic nervous system in this relationship is also discussed.

Treatment of Raynaud's phenomenon with the selective serotonin reuptake inhibitor fluoxetine.

OBJECTIVE: To compare fluoxetine, a selective serotonin reuptake inhibitor, with nifedipine as treatment for primary or secondary Raynaud's phenomenon. METHODS: Twenty-six patients with primary and 27 patients with secondary Raynaud's phenomenon were assigned randomly to receive 6 weeks of treatment with fluoxetine (20 mg daily) or nifedipine (40 mg daily). Following a 2-week washout period, each group was crossed over to the other treatment arm. The primary outcome variable was the frequency of attacks of Raynaud's phenomenon. Self-reported attack severity, thermographic recovery from cold challenge and plasma levels of von Willebrand factor and soluble P-selectin were also measured. RESULTS: There was a reduction in attack frequency and severity of Raynaud's phenomenon in patients treated with either fluoxetine or nifedipine, but the effect was statistically significant only in the fluoxetine-treated group (P=0.0002 for attack severity and P=0.003 for attack frequency). Subgroup analysis showed that the greatest response was seen in females and in patients with primary Raynaud's phenomenon. A significant improvement in the thermographic response to cold challenge was also seen in female patients with primary Raynaud's phenomenon treated with fluoxetine but not in those treated with nifedipine. There was no significant treatment effect on von Willebrand factor or soluble P-selectin. No significant adverse effects occurred in the fluoxetine-treated group. CONCLUSION: This pilot study confirms the tolerability of fluoxetine and suggests that it would be effective as a novel treatment for Raynaud's phenomenon. Larger and placebo-controlled trials are warranted to assess fluoxetine's therapeutic potential further in this vasospastic condition.

The effects of stress, anxiety, and outdoor temperature on the frequency and severity of Raynaud's attacks: the Raynaud's Treatment Study.

It was expected that stress and anxiety would be related to Raynaud's phenomenon (RP) attack characteristics when mild outdoor temperatures produced partial or no digital vasoconstriction. Hypotheses were that in warmer temperature categories, compared to those below 40 degrees F, higher stress or anxiety would be associated with more frequent, severe, and painful attacks. The Raynaud's Treatment Study recruited 313 participants with primary RP. Outcomes were attack rate, severity, and pain. Predictors were average daily outdoor temperature, stress, anxiety, age, gender, and a stress-by-temperature or an anxiety-by-temperature interaction. Outcomes were tested separately in multiple linear regression models. Stress and anxiety were tested in separate models. Stress was not a significant predictor of RP attack characteristics. Higher anxiety was related to more frequent attacks above 60 degrees F. It was also related to greater attack severity at all temperatures, and to greater pain above 60 degrees F and between 40 degrees and 49.9 degrees F.