Coleman C.E.; Sessoms S.L.; Gowin K.M.; Boston R.
Dr. S.L. Sessoms, 6550 Fannin Smith 1057, Houston, TX 77030 United States
Journal of Clinical Rheumatology (United States) 1998, 4/5 (270-273)

A 38-year-old man, who presented with Raynaud 's phenomenon and no symptoms or signs of thyroid hormone deficiency, was found to have hypothyroidism . The Raynaud 's phenomenon disappeared after 11/2 months of thyroid hormone replacement therapy. We review four case reports of Raynaud 's phenomenon that disappeared after thyroid replacement therapy. We suggest that thyroid deficiency should be considered a possible cause of Raynaud 's phenomenon.

Coffman J.D.
Department of Medicine, Boston University School of Medicine, Boston, MA United States
Drug Therapy (United States) 1992, 22/10 (45-48+53-56)

Estimates of the prevalence of Raynaud 's phenomenon range from 5% to 30% of the US population. Besides the primary disease, possible causes of the condition include connective tissue disease, carpal tunnel syndrome, arterial obstructions, hypothyroidism , adverse drug reactions, and use of vibrating tools. Although simple measures, such as keeping the hands, feet, and body warm, are effective in most patients, drug therapy may be necessary when vasospastic attacks interface with a patient's work or daily activities. Calcium channel blockers, sympatholytic agents, nitroglycerin, triiodothyronine, captopril, and prostaglandins have been used with varying degrees of success in symptomatic patients. Nifedipine is the current drug of choice.

Leppert J.; Myrdal U.; Hedner T.; Edvinsson L.; Tracz Z.; Ringqvist I.
Department of Research, University of Uppsala, Central Hospital,S-721 89 Vasteras Sweden
Angiology (United States) 1994, 45/7 (637-645)

The effect of a short-term magnesium sulfate (MgSOinf 4) infusion on venous plasma concentration of noradrenaline (NA) and neuropeptide-Y-like immunoreactivity (NPY-LI) was investigated in 12 women with primary Raynaud 's phenomenon (PRP) and in 12 healthy matched controls. The Raynaud 's patients did not demonstrate any significant changes in mean basal plasma NA concentration (0.29 +/- 0.15 vs 0.37 +/- 0.09 ng/mL, ns) after MgSOinf 4 infusion. However, in the controls there was more than twice the amount of circulating noradrenaline (cNA) (0.21 +/- 0.14 vs 0.54 +/- 0.22 ng/mL, P < 0.001) after MgSOinf 4 infusion, compared with the preinfusion value. Measurements during the cold pressor test prior to the MgSOinf 4 infusion showed a significant increase of cNA in both the PRP group and the control group (from 0.29 +/- 0.15 to 0.33 +/- 0.16 ng/mL, P < 0.05, and from 0.21 +/- 0.14 to 0.29 +/- 0.16 ng/mL, P < 0.005, respectively). After MgSOinf 4 infusion the levels of cNA during the cold pressor test increased significantly only in the PRP group (from 0.37 +/- 0.09 to 0.41 +/- 0.11 ng/mL, P < 0.05). Circulating NPY-LI concentrations increased significantly during MgSOinf 4 infusion in the Raynaud 's patients as well as in the controls from 105 +/- 21 to 127 +/- 23 pmol/L, P < 0.05, and from 107 +/- 17 to 132 +/- 27 pmol/L, P < 0.01, respectively. There were no detectable changes during the cold pressor tests in either group. In healthy women short-term MgSOinf 4 infusion induced a sympathetic response, shown by the increased concentration of cNA and NPY-LI, while in PRP patients there was only an increase in NPY-LI. The discrepancy between PRP patients and healthy controls supports the view of a so-called 'local fault' in the sympathetic nerve terminal of arterial/arteriolar walls in Raynaud 's patients.

Nowak J; Barregard L; Benthin G; Granung G; Wennmalm A
Department of Clinical Physiology, Huddinge University Hospital, Karolinska Institute, Stockholm, Sweden
Clin Physiol (England) Jul 1996, 16 (4) p361-7

As chronic exposure to hand-held vibrating tools may cause endothelial injury, a subsequent sustained platelet activation with the increased release of vasoconstricting thromboxane A2 (TxA2) could be of pathophysiological importance in vibration-induced Raynaud 's phenomenon. Therefore, the aim of this study was to elucidate whether or not hand-arm vibration syndrome is accompanied by increased endogenous TxA2 biosynthesis. The study involved 64 men, aged 23-61 years, stratified according to the exposure to vibrating tools, the presence of Raynaud 's phenomenon, and smoking habit. Forty of them were car mechanics and 24 were age-matched healthy volunteers who served as controls. The assessment of platelet TxA2 formation in vivo was performed by quantification of the urinary excretion of its major metabolite, 2,3-dinorthromboxane B2 (2,3-dinor-TxB2), employing gas chromatography-mass spectrometry. The average urinary excretion rate of 2,3-dinor-TxB2 in patients with Raynaud's phenomenon was 296 +/- 42 pg/mg creatinine and did not differ significantly from the corresponding values in controls (328 +/- 62 pg/mg creatinine) or individuals exposed to vibrating tools, but without any signs of vasospastic disease (232 +/- 29 pg/mg creatinine). The only statistically significant difference was found between smokers and non-smokers (P < 0.001), a finding confirming the existence of chronic platelet dysfunction in cigarette smokers. The present data indicate that chronic exposure to vibrating tools, with or without Raynaud 's phenomenon, is not associated with an enhanced platelet function as monitored by the urinary excretion of 2,3-dinor-TxB2. Hence, a possible vibration-induced vascular injury does not seem to provide a stimulus sufficient to induce a persistent platelet activation.

Ho M.; Belch J.J.F.
J.J.F. Belch, University Department of Medicine, Ninewells Hosp. and Medical School, Dundee DD1 9SY United Kingdom
Scandinavian Journal of Rheumatology (Norway) 1998, 27/5 (319-322)

Raynaud 's Phenomenon (RP) is a relatively common problem which may be troublesome and difficult to treat in a minority of patients. The state of the art in 1998 focusses on three key areas: the clinical spectrum of RP; its progression and prognosis; and its treatment. RP is a systemic disease, with a multifactorial aetiology and vasospasm affects not just the digits and skin but also major organs including the heart, lungs and kidneys. It is important to distinguish primary from secondary RP. RP may predate an associated connective tissue disease by many years and markers for this include severe RP symptoms with trophic skin changes, serological abnormalities and abnormal nailfold capillaries. Repeated attacks of vasospasm may cause ischaemic reperfusion injury to the endothelium, resulting in a vicious and self propagating cycle of cause and effect. Nifedipine remains the 'gold standard' of treatment but a number of new and promising drugs, eg relaxin, are currently under investigation. 'Vasodilator-plus' drugs, with the ability to also modulate some of the haemorrheological abnormalities in RP, are the drugs that are going to have a major clinical impact on the disease and hold promise for the future.

Freedman RR; Keegan D; Migaly P; Galloway MP; Mayes M
Lafayette Clinic, Detroit, MI 48207.
Psychosom Med (United States) Jul-Aug 1991, 53 (4) p433-9

We have previously demonstrated that the vasospastic attacks of Raynaud's disease can be induced despite blockade of efferent digital nerves and that feedback-induced vasodilation is mediated through a non-neural, beta-adrenergic mechanism. Here, we sought to determine the role of sympathetic activity, as measured by plasma epinephrine and norepinephrine, during finger temperature feedback and autogenic training . Thirty-one female patients with idiopathic Raynaud 's disease were randomly assigned to receive finger temperature feedback or autogenic training over 28 days. Half of each group began and finished training during the follicular phase of the menstrual cycle, the other half during the luteal phase. During training, significant temperature elevations were shown by feedback patients but not by autogenic patients. There were no significant effects for norepinephrine and epinephrine for either group. Cycle phase did not interact with training effects or with catecholamines. These findings do not support the role of decreased sympathetic activation in behavioral treatments for Raynaud s disease.

Freedman RR
Psychophysiology (United States) Jul 1989, 26 (4) p437-41

Quantitative measurements of finger blood flow have not been performed during temperature biofeedback or other treatments for Raynaud 's disease. In the present investigation, finger blood flow was determined with venous occlusion plethysmography, in addition to measurements of finger temperature, heart rate, blood pressure, and skin conductance level. After a maximum vasodilation test, subjects received 10 sessions of finger temperature biofeedback or autogenic training . There were no group differences during the maximum vasodilation test. During training, temperature feedback subjects showed significant elevations in finger blood flow, finger temperature, and skin conductance level, whereas those who received autogenic training did not. These findings could not be explained by group differences in other cardiovascular measures and are consistent with previous studies suggesting the involvement of an active vasodilating mechanism in temperature feedback.

Rose GD; Carlson JG
Department of Psychology, University of Hawaii, Honolulu 96822.
Biofeedback Self Regul (United States) Dec 1987, 12 (4) p257-72

Raynaud 's disease is a peripheral vascular system disorder characterized by episodes of vasoconstriction in the hands and feet resulting in a lowering of skin temperature and pain. Recent studies are reviewed that focus on the behavioral treatment of Raynaud 's disease--in particular, biofeedback and autogenic training . Methodological problems and other difficulties include the measurement of skin temperature, schedules of reinforcement/feedback, and characteristics of the experimenter and subject. Studies in this area indicate some promise for certain behavioral interventions, especially finger temperature biofeedback under cold stress conditions. On the other hand, further research is needed to clarify the mechanisms, especially that of vasodilation, and the applications of temperature biofeedback , as well as the role of attitudinal, interpersonal, and cognitive factors. (43 Refs.)

Crockett D; Bilsker D
Biofeedback Self Regul (United States) Dec 1984, 9 (4) p431-8

The biofeedback -assisted treatment of a case of Raynaud 's syndrome was examined in order to determine the relationship between learning of the hand-warming response and the subsequent ability to produce foot-warming responses. It was found that fluctuations in dermal hand and foot temperatures were not significantly related, either within or across treatment sessions. The obtained hand-warming response was of high magnitude and rapidly learned, while the foot-warming response was more modest and took substantially more trials to learn. These results indicate that an easy generalization of the hand-warming response cannot be assumed.

Freedman RR; Ianni P; Wenig P
J Behav Med (United States) Dec 1984, 7 (4) p343-53

Twenty-four patients with Raynaud 's phenomenon and scleroderma were randomly assigned to receive finger temperature biofeedback , frontalis EMG biofeedback , or autogenic training . Only those receiving temperature feedback showed significant increases in finger temperature during training and during a posttraining test of voluntary control, effects not attributable to general relaxation. However, no group demonstrated significant clinical improvement, assessed by symptom reports and by ambulatory monitoring of finger temperature. The need for careful classification of patients with Raynaud 's disease and Raynaud 's phenomenon in scleroderma is emphasized.

Keefe FJ; Surwit RS; Pilon RN
J Appl Behav Anal (United States) Spring 1980, 13 (1) p3-11

Twenty-one female patients suffering from diagnosed idiopathic Raynaud's Disease were trained to raise digital skin temperature using either autogenic training , progressive muscle relaxation, or a combination of autogenic training and skin temperature feedback. Patients were instructed in the treatment procedures in three one-hour group sessions spaced one week apart. All patients were instructed to practice what they had learned twice a day at home. Patients kept records of the frequency of vasospastic attacks occurring over a four-week baseline period, and during the first four weeks and the ninth week of training. In addition, patients underwent four laboratory cold stress tests during which they were instructed to maintain digital temperature as the ambient temperature was slowly dropped from 26 degrees to 17 degrees C. Cold stress tests were given during week 1 of baseline and during weeks 1, 3, and 5 of training. No significant differences between the three behavioral treatment procedures were obtained. In addition, the ability of patients to maintain digital temperature during the cold stress challenge showed significant improvement from the first to the last tests. Symptomatic improvement was maintained by all patients nine weeks after the start of training. The implications of these findings for the behavioral treatment of Raynaud 's Disease are discussed.

Surwit RS
Psychother Psychosom (Switzerland) 1981, 36 (3-4) p224-45

No abstract.

Keefe FJ; Surwit RS; Pilon RN
J Behav Med (United States) Dec 1979, 2 (4) p385-91

The purpose of this study was to assess to what degree learned control of digital temperature and vasospastic attacks can be retained by Raynaud 's patients over a full year period. Subjects were 19 patients suffering from diagnosed idiopathic Raynaud 's disease who had undergone behavioral training. These patients had been trained to increase digital temperature using either autogenic training , biofeedback , or a combination of autogenic training and temperature biofeedback . Results indicated that the mean number of vasospastic attacks per day occurring 1 year after training was approximately equal to the number occurring at the end of the initial training (1.2-1.3 per day). Patient satisfaction with the treatment program was above average (3.5 on a 5-point scale). The patients' ability to maintain digital temperature during the cold stress challenge was imparied, however. At 1-year follow-up, digital temperature readings taken in the laboratory were identical to baseline levels.

Surwit RS; Pilon RN; Fenton CH
J Behav Med (United States) Sep 1978, 1 (3) p323-35

In order to assess the efficacy of a behavioral intervention in the treatment of idiopathic Raynaud's disease, 30 female patients were trained to control their digital skin temperature using autogenic training or a combination of autogenic training and skin temperature feedback either in the laboratory or at home. All trained subjects demonstrated a significant ability to maintain digital skin temperature in the presence of a cold stress challenge and reported significant reductions in both frequency and intensity of vasospastic attacks. The addition of skin temperature feedback to autogenic training did not provide additional clinical benefit.

Freedman R.R.
Lafayette Clinic, Wayne State University, Detroit, MI 48207 United States
Behavior Therapy (United States) 1987, 18/4 (387-399)

Raynaud 's disease is characterized by episodic digital vasospasms of unknown etiology. Although surgical and pharmacologic treatments have been problematic, behavioral procedures have shown considerable efficacy. Temperature biofeedback reduces reported symptom frequency and enables patients to voluntarily incrfease finger temperature and capillary blood flow for 1 year after treatment. Symptomatic improvement persists for up to 3 years. This procedure is mediated by a nonneural beta-adrenergic vasodilating mechanism rather than through physiological relaxation. Relaxation-based procedures, such as autogenic training , produce smaller symptom reductions at one-year follow-up with no retention of physiological effects. The effects of classically conditioned vasodilation are retained for 1 year in normal persons and may be of value in the treatment of Raynaud 's disease.

Surwit R.S.
Dept. Med. Psychol., Duke Univ. Med. Cent., Durham, N.C. United States
Primary Cardiology (United States) 1980, 6/9 (34-48)

Biofeedback mechanisms have been shown to be effective in treating mild hypertension. Various forms include binary feedback training to lower blood pressure and heart rate, analogue feedback to control forearm and frontalis electromyographic activity, and meditation-relaxation procedures. The simple technique of having the patient take his own blood pressure and consciously attempt to lower it by whatever mechanism he can is quite effective. Thermal feedback training to control migraine headaches and Raynaud 's disease has been successful. Autogenic training to control skin temperature is also an effective instrument.

Pucciani F; Bechi P; Pantalone D; Panconesi R; Paparozzi C; Pagliai P; Cortesini C
Clin Ter (Italy) Dec 31 1989, 131 (6) p373-80

Twenty-four patients with Raynaud 's phenomenon, without ARA criteria for classification, were examined, after clinical history, by means of esophageal manometry, combined gastric and esophageal pH-monitoring, endoscopy. The results showed in these patients a high incidence of esophageal motor abnormalities (66.6%), of gastroesophageal reflux (50%), and of duodenogastric reflux (45.8%).

Kuyama T; Umemura H; Sudo T; Kawamura M; Shobu R; Tsubakimoto R; Nishimoro A
Second Department of Surgery, School of Medicine, Kinki University, Osaka, Japan.
Nippon Geka Gakkai Zasshi (Japan) May 1988, 89 (5) p763-70

In cases of ischemic extremities and diabetes mellitus, the trauma on finger and toe is very intractable. For such injuries amputation of extremity is indicated very often because of severe necrosis. The number of such cases has been increasing recently because many cases of these patients have arteriosclerotic arterial occlusion and diabetes mellitus, and these are correlated with the changes of aging. The number of cases of Buerger's disease has been also increasing and it is another etiology of intractable trauma in ischemic extremity. The repeated hyperbaric oxygenation, sympathetic block, warfarin therapy and insulin bath with bubbling of hyperbaric oxygen , were applied to has been of such necrosis. By these procedures, the rate of amputation of extremity decreasing. It was concluded that the surgical reconstruction of artery for ischemic extremity has never any meaning as the therapy of such intractable injuries, if blood flow in the peripheral tissue is not kept physiologically, before vascular reconstruction. In order to increase peripheral tissue circulation, the hyperbaric oxygenation, sympathetic block and warfarin therapy wer performed in many cases and these methods were very effective for intractable injuries with severe necrosis.

Kuyama T.; Tanabe H.; Umemura H.; Yabumoto E.
II Dept. Surg., Kinki Univ. Sch. Med., Osaka Japan
Acta Medica Kinki University (Japan) 1976, Vol. 1/- (1-16)

The authors reported the results of the hyperbaric therapy for patients with the disease which may have a genetic origin in part, namely certain forms of cancer and L.E.Raynaud 's syndrome, and furthermore, thromboangiitis obliterans which have a unclear origin and in addition Raynaud 's syndrome, chronic stage of arteritis luetica and ulcus cruris. The clinical results, finding, interpretations and implications are discussed. The phenomena of hyperbaric accumulation of venous partial pressure of oxygen are described and the authors supposed that wound healing of ischemic ulcers caused by successive hyperbaric oxygenation were due to subepithelial and in granulations of ulcers revascularity of capillaries. The above facts were assumed on the basis of the clinical results of thermocamera, optical pulse wave calculation and plasma ultra-centrifugation lipoprotein fraction, relating with decrease in sympathetic irritation.

Herrick AL; Rieley F; Schofield D; Hollis S; Braganza JM; Jayson MI
University of Manchester Rheumatic Diseases Centre, Hope Hospital, Salford, UK.
J Rheumatol (Canada) Aug 1994, 21 (8) p1477-83

OBJECTIVE. To investigate the possibility that micronutrient antioxidant status is an important factor in determining the severity of Raynaud 's phenomenon (RP) and in differentiating between patients with primary Raynaud 's phenomenon (PRP) and those in whom Raynaud 's is secondary to systemic sclerosis (SSc).

METHODS. Four micronutrient antioxidants (selenium, vitamin E , beta-carotene and ascorbic acid) and 2 "markers" of free radical associated activity were assayed in peripheral blood from 10 patients with PRP, 9 with limited cutaneous SSc (ISSc), 9 with diffuse SSc (dSSc) and 15 healthy control subjects.

RESULTS. Plasma ascorbic acid was reduced in all 3 groups of patients: median level 10.6 mg/l in controls, 4.8 mg/l in PRP (p < 0.01), 2.5 mg/l in ISSc (p < 0.01) and 6.8 mg/l in dSSc (p < 0.05). A reduction in serum selenium was especially found in dSSc (median 75 micrograms/l compared to 100 micrograms/l in controls, p < 0.05). In keeping with these deficiencies, the serum concentration of 9, 11, linoleic acid was elevated in RP patients: median values for the molar ratio of the isomer to the parent fatty acid were 1.91% in controls, 3.70% in ISSc (p < 0.05) and 3.85% in dSSc (p < 0.01). Smoking patients showed lower levels of ascorbic acid and higher levels of the linoleic isomer than nonsmokers.

CONCLUSION. Deficiencies of ascorbic acid and selenium may predispose towards irreversible tissue injury in RP patients and cigarette smoke may be an independent risk factor. Micronutrient antioxidant supplements may be of therapeutic value.

Yokota S; Kuriyama T; Takahashi Y; Mori M; Shike H; Ibe M; Mitsuda T; Aihara Y
Department of Pediatrics, Yokohama City University School of Medicine.
Ryumachi (Japan) Dec 1994, 34 (6) p955-60

To assess Raynaud 's phenomenon objectively, thermographic estimation of hands and fingers was performed before and after the disease- and Raynaud 's phenomenon-directed therapy in 3 children with mixed connective tissue disease. All the cases were positive in Raynaud 's phenomenon, and the surface temperature of their hands and fingers were decreased even before cold challenge. After the cold provocation test at 4 degrees C for 10 sec., the temperature of all or some of the fingers were rapidly decreased, and the recovery of surface temperature of these fingers were markedly delayed. Even after methylprednisolone pulse therapy the pattern of the finger temperature were essentially unchanged, suggesting that steroids are not effective in the treatment of Raynaud's phenomenon. The long-term administration of vitamin - E , oral prostaglandin E1, and/or serotonin-receptor inhibitor were also proved to be not beneficial in improving Raynaud 's phenomenon. Thus, thermography is useful in diagnosing Raynaud 's phenomenon objectively, in determining the efficacy of anti-Raynaud drugs, and in estimating long-term course of the phenomenon.

Ayres S Jr; Mihan R
Cutis (United States) Mar 1978, 21 (3) p321-5

Autoimmune diseases are characterized by an alteration of the body's defense mechanism, designed for protection against infections and toxic injuries, which for unknown reasons attacks and destroys normal tissue. Some evidence strongly suggests that such diseases are the result of hydrolytic enzymes that escape from lysosomes whose membranes have been damaged by lipid peroxidation or other causes and that combine with and denature normal tissue proteins--in effect converting them into foreign proteins--to which the body then reacts by producing antibodies. During the past ten years, in a private dermatologic practice, we have conducted clinical investigations on the possible therapeutic value of vitamin E in the management of a number of disabling skin diseases of unknown etiology as well as several muscular disorders. Among the diseases that were successfully controlled were a number in the autoimmune category, including scleroderma, discoid lupus erythematosus, porphyria cutanea tarda, several types of vasculitis, and polymyositis. Since vitamin E is a physiologic stabilizer of cellular and lysosomal membranes, and since some autoimmune diseases respond to vitamin E , we suggest that a relative deficiency of vitamin E damages lysosomal membranes, thus initiating the autoimmune process.

Matoba T; Kusumoto H; Mizuki Y; Yamada K
Tohoku J Exp Med (Japan) Sep 1977, 123 (1) p67-75

Sixty inpatients with vibration disease were examined on the effect of dl-alpha-tocopheryl nicotinate by comparative double-blind study. The observed period was 6 weeks and the dose was 6 capsules a day (600 mg as dl-alpha-tocopheryl nicotinate, Juvela Nicotinate, referred to as EN). The physical exercise therapy was applied to all patients throughout the test period. EN group became better with a significant difference from P (placebo) group in the subjective symptoms, the clinical examinations and the collective improving rate (p less than 0.01, 0.05, 0.01), respectively. The improvement of the subjective symptoms of both groups was higher 6 weeks than 3 weeks after administration. Most items in EN group became better significantly (p less than 0.05) as compared with those in P group. The examinations of the peripheral functions in EN group showed a significant improvement 6 weeks after administration in comparison with those in P group. Blood chemistry, blood cell counts and serum electrolytes changed within normal range. Thus, this preparation would be a curative agent for patients with vibration disease.

Murav'ev IuV; Loskutova TT; Anikina NV; Shcherbakov AB; Sokolov VB
Ter Arkh (USSR) 1989, 61 (12) p106-9

Using a blind method for assessing the results, a study was made of the effect of dimethylsulfoxide (DMSO) on fibrin formation and microcirculation in 42 patients with rheumatic diseases (rheumatoid arthritis, systemic scleroderma, Raynaud 's syndrome). It has been shown that the therapeutic effect of DMSO in rheumatic diseases is determined to a definite degree by its normalizing action on fibrin formation and microcirculation.

Arnot RS; Boroda C; Peacock JH
Angiology (United States) Jan 1978, 29 (1) p48-52

Despite the frequency of Raynaud 's disease in cold climates, the etiology of the condition remains uncertain. This report reviews the literature since Raynaud 's original description and Lewis and Pickering's addition to the concept, and several recent observations which add to our understanding of the disease are discussed. We investigated the effect of posture and a vasodilator drug on the digital capillary circulation; digital blood flow increases as the body moves from a recumbent, through a sitting, ti an upright position. Bradilan, a vasodilator drug, increases the circulation in the recumbent and sitting positions, but has no effect in standing patients, despite symptomatic relief.

Coffman J.D.
Boston Univ. Sch. Med., Boston, Mass. United States
New England Journal of Medicine (United States) 1979, 300/13 (713-717)

In vasospastic diseases, vasodilator drugs that act upon the sympathetic nervous system may have a beneficial effect in many patients by increasing cutaneous capillary blood flow. These agents may decrease persistent vasospasm or the number and intensity of attacks in Raynaud 's phenomenon but usually do not produce complete relief. Full benefit is often prevented by unpleasant and sometimes severe side effects that limit dosage. Reserpine or guanethidine is the drug of choice; tolazoline long-acting tablets are added when further relief is needed. Papaverine, niacin , isoxsuprine and cyclandelate are representative of vasodilator drugs that directly relax vascular smooth muscle. When administered by mouth, these drugs are not potent peripheral vasodilators, and it may be concluded that they are not of value in the treatment of peripheral vascular diseases. Review of the clinical studies of vasodilator drugs in obstructive vascular disease reveals little substantive evidence to support their use. They are not effective in the treatment of either intermittent claudication or ischemic symptoms or signs at rest. They fail to increase blood flow in most patients with ischemic limbs, even when administered locally by the intra-arterial route. No drug has been shown to increase muscle blood flow during exercise when patients with intermittent claudication experience symptoms.

Moriau M; Lavenne-Pardonge E; Crasborn L; von Frenckell R; Col-Debeys C
Department of Internal Medicine, University of Louvain, UCL, Brussels Belgium.
Arzneimittelforschung (Germany) May 1993, 43 (5) p526-35

Piracetam (Nootropil, CAS 7491-74-9) has been investigated in the treatment of primary and secondary Raynaud 's phenomenon in three sequential and complementary studies. The first study in 20 patients with primary Raynaud 's phenomenon, utilising clinical and ultrasound examination, capillaroscopy and laboratory tests established a daily dose of 8 g as most effective. The second study in 58 patients (47 primary, 11 secondary) confirmed the therapeutic efficacy of piracetam in both primary and secondary Raynaud 's phenomenon. The third study, of crossover design, in 30 patients with severe Raynaud 's syndrome, examined various agents given singly or in combination. The results not only confirmed the efficacy of piracetam but in addition allowed comparison of the efficacy of the principal therapeutic agents or regimens used in the treatment of Raynaud 's syndrome and the formulation of a list of these therapies in decreasing order of efficacy, thus: piracetam 4 g/d + buflomedil 600 mg/d; piracetam 8 g/d; buflomedil 600 mg/d; piracetam 4 g/d + acetylsalicylic acid 100 mg/d; pentoxifylline 1200 mg/d; calcium antagonists; ketanserin 120 mg/d. The particular efficacy of 8 g piracetam daily in 3 divided doses at 8-hourly intervals can be attributed to its unique dual mode of action; inhibition of platelet function by inhibition of thromboxane A2 synthetase or antagonism of thromboxane A2 and increased formation of prostaglandin I2, together with a rheological effect involving reduction in blood and plasma viscosity through an increase in cell membrane deformability and a reduction of 30-40% in the plasma concentrations of fibrinogen and von Willebrand's factor. In addition, the administration of piracetam appears to be devoided of adverse effects.

Merritt W.H.
Dr. W.H. Merritt, Plastic and Reconstructive Surgery, 2002 Bremo Road, Richmond, VA 23226 United States
Clinics in Plastic Surgery (United States) 1997, 24/1 (133-160)

Raynaud 's syndrome stands as a landmark to our ignorance of the mechanisms involved in the interrelationship of the central nervous system and peripheral circulatory physiology. Proper management for these unfortunate patients demands an integrated comprehensive effort of the pharmacologic, physical medical, and surgical disciplines.

Browne B.J.; Jotte R.S.; Rolnick M.
Division of Emergency Medicine, Department of Surgery, Maryland University Medical Center, 22 S. Greene St.,Baltimore, MD 21201-1595 United States
Journal of Emergency Medicine (United States) 1995, 13/3 (369-378)

Raynaud 's phenomenon manifests as triphasic color changes of the digits, induced by exposure to low temperature or emotional stress. It is a relatively common disorder, estimated to affect 5% to 10% of the general population and 25% to 30% of otherwise healthy women. Although usually self- limiting, it can be severely painful and debilitating, and complicated by ulcerations and tissue necrosis. For the emergency physician treating a patient with an acute presentation of the phenomenon, the main challenges are to achieve adequate pain control, reverse vasospasm, and maintain viable tissue. Emergency treatment can also extend to patient education and arrangement of appropriate referrals and follow-up care.