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****** DATA-MÉDICOS **********
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EL SÍNDROME DE RAYNAUD 
THE RAYNAUD'S SYNDROME
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****** DERMAGIC-EXPRESS No.48 ******* 
****** 28 ABRIL DE 1.999 *********** 
28 APRIL 1.999
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EDITORIAL ESPAÑOL:
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Hola amigos DERMAGICOS, los saludo desde Venezuela,,,,el tema de hoy,, el SÍNDROME DE RAYNAUD, el cual se presenta como enfermedad individual (ENFERMEDAD DE RAYNAUD), o síntoma secundario de otras patologías,
(FENÓMENO DE RAYNAUD), bastante difícil de tratar por cierto.

Espero que estas 30 referencias nos sean útiles para aclarar nuestros conceptos. 

En el attach una lámina ilustrativa de la enfermedad.

Saludos a TODOS !!!

PRÓXIMA EDICIÓN: * Lupus Eritematoso Discoideo.

Dr. José Lapenta R.,,,


EDITORIAL ENGLISH:
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Hello DERMAGIC friends, Greetings from Venezuela,,,, today's topic, the RAYNAUD'S SYNDROME,, that is presented as singular illness (RAYNAUD'S DISEASE), or secondary symptom of other pathologies (RAYNAUD'S PHENOMENON), quite difficult to treat, by the way.

I hope these 30 references are we useful to clarify our concepts. 

In the attach, an illustrative sheet of the topic.

NEXT EDITION: Discoid Lupus Erythematosus. 

Greetings to ALL, !!

Dr. José Lapenta R.,,,


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DERMAGIC/EXPRESS(48)
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EL SINDROME DE RAYNAUD / THE RAYNAUD'S SYNDROME
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1.) Raynaud's Syndrome: An Overview
2.) Raynaud's phenomenon. Practical considerations on the forms secondary to immunomediated systemic diseases]
3.) Cryofibrinogenemia with polyarthralgia, Raynaud's phenomenon and acral ulcer in a patient with Graves' disease treated with methimazole.
4.) [Raynaud's phenomenon: effects of terazosin]
5.) Plasma nitric oxide metabolite in women with primary Raynaud's phenomenon and in healthy subjects.
6.) Geographic variation in the prevalence of Raynaud's phenomenon: a 5 region comparison.
7.) Clinical studies of the vibration syndrome using a cold stress test measuring finger temperature.
8.) A new criterion proposed for the diagnosis of hand-arm vibration syndrome.
9.) [Comparative study of misoprostol and nifedipine in the treatment of Raynaud's 
phenomenon secondary to systemic diseases. Hemodynamic assessment with Doppler duplex]
10.) Risk factors for Raynaud's phenomenon among workers in poultry slaughterhouses and canning factories.
11.) The transcriptional activator Sp1, a novel autoantigen.
12.) [Raynaud syndrome complicated by digital gangrene during treatment with interferon-alpha]
13.) [The efferent therapy of Raynaud's phenomenon]
14.) Reaction of capillary blood cell velocity in nailfold capillaries to L-carnitine in patients with vasospastic disease.
15.) Prevalence of Raynaud phenomenon in Tartu and Tartumaa, southern Estonia.
16.) A novel anti-microfilament antibody, anti-135 kD, is associated with Raynaud's 
disease, undifferentiated connective tissue disease and systemic autoimmune diseases.
17.) Antibodies to fibrin-bound tissue-type plasminogen activator in systemic lupus erythematosus are associated with Raynaud's phenomenon and thrombosis.
18.) Pharmacotherapy of Raynaud's phenomenon.
19.) Treatment of ischaemic digital ulcers and prevention of gangrene with intravenous iloprost in systemic sclerosis.
20.) Circulating endothelin-1 levels in patients with "a frigore" vascular acrosyndromes.
21.) Treatment of primary Raynaud's syndrome with traditional Chinese acupuncture.
22.) Oral L-arginine supplementation and cutaneous vascular responses in patients with primary Raynaud's phenomenon.
23.) Digital vascular responses to cooling in subjects with cold sensitivity, primary Raynaud's phenomenon, or scleroderma spectrum disorders.
24.) A new examination system using photoplethysmography to evaluate skin blood flow during exposure to vibration.
25.) Raynaud's phenomenon in different groups of workers using hand-held vibrating tools.
25.) Raynaud's phenomenon and other features of scleroderma, including pulmonary hypertension.
26.) [Percutaneous thoracic sympathectomy under x-ray computed tomographic control in hyperhidrosis and refractory ischemia. Apropos of 17 cases]
27.) Controlled multicenter double blind trial of an oral analog of prostacyclin in the treatment of primary Raynaud's phenomenon. 
28.) Non-invasive assessment of vascular reactivity in forearm skin of patients with primary Raynaud's phenomenon and systemic sclerosis.
29.) [Thoracoscopic bilateral sympathectomy in Raynaud's syndrome. Anesthesiology problems]
30.) Raynaud's phenomenon
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1.) Raynaud's Syndrome: An Overview
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Source: SEMINARS IN DERMATOLOGY 
D'Anne M. Kleinsmith, M.D.


HISTORICAL PERSPECTIVE

Maurice Raynaud described "local asphyxia and symmetrical gangrene of the extremities" in 25 pa-tients in 1862.' He described the classic color changes and precipitating causes that have become known as Raynaud's phenomenon (RP). "The de-termining cause is offen the impression of coid sometimes even a simple mental emotion is enough (to bring on these changes). The pallor of the ex-tremities is repiaced by a cyanotic cobur . . . a vermilion cobur shows itself at the margin; little by little it gains ground"1 (PP 99-101). He stated that tbis condition is "characterized especially by a remarkable tendency to symmetry, so that it always affects similar parts, the two upper or lower limbs, or the four at the same time; further, in certain cases, the nose and the ears"' (PP. 7-8). In the early 1900s, Hutchinson wrote a senes of articles on digital ischemia.2~ He reported that this process could be due to heart failure, obstruc-tive arteriopathy, or scleroderma. He proposed that when Raynaud's symptoms were associated with an underlying disease, the term "Raynaud's phenomenon" should be employed.


DEFINITIONS

Today, many investigators diflerentiate be-tween Raynaud's phenomenon and Raynaud's dis-ease. In 1932, Alíen and Brown5 defined Ray-naud's disease as a vasospastic phenomenon precipitated by coid or emotions, usually bilateral, associated with little or no gangrene, and having no underlying medical disease br greater than 2 years. RP, on the other hand, was a marker for a variety of medical conditions, was frequently asym-metric, involved fewer digits, and had an increased risk of developing gangrene (Table 1).

Several controversial points have been raised


Department of Derm~to1ogy, Henry Ford Hospital, Detroit, Michigan following the definition proposed by Alíen and Brown. Lewis and Pickering6 objected to the term "Raynaud's disease" because they felt that a large proportion of these patients would eventually be found to have an underlying medical illness. Des-lgnating their problem as idiopathic would hinder the search br an underlying cause, in their opin-ion.6 de Takats and Fowler7 took issue with the Al-íen and Brown's concept that 2 years was a suffi-cient period of time to determine whetber or not the Raynaud's symptoms were a manifestation of another medical disease. In 1962 they reported on 66 patients with Raynaud's who had been followed from 1 to 25 years. Of these, 20 exhibited peripheral vascular disease, 35 were diagnosed as having collagen disease, 7 showed evidence of vasomotor hyperactivity, and 4 showed abnormal clumping of red blood celís. In approximately hall the patients with collagen diseases the interval between the on-set of the Raynaud's and the diagnosis of a connec-tive tissue disease was from 3 to 16 years. For this reason, they felt the criteria set forth by Alíen and Brown should be modified. Despite these objec-tions, the Alíen and Brown delinitions do serve as basic guidelines br distinguishing between these two entities. It may be advantageous to use the term "Raynaud's syndrome" (RS), however, to describe ah instances of the classic digital color change, and employ the term "Raynaud's phenomenon" when there is a known underlying medical disease.


PATHOPHYSIOLOGY

The classic triphasic color changes one sees in a patient with Raynaud's consist of pallor, due to a sudden vasoconstriction and loss of arterial blood flow, followed by cyanosis, as a small amount of blood enters the capillary system and desaturates, and hnally rubor, secondary to vasodilation. 
Many patients will not exhibit ah three components of this triad. Pallor and cyanosis occur most frequently.
The pathogenesis of Raynaud's is not com-pletely understood. A variety of theories have evolved to explain this phenomenon. Raynaud~ thought that the vasospasm was due to an increase in sympathetic vasomotor activity. In 1929, how-ever, Lewis9 concluded that the primary factor was an abnormal sensitivity of the digital arteries and arterioles to cooling. He also demonstrated that this local response was independent of sympathetic nervous impulses. The most convincing support of Lewis' explanation is the frequency of relapse after complete sympathectomies. Morton and Scott'0 agreed with Lewis' theory, but thought that vaso-constrictor influences from psychic and nervous channeis were also important initiating factors. Other theories have included: elaboration of vaso-active substances, heightened blood viscosity, cryo-precipitable proteins, decreased blood fibrinolytic activity, and enhanced platelet aggregation.11'12 Idiopathic vasospasm and organic occiusive disease are the primary causes of Raynaud's syn-drome in most patients. Young women with the id-iopathic form of the syndrome exhibit the purest form of vasospasm. Older male patients tend to have an obstructive vascular disease like atherosclerosis. RS observed in industrial workers is associated with vibration of a certain frequency (about 125 H). This vibration may cause direct arterial damage result-mg in arterial obstruction according to James and Galloway.'3

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Table 1. Criteria for the Diagnosis of Raynaud's Disease*
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Episodes of vasospastic color change, excited by coid or emotion Bilaterality
Normal pulsations in the palpable aneries
Absence of gangrene, or its limitation to minimal grades of cutaneous gangrene
Absence of any causal disease
Symptoms of 2-years or longer duration

Defined by Alíen and Brown.5
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EPIDEMIOLOGY

Women account for 60 to 90% of patients with Raynaud's.14 Women are more likely to have idio-pathic RS or RP in association with a connective tissue disease. Men with RS generally present at an older age and have a much higher incidence of atherosclerosis. The prevalence of RS is unknown. In order to study the prevalence of primary Raynaud's in a young female population, Olsen and Nielsen15 sent a questionnaire to healthy women aged 21 to 50 years working in a warm envlronment in Copen-hagen. They found that 22% of these women re-ported cold sensitivity.
Patients having certain occupations are at an increased risk for developing RS. Forty to 90% of loggers and 50% of mine workers using vibratory equipment have RS, according to two published studies.'6"7

ASSOCIATED CONDITIONS

A wide variety of medical conditions have been associated with Raynaud's phenomenon. The gen-eral categories of disease include: connective tissue diseases (most commonly scleroderma), hemato-logic abnormalities, arterial disease, neurovascular compression, occupational causes, and drugs and toxins (Table 2).

The connective tissue diseases are these most frequently linked with RP. In a study done by Por-ter et al in 1981,19 219 patients with RS were fully evaluated and followed for 10 years. Of this group, 109, or approximately one half, developed a deh-nite connective tissue disorder. Another 40 pa-tients were suspected of having a connective tissue disease. In only 64 patients, or 29%, no underlying condition was found. As a clinician, it is difficult to determine which patients presenting with RS will eventually develop an associated medical condition. Raynaud's is fre-quently the first symptom of a variety of connective tissue diseases. Seventy to 80% of scleroderma pa-tients present with Raynaud's. In systemic lupus erythematosus, the percentage is 8 to 10%. Many studies have been done in an attempt to determine which Raynaud's patients will develop a connective tissue disease. Kallenberg et a126 evalu-ated 91 patients who presented with RP. They found that the severity of the Raynaud's symptoms and titer of the antinuclear antibody (ANA) results were associated with a greater risk of developing a con-nective tissue disease.

The predictive value of nailfold capillary mi-croscopy was evaluated by Harper and Maricq21 in a 91-patient prospective study. Eight of the nine patients who showed progression from Raynaud's or an undifferentiated connective tissue disease to a more defined connective tissue disease had ab-normal nailfoid capillaries. Scleroderma patients showed large dilated capillaries with adjacent avas-cular skip areas. In patients with lupus erythema-tosus, tortuous capillary loops were seen.22 Burnham has also investigated the relation-ship between the true speckled ANA pattern (or anticentromere antibody), and scleroderma. The speckled-anticentromere pattern was found to be associated with scleroderma in 1964.23 In 1968 Burnham and associates24 reconlirmed the diag-nostic significance of the true speckled pattern for scleroderma. Upon reviewing the case histories of 5723 patients they stated: "Scleroderma is statisti-cally the best diagnosis in a clinically atypical pa-tient suspected of having a cutitiective tissue dis-case if speckled fluorescence is seen." In this same article they reported that 27.3% of patients with Raynaud's disease had the speckled ANA pattern. It was suggested that these patients would be the ones who could later develop scleroderma. In 1974, Burnham and Bank25 noted the as-sociation of the speckled pattern with the CRST syndrome (calcinosis, Raynaud's, sclerodactyly, te-langiectasia). This led Burnham to postulate in 197826 that patients with Raynaud's having the speckled pattern have a subclinical benign form of sclcroderma. He thereforc believed that the ANA pattcrns could serve as immunologic markers in sclerodcrma to idcntify specific subscts,just as they had in lupus erythcmatosus.

On the basis of these carlier observations, we conducted a study27 to determine whether the 06 spccklcd pattern was, in fact, a marker for a benign form of scleroderma. Ah 11 scleroderma patients evaluated with the specklcd pattern had relatively mud discase with many of the features of the CREST syndrome (calcinosis, Raynaud's, esophageal dys-motility, sclerodactyly, telangiectasias). None of them had pulmonary, renal, or cardiac involvcment. Along similar unes, Moroi et al2~ aud Fritzler et a129 reported on a "discrete spcckled" ANA pat-tern that was seen primarily in patients with thc CREST syndromc. Fítis pattcrn was found to rep-rescnt the anticentromere antibody.2~'26 As a result of a sera exchange with Tuffanelli et al,30 wc have established that the "true speckled" ANA pattcrn corresponds to thc anticentromere antibody as wcll. Wc are currently reviewing the case histories of patients who have been diagnosed as having RS with speckled anticentromere, nucleolar, and neg-ative ANA results. Preliminary data31 have shown that of 37 patients in the spcckled-anticentromere group, 23, or 62Q~, developed dcli nite sclero-derma. Another seven developed symptoms suggcstive of a connective tissue discase, possibly scleroderma. An average of 6 years elapsed be-tween the onsct of RP and the developmcnt of other clinical features. Only five patients, or 11%, contin-ucd to have Raynaud's as their only clinical hnding for greater than 2 years.

The vast majority of patients in this group werc women. The Raynaud's symptoms appeared at an older age than in the other two groups. Fheir disease tended to be of the ac-rosclerotic or CREST type, with minimal signifi-cant internal involvement. Eighteen patients with a negative ANA result and RS werc studied. Fifteen patients, or 83%, did not develop evidence of scleroderma or other con-nective tissue disease. Of the three rcmaining pa-tients, two had sclerodcrma and another had an unclassilied connective tissue discase. In each of these three cases, the signs of the underlying col-lagen disease appeared shortly after, or at the same time as, the Raynaud's. Patients in the negative ANA group were yotinger and had a greater proportion of males than their countcrparts in thc speckled category Despite the fact that the nucleolar pattern is commonly found in scleroderma patients, only a few patients in our files carried the initial diagnosis of RS. This would imply that mosí scleroderma pa-tients with the nucleolar pattcrn prcsent with othcr features of their disease. Ah four of the patients that we evaluated in this group developed a con-nective tissue disease. In two, the diagnosis of scle-roderma was established. This study demonstrates the usefulness of the ANA test in predicting which paticnts with RS have the greatest chance of devel-oping scleroderma.

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Table 2. Classification of Conditions Associated with Raynaud's Phenomenon *
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Connective tissue diseases:

Progressive systemic sclerosis
Systemic lupus ervthematosus
Rheumatoid arthritis
Dermatomyositis and polymyositis
Mixed connective tissue disease
Vasculitis

Hematologic abnormalities:

Cryoproteinemia
CoId hemagglutinins
Paraproteinemia
Polycythemia, thrombocythemia (rare)

Arterial disease:

Thromboangiitis obliterans (Buerger's disease)
Arteriosclerosis obliterans
Arteritis
Neurovascular compression:

Thoracic outlet syndrome (cervical first rib anomalies)
and shoulder-girdle compression syndrome (rare)
Crutch pressure 

Occupational:

Percussion and vibratorv tool workers, tree lellers
Traumatic occlusive arterial disease and vasospastic phenomena
Occupational acro-osteolysis (polyvinyl chloride)

Drugs and toxins:

Ergot compounds
Methysergide
Beta-adrenergic blockers
Sympathomimetic drugs
Heavy metals
Oral contraceptives
Cvtotoxic drugs 

Neoplasia:
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Adapted from Hoftman.18

CLINICAL EVALUATION

Clinical evaluation of the Raynaud's patient should begin witb a detailed description of the pa-tient's symptoms. The classic triphasic color change occurs in only two-thirds of patients. As stated in Raynauds' original article,' cooler temperatures or emotional stress are the most common initiating factors. Numbness, tingling, and burning fre-quently accompany thc color changes. To confirm the diagnosis, measuring the skin temperature of the flfth linger provides a simple mdcx of~blood How.32 Porter et a133 measured the digital temper-ature recovery time in patients with RS and normal controls aftcr immersing their hands in ice water br 20 seconds. In the 30 controls, recovery aver-aged 10 minutes, whereas in 23 patients with RS. the average was 30 minutes. They found that if thc initial temperature of the finger was lcss than 320C, the test was not reliable. If thc patient states that their symptoms are bilateral, symmetrical, and involve multiple digits, they are more apt to have RD. Asymmetric color changes with few digits involved is stronger cvi-dence for Raynaud's phenomenon secondary to arterial disease.

In obtaining a complete history and physical, special emphasis should be placed on signs and symptoms of connective tissue discases: arthral-gias, edema or induration of the skin, periungual telangiectasias or other telangiectasias, flngcrtip ul-cerations, pigmentary changes, skin eruptions, bis-tory of photosensitivity, sicca symptoms, aud dys-phagia. To exciude other etiologies, questions regarding the patient's occupation, hobbies, sports, medications, and history of prior vascular discase also need to be asked. The physical examination must include a thorough evaluation of the pres-ence aud quality of the peripheral pulses and tho-racic outlet maneuvers. Middle-aged or elderly pa-tients and men with Raynaud's are at a higher risk of having arterial occiusive disease, arteriosclerosis obliterans, and thromobangiitis obliterans. Dimin-ished peripheral pulses, as well as a history of an-gina, intermittent calf claudication, migratory thrombophlebitis, and "instcp" claudication will aid in making thcse diagnoses.

The selection of laboratory tests will be deter-mmcd on the basis of the patien's initial history and physical examination. A baseline workup should include a complete blood count, erythrocyte sedi-mentation rate, chemistry profile, ANA test, un-nalysis, and radiographs of the hand. Pulmonary function tests and esophagcal studies should be in-cluded if the diagnosis of sclcroderma is suspected. Additional immunologic tests that may be helpful include: serum protein electrophoresis, immuno-globulins, complement leveis, VDRL, rheumatoid factor, anti-DNA antibody, and antiextractable nu-clear antigens (ENA). Cryoproteinemia and coid agglutinin discase may be exciuded by tests for cry-ofibrinogen and cryoglobulins. A chest radiograph 15 necessary to determine the prc~ciicc of a cervical rib, which may cause vascular compression. Nerve conduction studies are needed to exciude nerve entrapmcnt syndromcs.
Spastic and occiusive vascular disease fre-quently coexist in these patients. Using cryody-namic hand arteriography, Rosch et a134 reported that 35 of 39 patients had basal digital vasospasm, whereas 34 of the same 39 patients also had or-ganic obstruction involving primarily digital arter-íes. Porter et al,35 a group nf vascular surgeons from the University of Oregon, reported that arteriog-raphy is seldom needed to establish the diagnosis since the advení of digital plethysmography. They currcntly utilize ateriography only to evaluate a suspected surgically correctable proximal arterial lesion. Plethysmography has been found to be a useful tool to follow the course of treatment in thesc patients.


THERAPY

The management of the Raynaud's patient must be tailored to the severity and etiologv of their disease (Table 3). Certain preventative measures, however, are beneficial to the majority of patients. They may be the only form of therapy required for patients with idiopathic Raynaud's disease.

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Table 3. Therapeutic Management of Raynaud's Syndrome
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Preventative measures: 

Layered clothing
Special fabrics: polypropylene, XR-30 gloves, Thinsulate, Gore-Tex, down No smoking
Avoidance of vibration-related jobs and hobbies
Whirling arm maneuver
Biofeedback

Topical therapy:

DMSO (controversial, not FDA approved)
Nitroglycerin

Oral medications:

Vasodilators
Fibrinolytic drugs 

Invasive measures:

Intra-arterial reserpine
lntravenous prostaglandins E1, 12 (experimental)
lntravenous l0w molecular weight dextran (controversial)
Plasmapheresis (experimental)
Surgical treatment
Sympathectomy:thoracic, lumbar, digital (probably not satis-factory in
Raynaud's disease or RP due fo scleroderma)
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PREVENTION

The most obvious preventative measure is avoidance of cxcessive exposure to coid. New high-tcchnology fabries, originally designed for olympic skiers and astronauts, are nowjoining the ranks of the traditional down, wool, and fur garments to keep people warm. These matenals have the advantage of providing optimal warmth with minimal bulk. Polypropylene, originally popularized by the Nor-weigian ski team, has found its way into "longjohns," hats, gloves, and socks. XR-30 gloves were devel-oped for America's space program. Metal beading, which resembles scquins, rcflects body hcat to in-crease warmth. Thinsulate, used in the lining of jackcts and coats, is purported to be twicc as warm as down. Thesc items may be casily found in spc-cialty camping or ski shops. Electrically heated gloves, developed by a medical engineering group, have also been reported to be useful in preventing attacks.36 Smoking is deleterious to anyone with periph-eral vascular disease. In normal subjects, smoking two cigarcttes has been shown to decrease cuta-neous blood flow by 40% and to increase vascular resistance by 100%. The passive inhalation of nic-otine can have the same effcct on the vascular sys-tem.37 Bocanegra ancí Espinoza38 reported a case of a 47-year-old woman who developed Raynaud's probably on the basis of being married to a person who smoked 4½ packs a day. Stressing the impor-tance of stopping smoking is one of the most im-portant messagcs the physician can give to the Ray-naud's patient. Enrolling in a 'Stop Smoking" clinic may be a helpful approach for some patients.

Stonecutters, chain saw and pheumatic ham-mer users, riveters, pianists, typists, handball en-thusiasts, obstetricians who rely on outlet forceps, and bowlers who use ill-fltting balís39 are ah at high risk for dcveloping vibration-induced RP. This form of RP is sometimes associated with nerve damage producing sensory loss and hand muscle weak-ness.4<) Nerem41 reported that the vibratory fre-qucncy of jackhammers could induce a tremen-dous amount of shear stress to the walls of the digital arteries. Fry42 demonstrated that thc magnitude of this strcss produced endothelial ccli damage suffl-cient to leave the basement membrane and under-lying structures exposed to the circulation. Vibra-tion-induced RP may be reversible in 25% ofpatients if they changejobs or avocations early in the cou rse of the discase.43

Patients can learn to abort a Raynaud's attack by using a whirling arm maneuver described by Mclntyre in 1978.~~ Whilc standing, the patient continuously swings bis arms in 3600 circíes in the l0~ manner of a soft bali pitcher. A combination of gravitational and centrifugal forces helps to re-store the circulation to the outstretchcd flngers in 1 to 2 minutes. Biofcedback training has been reported to be a successful tcchnique in treating Raynaud's by a number of investigators.4~5i When subjccts werc trained with the addition of cold stress, a greater reduction (92.5%) in symptom frequency was ob-served in one study.49 Although their initial re-ports demonstrated a decrease in Raynaud's at-tacks after biofeedback therapy, Keefe ct a152 found that 1 year later thcir subjects' digital temperature rcadings were identical to their baseline levels. For well-motivated patients, biofeedback may be a use-ful therapeutic tool. Refresher courses may be needed, however, to maintain temperature regu-la Don.


TOPICAL TREATMENTS

Dimethyl sulfoxide (DMSO) has been used by some practitioners for RS. The EDA has not ap-proved its use in this disorder, aud few well-con-trolled studies have been performed to establish its effcctiveness in relieving Raynaud's symptoms. In early 1980, on the advice of its Arthritis Advisory Committce, the EDA turned down an application for markcting DMSO for the treatment of ulcers of the hands in scleroderma. Although thcre was not sufflcient evidence to permit approval for mar-keting, they did feel that further research in this fleid was warrantcd. A clinical trial performed by Binnick et al in J97753 showed that topical DMSO did not improve the skin induration, range of mo-tion, or RP in 24 patients with scleroderma. Digital ulceration did not substantially improve, nor did DMSO prcvent the development of new ulcera-tions.

Pain relief was noted iii 10 of 16 patients be-cause of the analgesic effect of DMSO. Several articles have been writtcn about thc pros and cons of treating Raynaud's with various forms of nitroglycerin ointment.5~58 As early as 1948, Lund54 demonstrated that nitroglycerin ointment was a vasodilator that was effective in treating va-sospastic RP. This mode of therapy, howevcr, did not become widely used for a number of years. Side effccts, such as headaches and dizziness, may have been responsible. A report by Klcckner et a155 in 1951 also showed disappointing results with its use in RP. More recent studies have attcsted to thc beneflt of using thc topical nitrates for Ray-naud's.5~58 The effect is temporary ancí requires frequent reapplication of the ointment; in most studies it has been applied three times per day. In Franks' study group,56 the patients were able to use the glyceryl trinitrate ointmcnt during acute at-tacks, and they reported substantially reduced symptoms in the treated digits. Franks concluded that nitroglycerin ointment should be tried before such measures as intra-arterial reserpine are em-ployed.


ORAL MEDICATIONS

If patients with RP are rcfractory to conserva-tive measures, oral medications are the next logical thcrapeutic step. Oral mcdications can be divided into the vasodilator and flbrinolytic cate gories. The following vasodilators have been reported to be cf-fective in treating patients with RP: griseofulvin,59 inosital nicotinate,60'61 nifedipinc,62~6 captopril,67,68,69 70ketanserin, methyldopa, reserpine, guane-thedine,71 prazosin hydrochloride,72'73 phenoxy-benzomine,74 and tolazoline.75

The calcium channel blockecrs, nifedipine and verapamil, are relatively new mcdications. These drugs inhibit smooth muscle cdl contraction by re-ducing the uptake of calcium. Nifedipine tends to increase blood flow to the extremities, whereas ver-apamil has a more central effect. For this reason, nifedipine has been preferred for the treatment of Raynaud's. Most reports in the literature regard-mg the usefulness of nifedipine in Raynaud's have been favorable.62~66 The articles indicate that a re-duction iii frequency arid severity of attacks occurs while patients are taking the drug. Winston et a165 also noted digital ulcer healing in 4 of 5 patients treated with nifedipine. The medication is gener-ally well-tolerated by patients. Side effects include hypotension, light-headedness, and pedal edema. The usual therapeutic dose range is from 10 to 20 mg three times a day. Side cffects are dose-related. This has been one of thc most promising new mcd-ications for this disorder.

The angiotensin-converting cnzyme inhibitor, captopril, has also been shown to be successful in treating RP.67 Captopril is the flrst of a new class of antihypertensive agents that prcvents the con-version of angiotensin 1 to angiotensin II. It is one of the most effective medications used in the trcat-ment of seleroderma renal crisis. In 1979 Lopez-Ovejero et a176 described two paticnts with vascular sclcrodcrma and renal crisis in whom captopril re-lieved both digital ulcers aud exaggerated hyper-tension. Ketanserin is a selective antagonist of 5-hy-droxytryptamine (5-HT, serotonin) at the 5-11T2 receptor. A preliminarv clinical trial has shown that the drug improved vasospasm, promoted the heal-mg of ulcers, and reduced edema.68 Seiboid and Jageneau68 reported that 15 of 18 patients (83%) with systemic sclerosis and RP improved, whereas only 4 of 12 patients (33%) with RP due to other causes received such beneflt. The principal side effects of this medication have been minimal weight gain, dry mouth, and light-hcadedness. This medication is still experimental. Methyldopa (250 to 1000 mg as a single oral bedtime dose) or guanethedine (10 to 20 mg, once or twice daily) may be effective therapy for Ray-naud's according to Scssoms and Kovarsky.77 Symptomatic relief and few side cffects have also been reported with a combination of phenoxyben-zomine and guanethidinc.78 Porter et a119 achieved good results with a combination of guanethedine, 10 mg daily, and prazosin, 1 mg twice daily.

This low-dose regimen avoided side cffects seen with highcr dose, single drug therapy. Ancrod and stanozolol are anabolic hormones that possess the ability to enhance the natural blood flbrinolytic activity and are useful in small vessel vascular occiusive diseases. They have both been reported to be of value in treating severe RS.79'80 In a study by Jarrett et al,80 20 patients with ad-vanced RP were treated with stanozolol. Ah showed an increase in hand blood flow and reduction of symptoms during treatment. The increase in blood flow persisted in varying degrees for at least 3 months after stopping treatment, despite the fact that plasma fibrinogin leveis returned to their pre-viously high values. A second course of trcatment raised hand blood flow to an even greater level. Side effects of stanozolol include fluid retention, amenorrhea, acne, and hirsutism. Thesc agents may have limited usefulness because of their masculinizing side effects, since the preponderance of Raynaud's patients are womcn. Jarrett ct al felt that stanozolol could be considered when treating patients with advanced RP when othcr, more conventional methods have failed. Giving intermittent 3-month courscs, separated by periods of 1 to 2 months, would minimize side effects wbile still maintaining adequate control.


INVASIVE MEASURES

Much controvcrsy and speculation exist re-garding the modalities of trcatment tbat falí in this category. Intra-arterial resperine is perhaps the oldest member of this group. Numerous investí-gators have published their experience with tbis drug in patients with RP,81~8 with the reports being fairly evenly divided regarding its therapeutic ben-eflt. Articles in which it was stated that it did work also reported that the effect was short-lived, lasting from a few hours to a fcw weeks. One of thc most recent articles on this topic by Surwit et a188 found no signiflcant improvement in 24 Raynaud's pa-tients who had been treated with intra-arterial resperine. They concluded tbat given these flndings and thc potential risks of an intra-arterial injection,109

they could not justify the use of intra-arte rial resperine in the treatment of Raynaud's disease or RP. Further studies may be needed to settle this issue. At present, it is probably wise to use this treatment only if oral medications have failed. Infusion of prostaglandins PGE1 and PGI2 (prostacyclin), both potent vasodilators and inhibi-tors of platelet aggregation, are being evaluated in the treatment of recalcitrant RS. Most of the origi-nal research in this area came from England, with some investigational studies now being conducted on this continent.8~93 Twenty-flve patients with RP due to systemic sclerosis were infused with PGI2. In 88% of the patients there was objective im-provemcnt, monitored by thermography or radi-ometry.

The response lasted for 6 to 10 weeks. The patients werc closely monitored during the 72-hour infusion of the drug. The most common side cf-fects were: hypotension, headache, facial flushing, abdominal colic,jaw pain, vomiting, and diarrhea. Studics utilizing PGE1 showed similar favorable re-sults.91-93 The chief weaknesses of this form of therapy are its short duration of action and the nc-cessity of administering thc medication intrave-nously under close supervision. Pharmaceutical companies are currently devcloping oral PGI2 for eventual clinical use. Low molecular weight dextran (LMWD> has been used at some centers for treatment of RS and is reported to reduce red ccli aggregation within the vesscls, lower blood viscosity, and therby in-crease capillary flow. Rcsearchers are divided in their opinions on the usefulness of this form of treat-ment. Several researchers have written favorable reports on its usc.94~9~ Other studies showed no beneficial effect.99'1(>(> Although some uncertainty exists about the effectiveness of LMWD, it is known that some patients have developed acute renal fail-ure after its administration. Moillox et a1101 re-ported 14 cases of acute renal failure and Morgan et al'02 reported anothcr three cases, one of which was fatal, after prolonged LMWD treatment. Given the fact that this treatment has not been found to be universally successful in treating RS, these haz-ards are important to consider.

Plasmaphercsis for the trcatment of RP has improved digital blood flow and symptoms in a number of small groups of patients. A variety of mechanisms of action have been postulated for the succcss of plasmapheresis. It may result in deflbri-nation, alteration of platelet function, or reduction of circulating immune complexes.103~'04 It may therefore be most beneficial for patients with ab-normal serum protcins or increased blood viscos-ity. Because of the risks, expense, and lack of con-trolled studies, this procedure should be considered experimental, to be performed only as a last resort.

THE SURGICAL APPROACH

Cervicothoracic sympathectomy has been used in thc treatmcnt of severe RS. This techniquc ap-pears to be more beneficial in thosc patients with RP due to a peripheral vascular disease, than those with a collagen vascular disease.7'1(>~'<)7 Interpret-mg the conclusions reached in sorne studics is dif-flcult, since long-term follow-up is required to eval-uate the procedure's ultimate success. Relapscs frequently occur months to years after surgcry.78 Blunt and Porter,78 vascular surgeons, have aban-doned this procedure in favor of medical manage-ment. They reasoned that "if the effect of cervical sympathectomy is only temporary, then any con-ditions cured by it are likely to be temporary in nature." Surgical mortality from sympathectomies, although rare, has been reported. Another prob-1cm with this procedure is that thc local coid rcflex is not abolished by complete sympathetic denerva-tion. The operation seems to work due to a slight vasodilation that increases the baseline tempera-ture of the hands.

Adson and Brown108 reported that lumbar sympatbectomy was a successful treat-ment for RS of the lower extremities. Othcrs have confirmed their observations. Rccently, tbere have been reports of a prom-ising new trcatment, "superselective digital sym-pathectomy" for patients with RP.109~110 The oper-ation involves the removal of the adventitia from a portion of thc common digital artery andior the digital artery proper. Egloff et a11 '~ treated 18 dig-its in 13 patients. Of the patients in this group, 11 werc bctter, two were asymptomatic, and none was worse. The longest follow-up was 14 months and the shortest was 3 months. The question remains whether thcse results will persist with a longer fol-low-up period. Since the nerves are bcing ¡ntcr-rupted at a point where no furthcr collateralization occurs, alternate routes for innervation do not ex-ist. It is possiblc therefore that the digital sympa-thectomy may yield superior results to its more proximal countcrpart.


DISCUSSION

RS encompasses two conditions, RP and idio-pathic Raynaud's disease. When faced with a pa-tient with RS, the physician must obtain a thor-ough history and perform a complete physical to exciude associated medical conditions or contribu-tory factors. Once the patient has been adequately evaluated, therapy must be considered. Raynaud's discase, in contrast to RP, is relativcly benign, with an excellent prognosis and little chance of devel-oping gangrene or other complications. These pa-tients should be reassured about the course of their disease. Emphasis should be placed on preventa-tive measures, and avoidance of thcrmal, chemical, and mechanical trauma. Vasodilators need only be prescribed when vasospastic phenomena occur many times daily and prcvent the patient from pursuing normal activities.

In patients with RP, because of the frequent progression to chronic paronychia, digital ulcers, and gangrene, a different approach is required. Vasodilators such as nifedipine, prazosin, methyl-dopa, and topical nitroglycerin could ah be con-sidered as a flrst une of thcrapy. Other oral mcdi-cations, and certainly more invasive treatments should be reserved for those patients with intract-able symptoms or impcnding gangrene. Surgical therapy may be required for patients with occlu-sive arterial disease. Sympathectomy, although helpful for sorne patients with RP, is not usually recommended for RP secondary to sclcroderma or other connective tissue diseases.

There is still no perfect treatment for the Ray-naud's patient. New investigations with ketanserin, and thc prostaglandins show promise, but still have sorne drawbacks. It is hoped that the future will hold sorne new solutions for this T23-ycar-old problem.

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2.) Raynaud's phenomenon. Practical considerations on the forms secondary to  immunomediated systemic diseases] Fenomeno di Raynaud. Considerazioni pratiche sulle forme secondarie a malattie  sistemiche immunomediate.
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Marcolongo R; Cora F; Laveder F; Cavallo M; Busato A; Rigoli AM
Servizio Autonomo di Immunologia Clinica, Universita degli Studi, Padova. Minerva Med (ITALY) Jul-Aug 1997 88 (7-8) p307-10 ISSN: 0026-4806
Language: ITALIAN Summary Language: ENGLISH
Document Type: 
JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL English Abstract
Journal Announcement: 9711

Subfile: INDEX MEDICUS

Raynaud's phenomenon is a frequent asphyxial vascular syndrome interesting the 4%  of general population. In most of cases it is a functional problem (Raynaud's  disease). Less frequently it has an organic cause (Raynaud's syndrome). The  pathogenesis of primitive Raynaud's phenomenon remains an enigma. In secondary  Raynaud phenomenon the attacks of vasospasm can be explained by the physiopathologic  events characterizing the underlying disease. For example, multiple cytokines,  transforming grow factor beta, serum immunocomplexes are of great importance in the  contest of connective diseases. Clinical examination, some usual laboratory and  roentgenographic investigations and nailfold capillary microscopy are of particular  importance in orientating the diagnosis. (7 References)

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3.) Cryofibrinogenemia with polyarthralgia, Raynaud's phenomenon and acral ulcer in a  patient with Graves' disease treated with methimazole.
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Hosoi K; Makino S; Yamano Y; Sasaki M; Takeuchi T; Sakane S; Ohsawa N
First Department of Internal Medicine, Osaka Medical College.
Intern Med (JAPAN) Jun 1997 36 (6) p439-42 ISSN: 0918-2918
Language: ENGLISH
Document Type: JOURNAL ARTICLE 
Journal Announcement: 9711

Subfile: INDEX MEDICUS

Cryofibrinogenemia is a cryopathy in which hypersensitivity to cold is a prominent  feature. Cryofibrinogenemia developed in an 18-year-old Japanese female patient  during methimazole therapy for Graves' disease. She developed cryopathy (livedo  reticularis, Raynaud's phenomenon and acral ulcer) and polyarthralgia during  methimazole therapy, and we detected cryofibrinogen in her plasma. Her symptoms  resolved after administration of prostaglandins and anticoagulants. Several reports  indicate that methimazole therapy induces autoantibody-related disease. In the  present case, we cannot exclude the possibility that methimazole therapy contributed  to the cryofibrinogenemia.

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4.) [Raynaud's phenomenon: effects of terazosin] Il fenomeno di Raynaud: effetti della terazosina.
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Paterna S; Pinto A; Arrostuto A; Cannavo MG; Di Pasquale P; Cottone C; Licata G
Istituto di Patologia Medica, Universita degli Studi, Palermo. Minerva Cardioangiol (ITALY) May 1997 45 (5) p215-21 ISSN: 0026-4725
Language: ITALIAN Summary Language: ENGLISH
Document Type: 
CLINICAL TRIAL; JOURNAL ARTICLE English Abstract
Journal Announcement: 9710

Subfile: INDEX MEDICUS

After considering the clinical and physiopathological aspects of Raynaud's  phenomenon, the authors have evaluated the medium effects of therazosine in 2 groups  of patients, respectively with idiopathic and secondary Raynaud's phenomenon. The  results show that the therazosin determines a decrease of number, intensity and  duration of vasospastic attacks to the hands as well as an improvement of  telethermographic and ultrasonographic findings.

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5.) Plasma nitric oxide metabolite in women with primary Raynaud's phenomenon and in  healthy subjects.
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Ringqvist A; Leppert J; Myrdal U; Ahlner J; Ringqvist I; Wennmalm A
Department of Clinical Physiology, Goteborg University, Sweden.
Clin Physiol (ENGLAND) May 1997 17 (3) p269-77 ISSN: 0144-5979
Language: ENGLISH
Document Type: JOURNAL ARTICLE 
Journal Announcement: 9710

Subfile: INDEX MEDICUS

Primary Raynaud's phenomenon (PRP) is characterized by cold- or stress-induced  transient attacks of impaired skin circulation in fingers and/or toes. PRP displays  seasonal variation with less severe symptoms in the summer. The aetiology has not  been clarified.

The aims of the present study were (a) to assess the influence of  cold exposure on the plasma levels of the nitric oxide (NO) metabolite, nitrate, in  patients with PRP and in healthy control subjects; and (b) to investigate whether  there is a seasonal variation in these plasma levels. In a group of women with PRP  and matched control subjects, venous blood was sampled before and at the end of a 40- min period of whole-body cooling. The study was performed with the same protocol on  two occasions; once in the winter and once in the summer. A seasonal variation was  detected with higher plasma levels of nitrate in the winter than in the summer, both  in PRP and in control subjects.

However, the plasma level of nitrate was not changed  in response to cold exposure on any occasion, either in the patient or in the control  group. Our study indicates that NO formation is up-regulated in response to cold  weather in both study groups. However, NO formation does not seem to be increased in  response to whole-body cooling, either in PRP patients or in healthy subjects.  Further investigations are required to reveal whether the observed seasonal variation  in NO formation is a universal phenomenon in man.

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6.) Geographic variation in the prevalence of Raynaud's phenomenon: a 5 region  comparison.
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Maricq HR; Carpentier PH; Weinrich MC; Keil JE; Palesch Y; Biro C; Vionnet-Fuasset  M; Jiguet M; Valter I
Department of Medicine, Medical University of South Carolina, Charleston 29425,  USA.
J Rheumatol (CANADA) May 1997 24 (5) p879-89 ISSN: 0315-162X
Contract/Grant No.: AR-31283--AR--NIAMS; M01-RR-01070--RR--NCRR
Language: ENGLISH
Document Type: JOURNAL ARTICLE 
Journal Announcement: 9709

Subfile: INDEX MEDICUS

OBJECTIVE: To determine the population based prevalence of Raynaud's phenomenon  (RP) in 5 geographic regions: one in South Carolina, USA, and 4 in France; to explore  the relationship of RP to the climate; to investigate possible risk factors; and to  describe the characteristics of RP+ subjects in the general population.

METHODS: The  study consisted of 2 phases: a telephone survey of a randomly drawn sample of  households, with 10,149 completed interviews; these were followed by a face to face  interview and clinical evaluation (n = 1,534), including diagnosis of RP. The same  methodology was used in all 5 regions: for recruitment of subjects, criteria for RP,  method of RP diagnosis, and for gathering additional information.

RESULTS: The  prevalence of RP was found to be related to the climate. The relationship between RP  and climate was complicated, however, by the fact that many subjects had moved  between climate zones. The relationship of RP to a cold climate became more evident  after taking the migration patterns into account: the majority of RP+ subjects in the  2 coldest regions had lived all their lives in the same or a similar climate zone;  the majority of RP+ subjects in the 2 warmest regions had previously lived in a  colder climate. Other factors associated with RP were family history of RP,  cardiovascular diseases, older age, a low body mass index, use of vibrating tools,  and outings of a day or more. The classical triphasic RP was rarely encountered in  the general population and the most frequently observed signs and symptoms during an  RP attack were blanching accompanied by numbness.

CONCLUSION: In addition to being a  triggering factor for RP attacks, cold also appears to be an etiologic factor in the  pathogenesis of RP. A subclinical cold injury, more likely to occur in colder  climates, may be responsible for the "local fault" that has been implicated in the  pathogenesis of RP and, in association with other risk factors, may predispose  subjects to develop clinical RP.

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7.) Clinical studies of the vibration syndrome using a cold stress test measuring  finger temperature.
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Gautherie M
Department of Clinical Thermobiology, Faculty of Medicine, Louis Pasteur  University, Strasbourg, France.
Cent Eur J Public Health (CZECH REPUBLIC) 1995 3 Suppl p5-10 ISSN: 1210-7778
Language: ENGLISH
Document Type: JOURNAL ARTICLE; MULTICENTER STUDY 
Journal Announcement: 9709

Subfile: INDEX MEDICUS

Since nine years multicentre, transversal and longitudinal clinical studies on hand- arm, vibration-exposed patients are being performed in cooperation with French  occupational medicine centers and social security institutions. These studies are  based upon current clinical assessment and standardized, temperature-measuring  cooling tests. Data acquisition uses a portable, 10-channel, micro-processor-based  temperature recorder and miniature thermal sensors. Temperature is monitored at the  ten finger tips continuously, before, during and after a cold stress performed in  strictly controlled conditions.

Data from examinations performed at outlying sites  are transferred through the telephonic network to a central processing unit. Data  analysis uses a specific, expert-type software procedure based upon previous clinical  studies on (i) 238 "normal" subjects, and (ii) 3,046 patients with vascular  disturbances of the upper extremities of various etiologies. This procedure includes  a staging process which assigns each finger a class representing the degree of  severity of the abnormalities of response to cold ("dysthermia") related to vascular  disorders. All data processing is fully automatic and results in a printed  examination report. To date, over 1,623 vibration-exposed forestry, building and  mechanical workers were examined.

Sixty-three per cent of patients had received high  dose of vibration (daily use of chain saws, air hammers, ballast tampers over many  years). Typical white finger attacks or only neurological symptoms were found in 36%  and 23% of patients respectively. The rate of sever dysthermia was much higher in  patients with white finger attacks (83%) than in patients without (32%). In 90% of  the vibration-exposed patients, the severity of dysthermia has differed greatly from  one finger to another and between hands, while in non-exposed patients with primary  Raynaud syndrome the dysthermia are generally similar for all fingers but the thumbs. 

Of 208 forestry workers who were asymptomatic but had dysthermia on a first  examination, 31% have developed vascular or neural symptoms within subsequent follow- up. Of 223 symptomatic patients with more or less severe dysthermia at a first  examination performed in winter, 17% had the same abnormalities in summer and  microvascular lesions at capillaroscopy, while the other 83% had reversible  dysthermia and only functional capillaroscopic abnormalities. These studies suggest  that temperature-measuring cooling tests performed under well-defined, standard  conditions provide significant data for grading the severity and assessing the  reversibility of Raynaud phenomena, and for detecting subclinical vasomotor disorders  in asymptomatic patients.

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8.) A new criterion proposed for the diagnosis of hand-arm vibration syndrome
. ===================================================================
Matoba T; Ishitake T; Kihara T
Department of Environmental Medicine, Kurume University School of Medicine, Japan.
Cent Eur J Public Health (CZECH REPUBLIC) 1995 3 Suppl p37-9 ISSN: 1210-7778
Language: ENGLISH
Document Type: JOURNAL ARTICLE 
Journal Announcement: 9709

Subfile: INDEX MEDICUS

To propose a new criterion for the diagnosis of hand-arm vibration syndrome (HAVS),  we evaluated the severity of the patients in comparison with the criterion of the  Ministry of Labour in Japan (MLJ) and the Stockholm criterion. The characteristics  of the Stockholm criterion was to classify severe cases with vascular disorders,  because of evaluation due to the frequency of Raynaud's phenomenon alone. The  Stockholm criterion diagnosed the HAVS separately in vascular and sensorineural  disorders.

The MLJ criterion was able to subdivide light stages. In vascular  disorders, the MLJ criterion made serious consideration about cold sensation which  appeared long before the occurrence of Raynaud's phenomenon. The MLJ criterion  diagnosed the patients with vascular, sensorineural and motor (musculoskeletal)  system disorders comprehensively. A new criterion which we proposed includes  sensorineural, vascular and motor system disorders, the grade of which is evaluated  in each system. The diagnosis might be done comprehensively.

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9.) [Comparative study of misoprostol and nifedipine in the treatment of Raynaud's  phenomenon secondary to systemic diseases. Hemodynamic assessment with Doppler  duplex]
Estudio comparativo de misoprostol y nifedipino en el tratamiento del fenomeno de  Raynaud secundario a enfermedades sistemicas. Valoracion hemodinamica mediante  Doppler-duplex.
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Varela-Aguilar JM; Sanchez-Roman J; Talegon Melendez A; Castillo Palma MJ
Unidad de Colagenosis, Hospital Universitario Virgen del Rocio, Sevilla.
Rev Clin Esp (SPAIN) Feb 1997 197 (2) p77-83 ISSN: 0014-2565
Language: SPANISH Summary Language: ENGLISH
Document Type: 
CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
English Abstract
Journal Announcement: 9709

Subfile: INDEX MEDICUS

OBJECTIVE: To evaluate the mid-term efficiency and therapeutic safety at a mid term  of the orally administered misoprostol, a synthetic PGE1, analogue, compared with  nifedipine for the treatment of RP secondary to autoimmune systemic diseases. 

METHODS: A double blind, crossover study was designed. Patients were randomly  distributed to receive either retard nifedipine (20 mg/12 hourly) and misoprostol  (200 micrograms/12 hourly) in 10-day periods (washing period with placebo for 10  days). At the end of each period a clinical assessment was obtained on the frequency  and severity of symptoms as well as on secondary drug reactions. Simultaneously,  blood flow changes in radial artery were Doppler-duplex investigated (pulsatility  index, resistance index).

RESULTS: Twenty patients were studied (15 women and 5 men).  The mean basal daily frequency of attacks was 4.8 +/- 2.0 compared with 2.4 +/- 1.4  with nifedipine (p < 0.001) and 2.6 +/- 1.2 with misoprostol (p < 0.001). The mean  basal severity of attacks, according to a pre-established scale decreased from 3.7 +/- 0.6 to 1.9 +/- 0.9 with nifedipine (p < 0.001) and to 2.0 +/- 1.0 with misoprostol  (p < 0.001). The mean basal value of blood flow in radial artery was 24.9 +/- 14.4  ml/min; with nifedipine it increased to 43.0 +/- 19.2 ml/min (p < 0.001) and with  misoprostol to 46.9 +/- 19.2 ml/min (p < 0.001). Five patients (25%) had secondary  effects with nifedipine and three (15%) with misoprostol; in no case had therapy to  be discontinued.

CONCLUSIONS: Misoprostol was similar to nifedipine for the  treatment of Raynaud phenomenon secondary to systemic diseases and can be a  therapeutic alternative for these patients.

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10.) Risk factors for Raynaud's phenomenon among workers in poultry slaughterhouses and canning factories.
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Kaminski M; Bourgine M; Zins M; Touranchet A; Verger C INSERM Unit 149, Villejuif, France.
Int J Epidemiol (ENGLAND) Apr 1997 26 (2) p371-80 ISSN: 0300-5771
Language: ENGLISH
Document Type: JOURNAL ARTICLE; MULTICENTER STUDY 
Journal Announcement: 9709

Subfile: INDEX MEDICUS

BACKGROUND: Apart from the use of vibrating tools, little is known about risk  factors for Raynaud's phenomenon. However, it has been hypothesized that this  disorder may have a multifactorial aetiology, involving potential causal or  triggering factors which can be found in the workplace. The objective of the study  is to identify individual and occupational risk factors of Raynaud's phenomenon in a  population of workers not exposed to vibration, but exposed to cold.

METHODS: The  survey was carried out in 1987-1988 in 17 poultry slaughterhouses and six canning  factories and included 1474 employees. Data were collected at the annual visit to  the occupational health physician. Finger sensitivity to cold and Raynaud's  phenomenon were identified from a list of symptoms occurring from exposure to cold.  The role of potential risk factors was assessed using multiple logistic regression. 

RESULTS: A high prevalence of symptoms of finger sensitivity to cold was observed.  Raynaud's phenomenon was more common in women than in men, was related to family  history of the disease but not to smoking or alcohol consumption. After controlling  for non-occupational factors, the following working conditions appeared as risk  factors for Raynaud's phenomenon: use of plastic gloves, less than four rest breaks,  breaks in an unheated place, continual repetition of

 the same series of operations,  exertion of the arm or hand and being able to think of something else while working.  CONCLUSION: The study showed that a number of working conditions were associated with  an increased risk of Raynaud's phenomenon and finger sensitivity to cold. Changes in  working conditions might reduce the risk of this disorder in the food processing  industry.

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11.) The transcriptional activator Sp1, a novel autoantigen.
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Spain TA; Sun R; Gradzka M; Lin SF; Craft J; Miller G
Yale University School of Medicine, New Haven, Connecticut 06520-8064, USA.
Arthritis Rheum (UNITED STATES) Jun 1997 40 (6) p1085-95 ISSN: 0004-3591
Contract/Grant No.: CA-16038--CA--NCI; AI-22959--AI--NIAID;
AR-40072--AR--NIAMS; +
Language: ENGLISH
Document Type: JOURNAL ARTICLE 
Journal Announcement: 9708

Subfile: AIM; INDEX MEDICUS

OBJECTIVE: To identify one nuclear autoantigenic protein within a complex of DNA  binding proteins that bind to GC-rich sequences in Epstein-Barr virus and cellular  DNA, and to describe the clinical characteristics of patients whose sera contained  autoantibodies to this novel autoantigen.

METHODS: Antibodies to autoantigen Sp1  were initially measured by an electrophoretic mobility shift assay to detect DNA  binding proteins. Nuclear extracts and purified Sp1 protein were used in these  assays. Recognition of the autoantigen by autoimmune sera was confirmed by  immunoprecipitation and immunoblotting.

RESULTS: The autoantigen was identified as  Sp1. Anti-Sp1 was detected in sera from 8 (3%) of 230 patients. These sera  contained antinuclear antibodies, but lacked antibodies to double-stranded DNA or to  several extractable nuclear antigens. The patients whose sera contained antibodies  to Sp1 were white women with fatigue, arthritis, Raynaud's phenomenon, malar rash,  and photosensitivity.

CONCLUSION: Sp1 is the first described example of an RNA  polymerase II transcription activator as an autoantigen. The presence of Sp1  autoantibodies is associated with undifferentiated connective tissue disease.

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12.) [Raynaud syndrome complicated by digital gangrene during treatment with interferon- alpha]
Syndrome de Raynaud complique de gangrene digitale au cours d'un traitement par  l'interferon alpha.
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Liozon E; Delaire L; Lacroix P; Labrousse F; Ly K; Fauchais AL; Loustaud-Ratti V;  Vidal J; Liozon F; Vidal E
Service de medecine interne A, CHU Dupuytren, Limoges, France.
Rev Med Interne (FRANCE) 1997 18 (4) p316-9 ISSN: 0248-8663
Language: FRENCH Summary Language: ENGLISH
Document Type: 
JOURNAL ARTICLE English Abstract
Journal Announcement: 9708

Subfile: INDEX MEDICUS

In a 43-year old male suffering from idiopathic hypereosinophilic syndrome (HES)  since 1984, successfully treated with alpha interferon (alpha IFN) for 32 months, a  severe Raynaud's phenomenon of the four extremities occurred and eventually evolved  into digital necrosis within a few weeks. The arterial echography/doppler and  plethysmography patterns were suggestive of isolated small-to medium-size digital  artery occlusions. An extensive search for an aetiology of digital necrosis,  including complete tests of autoimmunity, remained negative. Two months later,  despite alpha IFN withdrawal and intravenous infusions of ilomedin, the digital  ischemia evolved to extensive necrosis that necessitated several amputations and a  definitive spinal chord stimulation. Pathologic examination of arteries showed no  vasculitis but diffuse arterial occlusions by thrombi.

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13.) [The efferent therapy of Raynaud's phenomenon] Eferentna terapiia fenomenu Reino.
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Loba MM; Orel IuH
Klin Khir (UKRAINE) 1994 (12) p51-3 ISSN: 0023-2130
Language: UKRAINIAN Summary Language: ENGLISH
Document Type: 
JOURNAL ARTICLE English Abstract
Journal Announcement: 9708

Subfile: INDEX MEDICUS

The method of discrete plasmacytapheresis was applied for the treatment of 8  patients with primary and 18 with secondary Raynaud's phenomenon. The incorporation  of this method in the therapeutic complex have promoted the achievement of clinical  improvement in the whole of the patients with primary and in 13 with secondary  Raynaud's phenomenon. Remission lasted from 1.5 months till 4.5 years. Positive  effect is caused by the improvement of blood rheological properties on the  hemodilution background, the excretion of pathological substances from blood flow.

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14.) Reaction of capillary blood cell velocity in nailfold capillaries to L-carnitine in patients with vasospastic disease.
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Gasser P; Martina B; Dubler B
Medical Outpatient Department, University Clinic, Basel, Switzerland.
Drugs Exp Clin Res (SWITZERLAND) 1997 23 (1) p39-43 ISSN: 0378-6501
Language: ENGLISH
Document Type: CLINICAL TRIAL; JOURNAL ARTICLE 
Journal Announcement: 9708

Subfile: INDEX MEDICUS

By using nailfold videomicroscopy in conjunction with local cold exposure, the  haemodynamic responses in capillary blood cell velocity were evaluated in 12 patients  with vasospastic disease after receiving L-carnitine 3 g per day orally for 20 days.  The results obtained showed that the cold-induced blood flow stop duration was  significantly (P < 0.05) decreased and capillary blood cell velocity significantly (P  < 0.05) increased after local cooling. Systolic blood pressure was significantly (P  < 0.05) decreased after treatment with L-carnitine. Diastolic blood pressure, heart  rate and skin temperature did not differ significantly before and after treatment. 

There were no significant differences in the meteorologic data such as atmospheric  temperature, atmospheric pressure or atmospheric hygrometry between the two  investigations. It is concluded that L-carnitine might be a useful agent in the  treatment of digital vasospastic disease. In addition, in vivo videomicroscopy is  one of the few non-invasive and clinically useful direct methods for evaluating the  effect of a drug on the microcirculation.

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15.) Prevalence of Raynaud phenomenon in Tartu and Tartumaa, southern Estonia.
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Valter I; Maricq HR
Department of Medicine, University of Tartu, Estonia.
Scand J Rheumatol (NORWAY) 1997 26 (2) p117-24 ISSN: 0300-9742
Language: ENGLISH
Document Type: CLINICAL TRIAL; CLINICAL TRIAL, PHASE I; CLINICAL TRIAL, PHASE II; 
JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL 
Journal Announcement: 9707

Subfile: INDEX MEDICUS

The aim of the present study was to estimate the prevalence of Raynaud phenomenon  (RP) among Estonians in the general population of Southern Estonia. A random sample  of 2626 Estonian subjects from the general population was asked about their fingers'  sensitivity to cold and color changes by a mail survey. A subsample of 457 subjects  was examined to confirm the diagnosis of RP, using a standard interview assisted by  color charts (a color scale and hand photographs). In addition to a short clinical  examination, the nailfold capillaries were examined by in vivo microscopy and a blood  sample was drawn for ANA testing.

The prevalence of RP, based on the presence of  blanching, alone or with cyanosis, was 8.3% +/- 0.91% (SE) for women and 7.9% +/-  1.62% for men. The prevalence increased with age and, in men, was related to  occupation. Smoking was also associated with RP among men but the effect was  difficult to separate from that of the occupational influences because of the high  proportion (84.2%) of current and past smokers among male manual workers. RP among  the Estonians in Southern Estonia has a lower prevalence than in other countries with  comparable climate, its female to male ratio is low, and it is related to occupation  and smoking in men.

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16.) A novel anti-microfilament antibody, anti-135 kD, is associated with Raynaud's  disease, undifferentiated connective tissue disease and systemic autoimmune diseases.
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Girard D; Senecal JL
Department of Medicine, University of Montreal School of Medicine and Hopital Notre- Dame, Quebec, Canada.
Autoimmunity (SWITZERLAND) 1996 24 (3) p167-77 ISSN: 0891-6934
Language: ENGLISH
Document Type: JOURNAL ARTICLE 
Journal Announcement: 9707

Subfile: INDEX MEDICUS

We report herein the characterization of a human IgG antibody reactive with a  nonmuscle 135 kD microfilament-associated protein, anti-135 kD. Using nonmuscle  epithelial PtK2 cells as substrate in indirect immunofluorescence, we identified a  distinctive pattern of reactivity with microfilaments in sera from 12 of 165 (7.3%)  patients investigated for systemic autoimmune diseases and in only 2 of 171 (1.2%)  normal and rheumatic disease controls (P < 0.006, 95% Cl 1.46 to 30.1).

 An  association between anti-135 kD and Raynaud's phenomenon (n = 12/14, 85.7%) with or  without an associated systemic autoimmune disease was noted. The anti-135 kD  specificity was established by several criteria.

(1) The fluorescence was  periodically distributed along microfilaments and concentrated at focal adhesions for  all sera (n = 14).

(2) On immunoblots, the 14 sera reacted with a PtK2 polypeptide  of 135 kD.

(3) IgG purified by blot-affinity from the 135 kD band (alpha-135)  reproduced the fluorescent pattern of the original sera while IgG purified from other  bands did not.

(4) Double immunofluorescence with alpha-135 and anti-alpha-actinin  mAb indicated absence of antibody fluorescence at ruffling membranes where a-actinin  was distributed.

(5) IgG subclass analysis of anti-135 kD revealed that 12 (85.7%)  sera are of IgG3 isotype and 2 (14.3%) are of IgG1 isotype while the light chain  expression was kappa restricted.

This is the first report of an antibody to a 135 kD  microfilament protein. Anti-135 kD expand the repertoire of anti-microfilament and  anticytoskeletal antibodies in human sera.

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17.) Antibodies to fibrin-bound tissue-type plasminogen activator in systemic lupus  erythematosus are associated with Raynaud's phenomenon and thrombosis.
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Salazar-Paramo M; Garcia de la Torre I; Fritzler MJ; Loyau S; Angles-Cano E University of Guadalajara, Mexico.
Lupus (ENGLAND) Aug 1996 5 (4) p275-8 ISSN: 0961-2033
Language: ENGLISH
Document Type: JOURNAL ARTICLE 
Journal Announcement: 9707

Subfile: INDEX MEDICUS

Fibrinolysis triggered by t-PA bound to fibrin is one of the main antithrombotic  mechanisms. Defects in the fibrinolytic system-decreased tissue-type plasminogen  activator (t-PA) activity and elevated levels of plasminogen activator inhibitor (PAI- 1), in patients with SLE have been associated with an increased tendency to  thrombosis. In the present study, 43 patients with SLE fulfilling the ACR criteria  for the disease, were studied for the presence of autoantibodies to fibrin-bound t- PA, i.e. the physiological active form of this plasminogen activator.

A solution of  200 IU/ml of t-PA was incubated with solid-phase fibrin prepared as previously  described (Anal Biochem 1986; 153; 201-210). Sera diluted 1:50 were incubated with  fibrin-bound t-PA, the plates were then washed, and bound immunoglobulins were  detected using a polyvalent peroxidase-labeled goat anti-human Ig.

Plates coated  with fibrin alone were used as controls. Sera were considered positive when A490/630  obtained with normal human sera in two independent test was greater than the mean  plus 2 SD. Eleven of 43 (26%) SLE sera demonstrated antibody reactivity against  fibrin-bound t-PA. Within the anti-t-PA positive group there was a higher proportion  of SLE patients with severe Raynaud's phenomenon and thrombotic events when compared  to the anti-t-PA negative group: 36% vs 6% and 18% vs 6% respectively.

These results  suggest that autoantibodies to fibrin-bound t-PA could play a role in the  pathogenesis of vascular disease in some SLE patients.

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18.) Pharmacotherapy of Raynaud's phenomenon.
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Belch JJ; Ho M
Department of Vascular Medicine, Ninewells Hospital and Medical School, Dundee,  Scotland. [email protected]
Drugs (NEW ZEALAND) Nov 1996 52 (5) p682-95 ISSN: 0012-6667
Language: ENGLISH
Document Type: JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL 
Journal Announcement: 9706

Subfile: INDEX MEDICUS

Primary Raynaud's phenomenon is common, particularly in younger women, and may be  familial. Vasospasm is not confined to the digits and may involve, for example, the  tongue and nose, and also visceral organs like the heart, oesophagus or lung and  cerebral circulation.

Symptoms tend to be milder in primary compared with secondary  Raynaud's phenomenon, which is associated with other disorders such as the connective  tissue diseases. Indeed, the severity of symptoms often acts as the predictor for  the much later onset of the associated systemic disease.

Occupational Raynaud's  phenomenon is related to the use of vibrating instruments, and a significant  proportion of patients may be cured by an early change in job. In those over 60  years of age, Raynaud's phenomenon is commonly a result of atherosclerotic  obstructive arterial disease, and screening for and treatment of the risk factors is  appropriate.

The best-studied mechanisms in Raynaud's phenomenon involve the blood  and vascular endothelium. Microcirculatory flow may be impeded by activated platelet  clumps, rigid red and white blood cells and damaged endothelium. These platelet  clumps, white blood cells and damaged endothelium also release  vasoactive/vasoconstrictive compounds which may additionally trigger the clotting  cascade and thrombosis. Initial management for mild disease should focus on support  and advice regarding avoidance of known precipitating factors, including vasospastic  drugs. Cold protection with warming agents, 'Abel' shoes and also electrically  heated gloves and socks is effective, but may be too cumbersome and inconvenient for  some patients.

Simple vasodilators like naftidrofuryl, inositol nicotinate and  possibly pentoxifylline (oxpentifylline) are useful in mild disease, with adverse  effects like headache and flushing being less problematic. The 'gold standard' of  Raynaud's phenomenon treatment is nifedipine, a calcium channel antagonist/blocker. 

Full dosage, however, can be limited by ankle swelling, headache and flushing, but  adverse effects may be reduced by using the 'retard' or long-acting preparations.  Adverse effects are also reduced with the newer calcium channel antagonists like  diltiazem but at the expense of efficacy. Useful, enhanced benefit is also achieved  by combination therapy with vasodilators.

Newer treatments include the prostaglandin  analogues which are effective but disadvantaged by their parenteral route of  administration, and lack of licence in some countries. Oral preparations are,  however, being studied and are in the pipeline. Essential fatty acid supplementation  is mildly effective, while ketanserin and calcitonin gene-related peptide both look  promising. Lumbar sympathectomy retains its important role in the treatment of  Raynaud's phenomenon involving the lower limbs. Satisfactory symptomatic relief is  now possible for many patients with Raynaud's phenomenon and this should certainly be  the aim for all patients seeking medical help. (73 References)

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19.) Treatment of ischaemic digital ulcers and prevention of gangrene with intravenous  iloprost in systemic sclerosis.
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Zachariae H; Halkier-Sorensen L; Bjerring P; Heickendorff L
Department of Dermatology, Marselisborg Hospital, Aarhus, Denmark.
Acta Derm Venereol (NORWAY) May 1996 76 (3) p236-8 ISSN: 0001-5555
Language: ENGLISH
Document Type: CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; JOURNAL ARTICLE

Journal Announcement: 9706
Subfile: INDEX MEDICUS

Twelve patients with systemic sclerosis were treated with intravenous infusions of  the prostacyclin-stable analogue iloprost 0.5-2.0 ng/kg/min for 6 h from 8 to 13 days.  Imminent gangrene was stopped in 2 patients and followed by healing. In 4 of 6  patients iloprost led to complete healing of ischaemic ulcers and in the remaining 2  patients to partial healing.

 One patient with severe Raynaud's phenomenon  discontinued the study after 3 days due to severe headache. The 2 remaining patients  with Raynaud's phenomenon as an indication improved, while no improvement was  recorded in a patient with vasculitis of the lower leg. Side-effects such as  headache, nausea and flushing were the reason that only 5 patients reached the  maximum infusion rate. No statistical differences were recorded in digital bloodflow  before and after the study or in plasma endothelin in the 9 patients investigated. 

Three of the 6 patients with healing ulcers, however, showed a pronounced decrease in  plasma endothelin. Iloprost appears useful as a treatment of imminent gangrene and  ischaemic ulcers in systemic sclerosis. This reparatory capacity could also be of a  more general importance in therapy of this disease.

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20.) Circulating endothelin-1 levels in patients with "a frigore" vascular  acrosyndromes.
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Mangiafico RA; Malatino LS; Spada RS; Santonocito M
Clinica Medica L. Condorelli Universita di Catania, Azienda Ospedali V. Emanuele,  Ferrarotto e S. Bambino Catania, Italy.
Panminerva Med (ITALY) Dec 1996 38 (4) p229-33 ISSN: 0031-0808
Language: ENGLISH
Document Type: JOURNAL ARTICLE 
Journal Announcement: 9706

Subfile: INDEX MEDICUS

The present study was designed to examine the role of endothelin-1 (ET-1), an  endothelium-derived potent long-acting vasoconstrictor peptide, in vascular  acrosyndromes with hypersensitivity to cold. Plasma ET-1 concentration was measured,  before and after cold test, in 12 subjects with "a frigore" vascular acrosyndromes (9  females and 3 males, age range 17-59 years), of whom 6 were with primary Raynaud's  phenomenon and 6 with essential acrocyanosis, and in 6 controls (5 females and 1  male, age range 21-37 years).

Cold stimulation was performed by immersion of one  hand into a water bath at 13 degrees C for 5 minutes. Blood samples were  simultaneously drawn from an antecubital vein in the cooled side and in the  contralateral arm at baseline, at the stop of cooling, at 10 and 90 minutes from the  beginning of the cold challenge. Mean (+/-SD) baseline ET-1 plasma levels, as  measured by radioimmunoassay, were higher in patients with "a frigore" vascular  acrosyndromes (4.8 +/- 0.3 pmol/l) than in control subjects (1.9 +/- 0.1 pmol/l, p <  0.001). After hand cooling ET-1 rose in patients with "a frigore" vascular disorders  to a peak value of 7.0 +/- 0.4 pmol/l, which was much greater than that observed in  healthy subjects (2.7 +/- 0.4 pmol/l, p < 0.001).

Absolute increase in ET-1 plasma  concentrations from baseline to peak value was significantly higher in patients with  "a frigore" vascular acrosyndromes than in normal subjects (2.2 +/- 0.3 vs 0.8 +/-  0.2 pmol/l, p < 0.001), being only in the former group the rise in ET-1 still  detected 90 minutes after cold test. Plasma levels of ET-1 in the controlateral arm  raised in a similar fashion, but absolute values were lower than in cooled arm. 

Circulating ET-1 levels in patients with primary Raynaud's phenomenon and essential  acrocyanosis showed a similar pattern during the study. Our data demonstrate that in  patients with "a frigore" vascular acrosyndromes baseline and cold-stimulated plasma  ET-1 concentrations are increased. Further, in these vascular disorders, exaggerated  ET-1 response to cold is prolonged.

These findings suggest that increased ET-1 may  contribute to an imbalance between vasoactive mediators in the cutaneous blood  vessels contributing to the abnormal vasoconstriction to cold in these disorders.  Alternatively, the increment in ET-1 release may represent a marker for endothelial  cell damage in "a frigore" vascular acrosyndromes.

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21.) Treatment of primary Raynaud's syndrome with traditional Chinese acupuncture.
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Appiah R; Hiller S; Caspary L; Alexander K; Creutzig A Medizinische Hochschule Hannover, Department of Angiology, Germany.
J Intern Med (ENGLAND) Feb 1997 241 (2) p119-24 ISSN: 0954-6820
Language: ENGLISH
Document Type: CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL 
Journal Announcement: 9706

Subfile: INDEX MEDICUS

OBJECTIVE: Evaluation of the effects of a standardized acupuncture treatment in  primary Raynaud's syndrome.

DESIGN: A controlled randomized prospective study. 

SETTING: A winter period of 23 weeks, angiological clinic of Hannover Medical School. 

SUBJECTS: Thirty-three patients with primary Raynaud's syndrome (16 control, 17  treatment).

 INTERVENTIONS: The patients of the treatment group were given seven  acupuncture treatments during the weeks 10 and 11 of the observation period.

MAIN  OUTCOME MEASURES: All patients kept a diary throughout the entire observation period  noting daily frequency, duration and severity of their vasospastic attacks. A local  cooling test combined with nailfold capillaroscopy was performed for all patients at  baseline (week 1) and in weeks 12 and 23, recording flowstop reactions of the  nailfold capillaries.

RESULTS: The treated patients showed a significant decrease in  the frequency of attacks from 1.4 day-1 to 0.6 day-1, P < 0.01 (control 1.6 to 1.2, P  = 0.08). The overall reduction of attacks was 63% (control 27%, P = 0.03). The mean  duration of the capillary flowstop reaction decreased from 71 to 24 s (week 1 vs.  week 12, P = 0.001) and 38 s (week 1 vs. week 23, P = 0.02) respectively. In the  control group the changes were not significant.

CONCLUSIONS: These findings suggest  that traditional Chinese acupuncture is a reasonable alternative in treating patients  with primary Raynaud's syndrome.

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22.) Oral L-arginine supplementation and cutaneous vascular responses in patients with  primary Raynaud's phenomenon.
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Khan F; Litchfield SJ; McLaren M; Veale DJ; Littleford RC; Belch JJ
University Department of Medicine, Ninewells Hospital and Medical School, Dundee,  Scotland, UK.
Arthritis Rheum (UNITED STATES) Feb 1997 40 (2) p352-7 ISSN: 0004-3591
Language: ENGLISH
Document Type: CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL 
Journal Announcement: 9705

Subfile: AIM; INDEX MEDICUS

OBJECTIVE: To assess the effects of oral L-arginine supplementation on cutaneous  vascular responses in patients with primary Raynaud's phenomenon (RP).

METHODS:  Double-blind, crossover comparison of placebo versus L-arginine (8 gm/day for 28  days). Cutaneous vascular responses in the fingers were assessed during  iontophoresis of acetylcholine and sodium nitroprusside, which are endothelium- dependent and endothelium-independent vasodilators.

RESULTS: In comparison with  control subjects, patients with primary RP had diminished endothelium-dependent and - independent vasodilatation (P < 0.05, and P < 0.005, respectively, by analysis of  variance). At the 3 doses used, vascular responses to acetylcholine were reduced by  71%, 64%, and 63%, respectively, and responses to sodium nitroprusside were reduced  by 67%, 73%, and 66%, respectively. L-arginine had no significant effect on  cutaneous vascular responses to acetylcholine or sodium nitroprusside in control  subjects or patients with primary RP.

CONCLUSION: Reduced vasodilator ability in  primary RP is unlikely to be due to an impairment in the L-arginine/nitric oxide  pathway.

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23.) Digital vascular responses to cooling in subjects with cold sensitivity, primary  Raynaud's phenomenon, or scleroderma spectrum disorders.
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Maricq HR; Weinrich MC; Valter I; Palesch YY; Maricq JG
Department of Medicine, Medical University of South Carolina, Charleston,  Charleston 29425, USA.
J Rheumatol (CANADA) Dec 1996 23 (12) p2068-78 ISSN: 0315-162X
Contract/Grant No.: AR-31283--AR--NIAMS; M01-RR-01070--RR--NCRR
Language: ENGLISH
Document Type: JOURNAL ARTICLE 
Journal Announcement: 9705

Subfile: INDEX MEDICUS

OBJECTIVE: To define differences in digital vascular responses to cooling and to  determine their usefulness for the differential diagnosis of 4 groups of subjects:  patients with primary Raynaud's phenomenon (RP) (n = 96), patients with RP associated  with scleroderma (systemic sclerosis, SSc) spectrum disorders (SSc spectrum RP) (n =  108), subjects complaining of cold sensitivity of the fingers (n = 88), and RP  negative controls (n = 120).

METHODS: Digital systolic blood pressure, digital blood  flow, and digital skin temperature were measured in a temperature controlled room at  18 or 23 degrees C; the effect of local finger cooling was tested at 30, 20, 15, and  10 degrees C.

RESULTS: Digital blood pressure responses clearly differentiate the 4  diagnostic groups from each other. By contrast, blood flow and skin temperature  measurements, although showing different group means, fail to reach statistical  significance due to a large variance. Digital pressure responses have high  sensitivity and specificity for distinguishing not only between patients with RP and  controls, but also between the 2 types of RP. A relative digital systolic pressure  (digital systolic pressure over brachial systolic pressure) of less than 70% at low  local finger cooling temperatures (15 and 10 degrees C) has a sensitivity of 97.1% in  differentiating SSc spectrum RP from primary RP. A zero reopening pressure shows a  specificity of 100% at 30 degrees C and 81.7% at 20 degrees C to separate the 2  groups. The zero reopening pressure is seldom associated with clinically visible RP  (10.3% among SSc spectrum RP, 4.3% among primary RP). Although the study was not  designed to investigate drug effects, our data from patients who failed to abstain  from vasodilators, as instructed, show they have a protective effect at 15 and 10  degrees C.

CONCLUSION: The digital pressure response to cooling is a useful test for  RP and cold sensitive subjects. It has high sensitivity and specificity to  differentiate between SSc spectrum RP and primary RP and between primary RP and cold  sensitive subjects. Our preliminary data on vasodilator use suggest that the digital  pressure response to cooling may also be useful in RP treatment studies.

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24.) A new examination system using photoplethysmography to evaluate skin blood flow  during exposure to vibration.
===================================================================
Klyscz T; Blazek V; Bussmann J; Keller M; Junger M
Department of Dermatology, University Hospital of Tubingen, Germany.
Cent Eur J Public Health (CZECH REPUBLIC) May 1996 4 (2) p145-8 ISSN: 1210-7778
Language: ENGLISH
Document Type: JOURNAL ARTICLE 
Journal Announcement: 9705

Subfile: INDEX MEDICUS

We introduce a new examination method developed at the University Dermatology  Hospital in Tubingen in cooperation with the Institute for High Frequency Techniques  of Aachen Technical College and the Metabo Factory in Nurtingen, Germany. The  Tubingen workplace simulator for studying vibration white finger (VWF) syndrome  standardized vibrations reproducing the vibration pattern of actual hand-held tools.  This stimulator makes it possible to evaluate on-line the effects of defined  vibrations on skin blood flow in the fingers and to investigate the etiopathogenesis  of vibration white finger syndrome.

The vibration simulator itself is modelled after  an altered router with two side-mounted handles. The electronic speed control and  exchangeable unbalance pins make it possible to adjust the frequency and amplitude of  the vibrations to simulate actual conditions in the job. New developed  photoplethysmographic sensors are fastened to the fingertips with double adhesive  rings and measure blood flow in the skin. Measurements are recorded simultaneously  with a multi-channel plotter.

This method is not only useful as a diagnostic tool  but has potential future applications in pre-employment screening in the affected  industries and in the development of reduced-vibration tools.

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25.) Raynaud's phenomenon in different groups of workers using hand-held vibrating  tools.
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Harazin B; Langauer-Lewowicka H
Institute of Occupational Medicine and Environmental Health, Sosnowiec, Poland.
Cent Eur J Public Health (CZECH REPUBLIC) May 1996 4 (2) p130-2 ISSN: 1210-7778
Language: ENGLISH
Document Type: JOURNAL ARTICLE 
Journal Announcement: 9705

Subfile: INDEX MEDICUS

The dose-effect relationship showed in the Annex A of the ISO standard 5349-1986  can be used for preventing vibration-induced white fingers (VWF) because it allows to  calculate the latent period for the lowest risk of VWF. The aim of this study was to  assess the risk of VWF in three different occupational groups of workers whose  members operated the same vibrating power tools and the same industrial processes  throughout the workday. Each occupational group was employed in two foundries and  they were considered to be very stable with a low turnover rate.

The mean frequency- weighted acceleration magnitudes measured from pneumatic rammers (25.3 +/- 3.3 ms-2)  where three times higher than from chipping hammers (8.4 +/- 3.8 ms-2) and six times  higher than from grinders (3.8 +/- 1.1 ms-2). Medical examinations were carried out  in 102 men consisting of 22 chippers, 42 rammers and 38 grinders.

The results of  this study showed that the relationship between lifetime exposure to hand-arm  vibration and the vascular disorders can be predicted quite well using the Annex A of  ISO standard only in one occupational group, that is, in chippers. Thirty-six  percent of chippers reported blanching symptoms, but only five percent of the rammers  and three percent of the grinders had these vascular disturbances.

Our results may  be explained by the fact that vibration received by an operator depends on the manner  in which the tool is used. In a foundry three following work processes are  performed: preparing forms in ramming mix, cleaning and grinding of castings during  which different forces are used by operators. It seems very likely that the energy  absorbtion in the hands and arms of chippers must be stronger than in other studied  groups.

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25.) Raynaud's phenomenon and other features of scleroderma, including pulmonary  hypertension.
===================================================================
Wigley FM
Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA.
Curr Opin Rheumatol (UNITED STATES) Nov 1996 8 (6) p561-8 ISSN: 1040-8711
Language: ENGLISH
Document Type: JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL 
Journal Announcement: 9705

Subfile: INDEX MEDICUS

Longitudinal studies of large cohorts of patients with Raynaud's Phenomenon have  addressed the predictors of developing a secondary disease. New insights have been  reported into the pathogenesis of Raynaud's phenomenon and the consequences of  ischemia.

Studies have suggested that more than one defect may cause Raynaud's  phenomenon, including increased alpha-2 sympathetic receptor activity on vessels,  endothelial dysfunction, deficiency of calcitonin gene related peptide protein-- containing nerves or some central thermoregulatory defect. The vasoconstricting and  profibrotic cytokine endothelin-1 was found to be elevated in scleroderma but did not  correlate with disease subset or with evidence of pulmonary hypertension.

Oxidant  stress is thought to be increased in scleroderma, causing tissue damage and provoking  fibrosis. Treatment with infusion of prostacyclin for primary pulmonary hypertension  was approved, paving the way for studies of secondary forms of pulmonary hypertension.  Oral prostanoids are being tested for the treatment of Raynaud's phenomenon. (92  References)

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26.) [Percutaneous thoracic sympathectomy under x-ray computed tomographic control in  hyperhidrosis and refractory ischemia. Apropos of 17 cases]
Sympatholyse thoracique percutanee sous controle scanographique dans les  hyperhidroses et les ischemies rebelles. A propos de 17 cas.
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Wazieres BD; Bartholomot B; Fest T; Combes J; Kastler B; Dupond JL
Service de Medecine Interne, Hopital Jean-Minjoz, Besancon.
Ann Med Interne (Paris) (FRANCE) 1996 147 (5) p299-303 ISSN: 0003-410X
Language: FRENCH Summary Language: ENGLISH
Document Type: 
JOURNAL ARTICLE English Abstract
Journal Announcement: 9705

Subfile: INDEX MEDICUS

We report our experience with percutaneous thoracic sympathectomy using computed  tomography-guided injection of phenol in 17 patients. A total of 24 neurolyses were  performed in outpatients. Indications were palmo-plantar hyperhidrosis in 10  patients and severe Raynaud phenomena in 7 cases (Sharp's syndrome = 2. sclerodermia  = 3, Raynaud's syndrome = 1, digital arteritis = 1). Conventional treatment had  failed in all patients. Cure was obtained in all cases of hyperhidrosis.

For the  patients with critical ischemia, there was temporary improvement which allowed wound  healing, but recurrence was the rule within 6 months on average. Complications  included pneumothorax, brachial nevralgia which persisted for 4 months and 3 partial  Claude-Bernard-Horner syndromes. This technique is an inexpensive reliable method  which can be used in case of contraindications or to avoid certain complications of  endoscopic surgery which remains the standard treatment.

Percutaneous sympatholysis  in thus an interesting simple alternative.

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27.) Controlled multicenter double blind trial of an oral analog of prostacyclin in the  treatment of primary Raynaud's phenomenon. 
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French Microcirculation Society Multicentre Group for the Study of Vascular Acrosyndromes.
Vayssairat M Hopital Tenon, Paris, France.
J Rheumatol (CANADA) Nov 1996 23 (11) p1917-20 ISSN: 0315-162X
Language: ENGLISH
Document Type: CLINICAL TRIAL; JOURNAL ARTICLE; MULTICENTER STUDY;
RANDOMIZED  CONTROLLED TRIAL 
Journal Announcement: 9705

Subfile: INDEX MEDICUS

OBJECTIVE: To compare the efficacy and tolerance of beraprost sodium, an oral  prostanoid prostaglandin I2 analog, with a placebo in patients with primary Raynaud's  phenomenon (RP).

METHODS: 125 patients with disabling primary RP participated in a  multicenter, randomized, double blind trial in 2 parallel groups, lasting 8 weeks,  and conducted during the winter months only; a meteorological survey was also  conducted for each patient. Main outcome measures were frequency and severity of  attacks of RP, overall disability, and digital cold challenge tests.

RESULTS: The  number of attacks decreased significantly in both groups (confidence intervals of  improvement: 35-53% in beraprost group and 25-49% in placebo group), but did not  differ significantly in the 2 groups. Similar results were found for the severity of  RP attacks and overall disability. No severe side effects occurred, but headache was  more frequent in the beraprost group (p = 0.001). Cold tests remained equally  abnormal in both groups throughout the study.

CONCLUSION: Although we observed 37%  improvement in the number of attacks of RP in the beraprost group, prostanoid  treatment proved no more beneficial than placebo.

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28.) Non-invasive assessment of vascular reactivity in forearm skin of patients with  primary Raynaud's phenomenon and systemic sclerosis.
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Anderson ME; Hollis S; Moore T; Jayson MI; Herrick AL
University of Manchester Rheumatic Diseases Centre, Hope Hospital, Salford.
Br J Rheumatol (ENGLAND) Dec 1996 35 (12) p1281-8 ISSN: 0263-7103
Language: ENGLISH
Document Type: JOURNAL ARTICLE 
Journal Announcement: 9704

Subfile: AIM; INDEX MEDICUS

We have non-invasively assessed neurovascular control mechanisms in forearm skin of  10 healthy control subjects, eight patients with primary Raynaud's phenomenon (PRP)  and 10 patients with systemic sclerosis (SSc) by iontophoresing acetylcholine  (endothelial dependent), sodium nitroprusside (endothelial independent) and  adrenaline, and measuring subsequent blood flow responses by dual-channel laser  Doppler.

Because basal forearm blood flow is low, adrenaline response was assessed  by attenuation of reperfusion hyperaemia following 60 s of upper arm occlusion.  Reperfusion hyperaemia prior to adrenaline iontophoresis differed significantly  between groups (F2.21 = 4.3, P = 0.03), being lowest in the SSc and highest in the  PRP group. However, the degree of attenuation of this hyperaemia by adrenaline did  not differ between groups and all groups demonstrated similar vasodilatory responses  to acetylcholine and to sodium nitroprusside.

These findings may reflect that  abnormalities in vascular tone in patients with Raynaud's phenomenon are local to the  digits, or that vasoactive agents not examined in this study play a key role.

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29.) [Thoracoscopic bilateral sympathectomy in Raynaud's syndrome. Anesthesiology  problems]
Simpaticectomia bilaterale per via toracoscopica nella sindrome di Raynaud.  Problemi anestesiologici.
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Delogu G; Marano M; Marandola M; Ciccioli T; Lombardi A; Costantini D
Istituto di Anestesia e Rianimazione, Universita degli Studi di Roma La Sapienza.
Ann Ital Chir (ITALY) May-Jun 1996 67 (3) p405-8; discussion 409 ISSN: 0003- 469X
Language: ITALIAN Summary Language: ENGLISH
Document Type: 
CLINICAL TRIAL; JOURNAL ARTICLE English Abstract
Journal Announcement: 9704

Subfile: INDEX MEDICUS

The objective of this paper was to examine the major anaesthetic problems during  transthoracic endoscopic sympathectomy without artificial pneumothorax and to present  our experience of 16 cases suffering from Raynaud's disease. For the perioperative  management we used a double lumen endo-bronchial tube and balanced anaesthesia  (intravenous agents plus isoflurane).

Arterial pressure, heart rate, ECG, end-tidal  carbon dioxide concentration, SatO2, blood gases and peak inspiratory pressures were  monitored. The results showed that no significant changes in these parameters  occurred during surgery. Since hypoxaemia is the main problem of the thoracoscopic  sympathectomy the A.A. emphasize the necessity to ensure a correct ventilation as  well as a haemodynamic stability throughout the procedure.

The combination of  balanced anaesthesia and double lumen endobronchial intubation seems an advisable  method when no artificial pnx is instituted. A close monitoring of the circulatory  and respiratory systems is imperative.

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30.) Raynaud's phenomenon.
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Wigley FM; Flavahan NA
Division of Rheumatology, Johns Hopkins University, Baltimore, MD 21205, USA.
Rheum Dis Clin North Am (UNITED STATES) Nov 1996 22 (4) p765-81 ISSN: 0889-857X
Language: ENGLISH
Document Type: JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC 
Journal Announcement: 9704

Subfile: INDEX MEDICUS

Raynaud's phenomenon is a common clinical problem occurring in 3% to 5% of the  general population. The first symptom of scleroderma is often Raynaud's phenomenon,  which is associated with a diffuse small vessel vasculopathy and ischemia and  reperfusion injury to skin and other organs targeted in this disease.

Current  studies support the concept that Raynaud's phenomenon is secondary to a local defect  in the regulation of regional blood flow. New evidence demonstrates that there is a  profound sensitivity to alpha 2-adrenoceptors mediated vasoconstriction in  scleroderma vessels.

Traditional treatment of Raynaud's phenomenon is cold avoidance  and the use of vasodilators. Oral prostaglandins have shown promise as therapeutic  agents. (121 References)

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DATA-MÉDICOS/DERMAGIC-EXPRESS No (48) 28/04/99 DR. JOSÉ LAPENTA R. 
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