EDITORIAL ESPANOL:

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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.

PRÓXIMA EDICIÓN: * Lupus eritematoso discoide.

Saludos,,,

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,,,

Dr. José Lapenta R. 

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DERMAGIC/EXPRESS(51)

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EL SYNDROME 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

106 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

pa-tients 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.

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.

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 70

ketanserin, 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 na-ture." 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.

=====================================================================

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.

===================================================================

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)

===================================================================

3.) Cryofibrinogenemia with polyarthralgia, Raynaud's phenomenon and acral

ulcer in a 

patient with Graves' disease treated with methimazole.

===================================================================

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.

===================================================================

4.) [Raynaud's phenomenon: effects of terazosin]

Il fenomeno di Raynaud: effetti della terazosina.

===================================================================

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.

===================================================================

5.) Plasma nitric oxide metabolite in women with primary Raynaud's

phenomenon and in 

healthy subjects.

===================================================================

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.

===================================================================

6.) Geographic variation in the prevalence of Raynaud's phenomenon: a 5

region 

comparison.

===================================================================

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.

===================================================================

7.) Clinical studies of the vibration syndrome using a cold stress test

measuring 

finger temperature.

===================================================================

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.

===================================================================

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.

===================================================================

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.

===================================================================

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.

===================================================================

10.) Risk factors for Raynaud's phenomenon among workers in poultry

slaughterhouses and canning factories.

===================================================================

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.

===================================================================

11.) The transcriptional activator Sp1, a novel autoantigen.

===================================================================

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.

===================================================================

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.

===================================================================

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.

===================================================================

13.) [The efferent therapy of Raynaud's phenomenon]

Eferentna terapiia fenomenu Reino.

===================================================================

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.

===================================================================

14.) Reaction of capillary blood cell velocity in nailfold capillaries to

L-carnitine in patients with vasospastic disease.

===================================================================

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.

===================================================================

15.) Prevalence of Raynaud phenomenon in Tartu and Tartumaa, southern Estonia.

===================================================================

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.

===================================================================

16.) A novel anti-microfilament antibody, anti-135 kD, is associated with

Raynaud's 

disease, undifferentiated connective tissue disease and systemic autoimmune

diseases.

===================================================================

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.

===================================================================

17.) Antibodies to fibrin-bound tissue-type plasminogen activator in

systemic lupus 

erythematosus are associated with Raynaud's phenomenon and thrombosis.

===================================================================

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.

===================================================================

18.) Pharmacotherapy of Raynaud's phenomenon.

===================================================================

Belch JJ; Ho M

Department of Vascular Medicine, Ninewells Hospital and Medical School,

Dundee, 

Scotland. jjfbelch@dundee.ac.ulc

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)

===================================================================

19.) Treatment of ischaemic digital ulcers and prevention of gangrene with

intravenous 

iloprost in systemic sclerosis.

===================================================================

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.

===================================================================

20.) Circulating endothelin-1 levels in patients with "a frigore" vascular 

acrosyndromes.

===================================================================

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.

===================================================================

21.) Treatment of primary Raynaud's syndrome with traditional Chinese

acupuncture.

===================================================================

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.

===================================================================

22.) Oral L-arginine supplementation and cutaneous vascular responses in

patients with 

primary Raynaud's phenomenon.

===================================================================

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.

===================================================================

23.) Digital vascular responses to cooling in subjects with cold

sensitivity, primary 

Raynaud's phenomenon, or scleroderma spectrum disorders.

===================================================================

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.

===================================================================

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.

===================================================================

25.) Raynaud's phenomenon in different groups of workers using hand-held

vibrating 

tools.

===================================================================

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.

===================================================================

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)

===================================================================

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.

===================================================================

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.

===================================================================

27.) Controlled multicenter double blind trial of an oral analog of

prostacyclin in the 

treatment of primary Raynaud's phenomenon. 

===================================================================

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.

===================================================================

28.) Non-invasive assessment of vascular reactivity in forearm skin of

patients with 

primary Raynaud's phenomenon and systemic sclerosis.

===================================================================

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.

===================================================================

29.) [Thoracoscopic bilateral sympathectomy in Raynaud's syndrome.

Anesthesiology 

problems]

Simpaticectomia bilaterale per via toracoscopica nella sindrome di Raynaud. 

Problemi anestesiologici.

===================================================================

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.

===================================================================

30.) Raynaud's phenomenon.

===================================================================

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 (51) 28/04/99 DR. JOSE LAPENTA R. 

======================================================================

Produced by Dr. José Lapenta R. Dermatologist
Venezuela 1.998-2.024

Producido por Dr. José Lapenta R. Dermatólogo Venezuela 1.998-2.0024

Tlf: 0414-2976087 - 04127766810