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****** DATA-MEDICOS **********
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EL SYNDROME DE RAYNAUD 
THE RAYNAUD'S SYNDROME
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****** DERMAGIC-EXPRESS No.51 ******* 
****** 28 ABRIL DE 1.999 *********** 
28 APRIL 1.999
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EDITORIAL ESPAÑOL
=================
Hola amigos DERMAGICOS, los saludo desde Venezuela,,,,el tema de hoy,, el
SINDROME DE RAYNAUD, el cual se presenta como enfermedad individual
(ENFERMEDAD DE RAYNAUD), o sintoma secundario de otras patologias,
(FENOMENO DE RAYNAUD), bastante dificil de tratar por cierto. Espero que
estas 30 referencias nos sean utiles para aclarar nuestros conceptos. 

En el attach una lámina ilustrativa de la enfermedad.

Saludos a TODOS !!!


PROXIMA EDICION: * Lupus eritematoso discoideo.

Dr. Jose Lapenta R.,,,

Hubo Problemas con el servidor de Colombia...

EDITORIAL ENGLISH
=================
Hello DERMAGIC friends, Greetings from Venezuela,,,, today's topic, the
RAYNAUD'S SYNDROME,, that is presented as singular illness (RAYNAUD'S
DISEASE), or secondary symptom of other pathologies (RAYNAUD'S PHENOMENON),
quite difficult to treat, by the way. I hope these 30 references are we
useful to clarify our concepts. 

In the attach, an illustrative sheet of the topic.

NEXT EDITION: Discoid lupus erythematosus. 


Greetings to ALL, !!

Dr. Jose Lapenta R.,,,
=====================================================================
DERMAGIC/EXPRESS(51)
=====================================================================
EL SYNDROME DE RAYNAUD / THE RAYNAUD'S SYNDROME
=====================================================================
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.
=====================================================================
=====================================================================
1.) Raynaud's Syndrome: An Overview
=====================================================================
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

========================================================
Table 1. Criteria for the Diagnosis of Raynaud's Disease*
----------------------------------------------------------
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
========================================================

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 *
===================================================
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:
======================================================
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
=========================================
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)
=========================================

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. [email protected]
Drugs (NEW ZEALAND) Nov 1996 52 (5) p682-95 ISSN: 0012-6667
Language: ENGLISH
Document Type: JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL 
Journal Announcement: 9706
Subfile: INDEX MEDICUS
Primary Raynaud's phenomenon is common, particularly in younger women,
and may be 
familial. Vasospasm is not confined to the digits and may involve, for
example, the 
tongue and nose, and also visceral organs like the heart, oesophagus or
lung and 
cerebral circulation. Symptoms tend to be milder in primary compared with
secondary 
Raynaud's phenomenon, which is associated with other disorders such as the
connective 
tissue diseases. Indeed, the severity of symptoms often acts as the
predictor for 
the much later onset of the associated systemic disease. Occupational
Raynaud's 
phenomenon is related to the use of vibrating instruments, and a significant 
proportion of patients may be cured by an early change in job. In those
over 60 
years of age, Raynaud's phenomenon is commonly a result of atherosclerotic 
obstructive arterial disease, and screening for and treatment of the risk
factors is 
appropriate. The best-studied mechanisms in Raynaud's phenomenon involve
the blood 
and vascular endothelium. Microcirculatory flow may be impeded by
activated platelet 
clumps, rigid red and white blood cells and damaged endothelium. These
platelet 
clumps, white blood cells and damaged endothelium also release 
vasoactive/vasoconstrictive compounds which may additionally trigger the
clotting 
cascade and thrombosis. Initial management for mild disease should focus
on support 
and advice regarding avoidance of known precipitating factors, including
vasospastic 
drugs. Cold protection with warming agents, 'Abel' shoes and also
electrically 
heated gloves and socks is effective, but may be too cumbersome and
inconvenient for 
some patients. Simple vasodilators like naftidrofuryl, inositol nicotinate
and 
possibly pentoxifylline (oxpentifylline) are useful in mild disease, with
adverse 
effects like headache and flushing being less problematic. The 'gold
standard' of 
Raynaud's phenomenon treatment is nifedipine, a calcium channel
antagonist/blocker. 
Full dosage, however, can be limited by ankle swelling, headache and
flushing, but 
adverse effects may be reduced by using the 'retard' or long-acting
preparations. 
Adverse effects are also reduced with the newer calcium channel antagonists
like 
diltiazem but at the expense of efficacy. Useful, enhanced benefit is also
achieved 
by combination therapy with vasodilators. Newer treatments include the
prostaglandin 
analogues which are effective but disadvantaged by their parenteral route of 
administration, and lack of licence in some countries. Oral preparations
are, 
however, being studied and are in the pipeline. Essential fatty acid
supplementation 
is mildly effective, while ketanserin and calcitonin gene-related peptide
both look 
promising. Lumbar sympathectomy retains its important role in the
treatment of 
Raynaud's phenomenon involving the lower limbs. Satisfactory symptomatic
relief is 
now possible for many patients with Raynaud's phenomenon and this should
certainly be 
the aim for all patients seeking medical help. (73 References)

===================================================================
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)

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26.) [Percutaneous thoracic sympathectomy under x-ray computed tomographic
control in 
hyperhidrosis and refractory ischemia. Apropos of 17 cases]
Sympatholyse thoracique percutanee sous controle scanographique dans les 
hyperhidroses et les ischemies rebelles. A propos de 17 cas.
===================================================================
Wazieres BD; Bartholomot B; Fest T; Combes J; Kastler B; Dupond JL
Service de Medecine Interne, Hopital Jean-Minjoz, Besancon.
Ann Med Interne (Paris) (FRANCE) 1996 147 (5) p299-303 ISSN: 0003-410X
Language: FRENCH Summary Language: ENGLISH
Document Type: 
JOURNAL ARTICLE English Abstract
Journal Announcement: 9705
Subfile: INDEX MEDICUS
We report our experience with percutaneous thoracic sympathectomy using
computed 
tomography-guided injection of phenol in 17 patients. A total of 24
neurolyses were 
performed in outpatients. Indications were palmo-plantar hyperhidrosis in 10 
patients and severe Raynaud phenomena in 7 cases (Sharp's syndrome = 2.
sclerodermia 
= 3, Raynaud's syndrome = 1, digital arteritis = 1). Conventional
treatment had 
failed in all patients. Cure was obtained in all cases of hyperhidrosis.
For the 
patients with critical ischemia, there was temporary improvement which
allowed wound 
healing, but recurrence was the rule within 6 months on average.
Complications 
included pneumothorax, brachial nevralgia which persisted for 4 months and
3 partial 
Claude-Bernard-Horner syndromes. This technique is an inexpensive reliable
method 
which can be used in case of contraindications or to avoid certain
complications of 
endoscopic surgery which remains the standard treatment. Percutaneous
sympatholysis 
in thus an interesting simple alternative.

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27.) Controlled multicenter double blind trial of an oral analog of
prostacyclin in the 
treatment of primary Raynaud's phenomenon. 
===================================================================
French Microcirculation Society Multicentre Group for the Study of Vascular
Acrosyndromes.
Vayssairat M
Hopital Tenon, Paris, France.
J Rheumatol (CANADA) Nov 1996 23 (11) p1917-20 ISSN: 0315-162X
Language: ENGLISH
Document Type: CLINICAL TRIAL; JOURNAL ARTICLE; MULTICENTER STUDY;
RANDOMIZED 
CONTROLLED TRIAL 
Journal Announcement: 9705
Subfile: INDEX MEDICUS
OBJECTIVE: To compare the efficacy and tolerance of beraprost sodium, an
oral 
prostanoid prostaglandin I2 analog, with a placebo in patients with primary
Raynaud's 
phenomenon (RP). METHODS: 125 patients with disabling primary RP
participated in a 
multicenter, randomized, double blind trial in 2 parallel groups, lasting 8
weeks, 
and conducted during the winter months only; a meteorological survey was also 
conducted for each patient. Main outcome measures were frequency and
severity of 
attacks of RP, overall disability, and digital cold challenge tests.
RESULTS: The 
number of attacks decreased significantly in both groups (confidence
intervals of 
improvement: 35-53% in beraprost group and 25-49% in placebo group), but
did not 
differ significantly in the 2 groups. Similar results were found for the
severity of 
RP attacks and overall disability. No severe side effects occurred, but
headache was 
more frequent in the beraprost group (p = 0.001). Cold tests remained
equally 
abnormal in both groups throughout the study. CONCLUSION: Although we
observed 37% 
improvement in the number of attacks of RP in the beraprost group, prostanoid 
treatment proved no more beneficial than placebo.

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28.) Non-invasive assessment of vascular reactivity in forearm skin of
patients with 
primary Raynaud's phenomenon and systemic sclerosis.
===================================================================
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-MEDICOS/DERMAGIC-EXPRESS No (51) 28/04/99 DR. JOSE LAPENTA R. 
======================================================================

 

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                 Maracay Estado Aragua Venezuela 1.999 
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