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Postural Vasoconstriction and Leg Ulceration in Homozygous Sickle Cell Disease

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J S Mohan
J S Mohan
J S Mohan
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Janice M Marshall at University of Birmingham
Janice M Marshall
H L Reid
H L Reid
H L Reid
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P W Thomas
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P W Thomas
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Abstract

1. Chronic leg ulceration is a major cause of morbidity in patients with homozygous sickle cell disease; the ulcers commonly resolve on bed rest. We have therefore compared the cutaneous vascular response to dependency in three groups of eight patients with sickle cell disease (those with an active ulcer, with an ulcer scar and with no history of ulceration) and in eight subjects with normal haemoglobin and no history of leg ulceration. 2. We monitored, with a laser Doppler flowmeter, the change in red cell (erythrocyte) flux induced in the skin of the leg, at two sites proximal to the malleoli, with the leg horizontal and 5 and 10 min after moving the leg to the dependent position. 3. With the leg horizontal, mean cutaneous red cell flux was substantially higher in normal skin of patients with sickle cell disease than in normal subjects and was higher still at the site of the ulcer or scar. On dependency, red cell flux fell not only in normal subjects but also in the patients with sickle cell disease, both in the normal skin and at the site of the ulcer or scar; there was no difference in any group between the 5- and 10-min values. The fall in red cell flux in normal skin of patients with sickle cell disease was smaller than in normal subjects when considered as a percentage of the control values (32%, 36%, 30% and 61% respectively in sickle cell patients with an active ulcer, with an ulcer scar and with no history of ulceration and in normal subjects), but in absolute terms the falls in red cell flux were similar in sickle cell patients and normal subjects. By contrast, the fall in red cell flux at the ulcer or scar site was greater than in normal skin from sickle cell patients whether considered as a percentage of the control value (48% and 49% respectively in those with an active ulcer or ulcer scar) or in absolute terms. 4. We propose that high resting perfusion is important in patients with sickle cell disease to maintain normal integrity of cutaneous tissue and that pronounced vasoconstriction on dependency hinders the healing and encourages recurrence of leg ulcers.
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CONTENTS
Volume
92,
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I
January
1997
Guidance for Authors
I997
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EDITORIAL REVIEWS
Regulation of adipose cell number
in
man
by
J. B. PRINS
and
S.
O'RAHILLY
Cardiovascular pharmacology of purines
by
G.
A.
RONGEN, J.
S.
FLORAS,
J. W. M. LENDERS,
T. THIEN
and
P. SMITS
GLAXO/MRS YOUNG INVESTIGATOR PRIZE
Studies
on
the interaction of T-cells with major histocompatibility complex class
I1
antigens
by
A.
N.
WARRENS
PAPERS
Neutrophil
CDllB
expression and neutrophil activation in pre-eclampsia
by
A.
BARDEN,
D. GRAHAM, L. J. BEILIN, J. RITCHIE, R. BAKER, B.
N.
WALTERS
and C. A.
MICHAEL
Urinary albumin excretion and atherosclerosis in essential hypertension
by
R. PEDRINELLI,
K.
LINDPAINTNER, G. DELL'OMO, V. NAPOLI, V. DI BELLO, R. DE CATERINA
and
R. PETRUCCI
Renal handling of urate and sodium during acute physiological hyperinsulinaemia in healthy
subjects
by
J.
C.
TER MAATEN,
A.
VOORBURG,
R.
J.
HEINE, P.
M.
TER WEE,
A.
J.
M. DONKER
and
R.
0.
B. GANS
Elevated plasma levels of human adrenomedullin in cardiovascular, respiratory, hepatic and renal
disorders
by
B. CHEUNG
and
R. LEUNG
Effects of silicon, citrate and the fasting state
on
the intestinal absorption of aluminium in rats
by
T. B. DRUEKE, P. JOUHANNEAU, H. BANIDE, B. LACOUR,
F.
YIOU
and
G.
RAISBECK
Association of antral mucosal levels
of
interleukin 8 and reactive oxygen radicals in patients
infected with
Helicobacterpylon by
Q.
B. ZHANG, J. B. DAWODU,
A.
HUSAIN, G. ETOLHI,
C.
G. GEMMELL
and
R.
I.
RUSSELL
Brisk walking reduces calcaneal bone loss in post-menopausal women
by
K.
BROOKE-WAVELL,
P. R. M. JONES
and A.
E.
HARDMAN
Assessment of postural differences in regional pulmonary perfusion in man by single-photo
emission computerized tomography
by
D.
J. Ross, P. Wu
and
Z.
MOHSENIFAR
i-x
1
3-11
13-24
25-36
37-44
45-50
51-58
59-62
63-67
69-73
75-80
81-85
iv
Contents
Plasma RRR-a-tocopherol concentrations are lower in smokers than in non-smokers after
ingestion
of
a similar oral load of this antioxidant vitamin
by
L.
H.
MUNRO, G. BURTON and
F. J.
KELLY
87-93
Dietary fish oil reduces survival and impairs bacterial clearance in C3When mice challenged with
Listeriu monocytogenes by
K.
L.
FRITSCHE,
L.
M. SHAHBAZIAN, C.
FENG
and J. N. BERG 95-101
Volume
92,
part
2
February
1997
EDITORIAL REVIEW
Pathogenesis of liver fibrosis
by
R. ALCOLADO, M. J. P. ARTHUR and J. P. IREDALE
GLAXO/MRS YOUNG INVESTIGATOR PRIZE
Understanding the molecular basis of cell migration; implications for clinical therapy in multiple
sclerosis
by
R. MILNER
PAPERS
Role of nitric oxide towards vasodilator effects
of
substance P and ATP in human forearm vessels
by
M. SHIRAMOTO, T. IMAIZUMI, Y. HIROOKA, T. ENDO, T. NAMBA, J. OYAMA,
K.
HIRONAGA
and A.
TAKESHITA
oxide
by
D.
E.
NEWBY, N.
A.
BOON and D. J. WEBB
normotensive subjects
by
M.
A.
JAMES, P.
A.
C. WA-IT,
J.
F.
POTTER, H. THURSTON and
J.
D.
SWALES
Wistar rats is nitric oxide dependent
by
A.
B.
WALKER, M. W. SAVAGE,
J.
DORES and
G. WILLIAMS
Postural vasoconstriction and leg ulceration in homozygous sickle cell disease
by
J.
S.
MOHAN,
J. M. MARSHALL,
H.
L.
REID, P. W. THOMAS and G. R. SERJEANT
Comparative bioactivity of atrial and brain natriuretic peptides in an ovine model of heart failure
by
M. T. RADEMAKER, C.
J.
CHARLES,
E.
A. ESPINER, C. M.
FRAMPTON,
M. G. NICHOLLS and
A. M. RICHARDS
Modulation of neurocardiac function by oesophageal stimulation in humans
by
G. TOUGAS,
M.
KAMATH,
G. WAITEEL, D. FITZPATRICK,
E.
L.
FALLEN,
R.
H.
HUNT
and
A.
R. M. UPTON
Isometric contraction
of
arm flexor muscles as a method of evaluating cardiac vagal tone in man
by
M.
AL-ANI,
K.
ROBINS,
A.
H.
AL-KHALIDI, J. VAILE,
J.
TOWNEND
and J.
H.
COOTE
Transfection of cardiac muscle: effects of overexpression of
c-myc
and c-fos proto-oncogene
proteins in primary cultures
of
neonatal rat cardiac myocytes
by
N.
K.
GREEN, J.
A.
FRANKLYN,
V. OHANIAN, A. M.
HEAGERTY
and M. D. GAMMAGE
Contraction failure of skeletal muscle of rats recovering from critical illness
by
0.
E.
ROOYACKERS,
M.
K.
C.
HESSELINK
and A. J. M. WAGENMAKERS
Phagocytic degradation
of
chylomicron remnants by fibroblasts from subjects with homozygous
familial hypercholesterolaemia
by
K.
C.-W. Yu, D. SMITH, A. YAMAMOTO,
A.
KAWAGUCHI,
M. HARADA-SHIBA,
T.
YAMAMURA and
J.
C.
L.
MAMO
Comparison of forearm vasodilatation to substance P and acetylcholine: contribution
of
nitric
Endothelial function in subcutaneous resistance arteries from elderly hypertensive and
Insulin-induced attenuation
of
noradrenaline-mediated vasoconstriction in resistance arteries from
103-112
113-122
123-131
133-138
139-145
147-152
153-158
159-165
167-174
175- 180
181-188
189-195
197-203
Contents
V
Effect of seed crystals of uric acid and monosodium urate
on
the crystallization
of
calcium oxalate
Down-regulation
of
the acute-phase response in patients with pancreatic cancer cachexia receiving
in undiluted human urine
in
vitro
by
P. K. GROVER and R. L. RYALL 205-213
oral eicosapentaenoic acid is mediated via suppression
of
interleukin-6
by
S.
J.
WIGMORE,
K. C. H. FEARON,
J.
P. MAINGAY and
J.
A. Ross 215-221
CORRECTION
Visualizing signal transduction: receptors, G-proteins, and adenylate cyclases
by
C. W. DESSAUER,
B. A. POSNER and A. G. GILMAN
(Clin
Sci
1996;
91:
527-37) 223
SUPPLEMENT
36
Communications for the Autumn Meeting
of
the Medical Research Society on 14 and 15
November 1996 in conjunction with the Science and Medicine Conference at the Royal College
of Physicians, London lP-2OP
Volume
92,
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3
March
1997
EDITORIAL REVIEW
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E.
J.
SHERRATT,
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J.
C.
ALCOLADO
PAPERS
Sodium-lithium countertransport, sodium-hydrogen exchange and membrane microviscosity in
patients with hyperlipidaemia
by
M.
J.
MACLEOD, W. K. LEE, A. M. DEVLIN, M. CASLAKE,
N. H.
ANDERSON,
C.
J.
PACKARD, M.
H.
DOMINICZAK,
J.
L.
REID
and A.
F.
DOMINICZAK
Na+,K+-ATPase expression in maleic-acid-induced Fanconi syndrome in rats
by
E.
CASTMO,
P. MARZABAL, F.
J.
CASADO, A.
FELIPE
and M. PASTOR-ANGLADA
Low-dose brain natriuretic peptide infusion in normal men and the influence
of
endopeptidase
inhibition
by
C. M. FLORKOWSKI, A. M. RICHARDS,
E.
A.
ESPINER,
T. G. YANDLE,
E.
SYBERTZ
and
C.
M.
FFWMPTON
An
analysis of arterial disease mortality and BUPA health screening data in men, in relation to
outdoor temperature
by
G. C. DONALDSON, D. ROBINSON and
S.
L.
ALLAWAY
Nitric oxide is involved in the inhibitory neurotransmission and endothelium-dependent
relaxations
of
human small penile arteries
by
U. SIMONSEN,
D.
PRIETO,
J.
A. DELGADO,
M.
HERNANDEZ,
L.
RESEL,
I.
SAENZ
DE
TEJADA and A. GARC~A-SACRISTAN
Evidence that nitric oxide inhibits steroidogenesis in cultured rat granulosa cells
by
S.
DAVE,
D. P.
FARRANCE
and
S.
A. WHITEHEAD
Comparison between reproducibility and sensitivity of muscle sympathetic nerve traffic and plasma
noradrenaline in man
by
G. GRASSI, G. BOLLA, G. SERAVALLE, C. TURRI, A. LANFRANCHI and
G.
MANCIA
C.
H.
THOMPSON,
A.
L. SANDERSON,
D.
SANDEMAN, C. STEIN, A. BORTHWICK, G. K.
RADDA
and
D.
I.
W. PHILLIPS
Fetal growth and insulin resistance in adult life: role of skeletal muscle morphology
by
225-235
237-246
247-253
255-260
261-268
269-275
277-284
285-289
291-296
vi
Contents
Dietary sulphur amino acid adequacy influences glutathione synthesis and glutathione-dependent
enzymes during the inflammatory response to endotoxin and tumour necrosis factor-cc in rats
by
E.
A. L. HUNTER
and
R.
F.
GRIMBLE 297-305
Differential excretion of leucocyte granule components in inflammatory bowel disease:
implications for pathogenesis
by
A. D. DWARAKANATH,
I.
A. FINNIE, C.
M.
BEESLEY,
G.
M.
O'DOWD, J. NASH, H. H. TSAI, N. PARKER
and
J.
M.
RHODES 307-313
Effect of
two
forms of granulocyte-colony-stimulating factor
on
hepatic regeneration after
70%
partial hepatectomy in rats
by
S.
E.
THEOCHARIS,
E.
B. AGAFTTOS, A. P. MARGELI,
N.
D. GOUTAS, C. N.
KITTAS
and
P.
S.
DAVARIS 315-320
Volume
92,
part
4
April
1997
EDITORIAL REVIEW
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by
K. DOCHERTY
RAPID COMMUNICATION
Could the
MA11
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by
G. RODAS,
G.
ERCILLA, C. JAVIERRE,
E.
GARRIDO,
M.
CALVO, R. SEGURA
and
J.
LI.
VENTURA
PAPERS
Heart rate variability in patients with daytime sleepiness suspected of having sleep apnoea
syndrome: a receiver-operating characteristic analysis
by
C.
KEYL, P. LEMBERGER,
M.
PFEIFER,
K. HOCHMUTH
and
P. GEISLER
Complementary and non-coincident increases in heart rate variability and irregularity during fetal
Autonomic nervous function during haernodialysis assessed by spectral analysis of heart-rate
development
by
L. A. FLEISHER, J. A. DIPIETRO, T. R. B. JOHNSON
and
S.
PINCUS
variability
by
S.
CAVALCANTI,
S.
SEVERI,
L.
CHIARI, G. AVANZOLINI, G. ENZMANN,
F.
BIANCO
and
G. PANZETTA
Combination oral antioxidant supplementation reduces blood pressure
by
H.
F.
GALLEY,
J. THORNTON, P. D. HOWDLE, B.
E.
WALKER
and
N. R. WEBSTER
Haemodynamic and biochemical responses to L-arginine and L-lysine infusions in normal subjects:
L-arginine-induced vasodilatation cannot be explained by non-specific effects of cationic amino
acids
by
R. A. SMULDERS,
M.
AARSEN, T. TEERLINK, P.
M.
J.
M.
DE VRIES, G. J. VAN
KAMP,
A. J.
M.
DONKER
and C.
D. A. STEHOUWER
M.
G. THOMAS, R. P. STURGESS
and
M.
LOMBARD
accelerator mass spectrometry
by
K. W. SCHONHOLZER, R. A. L. SUTTON, V. R. WALKER,
V.
SOSSI,
M.
SCHULZER, C. ORVIG, E. VENCZEL, R. R. JOHNSON, D. VETTERLI,
B. DITTRICH-HANNEN, P. KUBIK
and
M.
SUTER
A. G. CUMMINS,
B.
M.
DALE, D. KOTASEK, T. A. ROBB
and
R.
E.
SAGE
water contents
by
A.
M.
FORSBERG,
J. BERGSTROM, B. LINDHOLM
and
E.
HULTMAN
The steroid vitamin
D3
reduces cell proliferation in human duodenal epithelium
by
Intestinal absorption of trace amounts
of
aluminium in rats studied with 26aluminium and
Effect of high-dose chemotherapy
on
intestinal permeability in humans
by
D.
M.
K.
KEEFE,
Resting membrane potential of skeletal muscle calculated from plasma and muscle electrolyte and
321-330
331-333
335-343
345-349
351-359
361-365
367-374
375-377
379-383
385-389
391-396
Contents
vii
Effect of urodilatin infusion on renal haemodynamics, tubular function and vasoactive hormones
Comparison
of
the effects on urinary sodium excretion of indomethacin and
of
carbidopa in
by
J.
CARSTENS,
K.
T.
JENSEN
and
E.
B.
PEDERSEN
397-407
normal volunteers given an intravenous saline infusion
by
G.
A.
STOKES,
J.
C. MONAGHAN
and
D. N. PILLAI
409-414
Mild endotoxaemia and the inflammatory response induced by a marathon race
by
G. CAMUS,
Effects of ordinary meals on plasma concentrations of
3,4-dihydroxyphenylalanine,
dopamine
J. POORTMANS, M. NYS, G. DEBY-DUPONT,
J.
DUCHATEAU, C. DEBY
and
M.
LAMY
415-422
sulphate and
3,4-dihydroxyphenylacetic
acid
by
E.
ELDRUP, D.
E.
MmLLER, J.
ANDREASEN
and
N.
J.
CHRISTENSEN
423-430
CORRESPONDENCE
Lipid-lowering strategies for the prevention of coronary heart disease
by
C. MORRISON
and
J. MCMURRAY
43
1
Lipid-lowering strategies for the prevention of coronary heart disease: author’s reply
by
I.
H.
HAQ,
L.
E.
RAMSAY,
D. M. PICKIN, W. W. YEO, P. R.
JACKSON
and
J.
N. PAYNE
431-432
Volume
92,
part
5
May
1997
EDITORIAL REVIEW
The hepatorenal syndrome
by
K.
MOORE
GWO/MRS YOUNG INVESTIGATOR PRIZE
Signalling pathways involved in the mitogenic effects of
CAMP
by
D. J. WITHERS
RAPID COMMUNICATION
Serum levels of vascular endothelial growth factor in patients with acute myocardial infarction
undergoing reperfusion therapy
by
Y. SEKO, Y. IMAI,
S.
SUZUKI,
S.
KAMIJUKKOKU,
K.
HAYASAKI,
Y.
SAKOMURA,
K.
TOBE,
T. KADowm,
H.
MAEKAWA,
N.
TAKAHASHI
and
Y.
YAZAKI
PAPERS
Tissue expression of components of the renin-angiotensin system in experimental post-infarction
heart failure in rats: effects of heart failure and angiotensin-converting enzyme inhibitor
treatment
by
M. P.
KELLY,
0.
KAHR, C. AALKJAER,
F.
CUMIN
and
N.
J.
SWI
COY, N.-Y. JIANG,
L.
K.
LEWIS,
T.
G. YANDLE,
A.
M.
RICHARDS
and
M. G. NICHOLLS
Adrenomedullin: a hypotensive hormone in man
by
J. G. LAINCHBURY, G. J.
S.
COOPER, D.
H.
The effects
of
low-density lipoprotein and high-density lipoprotein on blood viscosity correlate
with their association with risk of atherosclerosis in humans
by
G.
D.
SLOOP
and
D. W. GARBER
Effects of hydroxyurea administration on the body weight, body composition and exercise
performance of patients with sickle-cell anaemia
by
A.
C.
HACKNEY, W.
HEZIER;
T.
P.
GULLEDGE,
S.
JONES, D. STRAYHORN, M. BUSBY,
E.
HOFFMAN
and
E.
P.
ORRINGER
Female sex hormones do not influence arterial wall properties during the normal menstrual cycle
hv
C.
WITLEKES.
H.
J.
HOOGLAND.
H.
A.
KEIZER.
A.
P.
HOEKS
and
R.
S.
RENEMAN
’
433-443
445-451
453-454
455-465
467-472
473-479
481-486
487-491
viii
Contents
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by
C. DABROSIN,
A.
HALLSTROM,
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is
associated
U. UNGERSTEDT
and
M. HAMMAR
493-496
with a family history of hypertension and uraemia in patients with renal disease
by
S.
J.
CARR,
Renal afferents responsive to chemical and mechanical pelvic stimuli in the rabbit
by
S.
GENOVESI,
HPLC
glycosaminoglycan analysis in patients with Graves’ disease
by
CH. HANSEN, B. FRAITURE,
Sepsis and endotoxaemia in mice stimulate the expression of interleukin-1 and interleukin-6 in the
central nervous system
by
T. A. MEYER,
J.
J.
WANG, G.
M.
TIAO, C. K. OGLE,
J.
E.
FISCHER
and
D. MOORE, K. SIKAND
and R.
I.
NORMAN
497-503
F. PIERUZZI, P. CAMISASCA,
R.
GOLIN, A. ZANCHETTI
and
A. STELLA
505-510
R.
ROUHI,
E.
OTTO,
G.
FORSTER
and
G.
KAHALY
5 11-517
P.-0.
HASSELGREN
519-525
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I+paired cyokine production by peripheral
T
lymphocytes in low responders to hepatitis
B
I
vaccination
by
M.
YAMASHIKI, Y.
KOSAKA,
I.
KONDO
and
M. NOMOTO
527-528
Volume
92,
part
6
June
1997
EDITORIAL REVIEW
The antibody response in human autoimmune thyroid disease
by
R.
S.
MCINTOSH, M.
S.
ASGHAR
and
A. P. WEETMAN
PAPERS
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Determination of appropriate recording force by non-invasive measurement of arterial pressure
failure
by
G. C. BUTLER,
S.4.
ANDO
and
J.
S.
FLORAS
hypertension
by
A. COOPER
and
A.
M.
HEAGERTY
pulses
by
M. D. DRISCOLL,
J.
M.
0.
ARNOLD, G.
E.
MARCHIORI, L. A.
HARKER
and
M. H. SHEREBRIN
Maternal serum vascular endothelial growth factor during early pregnancy
by
P. EVANS,
Serum leptin and short-term regulation of eating in obese women
by
L.
KARHUNEN,
S.
HAFFNER,
Renal endothelin system in obstructive jaundice: its role in impaired renal function of bile-duct
Effect of temperature reduction on myotonia in rat skeletal muscles
in
vitro
by
L. FANNING
and
T. WHEELER, F.
ANTHONY
and
C. OSMOND
R.
LAPPALAINEN, A. TURPEINEN, H. MIETITNEN
and
M. UUSITUPA
ligated rats
by
H.
J.
KRAMER,
K.
SCHWARTING, A. BACKER
and
H.
MEYER-LEHNERT
M. MACDERMOTT
529-541
543-550
551-557
599-566
567-571
573-578
579-585
587-592
Contents
ix
Hypoxia, hypocapnia and spirometry at altitude
by
A.
J.
POLLARD, P.
W.
BARRY,
N.
P.
MASON,
D.
J.
COLLIER,
R.
C.
POLLARD, P.
F.
A.
POLLARD,
I.
MARTIN,
R.
S.
FRASER,
M.
R.
MILLER
and
J.
S.
MILLEDGE
CORRECTION
AUTHOR
INDEX
593-598
599
SUBJECT
INDEX
... There is limited knowledge about the relationship between cutaneous perfusion and the risk of leg ulcers in patients with sickle cell disease. One study recorded skin blood flux on the peri-malleolar region of patients with active, healed, or no history of ulcers, and in healthy subjects matched on age and ethnicity, using LDF (335). Two probes were used in patients with active ulcers, one probe was placed 1 cm from the edge of the ulcer; in those with a healed ulcer, it was placed on the middle of the scar. ...
... In both groups, the second probe was placed at 6 to 10 cm distance. When the leg was horizontal, skin blood flux recorded at distance from the active ulcer was similar to that measured in patients with no history of ulcers but significantly higher than skin blood flux recorded in healthy controls (335). During postural change (lowering the leg), a venoarteriolar reflex, that is, decrease in skin blood flux, was observed in all groups of patients, irrespective of their history of ulceration and of whether measurement was performed on ulcerated, scarred, or non-affected skin. ...
... In a standing position, vasoconstriction is lower in patients than in controls, which may help to prevent ulcer formation. In those with ulcers, this mechanism is locally impaired and the higher relative drop in skin blood flow prevents proper healing (335). ...
Human Skin Microcirculation
Article
Full-text available
  • Jul 2020
The anatomy and physiology of the microcirculation in human skin are complex. Normal cutaneous microcirculation is organized in two parallel plexuses with capillary loops extending perpendicularly from the superficial plexus. The physiological regulation of cutaneous microcirculation includes specific sympathetic activation, which causes vasoconstriction through the release of norepinephrine, neuropeptide Y, and ATP. A sympathetic cholinergic system is mainly involved in vasodilation through the co-transmission of acetylcholine, vasoactive intestinal peptide, and pituitary adenylate cyclase-activating peptide. Sensory nerves play a major role through the release of calcitonin gene-related peptide and substance P. Endothelium-dependent vasomotion implicates nitric oxide, prostacyclin, endothelium-dependent hyperpolarizing factors, and endothelin. Myogenic response also plays a role and explains why autoregulation is weak but exists in glabrous human skin. Variations in skin blood flow result from highly complex interactions between these mechanisms. In this article, we will detail the anatomy, physiology, and current methods of exploring the human microcirculation. We will further discuss the part played by cutaneous microvascular impairment in the pathophysiology of cardiovascular and metabolic diseases, or diseases more specifically affecting the skin. © 2020 American Physiological Society. Compr Physiol 10:1105-1154, 2020.
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... 107 Additionally, Billet et al. and Mohan et al. observed rapid refill times using venous pulse recordings, venous plethysmography and laser Doppler flowmetry in SCD patients with leg ulcers compared to those without. 32,108 To better understand the origin of venous hyperpressure, venous incompetency has been studied. ...
Controversies in the pathophysiology of leg ulcers in sickle cell disease
Article
Full-text available
Patients with sickle cell disease (SCD) often experience painful vaso‐occlusive crises and chronic haemolytic anaemia, as well as various acute and chronic complications, such as leg ulcers. Leg ulcers are characterized by their unpredictability, debilitating pain and prolonged healing process. The pathophysiology of SCD leg ulcers is not well defined. Known risk factors include male gender, poor social conditions, malnutrition and a lack of compression therapy when oedema occurs. Leg ulcers typically start with spontaneous pain, followed by induration, hyperpigmentation, blister formation and destruction of the epidermis. SCD is characterized by chronic haemolysis, increased oxidative stress and decreased nitric oxide bioavailability, which promote ischaemia and inflammation and consequently impair vascular function in the skin. This cutaneous vasculopathy, coupled with venostasis around the ankle, creates an ideal environment for local vaso‐occlusive crises, which can result in the development of leg ulcers that resemble arterial ulcers. Following the development of the ulcer, healing is hindered as a result of factors commonly observed in venous ulceration, including venous insufficiency, oedema and impaired angiogenesis. All of these factors are modulated by genetic factors. However, our current understanding of these genetic factors remains limited and does not yet enable us to accurately predict ulceration susceptibility.
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... 13 Vasoocclusion, venous incompetence, and severe hemolytic anemia are reported to play a role in the pathogenesis, 12,14 and genetic factors such as polymorphisms in genes related to vascular injury, wound healing, and others may also contribute to the occurrence of leg ulcers. 12,[15][16][17][18] In Brazil, almost all individuals with SCD are treated at Hemocenters that were established in the late 1980s to focus on the safe collection and transfusion of blood and blood components and provide comprehensive care for patients with hemoglobinopathies, coagulopathies, and oncohematologic diseases. The treatment of SCD in Brazil has improved in recent years after the introduction of hydroxyurea (HU), improvements in the knowledge of the pathophysiology of the disease, easier access to comprehensive care centers, the establishment of protocols for chronic transfusion, and progress in blood safety. ...
Factors Associated with Leg Ulcers in Adults with Sickle Cell Disease in Brazil
Article
  • Feb 2023
  • Adv Skin Wound Care
Objective: To define the prevalence of leg ulcers and identify the clinical and laboratory factors associated with leg ulcers in adult participants. Methods: The authors conducted a cross-sectional study of 1,109 patients who were 18 years or older with SS or Sβ0-thalassemia genotypes from a Brazilian cohort. Investigators assessed the prevalence of factors associated with leg ulcers from 2013 to 2017. Results: The prevalence of leg ulcers was 21%. Increasing age (odds ratio [OR], 1.07; range, 1.06-1.09), male sex (OR, 2.03; range, 1.44-2.87), treatment with chronic transfusion therapy (OR, 1.88; range, 1.15-3.03), higher indirect bilirubin levels (OR, 1.48; range, 1.02-2.16), and low hemoglobin levels (OR, 2.17; range, 1.52-3.11) were associated with leg ulcers. Participants who self-reported as Black (OR, 6.75; range, 2.63-21.32), mixed (OR, 3.91; range, 1.55-12.20), and other/unknown (OR, 3.84; range, 1.04-15.24) were more likely to have leg ulcers compared with those who self-reported as White. Conclusions: The prevalence of leg ulcers in this Brazilian cohort was higher than the prevalence reported in developed countries. Known factors such as age and male sex were corroborated. The increased bilirubin level and decreased hemoglobin levels among participants with leg ulcers support the hypothesis that hemolysis is correlated with leg ulcer pathogenesis. Self-reported black skin color was an independent predictor of leg ulcers and warrants further study to understand the etiology and implications of this finding.
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... Considering the established role of NO as an essential mediator of vasodilation and proper endothelial function, lower levels of NO thus predispose individuals with SCD to vasoconstriction and endothelial dysfunction thought to contribute to the development of ischemia, infarction, and eventual ulceration [5,12,19,20]. Ongoing research is additionally examining the role of infection, venous incompetence, and autonomic dysfunction in ulcer development [15,20,21]. ...
Cutaneous manifestations of sickle cell disease: an updated review
Article
Full-text available
  • Nov 2022
  • ARCH DERMATOL RES
Sickle cell disease is a common and highly morbid genetic condition that is characterized by multi-system involvement, including numerous cutaneous manifestations. Persistent and recurrent leg ulceration has long been considered the dermatological hallmark of those with sickle cell disease, but there have been recent descriptions of associated infection with rare pathogens and episodes of liverdoid vasculopathy. Growing considerations for this population in the literature include cutaneous reactions to common treatments such as hydroxyurea and clinical management of the intersection between sickle cell disease and conditions like plaque psoriasis. Recent studies have also demonstrated an increased resistance to skin carcinogenesis for those with sickle cell disease through unclear mechanisms. However, though the body of knowledge regarding cutaneous manifestations and considerations of sickle cell disease is slowly expanding, it does not match the considerable disease and symptom burden faced by these patients. More research is needed to better delineate our understanding of these cutaneous manifestations of sickle cell disease to improve outcomes and further management.
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... This is further supported by evidence that LDL-C is also susceptible to oxidative modifications in SCA, based on the observation of increased binding of free heme to LDL-C Disease Markers fractions, which could favor the production of oxLDL [29]. Moreover, multiple vascular mechanisms have been attributed to the pathogenesis of leg ulcers in SCA, such as the physical obstruction caused by irreversibly sickled red blood cells, poor venous recirculation, bacterial infection, anemia, in situ thrombosis, and reduced NO bioavailability [40]. Patients with a previous history of leg ulcers exhibit elevated hemolytic laboratory parameters, increased uric acid, and 7 Disease Markers decreased albumin levels [41]. ...
Investigation of Lipid Profile and Clinical Manifestations in SCA Children
Article
Full-text available
  • Aug 2020
  • DIS MARKERS
Introduction: Clinical complications in sickle cell anemia (SCA) are heterogeneous and involve several molecules. It has been suggested that SCA individuals present a dyslipidemic phenotype and that lipid parameters are associated with severe clinical complications, such as pulmonary hypertension. We sought to investigate associations between lipid parameters and clinical manifestations, as well as other laboratory parameters in a population of pediatric SCA patients. Methods: Our cross-sectional evaluation included 126 SCA patients in steady state and who were not undergoing lipid-lowering therapy. Hematological and biochemical parameters were characterized, and previous clinical manifestations were investigated. Results: Total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels were increased in patients with a previous history of pneumonia, which also positively correlated with HbS levels. Decreased LDL-C levels were also associated with leg ulcers and anemia. Elevated high-density lipoprotein cholesterol (HDL-C) levels were associated with pain crises, increased viscosity, and decreased hemolysis. Several studies have determined that lipids play a role in the vascular impairment seen in SCA, which was corroborated by our findings. Conclusions: In sum, our results suggest that total cholesterol, HDL-C, and LDL-C levels are associated with hemolysis and anemia markers and, most importantly, with clinical complications related to vasculopathy in SCA.
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... 79 Leg ulcers may appear spontaneously or after infection or trauma, even minor, to an area of compromised blood supply may initiate an ulcer. Other reported factors that may enhance blood stasis and skin necrosis include reduced red blood cell deformability, 80 adherence of sickle red blood cells to the endothelium, 81 increased blood viscosity, 82 the presence of circulating immune complexes, 83 activated blood coagulation, 84 pulmonary hypertension, abnormal autonomic control with excessive vasoconstriction when in the dependent position, in situ thrombosis, anemia with a decrease in oxygen-carrying capacity, 85 and decreased nitric oxide bioavailability, leading to impaired endothelial function. 86 Secondary infection of the ulcer, with undermining of the edges, delays healing and causes progressive extension of skin ulceration. ...
Review/Overview of pain in sickle cell disease
Article
  • Feb 2020
  • COMPLEMENT THER MED
Sickle cell disease (SCD) is a highly complex inherited disorder of hemoglobin structure. Although the molecular lesion is a single-point mutation, the sickle gene is pleiotropic in nature causing multiple phenotypic expressions that constitute the various complications of the disease. Its manifestations could be acute, chronic, nociceptive, neuropathic that could occur singly or in various combinations. Pain continues to be the major factor of SCD phenotypic complications and the most common cause of admissions to the Emergency Department and/or the hospital. Although progress has been made in understanding the pathophysiology of SCD as well as in developing curative therapies such as hematopoietic stem cell transplantation and gene therapy, effective pain management continues to lag behind. Palliative therapies continue to be the major approach to the management of SCD and its complications. The advent of hydroxyurea made partial success in preventing the frequency of vaso-occlusive crises and l-glutamine awaits post-trial confirmation of benefits. The search for additional pharmacotherapeutic agents that could be used singly or in combination with hydroxyurea and/or l-glutamine awaits their dawn hopefully in the near future. The purpose of this review is to describe the various manifestations of SCD, their pathophysiology and their current management. Recent impressive advances in understanding the pathophysiology of pain promise the determination of agents that could replace or minimize the use of opioids.
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Micronutrients in the Patients with Sickle Cell Disease and Power Limb Ulcer
Chapter
Full-text available
  • Apr 2021
Sickle cell disease (SCD) is a more frequent hereditary hemoglobinopathy in Brazil, affecting predominantly black individuals ...
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Advanced Topics Of Clinical Nutrition In Hematology (Volume 1)
Book
Full-text available
  • Apr 2021
Advanced Topics in Nutrition in Hematology (Volume 1) aimed to describe essential aspects in the nutritional care of people with hematological diseases based on the experience of Nutritionists and Clinical Nutrition Interns at a Reference Center for Hematologic Disease in the State of Rio de Janeiro.This work was developed to gather information necessary for the practice of Clinical Nutrition in Hematology, prioritizing the scientific quality, relevance, and timeliness of the topics covered. Also, it came to fill some gaps concerning nutritional management in hematological diseases. In this scenario, the authors of this first volume contribute nine chapters distributed in three sessions. In the first part, the work process of Nutrition in Hematology will be addressed, contemplating the Brazilian health care network, the hematological diseases themselves and procedures for a first consultation of the patient with pharmacological disease. In the second session, the nutritional aspects of proliferative and infiltrative diseases will be addressed. It provides pertinent information about the drug-nutrient interaction and loss of body mass related to lymphocytic leukemia and essential thrombocytopenia. In its third session, anemia will be addressed, with an emphasis on nutritional management in sickle cell disease and its secondary complications Stroke and leg ulcer. Due to the relevance of its content, the book Advanced Topics in Clinical Nutrition in Hematology will serve as a foundation not only for nutritionists but for all professionals interested in gaining knowledge about nutrition in hematology. Several hematological processes occur in the blood for the maintenance of homeostasis and any changes in the hematopoietic system will negatively impact the functionality of its components.Adequate nutrition significantly influences the results of haematological processes and may promote or present health risks. Many hematopoietic disorders decrease the number of cells and nutrients in the plasma, thus interfering with their functions. At the same time, vitamins and minerals are indispensable for metabolic activities at the cellular level, ensuring the formation and proper functioning of blood cells. Disability and toxicity states, consequently, lead to a decrease in blood functionality, resulting in acute and/or chronic conditions that can impair the nutritional status of the individual with hematologic disease.
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Impaired Postural Vasoconstriction: A Contributory Cause of Oedema in Patients with Chronic Venous Insufficiency
Article
  • Sep 1988
Dependent oedema is a common feature in patients suffering from venous insufficiency. Postural vasoconstriction which prevents oedema has been shown to be impaired in several conditions complicated by dependent oedema. We therefore investigated the postural vasoconstrictor response, foot swelling rate and capillary density in eight patients with venous insufficiency and seven normal controls. Foot skin blood flow was measured on the pulp of the big toe using laser–Doppler flowmetry with the foot at heart level (H) and placed approximately 1 metre below the heart (D). Postural fall in flow was calculated as (H – D) × 100/H. Foot swelling rate was measured simultaneously using a strain gauge Plethysmograph. Postural vasoconstriction was impaired in venous insufficiency at 62 ± 12% compared to 88 ± 4% in controls (P < 0.02). Capillary density in the forefoot was assessed using television microscopy and was significantly reduced in the venous insufficiency group at 26.83 ± 2.74 per mm2 compared to 36.96 ± 1.09 per mm2 (P < 0.01). These findings suggest impaired postural vasoconstriction may contribute to the formation of oedema characteristic of venous insufficiency. The apparent reduction in capillary density may be implicated in the pathogenesis of venous ulceration to which such patients are prone.
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Microvascular reactions to postural changes in patients with sickle cell anaemia
Article
  • Jun 1994
Normal microcirculation of the lower extremity is characterized by the venoarteriolar vasoconstriction reflex and the disappearance of vasomotion in the dependent position. Patients with sickle cell disease are prone to develop ischemic leg ulcers at an early age. Dysfunction of the microcirculation might promote the development of leg ulcers in patients with sickle cell disease. Using laser Doppler equipment we have studied the changes of blood flux in the skin overlying the medial malleolus after leg lowering. Contrary to the normal physiological situation seen in our control persons, the venoarteriolar reflex was abolished and vasomotion preserved in the dependent position of the leg in both patients. We conclude that this may represent an adaptation to the dependent position in sickle cell disease.
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A comparative study in subjects with homozygous sickle cell disease and in normal subjects of responses evoked in forearm vasculature by mild indirect cooling
Article
  • May 1994
We have studied responses evoked in the forearm vasculature of twelve subjects with homozygous sickle cell disease (SS) and in eight dark-skinned controls of West Indian ancestry (AA) by mild cooling of the contralateral hand in water at 16 degrees C for 2 min; this stimulus was repeated six times at randomized time intervals. Total forearm blood flow was measured by venous occlusion plethysmography, cutaneous red cell flux was monitored by a laser Doppler flowmeter and arterial pressure was recorded by semi-automatic sphygmomanometry. Of the AA subjects, three showed a decrease in total forearm vascular resistance (FVR, of -10%) in response to the first immersion and this reversed to an increase in FVR (+7%) by the sixth immersion. The remaining five showed an increase in FVR (+65%) which persisted until the sixth immersion (26%). By contrast, all SS subjects showed an increase in FVR (+32%) which persisted to the sixth stimulus (+27%). Further, on a scale of discomfort of 0-10, none of the AA subjects rated the cool stimulus higher than 0, whereas SS subjects gave a rating of 7 for the first stimulus which decreased to 5 by the sixth stimulus. Both AA and SS subjects showed an increase in arterial pressure and a tendency towards vasoconstriction in forearm skin. We propose that, as in Caucasian AA subjects, dark-skinned AA subjects showed a primary reflex vasoconstriction in forearm muscle in response to mild, indirect cooling which was overcome in some individuals by muscle vasodilation of the alerting response that is evoked by novel or noxious stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)
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