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Cardiovascular Research 2003 57(3):615-624; doi:10.1016/S0008-6363(02)00728-9
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Copyright © 2003, European Society of Cardiology

Current pathophysiological views on vibration-induced Raynaud's phenomenon

Z Stoynevaa,*, M Lyapinab, D Tzvetkovb and E Vodenicharovb

aCentre of Occupational Diseases, University Hospital ‘St Ivan Rilsky’, 15 Dimitar Nestorov St., 1431 Sofia, Bulgaria
bDepartment of Hygiene, Ecology and Occupational Health, Medical University, 15 Dimitar Nestorov St, 1431 Sofia, Bulgaria

zlatka_stoyneva{at}yahoo.com

* Corresponding author. Tel.: +359-2-5812-415.

Received 16 April 2002; accepted 14 October 2002


   Abstract
Top
 Abstract
1. Neural dysfunction
 2. Local acral vasodysregulation
 3. Shear stresses
 4. Blood viscosity and...
 5. Conclusions
 References
 
This review attempts to summarize and discuss contemporary pathogenetic views on vibration-induced Raynaud's phenomenon assuming its multifactorial etiology. An increase in central and peripheral sympathetic nervous activity is discussed based on different physiological indicators of autonomic dysfunction and sympathetic hyperactivity. Local acral vasodysregulation is considered. Receptor and nerve endings dysfunction presented with predominance of {alpha}2-receptor function in the digital arteries and neuronal loss in those digital cutaneous perivascular nerves containing calcitonin gene-related peptide result in deficiency of endogenous release of this powerful vasodilator. Endothelial damage and dysregulation induced by vibration and increased shear stresses are demonstrated by the elevated plasma level of thrombomodulin and of von Willebrand factor and reduced endothelium-dependent vasodilator responses. The concentrations of endothelin-1 are high, the highest being in most advanced stages. Decreased plasma thiol level, indicating increased production and activity of free radicals, contribute to vasospastic paroxysms in vibration white finger patients. Dysbalance of local vasoactive factors with opposing effects on vascular smooth muscle like endothelin and nitric oxide, endothelin and calcitonin gene-related peptide, nitric oxide and superoxide anion are discussed. Disturbed smooth muscle response is supposed. Changes in hemostasis, fibrinolysis and hemorrheology, activation of blood cells with erythrocyte hyperaggregation and red cell hypodeformability, platelet aggregation with increased release of vasoconstricting thromboxane A2 and serotonin as well as leukocyte activation, entrapment within capillaries and post-capillary venules and increased reactive oxygen species and lysosomal lytic enzymes release might also contribute to digital vasospasms and tissue damage. Elevated soluble intercellular adhesion molecule-1 levels involved in the adherence of leukocytes to endothelium and to other leukocytes have been found in patients with hand–arm vibration syndrome.

KEYWORDS Autonomic nervous system; Endothelial function; Endothelins; Vasoconstriction/dilation

Raynaud's phenomenon (RP) is characterized by digital ischemic attacks, followed by cyanosis and erythema, as first described by Maurice Raynaud in 1862. It is usually bilateral, symmetric, mostly seen in young women and is considered as a primary (classic, idiopathic) form and a benign clinical problem. RP could be a manifestation of a connective tissue disease, vasculitis, cryoglobulinemia, drug induced, etc. (considered as secondary).

Vibration-induced Raynaud's phenomenon (VRP), associated with long-term exposure to hand-transmitted vibration at work, is a secondary form of RP. It is the main clinical manifestation of the hand–arm vibration syndrome (HAVS), characterized also by an evolution of early sensory neural disorders with gradually becoming persistent paresthesiae and pain, and increasing motor neural and musculoskeletal symptoms in hands and arms, which together with the occupational history for vibration exposure differentiate VRP from the idiopathic one.

VRP occasionally progresses towards scleroderma [1–4].

Loriga [5] and Hamilton [6] first described VRP at the beginning of the 20th century. Since then contradictory attitudes about the mechanisms of the vasospastic digital paroxysms have been dominating—from hyperactivity of the sympathetic nervous system and ‘local defect’ to statements of primary central nervous mechanisms.

This review attempts to summarize and discuss contemporary pathophysiological views on VRP assuming its multifactorial etiology.

An overview of the main pathophysiological mechanisms of VRP and their interactions is presented in Fig. 1.


Figure 1
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  		Fig. 1 The pathophysiological mechanisms of VRP and their interactions. ACTH, adrenocorticotropic hormone; cAMP, cyclic-adenosine monophosphate; cGMP, cyclic-guanine monophosphate; CGRP, calcitonin gene-related peptide; EDRF, endothelial-derived relaxing factors; EDCF, endothelial-derived constricting factors; EDHR, endothelium-derived hyperpolarizing factor; ET1, endothelin-1; 5HT2, 5-hydroxytryptamine, serotonin; IL-8, interleukin-8; NO, nitric oxide; PDGF, platelet-derived growth factor; PGl2, prostacyclin; Pts, plateletes; RBCs, red blood cells; T3, triiodthyronine; T4, thyroxine; TxA2, thromboxane A2; TxB2, thromboxane B2; sICAM-1, soluble intercellular adhesion molecule-1; WBCs, white blood cells.

 

   1. Neural dysfunction
Top
 Abstract
 1. Neural dysfunction
2. Local acral vasodysregulation
 3. Shear stresses
 4. Blood viscosity and...
 5. Conclusions
 References
 
1.1 Autonomic dysbalance
Autonomic dysbalance has long been implicated in the pathogenesis of VRP with increase in sympathetic activity and/or parasympathetic depression, probably initiated by overstimulation of Pacinian corpuscles [7,8]. Table 1 shows different aspects of autonomic disorders, sites of neural dysfunction and data about participation of definite pathophysiological mechanisms. Increased vascular peripheral resistance and hypothermy, changed skin vasomotor and sudomotor reactivity prove this statement. Abnormalities of other physiological indicators of autonomic function as heart rate variability, systolic time intervals, level of catecholamines also approve sympathetic hyperactivity [8,15–18]. Long-lasting vibration exposure may elicit central sympathetic vasoconstrictor reflex mechanisms, which trigger primarily episodic arterial closure typical of VRP [62,63].


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  		Table 1 Neural dysfunction in VRP

 
1.2 Receptor and nerve ending dysfunction
Hand–arm vibration is largely absorbed by skin structures causing mechanical damage to blood vessels and vasoregulatory nerve elements [64]. An excessive affinity of the efferent receptors to vasoactive substances potentiated by local cooling was suggested for the increase of the peripheral resistance of finger circulation in HAVS [35,36]. Adrenoreceptor dysfunction comprises weakened {alpha}1-receptor-mediated responses and predominance of {alpha}2-receptor function in the digital arteries [37]. Receptors and/or pain-mediating nerve fibers and sympathetic vasoconstrictor nerves or receptors in fingers are affected by hand–arm vibration [38]. Diminished cold-induced vasoconstriction in VRP patients [40] and the effective treatment of VRP with calcium-entry blockers also approve {alpha}2-adrenoceptor implication [65–68]. Peripheral sensory, motor, pain-mediating nerve fibers, temperature nerve-endings, slowly adapting type I (SAI) and fast-adapting types I and II (FAI and FAII) receptors at the fingertips are disturbed due to vibration (see Table 1). Vibration damages local nerve endings leading to general neuronal loss, especially in those digital cutaneous perivascular nerves containing the neuropeptide with powerful vasodilator properties, i.e. calcitonin gene-related peptide (CGRP) [59–61,69]. The neural deficit in digital skin of patients with VRP has a functional counterpart with reduced ability to propagate an axon-reflex vasodilator response [70].


   2. Local acral vasodysregulation
Top
 Abstract
 1. Neural dysfunction
 2. Local acral vasodysregulation
3. Shear stresses
 4. Blood viscosity and...
 5. Conclusions
 References
 
Various degrees and forms of endothelial dysfunction may derive as a result of hand–arm vibration exposure: impairment of G{alpha}i proteins (mediating endothelial-derived relaxing factors release); less release or increased metabolism and degradation of nitric oxide (NO), prostacyclin and/or endothelium-derived hyperpolarizing factor; increased release of endoperoxides or production of reactive oxygen species; increased generation of endothelin-1; decreased sensitivity of the vascular smooth muscle to NO, prostacyclin and/or endothelium-derived hyperpolarizing factor; impairments in endothelial cell signal transduction; deficiencies in the substrate (arginine) for the enzyme NO synthase; alterations in NO synthase or in one of its co-factors. Many other endothelium-mediated factors influence vascular tone (see Fig. 2) [60,71].


Figure 2
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  		Fig. 2 Local pathophysiological mechnisms of VRP. ACh, acetylcholine; ATP, adenosine triphosphate; CGRP, calcitonin gene-related peptide; EDCF, endothelial-derived constricting factors; EDHR, endothelium-derived hyperpolarizing factor; EDRF, endothelial-derived relaxing factors; 5HT2, serotonin; Hb, hemoglobin; Ht, hematocrit; NO, nitric oxide; PDGF, platelet-derived growth factor; PMN, polymorphonuclear leukocyte; RBC, red blood cell; ROS, reactive oxygen species; sICAM-1, soluble intercellular adhesion molecule-1; SP, substance P.

 
Local acral vasodysregulation data in VRP are presented at Table 2.


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  		Table 2 Local acral vasodysregulation in VRP

 
2.1 Endothelial damage
Endothelial damage was supported by the elevated plasma level of thrombomodulin established in vibration-exposed workers [72] and in HAVS patients with and without VRP [73]; elevated plasma levels of fibronectin in HAVS patients [74]; increased plasma levels of von Willebrand factor in acute vibration exposure [75–77] but not confirmed in chain-saw operators [78]. Endothelial damage at arteriolar level in exposed workers was proved by reduced laser Doppler vascular responses to iontophoretically applied methacholine (endothelium-dependent vasodilator) [79].

2.2 Endothelial dysregulation
Significantly lower endothelin level was found in workers exposed to vibration possibly due to a local adaptive axon-reflex resulting in vasodilation [80,81]. Taccola et al. [82] revealed increasing of serum endothelin level in such workers after cold test. But in HAVS patients the concentrations of endothelin-1 is found to be high, the highest being in most advanced stages [72,83]. Increased production of endothelin inhibits the direct myorelaxing effects of NO on vascular smooth muscle. Furthermore the imbalance between endothelin-1 and CGRP also contributes to the vasospastic phenomenon [86]. The absence or dysfunction of endothelium in HAVS patients favors the occurrence of vasospasm [37,75].

Endothelin-1 may be further involved in sympathetic nervous system activation. It is synthesized and secreted by post-ganglionic sympathetic neurons and by cells adjacent to these neurons as a mediator and modulator of post-ganglionic sympathetic neuronal development. Endothelin-1 modulates the release of neurotransmitter from post-ganglionic sympathetic nerve terminals. It is shown to modulate adrenergic neurotransmission at the neuro-effector junction [90]. Therefore endothelin-1 has multiple influences directed towards increasing microvascular tone.

Decreased plasma thiol concentration [84] and increased plasma levels of malondialdehyde [85] in VRP patients indicate increased oxidative stress, capable of oxidative damage, production of potentially toxic substances, negation of NO effects, interference in NO production, alteration of vascular tone modulation [91]. Therefore existing oxidative stress in VRP also contributes to vasospastic paroxysms.

Reduced blood flow responses to sodium nitroprusside (endothelium-independent vasodilator) found in VRP patients probably reflects disturbed smooth muscle response to NO [89].

Further investigations are needed to elucidate the implication of the rest of endothelial-dependent microvascular control mechanisms in VRP and their interactions in between and with other vasoregulatory factors.


   3. Shear stresses
Top
 Abstract
 1. Neural dysfunction
 2. Local acral vasodysregulation
 3. Shear stresses
4. Blood viscosity and...
 5. Conclusions
 References
 
Patients with VRP have experienced both mechanical trauma and shear stress enough to induce endothelial damage, swelling, and even endothelial cell loss resulting in endothelial dysfunction [92]. At the sites of arterial stenosis leukocytes and platelets are exposed to transient but extremely high shear stresses, which cause activation of these cells in vitro [93].


   4. Blood viscosity and cell activation
Top
 Abstract
 1. Neural dysfunction
 2. Local acral vasodysregulation
 3. Shear stresses
 4. Blood viscosity and...
5. Conclusions
 References
 
Blood and blood vessel wall interactions are discussed possible causes of VRP [84].

Changes in hemostasis, fibrinolysis and hemorrheology in vibration exposed and in HAVS patients has been reported (see Table 3). Blood and plasma hyperviscosity is induced in exposed workers [94,95]. Together with local edema formation they could further reduce the diffusion of oxygen across the capillary bed and increase tissue ischemia [95]. Other investigators found decreased plasma viscosity among VRP patients raising a hypothesis that it could be a compensatory mechanism to increase tissue blood circulation, thereby counteracting the effects of vasospasm [97]. Elevation of plasma levels of vitronectin and thrombin–antithrombin III complex, and {alpha}2-plasmin inhibitor–plasmin complex in VRP patients was established [74]. It was supposed that augmentation of coagulation and fibrinolysis induced a state of compensated disseminated intravascular coagulation [98].


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  		Table 3 Blood viscosity and cell activation in VRP

 
Changes in blood viscosity are related to the activation of blood cells.

4.1 Erythrocyte activation
Erythrocyte (RBC) aggregation significantly influences microcirculatory blood flow rate [99]. An acute vibration exposure increases capillary permeability probably as a result of vibration-induced endothelial damage and causes hemoconcentration with increases in RBC count, hemoglobin concentration and plasma viscosity [100]. It is associated also with RBC hypodeformability [96] and higher number of degenerative and reversibly changed RBC (echinocytes and stomatocytes) [74] found in HAVS patients. Possible mechanism could be the low oxygen partial pressure in the hands of HAVS patients and the pH reduction in their hand venous blood [96].

4.2 Platelete activation
Intravascular platelet aggregation is described probably as a result of vibration-induced endothelial damage [101,102]. It may lead to release of mitogenic mediators as platelet-derived growth factor causing focal proliferation of smooth muscle cells found in VRP [29] and of vasoconstricting thromboxane A2 (TxA2) whose metabolite thromboxane B2 is a potent vasoconstrictor. Slight nonsignificant increase of thromboxane B2 level after cold test is found in vibration exposed workers [104] and increased thromboxane B2 level is described in VRP [105]. Platelets release serotonin when they aggregate and may further induce digital vasospasm. But other data show that vibration-induced vascular injury does not seem to provide a sure stimulus sufficient to induce persistent platelet activation [103,106].

4.3 Leukocyte activation
Leukocytes (WBCs), especially polymorphonuclear leukocytes (PMNs), pass with relative difficulty through small capillaries even under normal condition [108]. By forming rigid structures, activated or abnormal leukocytes can impair blood flow within the microcirculation [109,110] aggregating to each other and adhering to the vascular wall as found in VRP patients who already have a tendency for vasospasm and thereby enhance tissue ischemia [84,85]. A subpopulation of hard and poorly deformable PMNs was found in VRP patients. Because of the trapping of the less deformable PMN within the microcirculation, a significant fall in single PMN count in venous blood was revealed in VRP. But acute hand-transmitted vibration had no in vitro effect on leukocyte rheology [85,95,99,107]. Leukocytes become more adhesive after shear stress exposure. Leukotrienes, chemotactic factors and cytokines released from the damaged and ischemic endothelium can further activate the leukocytes against a background of reduced prostacyclin and NO production. These mediators also can upregulate the expression of adhesion molecules on endothelial surfaces and on PMN cells [100,111].

Patients with VRP are found to have significantly increased leukocyte production of proinflammatory product leukotriene B4 [112], a potent aggregating agent and chemoattractant, active on multiple leukocytes. The increased levels of leukotriene B4 and free radical production support the leukocyte activation in VRP, which may contribute to the microvascular damage [84,113]. In summary WBCs may play some role in the pathogenesis of microvascular disorders and tissue ischemia in VRP; however, it is not elucidated if this is a cause or effect of the disease.

Cytokines and cell adhesion molecules both play an important role in blood and blood vessel wall interaction and basal vascular tone. Circulating levels of cell adhesion molecules are thought to be predictive of the extent of the cell to cell interaction [114]. Patients with HAVS are found to have elevated soluble intercellular adhesion molecule-1 (sICAM-1) levels involved in the adherence of WBCs to endothelium and to other WBCs, and thus decreasing blood flow in microcirculation. Significantly lower cytokine interleukin-8 (IL-8) levels are also found in HAVS patients [89]. The impeded flow of blood cells through the microcirculation may result in these low levels of circulating inflammatory cytokine due to its binding to erythrocytes. The elevation of sICAM-1 levels may be related to the decreased activity of NO, which is supported by the significantly reduced vascular responses to the NO donor, sodium nitroprusside in these patients.

The complex interactions of local vascular, humoral and blood cell factors are presented in Fig. 2, adapted by Wigley [115].

Genetic factors may play a role in susceptibility to and expression of VRP, systemic sclerosis, as well as primary RP [116,117].

The treatment of VRP is nonspecific. The more or less beneficial effects of: calcium-channel blockers with peripheral vasodilating, membrane-protecting and antioxidant effects (nifedipine, felodipine, isradipine, diltiazem, nicardipin); postsynaptic blockers of {alpha}-adrenoceptors with vasodilatory and hemorrheological effects (prazosin), sympatholitic drugs with microcirculatory effect (buflomedil, thymoxamine, guanethidine), surgical cervical or digital sympathectomy; prostacyclin analogues with vasodilative and platelete-antiaggregation effects (iloprost, beraprost); CGRP; selective serotonin reuptake inhibitors and serotoninergic receptor antagonists (fluoxetine, ketanserine), simple vasodilators (pentoxifylline) including topical ones (hexyl nicotinate, glyceryl trinitrate, nitric-oxidegenerating gel); angiotensin-converting enzyme inhibitors with potent vasodilator effect (captopril); fibrinolytic drugs (stanazolol) affirm the involvement of multiple pathophysiological mechanisms in VRP [29,42,60,65–68,86,118].


   5. Conclusions
Top
 Abstract
 1. Neural dysfunction
 2. Local acral vasodysregulation
 3. Shear stresses
 4. Blood viscosity and...
 5. Conclusions
References
 
Presented data give enough evidence to accept neural damage as a result of vibration exposure. Predominance of local acral peripheral neural dysfunctions of sympathetic vasomotor structures, peripheral nerves, nerve endings, and receptors prove their implication in the pathophisiology of VRP. They are influenced by the action of central neural mechanisms of sympathetic vasoconstrictor reflexes. VRP is probably a result of simultaneous and unidirectional action towards vasospasm of both neural and local vascular pathogenetic mechanisms, which play inseparable role. Endothelial damage and dysfunction of acral blood vessels due to the causing mechanical trauma and shear stresses hand-arm vibration together with the increased oxidative stress in VRP comprise that local vascular dysregulation. The rheological changes may further upset interactions with the abnormal vessel wall. The alterations in the rheology could activate leukocytes as they flow past, enhancing oxidative stress with a subsequent increase in free radical activity and further tissue damage. Erythrocyte and leukocyte activation probably contributes further to vasospastic paroxysms.

The multiplicity of vascular dysregulatory factors all in complex interactions directed towards vasospastic activity participates in the complex multifactorial pathogenesis of VRP.

Time for primary review 23 days.


   References
Top
 Abstract
 1. Neural dysfunction
 2. Local acral vasodysregulation
 3. Shear stresses
 4. Blood viscosity and...
 5. Conclusions
 References
 

  1. Nietert P.J., Silver R.M. Systemic sclerosis: environmental and occupational risk factors. Curr Opin Rheumatol (2000) 12(6):520–526.[CrossRef][Web of Science][Medline]
  2. Nagata C., Yoshida H., Mirbod S.M., Komura Y., Fujita S., Inaba R., Iwata H., Maeda M., Shikano Y., Ichiki Y., et al. Cutaneous signs (Raynaud's phenomenon, sclerodactylia, and edema of the hands) and hand-arm vibration exposure. Int Arch Occup Environ Health (1993) 64(8):587–591.[CrossRef][Web of Science][Medline]
  3. Maeda M., Ichiki Y., Shikano Y., Mori S., Kitajima Y. Detection of scleroderma with capillaroscopic abnormalities of nailfolds. Int J Dermatol (1996) 35(12):857–861.[CrossRef][Web of Science][Medline]
  4. Pelmear P.L., Roos J.O., Maehle W.M. Occupationally-induced scleroderma. J Occup Med (1992) 34(1):20–25.[Web of Science][Medline]
  5. Loriga G. Il Labora Coi Martelli Pneumatici. Boll Ispett Lavoro (1911) 2:35.
  6. Hamilton A. A study of spastic anaemia in the hands of stone cutters. Bulletin 236; US Bureau of Labour Statistics (1918) 19:53–66.
  7. Bovenzi M. Some pathophysiological aspects of vibration induced white finger. Eur J Appl Physiol (1986) 55:381–389.[CrossRef][Web of Science]
  8. Heinonen E., Fakkila M., Forsstrom J., Antila K., Jalonen J., Korhonen O., Pyykko I. Autonomic neuropathy and vibration exposure in forestry workers. Br J Ind Med (1987) 44:412–416.[Web of Science][Medline]
  9. Ekenvall L., Lindblad L.E., Bevegard S., Etzell B.M. High vascular tone but no obliterative lesions in vibration white fingers. Am J Ind Med (1987) 12(1):47–54.[CrossRef][Web of Science][Medline]
  10. Sakakibara H. Sympathetic responses to hand-arm vibration and symptoms of the foot. Nagoya J Med Sci (1994) 57(Suppl.):99–111.[Medline]
  11. Sakakibara H., Yamada S. Vibration syndrome and autonomic nervous system. Cent Eur J Public Health (1995) 3(Suppl.):11–14.[Medline]
  12. Matoba T., Ishitake T. Cardiovascular reflexes during vibration stress. Kurume Med J (1990) 37(Suppl.):S61–71.[Medline]
  13. Sakakibara H., Kondo T., Koike Y., Miyao M., Furuta M., Yamada S., Sakurai N., Ono Y. Combined effects of vibration and noise on palmar sweating in healthy subjects. Eur J Appl Physiol Occup Physiol (1989) 59(3):195–198.[CrossRef][Web of Science][Medline]
  14. Ando H., Ishitake T., Miyazaki Y., Kano M., Tsutsumi A., Matoba T. The mechanism of a human reaction to vibration stress by palmar sweating in relation to autonomic nerve tone. Int Arch Occup Environ Health (2000) 73(1):41–46.[CrossRef][Web of Science][Medline]
  15. Bovenzi M. Autonomic stimulation and cardiovascular reflex activity in the hand-arm vibration syndrome. Kurume Med J (1990) 37(Suppl.):S85–94.[Medline]
  16. Harada N. Autonomic nervous function of hand-arm vibration syndrome patients. Nagoya J Med Sci (1994) 57(Suppl.):77–85.[Medline]
  17. Laskar M.S., Iwamoto M., Toibana N., Morie T., Wakui T., Harada N. Heart rate variability in response to psychological test in hand-arm vibration syndrome patients assessed by frequency domain analysis. Ind Health (1999) 37(4):382–389.[Web of Science][Medline]
  18. Une H., Esaki H. Urinary excretion adrenaline and noradrenaline in lumberjacks with vibration syndrome. Br J Ind Med (1988) 45:570–571.[Web of Science][Medline]
  19. Mirbod S.M., Yoshida H., Jamali M., Miyashita K., Takada H., Inaba R., Iwata H. Finger skin temperature and laser-Doppler finger blood flow in subjects exposed to hand-arm vibration. Ind Health (1998) 36(2):171–178.[Web of Science][Medline]
  20. Virokannas H., Rintamaki H. Finger blood pressure and rewarming rate for screening and diagnosis of Raynaud's phenomenon in workers exposed to vibration. Br J Ind Med (1991) 48(7):480–484.[Web of Science][Medline]
  21. Lindsell C.J., Griffin M.J. Thermal thresholds, vibrotactile thresholds and finger systolic blood pressures in dockyard workers exposed to hand-transmitted vibration. Int Arch Occup Environ Health (1999) 72(6):377–386.[CrossRef][Web of Science][Medline]
  22. Bovenzi M. Vibration-induced white finger and cold response of digital arterial vessels in occupational groups with various patterns of exposure to hand-transmitted vibration. Scand J Work Environ Health (1998) 24(2):138–144.[Web of Science][Medline]
  23. Coughlin P., Chetter I.C., Kent P.J., Kester R.C. Vascular surgical society of great britain and ireland: analysis of cold provocation thermography in the objective diagnosis of the hand-arm vibration syndrome. Br J Surg (1999) 86(5):694–695.[Medline]
  24. Coughlin P.A., Chetter I.C., Kent P.J., Kester R.C. The analysis of sensitivity, specificity, positive predictive value and negative predictive value of cold provocation thermography in the objective diagnosis of the hand-arm vibration syndrome. Occup Med (Lond) (2001) 51(2):75–80.[CrossRef][Medline]
  25. von Bierbrauer A., Schilk I., Lucke C., Schmidt J.A. Infrared thermography in the diagnosis of Raynaud's phenomenon in vibration-induced white finger. Vasa (1998) 27(2):94–99.[Web of Science][Medline]
  26. Harada N., Kondo H., Kimura K. Assessment of autonomic nervous function in patients with vibration syndrome using heart rate variation and plasma cyclic nucleotides. Br J Ind Med (1990) 47(4):263–268.[Web of Science][Medline]
  27. Harada N., Nakamoto M., Kohno H., Kondo H., Tanaka M. Hormonal responses to cold exposure in subjects with vibration syndrome. Kurume Med J (1990) 37(Suppl.):S45–52.[Medline]
  28. Fakkila M., Pyykko I., Heinonen E. Vibration stress and the autonomic nervous system. Kurume Med J (1990) 37(Suppl.):S53–60.[Medline]
  29. Palmer R.A., Collin J. Vibration white finger. Br J Surg (1993) 80:705–709.[CrossRef][Web of Science][Medline]
  30. Matoba T., Kusomoto H., Mizuki Y., Kuwahara H., Inanaga K. Clinical features and laboratory findings of vibration disease: a review of 300 cases. Tohoku J Exp Med (1977) 123(1):57–65.[Web of Science][Medline]
  31. Taylor W., Ogston S.A., Brammer A.J. A clinical assessment of seventy-eight cases of hand-arm vibration syndrome. Scand J Work Environ Health (1986) 12(4 Spec No):265–268.[Web of Science][Medline]
  32. Taylor W. Biological effects of the hand-arm vibration syndrome: historical perspective and current research. J Acoust Soc Am (1988) 83(2):415–422.[CrossRef][Web of Science][Medline]
  33. Matoba T., Chiba M., Sakurai T. Body reactions during chain saw work. Br J Ind Med (1985) 42(10):667–671.[Web of Science][Medline]
  34. Hirata M., Matsumoto T., Toibana N., Hashiguchi T., Harada N., Yamada S. Involvement of the central nervous system in vibration syndrome. Int Arch Occup Environ Health (1995) 67(3):173–178.[Web of Science][Medline]
  35. Pyykko I., Starck J. Pathophysiological and hygienic aspects of hand-arm vibration. Scand J Work Environ Health (1986) 12(4 Spec No):237–241.[Web of Science][Medline]
  36. Pyykko I., Gemne G. Pathophysiological aspects of peripheral circulatory disorders in the vibration syndrome. Scand J Work Environ Health (1987) 13(4):313–316.[Web of Science][Medline]
  37. Ekenvall L., Lindblad L.E. Is vibration white finger a primary sympathetic nerve injury? Br J Ind Med (1986) 43(10):702–706.[Web of Science][Medline]
  38. Gemne G. Pathophysiology of white fingers in workers using hand-held vibrating tools. Nagoya J Med Sci (1994) 57(Suppl.):87–97.[Medline]
  39. Issley D.W., Greenstein D., Chetter I.C., Kester R.C. {alpha}2-Adrenoreceptors in vibration white finger. Cardiovasc Surg (1995) 3(Suppl. 1):39.[Medline]
  40. Lindblad L.E., Ekenvall L. Alpha 2-adrenoceptor inhibition in patients with vibration white fingers. Kurume Med J (1990) 37(Suppl.):S95–99.[Medline]
  41. Ekenvall L., Lindblad L.E., Carlsson A., Etzell B.M. Afferent and efferent nerve injury in vibration white fingers. J Auton Nerv Syst (1988) 24(3):261–266.[CrossRef][Web of Science][Medline]
  42. Matoba T., Chiba M. Effects of diltiazem on occupational Raynaud's syndrome (vibration disease). Angiology (1985) 36(12):850–856.[Abstract/Free Full Text]
  43. Matoba T. Pathophysiology and clinical picture of hand-arm vibration syndrome in Japanese workers. Nagoya J Med Sci (1994) 57(Suppl.):19–26.[Medline]
  44. Lindblad L.E., Ekenvall L. {alpha}2-Adrenoceptor inhibition in patients with vibration white fingers. Kurume Med J (1990) 37(Suppl.):S95–99.[Medline]
  45. Pelmear P.L., Taylor W. Hand-arm vibration syndrome. J Fam Pract (1994) 38(2):180–185.[Web of Science][Medline]
  46. Coutu-Wakulczyk G., Brammer A.J., Piercy J.E. Association between a quantitative measure of tactile acuity and hand symptoms reported by operators of power tools. J Hand Surg (Am) (1997) 22(5):873–881.[CrossRef][Medline]
  47. Brammer A.J., Taylor W., Piercy J.E. Assessing the severity of the neurological component of the hand-arm vibration syndrome. Scand J Work Environ Health (1986) 12(4 Spec No):428–431.[Web of Science][Medline]
  48. Sakakibara H., Hirata M., Hashiguchi T., Toibana N., Koshiyama H., Zhu S.K., Kondo T., Miyao M., Yamada S. Digital sensory nerve conduction velocity and vibration perception threshold in peripheral neurological test for hand-arm vibration syndrome. Am J Ind Med (1996) 30(2):219–224.[CrossRef][Web of Science][Medline]
  49. Lindsell C.J., Griffin M.J. Thermal thresholds, vibrotactile thresholds and finger systolic blood pressures in dockyard workers exposed to hand-transmitted vibration. Int Arch Occup Environ Health (1999) 72(6):377–386.[CrossRef][Web of Science][Medline]
  50. Sakakibara H., Hirata M., Hashiguchi T., Toibana N., Koshiyama H., Zhu S.K., Kondo T., Miyao M., Yamada S. Digital sensory nerve conduction velocity and vibration perception threshold in peripheral neurological test for hand-arm vibration syndrome. Am J Ind Med (1996) 30(2):219–224.[CrossRef][Web of Science][Medline]
  51. Sakakibara H., Hirata M., Hashiguchi T., Toibana N., Koshiyama H. Affected segments of the median nerve detected by fractionated nerve conduction measurement in vibration-induced neuropathy. Ind Health (1998) 36(2):155–159.[Web of Science][Medline]
  52. Brismar T., Ekenvall L. Nerve conduction in the hands of vibration exposed workers. Electroencephalogr Clin Neurophysiol (1992) 85(3):173–176.[CrossRef][Web of Science][Medline]
  53. Koskimies K., Farkkila M., Pyykko I., Jantti V., Aatola S., Starck J., Inaba R. Carpal tunnel syndrome in vibration disease. Br J Ind Med (1990) 47(6):411–416.[Web of Science][Medline]
  54. Toibana N., Sakakibara H., Hirata M., Kondo T., Toyoshima H. Thermal perception threshold testing for the evaluation of small sensory nerve fiber injury in patients with hand-arm vibration syndrome. Ind Health (2000) 38(4):366–371.[Web of Science][Medline]
  55. Kurozawa Y., Nasu Y. Current perception thresholds in vibration-induced neuropathy. Arch Environ Health (2001) 56(3):254–256.[Web of Science][Medline]
  56. Cederlund R., Isacsson A., Lundborg G. Hand function in workers with hand-arm vibration syndrome. J Hand Ther (1999) 12(1):16–24.[Medline]
  57. Toibana N., Sakakibara H., Hirata M., Kondo T., Toyoshima H. Thermal perception threshold testing for the evaluation of small sensory nerve fiber injury in patients with hand-arm vibration syndrome. Ind Health (2000) 38(4):366–371.[Web of Science][Medline]
  58. Lindsell C.J., Griffin M.J. Thermal thresholds, vibrotactile thresholds and finger systolic blood pressures in dockyard workers exposed to hand-transmitted vibration. Int Arch Occup Environ Health (1999) 72(6):377–386.[CrossRef][Web of Science][Medline]
  59. Goldsmith P.C., Molina F.A., Bunker C.B., Terenghi G., Leslie T.A., Fowler C.J., Polak J.M., Dowd P.M. Cutaneous nerve fiber depletion in vibration white finger. J R Soc Med (1994) 87(7):377–381.[Abstract]
  60. Dowd P.M., Goldsmith P.C., Burnstock G., Marshall I., Bull H., Foreman J.C. Raynaud's phenomenon. Lancet (1995) 346:283–290.[CrossRef][Web of Science][Medline]
  61. Bunker C.B., Goldsmith P.C., Leslie T.A., Hayes N., Foreman J.C., Dowd P.M. Calcitonin gene-related peptide, endothelin-1, the cutaneous microvasculature and Raynaud's phenomenon. Br J Dermatol (1996) 134(3):399–406.[CrossRef][Web of Science][Medline]
  62. Olsen N., Petring O.U. Vibration elicited vasoconstrictor reflex in Raynaud's phenomena. Br J Ind Med (1988) 45(6):415.[Web of Science][Medline]
  63. Olsen N. Hyperreactivity of the central sympathetic nervous system in vibration-induced white finger. Kurume Med J (1990) 37(Suppl.):S109–116.[Medline]
  64. Gemne G. Pathophysiology and pathogenesis of disorders in workers using hand-held vibration tools. In: Pelmear PL, Taylor W, Wasserman DE, editors, Hand-arm vibration: a comprehensive guide for occupational health proffessionals, New York: Van Nostrand Reinhold, 1992, pp. 41–64.
  65. Matoba T., Chiba M. Effects of diltiazem on occupational Raynaud's syndrome (vibration disease). Angiology (1985) 36(12):850–856.[Abstract/Free Full Text]
  66. Matoba T. Pathophysiology and clinical picture of hand-arm vibration syndrome in Japanese workers. Nagoya J Med Sci (1994) 57(Suppl.):19–26.[Medline]
  67. Lindblad L.E., Ekenvall L. {alpha}2-Adrenoceptor inhibition in patients with vibration white fingers. Kurume Med J (1990) 37(Suppl.):S95–99.[Medline]
  68. Pelmear P.L., Taylor W. Hand-arm vibration syndrome. J Fam Pract (1994) 38(2):180–185.[Web of Science][Medline]
  69. Shawket S., Dickerson C., Hazleman B., Brown M.J. Selective suprasensitivity to calcitonin-gene-related peptide in the hands in Raynaud's phenomenon. Lancet (1989) 2(8676):1354–1357.[Web of Science][Medline]
  70. Dowd P.M., Goldsmith P.C., Chopra S., Bull H.A., Foreman J.C. Cutaneous responses to endothelin-1 and histamine in patients with vibration white finger. J Invest Dermatol (1998) 110(2):127–131.[CrossRef][Web of Science][Medline]
  71. Harrison D.G. Endothelial dysfunction in atherosclerosis. Basic Res Cardiol (1994) 89(Suppl. 1):87–102.[Web of Science][Medline]
  72. Toibana N., Kanazuka M., Shigekiyo T. High level of plasma thrombomodulin (TM) concentration and correlation with endothelin (ET)-1 in vibration-exposed patients. Cent Eur J Public Health (1995) 3(Suppl.):40–42.[Medline]
  73. Kanazuka M., Shigekiyo T., Toibana N., Saito S. Increase in plasma thrombomodulin level in patients with vibration syndrome. Thromb Res (1996) 82(1):51–56.[CrossRef][Web of Science][Medline]
  74. Liubchenko P.N., Alekseeva G.A., Plaksina G.V., Pogorelov V.M. [Blood viscosity, deformability and morphological types of erythrocytes in vibration disease] (in Russian). Med Tr Prom Ekol (1997) 1:11–14.[Medline]
  75. Blann A.D., Allen J., McKenna K., Wilder D., Pope M.H., Kaigle A.M., Weinstein L.N., Jayson M.I.V. Vibration and induction of endothelial injury. Lancet (1992) 340(Sept 5):616.[Web of Science][Medline]
  76. McKenna K.M., McGrann S., Blann A.D., Allen J.A. An investigation into the acute vascular effects of riveting. Br J Ind Med (1993) 50(2):160–166.[Web of Science][Medline]
  77. Pope M.H., Jayson M.I., Blann A.D., Kaigle A.M., Weinstein J.N., Wilder D.G. The effect of vibration on back discomfort and serum levels of von Willebrand factor antigen: a preliminary communication. Eur Spine J (1994) 3(3):143–145.[CrossRef][Medline]
  78. McKenna K.M., Blann A.D., Allen J.A. Vascular responses in chain saw operators. Occup Environ Med (1994) 51(6):366–370.[Abstract/Free Full Text]
  79. Taccola A., Miotti D., Zambelli M. Esposizione professionale alla vibrazione: Fenomeno di Raynaud e la risposta vascolare allo iontophoresis di methacholine. G Ital Med Lav Ergonom (1998) 20(4):243–248.
  80. Nakamura H., Ariizumi M., Okazawa T., Nagase H., Yoshida M., Okada A. Involvement of endothelin in peripheral circulatory change induced by hand-arm vibration. Cent Eur J Public Health (1995) 3(Suppl.):27–30.[Medline]
  81. Palmer K.T., Mason H. Serum endothelin concentrations in workers exposed to vibration. Occup Environ Med (1996) 53(2):118–124.[Abstract/Free Full Text]
  82. Taccola A., Aprile C., Bacchella L. Sindromi professionali delle estremità. Il ruolo del endothelin nel vasospasm della freddo-prova: pathogenetic un’ ipotesi. G Ital Med Lav (1991) 13(1-6):71–75.[Medline]
  83. Kohout J., Topolcan O., Bejckova H. The serum level of endothelin in patients with hand-arm vibration syndrome. Cent Eur J Public Health (1995) 3(Suppl.):43–44.[Medline]
  84. Lau C.S., O'Dowd A., Belch J.J. White blood cell activation in Raynaud's phenomenon of systemic sclerosis and vibration induced white finger syndrome. Ann Rheum Dis. (1992) 51(2):249–252.[Abstract/Free Full Text]
  85. Lau C.S., Bridges A.B., Muir A., Scott N., Bancroft A., Belch J.J. Further evidence of increased polymorphonuclear cell activity in patients with Raynaud's phenomenon. Br J Rheumatol (1992) 31(6):375–380.[Abstract/Free Full Text]
  86. Noel B. Pathophysiology and classification of the vibration white finger. Int Arch Occup Environ Health (2000) 73(3):150–155.[CrossRef][Web of Science][Medline]
  87. Greenstein D., Parkin A., Maughan J., Kester R.C. Perfusion defects in vibration white finger: a clinical assessment using isotope limb blood flow. Cardiovasc Surg (1994) 2(3):354–358.[Medline]
  88. Nerem R.M. Vibration-induced arterial stress. Arch Environ Health (1973) 26:105–110.[Web of Science][Medline]
  89. Kennedy G., Khan F., McLaren M., Belch J.J. Endothelial activation and response in patients with hand arm vibration syndrome. Eur J Clin Invest (1999) 29(7):577–581.[CrossRef][Web of Science][Medline]
  90. Damon D.H. Postganglionic sympathetic neurons express endothelin. Am J Physiol (1998) 274(3 Pt 2):R873–878.[Web of Science][Medline]
  91. Munzel T., Heitzer T., Harrison D.G. The physiology and pathophysiology of the nitric oxide/superoxide system. Herz (1997) 22(3):158–172.[Web of Science][Medline]
  92. Greenstein D., Parkin A., Maughan J., Kester R.C. Perfusion defects in vibration white finger: a clinical assessment using isotope limb blood flow. Cardiovasc Surg (1994) 2(3):354–358.[Medline]
  93. Jen C.J., McIntire L.V. Characteristics of shear-induced aggregation in whole blood. J Lab Clin Med (1984) 103:115–124.[Web of Science][Medline]
  94. Okada A., Inaba R., Furino T., et al. Usefulness of blood parameters, especially viscosity, for the diagnosis and elucidation of pathogenic mechanisms of the hand-arm vibration syndrome. Scand J Work Environ Health (1987) 13:358–362.[Web of Science][Medline]
  95. Okada A., Inaba R., Furuno T., Nohara S., Ariizumi M. Usefulness of blood parameters, especially viscosity, for the diagnosis and elucidation of pathogenic mechanisms of the hand-arm vibration syndrome. Scand J Work Environ Health (1987) 13(4):358–362.[Web of Science][Medline]
  96. Lacombe C., Mouthon J.M., Bucherer C., Lelievre J.C., Bletry O., Godeau P. Phenomene de Raynaud et viscosite de sang. J Mal Vasc (1992) 17(Suppl. B):132–135.[Web of Science][Medline]
  97. Toren K., Berg M., Gudmunndson M., Tarcowski A. Rheological and immunological findings in dockers with vibration-induced white fingers. Int Arch Occup Environ Health (1992) 64:71–73.[CrossRef][Web of Science][Medline]
  98. Shunto R., Shirakami A., Ohara A., Toibana N., Saito S. Activation of blood coagulation and fibrinolysis in vibration syndrome. Int Arch Occup Environ Health (1991) 63(4):293–296.[CrossRef][Web of Science][Medline]
  99. Durussel J.J., Berthault M.F., Guiffant G., Dufaux J. Effects of red blood cell hyperaggregation on the rat microcirculation blood flow. Acta Physiol Scand (1998) 163(1):25–32.[CrossRef][Web of Science][Medline]
  100. Greenstein D. An investigation into the pathogenesis of Raynaud's phenomenon. Doctor of Medicine Thesis. The University of Leeds, 1996.
  101. Bovenzi M., Fiorito A., Giansate C., Calabrese S., Negro C. Platelet function and clotting parameters of vibration-exposed foundry workers. Scand J Work Environ Health (1983) 9:347–352.[Web of Science][Medline]
  102. Kent P.J., Williams G.A., Kester R.C. Platelet activation during hand vibration. Br J Surg (1994) 81(6):815–818.[CrossRef][Web of Science][Medline]
  103. Bovenzi M., Giansante C., Fiorito A., Calabrese S. Relation of haemostatic function, neurovascular impairment, and vibration exposure in workers with different stages of vibration induced white finger. Br J Ind Med (1985) 42(4):253–259.[Web of Science][Medline]
  104. Taccola A., Pisati P., Zaliani A., Di Maio D., Pierro A. Angiopathy causato vibrando gli strumenti: equilibrio della prova a freddo e della prostaglandina. Med Lav (1990) 81(1):45–49.[Medline]
  105. Wilkinson D., Vowden P., Gilks L., Latif A.B., Rajah S.M., Kester R.C. Plasma eicosanoids, platelet function and cold sensitivity. Br J Surg (1989) 76(4):401–405.[CrossRef][Web of Science][Medline]
  106. Nowak J., Barregard L., Benthin G., Granung G., Wennmalm A. Thromboxane metabolite excretion in patients with hand-arm vibration syndrome. Clin Physiol (1996) 16(4):361–367.[Web of Science][Medline]
  107. Greenstein R., Kester C. The role of leucocytes in the pathogenesis of vibration-induced white finger. Angiology (1998) 49(11):915–922.[Web of Science][Medline]
  108. Belch J.J.F. Coronary risk factor revisited. Shepherd J., ed. (1989) Amsterdam: Elsevier. 51–55.
  109. Bagge U., Braanemark P.I., Slalak R. Clinical aspects of blood viscosity and cell deformability. Lowe G.D.O., Barbenel J.C., Forbes C.D., eds. (1981) Berlin: Springer. 27–36.
  110. Fisher T.C., Belch J.J., Barbenel J.C., Fisher A.C. Human whole-blood granulocyte aggregation in vitro. Clin Sci (Colch) (1989) 76(2):183–187.[Medline]
  111. Fisher T.C., Meiselman H.J. Polymorphonuclear leukocytes in ischemic vascular disease. Thromb Res (1994) 74(Suppl.1):S21–S34.[Web of Science][Medline]
  112. Smith M.J.H. Advanses in prostaglandin, thromboxane and leucotriene research. Sammuelsson B., Paoletti R., eds. (1982) New York: Raven Press. 283–292.
  113. Belch JF, McLaren M, Chopra M. Blood coagulation and rheology in patients with vibration white finger disease. Symposium on Vibration White Finger, Institute of Occupational Health, The University of Birmingham, Proceedings 1989;2:18–31.
  114. Gearing A.J.H., Newman W. Circulating adhesion molecules in disease. Immunol Today (1993) 14:506–512.[CrossRef][Web of Science][Medline]
  115. Wigley F.M. Raynaud's phenomenon. Curr Opin Rheumatol (1993) 5(6):773–784.[Medline]
  116. Sideltseva E.V., Kolesov V.G., Aleksev L.P., Sideltsev V.V. [Immunogenetic markers in the course of vibration disease] (in Russian). Med Tr Prom Ekol (1993) 1112:27–30.
  117. Tan F.K., Arnett F.C. Genetic factors in the etiology of systemic sclerosis and Raynaud phenomenon. Curr Opin Rheumatol (2000) 12(6):511–519.[CrossRef][Web of Science][Medline]
  118. Coffman J.D. Raynaud's phenomenon. Curr Treat Options Cardiovasc Med (2000) 2(3):219–226.[CrossRef][Medline]

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