Therapeutic angiogenesis

McCarthy’s recent correspondence1 elegantlyarticulates a new direction for angiogenesisresearch in which more than one agent is adminis-tered and in which temporal considerations arefundamental. With an ever-increasing understand-ing of the biological properties of the multitude ofsubstances involved in new blood vessel formation,this attempt to mimic normal physiology moreclosely is a logical progression of the researchmilestones to which McCarthy refers.

Vascular endothelial growth factor (VEGF) andangiopoietin-1 have received specific reference inboth the aforementioned correspondence and inrecent published research.2–4 VEGF (A165) is themost studied and a particularly potent angiogen.Angiopoietin-1 is now recognised as an importantagent in stabilising newly formed blood vessels andpreventing leakage therefrom. To this list could beadded innumerable substances important in thehighly complex physiological process of angiogen-esis. The VEGF family for example, consists of atleast five members in the human (VEGF A, VEGF B,VEGF C, VEGF D, placental growth factor) each witha separate genetic locus. Splice isoforms of VEGF Aand VEGF B expand the family further. In almost allpublished work to date the term VEGF is used torefer to the specific isoform VEGF A165. It isbecoming important to use a more precise languageas the different isoforms are proving to have diversefunctions in the overlapping fields of angiogenesis,lymphangiogenesis and tumour growth. While VEGFA165 has been at the centre of most publishedresearch, the other splice isoforms of VEGF A, aswell as the VEGF B, VEGF C, VEGF D and placentalgrowth factor isoforms have been considered innoticeably fewer angiogenesis research studies todate. In the relative paucity of studies in whichthese proteins have been considered they havebeen shown to be of promise. There is justifiableoptimism that VEGF B and VEGF D may prove oftherapeutic value in the future.5,6 The potential ofthese angiogens in combination with VEGF A andangiopoietins should not be ignored. With theintention of determining the ideal cocktail ofrecombinant proteins to administer to ischaemictissue, each VEGF family member should beconsidered as a separate agent with a potentialapplication which differs from its siblings.

References

1. McCarthy MJ. Developing strategies for therapeutic angiogen-

esis: vascular endothelial growth factor alone may not be theanswer. Br J Plast Surg 2003;56:77.

2. Visconti RP, Richardson CD, Sato TN. Orchestration ofangiogenesis and arteriovenous contribution by angiopoietinsand vascular endothelial growth factor. Proc Natl Acad SciUSA 2002;99(12):8219—24. Epub 2002 June 04.

3. Thurston G. Complementary actions of VEGF and angiopoie-tin-1 on blood vessel growth and leakage. J Anat 2002;200(6):575—80.

4. Shyu KG, Chang H, Isner JM. Synergistic effect of angiopoietin-1 and vascular endothelial growth factor on neoangiogenesisin hypercholesterolemic rabbit model with acute hindlimbishaemia. Life Sci 2003;73(5):563—79.

5. Silvestre JS, Tamarat R, Ebrahimian TG, LeRoux A, Clergue M,Emmanuel F, Duriez M, Schwartz B, Branellec D, Levy BI.Vascular endothelial growth factor-B promotes in vivoangiogenesis. Circ Res 2003.

6. Rissanen TT, Markkanen JE, Gruchala M, Heikura T, PuranenA, Kettunen MI, Kholova I, Kauppinen RA, Achen MG, StackerSA, Alitalo K, Yla-Herttuala S. VEGF-D is the strongestangiogenic and lymphangiogenic effector among VEGFsdelivered into skeletal muscle via adenoviruses. Circ Res2003;92(10):1098—106.

Greg O’Toole, Duncan MacKenzie, Michael Poole18, Langland Court, The Avenue, Northwood,

Middlesex HA6 2NH, UK

doi:10.1016/j.bjps.2003.11.026

Post-operative splinting to maintain fullextension of the PIPJ after fasciectomy

In Dupuytren’s disease involving the proximalinterphalangeal joint (PIPJ), central slip attenu-ation can result in the finger immediately revertingto a flexed position despite achieving full extensionafter fasciectomy. Central slip attenuation usuallyoccurs in patients with a long-standing jointcontracture, where the flexion contracture exceeds608. It is important to recognize this intra-opera-tively with a passive Carducci test, performed bytesting central slip tenodesis with the wrist andmetacarpophalangeal joint of the involved finger ina fully flexed position.2 This situation can besuccessfully managed conservatively by post-oper-ative splinting of the PIPJ although in somecircumstances it may be appropriate to re-tensionthe extensor apparatus particularly if there is lossof flexion of the distal interphalangeal joint.1

Immediately following a fasciectomy, it is ourpractice to place the fingers in an intrinsic-plusposition with a dressing that includes a palmarplaster of Paris or equivalent splint. However,central slip attenuation can often result in thePIPJ reverting partially to a flexed position withinthe dressing overnight after surgery (Fig. 1). When

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