be made is that the long term survival of composite tissue grafts
will be dependant on the avoidance of chronic rejection.30
Only time and experience will tell us what is in store for us here.
Conclusion
There is much work still ongoing in the development of strategies
to counter transplant rejection in all areas of transplantation, and
possibly develop tolerance. There are still many areas in which
things can be improved. For example, the commonest cause for
loss of a renal transplant is death of the patient with a functioning
graft, at an age in advance of what would be predicted for a
healthy, age-matched individual32 Whilst part of this pathology
will reflect the impact of past renal disease and dialysis,
the adverse effects of immunosuppressive drugs will also have
played a role. Reducing this pathology is a major focus within
the transplant community today, and would greatly benefit
recipients of all types of transplant.
Conflicitng Interests - None declared
References
1. Irvine DJ, Purbhoo MA, Krogsgaard M, et al Direct observation of ligand
recognition by T cells. Nature. 2002; 419: 845-9.
2. Krensky AM. The HLA system, antigen processing and presentation. Kidney Int
Suppl. 1997; 58: S2-7.
3. Rocha PN, Plumb TJ, Crowley SD and Coffman TM. Effector mechanisms in
transplant rejection. Immunol Rev; 196: 51-64.
4. Djamali A, Premasathian N and Pirsch JD. Outcomes in kidney transplantation.
Semin Nephrol. 2003 ; 23: 306-16.
5. Warrens AN. On the horizon: tailor-made immun suppression in renal
transplantation. Nephron Clin Pract. 2003; 94: c5-10.
6. Brenner MJ, Tung TH, Jensen JN, et al. The spectrum of complications
of immunosuppression: is the time right for hand transplantation? J Bone Joint
Surg Am. 2002; 84-A: 1861-70.
7. The UNOS Scientific Renal Transplant Registry-ten years of kidney transplants.
Clin Transplants. 1997: 1-14.
8. Guttmann RD, Caudrelier P, Alberici G, et al. Pharmacokinetics, foreign protein
immune response, cytokine release, and lymphocyte subsets in patients receiving
thymoglobuline and mmunosuppression.Transplant Proc.1997; 29: 24S-26S.
9. Warrens AN. Pharmacological control of the immune response in renal
transplantation. BJU Int. 2002; 90: 784-91.
10. Aradhye S, Turka LA. Will tolerance become a clinical reality?. Am J Med Sci
1997; 313: 310-4
11. Miller JF. Transplantation. Immune self-tolerance mechanisms. 2001 27; S5-9.
12. Miller JF and Basten A. Curr Opin Immunol.Mechanisms of tolerance to self.
1996; 8: 815-21.
13. DeSilva DR, Urdahl KB and Jenkins MK. Clonal anergy is induced in vitro by
Tcell receptor occupancy in the absence of proliferation. J Immunol.
1991; 15; 147: 3261-7.
14. Li Y, Li XC, Zheng XX, Wells AD et al Blocking both signal 1 and signal 2 of
T-cell activation prevents apoptosis of alloreactive T cells and induction of
peripheral allograf tolerance. Nat Med. 1999; 5: 1298-302.
Progress Towards Randomised Controlled Trials in Facial Surgery
Iain Hutchison MB, FRCS, FRCS(Ed), FFDRCSI
Consultant Oral and Maxillofacial Surgeon, Bart’s and The London Hospitals Trust, London. United Kingdom.
Chief Executive of The Facial Surgery Research Foundation - Saving Faces
Correspondence to: Mr Iain Hutchison, Consultant Oral and Maxillofacial Surgeon, Bart’s and The London Hospitals Trust,
London. United Kingdom.
The mainstay of treatment for many diseases affecting the face and
mouth is still surgery. However, like so many medical problems,
there are different techniques and nuances for treating these
diseases and injuries. A lot of these subtleties of approach are
steeped in history and have stood the test of time. They are passed
from one generation of surgeons to the next with minor
modifications that naturally follow on from our method of
training, which is essentially an apprenticeship to surgical masters.
These methods do achieve success in most cases otherwise they
would have been discarded long ago, but comparisons between
different techniques for the same condition in prospective
randomised studies are sparse for many surgical groups.
The commonest form of evidence provided to support particular
treatment protocols is the case series (level III). It is still uncom-
mon to find level II (prospective randomised studies) or level I
(metanalyses). The consequence of this failure to compare
14
15. El-Azhary RA. Azathioprine: current status and future considerations. Int J
Dermatol. 2003; 42: 335-41.
16. Mathew TH. A blinded, long-term, randomised multicenter study of
mycophenolate mofetil in cadaveric renal transplantation: results at three years.
Tricontinental Mycophenolate Mofetil Renal Transplantation Study Group.
Transplantation. 1998; 15: 1450-4.
17. Opelz G. Critical evaluation of the association of acute with chronic graft rejection
in kidney and heart transplant recipients. The Collaborative Transplant Study.
Transplant Proc. 1997; 29: 73-6.
18. Warrens AN. The evolving role of mycophenolate mofetil in renal transplantation.
Q J Med 2000; 93: 15-20.
19. Saklatvala J. Glucocorticoids: do we know how they work? Arthritis Res.
2002; 4: 146-50.
20. De Bosscher K, Vanden Berghe W, Haegeman G. Mechanisms of anti-
inflammatory action and of immunosuppression by glucocorticoids:
negative interference of activated glucocorticoid receptor with transcription
factors. J Neuroimmunol 2000; 109: 16-22.
21. Mignen O, Thompson JL and Shuttleworth TJ. J Biol Chem. Calcineurin directs
the reciprocal regulation of calcium entry pathways in nonexcitable cells.
2003; 10; 278
22. Margreiter R. European Tacrolimus vs Ciclosporin Microemulsion Renal
Transplantation Study Group. Efficacy and safety of tacrolimus compared with|
ciclosporin microemulsion in renal Transplantation: a randomised
multicentre study. Lancet. 2002; 359: 741-6.
23. Trompeter R, Filler G, Webb NJ et al. Randomized trial of tacrolimus versus
cyclosporin microemulsion in renal transplantation. Pediatr Nephrol.
2002; 17: 141-9.
24. Cibrik DM, Kaplan B, Meier-Kriesche HU Role of anti-interleukin-2 receptor
antibodies in kidney transplantation. BioDrugs. 2001; 15: 655-66.
25. Kovarik JM, Burtin P. Immunosuppressants in advanced clinical development for
organ transplantation and selected autoimmune diseases. Expert Opin Emerg
Drugs. 2003; 8: 47-62.
26. Nashan B, Moore R, Amlot P, et al. Randomised trial of basiliximab versus
placebo for control of acute cellular rejection in renal allograft recipients.
CHIB 201 International Study Group. Lancet. 1997; 350: 1193-8. Erratum in:
Lancet 1997; 15: 1484.
27. Vincenti F, Kirkman R, Light S et al. Interleukin-2 receptor blockade with
daclizumab to prevent acute rejection in renal transplantation. Daclizumab Triple
Therapy Study Group. N Engl J Med. 1998; 338: 161-5.
28. MacDonald AS; RAPAMUNE Global Study Group. A worldwide, phase III, ra
domized, controlled, safety and efficacy study of a sirolimus/cyclosporine regimen
for prevention of acute rejection in recipients of primary mismatched renal
allografts. Transplantation. 2001; 71: 271-80.
29. Charpentier B, Groth CG, Backman L et al. Sirolimus European Renal Transplant
Study. Bicentre hospital experience with sirolimus-based therapy in human renal
transplantation: the Sirolimus European Renal Transplant Study. Transplant Proc.
2003; 35(3 Suppl): 58S-61S.
30. Hettiaratchy S, Butler PE, Lee WP. Lessons from hand transplantations. Lancet,
2001; 357: 494-5.
31. Francois CG, Breidenbach WC, Maldonado C, Kakoulidis TP, Hodges A,
Dubernard JM, Owen E, Pei G, Ren X, Barker JH. Hand transplantation:
comparisons and observations of the first four clinical cases. Microsurgery,
2000; 20: 360-71.
32. Hariharan S, Johnson CP, Bresnahan BA et al. Improved graft survival after renal
transplantation in the United States, 1988 to 1996. N Engl J Med.
2000; 342: 605-12.
33. Mijal J, Galkowska H, Olszewski WL.Formation of synapses between dendritic
cells and lymphocytes in skin lymph in an allogeneic reaction. Ann Transplant.
2002; 7: 36-41.
different techniques is difficulty in adducing evidence which
defines best treatment for these conditions, especially where it
relates to more subtle parameters such aspost-operative pain
experience, quality of life and complications.
The general public’s perception is that there are standard
operations for all conditions, particularly the common ones such
as hernia repair, varicose vein elimination or wisdom tooth
removal. They believe that all surgeons carry out these operations
in the same manner. They are shocked when they realise that
surgeons may perform these operations very differently.
There are several reasons why surgical techniques are not
compared in a prospective randomised fashion. Some of these
relate to practical problems whilst others are more philosophical.
Firstly, prospective randomised studies demand scrupulous data
The Journal of Surgery • Volume 2 • Issue 1 • 2004
Technology & Innovation
Handheld Computers for Surgical Logbooks
Mohammad Al-Ubaydli
Visiting Research Fellow at the National Center for Biotechnology Information
Correspondence to: Dr Mohammad Al-Ubaydli, Visiting Research Fellow, National Centre for Biotechnology Information,
5As47D-45, Building 45, National Institutes of Health, Bethesda, MD 20894, USA
Abstract
One of my favourite books is Michael Bliss’ biography of the great
Sir William Osler1. Osler is often described as the greatest of all
modern physicians, and it is a joy to read about his achievements.
One habit that he cultivated and encouraged his trainees to adopt
was taking their work with them wherever they went. He hated
wasting time, especially waiting in between his formal clinical
duties. For example on carriage rides in between appointments, he
would read scientific papers.
Had Osler been practicing today, my guess is that he would have
bought a handheld computer. On it he would store all the papers
that he wanted to study, all the textbooks that he needed to consult,
all the articles that he was writing, and a record of all the patients
that he had ever treated. For surgeons, that last application is
particularly important. Whether you are a trainee who wants to
document your experience or a consultant who wants to audit your
surgical outcomes, a surgical logbook is an important part of your
practice. Handheld computers simplify and advance the task of
keeping a logbook, and this article explains how you can go about
doing this yourself.
Background
A handheld computer is one that is small enough to hold in your
hand, or keep in your pocket. It helps you organise all the
information you need to keep track of as a doctor. Handhelds are
affordable, with prices starting at £100 for a good machine2. If you
want extras such as a colour screen, a camera, or even a car-navi-
gation system, you can pay more. Nevertheless, even the cheapest
model is powerful enough to handle most medical software. They
are also simple to use. Whereas your first brush with a desktop
computer was probably a painful learning experience, you will
find that a handheld is easy to pick up. You can write on one using
a pen (or even your finger) and the programs are clear and func-
tional. Nor do handheld computers crash frequently. Instead,
their reliability makes them attractive for the medical setting.
There are currently two types of handheld that you should choose
from: one has the “Palm Powered” logo, and the other the
Microsoft “Pocket PC” or “Windows Powered” logo. Palm
Powered machines are the cheapest and simplest to use, whereas
Pocket PCs are preferred by IT departments. Two things to be
aware of though are that most of your colleagues will have Palm
Powered machines, and sharing data is easier if you have the
same type of machine as your colleagues. All machines
work with Microsoft Office programs such as Word and Excel,
and ironically the Palm Powered machines do this job a little
better than the Microsoft Pocket PC machines3.
HanDBase Database Software
The reason that you must stick to Palm Powered or Pocket PC
machines is the software that the machines run. No matter how
advanced your phone is, there is little medical software available.
Palm Powered and Pocket PC machines, on the other hand, have
an impressive range.
One of the most important software packages that you should
invest in is called HanDBase4,5. This is database creation software.
In other words, it allows you to create electronic versions of any
of the paper forms that you fill out every day in the NHS. Because
The Journal of Surgery • Volume 2 • Issue 1 • 2004
the data is electronic you get the extra advantages such as fast
entry, efficient backups, and powerful searches.
For logbooks, these searches are important. If you have entered
the data correctly, you can search for all the patients that have had
DVTs as a post-operative complication; you can count all the
operations that you did without your consultant present; you can
tally how many operations you did in March; or you can print a
detailed report of every single operation that you took part in.
I have used HanDBase to create such a logbook. This is analogous
to using Microsoft Word to create a letter. When you buy the
software, you too can create your own logbook. By using my
logbook rather than designing your own version you will save
time and effort, and you can exchange data more easily with other
colleagues who are using the same logbook. I have based the
forms of my HanDBase logbook on the forms that you have to
complete for the Royal College of Surgeons paper logbook. I have
ensured that the translation into HanDBase format is faithful to the
spirit of the paper logbook, but takes advantage of the features of
handheld computers. For this I relied on my past experience in
converting the NHS Personal Development Plan paper forms into
HanDBase forms for GPs6. This logbook is freely available for
your use and distribution.
Because HanDBase runs on a handheld computer, it is easy for
you to enter the data correctly. First, handheld computers are easy
to take with you to theatre, so you can document every operation
straight after you do it. Second, I have designed the forms so that
they automatically fill out certain data, such as the date of the
operation. Third, the more you use the forms, the better HanDBase
gets at automatically filling in other data, such as the type of the
operation.
Surgical logbook HanDBase database
There are three steps to getting the surgical logbook onto your
handheld computer. The first is for you to buy HanDBase through
the web site7. The HanDBase Plus version costs $29.99 (about
£17) and will do the job perfectly well, but HanDBase Pro is worth
the $39.99 (about £22) price because of its advanced form
features. After buying the software, you need to download and
install it. www.PDAMD.com has an excellent guide that takes you
through downloading and installing software8.
The final step is to get the surgical logbook forms that I have
designed to work with HanDBase. You can get a free copy from
the The Journal of Surgery online (www.journal-surgery.com) or
from my own site9. The license for the logbook allows you to
make as many copies as you would like, and to share these with
your colleagues. Your colleagues will of course need to buy their
own copy of HanDBase to use the logbook. However if you make
improvements to the logbook, I would like you tell me about these
so that I can share them with other surgeons.
Filling out the forms
After you install HanDBase software and the surgical logbook, tap
the “HanDBase” icon on your handheld computer. Then tap the
”Surgical logbook” line, shown in figure 1.
The software asks you for the password (figure 2). Tap “OK”as the
default is for no password, but the next section will show you how
59
to change the password. The software then shows you a list of all
the operations (figure 3). Of course the list begins empty, and to
document your first operation, tap the “New” button. As figure 4
shows, the “Date” line has already been completed for you,
defaulting to the date on which you began completing the form.
You can change the date by tapping on it. The “Patient ID” line is
empty, waiting for you to add the identification number of your
patient. Tap on the dotted line and start writing.
The rest of the form is self-explanatory, and similar to the paper
forms from the surgical Royal Colleges (figures 5-6). However
the more effort you put into the logbook, the more effort it can
save you. For example, you can enter the operation name by
writing on the dotted line to the right of “Operation” (figure 4).
However if you tap on the triangle to the left of “Operation”, a list
pops up with “Edit Popup List” at the bottom. If you tap on “Edit
Popup List”, you have the opportunity to edit that list (figure 7).
Add the names of the operations that you do most commonly. For
example, if you are an ophthalmic surgeon, you could tap “New”,
write “Drainage of orbit” (figure 8), tap “OK” and then “OK”
again. From then on, if you tap on the triangle to the left of
“Operation” you will find “Drainage of orbit” is included in the
list (figure 9). If you tap on that, “Drainage of orbit” is automati-
cally filled in on the dotted line (figure 10). It is worth spending
a little time tailoring all the lists (including “Operation” and
“Complication”) to your speciality.
Security
The logbook does not allow you to enter a patient’s name. I did
this for security. First, cataloging identifiable data about your
patients makes you subject to the Data Protection Act. Although it
is reasonably straight-forward to comply10, in the case of a
logbook there is not much to gain. Furthermore the risks of data
falling into the wrong hands (if, for example, you lost your
machine) are too great.
As an additional security measure the logbook is encrypted and
password-protected. The encryption means that every time you
stop using the logbook HanDBase converts the data into a format
that can only be decoded if the right password is entered. It is
important that you choose a good password. At the beginning there
is no password so you must change this. Tap “DB Properties”
in the “Option” menu (figure 11) then tap “Security” and
60
“Set Access Password”. The software asks you to choose any
password, which can be as long as you want and contain any
combination of letters and numbers. For speed on the wards,
you should stick to numbers because HanDBase provides you with
a number pad. For security, you should choose a number at least
six digits in length, and avoid predictable sequences (like ‘111111’
or your date of birth).
Advanced features
The full advantages of using electronic logbooks become apparent
when you have to audit your surgical outcomes or summarise your
surgical experiences. HanDBase allows you to create reports,
search the data or highlight particular operations. The user
manual contains full documentation of these features and you
should read the sections about “Search Database”, “Filters” and
“Reports”. This software gives you more tools than Osler ever had
access to.
Conflicting Interests
I am the author of the book Handheld Computers for Doctors and
the accompanying website www.handheldsfordoctors.com which
sells handheld computers.
References
1. Bliss M. William Osler: A Life in Medicine. Oxford: Oxford University
Press 1999.
2. Al-Ubaydli M. Shop for Handhelds [online]. Available: http://www.handheldsfor
doctors.com/shop [accessed 1.1.2004]
3. Bush SG. Better than Pocket Office [online]? Available:
http://www.brighthand.com/article/Office_comparison [accessed 1.1.2004]
4. Hildebrandt SS. HanDBase from DDH Software [online]. Available:
http://www.pdacortex.com/HanDbase_Review.htm [accessed 1.1.2004]
5. Al-Ubaydli M. HanDBase 3.0 Review [online]. Available: http://www.handheld
fordoctors.com/learn/organisation/handbase3review.htm [accessed 1.1.2004]
6. Al-Ubaydli M. Handheld Computers for Doctors. London: John Wiley and Sons
2003. Chapter 13. Pages 75-84.
7. DDH Software Inc. HanDBase [online]. Available:
http://www.ddhsoftware.com/handbase.html [accessed 1.1.2004]
8. pdaMD.com. Installing Sofware [online].
Available: http://www.pdamd.com/vertical/tutorials/guides/installsoftware.xml
[accessed 1.1.2004]
9. Al-Ubaydli M. Surgical logbook [online]. Available:
http://www.handheldsfordoctors.com/learn/organisation/surgicallogbook.htm
[accessed 1.1.2004]
10. Information Commissioner. Welcome to the Information Commissioner’s Office
[online]. http://www.informationcommissioner.gov.uk/ [accessed 1.1.2004]
Figures 1-11
The Journal of Surgery • Volume 2 • Issue 1 • 2004
and anti-CD40L antibodies) have been investigated to prevent
‘signal two’ from being generated since, if signal one is delivered
in the absence of signal two then antigen specific tolerance is
induced.11, 12, 13 There is much ongoing interest in this area. A further
method of inducing tolerance is to encourage deletion of
graft-specific T-cells. Activated T-cells are susceptible to
activation-induced cell death (AICD). The final drug described
below, rapamycin, promotes the susceptibility of activated T-cells
to this apoptotic process, and this attractive method of inducing
tolerance is also under intense scrutiny.14
Immunosuppresive Drugs
Antimetabolites
Azathioprine inhibits purine metabolism, by competitively
antagonising an enzyme central to purine synthesis.15 More
recently, we have had access to the drug MMF, which is an ester
prodrug with higher bioavailability than its active agent,
mycophenolic acid (MPA).16 This drug acts in a far more targeted
way than azathioprine, acting on the enzyme inosine
monophosphate (IMP) dehydrogenase, which converts IMP to a
precursor of guanine. This pathway is important in nucleotide
synthesis in lymphocytes, but less so in other cells Furthermore
MPA is almost five times more potent in inhibiting the isotype of
IMP dehydrogenase present in activated compared to resting
lymphocytes. Studies have shown that MMF decreases the
frequency and severity of rejection compared to azathioprine.16
So far this difference has not been shown to improve graft
survival, though it is hard to perform a suitably powered study to
detect this difference.17 However MMF’s effects may in the long
term be shown to improve renal allograft survival.18
Corticosteroids
Prednisolone and methylprednisolone are both still used in
transplantation. They function by reducing gene activation,
which occurs if the signal induced by engagement of the T-cell
receptor is successfully transduced to the nucleus.3 Expression of
genes that lead to the production of pro-inflammatory cytokines
re among those inhibited by steroids, thus reducing T cell
activation. How exactly steroids do this is only now becoming
clearer and is thought to be based mainly on interference
with transcription factors, such as activator protein-1 (AP-1)
and nuclear factor kappa B (NF-kappa B).3
The reduction of lymphocyte proliferation seen with the use of
these drugs is likely to be due to the reduction of cytokine
production. Reduced expression of genes coding for adhesion
molecules leads to reduced leukocyte migration.19, 20 However,
their long term use has a well known plethora of adverse effects
(such as Cushing’s syndrome, osteoporosis, cataracts, peptic
ulcers, glucose intolerance, hypercholesterolemia, skin fragility,
and adrenal suppression) and many units thus aim relatively
rapidly to wean patients off corticosteroids.
Calcineurin Inhibitors.
Calcineurin is a phosphatase which is activated if an antigen
is recognised by a T-cell. It allows a promoter called “nuclear
factor of activated T cells” (NFAT) to enter the nucleus and
promote the transcription of several cytokine genes, including
IL-2. By inhibiting this enzyme, ciclosporin and, more recently,
tacrolimus prevent this from occurring.10, 21 Thus the message
that the T-cell receptor has recognised antigen does not
reach the nucleus.
Both drugs are in use, but evidence suggests that tacrolimus
is associated with a lower incidence of acute rejection.22, 23
They have differing adverse effects, but both require monitoring
of their blood levels, due to their narrow therapeutic windows23
The Journal of Surgery • Volume 2 • Issue 1 • 2004
Inteleukin-2 receptor blockade
The action of IL-2 can be blocked at its receptor (CD25),
which has lead to the development of two anti-CD25 antibodies,
basiliximab and daclizumab, produced by genetic engineering.
They were developed from mouse monoclonal antibodies specific
for the chain of the human interleukin-2 receptor, but importantly
only the variable domains of the light and heavy chains of
basiliximab, and the three complementarity-determining regions
of each variable domain in daclizumab are of mouse origin.24, 25
This means that both these antibodies are much less likely to
be seen as a foreign protein and thus be removed by the patient’s
immune system. Trials have shown that these drugs both reduce
acute rejection.26
mTOR Inhibitors
Successful interaction of IL-2 with its receptor leads to the
generation of a signal within the cell, starting the cell cycle and
leading to proliferation.27 Increasing evidence suggests that
mTOR, a regulatory kinase, acts as a central controller in this,
sensing cellular environment (mitogenic stimulation) and
regulating translation initiation through the eukaryotic initiation
factor 4E, and ribosomal p70 S6 kinase pathways, thus allowing
the cell to enter the cell cycle9, 27 Rapamycin (now called
sirolimus) inhibits this process. It is not yet clear how best to use
this agent. We do know that adding this drug to the regimen of
ciclosporin and prednisolone decreases acute rejection28, and it
can also be substituted for ciclosporin29, avoiding the
nephrotoxicity encountered with this drug.
Face, Hand and Other Composite
Tissue (CT) Transplantation
The arguments against performing a face transplant are similar to
those applied to hand transplantation. The performing of a hand
transplant was not uncontroversial6,30,31 many arguing that the risk
of long term adverse effects of immunosuppression did not
outweigh the benefits of gaining a hand. Indeed the first recipient
of such a transplant was unable to tolerate the side effects of his
drug regime and thus lost his transplant.31 However, as described
above, over 20 hand transplants have been performed to date,
and so far only two have been lost. The longest surviving hand
transplant has been in situ for more than five years, with reports in
the media of excellent function (CNN website, 28th February
2004). This has become possible because of the developments
both in understanding the rejection process and also the
continuing work in developing new drugs that target this process,
as well as improved microsurgical technique.30
The regime used for hand transplants (tacrolimus/MMF/
prednisolone) works by blocking the signals that generate an
immune response in three different areas as described above.
The fact that successful hand transplants have occurred
demonstrates well the power of modern immunosuppressive
drugs. The immunogenicity of composite tissues, particularly skin
should not be underestimated, due to the presence within it of a
large number of cells of the immune system, including high
numbers of dendritic cells, which easily trigger an immune
response.33 Furthermore it can be argued that there is a much more
limited functional reserve in composite tissues, so any rejection
episode may have more obvious effects than in solid organ
transplants30
High levels of immunosuppression are going to have long term
adverse effects, as described above, and thus the development of
mechanisms inducing tolerance would greatly benefit face
transplantation. Work in small animal models has shown that it is
possible to generate tolerance, though so far this has not been
reproduced in larger animal models. Obviously the ability
to induce tolerance to transplanted composite tissues would help
overcome the scepticism that many in the transplant community
have towards composite tissue transplantation. The final point to
13