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A review of surgical treatment for obstructive sleep apnoea/ hypopnoea syndrome
J.P. McDonald
Bute Medical School, University of St
Andrews, Fife, U.K.
Correspondence to: J.P. McDonald,
Orthodontic Department, Victoria Hospital,
Hayfield Road, Kirkcaldy, Fife, U.K.
Email: jimbomcd@btinternet.com
Keywords: Obstructive sleep apnoea/hypopnoea syndrome, uvulopalatopharyngoplasty
Surg J R Coll Surg Edinb Irel., 1 October 2003, 259-264
Surgical intervention and treatment of OSAHS and snoring has a considerable history, encompassing a number of operations all of which have the intention of reducing or by-passing the pharyngeal resistance that occurs during sleep. Review of the published literature presents some problems, however, due to the ethical difficulties of undertaking randomised controlled trials in surgery. Uncontrolled trials are less satisfactory due to the large ‘regression to the mean’ and placebo effects. However, there is a considerable body of literature available relating to surgical intervention
INTRODUCTION
Obstructive Sleep Apnoea/Hypopnoea
Syndrome (OSAHS) is a clinical condition
that occurs as a result of the repeated,
intermittent collapse of the upper airway
during sleep. This collapse can be complete
(apnoea) or partial (hypopnoea), with
apnoea being defined as a minimum of a 10
seconds pause in respiration, hypopnoea as
a minimum 10 second interval where there
is reduction of at least 50% in the baseline
ventilation, even though breathing continues.
During sleep, the muscle tone in the upper
pharyngeal airway decreases leading in turn
to some narrowing of the airway lumen.
There is a need to increase respiratory effort
in an attempt to overcome this narrowing,
which in turn leads to a transient arousal
from deep sleep to a lighter sleep phase,
allowing the normal airway muscular tone
to be re-established. This cycle can repeat
many times over the hours of sleep and leads
to a reduction in sleep quality, hence, the
symptoms of excessive daytime sleepiness
and poor concentration. The prevalence of
OSAHS in middle aged men (30-65 years) is
in the region of 1-2% and with middle aged
women it is about half that prevalence.1,2
| TABLE 1. FEATURES OF OBSTRUCTIVE SLEEP APNOEA/HYPOPNOEA SYNDROME |
| Snoring |
| Excessive daytime sleepiness (p.m.) |
| Impaired concentration |
| Restless, unrefreshing sleep |
| Witnessed apnoea |
| Personality change - irritability |
| Nocturia |
| Decreased libido |
Tracheostomy
Once it was realised that obstruction,
predominately pharyngeal, was the main
problem, the concept of bypassing the
obstruction site by performing a tracheostomy
was attractive. This was the first successful procedure for OSAHS and was reported
by Gastaut et al.(1966), and by Kuhlo et
al. in 1969.3,4 Kim et al. (1998) undertook
a retrospective study of all patients who
had received a tracheostomy and who
had been subjected to polysomnography
since 1981 at the Johns Hopkins Sleep
Disorder Centre.5 They concluded
that tracheostomy effectively treated
patients with ‘uncomplicated’ OSAHS,
but was considerably less effective in
the treatment of patients with overlying
cardiopulmonary decompensation.
Conway et al. (1981), published
an article on the adverse effects of
tracheostomy in which they highlighted
the fact that a number of patients
who had undergone tracheostomy
experienced tracheal granular
malformation or stomal stenosis,
necessitating revision procedures.6
This, coupled with the considerable social disadvantage of the operation, means that tracheostomy for OSAHS is generally only used as a last resort, never as a treatment of first choice.7
INTRANASAL PROCEDURES
Any increase in nasal airway resistance
may lead to the collapse of the pharynx
on inspiration, as the chest muscles
attempt to draw air into the lungs. This
increase in nasal airway resistance
may be as a result of septal deviation,
turbinate hypertrophy, polyps or
chronic nasal congestion. There is a
considerable variety of opinion in the
literature as to the efficacy of relieving
nasal obstruction in OSAHS, with
Olsen and Kern (1990) concluding
that relief of nasal obstruction does
not resolve OSAHS whilst El Sherif
and Hussein (1998) reported that 50%
of 96 patients in their study obtained
total relief, with a further 40% gaining
some improvement.8,9
Kuma and Sant’
Ambragio (1991) recommended that
intranasal procedures were useful in
facilitating other non-surgical treatment
regimens like nasal-continuous positive
airway pressure (nCPAP).10
This view
is supported by Freidmann et al. (2000)
who, in a study of 50 consecutive
patients with nasal airway obstruction and OSAHS, reported that although
there was some improvement in nasal
airway resistance, nasal surgery did
not consistently improve the situation
but may have contributed to a decrease
in the required nCPAP pressure level
and hence an improvement in oxygen
saturation.11
It would appear, therefore, from a review of the literature that intranasal surgical intervention is unpredictable in its effect on OSAHS.
MAXILLARY/MANDIBULAR
ADVANCEMENT SURGERY
In those cases with a cephalometrically
measured retrognathic mandible
it is possible to use a mandibular
repositioning appliance as a diagnostic
aid, in order to establish the efficacy of
moving the mandible forward before
undertaking actual surgery. Riley
and Powell (1990) found that 65%
of patients under their care improved
with mandibular forward osteostomy
surgery.12 Lowe (1993) agreed that
the procedure was beneficial but
only where the obstruction was in the hypopharynx.13
Yu (1994), however,
found mandibular advancement to be
an unpredictable procedure.14
Waite
(1998) and Krekmanov et al. (1998)
suggested that maxillary/mandibular
advancement (MMA) using Le Fort
1 and surgical splint mandibular
osteotomies, permitted greater forward
movement of the mandible whilst
preserving the occlusion (Figure 1).15,16
Figure 1: Maxillo mandibular advancement
Genioplasty or geniotubercular advancement may augment the pharyngeal space further when combined with maxillary/mandibular advancement. Conradt et al. (1998) in a controlled trial, compared nCPAP with MMA and concluded that the latter was successful in reducing OSAHS severity in a high percentage of patients selected by cephalometric and polysomnographic investigation.17 The success was stable over a two-year period. In cases where unequal jaw surgery advancement is necessary, orthodontics is essential to prepare the occlusion prior to surgery, to ensure that profile changes are minimised and that the post surgical occlusion is acceptable.18
Disadvantages of the technique are significant, however, including both intra and post-operative risks. The intra-operative effects may be airway obstruction, haemorrhage and infection; the post-operative effects include temporomandibular joint dysfunction and temporary or permanent anaesthesia due to damage to the inferior alveolar or lingual nerves.
On the evidence available, therefore, MMA remains largely untested.
TONGUE REDUCTION
Djuperland et al. (1992) and Midjejeig
(1992) described an operation
termed uvulopalatopharyngoglossop
lasty (UPPGP) which incorporated a
modified uvulopalatopharyngoplasty
(UPPP) with limited resection of the
tongue base.19,20
Fugita et al. (1990,1991) and Woodson et al. (1992)
undertook midline glossectomy and
lingualplasty to create an enlarged
retrolingual airway.21-23
Chabolle et al. (1999) combined tongue base reduction with hyoepiglossoplasty in a small study of 10 patients and reported considerable improvement.24
The intra-operative complications, however, that may occur in such procedures are those of any surgical intervention in the oral and pharyngeal cavity, namely that of haemorrhage, airway obstruction and anaesthetic risk.
BARIATRIC SURGERY
Weight loss is an effective treatment
for OSAHS, so it would follow
that bariatric surgery would be
efficacious.25-27 Mayer et al. (1996)
noted the relationship between BMI,
age and upper airway measurements
in snorers and sleep apnoea patients.28
Charuzi et al. (1992) reported on a case series of 47 morbidly obese subjects followed-up after one year and again after seven years following surgery.29 They reported a significant decrease in the number of apnoeic episodes per hour of sleep, due primarily to the weight loss. It was noted that those individuals who subsequently gained weight began to increase the frequency of apnoeic episodes.
Sugarman et al. (1992) reported on 126 patients treated by bariatric surgery over a 10-year-period.30 Of the 40 patients with pre- and post-weight reduction sleep polysomnograms, the sleep apnoea index fell from 64+- 39 to 26 +-26 (P<0.0001), and was associated with significant improvements in other measurable sleep indices.
Dhabuwala et al. (2000) noted an improvement in co-morbidity factors following weight loss from gastric bypass surgery.31
There is, however, as yet no controlled trial available on the efficacy of bariatric surgery in inducing weight loss and improvement in clinical outcomes.
SUPRAHYOID TENSING
It has long been suggested that the
position of the hyoid bone vertically,
in relation to standardised points, has
a relationship with the severity of OSAHS.32-34
Certainly, in longitudinal
studies it has been shown that changes
in the hyoid position are co-ordinated
both with changes in the mandibular
position and in head and cervical
posture.35,36 Surgical intervention,
therefore, to tense the suprahyoid
muscles (hyoid suspension) using
fascia lata harvested from the thigh,
was suggested as an efficacious way
forward. A randomised study of
this procedure, however, was halted
for, despite apparent symptomatic
improvement, there was significant
worsening of sleep study indices.37
UVULOPALATO
PHARYNGOPLASTY
The most widely used surgical
treatment for OSAHS, and indeed
snoring, is uvulopalato-pharyngoplasty
(UPPP), originally undertaken by
surgical excision, more commonly
now utilising a laser (LAUP).38
The
original procedure was proposed by
Ikematsu (1964), who reported on 152
patients with 82% relief from snoring.39 The technique was then introduced
into the USA by Fujita et al. (1981)
as an alternative to tracheostomy.40 The uvula, tonsils and some of the
soft palate, is excised, reorientating
the tonsillar pillars so as to enlarge the
oropharyngeal space, hence, decreasing
the propensity of the pharynx to
collapse. (Figure 2)
Figure 2: Uvulopalatopharyngoplasty
Fijita et al. (1981) suggested that the anatomical indications for UPPP were a long uvula, redundant pharyngeal wall tissue and/or excess tonsillar tissue.
A review of the literature relating to UPPP reveals, perhaps not surprisingly given the surgical nature of the procedure, no randomly controlled trials. There have, however, been two systematic reviews, both of which concluded that there was, at best, an uncontrolled case series showing a 50% improvement in 50% of the patients, with the results being somewhat unpredictable.41,42 Other case series studies have shown that where indicated, tonsillectomy in its own right may improve OSAHS; however, again no randomised controlled data exists.43,44
Other studies have attempted to control the ‘regression to the mean’ or placebo effects. Lojander et al. (1996), compared patients randomly assigned to UPPP or to conservative management, in order to remove the regression to the mean effect.45 No significant difference was shown in the measures of OSAHS severity, only an improvement in symptomatic assessment. Wilhelmsson et al. (1999) undertook a prospective randomised trial whereby mandibular repositioning dental appliances were compared with UPPP in patients with symptomatic OSAHS.46 Overall, the dental appliances were more successful than the surgical measures. A recent meta-analysis review of LAUP suggested that the procedure should not be used for the treatment of patients with any significant OSAHS.47 Battagel (1996) supported minimalist LAUP for those patients who snore loudly with no symptoms of OSAHS.18
It is important to differentiate, when using UPPP or related surgical operations, between those patients who are ‘simple snorers’ and those who exhibit clinical OSAHS. The operation is widely used on the former group and it is suggested that a sleep study assessment to exclude OSAHS is undertaken, given that there is considerable evidence that UPPP has an adverse effect on the patient’s subsequent ability to use nCPAP, should they subsequently develop OSAHS.48,49
The side effects of UPPP, both immediate and in the long-term, are considerable and should be made clear to the patient prior to surgery. An estimation of morbidity and mortality has been undertaken by Haavisto et al. (1994), and Sajkov et al. (1998), amongst others.50,51 Immediately postoperatively, acute morbidity and even death has occurred due to iatrogenic worsening of the upper airway obstruction, together with ventilatory drive depression. There is a case for the provision of nCPAP immediately postoperatively to counter these effects, particularly in those patients exhibiting comorbidity factors.52
Longer-term side effects include changes in voice pattern, and a worsening of gastro-oesophageal reflex disease.53,54
It is suggested by Loadsman et al. (2001), that even mild to moderate OSAHS patients undergoing any surgical procedure involving anaesthesia should be monitored with oximetry post-operatively.55
| TABLE 2. KEY FEATURES IN THE TREATMENT OF OSAHS |
All patients with suspected sleep apnoea/hypopnea syndrome and their partners should complete an Epworth questionnaire to assess the degree of pre-treatment sleepiness.56 If OSAHS is suspected, then polysomnography should be undertaken to confirm the diagnosis |
|
Weight loss without resort to bariatric surgery should be encouraged where it is contributing to OSAHS |
| CPAP therapy is the first choice therapy for moderate to severe patients; intra-oral devices are an appropriate therapy for snorers and mild OSAHS sufferers |
|
Use of UPPP or LAUP for the treatment of OSAHS, as opposed to simple snoring, is not recommended |
| Palatal surgery can compromise later CPAP use if the patient later develops OSAHS |
CONCLUSION
Any review of surgical procedures,
including all of those undertaken for OSAHS, is handicapped by
the difficulty of exposing them to
randomised controlled trials, given
the ethical considerations that must
inevitably occur. It is suggested that
in an attempt to answer the relevant
questions on surgical efficacy that an
accurate pre-operative OSAHS severity
level be ascertained, using repeated
baseline sleep studies, in an attempt to
overcome some of the regression to the
mean effects. Further careful research
is necessary to establish the optimum
strategy for these patients.
REFERENCES
1. Stradling JR, Crosby JH Predictors and
prevalence of obstructive sleep apnoea and
snoring in 1001 middle aged men. Thorax
1991; 46:85-90.
2. Young T, Palta M, Dempsey J, Skatrud J, Weber S, Bahr S. The occurrence of sleep-disordered breathing among middle-aged
adults. N Eng J Med 1993; 328: 1230-5.
3. Gastaut H, Tassimari CA, Duran B. Polygraphic study of the episodic diurnal
and nocturnal (hypnic and respiratory)
manifestations of the Pickwick Syndrome. Brain Res 1966; 1:167-86.
4. Kuhlow, Doll E, Frank MD: Enfolgreiche
behandlung eines Pickwick - syndroms
durch eine
dauestracheal kanule, Dtsch. Med.
Wochenschr 1969; 94:1286-1290.
5. Kim SH, Eisele D, Smith PL, Schneider H, Schwartz A. An evaluation of patients
with sleep apnoea after tracheostomy. Arch
Otolaryngol Head Neck Surg. 1998; 124:
996-1000.
6. Conway WA, Victor LD, Magilligan DJ, Fujitas, Zorick FJ, Doth T.Adverse effects
of tracheostomy for sleep apnoea. AMA
1981; 246: 347-50.
7. Meyer JB, Knudson RC The sleep apnoea
syndrome Part II: Treatment 1990; The
Journal of Pros. Dent. 63: 320-324.
8. Olsen KD, Kern EB, Nasal influences on
snoring and obstructive sleep apnoea. Mayo
Clin Proc 1990; 65: 1095-1105.
9. El Sherif I, Hussein SN The effect of nasal
surgery on snoring. Amer J Rhinol 1998;
12: 77-79. 10.Kuma ST, Sant’Ambrogio
G.Pathophysiology of uppr airway closure
during sleep. Journal Amer. Med. Assoc.
1991; 266: 1384-89.
11. Freidmann M, Tanyeri H, Lim JW, Landsberg R, Vaidyanathan K, Caldarelli
D. Effect of improved nasal breathing on
obstructive sleep apnoea. Otolaryngol
Head and Neck Surg 2002; 122:71-4.
12. Riley R, Powell NB. Maxillofacial surgery
and Obstructive Sleep Apnoea Syndrome. Otolaryngol Clinics of N.America 1990;
23:809-826.
13. Lowe A.A. How does the airway lend itself
to therapy? Can we predict the success
of dental appliances for the treatment of
obstructive sleep apnoea based on anatomic
considerations? Sleep 1993; 16:93-95.
14. Yu LF. Pogrel MA, Ajayi M. Pharyngeal
airway changes associated with mandibular
advancement. Journal of Oral and
Maxillofacial Surgery 1994; 52:40-43.
15. Waite PD. Obstructive sleep apnoea: a
review of the pathophysiology and surgical
management. Journal of Oral Surgery
1998; 85:352-361.
16. Krekmanov L, Andersson L, Ringquist M, et al Anterior-interior mandibular
osteotomy in treatment of obstructive
sleep apnoea syndrome. Int J Adult Orthod
Orthognathic Surg. 1998; 13:289-298.
17. Conradt R, Hochban W, Brandenburg V, Heitmann J, Peter
JH. Sleep fragmentation
and daytime vigilance in patients with OSA
treated by surgical maxillomandibular
advancement compared to CPAP therapy. J Sleep Res 1998; 7:217-223.
18. Battagel JM Obstructive Sleep Apnoea: Facts not Fiction.
BJO 1996; 23: 324-345.
19. Djuperland G. Schrader H. Lybery T. Refsurn H. Lileås F. Godtliksen OB. Pala
topharyngoglossoplasty in the treatment of
patients with obstructive sleep apnoea. Acta
Otolarygol 1992; 492:50-54.
20. Miljeteig H. Trinnereim M. Uvulopalato
pharyngoglossoplasty in the treatment of
obstructive sleep apnoea syndrome. Acta
Otolarygol 1992; 492:86-89.
21. Fujita S. Surgical Treatment of Obstructive Sleep
Apnoea: UPPP and lingoplasty (lasal
midline glossectomy). In obstructive Sleep
Apnoea Syndrome: clinical research and
treatment (Guilleminault and Pentinez)
1990; 129-151: Raven Press, New York.
22. Fujita S. Midline laser glossectomy with linguoplasty: a treatment of Sleep Apnoea
Syndrome. Op Otolarygol 1991; 2:127-131.
23. Woodson BT, Fujita S: Clinical experience
with linguoplasty as part of the treatment
of severe sleep apnoea. Otolarygol Head
/Neck Surgery 1992; 107:40-48.
24. Chabolle F, Wagner I, Blumen M, Sequert C, Fleury B, De Dieuleveult T. Tongue
base reduction with hyoepiglossoplasty.
A treatment for severe obstructive sleep apnoea. The Laryngoscope 1999; 109:
1273-1280.
25. Harman EF, Wynne JW, Block AJ. The
effect of weight loss on sleep disordered
breathing and oxygen desaturation in
morbidly obese men: Chest 1982; 82: 291-294.
26. Smith PL, Gold AR, Meyers DA, Haponik EF, B Bleeker ER. Weight loss in mildly
to moderate obese patients with obstructive
sleep apnoea. Ann Intern Med 1985; 103:
850-855.
27. Suratt PM, Turner BL, Wilhoit SC Effect
of intranasal breathing during sleep. Chest
1986; 90: 324-329.
28. Mayer P, Pepin JL, Bettaga G. Relationship
between B.M.I., age and upper airway
measurements in snorers and sleep apnoea
patients. Eur Respir J 1996; 9: 180-189.
29. Charuzi I, Lavie P, Peiser J, Peled R. Bariatric surgery in morbidly obese sleep
apnoea patients: short and long term follow-up. Am J Clin Nutr 1992; 55:594-596.
30. Sugerman HJ, Fairman RP, Baron PL, Kiventus JA. Long term effects of gastric
surgery for treating respiratory insufficiency
of obesity. Am J Clin Nutr 1992; 55:597-601.
31. Dhabuwala A, Cannon RJ, Stubbs RS. Improvement in co-morbidities following
weight loss from gastric bypass surgery. Obes Surg 2000; 10:428-435.
32. De Berry - Borowiecki B, Kukwa AA, Blanks RHI. Indications for
palatopharyngoplasty. Arch Otolaryngol
1985; 111:659-663.
33. Djuperland G, Lyberg T, Krogstad O.Cephalometric analysis and surgical
treatment of patients with obstructive sleep apnoea. Acta Oto-Laryngologica 1987;
103:551-557.
34. Tsuchiya M, Lowe AA, Pae EK. Obstructive
sleep apnoea subtypes by cluster analysis. Am J Orthod, Dentofac Orthop 1992;
101:
533-542.
35. Tallgren A, Solow B. Long term changes
in hyoid bone position and craniofacial
posture in complete denture wearers. Journal of Restorative Dentistry 1981;
60:473.
36. Tallgren A, Solow B. Hyoid bone position,
facial morphology and head posture in
adults. Eur J. Orthodontics 1987; 9: 1-8.
37. Riley R, Powell N, Guilleminault C Maxillary, mandibular and hyoid
advancement for treatment of obstructive
sleep apnoea: A review of 40 patients. J.
Oral Maxillofacial Surg 1990; 48: 20-26.
38. Kamami YV. Outpatient treatment of
snoring with CO2 laser: Laser assisted UPPP. Otolaryngol 1994; 23: 391-394.
39. Ikematsut T. Study of snoring 4th report. Therapy: J Jpn Otol Rhinol Larygol 1964;
64: 434-435.
40. Fujita S, Conway W, Zorick F, Roth T. Surgical correction of anatomical
abnormalities in obstructive sleep apnoea
syndromes. UVPP: Otolaryngol Head and
Neck Surgery 1981; 89: 923-934.
41. Sher AE, Schechtman KB, Piccirillo JF.The
efficacy of surgical modifications of the
upper airway in adults with obstructive
sleep apnoea syndrome. Sleep 1996; 19:
156-157.
42. Bridgeman SA, Dunn KM. Surgery for
obstructive sleep apnoea (Cochrane
Review). In: The Cochrane Library, Issue
4, 2000 Oxford: Update Software
43. Verse T, Kroker BA, Pirsig W, Brosch S. Tonsillectomy as a treatment of obstructive
sleep apnoea in adults with tonsillar
hypertrophy. Laryngoscope 2000; 110:
1556-1559.
44. Boot H, van Wegen R, Poublon RM, Bogaard JM, Schmitz PL, van der
Meche FG. Long term results of
uvulopalatopharygoplasty for obstructive
sleep apnoea syndrome. Laryngoscope
2000; 110: 469-475.
45. Logander J, Maasilta P, Partinen M, Brander PE, Salmi T, Lehtonen H. Nasal
CPAP,
surgery and conservative management
for treatment of obstructive sleep apmoea
syndrome. A randomised study: Chest
1996; 110: 114-119.
46. Wilhelmsson B, Tegelberg A, Walker-Engstrom ML. A prospective randomised
study of a dental appliance compared
with uvulopalatopharyngoplasty in the
treatment of obstructive sleep apnoea. Acta
Otolarygol 1999; 119: 503-509.
47. Verse T, Pirsig W. Meta-analysis of laser assisted uvulopalalopharyngoplasty.
What is clinically relevant up to now? Laryngorhinootologie 2000; 79: 273-284.
48. Mortimer IL, Bradley PA, Murray JA, Douglas NJ. UPPP may compromise nasal
CPAP therapy in sleep apnoea syndrome. AM. J. Respir. Care Med. 1996; 154: 1759-1762.
49. Janson C, Noges E, Svedberg-Randts, Lindberg E. What characterises patients
who are unable to tolerate CPAP treatment? Resp. Med 2000; 94: 145-149
50. Haavisto L. Suonpaa J. Complications of uvulopalatopharygoplasty. Chin Otolatygol
1994; 19: 243-247.
51. Sajkov D, Marshall R, Walker P. Sleep
apnoea related hypoxia is associated with
cognitive disturbances in patients with tetaplegia. Spinal Cord 1998; 36: 231-239.
52. Ulnick KM, Debo RF. Postoperative
treatment of the patient with obstructive
sleep apnoea. Otolaryngol Head Neck
Surgery 2000; 122: 233-236.
53. Brosch S, Matthes C, Pirsig W, Verse T. Uvulopalatopharygoplasty changes
fundamental frequency of the voice - a
prospective study. J Laryngol Otol 2000; 114: 113-118.
54. Konerman et al Weiner Medizinische 2001; Vol 161 (5-6): 142-146
55. Loadsman JA, Hillman DR. Anaesthesia Sleep Apnoea. Br J Anaesth 2001;
86(2):254-266.
56. Johns MW. A new method for measuring sleepiness: the Epworth
daytime Sleepiness Scale. Sleep 1991; 14: 540-5.
Copyright: 9 September 2003
THE ROYAL COLLEGE OF SURGEONS OF EDINBURGH FACULTY OF DENTAL SURGERY: DENTAL COLLOQUIUM
"Research and treatment strategies to reduce the health-care burden of craniofacial anomalies"
will be held in the
SYMPOSIUM HALL OF THE COLLEGE, HILL SQUARE, EDINBURGH
Thursday 4 March 2004
P R O G R A M M E
18.15 SUPPER
Moderator: Professor Peter Mossey, Consultant in Orthodontics, Dundee Dental School
19.00 The quest for evidence-based surgical intervention in clefts and other craniofacial anomalies, Professor WC Shaw, Manchester
19.30 Does an electronic patient record for patients with cleft lip improve patient care? Mr JD Clark, Dundee
20.00 Genetic pathology of human orofacial clefts, Dr D Fitzpatrick, Edinburgh
20.30 Environmental factors in the aetiology of orofacial clefts, Professor J Little, Aberdeen
21.00 Discussion
21.30 Close
This activity is recognised for 2 CPE Points
Further information may be obtained from The Secretary, The Royal College of Surgeons of
Edinburgh, 10 Hill Square, Edinburgh EH8 9DW
(0131 527 1608) (Fax 0131 527 1669) E-mail: dental@rcsed.ac.uk