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The Newsletter of the Australian and New Zealand Society of Paediatric Dentistry SSyynnooppsseess DECEMBER 2000, ISSUE 23 Approaching the Question of Microvascular Remodeling *Gue S, *Cameron A, +Zoellner H *Dept. of Paediatric Dentistry, Westmead Dental Clinical School, Westmead Hospital +Dept. of Oral Pathology, Faculty of Dentistry, The University of Sydney, Westmead Hospital Dental Clinical School Dr Sam Gue was the winner of the 2000 Colgate Oral Care Paediatric Dentistry Graduate Student Award. Address Correspondence to: Dr. Sam Gue, Paediatric Dentistry Registrar Paediatric Dental Department Westmead Hospital and New Children’s Hospital Darcy Road, Westmead 2145 University of Sydney, Sydney, New South Wales Microvascular Remodeling the change in color from granulation tissue This contrasts with necrosis, in which as a Model for Pattern Formation which is pink with new vessels to white homeostasis is lost due to toxic or other scar tissue containing very few blood noxious agents. In necrosis there is The microcirculation serves to supply vessels. This process is mediated by apoptosis disruption of membranous structures, nutrients to the tissues as well as to remove of the constituent endothelium while degeneration of mitochondria and waste products and this principal role endothelial cell apoptosis has also been ribosomal detachment from rough demands the formation of a complex shown to be responsible for microvascular endoplasmic reticulum. In addition to this, branching structure by the constituent remodeling during pressure induced atrophy DNA fragmentation in necrosis is random endothelial cells. Although numerous of the parotid and involution of the so DNA has a smeared appearance in gel signals have been identified as important mammary gland. In addition to this, electrophoresis. Further, since necrosis is for microvascular development including endothelial cell apoptosis has been found due to tissue damage it usually occurs in Fibroblast Growth Factor, Vascular to contribute to delayed wound healing in large groups of cells while apoptosis is Endothelial Growth Factor, Angiogenins diabetes, hypertensive vasculopathy and described as occurring in single cells. From and Ephrins, significant problems remain scleroderma. From this, it appears that this, apoptosis appears to be tightly to be solved in understanding microvascular endothelial cell apoptosis plays a central controlled at the level of individual cells morphogenesis. In particular, it is unclear role in both physiological and pathological rather than in a tissue wide manner. what mechanisms are responsible for microvascular remodeling and it is likely organization of individual endothelial cells that this is also important during orthodontic Continued on Page 3... into complex microvascular networks. The tooth movement and bone remodeling. difficulty of this problem becomes apparent when it is considered that microvascular Apoptosis: A Matter of Life and Death ttttthhhhhiiiiisssss iiiiissssssssssuuuuueeeee flow in each part of the microcirculation is functionally dependent upon flow in all of Apoptosis is currently accepted as the the remaining parts, while individual principal mechanism whereby excess cells endothelial cells are only in contact with are removed from the body. Morphologically 1. Approaching the Question of adjacent cells and so have no direct and ultrastructurally, apoptosis is Microvascular Remodelling. opportunity to communicate with their recognized by cellular fragmentation more distant but nonetheless functionally into apoptotic bodies often containing 2. President’s Report. dependent fellows. One approach to dealing fragments of condensed nuclear material with this problem is to study microvascular but with intact organellar structures. 4. Dental Project for Cambodia. networks undergoing remodeling. endothelial cell apoptosis appear to be ultrastructurally unique in that complex Endothelial Apoptosis in canalicular structures form in apoptotic 5. Oral Manifestations of Microvascular Remodeling particles. This has been proposed as a Oncology Treatmeant in Paediatric Patients. mechanism aiding the mechanical During wound healing, highly vascular fragmentation of apoptotic endothelial cells granulation tissue undergoes significant and thus minimizing the micro-embolic 10. Branch Reports. microvascular remodeling and maturation potential of these cellular fragments. to become mature scar tissue. The dramatic Internucleosomal cleavage of DNA into 12. Coming Events extent to which excess vessels are removed 180 base pair fragments is a widely during wound maturation is illustrated by accepted biochemical marker for apoptosis. PRESIDENT’S REPORT President’s Report PROFESSIONAL RESPONSIBILITY AND PATIENT WELFARE M y earliest recollections of children’s discovered alternatives to amalgam including therapy may be utilised for disease prevention, dentistry were occasional visits to composite resins, glass ionomer cements and subject to public acceptance. New techniques a mobile government dental clinic stainless steel crowns. Most importantly, for cavity debridement and restoration in a railway carriage at ten years of age. The there was a professional realisation that placement will evolve. Infants and pre- clinic visited country Queensland on a the age for a child’s first dental visit should schooler attendance will increase due to the regular annual run with the itinerant be much younger than five years. perceived importance of early identification dentist. To my best knowledge, I had After a few years in public hospital and intervention. The presence of child amalgam fillings done in my primary teeth practice and part time academics, it dawned friendly techniques will improve both and I can recall two distinct smells; one I on me that there must be a better approach compliance and behaviour management think was eugenol and the other may have to maintaining children’s oral heath than during the active treatment phase. been formocresol. I can vividly remember restoring decayed teeth. The surgical approach Paediatric dentistry is an exciting and being asked to mix the mercury with the to disease management has since been energetic field of dentistry but is not silver filings in a small bowl for the dentist, outdated by the medical model of disease without its share of controversy. However, following the struggle of slow speed cavity control and prevention. I am convinced that it is our professional responsibility to preparation without a local anaesthetic. dentists that treat children have a distinct embrace those concepts and techniques What was happening in the world of advantage over all other disciplines of that further our patient’s health and dentistry for children in the 1960’s? The dentistry. Only we can reduce the impact welfare. ANZSPD will continue to promote only available written documentation was of dental caries and it’s effect on oral and the practice and science of paediatric the Journal of Dentistry for Children. At somatic development through early dentistry through its organisational activities. the time, it was the only dedicated journal intervention and initiation of a comprehensive Even though the challenge to continue is to children’s dentistry and a quick scan of preventive program in high-risk children. great, the creativity, energy and intellect of the content of four issues suggests that Although dental decay in children will future members will allow the society to the problems in the 1960’s continue to be never be eradicated, the treatment options progress and develop. similar to those problems that children’s for disease management are extensive, Kerrod B Hallett dentists face today. For example, the including effective antimicrobial and fluoride journal issues included articles on general preparations. Most children in Australia anaesthesia, a technique on vital pulpotomy and New Zealand drink fluoridated water an invitation on young permanent teeth, dental and almost all paediatric toothpaste treatment for children with congenital contains fluoride. Fissure sealants reduce TO ALL ANZSPD MEMBERS heart disease, caries in hospitalised children, occlusal caries and there are hundreds of the Howe technique for pit and fissure toothbrush designs to effectively remove An invitation is extended to all members caries, concern over the availability of dental dental plaque. More importantly, increasing of the Australian and New Zealand Society of services for children and more interestingly, numbers of parents, doctors and dentists Paediatric Dentistry (ANZSPD), to participate dental care from birth to two years of age. recognise the importance of early in the development of “Oral Health Care Policies After reviewing the journal, I considered examination and guidance of the and Standards of Care Guidelines for Paediatric what had changed over the last 35 years. developing primary dentition and its Dentistry”, which is currently being produced When I entered dental school in 1972, importance for general growth and by the Australasian Academy of Paediatric I realised I was not the only student that development. In addition to the Journal of Dentistry (AAPD). had a lot of cavities as a youngster. In fact Dentistry for Children, there are a number A full day meeting will be held at Rydges some of those fillings still remain and are of journals that publish contemporary Southbank Hotel, Brisbane, Queensland (ADA working just a well, despite the concerted issues in paediatric dentistry. Congress Hotel) on Thursday 3 May 2000, just attempts from my dental student How about the next 35 years? prior to the 30th Australian Dental Congress. colleagues to replace them. Restoration in Discussion on pulp treatment in the Further details and copies of the proposed 1972 was limited to amalgam in the primary and permanent dentition will protocols may be obtained by contacting Ms posterior teeth and silicate cement in the continue, probably in the area of induced Sarah Raphael, Secretary, AAPD anterior teeth. Seldom were children osteogenic repair. With new medical younger than five years of age treated therapies to treat childhood diseases that Email: [email protected] (except for emergency extractions) and the were once fatal, I expect there will be more Address: 151 Woodland Street benefit of fluoride was only just beginning complex issues in managing children with Balgowlah NSW 2093 to emerge. When I finished my speciality special health care needs. The genes Telephone: (02) 9907 8123. training in 1991, dental decay in children responsible for tooth development will be was certainly on the wane. Systemic and mapped and a host of diagnostic tests will Peter J Gregory, President topical fluorides had decreased the be available to identify children at highest Australasian Academy of Paediatric Dentistry prevalence of smooth surface caries and I risk for dental disease. Gene replacement 2 SYNOPSES DECEMBER 2000 APPROACHING THE QUESTION OF MICROVASCULAR REMODELING ...Continued from Page 1 recently revisited the question of the quantitate the extent of endothelial possible effect of shear stress upon apoptosis by simply counting the number endothelial cell apoptosis. of cells surviving experiments. These were Co-ordination of Endothelial Apoptosis: are easy to separate from apoptotic cells A Significant Problem A Simple Rocking Platform Model because endothelial cells detach early to Stimulate Endothelium with Shear Stress during apoptosis and can be washed away, If, however, apoptosis is regulated at while surviving cells are all adherent to the the level of individual cells, additional Experiments stimulating cells with culture surface. problems become apparent in regulating shear stress are quite difficult, primarily apoptosis of endothelial cells during because highly specialized and complex Data Were the Opposite to What Was Expected vascular remodeling. It is clear that if apparatus is required. This makes endothelial cell apoptosis is not properly performing preliminary experiments Instead of finding that shear exposed coordinated, the microvascular network problematic, as significant expenditure on cells were protected from apoptosis, what will be disrupted resulting in either ischaemic new equipment can not always be justified we found was that fewer cells survived on necrosis or bleeding. Since this does not without any evidence that the new line of the rocking platform than in static culture. occur in-vivo, it is clear that there must be investigation might be fruitful. To get This was the absolute opposite of what was mechanisms to co-ordinate endothelial cell around this rather practical problem, we expected, as we had argued that functional apoptosis and maintain vascular perfusion established a very simple experimental signals should inhibit endothelial apoptosis during micro-vascular remodeling. system, in which endothelial cells grown and shear stress was clearly a functional Since the principal function of blood to confluence in tissue culture flasks were signal. Not only that, but while performing vessels is to carry blood, it is possible that these experiments, other workers had blood flow provides a mechanism linking published work with laminar flow microvascular function to regulation of “Instead of finding that shear chambers showing reduced endothelial endothelial cell apoptosis. Supporting this apoptosis in the presence of laminar shear exposed cells were protected from possibility is the observation that stress. At first, we rejected our data, apoptosis, what we found was microvessels carrying blood are maintained thinking that “something had gone during microvascular remodeling in-vivo, that fewer cells survived on the wrong”. However, the more experiments while those vessels which are poorly rocking platform than in static were repeated, the more clear it became that perfused or have oscillatory flow undergo culture. This was the absolute endothelial cells in our rocking platform degeneration. An important conclusion opposite of what was expected.” model die more quickly than parallel cells from this is that the default status of sitting on the incubator shelf. This endothelial cells appears to be apoptosis, difference was seen regardless of the culture with endothelial cells only surviving if medium used, although the gap between receiving survival signals from flowing simply rocked back and forth on a survival and death seemed most blood. This model is illustrated in Fig. 1, laboratory rocker. In this way, the culture pronounced when cells were cultured in where vessels having indifferent or medium overlying the cells was allowed to serum free conditions with albumin. conflicting flow in the “initial vasculature”, wash forwards and backwards over the It became important to check that cells are removed by endothelial apoptosis to cells, thus exposing the cells to shear stress. were actually apoptotic and not simply produce an optimized “final vasculature”. By aligning tissue culture plates in parallel necrotic. To look at this, we examined the with each other, as well as being careful to cells by transmission electron microscopy, Chemical Plasma Factors and Laminar Shear load equivalent amounts of culture DNA gel electrophoresis and FACS analysis Stress Inhibit Endothelial Apoptosis medium in each flask, it was possible to and have found that the cells are clearly stimulate sets of three or more flasks as apoptotic. The only conclusion left for us The two types of anti-apoptotic signal triplicates to facilitate statistical analysis. was that we were inducing endothelial which might act upon endothelial cells in Cells in these “rocking flasks” could then apoptosis by culture on the rocking platform. functional blood vessels are shear stress or be compared with parallel cultures treated chemical plasma factors. Laminar shear in the same way in the same incubator, Does Oscillating Shear Stress Affect stress has been shown to inhibit apoptosis but on a stable incubator shelf. We knew Endothelial Apoptosis Differently to Laminar in isolated cultured endothelial cells and it from earlier work that endothelial cells Shear Stress? is likely that this plays some role in-vivo. become more rapidly apoptotic in serum However, since isolated endothelial cells free conditions while albumin inhibits this As mentioned above, other workers had grow and survive in the absence of shear process. Also, we had shown that shown that laminar shear stress protects stress, it seems that although shear may endothelial cells do not proliferate in flasks endothelium from apoptosis so that our inhibit endothelial cell apoptosis, it is not a unless stimulated with specific growth task became one of trying to reconcile our critical anti-apoptotic factor for these cells. factors prepared from bovine observations with those of these other In contrast, serum deprivation causes rapid hypothalamus. Because of this, we workers. Comparing our work with that endothelial cell apoptosis in the absence of performed these experiments with both reported in the literature, the most obvious shear, suggesting that chemical plasma “rocking” and “static” cultures with three difference was that we had stimulated cells factors are critical anti-apoptotic signals for types of culture medium: i) medium in with oscillating shear stress while our endothelial cells. This laboratory has been which endothelium has very low levels of colleagues had stimulated their cells with investigating this possibility and we have apoptosis (M199 with 20% serum); ii) continuous laminar shear stress. Also, we found that serum contains potent anti- medium in which endothelum is slightly knew that increasing the rate of rocking in apoptotic factors for endothelium, with at more apoptotic (M199 with 4% serum our platform rocker model increased the least one of these factors being serum albumin); and iii) medium inducing high extent of apoptosis. From this, we concluded albumin. Although most effort has been levels of endothelial apoptosis (M199 that oscillating shear stress induces apoptosis directed towards understanding the way alone). Also, earlier work had shown that while laminar shear stress inhibits this. in which serum albumin may mediate this because endothelium does not proliferate anti-apoptotic activity, we have more in these conditions, it is possible to Continued on Page 4... SYNOPSES DECEMBER 2000 3 APPROACHING THE QUESTION OF MICROVASCULAR REMODELING ...Continued from Page 3 such excessively tortuous vessels might Dental Project for Cambodia help to optimize microvascular shape. 2001-2002 The Possible Biological Relevance If this is the case, it becomes interesting of Oscillating Shear Stress to speculate as to the possible ways in Since the 1980s, progress has been made in which this mechanism might be inhibited It is always difficult to meaningfully in conditions where vessels become re-establishing oral health services and training in extrapolate observations with isolated increasingly tortuous, such as chronic Cambodia following two decades of war, political cultured cells to the in-vivo situation. periodontitis. Perhaps inflammatory instability and hardship. The Faculty of Dentistry Cultured endothelial cells grown as a cytokines inhibit this process? Before in Phnom Penh has received some help in recent monolayer on a plastic plate are clearly a extending work to these sorts of questions, years from non-governmental organisations, and very poor model for endothelial cells in however, it is more important to properly a few Cambodian dentists have had the chance to actual micro-vessels. Nonetheless, it seems characterize the current observations with make short educational tours overseas to improve fair to assume that cells carry at least some oscillating shear. their knowledge. Unfortunately only 4 Cambodian of their in-vivo properties across into cell dentists have had the opportunity to study abroad. culture, and that the behavior of cultured The Need for an Improved Experimental Model Of these one has since retired and 2 have gone to endothelium usually reflects some aspect live in the US. In order for Cambodia to continue of the real biology we wish to study. Accepting As mentioned above, the rocking to improve oral health services for its people, the limitations of cell culture models, but platform model was used primarily as a upgrading the knowledge and skills of staff at the on the assumption that their behavior simple and inexpensive way of stimulating Faculty of Dentistry must be a priority. reflects some aspect of biology, it became endothelium with shear stress. Although The idea for this project came about during important to try and imagine some way in permitting experiments to be performed, it the Cambodian Dental Association Conference in which oscillating shear induced endothelial was not possible to directly compare the January 2000, when a group of foreign dentists apoptosis might be biologically important. response of these cells with others exposed who attended the meeting formed a group called In-vivo observations by other workers to true, uniform, unidirectional laminar have infact revealed that in remodeling shear stress. Also, because the flow varies “Friends of the Cambodian Dental Association”. apoptotic vessels, where flow is already in direction and velocity according to the Following discussion with the Cambodian dentists impaired, the blood often oscillates back and angle of the rocking platform, it was not the group proposed to help upgrade the forth. Further apoptosis in these vessels possible to properly quantitate the levels of knowledge and skills of the teachers at the Faculty eventually results in removal of these shear used. Worse still, turbulence generated of Dentistry by running 2-year part-time diploma microvascular limbs and it seems reasonable at the extremes of each cycle makes courses in each of the clinical disciplines. The to suggest that the increased apoptosis in calculation of shear stress impossible. Since first of the courses to be run is a Diploma of “rocking” cultures reflects a mechanism for we now have this interesting data, further Paediatric Dentistry and will begin in January 2001. accelerating endothelial apoptosis in these expenditure on more complex and expensive The course for 4-5 Cambodian dentists has sorts of degenerating blood vessels. Similar equipment seems justified. To this end, we been developed with Cambodia’s specific needs events may occur in vessels where there are are currently assembling an apparatus in mind, and will involve intermittent visits by up to flow conflicts (Figure 1). Another possibility, which will allow us to study these 8 overseas volunteer paediatric dentists, mainly is that the oscillatory shear stress generated phenomena more carefully. Despite from Australia and NZ. Each visiting lecturer will on the rocking platform mimics the numerous technical difficulties and setbacks, teach part of the course as well as providing clinical oscillations in flow or turbulence generated we hope to be able to initiate experiments supervision. The period of each visit will be 1-2 when vessels become excessively tortuous. with this much more sophisticated model weeks with about 2 months between visits during In this way, apoptosis of endothelium in system in the near future. which time students will continue to treat children on their own, and carry out prescribed readings and assignments. Those Cambodian dentists Initital Vasculature Final Vasculature invited to attend the course include teachers at the Faculty of Dentistry and the Dental Nurses training school, and one or two general dentists Arterlole who have a particular interest in or responsibility for treating children. The local coordinator for the course is Dr Poum Sen, Lecturer in Paediatric Dentistry at the Faculty of Dentistry in Phnom Penh. Capillary Remodelling by Along with the teaching, we intend to upgrade the sparsely furnished paediatric clinic at the Endothelial Apoptosis Faculty of Dentistry, by seeking donations of supplies, instruments and equipment. If this first course in paediatric dentistry is successful, it is Steady Laminar Shear? intended that courses in other clinical disciplines Venule will be introduced later. Anyone interested in helping support this Oscillating Shear? project should contact: Fig. 1. Illustration of the effect of blood flow in individual micro-vessels upon survival of vessel segments during microvascular remodeling. Callum Durward Blood enters the microvasculature via arterioles, passes through capillaries and exits via venules. Blood flow is indicated by arrows and Paediatric Dentist vessel segments where blood flow is poor are lost by endothelial apoptosis with the effect that microvascular structure is optimized. Poor Greenlane Hospital flow may result from flow conflicts or insufficient arterial supply relative to the dependent capillary bed. As discussed in the text of this article, we have found that chemical plasma factors have a central role in signaling the presence of flowing blood in functional blood Private Bag 92-189 vessels, inhibiting apoptosis and so helping to control the structure of the microcirculation. Other workers have demonstrated a protective Auckland New Zealand effect of steady laminar shear stress while we find that that oscillating shear seems to stimulate endothelial apoptosis. This may contribute to removal of vessel segments where there are flow conflicts as well as excessive tortuosity. E-mail: [email protected] 4 SYNOPSES DECEMBER 2000 ORAL MANIFESTATIONS OF ONCOLOGY TREATMENT Oral Manifestations of Oncology Treatment in Paediatric Patients Peter Readman, Paedodontic Registrar Princess Margaret Hospital Supervisor: Robert Bower, Consultant Periodontist Princess Margaret Hospital Inroduction A longitudinal study by Fayle and their apparent differing susceptibilities. Curzon investigated the oral complications Nonkeratinised mucosa generally contains Malignant disease ranks only second of 43 paediatric oncology patients aged two a loose connective lamina propria, which to accidents as the most common cause of to 14 years receiving treatment for offers little support and facilitates mobility death in children under 15 years of age.1 malignant disease.3 Forty (93 per cent) of the overlying epithelium. In contrast, The most commonly diagnosed paediatric developed oral complications during the keratinised mucosa is firmly bound to malignancies are leukaemias, followed by study period which emphasizes the need periosteum by a collagen rich lamina tumours in the central nervous system, for dental involvement in paediatric propria. Fourth, regional susceptibility may lymph nodes, bones, joints and cartilage, oncology patients. also be explained by the presence or absence and those of endocrine origin.2 The nature and incidence of oral of keratin, which offers physical protection Complications resulting from neoplasia, problems observed during treatment are to the epithelium. Fifth, neutropenia and or secondary to cancer treatment, frequently illustrated in Table 1. local secondary infection may progress to manifest in the oral cavity.3,4 Surgery, overt ulceration as a result of the patients radiation and cytotoxic chemotherapy Mucositis and Ulceration impaired healing response.12 disturb the normal integrity of the mouth Mucositis, ulceration and erosion are both anatomically, histologically and The oral mucosa is comprised of cells the most common oral complications of physiologically. This paper will review the with a high mitotic index, making these cancer treatment.1,3,13,14 Initial symptoms oral complications of both childhood tissues particularly vulnerable to the include a burning sensation, dryness of the neoplasia and cancer therapy. direct effects of cytotoxic chemotherapy.1,10 mouth, tingling of the lips and pain.1 By inhibiting cell growth, cytotoxic Depending on the chemotherapeutic Oral Complications of chemotherapy alters the integrity of the regimen used, erythematous mucositis Systemic Cytotoxic Chemotherapy oropharyngeal mucosa, thus creating a develops in three to five days after the portal of entry for the microbial flora found initiation of therapy and a localised or Cancer chemotherapy protocols are within the oral cavity.1,10 In addition, a generalised ulcerative mucositis in seven designed to obliterate malignant cells at the gross reduction in granulocyte numbers, to ten days.3,5,13 These painful ulcerative primary lesion and elsewhere throughout as well as modifications to their functional lesions are noted primarily on the body.6 In acute leukaemia, the drug capabilities (eg. reduction in migration, nonkeratinised tissues, such as the buccal schedules are targeted primarily against phagocytosis, and antibacterial effect), and labial mucosa, the ventral and lateral bone marrow, inducing a pancytopenia.6 leads to an increase in susceptibility to surfaces of the tongue and the floor of the The drug-induced myeloimmunosuppression infection.1,10,11 mouth. Keratinised tissues such as the hard correlates closely with vulnerability to Barrett proposed that five interrelated palate, attached gingivae and dorsal infection. Cytotoxic chemotherapeutic factors contribute to the clinical breakdown surface of the tongue are rarely subject to agents may therefore produce adverse side and ulceration of the oral mucosa following mucositis but may become painful.3,5,13 effects by direct toxicity at the cellular level cytotoxic chemotherapy.12 First, the Predicting which patients will suffer or indirectly, characterised by drug-induced relatively rapid rate of cell turnover in the mucositis remains difficult as the capacity pancytopenia.6 oral mucosa is important in explaining its to tolerate cytotoxic chemotherapy varies About 40 to 50 per cent of all patients susceptibility. Second, degenerative greatly between individuals.12,15 In almost receiving chemotherapy develop oral changes in the supportive submucosal all cases, patients involved have low changes, however, these figures approach collagen may play a key role in the neutrophil counts (less than 0.5 x 109/L). 3 90 per cent in children.1,5,7-9 The increased development of ulceration following The ulcers usually last five to ten days with mitotic index in children and associated cytotoxic chemotherapy. Third, the healing coinciding with an improvement rapid epithelial turnover and maturation structural characteristics of the mucosa and in the neutrophil count.3 rates is thought to be responsible for their submucosa in areas of keratinised and Cytotoxic chemotherapeutic agents greater susceptibility to cancer therapy.9 nonkeratinised mucosa may help explain associated with mucositis include antimetabolites and in particular methotrexate, cytarabine and 5-fluorouracil, and antitumour antibiotics such as ORAL PROBLEM NUMBER AFFECTED (N=43) daunorubicin, doxorubicin, bleomycin and Mucosal Ulcers 28 (65%) hydroxyurea.5 If cytotoxic chemotherapy is Lip Cracking 15 (35%) given in combination with total body irradiation prior to bone marrow Lymphadenopathy 15 (35%) transplantation a rapid-onset mucositis Mucositis/Erythema 13 (30%) may develop.1,5 Oral Bleeding 9 (21%) Treatment of mucositis is primarily Severe Gingivitis 8 (19%) palliative aimed at minimising mucosal trauma and improving patient comfort.13 Herpes Simplex 6 (14%) During radiation and chemotherapy, the Candidiasis 5 (12%) oral tissues should be kept moist by Dry Mouth 2 (5%) frequent water rinses.5 If mucous is thick Table 1. Incidence of oral problems observed during treatment3 Continued on Page 6... SYNOPSES DECEMBER 2000 5 ORAL MANIFESTATIONS OF ONCOLOGY TREATMENT ...Continued from Page 5 myeloimmunosupressed patients.13,18 The Cepacaine, Difflam mouth gel, Oratect Gel majority of oral bacterial infections in and systemic analgesics.5 There is no it can be diluted by rinsing with a five per children involve secondary involvement of experimental evidence, however, to cent solution of sodium bicarbonate.5 mucosal ulcerations due to therapy-related establish the efficiency of any one or Rinsing the mouth after brushing with a neutropenia.13,18 A wide range of bacteria, combination of these agents in the salt and soda (half a teaspoon salt and one including odontopathic, periodontopathic, management of pain.5 teaspoon baking soda in one pint of water) is and transient pathogens of the oral cavity Conventional tooth brushing during recommended. 14 Saline solutions are thought may infect ulcerative lesions.13 myeloimmunosuppression may increase to aid in formation of granulation tissue and Predisposing factors to infection include, the risk of bleeding and infection.13 A promote healing, while sodium bicarbonate neutropenia, mucosal damage, periodontal modified mechanical approach is dissolves mucin and loosens debris. 14 disease, dentoalveolar abscess, mobile recommended consisting of either irrigation To prevent oral mucositis, patients deciduous teeth, cellular immune with a Water Pik or cleaning with a undergoing cytotoxic chemotherapy dysfunction, haematologic immune disposable sponge, piece of gauze or cotton usually receive some form of prophylactic dysfunction and iatrogenic procedures.5 swab with a topical antimicrobial agent.13 mouthwash. 6 The double blind, The clinical appearance of potentially Patients receiving long-term randomised clinical trials of Ferretti et. al., severe local infections can be reduced or chemotherapy may experience subtle and Rutkauskas et. al., support even absent during chemotherapy as a changes in their saliva from microbial shifts prophylactic use of chlorhexidine in result of induced neutropenia.1,6,10,19 This to a decrease in the quality and quantity of immunocompromised patients. 7,16 These particularly applies to gingival and saliva.5 Brown et. al., reported a higher studies showed a significant reduction in periodontal inflammation. 20 concentration of Candida sp and both incidence and severity of mucositis in Staphylococcus sp in immunodeficient chlorhexidine treated patients. 7,16 patients. However, a lower recovery of S Consequently, patients undergoing mutans and a lower caries experience in “The incidence of oral infection cytotoxic treatment may achieve better immunodeficient patients was noted.21 nutrition, fewer septic episodes, and shorter These findings indicate that other protective is reduced when all definitive hospital stays. mechanisms may compensate for Benzydamine containing mouthwash immunoglobulin deficiency. 21 dental treatment is completed (Difflam) is often used in the treatment of mucositis.17 Benzydamine hydrochloride 2. Fungal Infections before the commencement of is a topical nonsteroidal anti-inflammatory drug with analgesic, antipyretic, Fungal infections in patients cytotoxic chemotherapy.” antimicrobial and local anaesthetic activity. undergoing cytotoxic chemotherapy most When applied topically as an oral rinse it commonly involve Candida albicans.13 offers the unique property of concentrating Other less common fungal infections in in inflamed tissues. Benzydamine is used The incidence of oral infection is immunosuppressed patients involve widely in the management of pharyngitis, reduced when all definitive dental Histoplasma capsulatum and Cryptococcus radiation mucositis, aphthous stomatitis treatment is completed before the neoformans. Under normal conditions in and post-operatively following dental commencement of cytotoxic the oral cavity, the growth of C. albicans is surgery. This mouthwash is also available chemotherapy.1 Patients who receive inhibited by commensal microorganisms with the addition of chlorhexidine (Difflam- cytotoxic chemotherapy should have a and by an intact immune system. Once C) improving its antimicrobial properties. 17 thorough oral examination including both pathogenic, C. albicans may spread to the Kamillosan is another mouth wash clinical and radiographic examination.13 If oesophagus or trachea via deglutition or which has been recently reviewed in the therapy has already commenced, it is still droplet aspiration, or via haematogenous dental literature. Research has been aimed recommended that patients be evaluated spread. The most serious infections involve towards developing an irrigation solution as early as possible to establish a baseline major organ involvement or disseminated that will prevent or reduce mucositis and examination which will assist in the candidiasis.13 promote epithelialization of desquamated monitoring and treatment of oral The incidence of candidiasis in regions of the oral mucosa.18 Kamillosan complications.13 paediatric patients receiving chemotherapy solution is prepared from the flower of the Optimal dental treatment should has been reported at 15 and 30 per cent.3,22 camomile plant. The main constituents include a prophylaxis, restoration of carious Candidiasis in children occurs most are chamazulene, levomenol, polyins, and teeth, replacement of unsatisfactory frequently on the dorsum and lateral flavinoids. These constituents are restorations, smoothing of fractured surfaces of the tongue, the commissures antiinflammatory and spasmolytic, and enamel or rough restorations, extraction of the lips, and the buccal, gingival and promote granulation and epithelialization of necrotic, infected or exfoliating teeth and palatal mucosa.1,6 Candida colonisation through a favourable effect on the energy- elimination of prostheses.13 Good plaque appears as raised, creamy white, curd-like dependant process of cell metabolism. Carl control before chemotherapy is essential to strands, beads, flecks and patches that et. al., studied the prophylactic and reduce the morbidity associated with soft adhere to the underlying mucosa and leave therapeutic use of Kamillosan oral rinse in tissue infection.1,13 painful shallow ulcers when removed.6 20 patients who received head and neck Oral hygiene procedures, both Patients receiving broad spectrum irradiation and 78 patients who received mechanical debridement and mouth rinses, antibiotics or steroids, may have atrophic systemic chemotherapy reporting a should be performed three times a day.5 If candidiasis which presents as a red often reduction in both intensity, onset and tissue complications develop or deteriorate, painful tongue.1 duration of mucositis.18 the frequency of oral care should increase Clinical management of oral candidiasis appropriately.5 A number of anaesthetics, in children is similar to that in adults and 1. Bacterial Infections analgesics and mucosal coating agents are consists of antifungal agents.1 Nystatin available for the control of pain. They oral suspension or amphotericin B syrup Bacterial infections are a significant include Benadril, Kaopectate, milk of or troches are often given after early cause of morbidity and mortality in magnesia, Orabase, viscous xylocaine, diagnosis of oral candidiasis.6 These agents 6 SYNOPSES DECEMBER 2000 ORAL MANIFESTATIONS OF ONCOLOGY TREATMENT can be cariogenic as a result of the high cumulative incidence of oral candidiasis in sero-positive patients to prevent and control sugar content and must therefore be the control group. 16 Furthermore, two HSV infection.5 accompanied by excellent oral hygiene in deaths from Candida sepsis occurred in the paediatric patients.1 control group during the early post- 4. Haemorrhage Epstein et. al., assessed the potential transplant period.16 role of prophylactic mouthwashes in the Nystatin and chlorhexidine should not Cytotoxic chemotherapeutic agents reduction of oral complications in patients be used simultaneously. Combining these may secondarily induce thrombocytopenia receiving chemotherapy for leukaemia.23 agents results in the formation of a which is the usual cause of intraoral This study, along with many other chlorhexidine-nystatin complex that haemorrhage.1,13,38 The haemorrhage may publications, did not identify any appears to be ineffective against candida.34 occur anywhere in the mouth and may prophylactic effects in Candida If the fungal infection becomes occur spontaneously or secondary to colonisation, clinical oropharyngeal disseminated, fluconazole or ketoconazole trauma or inflammation.13 Oral petechiae infection or fungaemia with the use of tablets may be effective.6 Intravenous occur most often in patients with a platelet nystatin. Other studies of Candida amphotericin B however, is the preferred count below 50 x 109/L, while prophylaxis using nystatin have often been drug for treating serious systemic spontaneous haemorrhage is associated based on small patient series which have infections.6 with platelet counts of less than 20 x 109/ produced inconsistent results.23-26,27-31 L.3,13 Compliance with nystatin rinsing is 3. Viral Infections Prevention is the most effective often limited by taste complaints, nausea technique used to avoid haemorrhage.13 and vomiting. Recent research has Herpes simplex virus (HSV) infection is Eliminating potential areas of trauma therefore focussed on fluconazole in (sharp restorations, fractured teeth, mobile Candida prophylaxis. Bodey et. al., studied deciduous teeth) and pre-existing intraoral oropharyngeal candidiasis in 112 adults disease before chemotherapy minimises “Radiation therapy involving undergoing therapy for metastatic haemorrhage.13 malignancies.32 In this double-blind study The oral mucosa should be kept moist only two per cent of patients receiving the head and neck region can with saline rinses, to avoid friction that fluconazole developed oropharyngeal may initiate bleeding.13 Management candidiasis compared to 28% for those requires removal of accumulated blood to result in temporary or permanent receiving placebo. Of the patients receiving identify the bleeding site and then pressure placebo, those who also received antibiotic should be applied with moist gauze, therapy or systemic adrenal corticosteroid destruction of salivary glands.” periodontal packing or a mucosal guard. therapy suffered a higher incidence of Management of haemorrhage may require oropharyngeal candidiasis at 30 per cent antihaemorrhagic agents such as topical and 44 per cent respectively. Candidiasis thrombin, absorbable gelatin sponges, was also evident in 54 per cent of placebo the most common viral infection associated oxidised cellulose, aminocaproic acid and patients who were colonized by Candida sp with cancer treatment.1 The virus may occur microfibrillar collagen haemostat. If the at the commencement of the study. as a primary infection, or more commonly bleeding episode is associated with an Fluconazole provided effective prophylactic as reactivation of the latent virus during infection requiring surgical intervention or cover for oropharyngeal candidiasis in this periods of immunosupression and intense if local measures are unsuccessful, platelet study with few reported side effects.32 chemotherapy.1 transfusion may be required.1,13 Quirk et. al., retrospectively studied 196 Oral infections caused by HSV may be patients who underwent bone marrow preceded by prodromal symptoms of pain, Oral Complications of Radiation transplantation.33 Patients were divided burning, tingling or itching.6 They often Therapy in the Head and Neck into two study groups; 1) those receiving begin as multiple vesicles at the vermillion oral nystatin/amphotericin or 2) those borders, which rupture leaving painful The major early side effects of head and receiving oral fluconazole. Fluconazole ulcers that subsequently become encrusted neck irradiation are mucositis, salivary significantly reduce the incidence and with dried exudate.6 HSV infections gland changes, candidiasis and severity of oropharyngeal candidiasis, often follow an atypical course in dysphagia.5,18 Among post-irradiation showed good compliance and had minimal immunocompromised patients.35 Lesions problems are radiation-associated dental side effects. Oropharyngeal candidiasis are often larger and require up to four caries, periodontal deterioration, occurred in 54 percent of those patients in weeks or even longer for complete healing xerostomia, reduced maxillomandibular the nystatin/amphotericin group and in without antiviral therapy.35 opening, decreased resiliency of perioral only seven per cent of those patients Diagnostic tests include immuno- tissues and intrinsic bone changes.5,18,39 receiving fluconazole.33 fluorescence, Tzanck test, polymerase chain Abnormalities in the developing dentition The prophylactic use 0.12 percent reaction, antibody titres, Western Blot include; enamel hypoplasia, diminutive chlorhexidine mouthrinse was shown by analysis, and electron microscopy. teeth, delay or failure of tooth development Ferretti et. al., to reduce the incidence of However, viral culturing offers the most and eruption and altered root formation.1 oral candidiasis in patients undergoing sensitive diagnostic test for the detection intense chemoradiotherapy after bone of HSV infections. 35 Early Effects marrow transplant.16 In a prospective, As a result of the increased susceptibility randomised, double-blind study, patients to HSV infections, the high frequency of 1. Salivary Changes were assigned mouthrinses containing atypical appearance and the prolonged either 0.12 per cent chlorhexidine or a clinical course of HSV infections, some Radiation therapy involving the head control mouthrinse identical in investigators recommend prophylactic and neck region can result in temporary or composition but without chlorhexidine. antiviral agents for patients who are permanent destruction of salivary glands.1 There was an absence of clinically evident severely myeloimmunosuppressed.36,37 An initial decrease in free flowing saliva is oral candidiasis in the chlorhexidine-treated Acyclovir is the preferred treatment both group compared with 64.7 per cent prophylactically and therapeutically in Continued on Page 8... SYNOPSES DECEMBER 2000 7 ORAL MANIFESTATIONS OF ONCOLOGY TREATMENT Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 ...Continued from Page 7 2. Mucositis followed by an accumulation of sticky Mucositis induced by irradiation is mucous, because the acini of serous glands defined as the reactive inflammatory-like are affected more than the acini of mucous process of the oropharyngeal mucous glands.5 The pH of affected saliva may fall membrane following therapeutic irradiation to below 5.5.5 The severity of salivary of patients who have head and neck changes is related to the radiation dosage, cancer.40 It is important to record the extent quantity of salivary tissue exposed and the of mucositis due to irradiation from both a patient’s age.1,5 Altered salivary gland clinical and research standpoint. A function predisposes such patients to pain, scoring system of mucositis enables inflammation, dysphagia, xerostomia communication between clinicians with and severe radiation-associated dental respect to generalised complaints such as caries.1 pain and dysphagia, as well documenting Managing xerostomia involves a the dose-response relation for that combination of strategies including patient.40 Figure 7 synthetic salivary substitutes, stimulation The first signs of mucositis, a whitish of remaining salivary tissue, maintenance appearing mucosa, occurs after exposure of good oral hygiene and use of topical to 1, 000 rads (10 Gy).5,41 Eventually, the fluoride.1 Patients with xerostomia whose mucosal surface becomes erythematous salivary glands can respond to stimulation with deposits of fibrin on the surface. In the may benefit from using simple dietary uncontrolled patient, islands of ulceration measures such as eating carrots or celery may appear after 3, 000 rads (30 Gy).5,41 or chewing sugarless gums.13 Pilocarpine As treatment progresses, the entire mucosa also appears to be effective in patients with may be involved and the patient loses taste residual salivary gland function, however sensation. Local factors such as poor oral patients with no functioning salivary hygiene, dentures and defective teeth glands require saliva substitutes.13 frequently aggravate the condition.5,41,42 8 SYNOPSES DECEMBER 2000 ORAL MANIFESTATIONS OF ONCOLOGY TREATMENT 3. Other Early Effects The use of megavoltage radiation has reduced root length of multiple teeth reduced the incidence of osteoradionecrosis secondary to chemotherapy. This patient Other acute complications of from around 37 percent to below 20 percent.45 sustained a palatal luxation injury of tooth radiotherapy include loss of taste, dysphagia, However, clinicians should perform 21 as shown in Figure 7. trismus, loss of appetite, nausea, malaise extractions carefully on patients who have and weight loss.5 Patients who have received radiotherapy.5 In susceptible 3. Other Late Effects received oral or radical neck surgery may patients the correct extraction technique also develop oedema of the buccal mucosa involves alveolectomy and primary closure The effect of radiotherapy predisposes and floor of the mouth as a result of of the socket to eliminate the potential for the periodontium to disease since both impaired venous and lymphatic drainage.5 sharp bony edges or spicules that may vascularity and the capacity of the damage the overlying mucosa.5,46 This is supporting bone to remodel and repair is Late Effects performed under the cover of broad also reduced.43 In addition, a reduction spectrum antibiotics.5,46 in the salivary flow increases plaque 1. Radiation Caries and Dental Erosion Wound healing of heavily irradiated deposition. Teeth with advanced bone following surgery can be enhanced periodontitis are also at risk of initiating A distinct type of rampant caries often with the use of hyperbaric oxygen.39 osteoradionecrosis through the invasion of occurs in patients receiving radiotherapy Hyperbaric oxygen treatment requires about microbes directly into the underlying bone.43 regardless of whether or not teeth are located four weeks and results in revascularization Candidiasis is also more common within the collimation of the beam.41,43 of irradiated tissue.39 The major difficulties following radiotherapy which has resulted A reduction in the salivary flow together of this treatment are time and expense. Soft in xerostomia. Altered salivary flow with a shift in the oral microflora towards and salivary histatin levels may be more cariogenic organisms increases the important predisposing factors. The risk of caries.43 “Children are particularly increased susceptibility to candidiasis is Radiation caries usually appears in the particularly evident in patients wearing cervical areas of teeth, if uncontrolled, caries susceptible to both the acute and dentures.43 will circle the entire tooth with subsequent Trismus is another chronic complication chronic oral manifestations of crown fracture at the gingival margin.5,43 of radiotherapy. A reduction in blood flow Caries is also observed on the incisal edges cancer treatment. Multidisciplinary to the muscles of mastication as a result of of anterior teeth and the cusp tips of the progressive endarteritis results in scarring treatment and coordination of care posterior teeth, which are normally bathed and fibrosis of the affected muscles.43 in saliva and caries resistant.5,43 is therefore essential.” As treatment for paediatric cancers A major side effect of cancer treatment improves, the increased survival of these is nausea and vomiting. The reduced patients may result in an increase in the salivary flow in patients who have received number of second primary malignancies. head and neck irradiation renders the tooth tissue oxygen partial pressure (tension) can Van der Waal reports on a case of oral surfaces particularly vulnerable to dental be raised to approximately 80 percent of squamous cell carcinoma following erosion. Erosion of the palatal surfaces of normal after a total of twenty, one and a treatment of acute lymphoblastic the upper anterior teeth are most frequently half hour treatments at 2.4 atmospheres leukaemia.48 It is tempting to speculate that affected as shown in Figures 1 and 2. of 100 percent oxygen.39 the previous oncology treatment, either Radiotherapy may also damage irradiation or cytotoxic chemotherapy, was 2. Bone Changes and developing tooth buds.5,43,44,47 If irradiated related to this second neoplasm rather than Developmental Defects before calcification is complete, the tooth a random event.48 buds may be destroyed.44 Exposure later in In a retrospective study of 9720 The most serious complication of the developmental process may arrest children treated for acute lymphoblastic radiotherapy is osteoradionecrosis.43 Bone growth and cause irregularities in enamel leukaemia, Neglia et. al., found a seven- absorbs a larger amount of radiation and dentine.44 Consequently these patients fold excess of all cancers and a 22-fold compared to an equal volume of soft tissue.5 may have missing teeth, enamel opacities, excess of central nervous system tumours Radiation reduces the number of bone cells hypocalcifications, thin or shortened roots when compared to prevalence rates in the as a result of endosteum atrophy and direct and developmental malocclusions.43,44 general population.49 Children who cell death of osteoblasts and osteocytes.5,44 Interestingly, teeth often fully erupt even if underwent cranial irradiation before five The bone becomes significantly acellular and the roots may fail to form.44 years of age had the greatest susceptibility avascular, with marrow spaces undergoing Figures 3 and 4 illustrate the same to brain tumours.49 fibrosis and fatty degeneration.5,44 patient with hypoplasia of the second These changes make the bone premolars and second molars. The OPG Conclusion vulnerable to trauma and infection impairing shown in Figure 5 presents a patient who its capacity to remodel and repair.43 The received irradiation for treatment of a Children are particularly susceptible mandible’s high bone density and low nasopharyngeal carcinoma. Note failure to both the acute and chronic oral vascularity makes it more vulnerable to of tooth development in the anterior manifestations of cancer treatment. osteoradionecrosis than the maxilla. If maxilla and impaction of the upper left Multidisciplinary treatment and growth centres are affected by irradiation, second molar. coordination of care is therefore essential the development of the facial bones may give The reduction in root length may result to reduce both the incidence and morbidity rise to facial asymmetry and malocclusion.43 in endodontic infections secondary to of these complications.The dentist involved The most common dental factors minimal periodontal breakdown.43 in the patients care must recognize the oral precipitating necrosis are pre- and post- Although it is not reported in the dental complications of cancer therapy which may radiation extractions and pre-existing literature, such teeth may also be affect cells either directly or secondarily periodontal disease.43 Dentures that cause predisposed to luxation injuries as a result through myeloimmunosuppression. ulceration to the underlying mucosa and of the reduced periodontal attachment. underlying bone are also contributing factors.43 Figure 6 is an OPG of a patient illustrating Please contact the Editor by email for references SYNOPSES DECEMBER 2000 9 BRANCH REPORTS New South Wales and Research Centre, Royal North Shore have an annual general meeting, being Hospital. Dr Walker addressed current addressed. As a result, the society is now President: Eduardo A Alcaino trends in pain management in the an incorporated body (many thanks to Secretary: Juliette Scott paediatric patient; she also discussed Mary Livingstone). Treasurer: Anthony Burges hierarchy of pharmacological Submissions were also reviewed and Committee Members: management, and also focussed in pain forwarded to NZDA on several issues Joanna Seppelt, Suzanne Turek, management for the paediatric dental including competency and continuing Richard Widmer, Angus patient. This was an excellent talk with education, along with a short submission Cameron, Kareen Mekertichian much interest from the audience. on registration requirements for foreign and Mary Moss graduates. Tuesday 7th November 2000 Auckland members ran a successful one There are approximately 50 active This event has been scheduled for the day course with Drs Callum Durwood, members of the Society for 2000. During afternoon of Melbourne Cup Day. A short Heather Keall, Kahtan Hameed, and Nina this year, the society held three meetings at general trivia Quiz and Luncheon has been Vassan. being speakers. the usual venue, The Duxton Hotel at arranged for the afternoon. We will then Fluoridation has been an issue again Milsons Point. Although 4 meetings are join Melbourne Cup festivities, including a in various centres. In New Plymouth the planned for each year, the 12th Biennial live coverage of the Melbourne Cup race. District Council opted to review the matter ANZSPD Conference in Adelaide (between The afternoon is meant to be a social, by having a public forum which lasted one the 24th-26th February 2000) also filled our informal and pleasurable event for all day, rather than a referendum or a series of calendar, with several of our members dentists and their staff. public meetings. This enabled interested attending to this meeting. The three parties to make submissions without meetings for the year 2000 were as follows: Eduardo A. Alcaino interjections, and in a controlled Hon Secretary ANZSPD 2000 (NSW Branch) environment. Submissions were varied & Tuesday 11th April 2000 came from a wide range of the community This meeting discussed “Contemporary including the youth council, Public Health New Zealand diet & nutrition and its effects on dental officials. various health workers, the Pure disease”. Our guest speaker was A/Professor Water association, and individuals wanting Linda Tapsell, Acting Director- Smart Foods The New Zealand Branch of ANZSPD to control the poisons in their drinking Centre, The University of Wollongong. A/ met in October at the NZDA biennial water and their right to choose. Several local Prof. Tapsell spoke about current aspects of Conference. There we thanked some very Maori groups spoke strongly in favour of dietary advise, the effects of high frequency long serving members being Mary retaining fluoride. Prior to the forum most eating (snacking) in children and dental Livingstone as Secretary/Treasurer and Alan councillors had indicated they wished to caries, erosive wear, and current protocols Issac as committee member and previous remove fluoride, but the decision was for pre-school children. president. The President is now Jo Pedlow strongly in favour of continued Of interest also was the 5th Congress of from Christchurch, President Elect is Callum fluoridation. Only one councillor out of the the European Academy of Paediatric Durwood (Auckland) & Secretary Mary twelve voted against continued fluoridation Dentistry held from June 7-11 in Bergen, Anne Costelloe (Stratford, Taranaki). New Next year the society is planning to Norway. This was attended by several Committee members are Nina Vassan have several visiting paediatric speakers members of our state branch, with papers (Auckland) and Christine Holloway (Timaru). including the ANSPD President Dr Kerrod being presented by A/Prof R. Widmer, Dr A. The conference enjoyed a good Hallet, but first we are all anticipating Cameron, Dr E. Alcaino, and two of our paediatric program (organised by Dr family time over Christmas and a restful, post-graduate students, Dr E. Mahoney Bernadette Drummond). Angus Cameron peaceful summer holiday which we hope and Dr Katherine Ngu. This was a highly was a key speaker and was very well our Australian members will also enjoy. successful meeting with approximately 350 received. Recent Otago Masters graduates delegates attending. Allison Meldrum and Katie Ayers were also Mary Anne Costelloe part of an interesting and well attended Tuesday 1st August 2000 program along with Dorothy Boyd Queensland This meeting discussed “Pain The society executive has convened management in the paediatric patient”. Our regularly by teleconference throughout the guest speaker was Dr Suellen Walker, a staff last two years. Here the branch’s The year is coming to a close for the specialist in the Department of Anaesthesia constitution has been reviewed and Qld Branch with our Annual Clinic Day and and Pain Management and Clinical Lecturer updated with one notable requirement of AGM in November. Under the auspices of in the University of Sydney Pain Management the NZ registrar of Societies, that we must our President, Dr. John Keys, the Branch 10 SYNOPSES DECEMBER 2000

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