Academic literature on the topic 'Intra-marrow penetration'

Purpose Fracture-related infections are difficult to treat because of the formation of biofilms around implants. Systemic antibiotics are notoriously ineffective against biofilms due to their insufficient penetration of tissues with poor vascularity. The goal of treating fracture-related infections is to achieve bone union while retaining the implant. Our proposal of continuous local antibiotic perfusion is a sustained local delivery system of sufficient antibiotics to bone and soft tissue infection sites, including to bone marrow via needles as intra-medullary antibiotics perfusion and to soft-tissue via double-lumen subcutaneous tubes as intra-soft tissue perfusion. Methods In this study, we examined the outcomes of 40 patients treated for fracture-related infections using continuous local antibiotic perfusion between 2015 and 2021 at Steel Memorial Hirohata Hospital, Himeji, Japan. Result The antibiotic used for continuous local antibiotic perfusion was gentamicin in all cases. Implant removal was required in five patients. Two patients required toe amputation and knee arthrodesis, while the remaining 38 patients achieved fracture union. Only one case of transient acute renal injury as a systemic side effect was observed, but it soon resolved. The blood concentration of gentamicin could be adjusted to less than the trough level. Conclusions Continuous local antibiotic perfusion is a novel local drug delivery system that has the potential of delivering sufficient concentrations of antibiotics with few systemic side effects; it is a useful option for the treatment of fracture-related infections.

ntroduction: Periodontitis is a multifactorial disease, which, when not adequately treated, is followed with progressive attachment loss which leads to tooth mobility and eventually tooth loss. Periodontal regenerative surgery aims to regenerate and reconstruct the lost periodontal tissue. Regeneration with novabone putty has shown to be effective in reducing probing pocket depth, gain in clinical attachment level and increase in horizontal bone level. Aim: This interventional clinical trial was to evaluate the osseous regenerative potential of a calcium phosphosilicate bioactive glass NOVABONE TM in the treatment of horizontal bone defects. Materials and method: A total of 20 sites with horizontal bone defect was treated with open flap debridement with intra marrow penetration and novabone putty. Statistical analysis: Plaque index, gingival index and radiographic determination were analysed by paired t test. Probing pocket depth and clinical attachment levels were analysed by Wilcoxon Signed Ranks Test. Result: There was significant reduction seen in plaque index, gingival index, probing pocket depth and radiographic crestal level when compared between baseline and 12 months respectively (2.48 ± 0.44, 2.92 ± 0.39, 6.80 ± 0.89, 8.29 ± 0.87) and (1.89 ± 0.42, 1.92± 0.51, 3.00± 0.67, 5.48 ± 0.89) and significant gain in clinical attachment level from 4.40 ± 0.96 to 1.20 ± 0.91. Conclusion: The present study showed novabone putty significantly improved the clinical parameters in horizontal bone defects.

Abstract Prognosis of refractory and relapsed ALL is poor and improvement requires the introduction of agents with a new mechanism of action. Bortezomib (BTZ) as a proteasome inhibitor is such an agent, and was safe as single agent in phase I studies in children (Blaney 2004; Horton 2007). Messinger et al. (2012) reported a single-arm study that BTZ can be combined safely with conventional drugs; the combination was remarkably effective. BTZ results in sensitization of malignant cells to anticancer agents, both in vitro for leukemias as well as for multiple myeloma patients. In patients with ALL, this effect regarding glucocorticoids has not been addressed yet. It also has not been studied whether BTZ reaches the cerebrospinal fluid (CSF), which is relevant in pediatric leukemias in view of the frequent leptomeningeal involvement. In the setting of the lack of clinical experience with BTZ in children in Europe, we developed a European multicentre feasibility/phase II study in refractory or relapsed ALL, in which all patients get BTZ (NTR 1881, EUDRaCT 2009-014037-25, ITCC 021). A randomisation is done for BTZ to start “early”, on day 1 of treatment, or “late”, on day 8 of treatment. Bortezomib is given as iv push for 4 doses at 1.3 mg/m2/dose, thus in group “early” on days 1, 4, 8 and 11 and in group “late” on days 8, 11, 15 and 18. In addition, all patients receive dexamethasone (10 mg/m2/day in 3 doses for 2 weeks, orally or iv) and vincristine (1.5 mg/m2/dose with a maximum of 2 mg as 1-hour infusion on days 8 and 15), and one intrathecal administration of methotrexate (dose age-adjusted) on day 1. Eligible patients have 2nd or greater relapsed ALL, 1st relapsed ALL after allogeneic stem cell transplantation (allo-SCT) in 1st complete remission (CR1), or refractory 1st relapsed ALL, bone marrow involvement and at least 100 leukemic cells per ul blood. Exclusion criteria includes symptomatic CNS leukemia, among other factors. It is planned to have 24 fully evaluable patients. This interim analysis is limited to a description of pharmacokinetic (PK) data, especially concerning the CSF. As per June 1, 2013 a total of 14 patients has been enrolled, 9 boys and 5 girls, median 8.7 years of age (range, 1.6-16.2). Most had 2nd relapsed ALL (n=9), others 1st relapsed ALL following allo-SCT in CR1 (n=3) or refractory 1st relapsed ALL (n=2). Regarding PK in the peripheral blood, there was remarkable intra- and inter-individual variability in peak plasma concentrations, between patients ranging from 4.7 to 2920 ng/ml 15 minutes after the first administration of BTZ, median 12.4 ng/ml (18.7 ng/ml in the group with BTZ “early”, 12.1 ng/ml in the group with BTZ “late”). Peak levels after the fourth administration were higher, median 41.1 ng/ml (29.5 ng/ml in the group with BTZ “early” and 158.9 ng/ml in the group with BTZ “late”). There was a 10-fold interindividual variation in the area-under the concentration versus time curve until 72 h (AUC[0-72h]) after administration. Median ratio of AUC[0-72h] fourth dose / AUC[0-72h] first dose was 2.7 (range 0.9 – 9.3), which is indicative of accumulation. In all patients, PK of BTZ was studied in the CSF 15 minutes after administration of the first and third dose (group “early” only) of BTZ, as well as 4 days (group “late”) or one week (group “early”) after the last administration. In general, no BTZ was detected with a lower detection limit of 0.1 ng/ml. In 4 patients some BTZ was detected in CSF, at 0.2 – 0.4 – 1.7 - 5.2 ng/ml. Of potential interest, the latter patient also had the highest peak plasma level of BTZ (2920 ng/ml) and the highest AUC. Future analyses in the complete cohort of 24 randomised patients will focus on more extensive population PK and pharmacodynamic analyses, as well as on efficacy of BTZ. The higher peak plasma levels after the fourth dose suggest decreased clearance (especially in the group which received bortezomib “late”), which indeed has been reported in adults and which requires careful monitoring of toxicity over time. Mean peak plasma concentrations in adults were reported to be 173 ng/ml, and thus seem higher. Meanwhile, BTZ does not or hardly penetrate the cerebrospinal fluid and is unlikely to be a drug that significantly adds to the treatment of leptomeningeal involvement in leukemia. Financially supported by the Dutch Foundation Children Cancer-free. Disclosures: Off Label Use: bortezomib in pediatric relapsed acute lymphoblastic leukemia.

Abstract Abstract 4895 Background: The treatment of primary central nervous system lymphoma (PCNSL) is characterized by high rates of toxicity and intracranial relapse despite initial response. High-dose methotrexate (HD-MTX), with or without cranial irradiation, has become the standard of care; combining this with other chemotherapeutic agents has improved complete remission rates but at the expense of increased treatment-related adverse events, particularly haematologic and neurologic toxicity. Cytarabine has been used in combination with etoposide (CYVE) as a salvage therapy for patients who have been refractory to or relapsed after HD-MTX-based regimens (Soussain C et al, J. Clin. Oncol. 2001; Soussain C et al, J. Clin. Oncol. 2008). In these studies, cytarabine was given as an infusion at a dose of 50mg/m2/d over 12 hours on days 1–5, and at a dose of 2g/m2/d over 3 hours on days 2–5 with etoposide at 200mg/m2/d on days 2–5. Both responders and non-responders were eligible to proceed to autologous stem cell transplant (autoSCT) using a conditioning regimen of thiotepa 250mg/m2/d on days -9 to -7, busulfan 10mg/kg total dose po or 8mg/kg total dose iv over days -6 to -4, and cyclophosphamide 60 mg/m2/d on days -3 to -2. Median OS was 58.6 months in patients able to undergo autoSCT, but with significant neurotoxicity that may have been related in part to prior therapies. Methods and Results: Given its excellent CNS penetration, CYVE may be an effective regimen in previously untreated patients, with lower risk of neurotoxicity. We have used CYVE as a first-line therapy for patients with PCNSL who are potentially eligible for subsequent autoSCT. Between January 1, 2005 and December 31, 2009, 7 patients with a diagnosis of PCNSL were treated with first-line CYVE using the regimen described above. All were HIV negative, showed no disease outside of the CNS on bone marrow biopsy and staging CT or PET scan, and had biopsy-proven PCNSL with diffuse large B-cell histology. Median age was 55 (42-61) with 4 female and 3 male patients. Median International Extranodal Lymphoma Study Group Prognostic Index score was 2 (0-2), although in actuality may have been higher, as 4 patients were not able to undergo lumbar puncture at diagnosis. ECOG status was < 2 in 3 patients, ≥ 2 in 3 patients, and not documented in 1 case. Patients received a median of 2 cycles of CYVE (1-3), with 2 receiving concurrent rituximab and the 1 patient with intra-ocular lymphoma receiving post-adjuvant orbital radiation. No cranial radiation was administered. Five patients achieved CR and proceeded to autoSCT. Two patients had a PR but later died of progressive disease at day +48 and day +117, respectively. In both cases, however, the patients were suspected of having disease long before they were treated with CYVE. The first had presented 3 years prior to the diagnosis with a solitary brain lesion that resolved with decadron monotherapy before pathologic documentation. The second had had a brain biopsy that failed to show malignant disease 4 months before the PCNSL diagnosis was confirmed and treatment initiated. Median OS and PFS for the group have not yet been reached with mean follow-up of 657 days. Among the 5 patients who achieved CR, all patients remain alive in CR with a mean follow-up of 841 days (320-1262 days), or 28 months. Toxicities included at least 1 episode of febrile neutropenia in all 7 patients, 2 possible but unconfirmed cases of pulmonary aspergillosis, 2 cases of drug-induced hepatitis (with ALT > 3x ULN), 1 case of toxic epidermal necrolysis secondary to imipenem use during an episode of febrile neutropenia, 1 small bowel obstruction requiring surgical intervention, and 1 case of late grade 2 neurotoxicity presenting 3 years after treatment. Conclusions: In this small cohort of patients, first-line CYVE has shown to be highly effective (ORR 100%, CR 71%) with minimal long-term toxicity compared to that which is seen using it as a salvage therapy. When followed by autoSCT, long-term survival with preserved quality of life may be possible. A prospective study would be necessary to confirm these initial results in practice. Disclosures: No relevant conflicts of interest to declare.

Injectable nanobioplatforms capable of locally fighting the inflammation in osteoarticular diseases, by reducing the number of administrations and prolonging the therapeutic effect is highly challenging. β-Cyclodextrin cationic polymers are promising cartilage-penetrating candidates by intra-articular injection due to the high biocompatibility and ability to entrap multiple therapeutic and diagnostic agents, thus monitoring and mitigating inflammation. In this study, nanoassemblies based on poly-β-amino-cyclodextrin (PolyCD) loaded with the non-steroidal anti-inflammatory drug diclofenac (DCF) and linked by supramolecular interactions with a fluorescent probe (adamantanyl-Rhodamine conjugate, Ada-Rhod) were developed to manage inflammation in osteoarticular diseases. PolyCD@Ada-Rhod/DCF supramolecular nanoassemblies were characterized by complementary spectroscopic techniques including UV-Vis, steady-state and time-resolved fluorescence, DLS and ζ-potential measurement. Stability and DCF release kinetics were investigated in medium mimicking the physiological conditions to ensure control over time and efficacy. Biological experiments evidenced the efficient cellular internalization of PolyCD@Ada-Rhod/DCF (within two hours) without significant cytotoxicity in primary human bone marrow-derived mesenchymal stromal cells (hMSCs). Finally, polyCD@Ada-Rhod/DCF significantly suppressed IL-1β production in hMSCs, revealing the anti-inflammatory properties of these nanoassemblies. With these premises, this study might open novel routes to exploit original CD-based nanobiomaterials for the treatment of osteoarticular diseases.

e13006 Background: Postoperative radiotherapy for glioma has been shown to improve survival with increased radiation doses. Dose escalation of external beam radiotherapy or brachytherapy is limited by normal brain radionecrosis. Radiolabeled targeting molecules can deliver localized radiation to tumor and reduce normal brain radionecrosis. TM601, or synthetic Chlorotoxin, is a peptide derived from scorpion venom that specifically binds to tumor cells. Here we report dosimetry results of an imaging sub-study of a phase II trial, in which weekly doses of 131I-TM601 were infused into surgically created tumor resection cavities for 3 or 6 weeks. Methods: Five out of 76 patients treated in a phase II trial were imaged after receiving 1, 3, or 6 doses of 40 mCi/0.8 mg 131I-TM601 intracavitarily. For each imaging study, 5 sequential SPECT images (1–168 hour) were registered with MRI to determine the 131I-TM601 radiation dose to the 2-cm tumor cavity margin. Five sequential body scans were also acquired to determine 131I-TM601 radiation dose to extra-cranial organs. Results: 131I-TM601 is a rapidly penetrating and clearing radiolabeled peptide. The median residual activity in the cavity at 7 days post injection was 8.4%. Median radiation dose to the cavity margin was 121 cGy/mCi and ranged 52- 338 cGy/mCi in 5 subjects. The median coefficient of variation (intra-patient inter-fraction) for the 2-cm margin dose was 14.7% and ranged 7.1–18.9%. Median tumor cavity volume was 11.4 mL, and ranged 5.2 - 35.5 mL. There was no observed correlation between the 2-cm margin dose and the cavity volume. Median radiation dose to thyroid, kidneys, red marrow, and body was 8.3, 1.3, 0.4, and 0.6 cGy/mCi, respectively. Conclusions: Radiation dose ratio for 2-cm cavity margin-to-normal tissues was quite high. While intra-patient reproducibility was relatively good, cumulative effect of the residual activity was only meaningful within a week. These results support the multi-dose fractionation scheme for 131I-TM601 to minimize normal tissue toxicity, including radiation necrosis, and extend continuous irradiation to clinical or sub-clinical residual tumor cells after surgery. [Table: see text]

I was born illegitimate. Born on an existential precipice. My unwed mother was 36 years old when she relinquished me. I was the fourth baby she was required to give away. After I emerged blood stained and blue tinged – abject, liminal – not only did the nurses refuse me my mother’s touch, I also lost the sound of her voice. Her smell. Her heart beat. Her taste. Her gaze. The silence was multi-sensory. When they told her I was dead, I also lost, within her memory and imagination, my life. I was adopted soon after but not told for over four decades. It was too shameful for even me to know. Imprinted at birth with a psychological ‘death’, I fell, as a Late Discovery Adoptee (LDA), into a socio-cultural and psychological abyss, frozen at birth at the bottom of a parturitive void from where, invisible within family, society, and self I was unable to form an undamaged sense of being.Throughout the 20th century (and for centuries before) this kind of ‘social abortion’ was the dominant script. An adoptee was regarded as a bastard, born of sin, the mother blamed, the father exonerated, and silence demanded (Lynch 28-74). My adoptive mother also sinned. She was infertile. But, in taking me on, she assumed the role of a womb worthy woman, good wife, and, in her case, reluctant mother (she secretly didn’t want children and was privately overwhelmed by the task). In this way, my mother, my adoptive mother, and myself are all the daughters of bereavement, all of us sacrificed on the altar of prejudice and fear that infertility, sex outside of marriage, and illegitimacy were unspeakable crimes for which a price must be paid and against which redemptive protection must be arranged. If, as Thomas Keneally (5) writes, “original sin is the mother fluid of history” then perhaps all three of us all lie in its abject waters. Grotevant, Dunbar, Kohler and Lash Esau (379) point out that adoption was used to ‘shield’ children from their illegitimacy, women from their ‘sexual indiscretions’, and adoptive parents from their infertility in the belief that “severing ties with birth family members would promote attachment between adopted children and parents”. For the adoptee in the closed record system, the socio/political/economic vortex that orchestrated their illegitimacy is born out of a deeply, self incriminating primal fear that reaches right back into the recesses of survival – the act of procreation is infested with easily transgressed life and death taboos within the ‘troop’ that require silence and the burial of many bodies (see Amanda Gardiner’s “Sex, Death and Desperation: Infanticide, Neonaticide, and Concealment of Birth in Colonial Western Australia” for a palpable, moving, and comprehensive exposition on the links between 'illegitimacy', the unmarried mother and child murder). As Nancy Verrier (24) states in Coming Home to Self, “what has to be understood is that separation trauma is an insidious experience, because, as a society, we fail to see this experience as a trauma”. Indeed, relinquishment/adoption for the baby and subsequent adult can be acutely and chronically painful. While I was never told the truth of my origins, of course, my body knew. It had been there. Sentient, aware, sane, sensually, organically articulate, it messaged me (and anyone who may have been interested) over the decades via the language of trauma, its lexicon and grammar cellular, hormonal, muscular (Howard & Crandall, 1-17; Pert, 72), the truth of my birth, of who I was an “unthought known” (Bollas 4). I have lived out my secret fatality in a miasmic nebula of what I know now to be the sequelae of adoption psychopathology: nausea, physical and psychological pain, agoraphobia, panic attacks, shame, internalised anger, depression, self-harm, genetic bewilderment, and generalised anxiety (Brodzinsky 25-47; Brodzinsky, Smith, & Brodzinsky 74; Kenny, Higgins, Soloff, & Sweid xiv; Levy-Shiff 97-98; Lifton 210-212; Verrier The Primal Wound 42-44; Wierzbicki 447-451) – including an all pervading sense of unreality experienced as dissociation (the experience of depersonalisation – where the self feels unreal – and derealisation – where the world feels unreal), disembodiment, and existential elision – all characteristics of Post Traumatic Stress Disorder (PTSD). In these ways, my body intervened, acted out, groaned in answer to the social overlay, and from beyond “the dermal veil” tried to procure access, as Vicky Kirby (77) writes, to “the body’s opaque ocean depths” through its illnesses, its eloquent, and incessantly aching and silent verbosities deepened and made impossibly fraught because I was not told. The aim of this paper is to discuss one aspect of how my body tried to channel the trauma of my secret fatality and liminality: my pre-disclosure art work (the cellular memory of my trauma also expressed itself, pre-disclosure, through my writings – poetry, journal entries – and also through post-coital glossolalia, all discussed at length in my Honours research “Womb Tongues” and my Doctoral Dissertation “The Womb Artist – A Novel: Translating Pre-verbal Late Discovery Adoption Trauma into Narrative”). From the age of thirty onwards I spent twelve years in therapy where the cause of my childhood and adult psychopathology remained a mystery. During this time, my embodied grief and memories found their way into my art work, a series of 5’ x 3’ acrylic paintings, some of which I offer now for discussion (figures 1-4). These paintings map and express what my body knew but could not verbalise (without language to express my grief, my body found other ways to vent). They are symptom and sign of my pre-verbal adoption trauma, evidence that my body ‘knew’ and laboured ceaselessly and silently to find creative ways to express the incarcerated trauma. Post disclosure, I have used my paintings as artefacts to inform, underpin, and nourish the writing of a collection of poetry “Womb Tongues” and a literary novel/memoir “The Womb Artist” (TWA) in an ongoing autoethnographical, performative, and critical inquiry. My practice-led research as a now conscious and creative witness, fashions the recontextualisation of my ‘self’ into my ‘self’ and society, this time with cognisant and reparative knowledge and facilitates the translation of my body’s psychopathology and memory (explicit and implicit) into a healing testimony that explores the traumatised body as text and politicizes the issues surrounding LDAs (Riley 205). If I use these paintings as a memoirist, I use them second hand, after the fact, after they have served their initial purpose, as the tangible art works of a baby buried beneath a culture’s prejudice, shame, and judgement and the personal cries from the illegitimate body/self. I use them now to explore and explain my subclinical and subterranean life as a LDA.My pre-disclosure paintings (Figures 1-4) – filled with vaginal, fetal, uterine, and umbilical references – provide some kind of ‘evidence’ that my body knew what had happened to me as if, with the tenacity of a poltergeist, my ‘spectral self’ found ways to communicate. Not simply clues, but the body’s translation of the intra-psychic landscape, a pictorial and artistic séance into the world, as if my amygdala – as quasar and signal, homing device and history lesson (a measure, container, and memoir) – knew how to paint a snap shot or an x-ray of the psyche, of my cellular marrow memories (a term formulated from fellow LDA Sandy McCutcheon’s (76) memoir, The Magician’s Son when he says, “What I really wanted was the history of my marrow”). If, as Salveet Talwar suggests, “trauma is processed from the body up”, then for the LDA pre-discovery, non-verbal somatic signage is one’s ‘mother tongue’(25). Talwar writes, “non-verbal expressive therapies such as art, dance, music, poetry and drama all activate the sub-cortical regions of the brain and access pre-verbal memories” (26). In these paintings, eerily divinatory and pointed traumatic, memories are made visible and access, as Gussie Klorer (213) explains in regard to brain function and art therapy, the limbic (emotional) system and the prefrontal cortex in sensorimotor integration. In this way, as Marie Angel and Anna Gibbs (168) suggest, “the visual image may serve as a kind of transitional mode in thought”. Ruth Skilbeck in her paper First Things: Reflections on Single-lens Reflex Digital Photography with a Wide-angled Lens, also discusses (with reference to her photographic record and artistic expression of her mother’s death) what she calls the “dark matter” – what has been overlooked, “left out”, and/or is inexplicable (55) – and the idea of art work as the “transitional object” as “a means that some artists use, conceptually and yet also viscerally, in response to the extreme ‘separation anxiety’ of losing a loved one, to the void of the Unknown” (57). In my case, non-disclosure prevented my literacy and the evolution of the image into language, prevented me from fully understanding the coded messages left for me in my art work. However, each of my paintings is now, with the benefit of full disclosure, a powerful, penetrating, and comprehensible intra and extra sensory cry from the body in kinaesthetic translation (Lusebrink, 125; Klorer, 217). In Figure 1, ‘Embrace’, the reference to the umbilical is palpable, described in my novel “The Womb Artist” (184) this way; “two ropes tightly entwine as one, like a dark and dirty umbilical cord snaking its way across a nether world of smudged umbers”. There is an ‘abject’ void surrounding it. The cord sapped of its colour, its blood, nutrients – the baby starved of oxygen, breath; the LDA starved of words and conscious understanding. It has two parts entwined that may be seen in many ways (without wanting to reduce these to static binaries): mother/baby; conscious/unconscious; first person/third person; child/adult; semiotic/symbolic – numerous dualities could be spun from this embrace – but in terms of my novel and of the adoptive experience, it reeks of need, life and death, a text choking on the poetic while at the same time nourished by it; a text made ‘available’ to the reader while at the same narrowing, limiting, and obscuring the indefinable nature of pre-verbal trauma. Figure 1. Embrace. 1993. Acrylic on canvas.The painting ‘Womb Tongues’ (Figure 2) is perhaps the last (and, obviously, lasting) memory of the infinite inchoate universe within the womb, the umbilical this time wrapped around in a phallic/clitorial embrace as the baby-self emerges into the constrictions of a Foucauldian world, where the adoptive script smothers the ‘body’ encased beneath the ‘coils’ of Judeo-Christian prejudice and centuries old taboo. In this way, the reassigned adoptee is an acute example of power (authority) controlling and defining the self and what knowledge of the self may be allowed. The baby in this painting is now a suffocated clitoris, a bound subject, a phallic representation, a gagged ‘tongue’ in the shape of the personally absent (but socially imposing) omni-present and punitive patriarchy. Figure 2. Womb Tongues. 1997. Acrylic on canvas.‘Germination’ (Figure 3) depicts an umbilical again, but this time as emerging from a seething underworld and is present in TWA (174) this way, “a colony of night crawlers that writhe and slither on the canvas, moving as one, dozens of them as thin as a finger, as long as a dream”. The rhizomic nature of this painting (and Figure 4), becomes a heaving horde of psychosomatic and psychopathological influences and experiences, a multitude of closely packed, intense, and dendridic compulsions and symptoms, a mass of interconnected (and by nature of the silence and lie) subterranean knowledges that force the germination of a ‘ghost baby/child/adult’ indicated by the pale and ashen seedling that emerges above ground. The umbilical is ghosted, pale and devoid of life. It is in the air now, reaching up, as if in germination to a psychological photosynthesis. There is the knot and swarm within the unconscious; something has, in true alien fashion, been incubated and is now emerging. In some ways, these paintings are hardly cryptic.Figure 3. Germination.1993. Acrylic on canvas.In Figure 4 ‘The Birthing Tree’, the overt symbolism reaches ‘clairvoyant status’. This could be read as the family ‘tree’ with its four faces screaming out of the ‘branches’. Do these represent the four babies relinquished by our mother (the larger of these ‘beings’ as myself, giving birth to the illegitimate, silenced, and abject self)? Are we all depicted in anguish and as wraithlike, grotesquely simplified into pure affect? This illegitimate self is painted as gestating a ‘blue’ baby, near full-term in a meld of tree and ‘self’, a blue umbilical cord, again, devoid of blood, ghosted, lifeless and yet still living, once again suffocated by the representation of the umbilical in the ‘bowels’ of the self, the abject part of the body, where refuse is stored and eliminated: The duodenum of the damned. The Devil may be seen as Christopher Bollas’s “shadow of the object”, or the Jungian archetypal shadow, not simply a Judeo-Christian fear-based spectre and curmudgeon, but a site of unprocessed and, therefore, feared psychological material, material that must be brought to consciousness and integrated. Perhaps the Devil also is the antithesis to ‘God’ as mother. The hell of ‘not mother’, no mother, not the right mother, the reluctant adoptive mother – the Devil as icon for the rich underbelly of the psyche and apophatic to the adopted/artificial/socially scripted self.Figure 4. The Birthing Tree. 1995. Acrylic on canvas.These paintings ache with the trauma of my relinquishment and LDA experience. They ache with my body’s truth, where the cellular and psychological, flesh and blood and feeling, leak from my wounds in unspeakable confluence (the two genital lips as the site of relinquishment, my speaking lips that have been sealed through non-disclosure and shame, the psychological trauma as Verrier’s ‘primal wound’) just as I leaked from my mother (and society) at birth, as blood and muck, and ooze and pus and death (Grosz 195) only to be quickly and silently mopped up and cleansed through adoption and life-long secrecy. Where I, as translator, fluent in both silence and signs, disclose the baby’s trauma, asking for legitimacy. My experience as a LDA sets up an interesting experiment, one that allows an examination of the pre-verbal/pre-disclosure body as a fleshed and breathing Rosetta Stone, as an interface between the language of the body and of the verbalised, painted, and written text. As a constructed body, written upon and invented legally, socially, and psychologically, I am, in Hélène Cixous’s (“To Live the Orange” 83) words, “un-forgetting”, “un-silencing” and “unearthing” my ‘self’ – I am re-writing, re-inventing and, under public scrutiny, legitimising my ‘self’. I am a site of inquiry, discovery, extrapolation, and becoming (Metta 492; Poulus 475) and, as Grosz (vii) suggests, a body with “all the explanatory power” of the mind. I am, as I embroider myself and my LDA experience into literary and critical texts, authoring myself into existence, referencing with particular relevance Peter Carnochan’s (361) suggestion that “analysis...acts as midwife to the birth of being”. I am, as I swim forever amorphous, invisible, and unspoken in my mother’s womb, fashioning a shore, landscaping my mind against the constant wet, my chronic liminality (Rambo 629) providing social landfall for other LDAs and silenced minorities. As Catherine Lynch (3) writes regarding LDAs, “Through the creation of text and theory I can formulate an intimate space for a family of adoptive subjects I might never know via our participation in a new discourse in Australian academia.” I participate through my creative, self-reflexive, process fuelled (Durey 22), practice-led enquiry. I use the intimacy (and also universality and multiplicity) and illegitimacy of my body as an alterative text, as a site of academic and creative augmentation in the understanding of LDA issues. The relinquished and silenced baby and LDA adult needs a voice, a ‘body’, and a ‘tender’ place in the consciousness of society, as Helen Riley (“Confronting the Conspiracy of Silence” 11) suggests, “voice, validation, and vindication”. Judith Herman (3) argues that, “Survivors challenge us to reconnect fragments, to reconstruct history, to make meaning of their present symptoms in the light of past events”. I seek to use the example of my experience – as Judith Durey (31) suggests, in “support of evocative, creative modes of representation as valid forms of research in their own right” – to unfurl the whole, to give impetus and precedence for other researchers into adoption and advocate for future babies who may be bought, sold, arranged, and/or created by various means. The recent controversy over Gammy, the baby boy born with Down Syndrome in Thailand, highlights the urgent and moral need for legislation with regard to surrogacy (see Kajsa Ekis Ekman’s Being and Being Bought: Prostitution, Surrogacy and the Split Self for a comprehensive examination of surrogacy issues). Indeed, Catherine Lynch in her paper Doubting Adoption Legislation links the experiences of LDAs and the children of born of surrogacy, most effectively arguing that, “if the fate that closed record adoptees suffered was a misplaced solution to the question of what to do with children already conceived how can you justify the deliberate conception of a child with the intention even before its creation of cruelly removing that child from their mother?” (6). Cixous (xxii) confesses, “All I want is to illustrate, depict fragments, events of human life and death...each unique and yet at the same time exchangeable. Not the law, the exception”. I, too, am a fragment, an illustration (a painting), and, as every individual always is – paradoxically – a communal and, therefore, deeply recognisable and generally applicable minority and exception. In my illegitimacy, I am some kind of evidence. Evidence of cellular memory. Evidence of embodiment. Evidence that silenced illegitimacies will manifest in symptom and non-verbal narratives, that they will ooze out and await translation, verification, and witness. This paper is offered with reverence and with feminist intention, as a revenant mouthpiece for other LDAs, babies born of surrogacy, and donor assisted offspring (and, indeed, any) who are marginalised, silenced, and obscured. It is also intended to promote discussion in the psychological and psychoanalytic fields and, as Helen Riley (202-207) advocates regarding late discovery offspring, more research within the social sciences and the bio-medical field that may encourage legislators to better understand what the ‘best interests of the child’ are in terms of late discovery of origins and the complexity of adoption/conception practices available today. As I write now (and always) the umbilical from my paintings curve and writhe across my soul, twist and morph into the swollen and throbbing organ of tongues, my throat aching to utter, my hands ready to craft latent affect into language in translation of, and in obedience to, my body’s knowledges. It is the art of mute witness that reverses genesis, that keeps the umbilical fat and supple and full of blood, and allows my conscious conception and creation. 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Background: Plasma Rich in Growth Factors (PRGF) is a mixture of autologous proteins and growth factors, prepared from a certain volume of platelet-rich plasma obtained from a small volume of blood, which does not contain leukocytes. Aim: The aim of the study was to evaluate the clinical and radiological efficacy of Plasma rich in growth factors (PRGF) in adjunct to open flap debridement (OFD) and intra-marrow penetration (IMP) compared to OFD and IMP alone for management of periodontal intra-osseous defects in periodontitis patients. Material and methods: Twenty patients with forty contra-lateral sites presenting with >5mm pocket depth and >3mm of intra-bony defect component were recruited in this double blind, split-mouth randomized controlled trial. The experimental site was surgically treated with PRGF in adjunct to OFD and IMP; and the control sites were treated with OFD and IMP alone. The clinical parameters like site specific plaque index (SSPI), site specific gingival index (SSGI), probing pocket depth (PPD), relative attachment level (RAL), gingival marginal level (GML), site-specific bleeding on probing (SSBOP) were recorded at baseline, 3, 6 and 9 months. The radiological parameters like intra-bony defect depth (IBDD), intra-bony defect area (IBDA) and percentage intra-bony defect area fill (%IBDAF) was recorded at baseline, 6 and 9 months. The patient reported outcomes on swelling, bleeding and level of pain in the area treated were also assessed at day 1 to day7. Results: No significant difference was observed for PI, GI and PPD. A Significant favorable improvement in GML was observed in PRGF treated group at all time points, suggesting continuous vertical creeping of the free gingival margin in the PRGF group at 3, 6 and 9 months. The clinical attachment gain (CAG) was significantly higher in the PRGF group at 3 months (p=0.005) and borderline significance at 6 months (p=0.067). The linear radiographic bone gain, i.e, change in IBDD, was significantly higher in the PRGF treated group at 6 months (p=0.02). At 6 months, the PRGF was significantly superior to the OFD (50% Vs 15%) in the number of sites that achieved CAG by 1.5 mm and linear radiographic bone gain of 1.0 mm. At 9 months, the PRGF was border-line significance than the OFD (83% Vs 50%) in the number of sites that achieved CAG by 1.5 mm and linear radiographic bone gain of 1.0 mm. Conclusion: PRGF was found to beneficial in terms of improved clinical attachment gain and radiographic linear bone gain, when used in adjunct to OFD and IMP for management of periodontal intra-osseous defects.