Tolerability and outcome of palliative treatment for metastatic pulmonary carcinoma in cats.

OBJECTIVES: Pulmonary carcinoma is uncommon in cats and reporting of outcomes following medical treatment is limited, especially in presence of metastases. The aim of this study was to describe the outcome of cats affected by metastatic primary pulmonary carcinoma and to evaluate the tolerability of palliative treatment in this patient population. MATERIALS AND METHODS: Medical records were searched for cats with a cytological or histopathological diagnosis of primary pulmonary carcinoma and evidence of metastatic disease. Cats were treated with antineoplastic agents, corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs) or received no systemic treatment. Cases in which thoracic CT was not performed, and those lacking definitive diagnosis by cytology or histopathology or receiving curative-intent surgery were excluded. RESULTS: Thirty-four cats were identified: 18 were treated with antineoplastic agents and 16 received corticosteroids, NSAIDs or no treatment. Presenting clinical signs included coughing (53%), tachypnoea (26%), gastrointestinal signs (35%) and lethargy (18%). CT scan identified metastases to the lung parenchyma in all cases and additional metastatic lesions in 10 of 34 (59%) cases; pleural effusion was detected in 11 cases (32%). The overall median survival time for all cats was 64 days [range 1-1352 days; 95% confidence interval (CI) 48-164]. Presence of respiratory signs at presentation was the only factor influencing survival in the multivariable analysis. CLINICAL SIGNIFICANCE: Medical treatment was well tolerated and appeared to palliate clinical signs in cats with metastatic pulmonary carcinoma, albeit with a modest duration and short overall survival. The role and benefit of chemotherapy/antineoplastic agents versus conventional palliative drugs in this setting remains unclear.

Boundary spanning at the science-policy interface: the practitioners' perspectives.

Cultivating a more dynamic relationship between science and policy is essential for responding to complex social challenges such as sustainability. One approach to doing so is to "span the boundaries" between science and decision making and create a more comprehensive and inclusive knowledge exchange process. The exact definition and role of boundary spanning, however, can be nebulous. Indeed, boundary spanning often gets conflated and confused with other approaches to connecting science and policy, such as science communication, applied science, and advocacy, which can hinder progress in the field of boundary spanning. To help overcome this, in this perspective, we present the outcomes from a recent workshop of boundary-spanning practitioners gathered to (1) articulate a definition of what it means to work at this interface ("boundary spanning") and the types of activities it encompasses; (2) present a value proposition of these efforts to build better relationships between science and policy; and (3) identify opportunities to more effectively mainstream boundary-spanning activities. Drawing on our collective experiences, we suggest that boundary spanning has the potential to increase the efficiency by which useful research is produced, foster the capacity to absorb new evidence and perspectives into sustainability decision-making, enhance research relevance for societal challenges, and open new policy windows. We provide examples from our work that illustrate this potential. By offering these propositions for the value of boundary spanning, we hope to encourage a more robust discussion of how to achieve evidence-informed decision-making for sustainability.

Inter- and intra-rater reliability and agreement in determining subcutaneous tumour margins in dogs.

The objective of this prospective study was to evaluate agreement and reliability of calliper-based measurements of locally invasive subcutaneous malignant tumours in dogs. Four raters measured the longest diameter of 12 subcutaneous tumours (7 soft tissue sarcomas and 5 mast cell tumours) from 11 client-owned dogs during 3 randomized, blinded measurement trials, both pre- and post-sedation. Inter- and intra-rater reliability was evaluated using intra-class correlation coefficient (ICC) and agreement was evaluated using Bland-Altman plots. Inter- and intra-rater reliability was good (ICC range of 0.8694-0.89520) and excellent (ICC range of 0.9720-0.9966), respectively. For agreement calculations, an a priori clinically relevant limit of agreement of 10 mm was set. Inter- and intra-rater agreement was unacceptable with inter-rater limits of agreement ranging from 15.9 to 55.6 mm and intra-rater limit of agreement ranging from 11.9 to 28.1 mm. Review of the measurement trial photographs revealed that calliper orientation changes were frequent, occurring in 9/12 (75%) and 8/12 (67%) pre- and post-sedation cases. No significant correlation was found between inter-rater measurement standard deviations and calliper orientation changes or dog body condition score. These findings suggest veterinarians may have poor agreement in determining the gross edge of tumours, which is expected to introduce bias and inconsistency in tumour staging, assessing response to therapy, and surgical margin planning. Due to the potential consequences for veterinary cancer patients, future studies are needed to validate the present findings.

Low-grade gastrointestinal lymphoma in dogs: 20 cases (2010 to 2016).

OBJECTIVES: To report the clinical presentation, treatment and prognosis of dogs with low-grade gastrointestinal lymphoma. MATERIALS AND METHODS: Cases were solicited from the American College of Veterinary Internal Medicine Oncology Diplomate listserv. Medical records of dogs with low-grade gastrointestinal lymphoma diagnosed via a combination of histology and immunohistochemistry with or without analysis of polymerase chain reaction for antigen receptor rearrangement were included. Signalment, clinical signs, diagnostic test results, chemotherapy protocol, response to treatment, date of first progression, rescue therapies and date and cause of death or last follow-up visit were collected. RESULTS: Twenty cases were included. Males and small breed dogs were over-represented. Frequent clinical signs included weight loss, vomiting and diarrhoea. Most lymphomas were T-cell phenotype (95%), and epitheliotropism was commonly described (60%). Immunohistochemistry, polymerase chain reaction for antigen receptor rearrangement or both were frequently required for definitive diagnosis. Two dogs had resection of an intestinal mass, and all dogs were treated with chemotherapy; chlorambucil and prednisone were most commonly prescribed. Overall response rate was 70%, and median survival time was 424 days (95% confidence interval: 105 to 1206 days). CLINICAL SIGNIFICANCE: Low-grade gastrointestinal lymphoma appears to be a rare condition in dogs, and treatment with chemotherapy results in a high response rate and favourable survival times. Further study is needed to determine its prevalence in dogs with chronic enteropathies.

An outbreak of Escherichia coli O157:H7 infections following a dairy education school field trip in Washington state, 2015.

On 27 April 2015, Washington health authorities identified Escherichia coli O157:H7 infections associated with dairy education school field trips held in a barn 20-24 April. Investigation objectives were to determine the magnitude of the outbreak, identify the source of infection, prevent secondary illness transmission and develop recommendations to prevent future outbreaks. Case-finding, hypothesis generating interviews, environmental site visits and a case-control study were conducted. Parents and children were interviewed regarding event activities. Odds ratios (OR) and 95% confidence intervals (CI) were computed. Environmental testing was conducted in the barn; isolates were compared to patient isolates using pulsed-field gel electrophoresis (PFGE). Sixty people were ill, 11 (18%) were hospitalised and six (10%) developed haemolytic uremic syndrome. Ill people ranged in age from <1 year to 47 years (median: 7), and 20 (33%) were female. Twenty-seven case-patients and 88 controls were enrolled in the case-control study. Among first-grade students, handwashing (i.e. soap and water, or hand sanitiser) before lunch was protective (adjusted OR 0.13; 95% CI 0.02-0.88, P = 0.04). Barn samples yielded E. coli O157:H7 with PFGE patterns indistinguishable from patient isolates. This investigation provided epidemiological, laboratory and environmental evidence for a large outbreak of E. coli O157:H7 infections from exposure to a contaminated barn. The investigation highlights the often overlooked risk of infection through exposure to animal environments as well as the importance of handwashing for disease prevention. Increased education and encouragement of infection prevention measures, such as handwashing, can prevent illness.

Characterizing Microscopical Invasion Patterns in Canine Mast Cell Tumours and Soft Tissue Sarcomas.

Stromal invasion is identified commonly in cutaneous malignancies; however, invasive patterns are defined inconsistently and their clinical relevance is uncertain. This study aimed to define objective, quantifiable histomorphological invasive patterns in low-grade canine mast cell tumours (MCTs) and grade I/II soft tissue sarcomas (STSs), and correlate invasive patterns with overall excisional status. Haematoxylin and eosin-stained glass slides prepared for routine histopathology of surgically-excised tumours from client-owned dogs were evaluated for invasion beyond their subgross edge, asymmetrical invasion, satellite lesions, lymphovascular invasion, perineurovascular growth, growth along fascial planes, intramuscular invasion and multicompartmental involvement. Digital histological tumour-free margins <1 mm in any direction were considered to represent an incomplete excision. Fifty-one dogs with 69 tumours (50 MCTs and 19 STSs) were included in the study. Invasion in both circumferential and deep directions was significantly greater in MCTs compared with STSs (exact 2-tailed P <0.0001 circumferential; P = 0.0095 deep). Within the MCT group, circumferential invasion was greater than deep invasion (P = 0.0076). Multivariate logistic regression analysis found two variables that were significantly associated with incomplete MCT excision: intraoperative grossly normal circumferential surgical margin size (odds ratio of 0.776, 95% confidence interval: 0.651-0.925) and asymmetry invasion index (odds ratio of 1.318, 95% confidence interval: 1.039-1.671). These data may help create evidence-based strategies for planning surgical resections of cutaneous malignancies. Presence of asymmetrical microscopical invasion might prompt pathologists to perform more comprehensive surgical margin evaluation.

BCL2 and MYC are expressed at high levels in canine diffuse large B-cell lymphoma but are not predictive for outcome in dogs treated with CHOP chemotherapy.

Diffuse large B-cell lymphoma (DLBCL) is the most common haematopoietic malignancy in dogs. Recently, MYC and BCL2 expression levels determined with immunohistochemistry (IHC) were found to be prognostic in people with DLBCL. We hypothesized that canine DLBCL can be similarly subdivided into prognostic subtypes based on expression of MYC and BCL2. Cases of canine DLBCL treated with CHOP chemotherapy were retrospectively collected and 43 dogs had available histologic tissue and complete clinical follow-up. Median values of percent immunoreactive versus immunonegative cells were used to determine positive or negative expression status. Completion of CHOP was significantly associated with a positive outcome. Compared with human patients, our canine DLBCL patients had high IHC expression of both MYC and BCL2, and relative expression levels of one or both markers were not associated with clinical outcome.

The challenge and impact of engaging hard-to-reach populations in regular physical activity and health behaviours: an examination of an English Premier League 'Football in the Community' men's health programme.

OBJECTIVES: To investigate the challenges that men from hard-to-reach (HTR) populations encounter when attempting to commit to regular participation in physical activity and health behaviours, and to explore the psychological and social effects of participation in a twelve week football-led health improvement intervention. STUDY DESIGN: A twelve week football specific physical activity intervention targeting men from HTR populations was delivered by Everton Football Clubs' Football in the Community (FitC) scheme as part of a national programme of men's health delivered in/by English Premier League (EPL) football clubs. Men living in homeless shelters and/or recovering from substance misuse were recruited over a period of three months. The programme consisted of a two hour football session, twice weekly, alongside the dissemination of healthy living messages. Football sessions were conducted by a qualified FitC coach. METHODS: This research was conducted during a twelve week period of immersed practitioner-research. Ethnographic and observational methodologies were adopted. Psychosocial issues were discussed with participants through informal client-researcher interactions and data were logged via field notes. Records of attendance were logged. Participants who failed to attend a session were contacted and their reason(s) for non-attendance were recorded. Data were analysed using deductive and inductive reasoning. RESULTS: Despite the apparent ambition of the participants to regularly participate in the FitC programme, adherence to the programme was poor. Economic, environmental and social barriers to engagement in the programme were apparent. Engagement in the programme resulted in positive psychosocial developments; the development of structure, social interaction and social capital. CONCLUSION: Community based football-led health improvement programmes endorsed by professional football clubs appear well positioned to connect with, and attract, men from HTR populations. The evidence suggests that such programmes can improve psychosocial health amongst these populations. However, a bottom-up programme design and management strategy is required in order to reduce the challenges facing HTR participants when attempting to regularly engage in physical activity and health behaviours.

Late effects in patients with Fanconi anemia following allogeneic hematopoietic stem cell transplantation from alternative donors.

Hematopoietic stem cell transplantation (HSCT) is curative for hematological manifestations of Fanconi anemia (FA). We performed a retrospective analysis of 22 patients with FA and aplastic anemia, myelodysplastic syndrome or acute myelogenous leukemia who underwent a HSCT at Memorial Sloan Kettering Cancer Center and survived at least 1 year post HSCT. Patients underwent either a TBI- (N=18) or busulfan- (N=4) based cytoreduction followed by T-cell-depleted transplants from alternative donors. Twenty patients were alive at time of the study with a 5- and 10-year overall survival of 100 and 84% and no evidence of chronic GvHD. Among the 18 patients receiving a TBI-based regimen, 11 (61%) had persistent hemochromatosis, 4 (22%) developed hypothyroidism, 7 (39%) had insulin resistance and 5 (27%) developed hypertriglyceridemia after transplant. Eleven of 16 evaluable patients (68%), receiving TBI, developed gonadal dysfunction. Two patients who received a TBI-based regimen died of squamous cell carcinoma. One patient developed hemochromatosis, hypothyroidism and gonadal dysfunction after busulfan-based cytoreduction. TBI appears to be a risk factor for malignant and endocrine late effects in the FA host. Multidisciplinary follow-up of patients with FA (including cancer screening) is essential for early detection and management of late complications, and improving long-term outcomes.

Horizontal nystagmus and multiple sclerosis using 3-Tesla magnetic resonance imaging.

BACKGROUND: Nystagmus in patients with multiple sclerosis (MS) is generally attributed to brainstem disease. Lesions in other regions may result in nystagmus. The identification of these other sites is enhanced by using 3-Tesla magnetic resonance imaging (3TMRI) due to increased signal-to-noise ratio. OBJECTIVE: We sought to evaluate the distribution of structural lesions and disruption of tracts in patients with horizontal nystagmus secondary to MS using 3TMRI. METHODS: Twenty-four patients (20 women, 4 men; age range 26-55 years) with horizontal nystagmus secondary to MS underwent 3TMRI brain scans; and 18 patients had diffusion tensor imaging (DTI) for tractography. RESULTS: Nystagmus was bidirectional in 11, right-sided in 6 and left-sided in 7. We identified 194 lesions in 20 regions within the neural integrator circuit in 24 patients; 140 were within the cortex and 54 were within the brainstem. Only two patients had no lesions in the cortex, and 9 had no lesions in the brainstem. There was no relationship between side of lesion and direction of nystagmus. Thirteen of 18 (72 %) had tract disruption with fractional anisotropy (FA) values below 0.2. FA was significantly lower in bidirectional compared to unidirectional nystagmus (p = 0.006). CONCLUSION: In MS patients with horizontal nystagmus, lesions in all cortical eye fields and their descending connections were evident. Technical improvements in tractography may help identify the specific site(s) resulting in nystagmus in MS.

Retrospective analysis for treatment of naïve canine multicentric lymphoma with a 15-week, maintenance-free CHOP protocol.

Standard of care treatment of dogs with multicentric lymphoma includes combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP); however, owners may be hesitant to commit the resources necessary to complete a lengthy, multi-drug protocol. One hundred thirty-four client-owned dogs with multicentric lymphoma were treated with a 15-week CHOP chemotherapy protocol. The overall response rate was 98% with 104 dogs experiencing a complete response (CR). The median progression-free survival (PFS) time for all dogs was 176 days, and the median disease-specific overall survival time was 311 days. Prognostic factors identified on multivariate analysis as significant for PFS included substage, immunophenotype, hospitalization for adverse events, need for dose reduction, presence of neutrophilia at diagnosis, presence of anemia and experiencing a CR as best response to therapy. In conclusion, this protocol may be a viable alternative to CHOP protocols using a larger number of treatments.

The use of novel lymphatic endothelial cell-specific immunohistochemical markers to differentiate cutaneous angiosarcomas in dogs.

Lymphangiosarcomas are uncommon vascular neoplasms that arise from lymphatic endothelial cells (LECs). They efface and replace normal subcutaneous tissue and are characterised by arborising, vascular channels lined by a single layer of pleomorphic endothelial cells and a paucity of erythrocytes. Lymphangiosarcomas are architecturally similar to hemangiosarcomas, a common malignancy of vascular origin arising from blood vascular endothelial cells. Common immunohistochemical markers for vascular endothelium, such as Factor VIII-related antigen (F8RA) and CD31, have traditionally been used to confirm the diagnosis of tumours of vascular origin. However, these markers fail to differentiate between lymphangiosarcoma and hemangiosarcoma, which often show overlapping morphologic features, disparate clinical behaviour and require different treatment modalities. Here we describe the use of two novel LEC-specific markers, lymphatic vessel endothelial receptor-1 (LYVE-1) and prospero-related homeobox gene-1 (PROX-1), to further differentiate between vascular tumours of lymphatic (lymphangiosarcoma) and blood (hemangiosarcoma) endothelial cell origin in the dog.

Lymphangiosarcoma in 12 dogs: a case series (1998-2013).

Lymphangiosarcoma (LAS) is an uncommon malignant neoplasia arising from lymphatic endothelium; little information exists regarding therapy. Single institutional retrospective review for canine LAS histopathology diagnoses over a 15-year period yielded 12 dogs. Ten dogs were presented for a mass and/or swelling at cervical, trunk or limb regions. Prior to diagnosis, 10 dogs received empiric wound therapy. Cytology performed in 10 consisted of mild inflammation. Survival ranged from 60, 168 and 876 days for three dogs with palliation; 90 days with prednisone in one; 182 days with chemotherapy in one; 240, 267, 487, 630 and 941 days for five receiving surgery; and 574 days for one receiving surgery, radiation and chemotherapy. One dog is alive with recurrence at 243 days following surgery and carboplatin chemotherapy. Clinical improvement existed in LAS dogs receiving multimodal therapies. Early tissue biopsies are recommended for progressive oedematous lesions of unknown origin.

Adolescent Experiences With Intrauterine Devices: A Qualitative Study.

PURPOSE: The purpose of this study was to improve understanding of adolescents' reasons for choosing an intrauterine device (IUD) and to explore experiences that led to continuation or discontinuation of the levonorgestrel intrauterine system (LNG-IUS) and the copper IUD (copper IUD). METHODS: We conducted focus groups (FGs) with adolescents and young women who were current or former IUD users stratified by IUD type and 12-month IUD continuation or discontinuation. All subjects were participants from the Contraceptive CHOICE Project. FG data were supplemented with in-depth interviews (IDIs). Data collection was continued until thematic saturation was reached. Transcripts were independently coded by two researchers, and interrater reliability was calculated using a Kappa coefficient. Analysis followed a standard text-analysis approach. RESULTS: Thirteen FGs and seven IDIs were conducted with 43 young women. Effectiveness, duration of use, convenience, and potential bleeding changes emerged as themes for both choosing and continuing IUDs. Some women chose the LNG-IUS to achieve amenorrhea, whereas copper IUD users wanted a nonhormonal method and continued menses. Copper IUD users cited expulsion and bleeding irregularities as reasons for discontinuation, whereas LNG-IUS users reported bleeding irregularities and continued pain as reasons for removal. IUD users noted an adjustment period of weeks to months in which side effects were present before lessening. CONCLUSIONS: Effectiveness, duration of use, convenience, and potential changes in bleeding patterns drove adolescents' choice and continuation of an IUD. Bleeding changes and pain contributed to IUD discontinuation. Discussion of effectiveness, duration and convenience, and anticipatory guidance regarding post-insertion side effects may be important in counseling young women about IUDs.

IL-12-secreting CD19-targeted cord blood-derived T cells for the immunotherapy of B-cell acute lymphoblastic leukemia.

Disease relapse or progression is a major cause of death following umbilical cord blood (UCB) transplantation (UCBT) in patients with high-risk, relapsed or refractory acute lymphoblastic leukemia (ALL). Adoptive transfer of donor-derived T cells modified to express a tumor-targeted chimeric antigen receptor (CAR) may eradicate persistent disease after transplantation. Such therapy has not been available to UCBT recipients, however, due to the low numbers of available UCB T cells and the limited capacity for ex vivo expansion of cytolytic cells. We have developed a novel strategy to expand UCB T cells to clinically relevant numbers in the context of exogenous cytokines. UCB-derived T cells cultured with interleukin (IL)-12 and IL-15 generated >150-fold expansion with a unique central memory/effector phenotype. Moreover, UCB T cells were modified to both express the CD19-specific CAR, 1928z, and secrete IL-12. 1928z/IL-12 UCB T cells retained a central memory-effector phenotype and had increased antitumor efficacy in vitro. Furthermore, adoptive transfer of 1928z/IL-12 UCB T cells resulted in significantly enhanced survival of CD19(+) tumor-bearing SCID-Beige mice. Clinical translation of CAR-modified UCB T cells could augment the graft-versus-leukemia effect after UCBT and thus further improve disease-free survival of transplant patients with B-cell ALL.

Temporary sacral neuromodulation under local anaesthesia using new anatomical reference points.

BACKGROUND: Prior to implantation of an expensive sacral nerve stimulator, a 'screening phase' is undertaken. This report examines the feasibility of temporary sacral neuromodulation under local anaesthesia in an outpatient setting. We report on our technique, results and patient satisfaction. METHODS: Percutaneous nerve evaluation was performed in 184 patients using a new set of reference points and local anaesthesia to guide insertion of a test wire without the need for fluoroscopy in an outpatient setting. Three bony landmarks were used: tip of the coccyx, sacro-coccygeal joint and posterior superior iliac spine. The technical success was defined as stimulation in the perineal/anal area at amperages <6 mAmp. A consecutive cohort of 24 patients was asked to grade their pain and satisfaction regarding the procedure. RESULTS: Successful placement of the test wire was accomplished in 171 patients (93 %). Twelve patients required placement under fluoroscopy due to lack of sensation during stimulation (N = 7) procedural pain (N = 4) or failure to identify S3 or S4 (N = 2). There were two lead infections, one lead dislocation and one lead fracture. 22 of 24 patients (92 %) would recommend the procedure under local anaesthesia to other patients. CONCLUSIONS: Temporary sacral neuromodulation can be reliably performed in a more practical, less expensive outpatient setting under local anaesthesia without adversely influencing test outcome.

Does the presence of a high grade internal rectal prolapse affect the outcome of pelvic floor retraining in patients with faecal incontinence or obstructed defaecation?

AIM: Pelvic floor retraining is considered first-line treatment for patients with faecal incontinence or obstructed defaecation. There are at present no data on the effect of a high grade internal rectal prolapse on outcomes of pelvic floor retraining. The current study aimed to assess this influence. METHOD: In all, 120 consecutive patients were offered pelvic floor retraining. The predominant symptom was faecal incontinence in 56 patients (47%) and obstructed defaecation in 64 patients (53%). Patients were assessed before and after therapy using the Fecal Incontinence Severity Index (FISI), the Patient Assessment of Constipation Symptoms (PAC-SYM) score and the Gastrointestinal Quality of Life Index (GIQLI). Defaecography and anorectal manometry were performed in all patients before pelvic floor retraining. RESULTS: A high grade internal rectal prolapse was observed in 42 patients (35%). In patients with faecal incontinence without a high grade internal rectal prolapse, the FISI score decreased from 36 to 27 (P < 0.01). The FISI score did not change (32 vs 32; P = 0.93) in patients with a high grade internal rectal prolapse. The PAC-SYM score improved significantly (24 vs 19; P = 0.01) in patients with obstructed defaecation without a high grade rectal prolapse compared with no significant change (26 vs 25; P = 0.21) in patients with a high grade rectal prolapse. Quality of life (GIQLI) improved only in patients without a high grade internal rectal prolapse. CONCLUSION: Pelvic floor retraining may be useful in patients with defaecation disorders not associated with a high grade internal rectal prolapse. Patients with a high grade internal rectal prolapse may be considered for surgery from the outset.

Differences in regional bone metabolism at the spine and hip: a quantitative study using (18)F-fluoride positron emission tomography.

SUMMARY: This study showed that regional bone blood flow and (18)F-fluoride bone plasma clearance measured by positron emission tomography are three times lower at the hip than the lumbar spine. INTRODUCTION: Measurements of effective bone plasma flow (K (1)), bone plasma clearance (K ( i )) and standardised uptake values (SUV) using (18)F-fluoride positron emission tomography ((18)F-PET) provide a useful means of studying regional bone metabolism at different sites in the skeleton. This study compares the regional (18)F-fluoride kinetics and SUV at the hip and lumbar spine (LS). METHODS: Twelve healthy postmenopausal women with no history of metabolic bone disease apart from two with untreated osteoporosis were recruited. Each subject underwent 60-min dynamic (18)F-PET scans at the LS and proximal femur two weeks apart. K (1), K ( i ) and SUV were measured at the LS (mean of L(1)-L(4)), femoral neck (FN), total hip (TH) and femoral shaft (FS). Differences between sites were assessed using the nonparametric Kruskal-Wallis test with a Bonferroni correction for multiple comparisons. RESULTS: Values of K (1), K ( i ) and SUV at the FN, TH and FS were three times lower than at the LS (p = 0.003). Amongst the proximal femur sites, K ( i ) and SUV were lower at the FS compared with the FN and TH, and SUV was lower at the TH compared with the FN (all p < 0.05). The volume of distribution was lower at the TH and FS compared with the LS (p < 0.05). CONCLUSION: The lower values of K (1), K ( i ) and SUV at the hip suggest that lower bone blood flow in the proximal femur is an important factor explaining the principal reason for the differences in bone fluoride kinetics between the LS and hip sites.

Vascular-targeted photodynamic therapy with BF2-chelated Tetraaryl-Azadipyrromethene agents: a multi-modality molecular imaging approach to therapeutic assessment.

BACKGROUND: Photodynamic therapy (PDT) is a treatment modality for a range of diseases including cancer. The BF(2)-chelated tetraaryl-azadipyrromethenes (ADPMs) are an emerging class of non-porphyrin PDT agent, which have previously shown excellent photochemical and photophysical properties for therapeutic application. Herein, in vivo efficacy and mechanism of action studies have been completed for the lead agent, ADMP06. METHODS: A multi-modality imaging approach was employed to assess efficacy of treatment, as well as probe the mechanism of action of ADPM06-mediated PDT. RESULTS: Tumour ablation in 71% of animals bearing mammary tumours was achieved after delivery of 2 mg kg(-1) of ADPM06 followed immediately by light irradiation with 150 J cm(-2). The inherent fluorescence of ADPM06 was utilised to monitor organ biodistribution patterns, with fluorescence reaching baseline levels in all organs within 24 h. Mechanism of action studies were carried out using dynamic positron emission tomography and magnetic resonance imaging techniques, which, when taken together, indicated a decrease in tumour vascular perfusion and concomitant reduction in tumour metabolism over time after treatment. CONCLUSION: The encouraging treatment responses in vivo and vascular-targeting mechanism of action continue to indicate therapeutic benefit for this new class of photosensitiser.