The effect of uterine-derived mesenchymal stromal cells for the treatment of canine atopic dermatitis: A pilot study.

Canine atopic dermatitis (cAD) is a common allergic skin condition among dogs that may respond to treatment with mesenchymal stromal cells (MSCs). The aim of this pilot study was to evaluate the safety and efficacy of allogeneic uterine tissue-derived MSCs (UMSCs) for the reduction and control of clinical signs associated with cAD. At two sites, seven client-owned dogs with cAD received two doses of approximately 3.6 x 107 UMSCs given intravenously over 30 min, on Day 0 and Day 14, with monthly clinical follow-up until Day 90 and optional owner phone interview on Day 180. Primary outcomes were pruritus and skin lesions. Pruritus was measured by the owner-assessed Pruritus Visual Analog Scale (PVAS), with treatment success defined as a 2-point reduction in PVAS score at any timepoint after treatment. Skin lesions were evaluated by two veterinarians according to the Canine Atopic Dermatitis Extent and Severity Index (CADESI-4). The secondary outcome was safety, which was evaluated via physical exam and hematology, including complete blood count (CBC), serum chemistry, and urinalysis (UA). Treatment was generally well tolerated and associated with a significant reduction in PVAS on Day 30 that was maintained through Day 180. On Day 60, five dogs (71%) achieved treatment success (at least 2-point reduction in PVAS), and three dogs (43%) had a PVAS improvement of 4-5 points. Mean CADESI-4 score was significantly improved on Day 14, Day 30, Day 60, and Day 90, with the lowest mean score observed on Day 60. Three dogs exhibited mild and transient adverse events. These findings suggest that IV-administered allogeneic UMSCs reduce and control clinical signs of cAD, with a durable benefit lasting 3-6 months.

Impact of allogeneic feline uterine-derived mesenchymal stromal cell intravenous treatment on renal function of nephrectomized cats with chronic kidney disease.

Chronic kidney disease (CKD) is a common condition and leading cause of mortality in cats. Mesenchymal stromal cells (MSCs) may have a therapeutic effect on CKD. The aim of this pilot study was to determine efficacy of systemically-administered allogeneic uterine tissue-derived MSCs (UMSCs) in cats with CKD. Eighteen renal-compromised, unilaterally nephrectomized cats received two doses of 3 × 107 allogeneic UMSCs given intravenously (IV) with a 2-week dose interval. The primary endpoint was renal function, with treatment success defined by a 20% increase in glomerular filtration rate (GFR; iohexol clearance) and/or a 20% decrease in plasma creatinine in 50% of the cats. Secondary endpoints included diet and water consumption, body weight, urine characteristics, and adverse events. Treatment was well tolerated and associated with a statistically meaningful increase in GFR on Days 13, 28, 57, 99, 121 and 182, compared with baseline (P < 0.0001 for Days 13 to 99 inclusive; P = 0.0029 and P = 0.0225 for Days 121 and 182, respectively). Greater than 50% of the cats demonstrated a 20% increase in GFR on all days except Day 150, at which point GFR measurements were consistently above baseline. Statistically meaningful increases in diet and water consumption were observed. Substantial improvements in GFR were observed throughout the six-month evaluation period (excluding Day 150) in more than 50% of cats, thereby meeting the primary endpoint. Therefore, this IV-administered, allogeneic cellular therapy may support both renal function and clinical status of cats with CKD.

Financial costs for teaching in rural and urban Australian general practices: is there a difference?

OBJECTIVE: To determine if the financial costs of teaching GP registrars differs between rural and urban practices. DESIGN: Cost-benefit analysis of teaching activities in private GP for GP vocational training. Data were obtained from a survey of general practitioners in South Australia and Western Australia. SETTING AND PARTICIPANTS: General practitioners and practices teaching in association with the Adelaide to Outback General Practice Training Program or the Western Australian General Practice Training. MAIN OUTCOME MEASURES: Net financial effect per week per practice. RESULTS: At all the training levels, rural practices experienced a financial loss for teaching GP registrars, while urban practices made a small financial gain. The differences in net benefit between rural and urban teaching practices was significant at the GPT2/PRRT2 (-$515 per week 95% CI -$1578, -$266) and GPT3/PRRT3 training levels (-$396 per week, 95% CI (-$2568, -$175). The variables contributing greatest to the difference were the higher infrastructure costs for a rural practice and higher income to the practice from the GP registrars in urban practices. CONCLUSION: There were significant differences in the financial costs and benefits for a teaching rural practice compared with an urban teaching practice. With infrastructure costs which include accommodation, being a key contributor to the difference found, it might be time to review the level of incentives paid to practices in this area. If not addressed, this cost difference might be a disincentive for rural practices to participate in teaching.

Is different better?: models of teaching and their influence on the net financial outcome for general practice teaching posts.

BACKGROUND: In Australia, training for general practice (GP) occurs within private practices and their involvement in teaching can have significant financial costs. At the same time there are growing demands for clinical places for all disciplines and for GP there is concern that there are insufficient teaching practices to meet the demand at the medical student, prevocational and vocational training levels. One option to address this may be to change how teaching occurs in the practice. A question that arises in posing such an option is whether different models of teaching change the costs for a teaching practice. The aim of this study is to determine the net financial outcome of teaching models in private GP. METHODS: Modelling the financial implications for a range of teaching options using a costing framework developed from a survey of teaching practices in South Australia. Each option was compared with the traditional model of teaching where one GP supervisor is singularly responsible for one learner. The main outcome measure was net financial outcome per week. Decisions on the model cost parameters were made by the study's Steering Group which comprised of experienced GP supervisors. Four teaching models are presented. Model 1 investigates the gains from teaching multiple same level learners, Models 2 and 3, the benefits of vertically integrated teaching using different permutations, and Model 4 the concept of a GP teacher who undertakes all the teaching. RESULTS: There was a significant increase in net benefits of Aus$547 per week (95% confidence intervals $459, $668) to the practice when a GP taught two same level learners (Model 1) and when a senior registrar participated in teaching a prevocational doctor (Model 3, Aus$263, 95% confidence intervals $80, $570). For Model 2, a practice could significantly reduce the loss if a registrar was involved in vertically integrated teaching which included the training of a medical student (Aus$551, 95% confidence intervals $419, $718). The GP teacher model resulted in a net remuneration of Aus$207,335 per year, sourced predominantly from the GP teacher activities, with no loss to the practice. CONCLUSIONS: Our study costed teaching options that can maximise the financial outcomes from teaching. The inclusion of GP registrars in the teaching model or the supervisor teaching more than one same level learner results in a greater financial benefit. This gain was achieved through a reduction in supervisor teaching time and the sharing of administrative and teaching activities with GP registrars. We also show that a GP teacher who carries a minimal patient load can be a sustainable option for a practice. Further, the costing framework used for the teaching models presented in this study has the ability to be applied to any number of teaching model permutations.

Getting governance right for a sustainable regionalised business model.

The 1998 Ministerial Review of General Practice Training identified several areas for improvement that led to major changes in the provision of general practice training, including the establishment of General Practice Education and Training (GPET) and the regionalisation of training. The regionalised training business model has been in place for nearly 10 years, and several key organisations have been involved in its evolution, including the Australian Government, speciality colleges, GPET and regionalised training providers. Both the college-focused and regionalised-focused models have had some successes. These include recognition and support of general practice as a vocational specialty, increased numbers of junior doctors undertaking placements in general practice, and increased numbers of registrars training in rural areas. This period has also seen changes in the governance and decision-making processes with creation of a new framework that is inclusive of all the key players in the new regionalised training system. The future holds challenges for the regionalised training business model as the general practice education and training landscape becomes more complex. The framework in the current model will provide a base to help meet these challenges and allow for further sustainable expansion.

To teach or not to teach? A cost-benefit analysis of teaching in private general practice.

OBJECTIVE: To identify the financial costs and benefits associated with teaching in private general practice. DESIGN: Cost-benefit analysis of teaching in private general practice across three levels of training--undergraduate medical training, prevocational training and general practice vocational training--using data from a 2007 survey of general practitioners in South Australia. SETTING AND PARTICIPANTS: GPs and practices teaching in association with the Adelaide to Outback GP Training Program or the Discipline of General Practice at the University of Adelaide. MAIN OUTCOME MEASURE: Net financial outcome per week. RESULTS: The net financial outcome of teaching varied across the training levels. Practices incurred a net financial cost from teaching medical students that was statistically significantly different from zero. With respect to vocational training and teaching junior doctors, there were small net financial benefits to practices, although the mean estimates were not statistically significantly different from zero. CONCLUSIONS: This study shows a net financial cost for practices teaching medical students, while at the prevocational and vocational training levels, adequate levels of subsidies and income generated by the trainees help offset the costs of teaching. Our results suggest that a review of subsidies for undergraduate teaching is necessary, particularly as the demand for teaching practices will increase substantially over the next 5 years.

Teaching capacity in general practice: results from a survey of practices and supervisors in South Australia.

OBJECTIVE: To ascertain the teaching load of general practices, the capacity for expansion of general practice-based teaching and the support required to achieve this. DESIGN, SETTING AND PARTICIPANTS: Questionnaire-based survey of general practitioners and practices who were teaching medical students, junior doctors or GP registrars in partnership with the Adelaide to Outback GP Training Program or the Discipline of General Practice at the University of Adelaide in South Australia in 2007. MAIN OUTCOME MEASURES: Current teaching load of general practices; GPs' reasons for teaching; capacity of practices to increase teaching loads; and support required to realise practices' full teaching capacity. RESULTS: In 2007, the 76 practices involved in the survey taught, in total, 326 medical students, 39 junior doctors and 84 GP registrars. Exposing students and doctors to general practice was cited most often by the 194 GP respondents as the reason for teaching. Few practices rated the support payments for teaching as adequate or fairly adequate. A number of practices were able to increase their teaching load within their current levels, with most being able to teach more medical students (39% of practices) or registrars (42% of practices). All practices able to increase their teaching load stated that their capacity to expand was conditional on extra resources, including more physical space, subsidies and teachers. CONCLUSION: Scope exists to increase teaching in the general practices surveyed and is related to the level, or levels, of teaching undertaken by the practices. Targeted support seems essential if practices are to increase their teaching load.

Effect of intraarticular injection of autologous adipose-derived mesenchymal stem and regenerative cells on clinical signs of chronic osteoarthritis of the elbow joint in dogs.

Autologous adipose-derived mesenchymal stem cell (AD-MSC) therapy involves harvesting fat from the patient, isolating the stem and regenerative cells, and administering the cells back to the patient. Autologous AD-MSC therapy in veterinary regenerative medicine has been commercially available since 2003. Previously reported results from a blinded, controlled trial in dogs with chronic osteoarthritis of the coxofemoral (hip) joint demonstrated efficacy of a single intraarticular injection of autologous AD-MSC therapy. The primary objective of the current study was to evaluate the effectiveness of this therapy in dogs with chronic osteoarthritis of the humeroradial (elbow) joints and to determine the duration of effect. Fourteen dogs were recruited. Veterinarians assessed each dog for lameness, pain on manipulation, range of motion, and functional disability using a numeric rating scale at baseline and specified intervals up to 180 days after treatment. Statistically significant improvement in outcome measures was demonstrated.

Evaluation of a novel precision template-guided biopsy system for detecting prostate cancer.

OBJECTIVE: To explore the ability of a novel transrectal ultrasonography (TRUS) device (TargetScan, Envisioneering Medical Technologies, St. Louis MO) that creates a three-dimensional map of the prostate and calculates an optimal biopsy scheme, to accurately sample the prostate and define the true extent of disease, as standard TRUS-guided prostate biopsy relies on the operator to distribute the biopsy sites, often resulting in under- and oversampling regions of the gland. PATIENTS AND METHODS: In a multicentre retrospective chart review evaluating patients who had a TargetScan prostate biopsy between January 2006 and June 2007, we determined the overall cancer detection rate in all patients and in subgroups based on prostate specific antigen level, digital rectal examination, and indication for biopsy. We assessed the pathological significance of cancer detected, defined as a Gleason score of > or = 7, positive margins, extracapsular disease or > 20% tumour volume in the prostatectomy specimen. We also evaluated the concordance in Gleason score between the biopsy and prostatectomy specimen. RESULTS: Cancer was detected in 50 (35.7%) of the 140 patients biopsied, including 39 (47.6%) with no previous biopsies. Of 23 prostatectomy specimens, 20 (87%) had pathologically significant disease. The biopsy predicted the prostatectomy Gleason score in 12 patients (52%), overestimated in two (9%), underestimated in eight (35%), and biopsy Gleason score could not be assigned in one (4%). CONCLUSIONS: Template-guided biopsy potentially produces a higher cancer detection rate and more accurate assessment of grade. Prostatectomy specimens did not have a high rate of pathologically insignificant disease.

Characterization and differentiation of equine umbilical cord-derived matrix cells.

Stem cells are being evaluated in numerous human clinical trials and are commercially used in veterinary medicine to treat horses and dogs. Stem cell differentiation, homing to disease sites, growth and cytokine factor modulation, and low antigenicity contribute to their therapeutic success. Bone marrow and adipose tissue are the two most common sources of adult-derived stem cells in animals. We report on the existence of an alternative source of primitive, multipotent stem cells from the equine umbilical cord cellular matrix (Wharton's jelly). Equine umbilical cord matrix (EUCM) cells can be cultured, cryogenically preserved, and differentiated into osteo-, adipo-, chondrogenic, and neuronal cell lineages. These results identify a source of stem cells that can be non-invasively collected at birth and stored for future use in that horse or used as donor cells for treating unrelated horses.

A person-practice-program fit--evaluation of a GP training placement process.

BACKGROUND: The placement of general practice registrars in vocational training practices can be a difficult process if both educational and organisational needs are to be met. METHODS: A telephone survey of 22 registrars and 24 supervisors was conducted to evaluate the placement matching process used by the Adelaide To Outback (A2O) GP Training Program. RESULTS: Overall, registrars and supervisors were satisfied with all components of the placement matching process. The majority of interviewees reported the interview component of the process as being a positive experience. DISCUSSION: The evaluation has shown that the model developed by A2O is successful, allowing input by registrars and supervisors while remaining manageable for the training provider. It is also a transparent and equitable process for all involved and is flexible enough to meet different regional needs. A number of suggested areas for improvement can be integrated easily into the model.

The challenges of teaching in a general practice setting.

An attractive strategy to meet the increasing need for medical education is teaching in community general practice. General practice will be in a position to meet and sustain this need only if various conditions are met, including: Teaching is undertaken in general practice at all levels of medical education (medical student, postgraduate years 1-3 and GP vocational training); Standards and quality of teaching are maintained while the number of sites involved increases; Further Australian research is conducted into innovative models of general practice teaching and their cost-effectiveness; and Appropriate remuneration and infrastructure is available to support practices and general practitioners involved in teaching.

General practice placements for pre-registration junior doctors: adding value to intern education and training.

OBJECTIVE: To examine pre-registration junior doctors' perceptions of the value of a general practice term in their training program. DESIGN, SETTING AND PARTICIPANTS: Semi-structured interviews, in five teaching hospitals in South Australia in 2005, with 20 pre-registration junior doctors (interns) who had completed a general practice term and at least one core term of intern training. MAIN OUTCOME MEASURE: Comparisons between general practice and teaching hospital core training terms with respect to the domains of junior doctor education. RESULTS: Interns perceived general practice and teaching hospital terms to be complementary in their overall training program. The general practice term provided them with knowledge and skills they would not have acquired in the teaching hospital terms alone. One-on-one consulting, initiating patient management, and the opportunity to practise a range of practical and procedural skills were seen to be of particular value. CONCLUSIONS: The general practice and teaching hospital terms both contribute to the training of interns, offering contrasting environments and experiences which enhance interns' professional and personal growth. General practice terms should be considered for inclusion in intern training programs across Australia.

Efficacy of a canarypox-vectored recombinant vaccine expressing the hemagglutinin gene of equine influenza H3N8 virus in the protection of ponies from viral challenge.

OBJECTIVE: To determine onset and duration of immunity provided by a 2- or 3-dose series of a new canarypox-vectored recombinant vaccine for equine influenza virus (rCP-EIV vaccine) expressing the hemagglutinin genes of influenza H3N8 virus strains A/eq/Kentucky/94 and A/eq/Newmarket/2/93 in ponies. ANIMALS: Forty-nine 1- to 3-year-old male Welsh Mountain Ponies that were seronegative for equine influenza virus. PROCEDURES: Vaccinated and control ponies were challenged with aerosolized influenza virus A/eq/Sussex/89 (H3N8), representative of the Eurasian lineage of circulating influenza viruses. In trial 1, control ponies and ponies that received rCP-EIV vaccine were challenged 2 weeks after completion of the 2-dose primary vaccination program. In trial 2, ponies were challenged 5 months after 2 doses of rCP-EIV vaccine or 1 year after the first boosting dose of rCP-EIV vaccine, administered 5 months after completion of the primary vaccination program. After challenge, ponies were observed daily for clinical signs of influenza and nasal swab specimens were taken to monitor virus excretion. RESULTS: The challenge reliably produced severe clinical signs consistent with influenza infection in the control ponies, and virus was shed for up to 7 days. The vaccination protocol provided clinical and virologic protection to vaccinates at 2 weeks and 5 months after completion of the primary vaccination program and at 12 months after the first booster. CONCLUSION AND CLINICAL RELEVANCE: The rCP-EIV vaccine provided protection of ponies to viral challenge. Of particular importance was the protection at 5 months after the second dose, indicating that this vaccine closes an immunity gap between the second and third vaccination.

Effect of adipose-derived mesenchymal stem and regenerative cells on lameness in dogs with chronic osteoarthritis of the coxofemoral joints: a randomized, double-blinded, multicenter, controlled trial.

Autologous stem cell therapy in the field of regenerative veterinary medicine involves harvesting tissue, such as fat, from the patient, isolating the stem and regenerative cells, and administering the cells back to the patient. Autologous adipose-derived stem cell therapy has been commercially available since 2003, and the current study evaluated such therapy in dogs with chronic osteoarthritis of the hip. Dogs treated with adipose-derived stem cell therapy had significantly improved scores for lameness and the compiled scores for lameness, pain, and range of motion compared with control dogs. This is the first randomized, blinded, placebo-controlled clinical trial reporting on the effectiveness of stem cell therapy in dogs.

Electrographic imaging of recognition memory in 34-38 week gestation intrauterine growth restricted newborns.

Electrophysiological imaging of recognition memory using event-related potentials (ERPs) in intrauterine growth-restricted (IUGR) newborns allows assessment of recognition memory before the onset of multiple confounding variables. Animal models that reproduce the physiologic components associated with IUGR have demonstrated adverse effects on the hippocampus, a structure that is essential to normal memory processing. Previous electrophysiologic studies have demonstrated shortened auditory-evoked potential (AEP) and visual-evoked potential (VEP) latencies in IUGR infants suggesting accelerated neural maturation in response to the adverse in-utero environment. The hypothesis of the current study was that newborns with IUGR and head-sparing would demonstrate altered auditory recognition memory when compared to controls and that the configuration of the alteration would evidence advanced maturation but still be different from that of typically grown newborns. Twelve IUGR newborns born at 34-38 weeks gestation with head-sparing and 16 age-matched control newborns were tested with both a speech/nonspeech paradigm to assess auditory sensory processing and a novel (stranger's voice) and familiar (mother's voice) paradigm to assess recognition memory. In the recognition memory experiment, a three-way interaction of condition, lead, and group was identified for the lateral leads T4, CM3, and CM4 with the response to the mother being of much greater area in the IUGR cohort than in the controls. This ERP configuration has previously been reported for the midline leads in term newborns. The findings indicate that IUGR newborns with head-sparing have electrophysiologic evidence of accelerated maturation of cognitive processing suggesting an atypical process of maturation that may not support typical cognitive development.