Search

The purpose of this study was to determine whether surgical repair of distal biceps tendon ruptures in professional football players would lead to a decrease in postinjury performance when compared to preinjury performance and control-matched peers. We also sought to define return to sport, postinjury career length, and games played per season in National Football League players following surgical repair of distal biceps tendon ruptures. Data for National Football League players who underwent surgical repair of distal biceps tendon ruptures during a 20-year time period were collected. A total of 25 cases in 22 players were included in the analysis. Matched controls based on player position, age, experience, and performance statistics were identified. Performance scores for cases and controls were calculated using a standardized scoring system specific to player position. Of the 25 cases, 21 (84%) were able to return to sport in the National Football League. The overall 1-year survival rate of return to play in players undergoing surgical repair of distal biceps tendon ruptures was 76% and overall 2-year survival was 56%. Players who underwent surgical repair of distal biceps tendon ruptures had significantly shorter postinjury career lengths and played fewer games per season postinjury than matched controls. There was no significant difference by position in postinjury performance scores when compared to matched controls. National Football League players undergoing surgical repair of distal biceps tendon ruptures have a high rate of return to sport, though many retire within the next few seasons following surgery. Players who do return to competition can be expected to perform at a level comparable to their peers. [ABSTRACT FROM AUTHOR]

Despite the ability of antiretroviral therapy to minimize human immunodeficiency virus type 1 (HIV-1) replication and increase the duration and quality of patients' lives, the health consequences and financial burden associated with the lifelong treatment regimen render a permanent cure highly attractive. Although T cells play an important role in controlling virus replication, they are themselves targets of HIV-mediated destruction. Direct genetic manipulation of T cells for adoptive cellular therapies could facilitate a functional cure by generating HIV-1-resistant cells, redirecting HIV-1-specific immune responses, or a combination of the two strategies. In contrast to a vaccine approach, which relies on the production and priming of HIV-1-specific lymphocytes within a patient's own body, adoptive T-cell therapy provides an opportunity to customize the therapeutic T cells prior to administration. However, at present, it is unclear how to best engineer T cells so that sustained control over HIV-1 replication can be achieved in the absence of antiretrovirals. This review focuses on T-cell gene-engineering and gene-editing strategies that have been performed in efforts to inhibit HIV-1 replication and highlights the requirements for a successful gene therapy-mediated functional cure. [ABSTRACT FROM AUTHOR]

Mesenchymal breast lesions encompass a variety of breast diseases. Many of these lesions are rare with only a few case reports in the literature. This article reviews the imaging findings of selected mesenchymal breast lesions, their clinical presentations and method of diagnosis. Mesenchymal lesions are diverse and include haemangioma, granular cell tumour, myofibroblastoma, fibromatosis, pseudoangiomatous stromal hyperplasia, and malignant fibrous histiocytoma. It is important for radiologists to be aware of these lesions as some of them may have malignant potential or demonstrate imaging features that overlap with other malignant lesions. [ABSTRACT FROM AUTHOR]

Purpose To evaluate clinical and radiographic outcomes in patients treated with limited-open retrograde intramedullary headless compression screw (IMHS) fixation for metacarpal neck and shaft fractures. Methods Retrospective review of prospectively collected data on a consecutive series of 39 patients (34 men; 5 women), mean age 28 years (range, 16–66 y) treated with IMHS fixation for acute displaced metacarpal neck/subcapital (N = 26) and shaft (N = 13) fractures at a single academic practice between 2010 and 2014. Preoperative magnitude of metacarpal neck angulation averaged 54° (range, 15° to 70°), and shaft angulation averaged 38° (range, 0° to 55°). Patients used a hand-based orthosis until suture removal and began active motion within the first week. Clinical outcomes were assessed with digital goniometry, pad-to-distal palmar crease distance, and grip strength. Time to union and radiographic arthrosis was assessed. Twenty patients reached minimum 3-month follow-up, with a mean of 13 months (range, 3–33 mo). Results All 20 patients with minimum 3 months of follow-up achieved full composite flexion, and extensor lag resolved by 3-week follow-up. All patients demonstrated full active metacarpophalangeal joint extension or hyperextension. Grip strength measured 105% (range, 58% to 230%) of the contralateral hand. No secondary surgeries were performed. There were 2 cases of shaft re-fracture from blunt trauma following prior evidence of full osseous union with the screw in place. All patients achieved radiographic union by 6 weeks. There was no radiographic arthrosis at latest follow-up. One patient reported occasional clicking with metacarpophalangeal joint motion not requiring further treatment. Conclusions Limited open retrograde IMHS fixation proved to be safe and reliable for metacarpal neck/subcapital and axially stable shaft fractures, allowed for early postoperative motion without affecting union rates, and obviated immobilization. This technique offers distinct advantages in select patients. Type of study/level of evidence Therapeutic IV. [ABSTRACT FROM AUTHOR]

We report a case of concomitant fractures of the volar lunate facet of the distal radius and capitate body. Surgical fixation was achieved with open reduction internal fixation using headless compression screws for both fractures. Because of the nature of complications seen after both operative and nonsurgical management, these fractures warrant particular attention. [ABSTRACT FROM AUTHOR]

We characterize a mechanism of injury, injury pattern, and treatment algorithm for adductor pollicis myotendinous injuries in 2 professional baseball players. Similar to myotendinous eccentric injuries in other anatomical areas, the adductor pollicis sustains a sudden forceful eccentric load during a jammed swing, resulting in intramuscular strain or tendon rupture. Based on the reported injury mechanism, and magnetic resonance imaging features of these myotendinous injuries, the thumb of the top hand during a jammed swing was suddenly and forcefully eccentrically abducted from a contracted and adducted position, resulting in injury patterns. [Copyright &y& Elsevier]

Purpose: To compare, in a prospective, randomized manner, the sugar tong splint with a short-arm radial gutter splint in terms of patient satisfaction and the ability to maintain reduction of distal radius fractures. Methods: A total of 118 patients with displaced distal radius fractures were enrolled; 85 patients (85 fractures) were available for follow-up evaluation and were included in the study population. There were 26 men and 59 women with a mean age of 64 years. Thirty-eight fractures were immobilized in a short-arm radial gutter splint and 47 in a sugar tong splint. Forty fractures had a stable pattern and 45 had an unstable fracture pattern. The initial patient follow-up examination occurred a mean of 8 days after splint application. Results: A total of 33 fractures showed loss of fracture reduction at the initial follow-up evaluation. Sixteen of 38 fractures immobilized with the radial gutter splint displaced, whereas displacement was seen in 17 of 47 fractures immobilized with a sugar tong splint; this difference was not significant. When the splint constructs were evaluated based on fracture stability no differences were found between the splints’ ability to maintain fracture reduction in both stable and unstable displaced fractures. Patients in the short-arm radial gutter splint group had significantly better Disabilities of the Arm, Shoulder, and Hand scores than those patients whose fractures were immobilized with a sugar tong splint. Conclusions: Both the sugar tong splint and the short-arm radial gutter splint had comparable performance in maintaining the initial reduction of distal radius fractures, with the short-arm splint tolerated better by patients. Based on our study we recommend the use of a short-arm radial gutter splint for initial immobilization of displaced distal radius fractures. Type of study/level of evidence: Prognostic, level II. [Copyright &y& Elsevier]

Neuropathy of the ulnar digital nerve of the thumb is a relatively rare clinical entity. We report 2 cases of ulnar-sided digital nerve tumors of the thumb in 2 professional baseball players who routinely used grip-adjusting batting equipment. Symptomatic relief was achieved with nonsurgical treatment that allowed both players to continue playing during critical times during their season. We postulate that there may be an association with the grip-adjusting batting equipment and the development of digital neuropathy. [ABSTRACT FROM AUTHOR]

Abstract: Internal jugular vein thrombosis is an uncommon entity with high morbidity and an increased risk of mortality. Spontaneous clotting of the internal jugular vein without any known risk factors is virtually unheard of, and intravenous drug use is the most common cause for thrombosis. Assisted reproductive techniques alone or in conjunction with ovarian hyperstimulation syndrome seem to predispose patients for thrombosis of the internal jugular vein. We present the case of a patient who, after in vitro fertilization, developed ovarian hyperstimulation syndrome and clotted the internal jugular vein. In the setting of the Emergency Department, the norm should be to “rule out internal jugular venous thrombosis” in pregnant patients who have undergone in vitro fertilization and present with neck pain, with or without swelling or distended collaterals. [Copyright &y& Elsevier]

Purpose: Fixation countersunk beneath the articular surface is well accepted for periarticular fractures. Limited open intramedullary headless compression screw (HCS) fixation offers clinical advantages over Kirschner wire and open techniques. We used quantitative 3-dimensional computed tomography to assess the articular starting point, surface area, and subchondral volumes used during HCS fixation of metacarpal neck fractures. Methods: We simulated retrograde intramedullary insertion of 2.4- and 3.0-mm HCS and 1.1-mm Kirschner wires for metacarpal neck fracture fixation in 3-dimensional models from 16 adults. We used metacarpal head articular surface area (mm2) and subchondral volumes (mm3) and coronal and sagittal plane arcs of motion, during which we analyzed the center and rim of the articular base of the proximal phalanx engaging the countersunk entry site. Results: Mean metacarpal head surface area mated to the proximal phalangeal base in neutral position was 93 mm2; through the coronal plane arc (45°) was 129 mm2, and through the sagittal plane arc (120°) was 265 mm2. The mean articular surface area used by countersunk HCS threads was 12%, 8%, and 4%, respectively, in each of these arcs. The 1.1-mm Kirschner wire occupied 1.2%, 0.9%, and 0.4%, respectively. Mean metacarpal head volume was 927 mm3. Mean subchondral volume occupied by the countersunk portion was 4%. The phalangeal base did not overlap the dorsally located countersunk entry site through most of the sagittal plane arc. During coronal plane motion in neutral extension, the center of the base never engaged the dorsally located countersunk entry site. Conclusions: Metacarpal head surface area and subchondral head volume occupied by HCS were minimal. Articular surface area violation was least during the more clinically relevant sagittal plane arc of motion. Clinical relevance: The dorsal articular starting point was in line with the medullary canal and avoided engaging the center of the articular base through most of the sagittal plane arc. Three-dimensional computed tomography data support the use of an articular starting point for these extra-articular fractures. [Copyright &y& Elsevier]

We present a case of traumatic cervical esophageal perforation complicated by delayed diagnosis and foreign body presence successfully repaired with acellular matrix biomaterial made from porcine submucosa (Surgisis mesh [Wilson-Cook, Winston-Salem, NC]). With metal plating eroding into the esophagus from a spinal fixation procedure, the mesh was applied to the defect just under the cricopharyngeus. The patient re-commenced oral intake after 7 days, and an endoscopy at 4 weeks revealed a well-incorporated mesh in an intact esophagus with normal caliber. In this case, Surgisis mesh (Wilson-Cook) proved effective in providing temporary esophageal integrity to allow healing in an infected field where diversion was impossible. [ABSTRACT FROM AUTHOR]

Objective: Numerous commercial pharmacogenetics panels are now widely available for clinical use in psychiatric practice. However, there is a paucity of literature evaluating the use of combinatorial pharmacogenetics panels to enhance outcomes in the treatment of adolescents with depression. This study sought to prospectively evaluate the clinical impact of combinatorial pharmacogenetics testing in a double-blind, randomized, controlled effectiveness study for the pharmacologic treatment of adolescents with depression.Method: Adolescents aged 13 to 18 years (N = 176) with moderate to severe major depressive disorder (MDD) were randomized to treatment arm guided by testing in which pharmacogenetic testing results were available at the baseline visit (GENE arm, n = 84) or a treatment-as-usual arm (TAU arm, n = 92) in which testing results were not available until an 8-week visit. Raters, participants, and families were blinded to group allocation. Symptom improvement, side effects, and satisfaction were assessed throughout the study at 4 weeks, 8 weeks, and 6 months.Results: There were no differences between the GENE and TAU arms at 8 weeks or 6 months for symptom improvement, side effect burden, or satisfaction. Selective serotonin reuptake inhibitors were prescribed at higher rates in the TAU arm compared to the GENE arm (p = .024).Conclusion: Combinatorial pharmacogenetics-guided treatment did not demonstrate improved outcomes compared to TAU in adolescents with MDD. Future research should examine how specific medication-gene pairs may affect clinical outcomes in the treatment of adolescents with depression and how best to integrate pharmacogenetics into clinical practice.Clinical Trial Registration Information: A PK/PD Genetic Variation Treatment Algorithm Versus Treatment As Usual for Adolescent Management Of Depression; https://www.clinicaltrials.gov; NCT02286440. [ABSTRACT FROM AUTHOR]

Introduction: ND0612 is a continuous, subcutaneous levodopa/carbidopa delivery system under development for patients with Parkinson's disease (PD) and motor fluctuations.Methods: This was a randomized, placebo-controlled, double-blind, 2-period study evaluating the safety and pharmacokinetics of ND0612 in PD patients on an optimized oral levodopa regimen and experiencing ≥2 h/day of OFF time. During Period-1, patients received their current standard of care (SoC) levodopa/carbidopa and were randomized (2:1) to 14 days treatment with adjunct ND0612 (daily levodopa/carbidopa dose of 270/63 mg) or placebo infusion +SoC. During Period-2, 16 patients were randomized to receive 7 days treatment with ND0612 or ND0612 plus oral entacapone. Reduction in OFF time was analyzed as an exploratory measure using a futility design with a predefined margin of 1.6 h.Results: ND0612 was well-tolerated; most patients experienced infusion site nodules (95% vs. 56% with placebo), which all resolved without sequelae. Patients treated with adjunct ND0612 during Period-1 avoided deep troughs in levodopa plasma levels and had a decreased fluctuation index versus placebo (1.6 ± 0.5 vs 3.1 ± 1.6 at end of Period-1, respectively). In Period-2, the coadministration of entacapone with continuous ND0612 SC infusion translated to an increase in mean levodopa AUC0-10h compared to baseline. Exploratory efficacy analysis of Period 1 showed mean ± SD OFF time reductions of -2.13 ± 2.24 [90%CI: -2.8, ∞] hours (p = 0.84 using H0 of μ0 ≤-1.6).Conclusion: Levodopa/carbidopa infusion with ND0612 was generally well-tolerated and resulted in reduced fluctuations in plasma levodopa concentrations when given with SoC oral levodopa. ND0612 met the efficacy endpoint for the futility design. [ABSTRACT FROM AUTHOR]

The quantification of vegetation height for the circumpolar Arctic tundra biome is of interest for a wide range of applications, including biomass and habitat studies as well as permafrost modelling in the context of climate change. To date, only indices from multispectral data have been used in these environments to address biomass and vegetation changes over time. The retrieval of vegetation height itself has not been attempted so far over larger areas. Synthetic Aperture Radar (SAR) holds promise for canopy modeling over large extents, but the high variability of near-surface soil moisture during the snow-free season is a major challenge for application of SAR in tundra for such a purpose. We hypothesized that tundra vegetation height can be derived from multispectral indices as well as from C-band SAR data acquired in winter (close to zero liquid water content). To test our hypothesis, we used C-band SAR data from Sentinel-1 and multi-spectral data from Sentinel-2. Results show that vegetation height can be derived with an RMSE of 44 cm from Normalized Difference Vegetation Index (NDVI) and 54 cm from Tasseled Cap Wetness index (TC). Retrieval from C-band SAR shows similar performance, but C-VV is more suitable than C-HH to derive vegetation height (RMSEs of 48 and 56 cm respectively). An exponential relationship with in situ height was evident for all tested parameters (NDVI, TC, C-VV and C-HH) suggesting that the C-band SAR and multi-spectral approaches possess similar capabilities including tundra biomass retrieval. Errors might occur in specific settings as a result of high surface roughness, high photosynthetic activity in wetlands or high snow density. We therefore introduce a method for combined use of Sentinel-1 and Sentinel-2 to address the ambiguities related to Arctic wetlands and barren rockfields. Snow-related deviations occur within tundra fire scars in permafrost areas in the case of C-VV use. The impact decreases with age of the fire scar, following permafrost and vegetation recovery. The evaluation of masked C-VV retrievals across different regions, tundra types and sources (in situ and circumpolar vegetation community classification from satellite data) suggests pan-Arctic applicability to map current conditions for heights up to 160 cm. The presented methodology will allow for new applications and provide advanced insight into changing environmental conditions in the Arctic. • Use of frozen condition backscatter allows vegetation height retrieval in tundra. • C-band SAR shows similar capabilities like multi-spectral indices. • The Tasseled Cap Wetness Index is specifically applicable in northern tundra. • The evaluation across different regions suggests circumpolar applicability of C-VV. • Combination of Sentinel-1 and Sentinel-2 allows treatment of ambiguities. [ABSTRACT FROM AUTHOR]

Objective To evaluate the performance (in terms of responsiveness to change, associations with other criterion standards, and indicators of Alzheimer’s disease [AD] severity) of a quality-of-life measure (Quality of Life in Alzheimer’s Disease [QOL-AD]) and a health utility measure (Health Utilities Index Mark 3 [HUI-3]) from two recently completed clinical trials of a new drug for AD. Methods Change from baseline scores was calculated, and treatment effects were analyzed using mixed models for repeated measures. Three separate models were then estimated to examine the association between the quality-of-life/utility end points and the clinical and other health outcome end points measured during the trials, including cognition, function, behavior, and dependence. Results The performance of the two measures differed. Subject-assessed QOL-AD was found to be weakly associated with clinical measures of cognition, and with caregiver reports of function, behavior, and dependence, and showed little movement over time and did not appear to differ by baseline AD severity. Proxy-assessed QOL-AD scores were consistently lower than subject-assessed scores, and the level of decline in QOL-AD was greater using proxy-assessed QOL-AD. Proxy-assessed HUI-3 scores were more strongly associated with clinical measures of cognition, function, behavior, and dependence than the subject- and proxy-assessed QOL-AD scores. Larger proportionate changes over 78 weeks were observed with HUI-3 scores and greater separation in HUI-3 scores by baseline severity. Conclusions Subject-assessed QOL-AD is less likely than proxy-assessed QOL-AD to respond to changes in clinical measures used to track progression in clinical trials of subjects with mild to moderate AD. Proxy-assessed HUI-3 assessments were more in line with other outcome assessments and could therefore be better outcome measures to evaluate clinical progression in mild to moderate AD. [ABSTRACT FROM AUTHOR]

Plant hormones act as chemical messengers, transducing cellular and organ-level cues, executing plant growth, development, reproduction, metabolism, and response to environmental stress. In addition to the production of hormones by plants, fungi can also produce compounds that are similar to phytohormones, and may modulate growth, physiology, and immunity in both plants and fungi. The "classical" plant growth hormone, cytokinin (CK) is known to have roles in plant-fungi interactions. In plants, CKs are involved in various processes including plant growth and development, seed germination, apical dominance, balance between shoot and root tissue, leaf senescence, and plant-pathogen-interactions. We recently reported that CK can also affect fungal development. CK is not produced solely by plants, as can be synthesized by plant-associated microorganisms such as bacteria and fungi. Fungal phytopathogens may also activate plant CK signalling/sensing via secretion of effector molecules. Fungal CKs secreted by (hemi)biotrophic pathogens can serve as virulence factors, however, most necrotrophic fungal plant pathogens have not been reported to secrete CKs during plant infection. Though a lifestyle-dependent role for CK signalling/perception was suggested for fungal plant pathogens, little is known about CK perception, sensing, and signalling in fungal organisms. In this review, we focus on the production of fungal CKs and their role in development and virulence, as well as the possibilities for CK perception and signalling in the fungal kingdom, where CHASE-domain containing proteins are largely absent. [ABSTRACT FROM AUTHOR]

Activity-dependent neuroprotective protein (ADNP) and its homologue ADNP2 belong to a homeodomain, the zinc finger-containing protein family. ADNP is essential for mouse embryonic brain formation. ADNP2 is associated with cell survival, but its role in embryogenesis has not been evaluated. Here, we describe the use of the zebrafish model to elucidate the developmental roles ofADNPand ADNP2. Although we expected brain defects, we were astonished to discover that the knockdown zebrafish embryos were actually lacking blood and suffered from defective hemoglobin production. Evolutionary conservation was established using mouse erythroleukemia (MEL) cells, a well studied erythropoiesis model, in which silencing ofADNP or ADNP2 produced similar results as in zebrafish. Exogenous RNAencodingADNP/ADNP2rescued theMELcell undifferentiated state, demonstrating phenotype specificity. Brg1, an ADNP-interacting chromatin-remodeling protein involved in erythropoiesis through regulation of the globin locus, was shown here to interact also with ADNP2. Furthermore, chromatin immunoprecipitation revealed recruitment of ADNP, similar to Brg1, to the mouse β-globin locus control region in MEL cells. This recruitment was apparently diminished upon dimethyl sulfoxide (DMSO)-induced erythrocyte differentiation compared with the nondifferentiated state. Importantly, exogenous RNA encoding ADNP/ADNP2 significantly increased β-globin expression in MEL cells in the absence of any other differentiation factors. Taken together, our results reveal an ancestral role for theADNPprotein family in maturation and differentiation of the erythroid lineage, associated with direct regulation of β-globin expression. [ABSTRACT FROM AUTHOR]

Abstract: Emergency Medicine (EM) was officially recognized as a specialty in Israel in 1999. In 2003 the first nine Israeli trained emergency physicians (EPs) were certified. This survey was undertaken to assess current staffing of Emergency Departments (ED) in Israel and to attempt to estimate future staffing needs for EPs. A survey was sent to all ED directors at general hospitals in Israel. We asked questions relating to staffing by number of physicians, type and level of training, and differential staffing by time of the day and week. In addition, we inquired as to the census, structure, hospital resources available, and size of the ED. Twenty-four of 25 (96%) EDs responded. There were 59 EM specialists registered in Israel; there were 37 EM residents. EDs reported a total of 1,872,500 visits annually. Emergency care is otherwise given by specialists and residents in other fields, and non-specialist physicians. At large hospitals there is an average of 2.5 EM specialists during daytime hours, and another four specialists of other types on duty. During the night in large hospitals, there is an average of <1 specialist of any kind (typically not EM) on duty. In most EDs, care is turned over to non-specialists (residents and others) during evenings and nights. The recognition of the need for Emergency Medicine as a specialty in Israel has not as yet translated into care of emergencies by EPs for most patients. To adequately staff EDs with physicians trained in EM, an emphasis needs to be placed on increasing EM staff and resident positions. The need seems most acute in medium-sized hospitals and during off hours and weekends. [Copyright &y& Elsevier]

Introduction: Computed tomography (CT) scans are often used in the evaluation of patients with blunt trauma. This study identifies the clinical features associated with further diagnostic information obtained on a CT chest scan compared with a standard chest X-ray in patients sustaining blunt trauma to the chest. Methods: A 2-year retrospective survey of 141 patients who attended a Level 1 trauma centre for blunt trauma and had a chest CT scan and a chest X-ray as part of an initial assessment was undertaken. Data extracted from the medical record included vital signs, laboratory findings, interventions and the type and severity of injury. Results: The CT chest scan is significantly more likely to provide further diagnostic information for the management of blunt trauma compared to a chest X-ray in patients with chest wall tenderness (OR=6.73, 95% CI=2.56, 17.70, p<0.001), reduced air-entry (OR=4.48, 95% CI=1.33, 15.02, p=0.015) and/or abnormal respiratory effort (OR=4.05, 95% CI=1.28, 12.66, p=0.017). CT scan was significantly more effective than routine chest X-ray in detecting lung contusions, pneumothoraces, mediastinal haematomas, as well as fractured ribs, scapulas, sternums and vertebrae. Conclusion: In alert patients without evidence of chest wall tenderness, reduced air-entry or abnormal respiratory effort, selective use of CT chest scanning as a screening tool could be adopted. This is supported by the fact that most chest injuries can be treated with simple observation. Intubated patients, in most instances, should receive a routine CT chest scan in their first assessment. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Canine malignant melanoma (CMM) is an aggressive neoplasm treated with surgery and/or fractionated RT; however, metastatic disease is common and chemoresistant. Preclinical and clinical studies by our laboratory and others have shown that xenogeneic DNA vaccination with tyrosinase family members can produce immune responses resulting in tumor rejection or protection and prolongation of survival. These studies provided the impetus for development of a xenogeneic DNA vaccine program in CMM. Materials and Methods: Cohorts of three dogs each received increasing doses of xenogeneic plasmid DNA encoding either human tyrosinase (huTyr; 100/500/1500mcg), murine GP75 (muGP75; 100/500/1500mcg), murine tyrosinase (muTyr; 5 dogs each at 100/500mcg), muTyr±HuGM-CSF (9 dogs at 50mcg muTyr, 3 dogs each at 100/400/800mcg HuGM-CSF, or 3 dogs each at 50mcg muTyr with 100/400/800mcg HuGM-CSF), or 50 mcg MuTyr intramuscularly biweekly for a total of four vaccinations. Results: The Kaplan–Meier median survival time (KM MST) for all stage II–IV dogs treated with huTyr, muGP75 and muTyr are 389, 153 and 224 days, respectively. Preliminarily, the KM MST for stage II–IV dogs treated with 50mcg MuTyr, 100/400/800mcg HuGM-CSF or combination MuTyr/HuGM-CSF are 242, 148 and >402 (median not reached) days, respectively. Thirty-three stage II–III dogs with loco-regionally controlled CMM across the xenogeneic vaccine studies have a KM MST of 569 days. Minimal to mild pain was noted on vaccination and one dog experienced vitiligo. We have recently investigated antibody responses in dogs vaccinated with HuTyr and found 2- to 5-fold increases in circulating antibodies to human tyrosinase. Conclusions: The results of these trials demonstrate that xenogeneic DNA vaccination in CMM: (1) is safe, (2) leads to the development of anti-tyrosinase antibodies, (3) is potentially therapeutic, and (4) is an attractive candidate for further evaluation in an adjuvant, minimal residual disease Phase II setting for CMM. [Copyright &y& Elsevier]