Survival Outcomes Following Discontinuation of Ipilimumab and Nivolumab for Advanced Melanoma in a Population-based Cohort.

AIMS: Induction ipilimumab and nivolumab followed by maintenance nivolumab improve overall survival compared with ipilimumab alone in patients with advanced melanoma, but immune-related adverse events (irAE) occur commonly. The need for induction discontinuation because of irAE and the relationship between irAE and survival in non-trials patients are unclear. MATERIALS AND METHODS: Patients with unresectable stage III-IV melanoma receiving first-line combination immunotherapy at one of six centres between December 2017 and February 2020 outside of trials were identified retrospectively. Landmark 12-week Kaplan-Meier analyses and log-rank tests were used to evaluate associations between discontinuation of induction therapy on overall survival and time to treatment failure (TTF). Multivariable analysis of factors influencing overall survival and TTF was undertaken. RESULTS: Among 95 patients, the median age was 62 years, 38.9% had Eastern Cooperative Oncology Group performance status ≥1 and 22.1% had brain metastases. The median follow-up for the whole cohort was 19.8 months by the reverse Kaplan-Meier method. Any grade and grade 3-4 irAE were noted in 78.9% and 44.2% of the cohort, respectively. 44.2% of patients completed induction immunotherapy, whereas 41.1% did not due to irAE. Twelve-week landmark overall survival and TTF were similar in patients who completed induction versus those who did not due to irAE. On multivariable analysis, any grade irAE (versus none) was associated with longer overall survival (hazard ratio = 0.35, 95% confidence interval 0.15-0.82, P = 0.02) and TTF (hazard ratio = 0.38, 95% confidence interval = 0.17-0.81, P = 0.01). Grade 3-4 irAE correlated with longer TTF (hazard ratio = 0.45, 95% confidence interval = 0.20-1.01, P = 0.05). CONCLUSION: In this population-based cohort, discontinuation of induction immunotherapy as a result of irAE did not adversely affect overall survival or TTF. irAE observed during ipilimumab and nivolumab induction were associated with improved survival outcomes.

Comparison of manual and semi-automatic registration in augmented reality image-guided liver surgery: a clinical feasibility study.

BACKGROUND: The laparoscopic approach to liver resection may reduce morbidity and hospital stay. However, uptake has been slow due to concerns about patient safety and oncological radicality. Image guidance systems may improve patient safety by enabling 3D visualisation of critical intra- and extrahepatic structures. Current systems suffer from non-intuitive visualisation and a complicated setup process. A novel image guidance system (SmartLiver), offering augmented reality visualisation and semi-automatic registration has been developed to address these issues. A clinical feasibility study evaluated the performance and usability of SmartLiver with either manual or semi-automatic registration. METHODS: Intraoperative image guidance data were recorded and analysed in patients undergoing laparoscopic liver resection or cancer staging. Stereoscopic surface reconstruction and iterative closest point matching facilitated semi-automatic registration. The primary endpoint was defined as successful registration as determined by the operating surgeon. Secondary endpoints were system usability as assessed by a surgeon questionnaire and comparison of manual vs. semi-automatic registration accuracy. Since SmartLiver is still in development no attempt was made to evaluate its impact on perioperative outcomes. RESULTS: The primary endpoint was achieved in 16 out of 18 patients. Initially semi-automatic registration failed because the IGS could not distinguish the liver surface from surrounding structures. Implementation of a deep learning algorithm enabled the IGS to overcome this issue and facilitate semi-automatic registration. Mean registration accuracy was 10.9 ± 4.2 mm (manual) vs. 13.9 ± 4.4 mm (semi-automatic) (Mean difference - 3 mm; p = 0.158). Surgeon feedback was positive about IGS handling and improved intraoperative orientation but also highlighted the need for a simpler setup process and better integration with laparoscopic ultrasound. CONCLUSION: The technical feasibility of using SmartLiver intraoperatively has been demonstrated. With further improvements semi-automatic registration may enhance user friendliness and workflow of SmartLiver. Manual and semi-automatic registration accuracy were comparable but evaluation on a larger patient cohort is required to confirm these findings.

Impact of total variation minimization in volume rendering visualization of breast tomosynthesis data.

BACKGROUND AND OBJECTIVE: Total Variation (TV) minimization algorithms have achieved great attention due to the virtue of decreasing noise while preserving edges. The purpose of this work is to implement and evaluate two TV minimization methods in 3D. Their performance is analyzed through 3D visualization of digital breast tomosynthesis (DBT) data with volume rendering. METHODS: Both filters were studied with real phantom and one clinical DBT data. One algorithm was applied sequentially to all slices and the other was applied to the entire volume at once. The suitable Lagrange multiplier used in each filter equation was studied to reach the minimum 3D TV and the maximum contrast-to-noise ratio (CNR). Imaging blur was measured at 0° and 90° using two disks with different diameters (0.5 mm and 5.0 mm) and equal thickness. The quality of unfiltered and filtered data was analyzed with volume rendering at 0° and 90°. RESULTS: For phantom data, with the sequential filter, a decrease of 25% in 3D TV value and an increase of 19% and 30% in CNR at 0° and 90°, respectively, were observed. When the filter is applied directly in 3D, TV value was reduced by 35% and an increase of 36% was achieved both for CNR at 0° and 90°. For the smaller disk, variations of 0% in width at half maximum (FWHM) at 0° and a decrease of about 2.5% for FWHM at 90° were observed for both filters. For the larger disk, there was a 2.5% increase in FWHM at 0° for both filters and a decrease of 6.28% and 1.69% in FWHM at 90° with the sequential filter and the 3D filter, respectively. When applied to clinical data, the performance of each filter was consistent with that obtained with the phantom. CONCLUSIONS: Data analysis confirmed the relevance of these methods in improving quality of DBT images. Additionally, this type of 3D visualization showed that it may play an important complementary role in DBT imaging. It allows to visualize all DBT data at once and to analyze properly filters applied to all the three dimensions. Concise Abstract Total Variation (TV) minimization algorithms are one compressed sensing technique that has achieved great attention due to the virtue of decrease noise while preserve edges transitions. The purpose of this work is to solve the same TV minimization problem in DBT data, by studying two 3D filters. The obtained results were analyzed at 0° and 90° with a 3D visualization through volume rendering. The filters differ in their application. One considers a slice-by-slice optimization, sequentially traversing all slices of the data. The other considers the intensity values of adjacent slices to make this optimization on each voxel. The performance of each filter was also tested with a clinical case. The results obtained were very encouraging with a significantly increased contrast to noise ratio at 0° and 90° and a small reduction in blur at 90° (slight reduction of the out-of-plane artifact).

Does the intervention of mindfulness reduce levels of burnout and compassion fatigue and increase resilience in pre-registration students? A pilot study.

INTRODUCTION: In the current clinical working environment it is important that therapeutic radiography students are fully prepared not just clinically but emotionally for a working professional life. Mindfulness has shown promise, as a self-care strategy, in the improvement of burnout, resilience and compassion fatigue in other professions; however, it has not been used with therapeutic radiography students. METHODS: Eight pre-registration therapeutic radiography students were recruited to undergo a five week mindfulness course; six students from the year below were recruited to act as a control arm (no mindfulness). Data was collected using a series of validated tools at baseline, week five, month three and 12 months after the start of the study: RESULTS: The MBI-SS scale demonstrated 29% of the sample experienced emotional exhaustion and 43% increased cynicism. The other tools showed a positive trend with the intervention; however, these were not statistically significant. CONCLUSION: Although no statistically significant differences were demonstrated between the study arms, some interesting trends have been noted. The key finding was the identification of burnout experienced by almost a third of the study sample. This suggests that a new area of study is warranted to further investigate the factors contributing to burnout in the student population.

Detection and modelling of contacts in explicit finite-element simulation of soft tissue biomechanics.

PURPOSE: Realistic modelling of soft tissue biomechanics and mechanical interactions between tissues is an important part of biomechanically-informed surgical image-guidance and surgical simulation. This submission details a contact-modelling pipeline suitable for implementation in explicit matrix-free FEM solvers. While these FEM algorithms have been shown to be very suitable for simulation of soft tissue biomechanics and successfully used in a number of image-guidance systems, contact modelling specifically for these solvers is rarely addressed, partly because the typically large number of time steps required with this class of FEM solvers has led to a perception of them being a poor choice for simulations requiring complex contact modelling. METHODS: The presented algorithm is capable of handling most scenarios typically encountered in image-guidance. The contact forces are computed with an evolution of the Lagrange-multiplier method first used by Taylor and Flanagan in PRONTO 3D extended with spatio-temporal smoothing heuristics for improved stability and edge-edge collision handling, and a new friction model. For contact search, a bounding-volume hierarchy (BVH) is employed, which is capable of identifying self-collisions by means of the surface-normal bounding cone of Volino and Magnenat-Thalmann, in turn computed with a novel formula. The BVH is further optimised for the small time steps by reducing the number of bounding-volume refittings between iterations through identification of regions with mostly rigid motion and negligible deformation. Further optimisation is achieved by integrating the self-collision criterion in the BVH creation and updating algorithms. RESULTS: The effectiveness of the algorithm is demonstrated on a number of artificial test cases and meshes derived from medical image data. It is shown that the proposed algorithm reduces the cost of BVH refitting to the point where it becomes a negligible part of the overall computation time of the simulation. It is also shown that the proposed surface-normal cone computation formula leads to about 40 % fewer BVH subtrees that must be checked for self-collisions compared with the widely used method of Provot. The proposed contact-force formulation and friction model are evaluated on artificial test cases that allow for a comparison with a ground truth. The quality of the proposed contact forces is assessed in terms of trajectories and energy conservation; a [Formula: see text]0.4 % drop off in total energy and highly plausible trajectories are found in the experiments. The friction model is evaluated through a benchmark problem with an analytical solution and a maximum displacement error of 8.2 %, and excellent agreement in terms of the stick/slip boundary is found. Finally, we show with realistic image-guidance examples that the entire contact-modelling pipeline can be executed within a timeframe that is of the same order of magnitude as that required for standard FEM computations.

A case of malignancy-associated cryoglobulinemia.

We present a case of type 1 cryoglobulinemia with an underlying hematological malignancy. Unusually, the entire unifying diagnosis was made on the basis of the renal biopsy. Initially, serum cryoglobulin was not identified; repeat samples were positive. It is important to note that there is a significant false-negative rate with laboratory testing for cryoglobulin, due, at least in part, to the specific conditions required for collection and processing. With that in mind, in all cases with strong clinical or histological evidence of cryoglobulin but negative testing, carefully repeated samples should be sent.

The incidence and clinical correlates of lithium toxicity: a retrospective review.

BACKGROUND: Lithium is a commonly prescribed pharmacological treatment for mood disorders. It is associated with a number of side effects and potentially serious toxicity. To date, there is little data from Irish samples on the subject of Lithium toxicity. AIM: To examine the incidence and clinical correlates of lithium toxicity in Cork, Ireland. RESULTS: Our study identified 130 cases of biochemical lithium toxicity over 5 years, with an incidence rate of approximately 5.4 cases per 100,000 per year. Mean toxic lithium level was 2.16 mmol/L ±SD 0.87 mmol/L. Of these, 36% cases were reviewed medically in the general hospital at the time of toxicity. A number of issues in relation to lithium toxicity were identified. Neurological symptoms were common, including tremor, confusion, ataxia, drowsiness. However, only 4.2% patients were reviewed by a neurologist while in hospital. Medications that interact with lithium were found in 50% cases, with significant polypharmacy in 15%. The psychiatric services were involved in patient care in 76% cases, and 85% patients presenting with toxicity were reviewed by a psychiatrist. Rates of admission to hospital and haemodialysis were 70 and 11%, respectively. CONCLUSION: Improvements in the standards of care in relation to lithium prescribing are required.

New insights in CD28-independent allograft rejection.

CD28 costimulatory blockade induces tolerance in most murine transplant models but fails to do so in stringent transplant models, such as skin transplantation. The precise immunological mechanisms of CD28-independent rejection remain to be fully defined. Using two novel mouse strains in which both CD28 and either CD4 or CD8 are knocked out (CD4(-/-)CD28(-/-) or CD8(-/-)CD28(-/-) mice), we examined mechanisms of CD28-independent CD4(+) or CD8(+) T-cell-mediated allograft rejection. CD4(-/-)CD28(-/-) and CD8(-/-)CD28(-/) deficient mice rejected fully allogeneic skin allografts at a tempo comparable with that in wild-type mice. Rejection proceeded despite significant reduction in alloreactive T-cell clone sizes suggesting the presence of a subset of T cells harnessing alternate CD28-independent costimulatory pathways. Blockade of CD40-CD154 and CD134-CD134L, but not ICOS-B7h pathways in combination significantly prolonged allograft survival in CD8(-/-)CD28(-/-) recipients and to a lesser extent in CD4(-/-)CD28(-/-) recipients. Prolongation in allograft survival was associated with reduced effector-memory T-cell generation, decreased allospecific Th1 cytokine generation and diminished alloreactive T-cell proliferation in vivo. In aggregate, the data identify these two pathways as critical mediators of CD28-independent rejection by CD4(+) and to a lesser extent CD8(+) T cells, and provide novel mechanistic insights into functions of novel T-cell co-stimulatory pathways in vivo.

Epithelium derived interleukin 15 regulates intraepithelial lymphocyte Th1 cytokine production, cytotoxicity, and survival in coeliac disease.

BACKGROUND AND AIMS: Epithelium derived interleukin (IL)-15 signalling via IL-15Ralpha is critical for the development, activation, and survival of intraepithelial lymphocytes (IEL). We aimed to better understand the IL-15 driven effects on IEL underlying mucosal damage and lymphomagenesis in coeliac disease (CD). METHODS: Enterocytes, IEL, and lamina propria mononuclear cells (LPMC) were isolated from 46 patients with uncomplicated CD (25 untreated and 21 treated) and 22 controls. IL-15 and IL-15Ralpha expression were determined by immunoblotting. Secretion of IL-15, interferon gamma (IFN-gamma), tumour necrosis factor alpha (TNF-alpha), and granzyme B into cell culture supernatants was assessed by ELISA. The ability of IL-15 to regulate IEL proliferation, perforin/granzyme dependent cytotoxicity, and apoptosis was tested by adding different combinations of IL-15, IL-15 blocking antibody, or chloroquine to IEL cultured alone or with Caco-2 cells as target. IL-15 mucosal levels were also determined by ELISA in five patients with complicated CD (two ulcerative jejunoileites, one refractory sprue, and two enteropathy associated T cell lymphomas) tested for T cell receptor gamma chain clonality. RESULTS: IL-15 was overexpressed in untreated CD enterocytes and LPMC, and in the mucosa of complicated CD patients and uncomplicated untreated CD patients, where its levels correlated with the degree of mucosal damage. Enterocytes from untreated, but not treated, CD patients and controls secreted IL-15. Untreated CD IEL, characterised by higher IL-15Ralpha expression, showed increased proliferation, production of IFN-gamma and TNF-alpha, and perforin/granzyme dependent cytotoxicity, and a decreased propensity to apoptosis in response to IL-15. CONCLUSIONS: Our findings suggest that IL-15 plays a crucial role in the generation of epithelial damage in active CD. Its promotion of IEL survival in CD may predispose to the emergence of T cell clonal proliferations. Blocking IL-15, by suppressing uncontrolled IEL activation and survival, has the potential to provide new therapeutic tools to prevent tissue damage and lymphomagenesis in CD.

Selected contribution: HSP20 phosphorylation in nitroglycerin- and forskolin-induced sustained reductions in swine carotid media tone.

Cyclic nucleotide-induced relaxation of maximally activated arterial smooth muscle has two phases. 1) The initial relaxation transient is typically characterized by a rapid reduction in force associated with brief reductions in myoplasmic Ca(2+) concentration ([Ca(2+)](i)) and myosin regulatory light chain (MRLC) phosphorylation on serine (Ser)-19 (Ser(19)). 2) The sustained inhibitory response is typically associated with Ser(16) phosphorylation of heat shock protein 20 (HSP20) without sustained reductions in [Ca(2+)](i) or MRLC phosphorylation. We investigated whether the extent of Ser(16)-HSP20 phosphorylation quantitatively correlated with the sustained inhibitory response. With addition of nitroglycerin to histamine-stimulated swine carotid media, the initial relaxation transient was associated with a decrease in MRLC phosphorylation without an increase in Ser(16)-HSP20 phosphorylation. During the sustained phase of nitroglycerin-induced relaxation and during force redevelopment induced by washout of nitroglycerin in the continued presence of histamine, the level of Ser(16)-HSP20 phosphorylation, but not MRLC phosphorylation, correlated with inhibition of force. Forskolin, which increases cAMP concentration, also induced a sustained inhibitory response that was associated with increases in Ser(16)-HSP20 phosphorylation without reductions in MRLC phosphorylation levels. Forskolin increased Ser(16)-HSP20 phosphorylation to a greater extent and inhibited force more completely than that observed with nitroglycerin. Increases in Ser(16)-HSP20 phosphorylation correlated with the degree of force inhibition regardless of whether the relaxation was induced by nitroglycerin or forskolin. These data are consistent with the hypothesis that Ser(16)-HSP20 phosphorylation may be a cyclic nucleotide-dependent, yet MRLC phosphorylation-independent, inhibitor of smooth muscle contractile force.

Readmission after cardiac operations: prevalence, patterns, and predisposing factors.

OBJECTIVES: This study was undertaken (1) to determine the prevalence of hospital readmission within 1 month of discharge after cardiac operations, (2) to categorize diagnoses responsible for readmission, and (3) to examine predischarge patient factors that influenced readmission. METHODS: Data at 1 month after discharge were obtained for 1665 (98.4%) of 1692 patients who underwent cardiac operations between January 1996 and July 1998. RESULTS: Two hundred twenty-five patients (13.5%) were readmitted to a hospital within a 1-month period after discharge. Forty-eight percent of readmissions were to other hospitals. The most common readmission problems were congestive heart failure (15.6%), atrial fibrillation (12.9%), chest pain (12.0%), wound problems (10.2%), and gastrointestinal problems (8.0%). Hospital discharge on or before the fifth postoperative day was associated with a lower prevalence of subsequent readmission. The independent predictors of a readmission for congestive heart failure were postoperative stay longer than 5 days, diabetes, New York Heart Association functional class IV, preoperative congestive heart failure, total blood product use, the need for postoperative inotropes, body mass index greater than 28 kg/m(2), and reoperation for bleeding. CONCLUSIONS: The prevalence of rehospitalization during the first month after discharge is not trivial. Other than postoperative atrial fibrillation, readmission is probably the single most likely adverse event to befall a patient in the early postoperative period. Patients who are discharged early do not appear to be at increased risk. Patterns in readmission diagnoses suggest opportunities for preventive strategies.

Analyses of the genomes of chlamydial isolates from ruminants and pigs support the adoption of the new species Chlamydia pecorum.

Analysis of the genomic DNAs of chlamydial isolates from sheep, cattle, and pigs was performed by Southern blot hybridization and by restriction endonuclease (RE) profiling of DNA amplified by PCR. The hybridization probes were derived from whole genomic DNA, the major outer membrane protein (MOMP) gene, the 16S rRNA gene, and an avian Chlamydia psittaci isolate plasmid. The PCR analysis used targets in the MOMP gene, the 16S rRNA gene, and the 60-kDa cysteine-rich protein gene. Together, the results showed that although there was considerable heterogeneity in the DNA sequence in the MOMP gene region, all the isolates had the same underlying total genomic RE profiles and yielded identical RE profiles for the rRNA and 60-kDa-protein gene regions. Most of the isolates were found to hybridize with the plasmid probe. Comparison of the MOMP sequence of one of the isolates (P787) with that of a known Chlamydia pecorum strain together with the results of the RE analyses allowed the conclusion that the isolates should all be classified within this new species.

Antigenic and morphological differentiation of placental and intestinal isolates of Chlamydia psittaci of ovine origin.

Ewe placental and lamb intestinal isolates of Chlamydia psittaci recovered from flocks affected with ovine enzootic abortion were examined by inclusion morphology, indirect immunofluorescence (IIF) and immunoblot analysis. Chlamydiae recovered from the faeces of sheep from two flocks free of clinical disease were also examined. In cell culture ovine abortion (OA) and intestinal isolates were distinguishable by inclusion development and morphology. Similarly, in two-way IIF tests with one week mouse antisera isolates fell into two distinct groups: abortion or intestinal. Immunoblotting with convalescent sheep abortion antiserum identified 30 out of at least 40 silver staining polypeptides as antigenic both in OA and intestinal isolates. The serum produced a similar reaction pattern to the resolved proteins of each OA isolate, indicating a higher degree of antigenic conservation among these isolates. Considerable cross reactivity between the OA and intestinal isolates was identified, but the serum also showed apparent molecular weight differences between antigens of the two types in the 87-116 kDa, 38-44 kDa and 26-28 kDa regions. Furthermore, the immunoblotting analysis revealed heterogeneity among the intestinal isolates, particularly in antigens between 87-116 kDa and 38-44 kDa.

The growth and development of Echinococcus granulosus of sheep origin in dogs and foxes in Britain.

Four separate experiments were carried out by dosing dogs (Beagles and Border collies) and red foxes with protoscoleces obtained from hydatid cysts in sheep from mid-Wales. The dogs and foxes were killed at intervals over a period from 34-180 days after infection and the intestines were examined for Echinococcus granulosus. Border collie dogs were efficient hosts in that large numbers of worms developed, with gravid segments present by 55 days after infection; but Beagle dogs were poor hosts in that only small numbers of immature worms developed. Foxes were poor hosts in that few or no worms developed, but gravid segments were seen in three of 29 foxes. The worms showed morphological features similar to the 'sheep' rather than the 'horse' strain.

Comparison of Albendazole and Praziquantel therapy of Echinococcus granulosus in naturally infected sheep.

The effects of albendazole (10 mg kg-1 day-1) and praziquantel (50 mg kg-1 day-1) for 6 weeks on naturally infected sheep with pulmonary cysts of Echinococcus granulosus of proven viability were studied. Immediately following therapy, one of three sheep treated with praziquantel had viable cysts and 7 months later one of two sheep had viable cysts. One sheep died during albendazole therapy, but 7 months following therapy only one of five sheep had viable cysts. Electron microscopy demonstrated necrotic germinal layer tissue in most albendazole-treated cysts and praziquantel also had an effect on cyst ultrastructure. These data suggest that recurrence in humans treated with albendazole may be small. Whilst praziquantel was not particularly effective in this animal model, its clear effect on the ultrastructure suggests that an increased dose and combination therapy with albendazole may be more effective.

The epidemiology of hydatid disease in England and Wales.

The epidemiology of hydatid disease in man in England and Wales, based on the data collected between 1981 and 1983 at the Hydatid Reference Laboratory of the Public Health Laboratory Service, is presented. The incidence of hydatid disease was 42 cases per annum, with 2 cases per million population occurring in Wales and 0.2 per million in England. The highest prevalence was in London amongst the immigrant population. The incidence in the indigenous population was 15.5 cases per annum, with 5.6 cases per million occurring in South Powys, parts of South Wales and Herefordshire. The population most at risk is the rural, farming community in that area, but the West Midlands is also an apparent focus of the disease.

Embryo transfer in sheep under practice conditions.

Embryo transfer was carried out on nine Texel donor ewes, one of them on two occasions, over two breeding seasons (1980 and 1981). The donors were prepared for superovulation on the farm by two different regimens and the recipients were also synchronised on the farm of origin. Surgery was carried out on donors and recipients at a veterinary practice and the techniques of anaesthesia, surgery and embryo transfer are described. Superovulation was variable and more than two ovulations were seen in only four of the 10 ewes. Forty-one corpora lutea were produced by the 10 ewes and 27 embryos were recovered. Twenty-one embryos were transferred to recipients and 14 lambs were produced. All the 10 donors except one produced lambs themselves. The value, economics and welfare aspects of the technique of embryo transfer under practice conditions are discussed and it is concluded that the procedure should not be carried out routinely but reserved for special circumstances.

Ovine hydatidosis: some immunological characteristics of the seronegative host.

The immune status of a group of sheep naturally infected with hydatid cysts was investigated. Low specific anti-hydatid antibody (Sab) titres and negative results in intradermal and leucocyte migration tests occurred in hosts with high hydatid antigen-stimulated lymphocyte transformation (LT). Total (non-specific) IgG was elevated in infected sheep and was positively correlated with LT. Circulating hydatid antigen (cAg) was detectable in some infected sheep, but not in all of those with low Sab. Relationships between cAg, Sab and immune complex levels suggest that most cAg is present in immune complexes.

Albendazole treatment of pulmonary hydatid cysts in naturally infected sheep: a study with relevance to the treatment of hydatid cysts in man.

Albendazole was given orally to sheep with naturally occurring live pulmonary and hepatic cysts. The viability of pulmonary cysts was established before treatment by thoracotomy and needle puncture. Both 10 and 20 mg/kg/day doses were found effective in that no viable protoscoleces were found after six weeks' treatment in either group while untreated controls still had viable cysts. In addition, treated animals showed macroscopic and electron microscopic changes. Bone marrow toxicity probably occurred in two sheep.