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Y-90 Selective Internal Radiotherapy (SIRT) is an ablative therapy used for inoperable liver metastasis. The purpose of this investigation was to examine the impact of local control after SIRT on overall survival (OS) in oligometastatic patients. A retrospective, single-institution study identified oligometastatic patients with ≤5 non-intracranial metastases receiving unilateral or bilateral lobar Y-90 SIRT from 2009 to 2021. The primary endpoint was OS defined from Y-90 SIRT completion to the date of death or last follow-up. Local failure was classified as a progressive disease at the target lesion(s) by RECIST v1.1 criteria starting at 3 months after SIRT. With a median follow-up of 15.7 months, 33 patients were identified who had a total of 79 oligometastatic lesions treated with SIRT, with the majority histology of colorectal adenocarcinoma ( n = 22). In total, 94% of patients completed the Y-90 lobectomy. Of the 79 individual lesions treated, 22 (27.8%) failed. Thirteen patients received salvage liver-directed therapy following intrahepatic failure; ten received repeat SIRT. Median OS (mOS) was 20.1 months, and 12-month OS was 68.2%. Intralesional failure was associated with worse 1 y OS (52.3% vs. 86.2%, p = 0.004). These results suggest that intralesional failure following Y-90 may be associated with inferior OS, emphasizing the importance of disease control in low-metastatic-burden patients.

Background: As total ankle arthroplasty (TAA) is an increasingly common surgical intervention for patients with end-stage ankle arthritis, there is a need to better understand the dynamic performance of prosthetic implants during activities of daily living. Our purpose was to quantify and compare relative tibiotalar motion during gait in persons with a fixed-bearing (FB) and mobile-bearing (MB) total ankle arthroplasty. We hypothesized a FB prosthesis would have lower tibiotalar range of motion (ROM)., Methods: Patients at least 12 months postoperative with either a FB (n=5) or MB (n=3) total ankle arthroplasty were tested. We used high-speed biplanar videoradiography to quantify tibiotalar kinematics during self-selected gait. Angular and linear ROM in three axes were compared between the groups., Results: ROM for dorsiflexion-plantarflexion, internal-external rotation, and inversion-eversion angles in FB subjects averaged 7.47±4.05°, 7.39±3.63°, and 4.51±2.13°, respectively. ROM in MB subjects averaged 6.74±2.04°, 6.28±4.51°, and 5.68±2.81°, respectively. Linear ROM along anteroposterior, mediolateral, and superior-inferior axes in FB subjects averaged 1.47±2.07 mm, 1.13±1.49 mm, and 0.28±0.30 mm, respectively. Linear ROM in MB subjects averaged 0.68±1.44 mm, 0.60±1.41 mm, and 0.20±0.13 mm, respectively. We found no significant difference between the two groups for any of these ROM parameters (p>0.05)., Conclusion: Total ankle arthroplasty using either FB or MB design appears to confer similar ankle motion during the gait cycle in this biplanar fluoroscopic model., Level of Evidence: Level IV, case series., Competing Interests: Declaration of Competing Interest This work was supported in part by Howmedica Osteonics Corp., also known as Stryker Orthopaedics., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Muscle spindles relay vital mechanosensory information for movement and posture, but muscle spindle feedback is coupled to skeletal motion by a compliant tendon. Little is known about the effects of tendon compliance on muscle spindle feedback during movement, and the complex firing of muscle spindles makes these effects difficult to predict. Our goal was to investigate changes in muscle spindle firing using added series elastic elements (SEEs) to mimic a more compliant tendon, and to characterize the accompanying changes in firing with respect to muscle-tendon unit (MTU) and muscle fascicle displacements (recorded via sonomicrometry). Sinusoidal, ramp-and-hold and triangular stretches were analysed to examine potential changes in muscle spindle instantaneous firing rates (IFRs) in locomotor- and perturbation-like stretches as well as serial history dependence. Added SEEs effectively reduced overall MTU stiffness and generally reduced muscle spindle firing rates, but the effect differed across stretch types. During sinusoidal stretches, peak and mean firing rates were not reduced and IFR was best-correlated with fascicle velocity. During ramp stretches, SEEs reduced the initial burst, dynamic and static responses of the spindle. Notably, IFR was negatively related to fascicle displacement during the hold phase. During triangular stretches, SEEs reduced the mean IFR during the first and second stretches, affecting the serial history dependence of mean IFR. Overall, these results demonstrate that tendon compliance may attenuate muscle spindle feedback during movement, but these changes cannot be fully explained by reduced muscle fascicle length or velocity, or MTU force., (© 2023 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

The emergence of effective radionuclide therapeutics, such as radium-223 dichloride, [ 177 Lu]Lu-DOTA-TATE and [ 177 Lu]Lu-PSMA ligands, over the last 10 years is driving a rapid expansion in molecular radiotherapy (MRT) research. Clinical trials that are underway will help to define optimal dosing protocols and identify groups of patients who are likely to benefit from this form of treatment. Clinical investigations are also being conducted to combine new MRT agents with other anticancer drugs, with particular emphasis on DNA repair inhibitors and immunotherapeutics. In this review, the case is presented for combining MRT with external beam radiotherapy (EBRT). The technical and dosimetric challenges of combining two radiotherapeutic modalities have impeded progress in the past. However, the need for research into the specific radiobiological effects of radionuclide therapy, which has lagged behind that for EBRT, has been recognised. This, together with innovations in imaging technology, MRT dosimetry tools and EBRT hardware, will facilitate the future use of this important combination of treatments., (Copyright © 2021 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

The purpose of this study was to establish the dose-response relationship of selective internal radiation therapy (SIRT) in patients with metastatic colorectal cancer (mCRC), when informed by radiobiological sensitivity parameters derived from mCRC cell lines exposed to 90 Y. Methods: Twenty-three mCRC patients with liver metastases refractory to chemotherapy were included. 90 Y bremsstrahlung SPECT images were transformed into dose maps assuming the local dose deposition method. Baseline and follow-up CT scans were segmented to derive liver and tumor volumes. Mean, median, and D 70 (minimum dose to 70% of tumor volume) values determined from dose maps were correlated with change in tumor volume and volumetric RECIST response using linear and logistic regression, respectively. Radiosensitivity parameters determined by clonogenic assays of mCRC cell lines HT-29 and DLD-1 after exposure to 90 Y or external beam radiotherapy (EBRT; 6 MV photons) were used in biologically effective dose (BED) calculations. Results: Mean administered radioactivity was 1,469 ± 428 MBq (range, 847-2,185 MBq), achieving a mean absorbed radiation dose to tumor of 35.5 ± 9.4 Gy and mean normal liver dose of 26.4 ± 6.8 Gy. A 1.0 Gy increase in mean, median, and D 70 absorbed dose was associated with a reduction in tumor volume of 1.8%, 1.8%, and 1.5%, respectively, and an increased probability of a volumetric RECIST response (odds ratio, 1.09, 1.09, and 1.10, respectively). Threshold mean, median and D 70 doses for response were 48.3, 48.8, and 41.8 Gy, respectively. EBRT-equivalent BEDs for 90 Y are up to 50% smaller than those calculated by applying protraction-corrected radiobiological parameters derived from EBRT alone. Conclusion: Dosimetric studies have assumed equivalence between 90 Y SIRT and EBRT, leading to inflation of BED for SIRT and possible undertreatment. Radiobiological parameters for 90 Y were applied to a BED model, providing a calculation method that has the potential to improve assessment of tumor control., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)

Animals can amplify the mechanical power output of their muscles as they jump to escape predators or strike to capture prey. One mechanism for amplification involves muscle-tendon unit (MT) systems in which a spring element (series elastic element [SEE]) is pre-stretched while held in place by a "latch" that prevents immediate transmission of muscle (or contractile element, CE) power to the load. In principle, this storage phase is followed by a triggered release of the latch, and elastic energy released from the SEE enables power amplification (PRATIO=PLOAD/PCE,max >1.0), whereby the peak power delivered from MT to the load exceeds the maximum power limit of the CE in isolation. Latches enable power amplification by increasing the muscle work generated during storage and reducing the duration over which that stored energy is released to power a movement. Previously described biological "latches" include: skeletal levers, anatomical triggers, accessory appendages, and even antagonist muscles. In fact, many species that rely on high-powered movements also have a large number of muscles arranged in antagonist pairs. Here, we examine whether a decaying antagonist force (e.g., from a muscle) could be useful as an active latch to achieve controlled energy transmission and modulate peak output power. We developed a computer model of a frog hindlimb driven by a compliant MT. We simulated MT power generated against an inertial load in the presence of an antagonist force "latch" (AFL) with relaxation time varying from very fast (10 ms) to very slow (1000 ms) to mirror physiological ranges of antagonist muscle. The fastest AFL produced power amplification (PRATIO=5.0) while the slowest AFL produced power attenuation (PRATIO=0.43). Notably, AFLs with relaxation times shorter than ∼300 ms also yielded greater power amplification (PRATIO>1.20) than the system driving the same inertial load using only an agonist MT without any AFL. Thus, animals that utilize a sufficiently fast relaxing AFL ought to be capable of achieving greater power output than systems confined to a single agonist MT tuned for maximum PRATIO against the same load., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.)

Approximately 50% of all colorectal cancer (CRC) patients will develop metastasis to the liver. 90 Y selective internal radiation therapy (SIRT) is an established treatment for metastatic CRC. There is still a fundamental lack of understanding regarding the radiobiology underlying the dose response. This study was designed to determine the radiosensitivity of two CRC cell lines (DLD-1 and HT-29) to 90 Y β - radiation exposure, and thus the relative effectiveness of 90 Y SIRT in relation to external beam radiotherapy (EBRT). A 90 Y-source dish was sandwiched between culture dishes to irradiate DLD-1 or HT-29 cells for a period of 6 d. Cell survival was determined by clonogenic assay. Dose absorbed per 90 Y disintegration was calculated using the PENELOPE Monte Carlo code. PENELOPE simulations were benchmarked against relative dose measurements using EBT3 GAFchromic ™ film. Statistical regression based on the linear-quadratic model was used to determine the radiosensitivity parameters [Formula: see text] and [Formula: see text] using R. These results were compared to radiosensitivity parameters determined for 6 MV clinical x-rays and 137 Cs γ-ray exposure. Equivalent dose of EBRT in 2 Gy ([Formula: see text]) and 10 Gy ([Formula: see text]) fractions were derived for 90 Y dose. HT-29 cells were more radioresistant than DLD-1 for all treatment modalities. Radiosensitivity parameters determined for 6 MV x-rays and 137 Cs γ-ray were equivalent for both cell lines. The [Formula: see text] ratio for 90 Y β - -particle exposure was over an order of magnitude higher than the other two modalities due to protraction of dose delivery. Consequently, an 90 Y SIRT absorbed dose of 60 Gy equates to an [Formula: see text] of 28.7 and 54.5 Gy and an [Formula: see text] of 17.6 and 19.3 Gy for DLD-1 and HT-29 cell lines, respectively. We derived radiosensitivity parameters for two CRC cell lines exposed to 90 Y β - -particles, 6 MV x-rays, and 137 Cs γ-ray irradiation. These radiobiological parameters are critical to understanding the dose response of CRC lesions and ultimately informs the efficacy of 90 Y SIRT relative to other radiation therapy modalities.

Excessive accumulation of neutrophils and their uncontrolled death by necrosis at the site of inflammation exacerbates inflammatory responses and leads to self-amplifying tissue injury and loss of organ function, as exemplified in a variety of respiratory diseases. In homeostasis, neutrophils are inactivated by apoptosis, and non phlogistically removed by neighboring macrophages in a process known as efferocytosis, which promotes the resolution of inflammation. The present study assessed the potential anti-inflammatory and pro-resolution benefits of tylvalosin, a recently developed broad-spectrum veterinary macrolide derived from tylosin. Recent findings indicate that tylvalosin may modulate inflammation by suppressing NF-κB activation. Neutrophils and monocyte-derived macrophages were isolated from fresh blood samples obtained from 12- to 22-week-old pigs. Leukocytes exposed to vehicle or to tylvalosin (0.1, 1.0, or 10 µg/mL; 0.096-9.6 µM) were assessed at various time points for apoptosis, necrosis, efferocytosis, and changes in the production of cytokines and lipid mediators. The findings indicate that tylvalosin increases porcine neutrophil and macrophage apoptosis in a concentration- and time-dependent manner, without altering levels of necrosis or reactive oxygen species production. Importantly, tylvalosin increased the release of pro-resolving Lipoxin A 4 (LXA 4 ) and Resolvin D1 (RvD 1 ) while inhibiting the production of pro-inflammatory Leukotriene B4 (LTB 4 ) in Ca 2+ ionophore-stimulated porcine neutrophils. Tylvalosin increased neutrophil phospholipase C activity, an enzyme involved in releasing arachidonic acid from membrane stores. Tylvalosin also inhibited pro-inflammatory chemokine (C-X-C motif) ligand 8 (CXCL-8, also known as Interleukin-8) and interleukin-1 alpha (IL-1α) protein secretion in bacterial lipopolysaccharide-stimulated macrophages. Together, these data illustrate that tylvalosin has potent immunomodulatory effects in porcine leukocytes in addition to its antimicrobial properties.

Objective: The objective of this study was to determine whether there is an association between under-reporting of body weight and social desirability as is found with self-reports of energy intake., Methods: Twenty-seven lean individuals (mean body mass index ± standard deviation = 21.6 ± 2.0 kg m -2 ) and 26 individuals with obesity (mean body mass index = 35.4 ± 4.8 kg m -2 ) were e-mailed a questionnaire on which they had to state their body weight and conduct a home food inventory. The next day, research team members went to their homes to weigh the participants, conduct their own food inventory and administer the Marlowe-Crowne scale for social desirability., Results: Among individuals with obesity, lower social desirability scores were associated with a greater degree of under-reporting body weight (r = +0.48, p < 0.02). Among lean individuals, the correlation was negative but statistically non-significant (p = -0.22, p > 0.10). Nine individuals with obesity were extreme under-reporters (2.27 kg or more), and eight of these had social desirability scores in the bottom half of the Marlowe-Crowne scale (p < 0.01). Six under-reported on the home food inventory by three or more items., Conclusions: Individuals with obesity and low social desirability scores are more likely than others to be extreme under-reporters of body weight, possibly due to a lack of awareness of their own weight.

A controlled landing, where an animal does not crash or topple, requires enough stability to allow muscles to effectively dissipate mechanical energy. Toads (Rhinella marina) are exemplary models for understanding the mechanics and motor control of landing given their ability to land consistently during bouts of continuous hopping. Previous studies in anurans have shown that ground reaction forces (GRFs) during landing are significantly higher compared with takeoff and can potentially impart large torques about the center of mass (COM), destabilizing the body at impact. We predict that in order to minimize such torques, toads will align their COM with the GRF vector during the aerial phase in anticipation of impact. We combined high-speed videography and force-plate ergometry to quantify torques at the COM and relate the magnitude of torques to limb posture at impact. We show that modulation of hindlimb posture can shift the position of the COM by about 20% of snout-vent length. Rapid hindlimb flexion during the aerial phase of a hop moved the COM anteriorly and reduced torque by aligning the COM with the GRF vector. We found that the addition of extrinsic loads did not significantly alter landing behavior but did change the torques experienced at impact. We conclude that anticipatory hindlimb flexion during the aerial phase of a hop is a critical feature of a mechanically stable landing that allows toads to quickly string together multiple, continuous hops., (© 2014. Published by The Company of Biologists Ltd.)

Study Design: Retrospective case-control study., Objective: To evaluate the hemostatic benefits of using a kaolin-impregnated dressing during pediatric spinal deformity correction surgery., Summary of Background Data: Minimizing blood loss and transfusions are clear benefits for patient safety. A technique common in both severe trauma and combat medicine that has not been reported in the spine literature is wound packing with a kaolin-impregnated hemostatic dressing., Methods: Estimated blood loss and transfusion amounts were analyzed in a total of 117 retrospectively identified cases. The control group included 65 patients (46 females, 19 males, 12.7±4.5 yr, 10.2±4.8 levels fused) who received standard operative care with gauze packing between June 2007 and March 2010. The treatment group included 52 patients (33 females, 19 males, 13.9±3.2 yr, 10.4±4.3 levels fused) who underwent intraoperative packing with QuikClot Trauma Pads (QCTP, Z-Medica Corporation) for all surgical procedures from July 2010 to August 2011. No other major changes in the use of antifibrinolytics or perioperative, surgical, or anesthesia technique were noted. Statistical differences were analyzed using analysis of covariance in R with P value of less than 0.05. The statistical model included sex, age, weight, scoliosis type, the number of vertebral levels fused, and surgery duration as covariates., Results: The treatment group had 40% less intraoperative estimated blood loss than the control group (974 mL vs. 1620 mL) (P<0.001). Patients who received the QCTP treatment also had 42% less total perioperative transfusion volume (499 mL vs. 862 mL) (P<0.01)., Conclusion: The use of a kaolin-impregnated intraoperative trauma pad seems to be an effective and inexpensive method to reduce intraoperative blood loss and transfusion volume in pediatric spinal deformity surgery., Level of Evidence: 3.

Maximal performance is an essential metric for understanding many aspects of an organism's biology, but it can be difficult to determine because a measured maximum may reflect only a peak level of effort, not a physiological limit. We used a unique opportunity provided by a frog jumping contest to evaluate the validity of existing laboratory estimates of maximum jumping performance in bullfrogs (Rana catesbeiana). We recorded video of 3124 bullfrog jumps over the course of the 4-day contest at the Calaveras County Jumping Frog Jubilee, and determined jump distance from these images and a calibration of the jump arena. Frogs were divided into two groups: 'rental' frogs collected by fair organizers and jumped by the general public, and frogs collected and jumped by experienced, 'professional' teams. A total of 58% of recorded jumps surpassed the maximum jump distance in the literature (1.295 m), and the longest jump was 2.2 m. Compared with rental frogs, professionally jumped frogs jumped farther, and the distribution of jump distances for this group was skewed towards long jumps. Calculated muscular work, historical records and the skewed distribution of jump distances all suggest that the longest jumps represent the true performance limit for this species. Using resampling, we estimated the probability of observing a given jump distance for various sample sizes, showing that large sample sizes are required to detect rare maximal jumps. These results show the importance of sample size, animal motivation and physiological conditions for accurate maximal performance estimates.

Two premix products containing the endectocide ivermectin were compared for pharmacokinetic profiles and bioequivalence in young pigs. Test and reference articles were administered to individual pigs in-feed at 12-h intervals for a total of 14 doses. Plasma concentration-time profiles were compared after provision of the final doses of medicated feed, by which time steady-state concentrations of ivermectin had been achieved. The pharmacokinetic variables monitored were peak concentration (Cmax ), area under the curve (AUC)0-last , elimination half-life of the terminal phase (T1/2 λz) and average steady-state concentration (Css ), determined by noncompartmental analysis. Logarithmic transformation of the variables was carried out when appropriate. Analysis of data by the Classic Method yielded confidence intervals of 80.59-114.47 (for AUC0-last ), 90.38-119.68 (for Cmax ) and 84.70-111.96 (for Css ). It was concluded that the two articles were bioequivalent for ivermectin., (© 2012 John Wiley & Sons Ltd.)

To safely land after a jump or hop, muscles must be actively stretched to dissipate mechanical energy. Muscles that dissipate energy can be damaged if stretched to long lengths. The likelihood of damage may be mitigated by the nervous system, if anticipatory activation of muscles prior to impact alters the muscle's operating length. Anticipatory motor recruitment is well established in landing studies and motor patterns have been shown to be modulated based on the perceived magnitude of the impact. In this study, we examine whether motor recruitment in anticipation of landing can serve a protective function by limiting maximum muscle length during a landing event. We use the anconeus muscle of toads, a landing muscle whose recruitment is modulated in anticipation of landing. We combine in vivo measurements of muscle length during landing with in vitro characterization of the force-length curve to determine the muscle's operating length. We show that muscle shortening prior to impact increases with increasing hop distance. This initial increase in muscle shortening functions to accommodate the larger stretches required when landing after long hops. These predictive motor strategies may function to reduce stretch-induced muscle damage by constraining maximum muscle length, despite variation in the magnitude of impact.

Muscles power movement, yet the conceptual link between muscle performance and locomotor performance is poorly developed. Frog jumping provides an ideal system to probe the relationship between muscle capacity and locomotor performance, because a jump is a single discrete event and mechanical power output is a critical determinant of jump distance. We tested the hypothesis that interspecific variation in jump performance could be explained by variability in available muscle power. We used force plate ergometry to measure power produced during jumping in Cuban tree frogs (Osteopilus septentrionalis), leopard frogs (Rana pipiens) and cane toads (Bufo marinus). We also measured peak isotonic power output in isolated plantaris muscles for each species. As expected, jump performance varied widely. Osteopilus septentrionalis developed peak power outputs of 1047.0 ± 119.7 W kg(-1) hindlimb muscle mass, about five times that of B. marinus (198.5 ± 54.5 W kg(-1)). Values for R. pipiens were intermediate (543.9 ± 96.2 W kg(-1)). These differences in jump power were not matched by differences in available muscle power, which were 312.7 ± 28.9, 321.8 ± 48.5 and 262.8 ± 23.2 W kg(-1) muscle mass for O. septentrionalis, R. pipiens and B. marinus, respectively. The lack of correlation between available muscle power and jump power suggests that non-muscular mechanisms (e.g. elastic energy storage) can obscure the link between muscle mechanical performance and locomotor performance.

A study was conducted to evaluate and compare the efficacy of two injectable formulations of ivermectin (IVM-1 and IVM-2) at a dose rate of 0.3 mg/kg bodyweight versus placebo in the treatment and control of larval and adult stages of Ascaris suum and Oesophagostomum spp. in experimentally infected pigs. Seventy helminth free pigs were allocated on a liveweight basis to 7 groups each comprising 10 pigs (A-G). Group A served as an untreated control group. Groups B and C were used to investigate the efficacy of both formulations against adult stages of A. suum and Oesophagostomum spp., Groups D and E for efficacy against larval stages of A. suum and Groups F and G for efficacy against larval stages of Oesophagostomum spp. Pigs of groups A, B, C, D and E were infected on Day-0 with 1000 infective A. suum eggs each. Infective larvae of Oesophagostomum spp. (10,000/pig) were given on Day-0 to pigs of Groups F and G and on Day-21 to pigs of Groups A, B and C. Treatment was given to pigs of Group A (saline as placebo) on Day-7 and -28, IVM-1 to pigs of Group F on Day-7, pigs of Group D on Day-14 and pigs of Group B on Day-49. IVM-2 was given to pigs of Group G on Day-7, Group E on Day-28 and Group C on Day-49. Pigs of Groups F and G were sacrificed on Day-28, pigs of Groups A, D and E on Day-49 and pigs of Groups B and C on Day-56. Post mortem worm counts showed the following efficacies: (IVM-1) against larval A. suum 100%, against adult A. suum 94.4%, against larval Oesophagostomum spp. 52.0% and against adult Oesophagostomum spp. 83.0%. (IVM-2) against larval A. suum 100%, against adult A. suum 90.3%, against larval Oesophagostomum spp. 94.0% and against adult Oesophagostomum spp. 94.7%.

These guidelines have been designed to assist in the planning, operation and interpretation of studies which would serve to assess the efficacy of drugs against internal parasites of horses. Although the term anthelmintic is used in the title and text, these guidelines include studies on drug efficacy against larvae of horse bot flies, Gasterophilus spp., which are non-helminth parasites commonly occurring in the stomach of horses. The advantages, disadvantages and application of critical and controlled tests are presented. Information is also provided on selection of animals, housing, feed, dose titration, confirmatory and clinical trials, record keeping and necropsy procedures. These guidelines should assist both investigators and registration authorities in the evaluation of compounds using comparable and standard procedures with the minimum number of animals.

The efficacy of five daily treatments with 7.5 mg fenbendazole/kg bodyweight against mucosal cyathostome larvae was evaluated in 20 12- and 24-month-old ponies with naturally acquired cyathostome infections. After three weeks communal grazing on infected pasture and six weeks indoors, one group of 10 ponies were treated. Six weeks later, both groups of ponies were humanely destroyed and their burdens of large intestinal cyathostome worms, including luminal parasites and mucosal larvae, were assessed. In the control animals approximately 7 per cent of the total worm burden was present in the gut lumen and 93 per cent was present as larvae in the large intestinal mucosa. The efficacy of fenbendazole against the luminal cyathostomes was 90.7 per cent (P < 0.01). The total numbers of mucosal larvae, recovered after digestion, were reduced by 95.3 per cent (P < 0.0005); mucosal late third and fourth stage larvae were reduced by 99.4 per cent (P < 0.0001), and early inhibited third stage larvae by 91.5 per cent (P < 0.005).

Each of 10 set-stocked calves was given a fenbendazole sustained-release intraruminal bolus at turnout for the control of parasitic bronchitis while a group of 10 similar calves was left untreated. The respiratory rates of the control calves were not greatly increased during the grazing season, but persistent coughing was evident from early July when they all had patent lungworm infections. Only occasional coughing was reported from the bolus-treated calves except for a transient increase in its frequency in late September. In mid-August, one of the treated calves was passing lungworm larvae and when they were housed six of the 10 had patent infections. In August tracer calves picked up an average of 23.5 lungworms per day from the control paddock but only 2.1 from the paddock grazed by the treated calves. In September the corresponding figures were 7.6 and 19.2 lungworms per day, respectively, from the control and 'treated' paddocks. After housing, the post mortem worm counts after an experimental challenge with Dictyocaulus viviparus larvae were reduced by 99.2 and 98.7 per cent (P < 0.0001), respectively, for the control and bolus-treated calves in comparison with weight-matched parasite-naive calves. Thus, despite a relatively low level of challenge during the grazing season, the treated animals had developed a considerable degree of protective immunity.

In a series of controlled trials involving 59 naturally infected greyhounds, fenbendazole at a dose rate of 50 mg/kg/day for three consecutive days reduced the overall numbers of third and fourth stage Toxocara canis by 94.0 per cent and third stage, fourth stage and immature adult stages of Toxascaris leonina by 92.4 per cent. In contrast, piperazine at 100 mg/kg had little or no useful effect against the larval stages of T canis and T leonina and variable efficacy against immature adult T leonina. Fenbendazole was also 100 per cent effective against immature Trichuris vulpis. In a separate controlled experiment, puppies in three litters exposed to reinfection with T canis were treated with fenbendazole at two weeks old and again only after their mean faecal egg counts exceeded 200 epg. Between one and three doses were required to suppress the output of eggs during the puppies' first 12 weeks of life.

Twenty helminth-free lambs were fed diets containing either 169 g crude protein (CP) kg-1 dry matter (DM) or 88 g CP kg-1 DM from the age of seven months. One month later five lambs from each dietary group were vaccinated against Haemonchus contortus by the oral administration of 10,000 irradiated larvae on two occasions, four weeks apart. Four weeks following the administration of the second dose of irradiated larvae both the vaccinated and unvaccinated lambs were exposed to an experimental infection of 10,000 non-irradiated H contortus larvae Faecal egg output and haematological changes were monitored throughout the study. The lambs were slaughtered 28 days after challenge when worm burdens were assessed. Vaccination was equally successful in inducing a strong resistance to the challenge infection regardless of dietary status. It was concluded that dietary protein does not influence the response to vaccination with irradiated H contortus larvae of lambs more than seven months old.

Local antibody responses to challenge with 10,000 normal Haemonchus contortus larvae were evaluated in vaccinated and control Blackface sheep fed either a high or low protein diet. Anti-parasite antibody activity was found in faecal extracts of both vaccinated and control animals after infection. The coproantibody levels showed some correlation with abomasal mucosa antibody levels and faecal antibody activity was mostly associated with IgA. The low protein diet reduced local antibody responses in vaccinated and control sheep. However despite lower antibody levels the efficacy of vaccination was not diminished in sheep fed a low protein diet.

An experiment was conducted to examine the influence of dietary protein on parasite establishment and pathogenesis of Haemonchus contortus in lambs of two breeds. Finn Dorset and Scottish Blackface. The lambs were introduced to high protein (170 g crude protein (CP) kg-1 dry matter (DM) or low protein (88 g CP kg-1 DM) diets at three months old and infected one month later with 125 larvae (kg bodyweight)-1. Blood and faecal samples were collected for analysis and bodyweights recorded weekly. The lambs were killed 20 weeks after infection. A second experiment was conducted in Blackface lambs solely to determine the influence on parasite establishment of the high and low protein diets following infection with 125 larvae kg-1. These lambs were killed five or 14 weeks after infection. Results showed that in Scottish Blackface lambs dietary protein did not significantly influence the establishment of H contortus. However, in Finn Dorset lambs dietary protein may have influenced parasite establishment since lambs on the low protein diet had a higher faecal egg output four weeks after infection and more severe clinical signs than infected lambs of the same breed on a high protein diet.

An experiment was conducted to examine, under laboratory conditions, the pathophysiology of chronic ovine haemonchosis. In the present study, groups of Merino and Scottish Blackface lambs were maintained on a low plane of nutrition and infected with 50 Haemonchus contortus larvae/kg live weight. The parasitized lambs along with respective breed controls were examined over a 27-week period. In addition to the body weight, haematological and parasitological parameters, erythrokinetic, metabolic, digestibility and nitrogen balance studies were conducted in the early stages of the infection. The results demonstrated that a low level of infection with H. contortus in lambs on a poor plane of nutrition caused the development of a normochromic normocytic anaemia which was associated with a modest but significant increase in abomasal blood loss and slightly elevated erythropoiesis in both breeds relative to the controls. The level of anaemia, hypoproteinaemia and pathophysiological changes were more marked in the Merino lambs and they also had higher faecal egg counts than the Blackface lambs.

Mixed-sex groups of three-month-old Finn Dorset and Dorset Horn lambs were given complete diets containing either high or low protein. A trickle infection with Haemonchus contortus of 200 larvae, given three times a week, began one month later for a 17 week period. Erythrokinetic, metabolic, digestibility and balance studies were conducted with the male lambs during weeks 12 to 14 of the infection. Clinical signs of haemonchosis became evident only in the low protein diet group. The infection was characterised by severe macrocytic anaemia, hypoproteinaemia, hypoalbuminaemia, reduced survival, high egg counts and a significantly greater worm burden. In the high protein diet group many lambs developed resistance to further infection in contrast to the low protein group in which no resistance developed. Live-weight gain was not affected by infection in the high protein diet group but decreased in the lambs given the low protein diet compared with uninfected controls. However, infection did not appear adversely to affect the digestive efficiency, nitrogen retention or iron absorption in either dietary group although loss of appetite occurred in the low protein group. Examination of a sample joint from the carcases showed infection was associated with a marked reduction in muscle mass in lambs given the low protein diet relative to the control animals.

Two experiments were conducted to examine the influence of dietary protein on parasite establishment and pathogenesis in Finn Dorset/Dorset Horn lambs infected with Haemonchus contortus. The lambs were introduced to high (169 g) or low (88 g crude protein (CP) kg-1 dry matter (DM)) protein diets at 3 months of age and infected 1 month later with 350 larvae kg-1 body weight (BW). Blood and faecal samples were collected for analysis and body weights recorded weekly. In the first experiment some of the infected lambs were killed 6 weeks after infection and the remainder 5 weeks later. In the second experiment all the infected lambs were killed 4 weeks after infection. The results showed that lambs on a low protein diet were less able to withstand the pathogenic effects of infection with 350 H. contortus larvae kg-1 BW than lambs given the higher protein diet. Thus mortality was greater in the low protein group and adverse clinical signs, such as inappetence, weight loss and oedema were observed more frequently. This group also had a more severe anaemia, hypoproteinaemia and hypoalbuminaemia than the high protein group. In contrast, faecal egg counts, total daily faecal egg output and worm burdens were similar in all groups of infected lambs, indicating that the diets did not influence parasite establishment.

Two experiments were conducted to examine the influence of dietary protein on the pathophysiology of Haemonchus contortus in lambs of two breeds, namely Finn Dorset and Scottish Blackface. Erythrokinetic and metabolic studies using 51Cr-red cells, 59Fe-transferrin and 125I-albumin, and digestive efficiency and nitrogen balance measurements were conducted between four and six weeks after infection. Identical radioisotopic and nutritional studies were also conducted on pair-fed control lambs of both breeds. The results demonstrated that in normal control animals, there were no significant effects of diet or breed on any of the erythrokinetic, metabolic or nutritional parameters, with the possible exception of red cell survival which was considerably longer in the Finn Dorset lambs. However, in the infected animals diet and breed did influence those parameters. The severest effects were seen in the infected Finn Dorset lambs given the low protein diet. These animals had the highest level of abomasal blood loss and this was associated with low red cell volumes and high levels of both albumin catabolism and plasma iron turnover. These animals were also in negative nitrogen balance which was partly accounted for by a significantly greater urinary nitrogen loss compared with their pair-fed controls and partly due to the poorer digestibility of the crude protein fraction of the diet. In contrast, although the infected Scottish Blackface lambs had high levels of blood loss and associated pathophysiological changes, these did not differ between dietary treatments and were similar to the changes in the infected Finn Dorset lambs given the high protein diet.

An experiment was conducted to examine the effect of dietary protein on the pathophysiology of acute haemonchosis in Finn Dorset/Dorset Horn lambs. Erythrokinetic and metabolic studies using 51Cr-red cells, 59Fe-transferrin and 125I-albumin and digestive efficiency and nitrogen balance measurements were conducted between 19 and 39 days after infection. Identical radioisotopic and nutritional studies were conducted later on pair-fed control lambs. The results demonstrated that lambs on a low protein diet (88 g crude protein (CP) kg-1 dry matter (DM)) were less able to withstand the pathophysiological consequences of infection with 350 Haemonchus contortus larvae kg-1 body weight than lambs given a high protein (170 g CP kg-1 DM) diet, despite similar worm burdens. Erythrokinetic studies indicated that abomasal blood loss was similar in both groups of infected lambs, and circulating red cell volumes were reduced and plasma volumes were expanded to a similar degree in both groups. The majority of infected lambs in both dietary groups responded equally well to the gastric haemorrhage by increasing the rate of red cell production and their absorption of dietary iron was greater than in the control lambs. Albumin catabolism was increased in both groups of infected lambs, particularly in those given the low protein diet. Within each dietary group there were no differences in the digestibilities of the various proximate fractions of the experimental diets and no differences in the urinary or faecal nitrogen losses between infected lambs and their pair-fed controls. However, loss of appetite was a major feature of the disease, particularly in the lambs given the low protein diet and this feature appeared to be crucial in determining the ability of the infected sheep to withstand the pathophysiological effects of the parasite.