Search

Geriatric animals account for half of the pet population in the United States with their numbers increasing annually. Furthermore, a significant percentage of veterinary patients with movement limitations could be grossly categorized as geriatric and living within the end stage of their predicted lifespans. Because mobility is correlated to quality of life and time to death in aging dogs, a major goal in optimizing canine geriatric health is to improve functional movement. Within the geriatric population, identifying disabilities that affect daily living and quality of life may be used by the rehabilitation practitioner to provide stronger prognoses, treatment goals, and outcome measures. Examples of such means are described within this review. In human medicine, the concept of “optimal aging”, or “healthy aging”, has emerged in which inevitable detrimental age-related changes can be minimized or avoided at various levels of physical, mental, emotional, and social health. Both environment and genetics may influence aging. Identifying and improving environmental variables we can control remain a key component in optimizing aging. Furthermore, diagnosing and treating age related comorbidities common to older populations allows for improved quality of life and is often directly or indirectly affecting mobility. Obesity, sarcopenia, and a sedentary lifestyle are a trifecta of age-related morbidity common to both people and dogs. Healthy lifestyle choices including good nutrition and targeted exercise play key roles in reducing this morbidity and improving aging. Disablement models act as essential tools for creating more effective physiotherapy plans in an effort to counter dysfunction and disability. Within these models, functional testing represents a standard and validated means of scoring human geriatric function as well as monitoring response to therapy. Because of the great need in dogs, this review aims to provide a reasonable and testable standardized framework for canine functional scoring. We believe a complete assessment of canine geriatric patients should comprise of identifying environmental variables contributing to health status; diagnosing comorbidities related to disease and aging; and characterizing disability with standardized methods. Only through this process can we construct a comprehensive, reasonable, and targeted rehabilitation plan with appropriate follow up aimed at healthy aging.

Objective: To quantitate key parameters of the platelet-rich plasma (PRP) product from a commercially available system1 in healthy, adult felines.Materials and methods: A prospective study was performed from January 2019 to April 2019. 11 adult, healthy cats were used to prospectively analyze a commercially available PRP system1. A whole blood sample and a PRP sample that was processed immediately following blood draw according to the manufacturer's protocol were collected from each cat. The mean whole blood and PRP product platelet, RBC, WBC, neutrophil, monocyte, and lymphocyte concentrations were determined. The mean PRP product values were compared to the mean whole blood baseline values using a paired t-test with significance established at p = 0.05.Results: Mean platelet concentration was significantly increased (p = 0.0155). Mean RBC concentration was significantly decreased (p < 0.0001). Mean neutrophil concentration was significantly decreased (p < 0.0001). There was no statistically significant difference in mean WBC, monocyte, and lymphocyte concentrations.Clinical Relevance: The analyzed PRP system increased platelet concentration, while significantly reducing the RBC and neutrophil concentrations. Further study is warranted to determine the clinical applications and efficacy of PRP in felines, and the ideal concentrations of and relationships between platelets, red blood cells, and leukocytes needed for therapeutic effect.

OBJECTIVE To determine rate of and factors associated with return to agility competition for dogs with cranial cruciate ligament (CrCL) rupture treated with tibial plateau leveling osteotomy (TPLO). DESIGN Retrospective case series with nested case-control study. ANIMALS 31 dogs involved in agility competition with CrCL tears treated by TPLO at a private veterinary clinic from 2007 through 2013. PROCEDURES Medical records were reviewed to collect information on dog signalment, lesion characteristics, and surgical data. Owners completed a survey regarding whether and when their dog returned to agility competition after TPLO and, if so, how the dog performed. Performance data before and after TPLO were compared. RESULTS 20 of 31 (65%) dogs returned to agility competition after TPLO, 16 (80%) of which returned within 9 months after TPLO. The mean convalescent period for returning dogs was 7.5 months (range, 3 to 12 months). No dog that returned to competition sustained an injury to the affected limb during the follow-up period. No significant difference was identified between dogs that returned or did not return to agility competition regarding severity of osteoarthritis or proportions with meniscal injury or partial (vs complete) CrCL tears. CONCLUSIONS AND CLINICAL RELEVANCE These data suggested that the prognosis for returning to agility competition was good for dogs undergoing TPLO. None of the evaluated lesion characteristics were associated with return to competition. Rate of return to competition and duration of the convalescent period may be useful outcome variables for future investigations involving orthopedic procedures in dogs.

Objective: The purpose of this retrospective study is to provide data regarding external prosthetic use in small animal patients, evaluate the common complications associated with external prosthetics, and evaluate the outcome of patients using an external prosthetic.Background: The use of external canine limb prosthetics is relatively uncommon in veterinary medicine today. However, there is growing interest in prosthetics and their clinical application because these devices may offer an alternative to euthanasia in severe cases where full amputation or alternative methods of limb spare are not an option. The goal of the prosthesis is to provide a better quality of life, help prevent further deformation and degeneration of existing joints, decrease leg length discrepancies, increase exercise and activity levels, provide a means to participate in rehabilitation therapy and maintain the ability to perform daily acts of living. To the author’s knowledge, there is no report of external prosthetic use in small animal veterinary medicine, providing the profession with baseline information for use in, not only general practice or referral practice, but also future research.Evidentiary value: This retrospective study provides data regarding external prosthetic use in small animal patients, evaluates the procedures, manufacturing, rehabilitation and common complications associated with external prosthetics, and evaluates the factors that determine a patient’s prosthetic candidacy.Methods: Patients that had an external prosthesis custom manufactured for them at Animal Orthocare, LLC and had a complete medical record were identified for this study. A client survey was completed via e-mail or telephone to collect further data about the patients, including age, weight, breed, sex, affected limb(s), reason for prosthesis, level of amputation, activities patient could perform with prosthesis in place, prosthetic fit, prosthetic migration (e.g. rotating or slippage), quality of mobility comparing pre-prosthetic mobility to post-prosthetic mobility, prosthetic integrity, client’s post-prosthetic mobility expectations, complications encountered post-prosthetic application, and client’s perspective of patient’s quality of life comparing pre-prosthetic and post-prosthetic placement. Results: Of the 76 patients who were identified for this study and received a survey, survey information was obtained for 24 patients. There were 50% (n=12) forelimbs affected and 50% (n=12) hind limbs affected. Bilateral hind limb prosthesis was found in 8.33% (n=2) of the 24 cases included. Causes for the prosthesis were found to be due to trauma in 37.5% (n=9) of cases, congenital causes in 37.5% (n=9) of cases, neoplasia in 16.66% (n=4) of cases, infectious in 4.17% (n=1) of cases, and unknown in 4.17% (n=1) of cases. Of the 24 patients, 50% (n=12) of clients felt the prosthesis had an excellent fit; 20.83% (n=5) felt the prosthesis had a good fit; 16.67% (n=4) felt the prosthesis had an acceptable fit; 4.17% (n=1) felt the prosthesis had a less than satisfactory fit; lastly, 8.33% (n=2) felt the prosthetic had a poor fit. Of the 24 patients, 91.66% (n=22) were able to stand using the prosthesis; 87.5% (n=21) were able to walk using the prosthesis; 79.17% (n=19) were able to trot using the prosthesis; 70.83% (n=17) were able to climb stairs using the prosthesis; 54.17% (n=13) were able to jump on or off furniture using the prosthesis; 79.17% (n=19) were able to play fetch using the prosthesis. From these cases, 50% (n=12) of clients felt the patient’s mobility improved post-prosthetic placement. Expectations were met in 70.83% (n=17) of cases; expectations were somewhat met in 4.17% (n=1) of cases; expectations were not met in 25% (n=6) of cases. Prosthetic migration affected 37.5% (n=9) of cases; residuum sore or infection affected 20.83% (n=5); refusal to use the prosthetic limb occurred in 20.83% (n=5) of cases; concurrent orthopedic disease occurred in 0% of patients; prosthetic failure (breaking) occurred in 20.83% (n=5) of cases. Finally, clients were asked to rate the quality of life of patients after prosthetic placement when compared to pre-prosthetic placement on a scale of 1 – 5 (1 = much worse than before, 5 = much better than before). Patients rated a quality of life of 5 were 20.83% (n=5); a rating of 4 was given to 20.83% (n=5); a rating of 3 was given to 45.83% (n=11); a rating of 2 was given to 4.17% (n=1); a rating of 1 was given to 8.33% (n=2). Conclusion: External prosthetics may help improve quality of life and should be considered as an alternative to euthanasia where full amputation or alternative methods of limb spare are not an option.Application: These results should be considered by veterinarians and prosthetists when searching for an alternative to full amputation or other limb spare surgical methods.

Objective: Iliopsoas injury and strain is a commonly diagnosed disease process, especially amongst working and sporting canines. There has been very little published literature regarding iliopsoas injuries and there is no information regarding the ultrasound evaluation of abnormal iliopsoas muscles. This manuscript is intended to describe the ultrasound findings in 73 canine agility athletes who had physical examination findings consistent with iliopsoas discomfort. The population was chosen given the high incidence of these animals for the development of iliopsoas injury; likely due to repetitive stress.Methods: Medical records of 73 agility performance canines that underwent musculoskeletal ultrasound evaluation of bilateral iliopsoas muscle groups were retrospectively reviewed. Data included signalment, previous radiographic findings, and ultrasound findings. A 3-tier grading scheme for acute strains was used while the practitioner also evaluated for evidence of chronic injury and bursitis.Results: The majority of pathologies were localised to the tendon of insertion, with the majority being low grade I-II strains (80.8%). Tendon fibre disruption (71.2%) and indistinct hypoechoic lesions (91.8%) were the most common of acute changes noted. Hyperechoic chronic changes were noted in 84.9 percent of cases. Acute and chronic changes were commonly seen together (62.8%).Conclusion: Diagnostic musculoskeletal ultrasound was used to identify lesions of the iliopsoas tendon consistent with acute and chronic injury, as well as identifying the region of pathology. The majority of agility performance dogs had low grade acute strains based on the tiered system, with mixed acute and chronic lesions being noted frequently.Application: Diagnostic musculoskeletal ultrasound provides a non-invasive diagnostic modality for patients suspected of having an iliopsoas strain.

Objective To evaluate outcomes in 36 dogs with a partial cranial cruciate ligament (CCL) tear treated with autologous bone marrow aspirate concentrate (BMAC) or adipose-derived progenitor cells (ADPC) with platelet-rich plasma (PRP) combination. Materials and methods Medical records of client-owned dogs diagnosed with an early partial (≤50%) tear of the craniomedial band of the CCL that was treated with BMAC–PRP or ADPC–PRP were reviewed from 2010 to 2015. Signalment, medical history, physical and orthopedic examination, objective temporospatial gait analyses, radiographs, day 0 and day 90 diagnostic arthroscopy findings, treatment, and outcome were among the data collected. A functional owner questionnaire, including the validated Helsinki chronic pain index (HCPI), was sent to owners whose dog was known to not have had a tibial plateau leveling osteotomy (TPLO). Statistical analysis was performed on data, where significance was established at p 50% CCL tear, and a TPLO was performed. Four additional dogs were known to have had a TPLO performed elsewhere. Baseline and day 90 posttreatment objective gait analyses were available on 11 of the 36 dogs. A significant difference was found between the treated limb total pressure index percent (TPI%) at day 0 and day 90 (p = 0.0124), and between the treated limb and contralateral limb TPI% at day 0 (p = 0.0003). No significant difference was found between the treated limb and contralateral limb TPI% at day 90 (p = 0.7466). Twelve questionnaires were returned, of which eight were performance/sporting dogs. Seven of the eight had returned to sport; the remaining dog had just begun a return to sport conditioning program 6 months posttreatment. All 12 respondents believed that their dog had an excellent or very good quality of life and rated their dog’s procedural outcome as excellent or good. Conclusion The use of BMAC–PRP and ADPC–PRP shows promise for the treatment of early partial CCL tears in dogs. Further studies are needed and should be randomized, blinded, and controlled.

Objective: To report clinical findings and outcomes for 55 dogs with supraspinatus tendinopathy treated with adipose derived progenitor cells and platelet rich plasma therapy. Methods: Medical records of client-owned dogs diagnosed with supraspinatus tendinopathy that were treated with adipose derived progenitor cells and platelet rich plasma (ADPC-PRP) combination therapy were reviewed from 2006-2013. Data collected included signalment, medical history, limb involvement, prior treatments, physical and orthopedic examination, objective temporospatial gait analysis findings, diagnostic imaging results (radiography, magnetic resonance imaging, musculoskeletal ultrasonography), arthroscopy findings, and outcome. Results: Following ultrasound-guided injection of ADPC-PRP, objective gait analysis was available on 25 of the 55 dogs at 90 days post ADPC-PRP therapy. Following treatment, a significant increase in total pressure index percentage (TPI%) was noted in the injured (treated) forelimb at 90 days post treatment (p = 0.036). At 90 days following treatment, 88% of cases had no significant difference in TPI% of the injured limb to the contralateral limb. The remaining 12% of cases had significantly improved (p=0.036). Bilateral shoulder diagnostic musculoskeletal ultrasound revealed a significant reduction in tendon size (CSA) in the treated tendon at 90 days following treatment when compared to the initial CSA (p=0.005). All cases showed significant improvement in fiber pattern of the affected supraspinatus tendon by the ultrasound shoulder pathology rating scale. Clinical Relevance: These findings suggest that ADPC-PRP therapy should be considered for dogs with supraspinatus tendinopathy. Abbreviations: ST: supraspinatus tendinopathy ADPC: adipose derived progenitor cells MSC: mesenchymal stem cells PRP: platelet rich plasma TPI%: total pressure index percentage

Objective: To report clinical findings and treatments for dogs with supraspinatus tendinopathy (ST).Background: ST is a term used to describe tears, calcifying tendinopathy, tendinosis and/or injuries in and around the tendon of the supraspinatus muscle, and is a cause of forelimb lameness, especially in sporting and performance dogs.Evidentiary value: This is a retrospective study of 327 dogs diagnosed with ST.Methods: Medical records (2006 to 2013) were reviewed for history, signalment, prior treatments, physical examination findings, diagnostic imaging and arthroscopic findings, concurrent shoulder and elbow pathologies, and treatments performed.Results: Dogs aged 4 months to 14 years (average 6.5 years; median 6 years) were diagnosed with ST. Performance and sporting dogs were 39.4% of the population, with 58.1% of them being agility dogs. Pain was elicited on palpation of the supraspinatus tendon in 49.3% of dogs. Shoulder radiographs in 283 dogs showed mineralisation in 13% of cases. MRI of the shoulder was performed in 31 cases and revealed findings indicative of ST, including hyperintensity of signal on T1 weighted image (or “spin-lattice”) and Short T1 Inversion Recovery (STIR) sequences of the supraspinatus tendon at its insertion on the greater tubercle and mineralisation of the supraspinatus tendon. Common ultrasonographic findings included increased tendon size (76%), irregular fibre pattern (74%), and non-homogeneous echogenicity (92.5%). The most common findings on shoulder arthroscopy were supraspinatus bulge (82.2%) and subscapularis pathology (62.4%). Elbow pathology was recorded in 54.5% of dogs. Treatment outcomes showed 74.6% of dogs failed to respond to non-steroidal anti-inflammatory drugs (NSAID) and 40.8% failed to respond to rehabilitation. Conclusions: These findings suggest concurrent shoulder and/or elbow pathology is not uncommon in dogs with ST. Further, ST often fails to respond to NSAID therapy and rehabilitation therapy. Application: Other treatments such as regenerative medicine should be considered. Future studies are still needed to assess the use and efficacy of regenerative medicine for ST.

Objective: To describe clinical and diagnostic findings as well as management of adhesive capsulitis in dogs.Background: Adhesive capsulitis, also known as frozen shoulder, is a syndrome defined by loss of range of motion of the shoulder and may be the end-stage manifestation of several primary conditions.Evidentiary Value: This is a case report series of eight dogs with chronic forelimb lameness diagnosed with adhesive capsulitis.Methods: Medical records (June 1, 2010 to September 1, 2015) including, physical examination findings, radiographic findings, magnetic resonance imaging findings, arthroscopy findings, and treatment plans were reviewed. Results: All dogs presented with a chronic, grade III-VI/VI forelimb lameness. On orthopedic examination all dogs had moderate to significant discomfort on shoulder extension and flexion and severe restriction of range of motion. Six of the eight dogs had evidence of bone remodeling and sclerosis in the affected shoulder on radiographs. Six of had an initial diagnostic ultrasound performed, which revealed evidence of fibrous scar tissue. Five dogs had magnetic resonance imaging performed that revealed moderate shoulder effusion and enhancement of the synovial lining of the shoulder. Arthroscopy was performed in five of the eight patients. Three were noted to have significant contracture, adhesions and fibrous scar tissue of the joint capsule. Severe inflammation was noted throughout the synovium of two patients. All eight patients tried conservative management consisting of oral medications and rehabilitation therapy. Five of the eight patients received extracorporeal shockwave therapy. Three patients received regenerative medicine treatment in the affected supraspinatus and shoulder. Regardless of the treatment elected, none of the dogs were reported to have significant improvement. Conclusion: Adhesive capsulitis is an uncommon cause of chronic forelimb lameness. Further investigation is needed to describe the etiology and pathogenesis of adhesive capsulitis in dogs to evaluate the effectiveness of both non-surgical and surgical treatment modalities, establish treatment protocols, and evaluate short- and long-term clinical outcome of patients.Application: Adhesive capsulitis should be considered in patients with chronic forelimb lameness and moderate to significant discomfort and restriction on shoulder range of motion.

Objective: To describe clinical and diagnostic findings as well as management of adhesive capsulitis in dogs. Background: Adhesive capsulitis, also known as frozen shoulder, is a syndrome defined by loss of range of motion of the shoulder and may be the end-stage manifestation of several primary conditions. Evidentiary Value: This is a case report series of eight dogs with chronic forelimb lameness diagnosed with adhesive capsulitis. Methods: Medical records (June 1, 2010 to September 1, 2015) including, physical examination findings, radiographic findings, magnetic resonance imaging findings, arthroscopy findings, and treatment plans were reviewed. Results: All dogs presented with a chronic, grade III-VI/VI forelimb lameness. On orthopedic examination all dogs had moderate to significant discomfort on shoulder extension and flexion and severe restriction of range of motion. Six of the eight dogs had evidence of bone remodeling and sclerosis in the affected shoulder on radiographs. Six of had an initial diagnostic ultrasound performed, which revealed evidence of fibrous scar tissue. Five dogs had magnetic resonance imaging performed that revealed moderate shoulder effusion and enhancement of the synovial lining of the shoulder. Arthroscopy was performed in five of the eight patients. Three were noted to have significant contracture, adhesions and fibrous scar tissue of the joint capsule. Severe inflammation was noted throughout the synovium of two patients. All eight patients tried conservative management consisting of oral medications and rehabilitation therapy. Five of the eight patients received extracorporeal shockwave therapy. Three patients received regenerative medicine treatment in the affected supraspinatus and shoulder. Regardless of the treatment elected, none of the dogs were reported to have significant improvement. Conclusion: Adhesive capsulitis is an uncommon cause of chronic forelimb lameness. Further investigation is needed to describe the etiology and pathogenesis of adhesive capsulitis in dogs to evaluate the effectiveness of both non-surgical and surgical treatment modalities, establish treatment protocols, and evaluate short- and long-term clinical outcome of patients. Application: Adhesive capsulitis should be considered in patients with chronic forelimb lameness and moderate to significant discomfort and restriction on shoulder range of motion.

Objective: To assess weight bearing of dogs treated for unilateral cranial cruciate ligament insufficiency with a custom stifle orthotic.Background: Cranial cruciate ligament (CCL) insufficiency is the most common cause of hind limb lameness in dogs. While there are numerous options for surgical management, surgery is not always an option. Recently, the use of canine stifle orthotics has also emerged as a means to non-surgically manage patients with cranial cruciate ligament insufficiency. Evidentiary value: This is a retrospective study of ten dogs treated for unilateral cranial cruciate ligament rupture with a stifle orthotic.Methods: Medical records (January 2005- December 2012) of ten dogs treated for unilateral cranial cruciate ligament rupture with a stifle orthotic were reviewed. Temporospatial gait analysis was performed using a pressure sensing walkway at baseline and 90 days or greater post orthotic placement to identify weight bearing with total pressure index % (TPI%).Results: TPI% improved significantly by 5.1% in the affected limb when compared to baseline (p = 0.0020). At final gait analysis, TPI% significantly improved by 3% in the affected limb with the orthotic off when compared to the unaffected limb (p = 0.0020).Conclusion: Custom canine stifle orthotics allow for improved weight bearing in the affected limb.Application: Custom canine stifle orthotics should be considered for cases with concurrent medical conditions or financial constraints that do not allow for surgical intervention.

Objective: To quantitate key parameters of the platelet rich plasma (PRP) product from five commercial canine PRP systems in healthy, adult canines. Materials and Methods: A prospective study was performed from January 2013 to April 2014. Five commercial systems were analyzed using ten healthy dogs per system.a-e Blood was obtained according to the manufacturer’s protocol for each system. The mean baseline whole blood platelet, RBC, WBC, neutrophil, monocyte, and lymphocyte concentrations were determined for each PRP system. All blood samples were processed according to the manufacturer’s protocols. The mean PRP product platelet, RBC, WBC, neutrophil, monocyte, and lymphocyte concentrations were determined for each PRP system. These values were then compared to the mean baseline values. Comparisons of mean whole blood and mean PRP product parameters were calculated using a paired t-test with significance established at p = 0.05.g Results: Platelet concentration was significantly increased for System 1 (p=0.0088) and System 3 (p

The accumulation of organic solutes was investigated in the thermophilic bacteria Persephonella marina and Marinitoga piezophila, two representatives of the deepest lineages in the domain Bacteria. These organisms grow optimally at around 70 °C in medium containing 3 % NaCl. A new disaccharide, accumulating in Persephonella marina, was identified as α(1-6)glucosyl-α(1-2)glucosylglycerate (GGG), by nuclear magnetic resonance. This identification was validated by comparison with the spectra of the compound obtained by chemical synthesis. Besides GGG, the solute pool of Persephonella marina comprised β-glutamate, di-myo-inositol-1,3'-phosphate and 2-O-α-glucosylglycerate. In contrast, amino acids such as α-glutamate, proline and alanine were the dominant components of the solute pool of Marinitoga piezophila and sugar derivatives were absent. The ability of GGG to protect protein structure against heat denaturation was assessed using model proteins. A genomic search for the biosynthetic pathways of known ionic solutes in Aquificales and Thermotogales shows the inability of this analysis to predict the nature of compatible solutes and underlines the need for efficient cultivation techniques.

Introduction We hypothesized that breed differences of Border Collies and Labrador Retrievers would be reflected in the temporospatial characteristics of the walk and trot. Materials and Methods Twenty healthy Border Collies and 20 healthy Labrador Retrievers made three passes across a pressure sensing walkway system that recorded quantitative temporospatial information at a walk and a trot. The following variables were measured for each dog: velocity, total pressure index percentage (TPI%), ratio of weight borne on the thoracic vs. pelvic limbs (T/P TPI%), stance time percentage (ST%), and thoracic limb stride length (TSrL). Results The mean T/P TPI% for Border Collies at a walk and at a trot were significantly lower than for Labrador Retrievers (p = 0.0007 and p = 0.0003). Border Collies had a significantly lower ST% than Labrador Retrievers for the thoracic limbs and pelvic limbs at a walk (p = 0.0058 and 0.0003) and the trot (p = 0.0280 and 0.0448). There was no relationship between ST% and TSrL in Border Collies and an inverse correlation between ST% and TSrL in Labrador Retrievers (p = 0.0002). Discussion Key quantitative gait differences were identified in Border Collies and Labrador Retrievers, which could potentially provide each breed with an advantage for their working function.

The use of explicit criteria to evaluate how well processes of care conform to accepted standards is a key method of quality assessment. Synthesizing four decades of literature, we devised an inexpensive, 6-step method of developing reliable, content-valid, explicit process criteria. This paper describes the method using a set of congestive heart failure criteria. In step 1 of the Criteria Development Method, criteria are derived from state-of-the-art clinical literature. In step 2, criteria are refined by expert panels. In this study, panelists refined the items by mail in a three-round Delphi process. In step 3, decisions about unit-or differential item weighting are made; we derived differential item weights from the panelists' third-round ratings. Step 4 consists of flagging items which may yield little information, i.e., consensus items of low import, and nonconsensus items. Numeric flags were computed using third-round median ratings and their interquartile ranges. Selection of a scoring method to summarize scores and communicate results is done in step 5. In step 6, chart reviewers are trained, inter-rater reliability is measured, and items with poor reliability are culled. This straightforward developmental method can be used to devise explicit process criteria for use in ambulatory or hospital settings and to evaluate care delivered by different types of providers. The method yields reliable criteria representing accepted standards of current clinical practice. This high content validity is a sine qua non for convergent and predictive validity, both of which must be demonstrated in empirical studies in which the criteria are compared against external yardsticks.

Thermostable proteases have been investigated for their ability to provide a novel biological solution to decontamination of prion agents responsible for transmissible spongiform encephalopathies (TSEs). Proteases were identified that digested total mouse brain homogenate (MBH) protein from uninfected mice. These proteases were then evaluated for digestion of BSE (301V) infectious MBH over a range of pH and temperatures, screened for loss of anti-prion antibody 6H4 immunoreactivity and protease-treated infectious MBH assessed in mouse bioassay using VM mice. Despite a number of proteases eliminating all 6H4-immunoreactive material, only the subtilisin-enzyme Properase showed a significant extension in incubation period in mouse bioassays following a 30-min incubation at 60 degrees C and pH 12. These results demonstrate the potential of the method to provide a practical solution to the problems of TSE contamination of surgical instruments and highlight the inadequacy of using Western blot for assessment of decontamination/inactivation of TSE agents.

Heparin at a dose of 50–100 units/kg intravenously will suppress increased vascular permeability induced by logarithmic doses of histamine (p

A model of lymphatic metastasis established by injecting Walker rat carcinoma cells into the rat footpad was used to study the output of tumour cells from the footpad. The lymphatic efferent from the footpad was cannulated in a group of rats with advanced neoplasm; it was shown that the output of tumour cells was continuous over periods up to 90 min and ranged from 10(2)-10(5) cells/min.

When twenty million Walker rat carcinoma cells are injected into the footpad of albino outbred rats, there is progressive metastasis to the draining popliteal and thence para-aortic lymph nodes. The lymphatic duct efferent from the footpad and afferent to the popliteal node has been cannulated; it has been shown that there is a continuous and progressively increasing output of tumour cells, small and large lymphocytes, macrophages and polymorphs from the footpad. About 20 per cent of the cells are tumour cells. The number of tumour cells in the popliteal and para-aortic nodes has been counted using a Coulter counter and subsequent differential counting of stained smears; the nodes contain a progressively increasing number of both tumour cells and lymphoreticular cells. The early accumulation of tumour cells in the para-aortic nodes makes it evident that tumour cells pass rapidly through the primary node. Examination of the simulated primary tumour by transmission electron microscopy suggests that tumour cells move actively toward lymphatics and protrude cytoplasmic processes through gaps in the endothelium. The endothelial cell then degenerates in close proximity to tumour cell processes. This leaves gaps through which tumour cells may pass and ultimately results in lymphatics with large defects in their walls.

The output of lysozyme into the venous and lymphatic drainage of a B.C.G. experimental granuloma has been studied. There is a massive output of lysozyme by both routes maximal in the lymph at 28 days, and in the serum at 35 days after induction of the granuloma. There is no similar excretion of acid phosphatase. The lactic dehydrogenase level both in blood draining the granuloma and blood draining the normal limb is elevated but not in precise synchrony with lysozyme output. Macrophages in the granuloma show ultrastructural features suggestive of secretion of dense granules, by appearance of electron dense material in the Golgi zone, and condensation therefrom. Granules are discharged on to the surface of lipid droplets, presumably representing attempted phagocytosis, but are not discharged elsewhere on the cell surface. Granules are released by cell disintegration both of macrophages and polymorphs. Lysozyme was demonstrated immunocytochemically in macrophage granules. The macrophages in the granuloma are biosynthetically active as shown by uptake of tritiated tyrosine. The findings support the view that granulomas export lysozyme and that this is due partly to exocytosis of material by macrophages on to the surface of lipid globules and partly to cell disintegration.