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A 2-year-old, 210-kg, Duroc boar manifested with a grade II–III left front lameness. The boar was treated systemically with isolfupredone acetate and a 5-week course of ketoprofen. The lameness resolved and the ketoprofen was discontinued; however, the lameness returned and the boar was euthanized humanely. Postmortem examination was consistent with osteochondrosis dessicans.

Background:

Osteochondritis dissecans (OCD) primarily affects subchondral bone. Multiple drilling, fixation implant or autogenous osteochondral grafts are reported as treatment options. We present the midterm results of cases in which an OCD lesion was treated by osteochondral autograft transfer and drilling.

Materials and Methods:

Between 2002 and 2006, 14 knees with International Cartilage Repair Society (ICRS-OCD) type II and III lesions were treated in our clinic using osteochondral autograft transfer and drilling by arthroscopic or open surgery. The average age of our patients was 22.14 years (range 17-29 years) and average followup was of 24.3 months (range 11-40 months). Lesion type was ICRS type II in five patients (35.7%) and ICRS type III in nine patients (64.3%). In cases with ICRS-OCD type II lesions, in situ fixation was applied following circumferential multiple drilling, while mosaicplasty was done following debridement and multiple drilling in cases with ICRS-OCD type III lesion. Mosaicplasty was performed in the lesion area by an average of 2.5 (range 1-3) cylindrical osteochondral autografts. Patients were not allowed to perform loading activities for 3 weeks in the postoperative period; movement was initiated by using CPM device in the early phase; full range of motion was achieved in third week, and full weight bearing was permitted in 6 to 8 weeks

Results:

While 6 and 8 patients were classified preoperatively as fair and poor, respectively, according to Hughston scale, excellent and good results were obtained postoperatively in 10 and 4 patients, respectively. During the followup, no problems were detected in any of the patients in the regions where osteochondral graft was harvested.

Conclusion:

Biologic fixation or mosaicplasty and drilling as a technique to treatment of the lesion in OCD by osteochondral autograft transfer has resulted in good and excellent clinical outcomes in our patients and it is considered that providing blood flow to subchondral bone by circumferencial drilling leads to an increase in the robustness of biological internal fixation and shortens the duration of recovery.

Data are lacking in the literature regarding the incidence of osteochondrosis (dissecans) [OC(D)] in relation to lameness evaluation in Dutch Warmblood horses. The objective of this retrospective study was to assess the incidence of radiological abnormalities consistent with osteochondrosis or osteochondrosis dissecans in 1,231 sound Dutch Warmblood (DW) horses presented for pre-purchase examination. Standardised (Dutch) pre-purchase examination protocols were evaluated. The pre-purchase examination included a clinical, lameness and radiological evaluation, performed at a private equine clinic in the Netherlands. Radiographical examination included views of the distal (DIP) and proximal (PIP) interphalangeal, metacarpo- and metatarsophalangeal (MCP/MTP), tarsocrural (TC) and femoropatellar (FP) joints. Radiographical evidence of OC(D) was found in 44.3% of clinically sound DW horses. In this study, 443 horses (36%, n = 1,231) had evidence of OCD and 102 horses (8.3%, n = 1,231) had evidence of OC on pre-purchase radiographs. The results also indicated that the TC joints were significantly more likely to be affected. A considerable number of horses did not demonstrate any lameness, although radiographs revealed OC(D).

Navicular bones from 74 horses were examined at necropsy. Animals ranged in age from eight months to 30 years. Eight horses had a clinical history of navicular disease. Degenerative lesions in the fibrocartilaginous surface of the navicular bone and of the surface of the deep flexor tendons were age related changes not necessarily related to lameness. These lesions were more extensive in horses with a history of navicular disease, and were often accompanied by adhesions and subchondral cavitation of the fibrocartilaginous surface of the navicular bone. Osteophytes, present in 12 of the 74 horses, appeared to be age-related and were uncommon in horses with a history of navicular disease. Nutrient foramina on the distal border of the navicular bone were highly variable in size and shape; in horses with a history of navicular disease they often had a small external opening that became larger as it penetrated the bone. Occlusive vascular disease (arteriosclerosis) was found in sound horses and in horses with a history of navicular disease. Thrombosis of arteries or ischemic necrosis of bone was not identified in any case.

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The mechanisms and completeness of equine articular cartilage repair were studied in ten horses over a nine month period. Large (15 mm square) and small (5 mm square) full-thickness lesions were made in weight bearing and nonweight bearing areas of the radiocarpal, middle carpal and femoropatellar joints. The horses were euthanized in groups of two 1, 2.5, 4, 5 and 9 months later. Gross pathology, microradiography, and histopathology were used to evaluate qualitative aspects of articular repair. Computer assisted microdensitometry of safranin-O stained cartilage sections was used to quantitate cartilage matrix proteoglycan levels. Structural repair had occurred in most small defects at the end of nine months by a combination of matrix flow and extrinsic repair mechanisms. Elaboration of matrix proteoglycans was not complete at this time. Statistically better healing occurred in small weight bearing lesions, compared to large or nonweight bearing lesions. Synovial and perichondrial pannus interfered with healing of osteochondral defects that were adjacent to the cranial rim of the third carpal bone. Clinical and experimental experience suggests that these lesions are unlikely to heal, whereas similar lesions in the radiocarpal and femoropatellar joints had satisfactory outcomes. Observations made in this study support the use of early postoperative ambulation, passive flexion of operated joints, and recuperative periods of up to a year for large cartilage defects.

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As the understanding of interactions between articular cartilage and subchondral bone continues to evolve, increased attention is being directed at treatment options for the entire osteochondral unit, rather than focusing on the articular surface only. It is becoming apparent that without support from an intact subchondral bed, any treatment of the surface chondral lesion is likely to fail. This article reviews issues affecting the entire osteochondral unit, such as subchondral changes after marrow-stimulation techniques and meniscectomy or large osteochondral defects created by prosthetic resurfacing techniques. Also discussed are surgical techniques designed to address these issues, including the use of osteochondral allografts, autologous bone grafting, next generation cell-based implants, as well as strategies after failed subchondral repair and problems specific to the ankle joint. Lastly, since this area remains in constant evolution, the requirements for prospective studies needed to evaluate these emerging technologies will be reviewed.

Records of two veterinary teaching hospitals from January 1, 1976 to June 1, 1982 were searched for diagnoses of stifle lameness. Forty-two records were found and information was recorded regarding signalment, history and clinical presentation. The following abnormalities were associated with stifle lameness: subchondral bone cyst (18 cases), joint instability (15 cases), degenerative joint disease (12 cases), cranial cruciate ligament injury (9 cases), cytological or bacteriological evidence of sepsis (9 cases), collateral ligament injury (3 cases), femorotibial luxation (2 cases) and intra-articular fracture (2 cases). The duration of lameness presentation ranged from 0.3 to 24 weeks and the mean follow-up period was 20.47 ± 11.44 months (three animals were lost to follow-up). Animals (n = 15) with subchondral bone cysts as the sole association with lameness presented at an early age (range — 6 to 18 months) and apparently regardless of treatment, had a good prognosis as determined by 75% (three lost to follow-up) returning to their intended function. Cattle (n = 9) with septic arthritis were presented at an age ranging from two months to seven years and only 22.2% returned to function. Cattle (n = 15) with joint instability presented at an age varying from nine months to 13 years also did poorly as only 26.6% returned to function.

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Culicoides hypersensitivity is a chronic, recurrent, seasonal dermatitis of horses that has a worldwide distribution, but has only recently been reported in Canada. It is characterized by intense pruritus resulting in lesions associated with self-induced trauma.

A survey of veterinarians and horse-owners in British Columbia showed no differences in susceptibility due to the sex, color, breed, or height of the horses. The prevalence of the disease in the 209 horses surveyed was 26%. Horses sharing the same pasture could be unaffected. The disease was reported primarily from southwestern British Columbia; it occurred between April and October and usually affected the ventral midline, mane, and tail. Horses were generally less than nine years old when the clinical signs first appeared ([unk]=5.9 yr). Culicoides hypersensitivity was common in the lineage of several affected horses, possibly indicating a genetic susceptibility. Most cases were severe enough to require veterinary attention and some horses were euthanized.

Osteochondral defects of the ankle can either heal and remain asymptomatic or progress to deep ankle pain on weight bearing and formation of subchondral bone cysts. The development of a symptomatic OD depends on various factors, including the damage and insufficient repair of the subchondral bone plate. The ankle joint has a high congruency. During loading, compressed cartilage forces its water into the microfractured subchondral bone, leading to a localized high increased flow and pressure of fluid in the subchondral bone. This will result in local osteolysis and can explain the slow development of a subchondral cyst. The pain does not arise from the cartilage lesion, but is most probably caused by repetitive high fluid pressure during walking, which results in stimulation of the highly innervated subchondral bone underneath the cartilage defect. Understanding the natural history of osteochondral defects could lead to the development of strategies for preventing progressive joint damage.

Background

Degenerative suspensory ligament desmitis (DSLD) is a debilitating disorder thought to be limited to suspensory ligaments of Peruvian Pasos, Peruvian Paso crosses, Arabians, American Saddlebreds, American Quarter Horses, Thoroughbreds, and some European breeds. It frequently leads to persistent, incurable lameness and need to euthanize affected horses. The pathogenesis remains unclear, though the disease appears to run in families. Treatment and prevention are empirical and supportive, and not effective in halting the progression of the disease. Presently, the presumptive diagnosis of DSLD is obtained from patient signalment and history, clinical examination, and ultrasonographic examination of clinically affected horses, and is confirmed at post mortem examination. Presently, there are no reliable methods of diagnosing DSLD in asymptomatic horses. The goal of this study was to characterize and define the disorder in terms of tissue involvement at the macroscopic and microscopic levels.

Results

We examined tissues and organs from 28 affected horses (22 Peruvian Pasos, 6 horses of other breeds) and from 8 control horses. Histopathological examination revealed the presence of excessive amounts of proteoglycans in the following tissues removed from DSLD-affected horses: suspensory ligaments, superficial and deep digital flexor tendons, patellar and nuchal ligaments, cardiovascular system, and sclerae. Electron microscopy demonstrated changes in diameters of collagen fibrils in the tendon, and in smooth muscle cells of the media of the aorta compatible with increased cell permeability in DSLD-affected cells. Separation of tendon extracts by gel chromatography revealed the presence of additional proteoglycan(s) in extracts from affected, but not control extracts.

Conclusion

This study demonstrates for the first time that DSLD, a disease process previously thought to be limited to the suspensory ligaments of the distal limbs of affected horses, is in fact a systemic disorder involving tissues and organs with significant connective tissue component. Abnormal accumulation of proteoglycans between collagen and elastic fibers rather than specific collagen fibril abnormalities is the most prominent histological feature of DSLD. Because of this observation and because of the involvement of many other tendons and ligaments beside the suspensory ligament, and of non-ligamentous tissue we, therefore, propose that equine systemic proteoglycan accumulation or ESPA rather than DSLD is a more appropriate name for this condition.

Osteoarthrosis (OA) of the antebrachiocarpal joint from 7 riding horses is described. The horses were old mares and developed severe OA, with ankylosis in some of the joints. The lesions were bilateral, and the owners noticed the lameness in a late event. The cause of severe OA in these mares is not clear. The fact that OA was bilateral indicates that a single traumatic injury is unlikely as an etiologic factor. Considering the severe joint lesions it took long time before the horse-owners noticed the lameness. It is discussed if the threshold of pain is higher in the antebrachiocarpal joint compared with the middle carpal joint.

The use of monoiodoacetate (MIA) for arthrodesis of the proximal interphalangeal joint (PIJ) and the effect of exercise on the degree of fusion were investigated. Eight horses received 3 injections (Weeks 0, 3, 6) of MIA (2 mL; 60 mg/mL) into the right or left front PIJ. Peri-operatively, the horses received phenylbutazone, butorphanol, and abaxial sesamoidean nerve blocks to relieve pain. During the study, the horses were monitored for general health, lameness, and swelling around the injection area. Radiographs were taken biweekly to evaluate bony fusion. Horses were randomly divided into non-exercised and exercised groups. Exercise consisted of 20 minutes of trotting on a treadmill (4 m/s), 3 days per week for 13 weeks. The horses were euthanized at 24 weeks. Slab sections of the PIJ were evaluated grossly and radiographically for bony fusion. Histologic examinations were performed to evaluate articular cartilage. Three horses were excluded from the study after developing soft tissue necrosis around the injection site, septic arthritis, and necrotic tendinitis. The remaining horses remained healthy, developed a grade 1 to 4 lameness with minimal to severe swelling in the PIJ region. All 5 horses showed radiographic evidence of bony fusion, however, no fusion was present when injected joints were examined on postmortem examination. Histologic examination revealed thinning of the cartilage, diffuse necrosis of chondrocytes, with the calcified zone intact. Subjectively, exercise did not influence the degree of cartilage destruction. Based on this study, chemical arthrodesis cannot be advocated in clinical cases because of the high complication rate and lack of bony fusion.

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The lame sire, unsound for breeding, can cause substantial economic loss due to reduced pregnancies in the beef-producing herd.

To test the hypothesis that joint disorder is a possible cause of infertility in beef sires, right and left hind limb bones from 34 beef sires were examined postmortem to identify lesions in the femorotibial, femoropatellar (stifle), tarsocrural, talocalcaneus, and proximal intertarsal (tarsal) joints. The bulls were slaughtered during or after the breeding season due to poor fertility results. Aliquots of the cauda epididymal contents taken postmortem from 26 bulls were used for sperm morphology evaluation. As a control, hind limbs (but no semen samples) from 11 beef bulls with good fertility results were included.

Almost all infertile bulls (30/34) had lesions in at least one joint. Twenty-eight bulls (28/30, 93%) had lesions in the stifle joint, and 24 (24/28, 86%) of these were bilateral. Fourteen bulls (14/30, 47%) had lesions in the tarsal joint, and 10 (10/14, 71%) of these were bilateral. Four bulls (4/34, 12%) had no lesions, three bulls (3/34, 9%) had mild osteoarthritis (OA), 5 (5/34, 15%) moderate OA, 17 (17/34, 50%) severe OA and 5 (5/34, 15%) deformed OA. Almost all OA lesions (97%) were characterized as lesions secondary to osteochondrosis dissecans. All the bulls with satisfactory sperm morphology (n = 12/34) had joint lesions, with mostly severe or deformed bilateral lesions (83%). Consequently, the most likely cause of infertility in these 12 bulls was joint disease. Almost all control bulls (10/11) had OA lesions, but most of them were graded as mild (55%) or moderate (36%). None of the control bulls had severe lesions or deformed OA.

We suggest that joint lesions should be taken into consideration as a contributory cause of reproductive failure in beef sires without symptoms of lameness.

A lateral or medial angulation of the shaft of the distal tibiotarsal bone resulting in deviation of the lower part of the leg and frequently with bending of the proximal shaft of the tarsometatarsus is the most common leg deformity in broiler chickens. This lateral or medial deviation of the legs in broiler chickens, which has been described by many workers, deserves a specific name such as angular bone deformity or valgus-varus deformity of intertarsal joint, so that it may be separated from other varieties of lameness in broilers.

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Subchondral metastasis is a rare occurrence and poses a diagnostic dilemma as initial films may show a lytic lesion in the subchondral region often misinterpreted as being benign.. We present five cases of subchondral metastasis as well as a review of the literature. In our cases, we present subchondral metastasis in the elbow, shoulder, and hip joints. All patients had pain over the affected joint and most presented with a lytic lesion in the subchondral bone. Three patients have died since presentation and two are doing well at last follow up visit. Subchondral metastasis is a rare entity, but it should be included in the differential of a lytic lesion in the subchondral bone.

Introduction

Osteochondritis dissecans (OCD) of the femoral condyle is a rare lesion.

Materials and methods

A retrospective study (level IV evidence) analyzing a series of 40 pediatric cases with juvenile femoral condyles osteochondritis treated by arthroscopic multiple transchondral drilling between February 1999 and June 2008 was undertaken. This lesion affected the medial condyle in 87.5% of cases. The average age at treatment was 13.4 years. Our study took into account the location of the lesion and its radiological evolutionary stage. The average follow up was 14.8 months. The postoperative evaluation was based on the clinical and radiological scores of Hughston.

Results

Good clinical and radiological results in 97.5 and 95% of cases, respectively were obtained, with a significant correlation (P < 0.001) between clinical scores and radiological Hughston scores. The closed nature of the growth plate during surgery has a significant deleterious effect (P < 0.001) on the clinical and radiological score of Hughston.

Conclusion

All patients presenting juvenile condylar osteochondritis with open growth plate during treatment had good clinical and radiological results, confirming the validity and effectiveness of multiple transchondral drilling in this type of lesion.

Purpose

It is unknown what causes donor site morbidity following the osteochondral autograft transfer procedure or how donor sites heal. Contact pressure and edge loading at donor sites may play a role in the healing process. It was hypothesized that an artificially created osteochondral defect in a weightbearing area of an ovine femoral condyle will cause osseous bridging of the defect from the upper edges, resulting in incomplete and irregular repair of the subchondral bone plate.

Methods

To simulate edge loading, large osteochondral defects were created in the most unfavourable weightbearing area of 24 ovine femoral condyles. After killing at 3 and 6 months, osteochondral defects were histologically and histomorphometrically evaluated with specific attention to subchondral bone healing and subchondral bone plate restoration.

Results

Osteochondral defect healing showed progressive osseous defect bridging by sclerotic circumferential bone apposition. Unfilled area decreased significantly from 3 to 6 months (P = 0.004), whereas bone content increased (n.s.). Complete but irregular subchondral bone plate restoration occurred in ten animals. In fourteen animals, an incomplete subchondral bone plate was found. Further common findings included cavitary lesion formation, degenerative cartilage changes and cartilage and subchondral bone collapse.

Conclusions

Osteochondral defect healing starts with subchondral bone plate restoration. However, after 6 months, incomplete or irregular subchondral bone plate restoration and subsequent failure of osteochondral defect closure is common. Graft harvesting in the osteochondral autograft transfer procedure must be viewed critically, as similar changes are also present in humans.

Level of evidence

Prognostic study, Level III.

Abstract

The purpose of the study was to identify factors influencing the outcome and prognosis of rupture of the tendon of the peroneus tertius muscle in 27 horses. Information on history, physical examination findings, diagnosis, treatment, and final outcome was summarized from medical records. Long-term follow-up information on horses was obtained by telephone survey. A stepwise logistic regression model was used to analyze factors influencing the outcome. Rupture occurred in the midbody of the tendon in 11 horses, at the insertion site in 11 horses, and at the origin in 2 horses. Overall, 18/23 (78.3%) horses returned to their previous level of exercise, 5/23 (21.7%) horses were euthanized due to persistent lameness. If the horse was racing at the time of injury or had an additional structure injured besides the peroneus tertius tendon, it was less likely to return to its intended use.

A survival analysis was used to compare the culling rate of Icelandic horses due to the presence of radiographic and clinical signs of bone spavin. A follow-up study of 508 horses from a survey five years earlier was performed. In the original survey 46% of the horses had radiographic signs of bone spavin (RS) and/or lameness after flexion test of the tarsus. The horse owners were interviewed by telephone. The owners were asked if the horses were still used for riding and if not, they were regarded as culled. The owners were then asked when and why the horses were culled. During the 5 years, 98 horses had been culled, 151 had been withdrawn (sold or selected for breeding) and 259 were still used for riding. Hind limb lameness (HLL) was the most common reason for culling (n = 42). The rate of culling was low up to the age of 11 years, when it rose to 0.05 for horses with RS. The risk ratio for culling was twice as high for horses with RS compared with horses without RS and 5.5 times higher for culling because of HLL. The risk of culling (prognostic value) was highest for the combination of RS with lameness after flexion test, next highest for RS and lowest for lameness after flexion test as the only finding.

It was concluded that bone spavin affects the duration of use of Icelandic horses and is the most common cause of culling due to disease of riding horses in the age range of 7–17 years.

A total of 43 horses were used for the study of the pharyngeal bacterial flora. The median value of the number of bacteria in the group of 19 normal horses was 3.8 × 104 cfu/g of secretions. This value was 6.4 × 104cfu/g in horses with grade I pharyngitis, 1.3 × 105 cfu/g in horses with grade II pharyngitis and 3.5 × 106 cfu/g in horses affected with grades III and IV pharyngitis. Corynebacterium spp, coagulase-negative staphylococci, Nocardia spp, Moraxella spp and Enterobacter spp were the most frequently encountered bacteria in the normal animals as well as in horses affected with pharyngitis of grades I or II. Moraxella spp were isolated in 87.5% of the horses with pharyngitis of grades III and IV, followed by Streptococcus zooepidemicus, Pseudomonas aeruginosa, coagulase-negative staphylococci and Enterobacter spp. No fastidious bacteria, nor strict anaerobes were isolated from any of the 43 horses. None of the microorganisms were found in 100% of the animals and the majority of the isolates were opportunistic bacteria. These results demonstrate that the isolation of Moraxella spp and S. zooepidemicus in large numbers is frequent in horses with lymphoid follicular hyperplasia grades III and IV. Fungi were isolated in small numbers from two or three horses in each group.

Equine protozoal myeloencephalitis is a progressive neurologic disease of horses most commonly caused by infection with the apicomplexan parasite Sarcocystis neurona. Factors affecting neuroinvasion and neurovirulence have not been determined. We investigated the pathogenesis of infection with S. neurona in horses with severe combined immune deficiency (SCID). Two immunocompetent (IC) Arabian horses and two Arabian horses with SCID were infected orally with 5 × 105 sporocysts of S. neurona. Four IC horses and one SCID horse were infected intravenously (i.v.) with 5 × 108 merozoites of the WSU-1 isolate of S. neurona. Despite prolonged parasitemia and persistent infection of visceral tissues (skeletal muscle, cardiac muscle, lung, liver, and spleen) as demonstrated by PCR and culture, SCID horses did not develop neurologic signs after oral or i.v. infection. S. neurona was undetectable in the neuronal tissues of SCID horses by either PCR, immunohistochemistry, or culture. In contrast, although parasitemia was undetectable in orally infected IC horses and of only short duration in i.v. infected IC horses, four of six IC horses developed neurologic signs. S. neurona was detectable by PCR and/or culture of neural tissue but not visceral tissue of IC horses with neurologic disease. Infected SCID horses are unable to clear S. neurona from visceral tissues, but the infection does not result in neurologic signs; in contrast, IC horses rapidly control parasitemia and infection of visceral tissues but frequently experience neuroinvasion and exhibit clinical signs of neurologic disease.

The case records of 13 horses with acquired incarcerated inguinal hernia in January-August 1983, were reviewed. Nine cases were in stallions. The remaining four involved eventration 5-48 hours following castration. Ages ranged from 1-17 years. Horses showed a variable degree of colic. Bowel was felt to pass through the internal inguinal ring on rectal examination in most cases. The physical features of the scrotum varied considerably. Resection of ischemic jejunum and/or ileum was necessary in three horses. Two horses were euthanized at surgery (one with bilateral ischemic jejunum, one with bowel perforation), and a further horse on day 16 postsurgery following development of multiple adhesions. All stallions were castrated. Follow-up for 6-24 months (mean 12.7) disclosed that all ten discharged horses were alive and healthy (recovery rate 77%).

We examined 18 horses with clinical signs of chronic obstructive pulmonary disease (COPD) using physical examination, cytological and bacteriological evaluation of bronchoalveolar fluid, and percutaneous lung biopsy. In 16 cases, histological examination of lung tissue confirmed the diagnosis of COPD. Two horses were excluded: one had uncomplicated bacterial pneumonia and in the other a satisfactory lung biopsy could not be obtained. In horses with COPD, the most common historical complaint was coughing, which was reported in 88%. The most frequently detected abnormal finding on physical examination was abnormal lung sounds; these were detected in 69% of horses at rest and in 88% of horses breathing deeply into a bag. A novel finding was that 29% of horses had lung sounds that were quieter than would be expected for the degree of respiratory effort. Horses with COPD had increased percentages of neutrophils and decreased percentages of lymphocytes and macrophages in their bronchoalveolar lavage fluid. Bronchiolar neutrophil infiltration and peribronchiolar mast cell accumulation in lung biopsy tissue had the highest correlation with clinical condition. The severity of pathological changes in biopsies of lung did not predict whether the horse would die in the two to four year follow-up period. Horses that died in the follow-up period were more severely affected clinically at initial presentation than horses that were alive at the end of the follow-up period.

A kindred of German shepherd dogs with a moderately severe form of classic hemophilia was studied. The propositus was presented at five months of age because of a persistent hind limb lameness and swelling of the left stifle joint. Unclotted blood was aspirated from the swelling. A brother of this dog's dam had been diagnosed as a hemophiliac.

Hemostatic tests were performed on the propositus and on ten available related dogs. On the basis of pedigree analysis, sex and specific factor VIII related activity levels in their plasmas, the dogs were classified as affected, carriers, or unaffected. The propositus and one male relative were identified as classical hemophiliacs and were classified as moderately severely affected on the basis of apparent bleeding tendency and factor VIII procoagulant levels (FVIII:C 8-10% of normal). The propositus' signs were confined to those of lameness and joint soreness and postmortem lesions were confined to a few joints (hemarthrosis). The affected male relative was asymptomatic up to the time of euthanasia (three months of age) and did not have postmortem lesions attributable to hemophilia.

Although classic hemophilia (particularly in large breeds of dogs) is often a severe clinical disease, more moderate forms of the disease do occur. Such forms may be more difficult to recognize early in life.

The effects of daily subcutaneous administration of prostaglandin E1 (PGE1), theophylline, and of both drugs together were studied on the Freund's adjuvant-induced inflammatory and arthritic syndrome in rats. In the doses used, neither drug affected the acute inflammatory response in the adjuvant-treated paw, but together they caused marked inhibition. Chronic inflammation in the contralateral (nontreated) hind paws was slightly inhibited by each drug and combined treatment resulted in marked inhibition. The drugs also counteracted splenomegaly in adjuvant-diseased rats and their effects on spleen weight paralleled the inhibition of chronic inflammation. Arthritic lesions, as judged by x-rays of tibiotarsal joint destruction in the nontreated paws, were partially prevented by PGE1 alone, but not by theophylline. The combined treatment entirely prevented these joint lesions. PGE1 did not cause an increase in adrenal weight, but enhanced the effect of theophylline on adrenal weight. Only PGE1 improved gait in arthritic rats, simultaneous theophylline treatement having little additional effect. Other workers have found the PGE1 increases intracellular cAMP and that this effect is enhanced by the phosphodiesterase inhibitor, theophylline. We propose that the anti-inflammatory and anti-arthritic effects of combined drug treatment involve cAMP changes in phagocytic cells at the site of tissue injury and in systemic lymphocytes.

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